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The American Journal of Tropical Medicine and Hygiene - Online First
In order to provide our readers with timely access to new content, papers accepted by the American Journal of Tropical Medicine and Hygiene are posted online ahead of print publication. Papers that have been accepted for publication are peer-reviewed and copy edited but do not incorporate all corrections or constitute the final versions that will appear in the Journal. Final, corrected papers will be published online concurrent with the release of the print issue.
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Burden of Influenza in Less Than 5-Year-Old Children Admitted to Hospital with Pneumonia in Developing and Emerging Countries: A Descriptive, Multicenter Study
Authors: Cédric Dananché, Valentina Sánchez Picot, Thomas Bénet, Mélina Messaoudi, Monidarin Chou, Jianwei Wang, Jean-William Pape, Shally Awasthi, Ashish Bavdekar, Mala Rakoto-Andrianarivelo, Mariam Sylla, Pagbajabyn Nymadawa, Graciela Russomando, Florence Komurian-Pradel, Hubert Endtz, Gláucia Paranhos-Baccalà, Philippe Vanhems and on behalf of the Pneumonia GABRIEL NetworkAvailable online: 16 April 2018More LessThis descriptive 4-year study reports the proportion of detection of influenza viruses in less than 5-year-old children hospitalized for pneumonia in eight developing and emerging countries and describes clinical and microbiological characteristics of influenza-related pneumonia cases. Hospitalized children presenting radiologically confirmed pneumonia aged 2–60 months were prospectively enrolled in this observational standardized study. Mean proportion of isolated influenza virus was 9.7% (95% confidence interval: 7.9–11.8%) among 888 pneumonia children analyzed, with moderate heterogeneity between countries—ranging from 6.2% in Cambodia to 18.8% in Haiti. The clinical characteristics of children with influenza-related pneumonia were not substantially different from those of other pneumonia cases. Influenza A H1N1-related pneumonia cases appeared as more severe than pneumonia cases related to other strains of influenza. Streptococcus pneumoniae was detected more often in blood samples from influenza-related cases than in those without detected influenza viruses (19.7% versus 9.5%, P = 0.018). Influenza-related pneumonia is frequent among children less than 5 years old with pneumonia, living in developing and emerging countries. Influenza might be a frequent etiologic agent responsible for pneumonia or a predisposing status factor for pneumococcal-related pneumonia in this population.
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Congenital Toxoplasmosis in Tunisia: Prenatal and Neonatal Diagnosis and Postnatal Follow-up of 35 Cases
Authors: Boudaouara Yosr, Aoun Karim, Maatoug Rania, Souissi Olfa, Bouratbine Aïda and Ben Abdallah RymAvailable online: 16 April 2018More LessCongenital toxoplasmosis (CT) results from transplacental passage of Toxoplasma gondii to the fetus during acute maternal infection. Our study aims to report clinical and biological patterns of 35 cases of CT diagnosed at the department of the Parasitology of the Pasteur Institute of Tunis and to access the performance of prenatal and early postnatal diagnosis techniques. Serological screening of maternal infection was performed by Immunoglobulin (Ig) M and IgG detection and IgG avidity determination. Prenatal diagnosis was based on both Toxoplasma DNA detection in the amniotic fluid and monthly ultrasound examinations. PCR analysis on amniotic fluid, performed only in 15 cases, detected Toxoplasma’s DNA in five cases (33.3%). Ultrasound examination did not reveal any morphological abnormalities. Thirty newborns had serological criteria of Toxoplasma infection. Congenital toxoplasmosis diagnosis was confirmed in 23 cases (76.6%) by immunoblot. Among the 35 born-infants, five (14.3%) were symptomatic: three had chorioretinitis at the first clinical ocular examination, one had neurological symptoms (seizures) with positive parasite DNA in cerebral spinal fluid, and one had both ophthalmological and neurological damages— chorioretinitis and intracranial calcifications in the computed tomography scan. Thirty-four of 35 infected children were treated with pyrimethamine–sulfadiazine combination. Four (11.7%) of the treated infants showed abnormal hematological values because of the treatment side effect. Serological rebound was observed in seven infants. A screening program and a diagnostic algorithm in pregnant women should be implemented in Tunisia to improve the follow-up of seronegative ones and to prevent CT cases.
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Causal Beliefs Affect Treatment Practices and Preferences for Neonatal Danger Signs in Northwest Ethiopia: A Qualitative Study
Available online: 16 April 2018More LessThis study was conducted to explore the experiences of community members, particularly mothers, concerning their beliefs about the causes, treatment practices, and preferences for WHO-defined neonatal danger signs in northwest Ethiopia. A phenomenological qualitative study was conducted in three districts of north Gondar Zone, Amhara region, Ethiopia, from March 10 to 28, 2016. Twelve focus group discussions were conducted involving 98 individuals. In-depth interviews were conducted with six health extension workers and 30 women who were either pregnant or who delivered in the past 6 months. Six subthemes emerged explaining the causes of neonatal danger signs. The causes varied from danger sign to danger sign and from person to person. Most of the perceived causes of danger signs in neonates do not align with the current biomedical science. Causal assumptions and perceived seriousness of danger signs influenced treatment practices and preferences. Four subthemes also emerged for treatment practices and preferences. In some cases, respondents indicated that non-biomedical sources of treatment were superior in outcome compared with biomedical treatment options. Unsatisfactory outcomes were mentioned as major reasons to opt for treatments from non-biomedical sources. Religious and cultural reasons were reported to be major impediments for treatment seeking for newborn danger signs. There is an urgent need to introduce or expand locally modified program interventions, such as community-based newborn care, to educate the community on the causes of neonatal danger signs and the need for prompt care seeking from qualified providers.
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Barriers to Participation in a Community-Based Program to Control Transmission of Taenia solium in Peru
Available online: 16 April 2018More LessInfection of the brain with Taenia solium larvae (neurocysticercosis) is a leading cause of preventable epilepsy worldwide. Effective and sustainable strategies to control parasite transmission in rural endemic communities are needed to prevent the disease. Surveillance and targeted intervention around infected pigs (ring control strategy) have been shown to be effective when carried out by research teams. However, this strategy has not been implemented or tested as a community-based program. In this small trial in northern Peru, eight villages were randomly assigned to community-led surveillance and treatment (five villages, 997 residents) or control (three villages, 1,192 residents). In intervention villages, community-led surveillance and reporting were promoted by community health workers, radio advertisement, and school and household education. Each suspected pig infection was verified, with confirmed cases resulting in treatment with niclosamide for taeniasis and oxfendazole for pigs in clusters of homes nearby. No incentives beyond human and pig treatment were offered. Control villages received basic disease education but no treatment intervention in response to reports. Despite 14 case reports, community-based replication of ring control strategy did not replicate prior results. After 12 months, there was no change in seroincidence in intervention villages between the baseline and study end, and no difference compared with control villages. There was no difference in prevalence of taeniasis or porcine cysticercosis at study end. Community members described lack of knowledge as the main reason for not reporting infected pigs. Further exploration of methods to transfer ring strategy and other control interventions for cysticercosis to the community is needed.
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Analysis of Health-Care Charges in Murine Typhus: Need for Improved Clinical Recognition and Diagnostics for Acute Disease
Authors: Rahat F. Vohra, David H. Walker and Lucas S. BlantonAvailable online: 09 April 2018More LessMurine typhus, caused by Rickettsia typhi, is an undifferentiated febrile illness with no available rapid and sensitive diagnostic assay for use during early disease. We aimed to compare the health-care charges in those diagnosed with murine typhus to those with influenza, a febrile illness with an available rapid diagnostic test. A comparison of health-care–associated charges at the University of Texas Medical Branch at Galveston demonstrated a median of $817 for influenza versus $16,760 for murine typhus (P < 0.0001). Median laboratory ($184 versus $3,254 [P < 0.0001]) and imaging charges ($0 versus $514 [P < 0.0001]) were also higher in those with murine typhus. Those receiving at least one imaging study during their illness were greater in the murine typhus group (91.3% versus 20.3%) (P < 0.0001). The median time needed to establish a confirmed or presumptive diagnosis was 2 days for influenza compared with 9 days for murine typhus (P < 0.0001). The median number of health-care encounters was greater for those with murine typhus (2 versus 1) (P < 0.0001). Eleven patients (15.9%) with influenza were hospitalized as a result of their illness compared with 16 (69.6%) with murine typhus (P < 0.0001). The estimated mortality based on disease severity at presentation by APACHE II scoring was similar in the two groups—both had a median 4% mortality risk (P = 0.0893). These results highlight the need for improved clinical recognition and diagnostics for acute rickettsioses such as murine typhus.
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An Acarological Risk Model Predicting the Density and Distribution of Host-Seeking Ixodes scapularis Nymphs in Minnesota
Available online: 09 April 2018More LessIxodes scapularis is the vector of at least seven human pathogens in Minnesota, two of which are known to cause Lyme disease (Borrelia burgdorferi sensu stricto and Borrelia mayonii). In Minnesota, the statewide incidence of Lyme disease and other I. scapularis–borne diseases and the geographic extent over which cases have been reported have both increased substantially over the last two decades. These changes correspond with an expanding distribution of I. scapularis over a similar time frame. Because the risk of exposure to I. scapularis–borne pathogens is likely related to the number of ticks encountered, we developed an acarological risk model predicting the density of host-seeking I. scapularis nymphs (DON) in Minnesota. The model was informed by sampling 81 sites located in 42 counties in Minnesota. Two main foci were predicted by the model to support elevated densities of host-seeking I. scapularis nymphs, which included the seven-county Minneapolis-St. Paul metropolitan area and counties in northern Minnesota, including Lake of the Woods and Koochiching counties. There was substantial heterogeneity observed in predicted DON across the state at the county scale; however, counties classified as high risk for I. scapularis–borne diseases and counties with known established populations of I. scapularis had the highest proportion of the county predicted as suitable for host-seeking nymphs (≥ 0.13 nymphs/100 m2). The model provides insight into areas of potential I. scapularis population expansion and identifies focal areas of predicted suitable habitat within counties where the incidence of I. scapularis–borne diseases has been historically low.
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Prevalence of Depressive Symptoms and Related Risk Factors among Patients with Tuberculosis in China: A Multistage Cross-Sectional Study
Authors: Yanhong Gong, Shijiao Yan, Lei Qiu, Shengchao Zhang, Zuxun Lu, Yeqing Tong, Pengqian Fang and Xiaoxv YinAvailable online: 09 April 2018More LessPoor mental health among tuberculosis (TB) patients affects not only their compliance with treatments but also their daily lives. Few studies in China have evaluated depressive symptoms among TB patients. The present study aimed to determine the prevalence of depressive symptoms and its associated risk factors among Chinese TB patients. A total of 1,342 TB patients were recruited using a multistage sampling method and interviewed using a structured questionnaire. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Multinomial logistic regression analysis was performed to identify risk factors of depressive symptoms. Of the 1,342 participants included in this study, 48.0% had depressive symptoms. Of these, 34.8% and 13.2% had mild and moderate-to-severe depressive symptoms, respectively. Factors associated with depressive symptoms included family dysfunction, TB-related stigma, poor doctor–patient communication, and lack of knowledge about TB. Depressive symptoms are common among TB patients in China. Efforts of government and stakeholders in the development of relevant policy documents to prevent stigma and create social support for TB patients are necessary. This would not only promote their mental health but also improve their compliance with treatments.
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Parapoxvirus Infections in the Country of Georgia: A Case Series
Available online: 09 April 2018More LessInfections caused by viruses of the parapoxvirus (PPV) genus, including orf and pseudocowpox viruses, are frequently seen in both humans and animals in many regions of the world. These infections are often misdiagnosed or neglected because of the lack of clinician awareness, inadequate diagnostic capacity, and their relatively mild disease presentation, which may result in affected individuals not seeking medical attention. Although PPV infections should be routinely considered in patients with cutaneous lesions, especially in those who have occupational exposure to farm animals, they are often excluded from the differential diagnosis because they are not perceived as serious, resulting in underestimation of the burden of disease. Since 2014, significant enhancements to Georgia’s epidemiologic and laboratory capacity have made PPV surveillance and detection possible. In this study, we present information on 27 confirmed cases of PPV infection reported to Georgia’s national surveillance system from January 2016 through January 2017.
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Biomarkers for the Diagnosis of Cholangiocarcinoma: A Systematic Review
Authors: Gyem Tshering, Palden Wangyel Dorji, Wanna Chaijaroenkul and Kesara Na-BangchangAvailable online: 09 April 2018More LessCholangiocarcinoma (CCA), a malignant tumor of the bile duct, is a major public health problem in many Southeast Asian countries, particularly Thailand. The slow progression makes it difficult for early diagnosis and most patients are detected in advanced stages. This study aimed to review all relevant articles related to the biomarkers for the diagnosis of CCA and point out potential biomarkers. A thorough search was performed in PubMed and ScienceDirect for CCA biomarker articles. Required data were extracted. A total of 46 articles that fulfilled the inclusion and had none of the exclusion criteria were included in the analysis (17, 22, 3, 4, and 1 articles on blood, tissue, bile, both blood and tissue, and urine biomarkers, respectively). Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA), either alone or in combination with other biomarkers, are the most commonly studied biomarkers in the serum. Their sensitivity and specificity ranged from 47.2% to 98.2% and 89.7% to 100%, respectively. However, in the tissue, gene methylations and DNA-related markers were the most studied CCA biomarkers. Their sensitivity and specificity ranged from 58% to 87% and 98% to 100%, respectively. Some articles investigated biomarkers both in blood and tissues, particularly CA19-9 and CEA, with sensitivity and specificity ranging from 33% to 100% and 50% to 97.7%, respectively. Although quite a number of biomarkers with a potential role in the early detection of CCA have been established, it is difficult to single out any particular marker that could be used in the routine clinical settings.
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Type I Interferon Receptor Variants in Gene Regulatory Regions are Associated with Susceptibility to Cerebral Malaria in Malawi
Available online: 09 April 2018More LessCerebral malaria (CM) remains an important cause of morbidity and mortality. Risk for developing CM partially depends on host genetic factors, including variants encoded in the type I interferon (IFN) receptor (IFNAR1). Type I IFNs bind to IFNAR1 resulting in increased expression of IFN responsive genes, which modulate innate and adaptive immune responses. To comprehensively study IFNAR1 genetic variant associations in Malawians with CM or uncomplicated malaria, we used a tag SNP approach, based on the HapMap Yoruba in Ibadan, Nigeria, population database. We identified three novel (rs914142, rs12626750, and rs1041867) and one previously published (Chr21:34696785 [C > G]) IFNAR1 variants to be associated with CM. Some of these variants are in gene regulatory regions. Chr21:34696785 (C > G) is in a region encoding histone modifications and transcription factor–binding sites, which suggests gene regulatory activity. Rs12626750 is predicted to bind ELAV-like RNA-binding protein 1, an RNA-binding protein which can increase the type I IFN response. Furthermore, we examined these variants in an expression quantitative trait loci database and found that a protective variant, rs914142, is associated with lower expression of IFNAR1, whereas the CM-associated variant rs12626750 was associated with increased IFNAR1 expression, suggesting that activation of the type I IFN pathway may contribute to pathogenesis of CM. Future functional studies of IFNAR1 variants are now needed to clarify the role of this pathway in severe malarial diseases.
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A Comparison of Patients’ Local Conceptions of Illness and Medicines in the Context of C-Reactive Protein Biomarker Testing in Chiang Rai and Yangon
Authors: Yuzana Khine Zaw, Nutcha Charoenboon, Marco J. Haenssgen and Yoel LubellAvailable online: 09 April 2018More LessAntibiotic resistance is not solely a medical but also a social problem, influenced partly by patients’ treatment-seeking behavior and their conceptions of illness and medicines. Situated within the context of a clinical trial of C-reactive protein (CRP) biomarker testing to reduce antibiotic over-prescription at the primary care level, our study explores and compares the narratives of 58 fever patients in Chiang Rai (Thailand) and Yangon (Myanmar). Our objectives are to 1) compare local conceptions of illness and medicines in relation to health-care seeking and antibiotic demand; and to 2) understand how these conceptions could influence CRP point-of-care testing (POCT) at the primary care level in low- and middle-income country settings. We thereby go beyond the current knowledge about antimicrobial resistance and CRP POCT, which consists primarily of clinical research and quantitative data. We find that CRP POCT in Chiang Rai and Yangon interacted with fever patients’ preexisting conceptions of illness and medicine, their treatment-seeking behavior, and their health-care experiences, which has led to new interpretations of the test, potentially unforeseen exclusion patterns, implications for patients’ self-assessed illness severity, and an increase in the status of the formal health-care facilities that provide the test. Although we expected that local conceptions of illness diverge from inbuilt assumptions of clinical interventions, we conclude that this mismatch can undermine the intervention and potentially reproduce problematic equity patterns among CRP POCT users and nonusers. As a partial solution, implementers may consider applying the test after clinical examination to validate rather than direct prescription processes.
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Comparative Vector Competence of North American Culex pipiens and Culex quinquefasciatus for African and European Lineage 2 West Nile Viruses
Authors: Hannah Romo, Anna Papa, Rebekah Kading, Rebecca Clark, Mark Delorey and Aaron C. BraultAvailable online: 09 April 2018More LessWest Nile virus (WNV) is a mosquito-borne flavivirus that is phylogenetically separated into distinct lineages. Lineage 1 (L1) and lineage 2 (L2) encompass all WNV isolates associated with human and veterinary disease cases. Although L1 WNV is globally distributed, including North America, L2 WNV only recently emerged out of sub-Saharan Africa into Europe and Russia. The spread of L2 WNV throughout and beyond Europe depends, in part, on availability of competent vectors. The vector competence of mosquitoes within the Culex genus for WNV is well established for L1 WNV but less extensively studied for L2 WNV. Assessing the vector competence of North American Culex mosquitoes for L2 WNV will be critical for predicting the potential for L2 WNV emergence in North America. We address the vector competence of North American Culex pipiens and Culex quinquefasciatus for L2 WNV. Both mosquito species were highly competent for each of the L2 WNV strains assessed, but variation in infection, dissemination, and transmission was observed. An L2 WNV strain (NS10) isolated during the Greek outbreak in 2010 exhibited a reduced capacity to infect Cx. pipiens compared with other L2 WNV strains. In addition, a South African L2 WNV strain (SA89) displayed a significantly shorter extrinsic incubation period in Cx. quinquefasciatus compared with other L2 WNV strains. These results demonstrate that North American Culex mosquito species are competent vectors of African and European L2 WNV and that emergence of L2 WNV is unlikely to be hindered by poor competence of North American vectors.
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Elevated Levels of Urinary 8-oxodG Correlate with Persistent Periductal Fibrosis after Praziquantel Treatment in Chronic Opisthorchiasis
Available online: 09 April 2018More LessPrevious studies demonstrated that urinary 8-oxodG is a predictive biomarker for Opisthorchis viverrini (OV)–associated hepatobiliary disease (HBD) and cholangiocarcinoma (CCA). This study examined the effects of praziquantel treatment on the profile of urinary 8-oxodG in relation to HBD status. Infection with OV, levels of urinary 8-oxodG, and HBD status in terms of periductal fibrosis (PDF) assessed by abdominal ultrasonography (US) were monitored and compared in cohorts of participants in Khon Kaen, Thailand, before and 1 year after praziquantel treatment. Urinary 8-oxodG levels significantly decreased after treatment compared with the baseline level in OV-infected participants who had no HBD (PDF negative; PDF−ve) (N = 14). Levels of 8-oxodG were unchanged after treatment in OV-infected subjects (OV+ve) who had positive PDF (N = 52). Within the positive PDF (PDF+ve) group who became PDF−ve after treatment, there was no significant change in 8-oxodG levels between pre-and posttreatment (reversible PDF = 65.3%). In those who had persistent PDF+ve at both ultrasound sampling points, there was no significant difference in urinary 8-oxodG levels between pre- and posttreatment (persistent PDF = 34.6%). Based on a logistic regression model and receiver operation curve analysis, the increase of 8-oxodG levels was found to be associated with increasing risk of PDF. Measurement of urinary 8-oxodG and US increased the likelihood of discovering persistent PDF, which is a predictable condition for the patients at risk of OV-associated CCA. To identify high-risk individuals for CCA, it is useful to perform US in combination with urinary 8-oxodG measurement.
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Zika Virus Outbreak, Barbados, 2015–2016
Available online: 09 April 2018More LessBarbados is a Caribbean island country of approximately 285,000 people, with a thriving tourism industry. In 2015, Zika spread rapidly throughout the Americas, and its proliferation through the Caribbean islands followed suit. Barbados reported its first confirmed autochthonous Zika transmission to the Pan American Health Organization in January 2016, a month before the global public health emergency was declared. After detection of suspected Zika cases on Barbados in 2015, 926 individuals were described as suspected cases, and 147 laboratory-confirmed cases were reported through December 2016, the end of the most recent epidemiological year. In this short report, we describe the epidemiological characteristics of 926 clinical case records that were originally suspected as cases of Zika, and which were subsequently sent for testing and confirmation; 147 were found positive for Zika, using RT-PCR methods, another 276 tested negative, and the remaining 503 were either pending results or still in the suspected category. Women were represented at about twice the rate of men in case records where gender was reported (71.9%), and confirmed cases (78.2%), and 19 of the confirmed positive cases were children under the age of 10.
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Genomic Characterization and Seroprevalence Studies on Alphaviruses in Uruguay
Available online: 09 April 2018More LessAlphaviruses (Togaviridae) are arboviruses frequently associated with emerging infectious diseases. In this study, we aimed to investigate the presence of alphaviruses in Uruguay by detecting the viral genome in mosquitoes and neutralizing antibodies in equines. A total of 3,575 mosquitoes were analyzed for alphavirus genome detection. Serologic studies were performed on 425 horse sera by plaque reduction neutralization test (PRNT80) against Venezuelan equine encephalitis virus (VEEV) subtype IAB, Pixuna virus (PIXV), Rio Negro virus (RNV), western equine encephalitis virus (WEEV), and Madariaga virus (MADV). Mosquitoes belonging to six genera were captured and 82.9% were identified as Culex pipiens. Two Cx. pipiens pools collected in Fray Bentos and Las Toscas localities were alphavirus positive, and phylogenetic analyses showed that the sequences grouped into two different clusters: the lineage I of eastern equine encephalitis virus and RNV (VEEV complex), respectively. Plaque reduction neutralization test assays showed antibodies against strains of the VEEV complex, MADV, and WEEV. Rio Negro virus was the most geographically widespread virus, showing higher seroprevalences (up to 20%). Seroprevalences against VEEV IAB ranged between 4.6% and 13%; antibodies against PIXV, WEEV, and MADV were less frequent (3–4%). In conclusion, RNV exhibited the highest seroprevalence in horses, a wide geographical distribution, and viral genome was detected in Cx. pipiens mosquitoes. Madariaga virus had a low seroprevalence in equines, but an epizootic lineage typical of North America was detected in Cx. pipiens mosquitoes. Taken together, our results show that alphaviruses are present in Uruguay with variable occurrence and geographical distribution being a potential threat for human and equine health.
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Babesia microti and Malaria Infection in Africa: A Pilot Serosurvey in Kilosa District, Tanzania
Authors: Evan M. Bloch, Kasubi Mabula, Andrew Levin, Zakayo Mrango, Jerusha Weaver, Beatriz Munoz and Sheila K. WestAvailable online: 09 April 2018More LessBabesia is a tick-borne intraerythrocytic parasite that is clinically and diagnostically similar to malaria parasite, conferring risk of misdiagnosis in areas where both parasites are endemic. Data on Babesia in humans in Africa are lacking, despite evidence that it is present in regional animal populations. Samples that were collected in November 2014 to July 2015 in Kilosa district, Tanzania, were evaluated for evidence of malaria and Babesia infection. Clinical data and laboratory samples (i.e., hemoglobin, rapid diagnostic testing [RDT] for malaria, peripheral blood smear, and dried blood spots) from a routine survey were available for analysis. Dried blood spots were tested using an investigational ELISA against Babesia microti. A total of 1,030 children aged 1 month to < 5 years were evaluated; 186 (18.1%) were malaria RDT positive, 180 (96.8%) of whom had peripheral smears reviewed; 70/180 (38.9%) were smear positive for parasites. The median (inter quartile range) and range of B. microti ELISA signal to cutoff (S/C) ratio was 0.10 (0.06–0.15) and 0.01–1.65, respectively; the S/C ratios were significantly higher in subjects ≥ 1 year as compared with those < 1 year old (P < 0.001). There was also a statistically significant association between a positive RDT for malaria and the Babesia S/C (median 0.09 versus 0.13 in RDT negative versus RDT positive, respectively; P < 0.001). The highest S/C ratios were disproportionately clustered in a few hamlets. The findings suggest that Babesia may be present in Kilosa district, Tanzania. However, serological cross-reactivity and false positivity, notably between Babesia and Plasmodium spp., cannot be definitively excluded and have implications for testing in other settings.
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Case Report: Role of Interventional Radiology in the Management of Patients with Alveolar Echinococcus: Successful Management of Three Cases
Authors: Merve Gulbiz Dagoglu-Kartal, Turkmen Ciftci, Cigdem Ozer, Devrim Akinci and Okan AkhanAvailable online: 02 April 2018More LessAlveolar echinococcus (AE) is an infestation by Echinococcus multilocularis. Partial hepatectomy or liver transplantation is the first choice of treatment. However, the disease is usually diagnosed at an unresectable stage. In those cases, invasion of the bile ducts and vessels, and necrosis in the center of the lesion lead to severe complications, such as cholangitis and liver abscesses. Palliative surgery has been reported to not offer advantages in management, and percutaneous and endoscopic interventions have become more prominent in management. In this case series, outcomes in three cases with unresectable AE were reported. In one of the cases, interventional procedures were used to manage the complications after surgery. In the second case, the cystic component was aspirated to decrease the size before the surgery and in the third case, it was used to drain biliary tree and no surgery was done.
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Epidemiological and Clinical Features of Melioidosis: A Report of Seven Cases from Southern Inland China
Authors: Yanping Tang, Jingmin Deng, Jianquan Zhang, Xiaoning Zhong, Ye Qiu, Hui Zhang and Haiguang XuAvailable online: 02 April 2018More LessSome subtropical regions with similar climatic conditions to melioidosis-endemic areas, such as southern Guangxi, may be new endemic zones for melioidosis. We retrospectively reviewed seven culture-proven melioidosis patients from October 2006 to March 2015. Their clinical characteristics, diagnosis, and treatment, and the geographical and environmental factors were analyzed. Seven male patients lived at latitudes of 21–23°N in Beihai, Nanning, Chongzuo City of the Guangxi Province. Symptom onset occurred during the rainy season. All patients had pneumonia, six patients had diabetes, five patients had a history of wounds or exposure to soil or water, and two patients had liver and spleen abscesses. Most patients were misdiagnosed before the confirmatory laboratory testing. The final diagnosis was confirmed as melioidosis by isolation of Burkholderia pseudomallei in a culture of blood or pus. The 6- to 17-month treatment included carbapenems, ceftazidime, or other antibiotics active against the organism in vitro. All patients initially appeared cured, but two subsequently had recurrent melioidosis. In non-highly endemic areas, there is often a lack of awareness of melioidosis, and this leads to misdiagnoses. Other subtropical regions with climatic conditions similar to the highly melioidosis-endemic areas such as southern Guangxi may also be melioidosis endemic.
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Environmental Enteropathy in Undernourished Pakistani Children: Clinical and Histomorphometric Analyses
Available online: 02 April 2018More LessDespite nutrition interventions, stunting thought to be secondary to underlying environmental enteropathy (EE) remains pervasive among infants residing in resource-poor countries and remains poorly characterized. From a birth cohort of 380 children, 65 malnourished infants received 12 weeks of nutritional supplementation with ready-to-use therapeutic food (RUTF). Eleven children with insufficient response to RUTF underwent upper endoscopy with duodenal biopsies, which were compared with U.S., age-matched specimens for healthy, celiac disease, non-celiac villous atrophy, non-celiac intraepithelial lymphocytosis, and graft-versus-host disease patients. Of the 11 children biopsied, EE was found in 10 (91%) with one subject with celiac disease. Morphometry demonstrated decreased villus-to-crypt (V:C) ratios in EE relative to healthy and non-celiac lymphocytosis patients. Environmental enteropathy villus volumes were significantly decreased relative to healthy controls. In EE, average CD3+ cells per 100 epithelial cells and per 1,000 µm2 of lamina propria and the number of lamina propria CD20+ B-cell aggregates were increased relative to all other groups. Our results indicate that V:C ratios are reduced in EE but are less severe than in celiac disease. Environmental enteropathy intraepithelial and lamina propria T lymphocytosis is of greater magnitude than that in celiac disease. The increases in lamina propria B and T lymphocytes suggest that non-cytolytic lymphocytic activation may be a more prominent feature of EE relative to celiac disease. These results provide new insights into shared yet distinct histological and immunological features of EE and celiac disease in children.
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Hospitalized Bacteremic Melioidosis in Rural Thailand; 2009–2013
Available online: 02 April 2018More LessMelioidosis incidence and mortality have reportedly been increasing in endemic areas of Thailand, but little population-based data on culture-confirmed Burkholderia pseudomallei infections exist. We provide updated estimates of melioidosis bacteremia incidence and in-hospital mortality rate using integration of two population-based surveillance databases in Nakhon Phanom, Thailand, since automated blood culture became available in 2005. From 2009 to 2013, 564 hospitalized bacteremic melioidosis patients were identified. The annual incidence of bacteremic melioidosis ranged from 14 to 17 per 100,000 persons, and average population mortality rate was 2 per 100,000 persons per year. In-hospital mortality rate declined nonsignificantly from 15% (15/102) to 13% (15/118). Of 313 (56%) bacteremic melioidosis patients who met criteria for acute lower respiratory infection and were included in the hospital-based pneumonia surveillance system, 65% (202/313) had a chest radiograph performed within 48 hours of admission; 46% (92/202) showed radiographic evidence of pneumonia. Annual incidence of bacteremic melioidosis with pneumonia was 2.4 per 100,000 persons (95% confidence intervals; 1.9–2.9). In-hospital death was more likely among bacteremic melioidosis patients with pneumonia (34%; 20/59) compared with non-pneumonia patients (18%; 59/321) (P-value = 0.007). The overall mortality could have been as high as 46% (257/564) if patients with poor clinical condition at the time of discharge had died. The continued high incidence of bacteremic melioidosis, pneumonia, and deaths in an endemic area highlights the need for early diagnosis and treatment and additional interventions for the prevention and control for melioidosis.
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Albendazole Treatment Improves Work Capacity in Women Smallholder Farmers Infected with Hookworm: A Double-Blind Randomized Control Trial
Available online: 02 April 2018More LessAn estimated 4.7 billion people live in regions exposed to soil-transmitted helminths, intestinal parasites that have significant impacts on the health of women smallholder farmers. The goal of this trial was to determine whether treatment with albendazole impacts the work capacity of these farmers. This is a prospective double-blind, randomized effectiveness trial. Participants (N = 250) were randomly selected from safe motherhood groups in the Democratic Republic of Congo. Prevalence/intensity of hookworm infection, hemoglobin, and demographics was obtained. At study (Time = 0), participants were randomized into treatment (albendazole 400 mg) and placebo (similar placebo tablet) groups. A step test was administered as a proxy metric for work capacity. Work capacity was defined as ∆heart rate before and after 3 minutes of step testing, in beats per minute. At study (time = 7 months), the step test was repeated and work capacity remeasured. The ∆work capacity (time = 0 minus time = 7 months) was the primary outcome. Investigators/field assistants were blinded to who was enrolled in groups, hookworm status, and step test results. Regression showed highly significant interactive effects of hookworm status and treatment group relative to ∆work capacity after controlling for resting pulse rate and age (P < 0.002). Estimated marginal means for work capacity (WC) for each of four groups (hookworm positive plus placebo, hookworm positive plus treatment, hookworm negative plus placebo, and hookworm negative plus treatment) showed women who were hookworm positive and received treatment decreased heart rate by 9.744 (95% confidence interval [CI]: 6.42, 13.07) beats per minute (increased WC), whereas women who were hookworm positive and received placebo saw a nonsignificant decrease of 0.034 (95% CI: −3.16, 3.84) beats per minute. Treatment with albendazole was associated with improved aerobic work capacity posttreatment. Given modest costs of drug distributions, risk benefits of periodic deworming warrants further study in larger controlled trials.
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Survey to Identify Substandard and Falsified Tablets in Several Asian Countries with Pharmacopeial Quality Control Tests and Principal Component Analysis of Handheld Raman Spectroscopy
Available online: 02 April 2018More LessThe World Health Organization has warned that substandard and falsified medical products (SFs) can harm patients and fail to treat the diseases for which they were intended, and they affect every region of the world, leading to loss of confidence in medicines, health-care providers, and health systems. Therefore, development of analytical procedures to detect SFs is extremely important. In this study, we investigated the quality of pharmaceutical tablets containing the antihypertensive candesartan cilexetil, collected in China, Indonesia, Japan, and Myanmar, using the Japanese pharmacopeial analytical procedures for quality control, together with principal component analysis (PCA) of Raman spectrum obtained with handheld Raman spectrometer. Some samples showed delayed dissolution and failed to meet the pharmacopeial specification, whereas others failed the assay test. These products appeared to be substandard. Principal component analysis showed that all Raman spectra could be explained in terms of two components: the amount of the active pharmaceutical ingredient and the kinds of excipients. Principal component analysis score plot indicated one substandard, and the falsified tablets have similar principal components in Raman spectra, in contrast to authentic products. The locations of samples within the PCA score plot varied according to the source country, suggesting that manufacturers in different countries use different excipients. Our results indicate that the handheld Raman device will be useful for detection of SFs in the field. Principal component analysis of that Raman data clarify the difference in chemical properties between good quality products and SFs that circulate in the Asian market.
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A Randomized Controlled Trial to Assess the Impact of Ceramic Water Filters on Prevention of Diarrhea and Cryptosporidiosis in Infants and Young Children—Western Kenya, 2013
Available online: 02 April 2018More LessCryptosporidium is a leading cause of diarrhea among Kenyan infants. Ceramic water filters (CWFs) are used for household water treatment. We assessed the impact of CWFs on diarrhea, cryptosporidiosis prevention, and water quality in rural western Kenya. A randomized, controlled intervention trial was conducted in 240 households with infants 4–10 months old. Twenty-six weekly household surveys assessed infant diarrhea and health facility visits. Stool specimens from infants with diarrhea were examined for Cryptosporidium. Source water, filtered water, and filter retentate were tested for Cryptosporidium and/or microbial indicators. To estimate the effect of CWFs on health outcomes, logistic regression models using generalized estimating equations were performed; odds ratios (ORs) and 95% confidence intervals (CIs) are reported. Households reported using surface water (36%), public taps (29%), or rainwater (17%) as their primary drinking water sources, with no differences in treatment groups. Intervention households reported less diarrhea (7.6% versus 8.9%; OR: 0.86 [0.64–1.16]) and significantly fewer health facility visits for diarrhea (1.0% versus 1.9%; OR: 0.50 [0.30–0.83]). In total, 15% of intervention and 12% of control stools yielded Cryptosporidium (P = 0.26). Escherichia coli was detected in 93% of source water samples; 71% of filtered water samples met World Health Organization recommendations of < 1 E. coli/100 mL. Cryptosporidium was not detected in source water and was detected in just 2% of filter rinses following passage of large volumes of source water. Water quality was improved among CWF users; however, the short study duration and small sample size limited our ability to observe reductions in cryptosporidiosis.
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Comparison of PCR Methods for Onchocerca volvulus Detection in Skin Snip Biopsies from the Tshopo Province, Democratic Republic of the Congo
Available online: 02 April 2018More LessDefining the optimal diagnostic tools for evaluating onchocerciasis elimination efforts in areas co-endemic for other filarial nematodes is imperative. This study compared three published PCR methods: the Onchocerca volvulus–specific qPCR-O150, the pan-filarial qPCR melt curve analysis (MCA), and the O150-PCR ELISA currently used for vector surveillance in skin snip biopsies (skin snips) collected from the Democratic Republic of the Congo. The pan-filarial qPCR-MCA was compared with species-specific qPCRs for Loa loa and Mansonella perstans. Among the 471 skin snips, 47.5%, 43.5%, and 27% were O. volvulus positive by qPCR-O150, qPCR-MCA, and O150-PCR ELISA, respectively. Using qPCR-O150 as the comparator, the sensitivity and specificity of qPCR-MCA were 89.3% and 98%, respectively, whereas for O150-PCR ELISA, they were 56.7% and 100%, respectively. Although qPCR-MCA identified the presence of L. loa and Mansonella spp. in skin snips, species-specific qPCRs had greater sensitivity and were needed to identify M. perstans. Most of the qPCR-MCA misclassifications occurred in mixed infections. The reduced sensitivity of O150-PCR ELISA was associated with lower microfilaria burden and with lower amounts of O. volvulus DNA. Although qPCR-MCA identified most of the O. volvulus–positive skin snips, it is not sufficiently robust to be used for stop-mass drug administration (MDA) evaluations in areas co-endemic for other filariae. Because O150-PCR ELISA missed 43.3% of qPCR-O150–positive skin snips, the qPCR-O150 assay is more appropriate for evaluating skin snips of OV-16 + children in stop-MDA assessments. Although improving the sensitivity of the O150-PCR ELISA as an alternative to qPCR might be possible, qPCR-O150 offers distinct advantages aside from increased sensitivity.
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Clinical and Neurophysiological Features of Leprosy Patients with Neuropathic Pain
Available online: 02 April 2018More LessNeural pain is a frequent symptom in leprosy disease. There is a paucity of data regarding neural pain diagnostics resulting in common prescriptive errors when neuritis is confused with neuropathic or mixed nociceptive–neuropathic pain. The present study identified important demographic, clinical, and neurophysiological features of 42 leprosy neuropathy patients presenting neuropathic pain (NP). During routine evaluations, patients were selected asking if they had ever experienced neural pain. Data analyses of their pain characteristics, clinical examination results, and both the Douleur Neuropathique 4 Questionnaire and Hamilton Depression Scale scores were used to classify these patients. The most common word they used to describe the sensation of pain for 25 (60%) of these patients was “burning.” In the early stages of the disease and before leprosy diagnosis, 19 (45%) had already complained about NP and leprosy treatment was unable to prevent its occurrence in 15 (36%). Leprosy reactions, considered NP risk factors, occurred in 32 (76%) cases. Knowledge of typical NP characteristics could be used to develop more effective therapeutic approaches for a notoriously difficult-to-treat pain condition.
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Empowering Girls and Women through Hookworm Prevention
Author: Peter J. HotezAvailable online: 02 April 2018More Less
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Validity of Time to Sputum Culture Conversion to Predict Cure in Patients with Multidrug-Resistant Tuberculosis: A Retrospective Single-Center Study
Authors: Nafees Ahmad, Arshad Javaid, Afsar Khan Afridi, Anila Basit, Amer Hayat Khan, Izaz Ahmad and Muhammad AtifAvailable online: 02 April 2018More LessTo evaluate the predictive value of time to sputum culture conversion (SCC) in predicting cure and factors associated with time to SCC and cure in multidrug-resistant tuberculosis (MDR-TB) patients, a retrospective study was conducted at programmatic management unit of drug resistant tuberculosis (TB), Peshawar. A total of 428 pulmonary MDR-TB patients enrolled at the study site from January 1, 2012 to August 31, 2014 were followed until treatment outcome was recorded. Survival analysis using Cox proportional hazards model and multivariate binary logistic regression were, respectively, used to identify factors associated with time to SCC and cure. A P value < 0.05 was considered statistically significant. Overall, 90.9% patients achieved SCC, and 76.9% were cured. Previous use of second-line drugs (SLDs) (hazard ratio [HR] = 0.637; 95% confidence interval [CI] = 0.429–0.947), ofloxacin resistance (HR = 0.656; 95% CI = 0.522–0.825) and lung cavitation (HR = 0.744; 95% CI = 0.595–0.931) were significantly associated with time to SCC. In predicting cure, sensitivities of SCC at 2, 4, and 6 months were 64.1% (95% CI = 58.69–69.32), 93.0% (95% CI = 89.69–95.52), and 97.6% (95% CI = 95.27–98.94), respectively, whereas specificities were 67.7% (95% CI = 57.53–76.73), 51.5% (95% CI = 41.25–61.68), and 44.4% (95% CI = 34.45–54.78), respectively. Furthermore, patients’ age of 41–60 (odds ratio [OR] = 0.202; 95% CI = 0.067–0.605) and > 60 years (OR = 0.051; 95% CI = 0.011–0.224), body weight > 40 kg (OR = 2.950; 95% CI = 1.462–5.952), previous SLD use (OR = 0.270; 95% CI = 0.097–0.789), lung cavitation (OR = 0.196; 95% CI = 0.103–0.371) and ofloxacin resistance (OR = 0.386; 95% CI = 0.198–0.749) were significantly associated with cure. Association of SCC with cure was substantially stronger at 6 months (OR = 32.10; 95% CI = 14.34–71.85) than at 4 months (OR = 14.13; 95% CI = 7.92–25.21). However in predicting treatment outcomes, the combined sensitivity and specificity of SCC at 4 months was comparable to SCC at 6 months. Patients with risk factors for delayed SCC were also at high risk of unsuccessful outcomes.
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Case Report: Paederus Dermatitis in the Returning Traveler
Authors: Jacob W. Pierce, Barry Rittman and Jillian E. RaybouldAvailable online: 02 April 2018More LessRash in the returned traveler can provide a diagnostic dilemma for clinicians, but a detailed history including epidemiologic exposures can allow prompt diagnosis of etiologies uncommon in the United States. One such disease is Paederus dermatitis, an irritant contact dermatitis related to exposure to the rove beetle characterized by bullous lesions with surrounding erythema. Although cases and outbreaks have commonly been reported throughout the world, they are rarely reported in travelers returning to the United States. Here, we describe a patient who presented to an academic medical center in Virginia after travel to Sierra Leone with clinical presentation including exposure history and histopathology consistent with Paederus dermatitis. Our patient’s clinic course is described in detail including treatment. Usual treatment includes antihistamines, topical steroids, and oral antibiotics, particularly with antimicrobials with activity against Pseudomonas sp. In addition, this case suggests a potential role for oral steroids in the treatment of this condition but further investigation is required. This case demonstrates the importance of considering a patient’s travel and exposure history, as well as having familiarity with disease processes common in other parts of the world that are rarely seen in the United States.
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Accuracy of the Lee–White Clotting Time Performed in the Hospital Routine to Detect Coagulopathy in Bothrops atrox Envenomation
Available online: 02 April 2018More LessSnake envenomation is a major public health problem in Brazil. Systemic complications that may arise from snakebites are mainly related to coagulopathy. The Lee–White clotting time (LWCT) is a simple and inexpensive test and available even in remote health facilities. However, the diagnostic value of such test needs to be evaluated to accurately diagnose coagulopathy in the clinical practice. This study aimed to assess the reliability of the LWCT performed in hospital routine to diagnose venom-induced coagulopathy. We studied 186 patients admitted at the Tropical Medicine Foundation Dr. Heitor Vieira Dourado in Manaus, Amazonas, Brazil, with Bothrops envenomation diagnosis. At admission, blood samples were collected for performing LWCT and the concentration of fibrinogen. Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios, diagnostic odds ratio, and accuracy were calculated with 95% confidence intervals. From the total, 85.5% had hypofibrinogenemia. The sensitivity of the LWCT to the diagnosis of hypofibrinogenemia was 78.0% and the specificity 40.7%. The accuracy of the test was 72.6%, and patients with a prolonged LWCT had 2.4 higher odds of developing hypofibrinogenemia. In addition, the LWCT was also compared with venom antigen levels and systemic hemorrhage. The LWCT showed moderate sensitivity to detect consumption coagulopathy and constitutes a valuable tool for the diagnosis of Bothrops snake envenomation and indication of antivenom therapy.
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Trends in Public and Global Health Education among Nationally Recognized Undergraduate Liberal Arts Colleges in the United States
Available online: 02 April 2018More LessThe prevalence of public health and global health (PH/GH) curricular offerings appear to be increasing in terms of undergraduate curricula and in the context of liberal arts education in the United States. Liberal arts colleges (LACs) represent stand-alone institutions, which exclusively focus on undergraduate education. The objective of this study was to assess the prevalence of PH/GH study pathways and PH/GH course offerings among LACs. All LACs identified through the US News and World Report (USNWR) college rankings were contacted with a survey about the following: formal majors, minors, or concentrations in PH/GH; independent study (IS) pathways for PH/GH; specific PH/GH courses offered; and the number of students graduating in 2016, 2017, and 2018 with formal and IS degrees in PH/GH. Demographic characteristics of the colleges came from the USNWR database. Almost half (43%) of all LACs in our sample offer a PH/GH major, minor, concentration, or IS pathway. Almost all (90%) colleges offer at least one course in PH/GH. Approximately 2,000 students attending these LACs pursued or are pursuing graduation with majors, minors, or concentrations in PH/GH for the years 2016–2018. The number of students pursuing formal PH/GH programs has increased by 25% from 2016 to 2018. Student interest in public health is rising in U.S. LACs, with more students seeking formal curricular or IS PH degree pathways. Public health messages are prevalent even among institutions without formal programs. Colleges without programs should consider integrating public health into their curriculum.
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Internally Controlled, Multiplex Real-Time Reverse Transcription PCR for Dengue Virus and Yellow Fever Virus Detection
Available online: 02 April 2018More LessThe differential diagnosis of dengue virus (DENV) and yellow fever virus (YFV) infections in endemic areas is complicated by nonspecific early clinical manifestations. In this study, we describe an internally controlled, multiplex real-time reverse transcription PCR (rRT-PCR) for the detection of DENV and YFV. The DENV–YFV assay demonstrated specific detection and had a dynamic range of 2.0–8.0 log10 copies/μL of eluate for each DENV serotype and YFV. Clinical performance was similar to a published pan-DENV assay: 48/48 acute-phase samples from dengue cases were detected in both assays. For YFV detection, mock samples were prepared with nine geographically diverse YFV isolates over a range of concentrations. The DENV–YFV assay detected 62/65 replicates, whereas 54/65 were detected using a reference YFV rRT-PCR. Given the reemergence of DENV and YFV in areas around the world, the DENV–YFV assay should be a useful tool to narrow the differential diagnosis and provide early case detection.
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Use of TaqMan Array Cards to Screen Outbreak Specimens for Causes of Febrile Illness in Tanzania
Available online: 02 April 2018More LessWe describe the deployment of a custom-designed molecular diagnostic TaqMan Array Card (TAC) to screen for 31 bacterial, protozoal, and viral etiologies in blood from outbreaks of acute febrile illness in Tanzania during 2015–2017. On outbreaks notified to the Tanzanian Ministry of Health, epidemiologists were dispatched and specimens were collected, transported to a central national laboratory, and tested by TAC within 2 days. This algorithm streamlined investigation, diagnosed a typhoid outbreak, and excluded dozens of other etiologies. This method is usable in-country and may be incorporated into algorithms for diagnosing outbreaks.
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Real-Time Modeling Should Be Routinely Integrated into Outbreak Response
Authors: Daniel G. Bausch and John EdmundsAvailable online: 02 April 2018More Less
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Detection of Immunoglobulin G Antibodies to Taenia solium Cysticercosis Antigen Glutathione-S-Transferase–rT24H in Malian Children Using Multiplex Bead Assay
Available online: 26 March 2018More LessBlood samples from 805 students attending 42 elementary schools in Mopti, Sikasso, and Koulikoro regions, and Bamako district in Mali participated in a school water, sanitation, and hygiene intervention. Immunoglobulin (Ig) G responses to several antigens/pathogens were assessed by a multiplex bead assay (MBA), and the recombinant Taenia solium T24H antigen was included. Of all students tested, 8.0% were positive to rT24H, but in some schools 25–30%. A cluster of 12 widespread school locations showed not only a relative risk of 3.23 for T. solium exposure and significantly higher IgG responses (P < 0.001) but also significantly lower elevation (P = 0.04) (m, above sea level) compared with schools outside the cluster. All schools at elevations < 425 m showed significantly higher IgG responses (P = 0.017) than schools at elevations ≥ 425 m. The MBA is an excellent serological platform that provides cost-effective opportunities to expand testing in serosurveys.
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Safe Water and Hygiene Integration with Human Immunodeficiency Virus and Antenatal Services: Leveraging Opportunities for Public Health Interventions and Improved Service Uptake
Available online: 26 March 2018More LessIntegrating public health interventions with antenatal clinic (ANC) visits may motivate women to attend ANC, thereby improving maternal and neonatal health, particularly for human immunodeficiency virus (HIV)-infected persons. In 2009, in an integrated ANC/Preventing Mother-to-Child Transmission program, we provided free hygiene kits (safe storage containers, WaterGuard water treatment solution, soap, and oral rehydration salts) to women at their first ANC visit and refills at subsequent visits. To increase fathers’ participation, we required partners’ presence for women to receive hygiene kits. We surveyed pregnant women at baseline and at 12-month follow-up to assess ANC service utilization, HIV counseling and testing (HCT), test drinking water for residual chlorine, and observe handwashing. We conducted in-depth interviews with pregnant women, partners, and health workers. We enrolled 106 participants; 97 (92%) were found at follow-up. During the program, 99% of pregnant women and their partners received HCT, and 99% mutually disclosed. Fifty-six percent of respondents had ≥ 4 ANC visits and 90% delivered at health facilities. From baseline to follow-up, the percentage of women who knew how to use WaterGuard (23% versus 80%, P < 0.0001), had residual chlorine in stored water (0% versus 73%, P < 0.0001), had confirmed WaterGuard use (0% versus 70%, P < 0.0003), and demonstrated proper handwashing technique (21% versus 64% P < 0.0001) increased. Program participants showed significant improvements in water treatment and hygiene, and high use of ANC services and HCT. This evaluation suggests that integration of hygiene kits, refills, and HIV testing during ANC is feasible and may help improve household hygiene and increase use of health services.
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Polymorphisms in the K13 Gene in Plasmodium falciparum from Different Malaria Transmission Areas of Kenya
Available online: 26 March 2018More LessThe development of artemisinin (ART)-resistant parasites in Southeast Asia (SEA) threatens malaria control globally. Mutations in the Kelch 13 (K13)-propeller domain have been useful in identifying ART resistance in SEA. ART combination therapy (ACT) remains highly efficacious in the treatment of uncomplicated malaria in Sub-Saharan Africa (SSA). However, it is crucial that the efficacy of ACT is closely monitored. Toward this effort, this study profiled the prevalence of K13 nonsynonymous mutations in different malaria ecological zones of Kenya and in different time periods, before (pre) and after (post) the introduction of ACT as the first-line treatment of malaria. Nineteen nonsynonymous mutations were present in the pre-ACT samples (N = 64) compared with 22 in the post-ACT samples (N = 251). Eight of these mutations were present in both pre- and post-ACT parasites. Interestingly, seven of the shared single-nucleotide polymorphisms were at higher frequencies in the pre-ACT than the post-ACT parasites. The A578S mutation reported in SSA and the V568G mutation reported in SEA were found in both pre- and post-ACT parasites, with their frequencies declining post-ACT. D584Y and R539K mutations were found only in post-ACT parasites; changes in these codons have also been reported in SEA with different amino acids. The N585K mutation described for the first time in this study was present only in post-ACT parasites, and it was the most prevalent mutation at a frequency of 5.2%. This study showed the type, prevalence, and frequency of K13 mutations that varied based on the malaria ecological zones and also between the pre- and post-ACT time periods.
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Vector-Borne Disease is a Common Cause of Hospitalized Febrile Illness in India
Authors: Matthew L. Robinson, Dileep Kadam, Sandhya Khadse, Usha Balasubramanian, Priyanka Raichur, Chhaya Valvi, Ivan Marbaniang, Savita Kanade, Jonathan Sachs, Anita Basavaraj, Renu Bharadwaj, Anju Kagal, Vandana Kulkarni, Jonathan Zenilman, George Nelson, Yukari C. Manabe, Aarti Kinikar, Amita Gupta and Vidya MaveAvailable online: 26 March 2018More LessAcute febrile illness (AFI) is a major cause of morbidity and mortality in India and other resource-limited settings, yet systematic etiologic characterization of AFI has been limited. We prospectively enrolled adults (N = 970) and children (age 6 months to 12 years, N = 755) admitted with fever from the community to Sassoon General Hospital in Pune, India, from July 2013 to December 2015. We systematically performed a standardized clinical history, clinical laboratories, and diagnostics. Results from additional testing ordered by treating clinicians were also recorded. A microbiological diagnosis was found in 549 (32%) participants; 211 (12%) met standardized case definitions for pneumonia and meningitis without an identified organism; 559 (32%) were assigned a clinical diagnosis in the absence of a confirmed diagnosis; and 406 (24%) had no diagnosis. Vector-borne diseases were the most common cause of AFI in adults including dengue (N = 188, 19%), malaria (N = 74, 8%), chikungunya (N = 15, 2%), and concurrent mosquito-borne infections (N = 23, 2%) occurring most frequently in the 3 months after the monsoon. In children, pneumonia was the most common cause of AFI (N = 214, 28%) and death. Bacteremia was found in 68 (4%) participants. Central nervous system infections occurred in 58 (6%) adults and 64 (8%) children. Etiology of AFI in India is diverse, highly seasonal, and difficult to differentiate on clinical grounds alone. Diagnostic strategies adapted for season and age may reduce diagnostic uncertainty and identify causative organisms in treatable, fatal causes of AFI.
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The Elderly Respond to Antimony Therapy for Cutaneous Leishmaniasis Similarly to Young Patients but Have Severe Adverse Reactions
Available online: 26 March 2018More LessThere is evidence that elderly patients with cutaneous leishmaniasis (CL) have more mucosal and disseminated diseases than young patients and their cells produce less antigen-induced interferon (IFN)-γ. Herein, we compared the roles of interleukin (IL)-10 and IL-15 as modulators of antigen-induced immune responses and the incidence of adverse reaction and response to therapy in young versus elderly patients with CL. Study participants included 35 senior (60–85 years) and 35 young (18–40 years) patients who had a diagnosis of CL documented by typical cutaneous lesions containing Leishmania braziliensis DNA. Elderly patients had less lymph node enlargement. Antigen-induced blood cell cytokine responses were studied in the absence or presence of IL-10 Ab or exogenously added recombinant IL-15. The ratio of IFN-γ/IL-10 was lower in elderly patients, and IFN-γ production was enhanced by either neutralization of IL-10 or exogenous recombinant IL-15 in blood cells from elderly but not young patients. Patients were treated three times weekly with antimony at 20 mg/kg/day for 20 doses. Although there was no difference in response to therapy between the two groups, two young patients needed rescue therapy with amphotericin B. Ventricular arrhythmias and ventricular overload were more frequent in elderly patients. We conclude that elderly patients have alterations in the immune response that may influence clinical manifestations, but we did not find that they had a higher failure rate than young subjects to antimony therapy. However, because of the high rate of electrocardiographic abnormalities during therapy, antimony should not be used in elderly patients with CL.
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Seroprevalence of Hepatitis A Virus, Hepatitis E Virus, and Helicobacter pylori in Rural Communities of the Bolivian Chaco, 2013
Available online: 26 March 2018More LessIn the Bolivian Chaco, south-east of Bolivia, studies conducted over the past three decades reported hepatitis A virus (HAV) and Helicobacter pylori seroprevalences above 90% and 60%, respectively. Hepatitis E virus (HEV) prevalence was previously found to be 6–7% but is probably an underestimate because of the poor sensitivity of the assays used. In November 2013, we conducted a cross-sectional study of 263 healthy volunteers from two rural communities of the Bolivian Chaco, aiming to reassess HAV, HEV, and H. pylori seroprevalence 10–20 years following the previous surveys. Hepatitis A virus seroprevalence was 95%, with universal exposure after the first decade of life; HEV seroprevalence was considerably higher (31–35%) than that previously reported; H. pylori seroprevalence was 59%, with an age-dependent distribution. The high prevalence of these infections suggests that major efforts are still needed to reduce fecal–oral transmission and to improve human health in the Bolivian Chaco.
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Case Report: Diffuse Cutaneous Leishmaniasis by Leishmania infantum in a Patient Undergoing Immunosuppressive Therapy: Risk Status in an Endemic Mediterranean Area
Available online: 26 March 2018More LessThis case report highlights the risk of severe cutaneous leishmaniasis (CL) by Leishmania infantum in patients undergoing immunosuppressant therapy who either live in an endemic area or are visiting in the transmission season. The case patient, resident in Majorca (Balearic Islands), presented 12 disseminated erythematous skin lesions, 1–6 cm in diameter, located on the scalp, cheek, umbilical region, and lower extremities 8 years after undergoing anti–tumor necrosis factor (TNF) therapy. Parasite presence in peripheral blood and high levels of specific antibodies were also observed, indicating a possible risk of CL shifting toward a visceral infection. However, once CL was diagnosed, anti-TNF therapy was discontinued and liposomal amphotericin B was administered, resulting in a complete healing of lesions, no Leishmania DNA detection in blood, and an important serological decrease in antibodies. The lack of data on the supposed epidemiological association between leishmaniasis and immunosuppressive therapy highlights the importance of implementing surveillance systems in endemic areas. No obvious relationship was found based on the data provided by the Balearic Islands Epidemiological System, in contrast with data reported in nearby endemic areas. This indicates that if the suspected association is to be clarified, greater efforts are needed to report information about concomitant diseases and therapies in leishmaniasis patients.
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Knowledge of Norovirus and Attitudes toward a Potential Norovirus Vaccine in Rural Guatemala: A Cross-Sectional Exploratory Survey
Authors: Daniel Olson, Steven Krager, Molly Lamb, Anne-Marie Rick and Edwin J. AsturiasAvailable online: 26 March 2018More LessGiven limited data on norovirus vaccine acceptance, we performed an exploratory survey in a rural Guatemalan community on knowledge, interest, and willingness to pay (WTP) for a norovirus vaccine. Cluster-randomized households with children aged 6 weeks to 17 years were enrolled into one of two norovirus surveillance studies: 1) a prospective cohort (N = 207 households) and 2) two separate, community-based, cross-sectional surveys (N = 420 households). After completion of the surveillance study, vaccine surveys were completed by 564 (90%) of 627 households. Most households correctly answered questions regarding norovirus symptoms and transmission; 97% indicated interest in a hypothetical norovirus vaccine. Households with higher education had greater WTP for a vaccine (prevalence ratios = 2.2, 95% confidence interval: 1.2–3.1) and households with lower WTP were more likely to use pharmacies, the Ministry of Health, and radios for health care and information. These results suggest that a future norovirus vaccination program could be acceptable and feasible even in rural areas.
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Molecular Markers of Plasmodium falciparum Drug Resistance in Parasitemic Pregnant Women in the Middle Forest Belt of Ghana
Authors: Joseph Osarfo, Harry Tagbor, Pascal Magnussen and Michael AlifrangisAvailable online: 26 March 2018More LessData on prevalence of antimalarial molecular resistance markers in pregnant women in Ghana is scarce. Prevalence of single nucleotide polymorphisms/haplotypes in the Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps genes was assessed in a cross-sectional study involving 200 pregnant women. Almost 90% of infections were wild type at the Pfcrt gene whereas the Pfmdr1 NFD mutant haplotype occurred in 43% of samples. Prevalence of Pfdhfr/Pfdhps quadruple mutation was 92.6% whereas Pfdfr/Pfdhps quintuple mutation with K540E was not observed. The study provides important updates of antimalarial resistance markers in Ghanaian pregnant women and suggests increased tolerance to one of the first-line treatment options in Ghana: artemether–lumefantrine. The data support the view that sulfadoxine–pyrimethamine is still efficacious for intermittent preventive treatment in Ghana, but the impact of increased doses on selection of mutations needs to be assessed. Continuing the surveillance of resistance markers is important to inform changes in antimalarial drug policy in pregnancy.
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A Revival of Epidemiological Entomology in Senegal
Author: Gerry F. KilleenAvailable online: 26 March 2018More LessThe term epidemiological entomology was first coined by Garrett-Jones over half a century ago1 but has been out of fashion for far too long.2 In this issue, Sougoufara et al.3 illustrate clearly just how insightful such an approach can be when applied to characterizing key properties of a dynamic malaria transmission system before and after the scale-up of vector control with long-lasting insecticidal nets in Dielmo, Senegal. Using simple analytical models first pioneered by Garrett-Jones himself,4 these authors illustrate how not all may be as it appears based on direct interpretation of entomological data alone. Allowing for the fact that malaria transmission requires both humans and mosquitoes to meet at the same time and place, they show that insecticidal bed nets failed to provide direct personal protection against more than one-third of inoculation events at the outset. Even more worryingly, they demonstrate that this gap in personal protection is growing as mosquitoes adapt to bed nets as a normal part of their environment.
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The Impact of Periodic Distribution Campaigns of Long-Lasting Insecticidal-Treated Bed Nets on Malaria Vector Dynamics and Human Exposure in Dielmo, Senegal
Available online: 19 March 2018More LessThe implementation of long-lasting insecticidal-treated bed nets (LLINs) has contributed to halving the mortality rate due to malaria since 2000 in sub-Saharan Africa. These tools are highly effective against indoor-feeding malaria vectors. Thus, to achieve the World Health Assembly’s new target to reduce the burden of malaria over the next 15 years by 90%, it is necessary to understand how the spatiotemporal dynamics of malaria vectors and human exposure to bites is modified in the context of scaling up global efforts to control malaria transmission. This study was conducted in Dielmo, a Senegalese village, after the introduction of LLINs and two rounds of LLINs renewals. Data analysis showed that implementation of LLINs correlated with a significant decrease in the biting densities of the main malaria vectors, Anopheles gambiae s.l. and Anopheles funestus, reducing malaria transmission. Other environment factors likely contributed to the decrease in An. funestus, but this trend was enhanced with the introduction of LLINs. The bulk of bites occurred during sleeping hours, but the residual vector populations of An. gambiae s.l. and An. funestus had an increased propensity to bite outdoors, so a risk of infectious bites remained for LLINs users. These results highlight the need to increase the level and correct use of LLINs and to combine this intervention with complementary control measures against residual exposure, such as spatial repellents and larval source management, to achieve the goal of eliminating malaria transmission.
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Antibiotic Residues in Milk from Three Popular Kenyan Milk Vending Machines
Authors: Amos Kosgey, Anakalo Shitandi and Jason W. MarionAvailable online: 19 March 2018More LessMilk vending machines (MVMs) are growing in popularity in Kenya and worldwide. Milk vending machines dispense varying quantities of locally sourced, pasteurized milk. The Kenya Dairy Board has a regulatory framework, but surveillance is weak because of several factors. Milk vending machines’ milk is not routinely screened for antibiotics, thereby increasing potential for antibiotic misuse. To investigate, a total of 80 milk samples from four commercial providers (N = 25), street vendors (N = 21), and three MVMs (N = 34) were collected and screened in Eldoret, Kenya. Antibiotic residue surveillance occurred during December 2016 and January 2017 using Idexx SNAP tests for tetracyclines, sulfamethazine, beta-lactams, and gentamicin. Overall, 24% of MVM samples and 24% of street vendor samples were presumably positive for at least one antibiotic. No commercial samples were positive. Research into cost-effective screening methods and increased monitoring by food safety agencies are needed to uphold HAACP for improving antibiotic stewardship throughout the Kenyan private dairy industry.
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What It Means to Be Guinea Worm Free: An Insider’s Account from Ghana’s Northern Region
Available online: 19 March 2018More LessDespite several periods of stagnating guinea worm disease (GWD) incidence in Ghana during its national eradication campaign in the 1990s and early 2000s, the last reported case of GWD was in May 2010. In July 2011, Ghana celebrated the interruption of guinea worm (GW) transmission. Although it has been established that GWD causes disability, pain, and socioeconomic hardship, there is a dearth of population-based evidence collected in post-GW–endemic countries to document the value attributed to GWD eradication by residents in formerly endemic communities. Given Ghana’s recent history of GWD and a concentrated burden of the disease in its Northern Region, a pattern which remained true through to the final stage of the eradication campaign, seven villages in the Northern Region were targeted for a retrospective, cross-sectional study to detail the perceptions, attitudes, and beliefs about the impact of eradication of GWD in northern Ghana. The study revealed that respondents from the sampled communities felt GW eradication improved their socioeconomic conditions, as the impact of infection prohibited the pursuit of individual and social advancement. The value residents placed on the absence of GWD highlights both the impact infection had on the pursuit of social and economic advancement and the newfound ability to be disease-free and productive. Of the 143 respondents, 133 had GWD in the past and were incapacitated for an average of 6 weeks annually per GW infection, with each infected person affected nearly four times in his or her lifetime.
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Dengue Fever as an Emerging Infection in Southeast Iran
Available online: 19 March 2018More LessDengue fever (DF) is a mosquito-borne acute viral disease presenting with hemorrhagic manifestations in severe cases. Southeast Iran is in close proximity to Pakistan, an endemic country for DF. This cross-sectional study was conducted in the Sistan and Baluchestan province in the southeast of Iran to investigate possibility of DF (immunoglobulin M [IgM], immunoglobulin G [IgG], and nonstructural protein 1 [NS1] antigen tests) in 60 clinically suspected patients (April 2013 to August 2015). NS1 protein was detected in 5% (N = 3), at least one of the antibodies (IgM and/ or IgG) was detected in 11% (N = 7) of the samples. Five patients identified as of acutely infected. There was a simultaneous presence of NS1 protein and IgG or IgM antibodies in 4% (N = 2) of patients. Previous studies show establishment of potential vectors in this area. These evidences support the hypothesis that DF can be a health concern in Southeast Iran with potential future outbreaks.
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Within-Compound Versus Public Latrine Access and Child Feces Disposal Practices in Low-Income Neighborhoods of Accra, Ghana
Available online: 19 March 2018More LessIn crowded urban settlements in low-income countries, many households rely on shared sanitation facilities. Shared facilities are not currently considered “improved sanitation” because of concerns about whether hygiene conditions sufficiently protect users from the feces of others. Prevention of fecal exposure at a latrine is only one aspect of sanitary safety. Ensuring consistent use of latrines for feces disposal, especially child feces, is required to reduce fecal contamination in households and communities. Household crowding and shared latrine access are correlated in these settings, rendering latrine use by neighbors sharing communal living areas as critically important for protecting one’s own household. This study in Accra, Ghana, found that household access to a within-compound basic latrine was associated with higher latrine use by children of ages 5–12 years and for disposal of feces of children < 5 years, compared with households using public latrines. However, within-compound access was not associated with improved child feces disposal by other caregivers in the compound. Feces was rarely observed in household compounds but was observed more often in compounds with latrines versus compounds relying on public latrines. Escherichia coli and human adenovirus were detected frequently on household surfaces, but concentrations did not differ when compared by latrine access or usage practices. The differences in latrine use for households sharing within-compound versus public latrines in Accra suggest that disaggregated shared sanitation categories may be useful in monitoring global progress in sanitation coverage. However, compound access did not completely ensure that households were protected from feces and microbial contamination.
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Barriers and Opportunities to Advancing Women in Leadership Roles in Vector Control: Perspectives from a Stakeholder Survey
Available online: 19 March 2018More LessIncreasing the active participation of professional women in vector control (VC) activities may help promote greater gender equity in the workplace and reduce the burden of vector-borne diseases. This stakeholder survey examined the current roles and perspective of professionals employed in the VC sector in Kenya, Indonesia, India, and other countries. The largest barriers that women face in pursuing leadership roles in the VC sector include lack of awareness of career opportunities, limitations based on cultural norms, and the belief that VC is men’s work. These barriers could be addressed through improving education and recruitment campaigns, as well as supporting higher education and mentoring programs. Females were almost six times more likely to be encouraged to pursue leadership positions in their organization compared with male respondents (OR = 5.9, P > 0.03, 95% confidence interval: 1.19, 29.42). These findings suggest that once women are recruited into the VC workforce, they face minimal discrimination and have increased leadership opportunities.
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Use of Rapid Enzyme-Linked Immunosorbent Assay for Serological Screening of Melioidosis in Myanmar
Available online: 19 March 2018More LessBurkholderia pseudomallei, the etiologic agent of melioidosis, is an important but under-recognized cause of disease in the tropics. Although first described over a century ago as a septicemic illness associated with morphine addicts in Rangoon, Burma, there is little information regarding the incidence of melioidosis in present-day Myanmar. To address this issue, we used two recently developed and validated serological assays to detect B. pseudomallei–specific antibodies in 124 serum samples obtained from febrile patients in the delta region of Myanmar. Using cutoff values derived from culture-confirmed melioidosis cases in neighboring Thailand, 3.2% of the samples exhibited reactivity profiles consistent with active B. pseudomallei infections. Collectively, these findings indicate that melioidosis likely represents a significant cause of morbidity and mortality in Myanmar and support the need for further studies to assess the true burden of disease in this country.
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Yemen in a Time of Cholera: Current Situation and Challenges
Author: Hesham M. Al-MekhlafiAvailable online: 19 March 2018More LessSince early 2015, Yemen has been in the throes of a grueling civil war, which has devastated the health system and public services, and created one of the world’s worst humanitarian disasters. The country is currently facing a cholera epidemic the world’s largest on record, surpassing one million (1,061,548) suspected cases, with 2,373 related deaths since October 2016. Cases were first confirmed in Sana’a city and then spread to almost all governorates except Socotra Island. Continued efforts are being made by the World Health Organization and international partners to contain the epidemic through improving water, sanitation and hygiene, setting up diarrhea treatment centers, and improving the population’s awareness about the disease. The provision of clean water and adequate sanitation is imperative as an effective long-term solution to prevent the further spread of this epidemic. Cholera vaccination campaigns should also be conducted as a preventive measure.
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Food Insecurity as a Risk Factor for Outcomes Related to Ebola Virus Disease in Kono District, Sierra Leone: A Cross-Sectional Study
Available online: 19 March 2018More LessStudies have shown that people suffering from food insecurity are at higher risk for infectious and noncommunicable diseases and have poorer health outcomes. No study, however, has examined the association between food insecurity and outcomes related to Ebola virus disease (EVD). We conducted a cross-sectional study in two Ebola-affected communities in Kono district, Sierra Leone, from November 2015 to September 2016. We enrolled persons who were determined to have been exposed to Ebola virus. We assessed the association of food insecurity, using an adapted version of the Household Food Insecurity Access Scale, a nine-item scale well validated across Africa, with having been diagnosed with EVD and having died of EVD, using logistic regression models with cluster-adjusted standard errors. We interviewed 326 persons who were exposed to Ebola virus; 61 (19%) were diagnosed with EVD and 45/61 (74%) died. We found high levels (87%) of food insecurity, but there was no association between food insecurity and having been diagnosed with EVD. Among EVD cases, those who were food insecure had 18.3 times the adjusted odds of death than those who were food secure (P = 0.03). This is the first study to demonstrate a potential relationship between food insecurity and having died of EVD, although larger prospective studies are needed to confirm these findings.
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Insights into the Performance of SD Bioline Malaria Ag P.f/Pan Rapid Diagnostic Test and Plasmodium falciparum Histidine-Rich Protein 2 Gene Variation in Madagascar
Available online: 19 March 2018More LessPlasmodium falciparum histidine-rich protein 2 (PfHRP2) forms the basis of many current malaria rapid diagnostic tests (RDTs). However, the parasites lacking part or all of the pfhrp2 gene do not express the PfHRP2 protein and are, therefore, not identifiable by PfHRP2-detecting RDTs. We evaluated the performance of the SD Bioline Malaria Ag P.f/Pan RDT together with pfhrp2 variation in Madagascar. Genomic DNA isolated from 260 patient blood samples were polymerase chain reaction (PCR)–amplified for the parasite 18S rRNA and pfhrp2 genes. Post-PCR ligation detection reaction-fluorescent microsphere assay (LDR-FMA) was performed for the identification of parasite species. Plasmodium falciparum histidine-rich protein 2 amplicons were sequenced. Polymerase chain reaction diagnosis of patient samples showed that 29% (75/260) were infected and P. falciparum was present in 95% (71/75) of these PCR-positive samples. Comparing RDT and P. falciparum detection by LDR-FMA, eight samples were RDT negative but P. falciparum positive (false negatives), all of which were pfhrp2 positive. The sensitivity and specificity of the RDT were 87% and 90%, respectively. Seventy-three samples were amplified for pfhrp2, from which nine randomly selected amplicons were sequenced, yielding 13 sequences. Amplification of pfhrp2, combined with RDT analysis and P. falciparum detection by LDR-FMA, showed that there was no indication of pfhrp2 deletion. Sequence analysis of pfhrp2 showed that the correlation between pfhrp2 sequence structure and RDT detection rates was unclear. Although the observed absence of pfhrp2 deletion from the samples screened here is encouraging, continued monitoring of the efficacy of the SD Bioline Malaria Ag P.f/Pan RDT for malaria diagnosis in Madagascar is warranted.
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Development of Visually Improved Loop Mediated Isothermal Amplification for the Diagnosis of Plasmodium vivax Malaria in a Tertiary Hospital in Chandigarh, North India
Authors: Hargobinder Kaur, Rakesh Sehgal, Devendra Bansal, Ali A. Sultan, Ashish Bhalla and Sunit C. SinghiAvailable online: 19 March 2018More LessMore than 80% of the global burden of the Plasmodium vivax is contributed by mainly three countries (India, Indonesia, and Pakistan). Reports from last decades have highlighted the occurrence of severe P. vivax malaria which was earlier considered to be benign. The recent trends of increasing P. vivax–associated morbidity and mortality emphasizes the need for early and accurate diagnosis of P. vivax malaria for the timely management of patients. Microscopy is considered a gold standard but needs experienced laboratory technologists. Over the last few years, Polymerase chain reaction (PCR) is being used as a highly sensitive and specific test but it requires expensive equipment which limits its use in the field. Therefore, in the present study, utility of visually improved loop-mediated isothermal amplification (LAMP) for the detection of P. vivax was evaluated targeting 18SrRNA gene in 145 microscopically confirmed P. vivax and 20 P. vivax negative patients. Sensitivity and specificity of LAMP was assessed with respect to microscopy and multiplex nested PCR (nPCR). Results of the LAMP assay was also correlated with rapid diagnostic test, multiplex nPCR and real-time PCR results. Overall, sensitivity and specificity of P. vivax–specific LAMP compared with microscopy were found to be 100% and 85%, respectively. Furthermore, detection limit for LAMP was found to be 0.8 copies/μL and it was also able to detect three complicated cases of P. vivax which were missed by microscopy. This study showed a LAMP assay to be a rapid and very sensitive method for the early diagnosis of both complicated and uncomplicated P. vivax malaria.
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Efficiency of a Malaria-Reactive Test-and-Treat Program in Southern Zambia: A Prospective, Observational Study
Available online: 19 March 2018More LessTo improve malaria surveillance and achieve elimination, the Zambian National Malaria Elimination Program implemented a reactive test-and-treat program in Southern Province in 2013 in which individuals with rapid diagnostic test (RDT)–confirmed malaria are followed-up at their home within 1 week of diagnosis. Individuals present at the index case household and those residing within 140 m of the index case are tested with an RDT and treated with artemether–lumefantrine if positive. This study evaluated the efficiency of this reactive test-and-treat strategy by characterizing infected individuals missed by the RDT and the current screening radius. The radius was expanded to 250 m, and a quantitative polymerase chain reaction (qPCR) test was performed on dried blood spot specimens. From January 2015 through March 2016, 145 index cases were identified at health centers and health posts. A total of 3,333 individuals residing in 525 households were screened. Excluding index cases, the parasite prevalence was 1.1% by RDT (33 positives of 3,016 participants) and 2.4% by qPCR (73 positives of 3,016 participants). Of the qPCR-positive cases, 62% of 73 individuals tested negative by RDT. Approximately half of the infected individuals resided within the index case household (58% of RDT-positive individuals and 48% of qPCR-positive individuals). The low sensitivity of the RDT and the high proportion of secondary cases within the index case household decreased the efficiency of this reactive test-and-treat strategy. Reactive focal drug administration in index case households would be a more efficient approach to treating infected individuals associated with a symptomatic case.
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Mosquito-Borne Human Viral Diseases: Why Aedes aegypti?
Author: Jeffrey R. PowellAvailable online: 19 March 2018More LessAlthough numerous viruses are transmitted by mosquitoes, four have caused the most human suffering over the centuries and continuing today. These are the viruses causing yellow fever, dengue, chikungunya, and Zika fevers. Africa is clearly the ancestral home of yellow fever, chikungunya, and Zika viruses and likely the dengue virus. Several species of mosquitoes, primarily in the genus Aedes, have been transmitting these viruses and their direct ancestors among African primates for millennia allowing for coadaptation among viruses, mosquitoes, and primates. One African primate (humans) and one African Aedes mosquito (Aedes aegypti) have escaped Africa and spread around the world. Thus it is not surprising that this native African mosquito is the most efficient vector of these native African viruses to this native African primate. This makes it likely that when the next disease-causing virus comes out of Africa, Ae. aegypti will be the major vector to humans.
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Eastern Equine Encephalitis Virus in the United States, 2003–2016
Authors: Nicole P. Lindsey, J. Erin Staples and Marc FischerAvailable online: 19 March 2018More LessEastern equine encephalitis virus (EEEV) is a mosquito-borne alphavirus found in the eastern United States. Eastern equine encephalitis virus disease in humans is rare but can result in severe, often fatal, illness. This report summarizes the national EEEV surveillance data for 2003 through 2016, including human disease cases and nonhuman infections. Over the 14-year period, 633 counties from 33 states reported EEEV activity; 88% of those counties reported EEEV activity only in nonhuman species. A total of 121 human cases of EEEV disease were reported, with a median of eight cases reported annually. The national average annual incidence of EEEV neuroinvasive disease was 0.03 cases per million population. States with the highest average annual incidence included New Hampshire, Massachusetts, Vermont, Maine, and Alabama. Eastern equine encephalitis virus neuroinvasive disease incidence was highest among males and among persons aged < 5 and > 60 years. Overall, 118 (98%) case patients were hospitalized and 50 (41%) died. The case fatality ratio was highest among case patients aged ≥ 70 years. Nonhuman surveillance data indicate that the geographic range of EEEV is much greater than human cases alone might suggest. In areas where the virus circulates, health-care providers should consider EEEV infection in the differential diagnosis for meningitis and encephalitis. Providers are encouraged to report suspected cases to their public health department to facilitate diagnosis and consider interventions to mitigate the risk of further transmission. Because human vaccines against EEEV are not available, prevention depends on community efforts to reduce mosquito populations and personal protective measures to decrease exposure to mosquitoes.
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Dengue Virus Infection in Aedes albopictus during the 2014 Autochthonous Dengue Outbreak in Tokyo Metropolis, Japan
Available online: 19 March 2018More LessIn 2014 in Japan, 162 autochthonous dengue cases were reported for the first time in nearly 70 years. Here, we report the results of the detection and isolation of dengue virus (DENV) from mosquitoes collected in Tokyo Metropolis in 2014 and 2015. The phylogenetic relationship among DENV isolates from mosquitoes and from patients based on both the entire envelope gene and whole coding sequences was evaluated. Herein, 2,298 female and 956 male Aedes albopictus mosquitoes were collected at six suspected locations of DENV infection in Tokyo Metropolis from August to October in 2014 and grouped into 124 and 35 pools, respectively, for viral genome detection and DENV isolation. Dengue virus RNA was detected using reverse transcription polymerase chain reaction and TaqMan assays from 49 female pools; 16 isolates were obtained using C6/36 and Vero cells. High minimum infection rates (11.2–66.7) persisted until mid-September. All DENV isolates belonged to the genotype I in serotype 1 (DENV-1), and its sequences demonstrated > 99% homology to the sequence of the DENV isolated from a patient in the vicinity of Tokyo Metropolis in 2014. Therefore, Ae. albopictus was a major DENV vector, and a single DENV-1 strain circulated in Tokyo Metropolis in 2014. Dengue virus was not detected from male mosquitoes in 2014 and wild larvae in April 2015. Thus, the possibility of both vertical transmission and overwintering of DENV was extremely low, even in dengue-epidemic areas. This study reports the first entomological information on a dengue outbreak in a temperate region, where no Aedes aegypti mosquitoes are distributed.
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Association between Severe Fever with Thrombocytopenia Syndrome Incidence and Ambient Temperature
Available online: 19 March 2018More LessSevere fever with thrombocytopenia syndrome (SFTS) is emerging in China. To explore the lagged effects and nonlinear association between temperature and SFTS, we collected data on ambient temperature and SFTS cases and analyzed the data using a distributed lag nonlinear model. A total of 1,933 SFTS cases were reported in the study area from 2011 to 2015. Our study revealed a nonlinear relationship between weekly temperature and SFTS. The exposure–response curve was an approximately reversed U-shaped peak at 23°C. High temperatures had acute and short-term effects, whereas low temperatures had persistent and long-term effects. The effects of lower temperatures (1.62°C and 6.97°C) could last 24 weeks, but the effect of 29.30°C was not significant at lag 8 weeks. Our results provide information to better understand the effect of temperature variation on SFTS and may have policy implications for disease prevention and control.
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Characterization of Plasmodium Lactate Dehydrogenase and Histidine-Rich Protein 2 Clearance Patterns via Rapid On-Bead Detection from a Single Dried Blood Spot
Available online: 19 March 2018More LessA rapid, on-bead ELISA for Plasmodium lactate dehydrogenase (pLDH) and Plasmodium falciparum histidine-rich protein 2 (HRP2) was adapted for use with dried blood spot (DBS) samples. This assay detected both biomarkers from a single DBS sample with only 45 minutes of total incubation time and detection limits of 600 ± 500 pM (pLDH) and 69 ± 30 pM (HRP2), corresponding to 150 and 24 parasites/μL, respectively. This sensitive and reproducible on-bead detection method was used to quantify pLDH and HRP2 in patient DBS samples from rural Zambia collected at multiple time points after treatment. Biomarker clearance patterns relative to parasite clearance were determined; pLDH clearance followed closely with parasite clearance, whereas most patients maintained detectable levels of HRP2 for 35–52 days after treatment. Furthermore, weak-to-moderate correlations between biomarker concentration and parasite densities were found for both biomarkers. This work demonstrates the utility of the developed assay for epidemiological study and surveillance of malaria.
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Continued Need for Comprehensive Genetic and Phenotypic Characterization of Viruses: Benefits of Complementing Sequence Analyses with Functional Determinations
Authors: Aaron C. Brault and Bradley J. BlitvichAvailable online: 19 March 2018More LessThe expanded use of next generation sequencing tools has led to an explosion in the rate of discovery of novel viral agents and has had a measured effect on the capacity to genetically identify the presence of previously described viruses in new geographic environments and within different hosts and vectors. For example, more than 30 flaviviruses (Flavivirus; Flaviviridae) with the capacity to infect only mosquitoes have been described in the last 10 years. By contrast, only two such viruses had been described in the previous 33 years.1 This burgeoning expansion of the known virome has largely outpaced the scientific capacity for characterizing these agents in any detail. Furthermore, many of the methodologies used for rapid genetic detection (such as placing mosquitoes directly in nucleic acid extraction buffers and the use of FTA cards for blood samples) preclude the isolation of the agents.
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Leptospirosis Outbreak After the 2014 Major Flooding Event in Kelantan, Malaysia: A Spatial-Temporal Analysis
Available online: 12 March 2018More LessSevere floods increase the risk of leptospirosis outbreaks in endemic areas. This study determines the spatial-temporal distribution of leptospirosis in relation to environmental factors after a major flooding event in Kelantan, Malaysia. We conducted a cross-sectional study involving incident leptospirosis cases, from the 3 months before, during, and three months after flood, in reference to the severe 2014 Kelantan flooding event. Geographical information system was used to determine the spatial distribution while climatic factors that influenced the cases were also analyzed. A total of 1,229 leptospirosis cases were notified within the three study periods where incidence doubled in the postflood period. Twelve of 78 subdistricts recorded incidence rates of over 100 per 100,000 population in the postflood periods, in comparison with only four subdistricts in the preflooding period. Average nearest neighborhood indicated that the cases were more clustered in the postflood period as compared with the preflood period, with observed mean distance of 1,138.8 meters and 1,665.7 meters, respectively (both at P < 0.01). Global Moran’s I was higher in the postflooding period (0.19; P < 0.01) as compared with the preflood period (0.06; P < 0.01). Geographic weighted regression showed that living close to water bodies increased the risk of contracting the disease. Postflooding hotspots were concentrated in areas where garbage cleanup occurred and the incidence was significantly associated with temperature, humidity, rainfall, and river levels. Leptospirosis outbreak postflooding was associated with several factors. Understanding the spatial distribution and associated factors of leptospirosis can help improve future disease outbreak management after the floods.
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Detection of Histoplasma capsulatum in Organic Fertilizers by Hc100 Nested Polymerase Chain Reaction and Its Correlation with the Physicochemical and Microbiological Characteristics of the Samples
Available online: 12 March 2018More LessHistoplasma capsulatum is the causative agent of histoplasmosis and this fungus inhabits soils rich in phosphorus and nitrogen that are enriched with bird and bat manure. The replacement of organic matter in agroecosystems is necessary in the tropics, and the use of organic fertilizers has increased. Cases and outbreaks due to the presence of the fungus in these components have been reported. The Instituto Colombiano Agropecuario resolution 150 of 2003 contains the parameters set by the Colombian Technical Standard (NTC 5167) on the physicochemical and microbiological features of fertilizers, but it does not regulate the search for H. capsulatum. The aim of this study was to demonstrate H. capsulatum presence in organic fertilizers by nested polymerase chain reaction (PCR). A total of 239 samples were collected: 201 (84.1%) corresponded to organic fertilizers, 30 (12.5%) to bird excrement, and 8 (3.4%) to cave soils. The Hc100 nested PCR had a detection limit of 0.1 pg/µL and a specificity of 100%. A total of 25 (10.5%) samples were positive and validated by sequencing. Seven of the positive samples represented locations where H. capsulatum was previously detected, suggesting the persistence of the fungus. No significant correlations were detected between the physicochemical and microbiological parameters with the presence of H. capsulatum by nested PCR, indicating the fungus existence in organic fertilizers that complied with the NTC 5167. The Hc100 nested PCR targeting H. capsulatum standardized in this work will improve the evaluation of organic fertilizers and ensure the prevention of outbreaks and cases due to manufacturing, marketing, and use of fertilizers contaminated with H. capsulatum.
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Challenges and Opportunities in Disease Forecasting in Outbreak Settings: A Case Study of Measles in Lola Prefecture, Guinea
Available online: 12 March 2018More LessWe report on and evaluate the process and findings of a real-time modeling exercise in response to an outbreak of measles in Lola prefecture, Guinea, in early 2015 in the wake of the Ebola crisis. Multiple statistical methods for the estimation of the size of the susceptible (i.e., unvaccinated) population were applied to weekly reported measles case data on seven subprefectures throughout Lola. Stochastic compartmental models were used to project future measles incidence in each subprefecture in both an initial and a follow-up iteration of forecasting. Measles susceptibility among 1- to 5-year-olds was estimated to be between 24% and 43% at the beginning of the outbreak. Based on this high baseline susceptibility, initial projections forecasted a large outbreak occurring over approximately 10 weeks and infecting 40 children per 1,000. Subsequent forecasts based on updated data mitigated this initial projection, but still predicted a significant outbreak. A catch-up vaccination campaign took place at the same time as this second forecast and measles cases quickly receded. Of note, case reports used to fit models changed significantly between forecast rounds. Model-based projections of both current population risk and future incidence can help in setting priorities and planning during an outbreak response. A swiftly changing situation on the ground, coupled with data uncertainties and the need to adjust standard analytical approaches to deal with sparse data, presents significant challenges. Appropriate presentation of results as planning scenarios, as well as presentations of uncertainty and two-way communication, is essential to the effective use of modeling studies in outbreak response.
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Water, Sanitation and Hygiene Practices Associated with Nutritional Status of Under-Five Children in Semi-Pastoral Communities Tanzania
Authors: Hoyce Amini Mshida, Neema Kassim, Emmanuel Mpolya and Martin KimanyaAvailable online: 12 March 2018More LessUndernutrition among under-five children is a public health concern in developing countries and has been linked with poor water, sanitation and hygiene (WASH) practices. This study aimed at assessing WASH practices and its association with nutritional status of under-five children in semi-pastoral communities of Arusha. The study was cross-sectional in design. Mother–child pairs from 310 households in four villages of Monduli and Longido were involved. Weight and height of children were measured using weighing scale and length/height board, respectively. Children’s age was recorded using clinic cards. Hemoglobin level of each child was tested using Hemo Cue® Hb 201 + photometer (AB, Sweden) machine. Structured questionnaire was used to gather information on WASH, child morbidity, demographic, and sociocultural characteristics. Prevalence of stunted, underweight, wasted, anemia, and diarrhea were 31.6%, 15.5%, 4.5% 61.2%, and 15.5%, respectively. Children with diarrhea 2 weeks preceding the survey (P = 0.004), children using surface water for domestic purposes (P < 0.001), and those with uneducated mothers (P = 0.001) had increased risk of being stunted and underweight. Children introduced to complementary foods before 6 months of age (P = 0.02) or belonging to polygamous families (P = 0.03) had increased risk of being stunted. Consumption of cow’s milk that is not boiled (P = 0.05) or being a boy (P = 0.03) was associated with underweight. Prevalence of undernutrition among under-five children in the population under study was alarming and it could be associated with poor WASH practices and other sociocultural factors. This study underlines the importance of incorporating WASH strategies in formulation of interventions targeting on promotion of nutrition and disease prevention in pastoral communities.
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Analytical Performance of a Loop-Mediated Isothermal Amplification Assay for Leishmania DNA Detection in Sandflies and Direct Smears of Patients with Cutaneous Leishmaniasis
Available online: 12 March 2018More LessLoop-mediated isothermal amplification (LAMP) is ideal for the detection of Leishmania DNA as it is a quick and easy-to-perform test that does not require complex or sophisticated equipment or infrastructure. However, the application of this technique in the detection of Leishmania DNA has not been comprehensively analyzed to date (analytical validation). Our objective was to evaluate the sensitivity and analytical specificity (anticipated reportable range [ARR], the limit of detection [LoD], and accuracy) of LAMP targeting the 18S rRNA gene in the diagnosis of six New World Leishmania species. We then applied the validated LAMP assay across 50 samples of sandflies and 50 direct smears from a recent outbreak of cutaneous leishmaniasis in Colombia to determine its diagnostic performance. The LAMP assay exclusively amplified the DNA of Leishmania spp., and an ARR of between 1 × 104 and 1 × 10−2 equivalent parasites/mL was determined. An LoD of 1 × 10−2 equivalent parasites/mL was established and there was no statistically significant variation in terms of accuracy. Finally, a sensitivity of 100% in direct smears and sandflies samples was calculated and a specificity of 90.9% for direct smears using microscopy as reference and 96.8% for sandflies using real-time polymerase chain reaction as reference were determined. To our knowledge, this is the first attempt to analytically validate a LAMP test to detect Leishmania DNA, which showed good diagnostic potential from sandflies and direct smear samples.
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Natural Infection of Phlebotomus sergenti by Leishmania tropica in Libya
Available online: 12 March 2018More LessCutaneous leishmaniasis (CL) is a public health concern caused by Leishmania (L.) major and (L.) tropica in Libya. Information on sandfly vectors, as well as their associated Leishmania species, is of paramount importance because vector dispersion is one of the major factors responsible for pathogen dissemination. A number of 515 sandflies (275 males and 240 females) were collected during June–November 2012 using the CDC miniature light traps from Al Rabta, northwest of Libya. Two hundred and forty unfed females were identified; Phlebotomus (Ph.) papatasi (N = 97), Ph. sergenti (N = 27), Ph. longicuspis (N = 32), Sergentomyia (Se.) minuta (N = 38), and Se. fallax (N = 46). These flies were screened for Leishmania DNA using the polymerase chain reaction–restriction fragment length polymorphism analysis of the internal transcribed spacer 1 and sequencing. Two Ph. sergenti were found positive to L. tropica DNA. This finding should be considered for any further vector surveillance and epidemiological studies of CL in endemic areas across Libya.
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Impact of Four Years of Annual Mass Drug Administration on Prevalence and Intensity of Schistosomiasis among Primary and High School Children in Western Kenya: A Repeated Cross-Sectional Study
Available online: 12 March 2018More LessSchistosomiasis remains a major public health problem in Kenya. The World Health Organization recommends preventive chemotherapy with praziquantel (PZQ) to control morbidity due to schistosomiasis. Morbidity is considered linked to intensity of infection, which along with prevalence is used to determine the frequency of mass drug administration (MDA) to school-age children. We determined the impact of annual school-based MDA on children across all primary and high school years using a repeated cross-sectional study design in five schools near Lake Victoria in western Kenya, an area endemic for Schistosoma mansoni. At baseline and for the following four consecutive years, between 897 and 1,440 school children in Grades 1–12 were enrolled and evaluated by Kato-Katz for S. mansoni and soil-transmitted helminths (STH), followed by annual MDA with PZQ and albendazole. Four annual rounds of MDA with PZQ were associated with reduced S. mansoni prevalence in all school children (44.7–14.0%; P < 0.001) and mean intensity of infection by 91% (90.4 to 8.1 eggs per gram [epg] of stool; P < 0.001). Prevalence of high-intensity infection (≥ 400 epg) decreased from 6.8% at baseline to 0.3% by the end of the study. Soil-transmitted helminth infections, already low at baseline, also decreased significantly over the years. In this high prevalence area, annual school-based MDA with high coverage across all Grades (1–12) resulted in rapid and progressive declines in overall prevalence and intensity of infection. This decrease was dramatic in regard to heavy infections in older school-attending children.
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Evaluation of Malaria Urban Risk Using an Immuno-Epidemiological Biomarker of Human Exposure to Anopheles Bites
Available online: 05 March 2018More LessUrban malaria is an underestimated serious health concern in African countries. This study aimed to evaluate the risk of malaria transmission in an urban area by evaluating the level of human exposure to Anopheles bites using an Anopheles salivary biomarker (gambiae Salivary Gland Protein-6 peptide 1 [gSG6-P1] peptide). Two multidisciplinary cross-sectional studies were undertaken in five sites of Bouaké city (three urban districts and two surrounding villages, used as control; Côte d’Ivoire) during the rainy season and the dry season. Blood samples were obtained from children 6 months to 14 years of age for immunological tests. The level of anti-gSG6-P1 immunoglobulin G (IgG) antibodies was significantly higher in the rainy season than the dry season in both urban and rural sites (P < 0.0001). Interestingly, children with the highest anti-gSG6-P1 IgG responses in the rainy season were infected by Plasmodium falciparum. Surprisingly, no difference of anti-gSG6-P1 IgG level was observed between urban and rural areas, for either season. The current data suggest that children in the urban city of Bouaké could be as highly exposed to Anopheles bites as children living in surrounding villages. The immunological biomarker of human exposure to Anopheles bites may be used to accurately assess the potential risk of malaria transmission in African urban settings.
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Frequent Community Use of Antibiotics among a Low-Economic Status Population in Manila, the Philippines: A Prospective Assessment Using a Urine Antibiotic Bioassay
Available online: 05 March 2018More LessThe widespread unregulated use of antibiotics without medical consultation contributes to the burden of antibiotic resistance in Southeast Asian countries. This study investigated antibiotic use before hospital consultation. In a prospective observational study from February 2, 2015, to July 2, 2015, we enrolled febrile patients attending the emergency room in San Lazaro Hospital, Manila, the Philippines. A urine sample was collected and a bioassay was used to detect antibiotic activity in urine using Bacillus stearothermophilus (ATCC7953), Escherichia coli (ATCC25922), and Streptococcus pyogenes (ATCC19615). Patients or caregivers reported their medication history, clinical information, and socioeconomic status. During the study period, 410 patients were enrolled. The median (interquartile range) age was 14 (7–23) years and 158 (39%) reported prior antibiotic use, predominantly a beta-lactam antibiotic. A total of 164 (40%, 95% confidence interval [CI]: 35–45) patients were urine bioassay positive with any of three organisms. The Bacillus assay was the most sensitive, detecting 162 (99%, 95% CI: 96–100) cases. Among bioassay positive patients, dengue (N = 91, 55%, 95% CI: 48–63) was the most frequent diagnosis, followed by other viral infections, including measles, rubella, and mumps (N = 17, 10%, 95% CI: 6–16). Patients with a positive bioassay were significantly more likely to be from the lowest-income group (adjusted odds ratio [AOR]: 1.7; 95% CI: 1.1–2.6) and required hospital admission (AOR: 2.1; 95% CI: 1.3–3.5). Unnecessary antibiotic use for febrile illnesses before hospital consultation is common in a low-income, highly populated urban community in Manila. Education targeting this group should be implemented to reduce unnecessary antibiotic use.
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Knowledge and Adherence to the National Guidelines for Malaria Diagnosis in Pregnancy among Health-Care Providers and Drug-Outlet Dispensers in Rural Western Kenya
Available online: 05 March 2018More LessPrompt diagnosis and effective treatment of acute malaria in pregnancy (MiP) is important for the mother and fetus; data on health-care provider adherence to diagnostic guidelines in pregnancy are limited. From September to November 2013, a cross-sectional survey was conducted in 51 health facilities and 39 drug outlets in Western Kenya. Provider knowledge of national diagnostic guidelines for uncomplicated MiP were assessed using standardized questionnaires. The use of parasitologic testing was assessed in health facilities via exit interviews with febrile women of childbearing age and in drug outlets via simulated-client scenarios, posing as pregnant women or their spouses. Overall, 93% of providers tested for malaria or accurately described signs and symptoms consistent with clinical malaria. Malaria was parasitologically confirmed in 77% of all patients presenting with febrile illness at health facilities and 5% of simulated clients at drug outlets. Parasitological testing was available in 80% of health facilities; 92% of patients evaluated at these facilities were tested. Only 23% of drug outlets had malaria rapid diagnostic tests (RDTs); at these outlets, RDTs were offered in 17% of client simulations. No differences were observed in testing rates by pregnancy trimester. The study highlights gaps among health providers in diagnostic knowledge and practice related to MiP, and the lack of malaria diagnostic capacity, particularly in drug outlets. The most important factor associated with malaria testing of pregnant women was the availability of diagnostics at the point of service. Interventions that increase the availability of malaria diagnostic services might improve malaria case management in pregnant women.
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Phase 1 Randomized Study of a Tetravalent Dengue Purified Inactivated Vaccine in Healthy Adults from Puerto Rico
Available online: 05 March 2018More LessThe safety and immunogenicity of four adjuvanted formulations of an investigational tetravalent dengue purified inactivated vaccine (DPIV) were evaluated in a predominantly dengue-primed population in Puerto Rico. In this placebo-controlled, randomized, observer-blind, phase I trial, 100 healthy adults were randomized 1:1:1:1:1 to receive DPIV at Day (D)0 and D28 (1 μg per dengue virus [DENV] type 1–4 adjuvanted with either alum, AS01E or AS03B, or 4 μg per DENV type adjuvanted with alum) or saline placebo. Functional antibody responses were assessed using a microneutralization assay at D56, Month (M)7, and M13. All DPIV formulations were well tolerated and no safety signals were identified through M13. The M13 according-to-protocol (ATP) immunogenicity cohort included 83 participants. The ATP analysis of immunogenicity was performed only on the 78 subjects seropositive for ≥ 1 DENV type at baseline: 69 tetravalent, three trivalent, two bivalent, and four monovalent. In all DPIV groups, geometric mean antibody titers (GMTs) increased from D0 to D56 and waned modestly through M13, while remaining well above prevaccination levels. The 4 μg + alum and the AS01E- and AS03B-adjuvanted formulations were highly immunogenic, with M13-neutralizing antibody GMTs against all four DENV types above 1,000. M13/D0 GMT ratios were highest in the 1 μg + AS03B group (ranging 3.2–3.7 depending on the DENV type). These results encourage continued clinical development of DPIV (ClinicalTrials.gov: NCT01702857).
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Dried Blood Spot RNA Transcriptomes Correlate with Transcriptomes Derived from Whole Blood RNA
Authors: Mary J. Reust, Myung Hee Lee, Jenny Xiang, Wei Zhang, Dong Xu, Tatiana Batson, Tuo Zhang, Jennifer A. Downs and Kathryn M. DupnikAvailable online: 05 March 2018More LessObtaining RNA from clinical samples collected in resource-limited settings can be costly and challenging. The goals of this study were to 1) optimize messenger RNA extraction from dried blood spots (DBS) and 2) determine how transcriptomes generated from DBS RNA compared with whole blood RNA isolated from blood collected in Tempus tubes. We studied paired samples collected from eight adults in rural Tanzania. Venous blood was collected on Whatman 903 Protein Saver cards and in tubes with RNA preservation solution. Our optimal DBS RNA extraction used 8 × 3-mm DBS punches as the starting material, bead beater disruption at maximum speed for 60 seconds, extraction with Illustra RNAspin Mini RNA Isolation kit, and purification with Zymo RNA Concentrator kit. Spearman correlations of normalized gene counts in DBS versus whole blood ranged from 0.887 to 0.941. Bland–Altman plots did not show a trend toward over- or under-counting at any gene size. We report a method to obtain sufficient RNA from DBS to generate a transcriptome. The DBS transcriptome gene counts correlated well with whole blood transcriptome gene counts. Dried blood spot for transcriptome studies could be an option when field conditions preclude appropriate collection, storage, or transport of whole blood for RNA studies.
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The Burden of Dengue Fever and Chikungunya in Southern Coastal Ecuador: Epidemiology, Clinical Presentation, and Phylogenetics from the First Two Years of a Prospective Study
Authors: Anna M. Stewart-Ibarra, Sadie J. Ryan, Aileen Kenneson, Christine A. King, Mark Abbott, Arturo Barbachano-Guerrero, Efraín Beltrán-Ayala, Mercy J. Borbor-Cordova, Washington B. Cárdenas, Cinthya Cueva, Julia L. Finkelstein, Christina D. Lupone, Richard G. Jarman, Irina Maljkovic Berry, Saurabh Mehta, Mark Polhemus, Mercy Silva and Timothy P. EndyAvailable online: 05 March 2018More LessHere, we report the findings from the first 2 years of an arbovirus surveillance study conducted in Machala, Ecuador, a dengue-endemic region (2014–2015). Patients with suspected dengue virus (DENV) infections (index cases, N = 324) were referred from five Ministry of Health clinical sites. A subset of DENV-positive index cases (N = 44) were selected, and individuals from the index household and four neighboring homes within 200 m were recruited (N = 400). Individuals who entered the study, other than the index cases, are referred to as associates. In 2014, 70.9% of index cases and 35.6% of associates had acute or recent DENV infections. In 2015, 28.3% of index cases and 12.8% of associates had acute or recent DENV infections. For every DENV infection captured by passive surveillance, we detected an additional three acute or recent DENV infections in associates. Of associates with acute DENV infections, 68% reported dengue-like symptoms, with the highest prevalence of symptomatic acute infections in children aged less than 10 years. The first chikungunya virus (CHIKV) infections were detected on epidemiological week 12 in 2015; 43.1% of index cases and 3.5% of associates had acute CHIKV infections. No Zika virus infections were detected. Phylogenetic analyses of isolates of DENV from 2014 revealed genetic relatedness and shared ancestry of DENV1, DENV2, and DENV4 genomes from Ecuador with those from Venezuela and Colombia, indicating the presence of viral flow between Ecuador and surrounding countries. Enhanced surveillance studies, such as this, provide high-resolution data on symptomatic and inapparent infections across the population.
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Exploring Droughts and Floods and Their Association with Cholera Outbreaks in Sub-Saharan Africa: A Register-Based Ecological Study from 1990 to 2010
Available online: 05 March 2018More LessAn increased risk for cholera was witnessed during both droughts and floods in sub-Saharan Africa; these findings call for increased preparedness and surveillance during droughts in addition to floods. Cholera outbreaks in Africa have been attributed to both droughts and floods, but whether the risk of a cholera outbreak is elevated during droughts is unknown. We estimated the risk of cholera outbreaks during droughts and floods compared with drought- and flood-free periods in 40 sub-Saharan African countries during 1990–2010 based on data from EM-DAT: the OFDA/CRED International Disaster Database (www.emdat.be). A cholera outbreak was registered in one of every three droughts and one of every 15 floods. We observed an increased incidence rate of cholera outbreaks during drought periods (IRR = 4.3, 95% confidence interval [CI] = 2.9–7.2) and during flood periods (IRR = 144, 95% CI = 101–208) when compared with drought/flood-free periods. Floods are more strongly associated with cholera outbreaks, yet the prevalence of cholera outbreaks is higher during droughts because of droughts’ long durations. The results suggest that droughts in addition to floods call for increased cholera preparedness.
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Pediatric Acute Severe Neurologic Illness and Injury in an Urban and a Rural Hospital in the Democratic Republic of the Congo
Authors: Taty Tshimangani, Jean Pongo, Joseph Bodi Mabiala, Marcel Yotebieng and Nicole F. O’BrienAvailable online: 05 March 2018More LessEmpirical knowledge suggests that acute neurologic disorders are common in sub-Saharan Africa, but studies examining the true burden of these diseases in children are scarce. We performed this prospective, observational study to evaluate the prevalence, clinical characteristics, treatment approaches, and outcomes of children suffering acute neurologic illness or injury (ANI) in an urban and rural site in the Democratic Republic of the Congo. Over 12 months, 471 out of 6,563 children admitted met diagnostic criteria for ANI, giving a hospital-based prevalence of 72/1,000 admissions. Two hundred and seventy-two children had clinical findings consistent with central nervous system infection but lacked complete diagnostic evaluation for definitive classification. Another 151 children were confirmed to have cerebral malaria (N = 109, 23% of admissions), bacterial meningitis (N = 38, 8% of admissions), tuberculous meningitis (N = 3, 0.6% of admissions), or herpes encephalitis (N = 1, 0.21% of admissions). Febrile convulsions, traumatic brain injury, and epilepsy contributed less significantly to overall hospital prevalence of ANI (3.19/1,000, 1.37/1,000, and 1.06/1,000, respectively). Overall mortality for the cohort was 21% (97/471). Neurologic sequelae were seen in another 31% of participants, with only 45% completing the study with a normal neurologic examination. This type of data is imperative to help plan effective strategies for illness and injury prevention and control, and to allow optimal use of limited resources in terms of provision of acute care and rehabilitation for these children.
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Safety Analysis of Leishmania Vaccine Used in a Randomized Canine Vaccine/Immunotherapy Trial
Available online: 05 March 2018More LessIn Leishmania infantum–endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum, the causative agent of canine leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.
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Challenges in Assessing Combined Interventions to Promote Linear Growth
Available online: 12 February 2018More LessDespite the recognition of stunting as a public health priority, nutritional and nonnutritional interventions to reduce or prevent linear growth failure have demonstrated minimal impact. Investigators and policymakers face several challenges that limit their ability to assess the potential benefits of combining available interventions into a linear growth promotion package. We use two common but very different interventions, deworming and multiple micronutrient supplements, to illustrate barriers to recommending an optimal linear growth promotion package based on the currently available literature. These challenges suggest that combining individual- and population-based as well as model-based approaches would complement existing research using systematic review, meta-analysis, and factorial randomized trials, and help integrate existing fields of research to inform the development of optimal linear growth promotion packages for children living in resource-limited settings.
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Characterization of the Gamboa Virus Serogroup (Orthobunyavirus Genus, Peribunyaviridae Family)
Authors: Jannifer Oliveira Chiang, William Marciel de Souza, Márcio Roberto Teixeira Nunes, Gustavo Olszanski Acrani, Amélia Paes de Andrade Travassos da Rosa, Nelma Mesquita de Freitas, Sandro Patroca da Silva, Pedro Henrique Dorta de Silva, Alana Watanabe de Sousa, Sueli Guerreiro Rodrigues, Juarez Antônio Simões Quaresma, Bedsy Dutary, Hilda Guzmán, Nikos Vasilakis, Robert B. Tesh and Pedro Fernando da Costa VasconcelosAvailable online: 12 February 2018More LessComprehensive comparative phylogenetic analyses were performed on 17 Gamboa serogroup viruses (GAMSVs) from distinct geographic regions in the Americas and other representative members of the genus Orthobunyavirus (Peribunyaviridae), based on small (S), medium (M), and large (L) open reading frame full-length and partial sequences. Genome characterization showed that the GAMSVs divide into four clades or genotypes. The GAMSVs have a genetic organization similar to other orthobunyaviruses, except that they have a larger NSm protein than other orthobunyaviruses. A serosurvey for Gamboa virus antibodies was performed in plasma from birds, other wild animals, and humans living around the Tucuruí hydroelectric dam in Pará state, northern Brazil, a known focus of GAMSV activity. Newborn chicks (Gallus gallus domesticus) were experimentally infected with a GAMSV, and the pathogenesis is described. Histopathological changes were primarily in the lungs and liver. Also, a review of the ecology of the GAMSVs in the Americas is included. In sum, this study presents the genomic and evolutionary characterization of the Gamboa group and the potential model of pathogenesis, which would be helpful for diagnostic purposes, epidemiology, and immunopathogenesis studies.
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Association between Severity of Liver Disease, Frequency of Helicobacter pylori Infection, and Degree of Gastric Lesion in Egyptian Patients with Hepatitis B Virus Infection
Available online: 30 October 2017More LessThe relationship between hepatitis B virus (HBV) infection, severity of liver disease, frequency of Helicobacter pylori infection, and degree of gastric lesions was not yet fully investigated in Egyptian patients. The present work was performed on 100 Egyptian patients with HBV from the National Hepatology and Tropical Medicine Institute and 70 healthy volunteers as control group. The participants were subjected to full medical history taking, clinical examination, and laboratory investigations. All patients were positive for HBV surface antigen (HBV sAg), HBV DNA, and negative for hepatitis C virus antibodies. The severity of the liver disease was assessed using Child–Pugh scoring system. Screening of all participants for H. pylori Ag in stool was performed. Biopsy specimens were taken from the gastric lesions of H. pylori-infected patients for histopathological examination. The mean age of the patients and control group were 34.9 and 33.4 years, respectively. The levels of the liver enzymes were statistically higher in HBV patients than the control group. Helicobacter pylori Ag in stool was detected in 45.7% of the control group, and a higher percentage (60%) was detected in the patients group. Chronic gastritis with glandular atrophy and metaplasia was found in 15.6% of patients of Child–Pugh A, 70% of Child–Pugh B, and 100% of Child–Pugh C. It could be concluded that the prognosis of the liver disease significantly influences the severity of the gastric pathology in H. pylori infection.
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Molecular Identification of Onchocerca spp. Larvae in Simulium damnosum sensu lato Collected in Northern Uganda
Available online: 02 October 2017More LessPrevious studies have demonstrated that the presence of larvae of other filarial species in Simulium damnosum sensu lato can distort estimates of transmission potential for Onchocerca volvulus in West Africa. However, studies conducted in foci of onchocerciasis in West Central Uganda indicated that larvae other than O. volvulus were not common in vectors collected there. Recent data collected in Northern Uganda revealed a striking discordance between estimates of the prevalence of flies carrying O. volvulus infective larvae obtained from molecular pool screening and dissection methods. To resolve this discrepancy, sequences from three mitochondrially encoded genes were analyzed from the larvae collected by dissection. All larvae analyzed were Onchocerca ochengi v. Siisa, a parasite of cattle, or Onchocerca ramachandrini, a parasite of warthogs. These results suggest that nonhuman parasite larvae are common in vectors in Northern Uganda, underscoring the necessity for molecular identification methods to accurately estimate O. volvulus transmission.
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Dengue Virus Serotypes 1 and 2 Responsible for Major Dengue Outbreaks in Nepal: Clinical, Laboratory, and Epidemiological Features
Available online: 31 July 2017More LessDengue virus (DENV) is expanding toward previously nonendemic areas. DENV has recently been introduced in Nepal with limited information. We report the clinical features and serotype distribution of DENV in Nepal during the major outbreaks. A total of 1,215 clinical dengue cases at two major hospitals of central and western Nepal were investigated. Demographic, clinical, and laboratory parameters were recorded. Serum specimens were tested for DENV by IgM/IgG enzyme-linked immunosorbent assays (ELISAs) and reverse transcription polymerase chain reaction (RT-PCR). We confirmed DENV infection in 403 (33%) patients from 12 districts with an estimated case fatality rate of 1.5%. DENV infection was more common in adults (87%) and urban settings (74%). We detected all four serotypes but DENV-1 and -2 were mainly responsible for major outbreaks (92%). Overall, 60% of all DENV infections were secondary and 17% were severe dengue; both being more frequent among the DENV-2 infections. Rash, bleeding, abdominal pain, hepatomegaly, elevated liver enzymes, and thrombocytopenia were significantly more common in severe dengue compared with nonsevere infections. We also confirmed the expansion of dengue to hill urban areas (DENV-1 and -2), including the capital Kathmandu (altitude, 1,300 m) though > 90% cases were from southern plains. Differential clinical and laboratory features probably helps in clinical decisions. Multiple serotypes circulation and elevated secondary infections pose potential risk of severe outbreaks and deaths in the future. Therefore, a country with recent dengue introduction, like Nepal, urgently requires a systematic surveillance and appropriate control measures in place to respond any disastrous outbreaks.
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Evaluation of Community-Directed Operation of Black Fly Traps for Entomological Surveillance of Onchocerca volvulus Transmission in the Madi-Mid North Focus of Onchocerciasis in Northern Uganda
Available online: 31 July 2017More LessEntomological measures of transmission are important metrics specified by the World Health Organization to document the suppression and interruption of transmission of Onchocerca volvulus, the causative agent of onchocerciasis. These metrics require testing of large numbers of vector black flies. Black fly collection has relied on human landing collections, which are inefficient and potentially hazardous. As the focus of the international community has shifted from onchocerciasis control to elimination, replacement of human landing collections has become a priority. The Esperanza window trap (EWT) has shown promise as an alternative method for collection of Simulium damnosum s.l., the primary vector of O. volvulus in Africa. Here, we report the results of a community-based trial of the EWT in northern Uganda. Traps operated by residents were compared with human landing collections in two communities over 5 months. Three traps, when operated by a single village resident, collected over four times as many S. damnosum as did the two-men collection team. No significant differences were noted among the bait formulations. The results suggest that EWTs may be effectively operated by community residents and that the trap represents a viable alternative to human landing collections for entomological surveillance of O. volvulus transmission.
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Case Report: Old World Mucosal Leishmaniasis: Report of Five Imported Cases to the Hospital for Tropical Diseases, London, United Kingdom
Authors: Trupti A. Patel, Glenis K. Scadding, David E. Phillips and Diana N. LockwoodAvailable online: 24 July 2017More LessOld World species of Leishmania typically cause visceral and cutaneous leishmaniasis. Mucosal involvement is typically seen with infection by Leishmania species found in South America, usually after the healing of cutaneous leishmaniasis. We present five imported cases of mucosal leishmaniasis caused by Old World Mediterranean Leishmania infantum exclusively affecting the nasal mucosa or vocal cord. In only one case was there a recollection of a preceding cutaneous lesion compatible with cutaneous Leishmaniasis. Of significance was that four out of five cases were receiving local corticosteroids for chronic lung disorders and four were systemically immunosuppressed. This report highlights the importance of considering mucosal leishmaniasis in the differential diagnosis in those presenting with upper respiratory tract mucosal lesions with a relevant travel history to the Mediterranean and in whom malignancy has been excluded.
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