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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.
1 - 20 of 76 results
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Brain and Spinal Cord Lesions in Leprosy: A Magnetic Resonance Imaging–Based Study
Kiran Polavarapu, Veeramani Preethish-Kumar, Seena Vengalil, Saraswati Nashi, Mallika Lavania, Kajari Bhattacharya, Anita Mahadevan, T. Chickabasaviah Yasha, Jitender Saini, Utpal Sengupta, Shumyla Jabeen, B. N. Nandeesh, Itu Singh, Niranjan P. Mahajan, Pradeep Reddy, Gareth J. Parry and Atchayaram NaliniAvailable online: 11 February 2019More LessNeurotropism and infiltration by Mycobacterium leprae of peripheral nerves causing neuropathy are well established, but reports of central nervous system (CNS) damage are exceptional. We report CNS magnetic resonance imaging (MRI) abnormalities of the brain and spinal cord as well as lesions in nerve roots and plexus in leprosy patients. Eight patients aged between 17 and 41 years underwent detailed clinical, histopathological, and MRI evaluation. All had prominent sensory–motor deficits with hypopigmented and hypo/anesthetic skin patches and thickened peripheral nerves. All demonstrated M. Leprae DNA in affected peripheral nerve tissue. All received multidrug therapy (MDT). Two patients had brainstem lesions with enhancing facial nuclei and nerves, and one patient had a lesion in the nucleus ambiguus. Two patients had enhancing spinal cord lesions. Follow-up MRI performed in four cases showed resolution of brainstem and cord lesions after starting on MDT. Thickened brachial and lumbosacral plexus nerves were observed in six and two patients, respectively, which partially resolved on follow-up MRI in the two cases who had reimaging. The site and side of the MRI lesions corresponded with the location and side of neurological deficits. This precise clinico-radiological correlation of proximal lesions could be explained by an immune reaction in the gray matter corresponding to the involved peripheral nerves, retrograde axonal and gray matter changes, or infection of the CNS and plexus by lepra bacilli. Further study of the CNS in patients with leprous neuropathy is needed to establish the exact nature of these CNS MRI findings.
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Association between Insulin-Like Growth Factor-I Levels and the Disease Progression and Anemia in Visceral Leishmaniasis
Available online: 11 February 2019More LessWe analyzed the association between insulin-like growth factor-I (IGF-I) and the pathogenesis of anemia during active visceral leishmaniasis (VL). Serum levels of IGF-I, IGF-binding protein 3 (IGFBP3), and cytokines were measured in samples from individuals with active VL and cured VL, asymptomatic Leishmania-infected, and noninfected individuals. Then, we extended our analysis to VL dogs to evaluate hematimetric parameters, bone marrow alterations, and cytokine and IGF-I expression. We identified a positive correlation between lower IGF-I and IGFBP3 levels in active VL patients and lower hemoglobin levels. In infected dogs, there was a positive correlation between lower IGF-I expression in the bone marrow and lower peripheral blood hematocrit and hemoglobin levels. There was no correlation between decreased IGF-I level/expression and any measured cytokine serum levels in either host. The data suggest that low IGF-I expression is associated with pathogenesis of anemia in active VL, primarily in severe cases, by mechanisms other than alterations in cytokine production.
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High Morbidity Due to Murine Typhus Upsurge in Urban Neighborhoods in Central Israel
Available online: 11 February 2019More LessThe incidence of murine typhus in Israel has decreased substantially since 1950 to a low of 0.04/100,000 population in 2010. We present the experience of a single university medical center in central Israel. Hospitalized patients serologically positive for Rickettsia typhi by indirect immunofluorescence antibody assay during 2006–2016 were retrospectively identified. Clinical and laboratory data from patients’ charts were used to analyze disease trends and distribution. Seventy-eight patients were studied (mean age: 27.9 years), mostly of Arab ethnicity (68, 87.2%). Seventy-one (91%) patients resided in two large mixed Jewish-Arab cities—Lod and Ramla. The incidence of murine typhus among the Arab population in Lod increased 8.4-fold from 6.4/100,000 in 2006 to a peak of 53.4/100,000 in 2013. The average annual incidence among Arabs in Ramla was 10.1/100,000. Among Jews, incidences were 0.8/100,000 in Lod and 0.4/100,000 in Ramla. The classical triad of fever, headache, and rash was noted in 20.8% patients. Substantial morbidity included prolonged fever before hospitalization and hospital stay (mean of 8.4 and 5.1 days, respectively), and severe complications in six patients, including pneumonitis in three patients, and splenic infarctions, pericardial effusion, and retinitis, each in one each. One previously healthy patient died of multiorgan failure. The study describes a high incidence of murine typhus with a recent upsurge in an urban setting in central Israel. High morbidity and a single fatal outcome challenge the concept of murine typhus being a mild disease. The study calls for better rodent control and sanitation measures in the affected neighborhoods.
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Differences in the Clinical and Laboratory Features of Imported Onchocerciasis in Endemic Individuals and Temporary Residents
Available online: 11 February 2019More LessMany parasitic infections have different presenting features in endemic individuals (ENDs) and immunologically naive temporary residents (TRs). Temporary residents with loiasis often display acute symptoms and hypereosinophilia, in contrast to a parasite-induced subclinical state in chronically infected ENDs. Few studies have examined differences in ENDs and TRs infected with the related filarial parasite Onchocerca volvulus. We identified 40 TRs and 36 ENDs with imported onchocerciasis at the National Institutes of Health between 1976 and 2016. All study subjects received an extensive pretreatment history review, physical examination, and laboratory investigations. We performed additional parasite-specific serologic testing on stored patient sera. Asymptomatic infection occurred in 12.5% of TRs and no ENDs (P = 0.06). Papular dermatitis was more common in TRs (47.5% versus 2.7%, P < 0.001), whereas more pigmentation changes occurred in ENDs (41.7% versus 15%, P = 0.01). Only endemic patients reported visual disturbance (13% versus 0%, P = 0.03). One TR (3.3%) had onchocercal eye disease, compared with 22.6% of ENDs (P = 0.053). Absolute eosinophil counts (AECs) were similar in ENDs and TRs (P = 0.5), and one-third of subjects had a normal AEC. Endemic individuals had higher filarial-specific IgG4 and were more likely to be positive for IgG4 antibodies to Ov-16. Temporary residents and ENDs with imported O. volvulus infection presented with different dermatologic manifestations; ocular involvement occurred almost exclusively in ENDs. Unlike Loa loa, clinical differences appear not to be eosinophil mediated and may reflect chronicity, intensity of infection, or the presence of Wolbachia in O. volvulus.
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Significance of Autophagy in Dengue Virus Infection: A Brief Review
Available online: 11 February 2019More LessDengue virus (DENV) causes asymptomatic to severe life-threatening infections and affects millions of people worldwide. Autophagy, a cellular degradative pathway, has both proviral and antiviral functions. Dengue virus triggers the autophagy pathway for the successful replication of its genome. However, the exact mechanism and the viral factors involved in activating this pathway remain unclear. This review summarizes the existing knowledge on the mechanism of autophagy induction and its significance during DENV infection.
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A Personal Account Regarding the Origin and Evolution of Controversies in the Management of Neurocysticercosis
Available online: 11 February 2019More LessA panel of experts from the Infectious Disease Society of America and The American Society of Tropical Medicine and Hygiene recently published guidelines for management of neurocysticercosis, showing that clinical manifestations as well as the stage of involution and the anatomical location of parasites must be taken into account before the start of a rational therapy. Soon thereafter, isolated opinions attempted to discredit these guidelines, arguing insufficient or inadequate evidence and suggesting that they should not be followed worldwide. In view of these conflicting reports, it is appropriate to review the origin and evolution of the controversy on the medical treatment of neurocysticercosis.
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Efficacy of Mass Azithromycin Distribution for Reducing Childhood Mortality Across Geographic Regions
Available online: 07 February 2019More LessMass azithromycin distribution has been shown to reduce all-cause mortality in preschool children in sub-Saharan Africa. However, substantial heterogeneity in the apparent effect has been noted across geographic settings, suggesting a greater relative benefit in higher mortality settings. Here, we evaluated the relationship between the underlying mortality rate and the efficacy of azithromycin for the prevention of child mortality using data from multiple sites in Ethiopia, Malawi, Niger, and Tanzania. Between regions, we find no strong evidence of effect modification of the efficacy of azithromycin distribution for the prevention of child mortality by the underlying mortality rate (P = 0.12), although a modest effect is consistent with our findings. Higher mortality settings could be prioritized, however, because of the larger number of deaths which could be averted with azithromycin distribution.
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Effect Modification by Baseline Mortality in the MORDOR Azithromycin Trial
Available online: 07 February 2019More LessWe examined whether baseline mortality risk, as a function of child age and site, modified the azithromycin mortality-reduction effect in the Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) clinical trial. We used the Cox proportional hazards model with an interaction term. Three models were examined representing three sources for the baseline-risk covariate: two using sources external to MORDOR and the third leveraging data within MORDOR. All three models provided moderate evidence for the effect becoming stronger with increasing baseline mortality (P = 0.02, 0.02, and 0.07, respectively) at the rate of approximately 6–12% additional mortality reduction per doubling of baseline mortality. Etiological and programmatic implications of these findings are discussed.
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Mass Drug Administration of Azithromycin to Reduce Child Mortality: Only for High-Mortality Settings?
Available online: 07 February 2019More LessMass Drug Administration of Azithromycin to Reduce Child Mortality: Only for High-Mortality Settings?
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Integration of Human African Trypanosomiasis Control Activities into Primary Health Services in the Democratic Republic of the Congo: A Qualitative Study of Stakeholder Perceptions
Available online: 04 February 2019More LessHuman African trypanosomiasis is close to elimination in several countries in sub-Saharan Africa. The diagnosis and treatment is currently rapidly being integrated into first-line health services. We aimed to document the perspective of stakeholders on this integration process. We conducted 12 focus groups with communities in three health zones of the Democratic Republic of the Congo and held 32 interviews with health-care providers, managers, policy makers, and public health experts. The topic guide focused on enabling and blocking factors related to the integrated diagnosis and treatment approach. The data were analyzed with NVivo using a thematic analysis process. The results showed that the community mostly welcomed integrated care for diagnosis and treatment of sleeping sickness, as they value the proximity of first-line health services, but feared possible financial barriers. Health-care professionals thought integration contributed to the elimination goal but identified several implementation challenges, such as the lack of skills, equipment, motivation and financial resources in these basic health services. Patients often use multiple therapeutic itineraries that do not necessarily lead them to health centers where screening is available. Financial barriers are important, as health care is not free in first-line health centers, in contrast to the population screening campaigns. Communities and providers signal several challenges regarding the integration process. To succeed, the required training of health professionals, as well as staff deployment and remuneration policy and the financial barriers in the primary care system need to be addressed, to ensure coverage for those most in need.
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Absence of Serological Evidence of Exposure to Treponema pallidum among Children Suggests Yaws Is No Longer Endemic in Kiribati
Available online: 04 February 2019More LessYaws is a neglected tropical disease targeted for eradication by 2020. Kiribati, a Pacific Island nation, was previously endemic for yaws but lacks recent data from which its current endemicity status could be determined. This study tested antibody responses to Treponema pallidum to determine if transmission of yaws is taking place among children in Kiribati. Using a commercially available T. pallidum particle agglutination kit (Serodia®, MAST Diagnostics), we tested dried blood spots, collected during population-based trachoma prevalence surveys on Tarawa Atoll and Kiritimati Island, for long-lived treponemal antibodies. Dried blood spots from 1,420 children aged 1–9 years were tested. Only two were positive, suggesting T. pallidum is not being widely transmitted among children in the settings sampled. These data require support from additional surveys to demonstrate the absence of clinical signs of disease and molecular evidence of infection, to confirm that yaws is no longer endemic in Kiribati.
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The Search for Plasmodium falciparum histidine–rich protein 2/3 Deletions in Zambia and Implications for Plasmodium falciparum histidine rich–protein 2-Based Rapid Diagnostic Tests
Available online: 04 February 2019More LessWe attempted to identify Plasmodium falciparum histidine–rich protein 2/3 (pfhrp2/3) deletions among rapid diagnostic test (RDT)–negative but PCR- or microscopy-positive P. falciparum–infected individuals in areas of low transmission (Choma District, 2009–2011) and high transmission (Nchelenge District, 2015–2017) in Zambia. Through community-based surveys, 5,167 participants were screened at 1,147 households by PfHRP2-based RDTs. Slides were made and dried blood spots were obtained for molecular analysis. Of 28 samples with detectable P. falciparum DNA, none from Nchelenge District were pfhrp2/3 negative. All eight samples from Choma District had detectable pfhrp3 genes, but pfhrp2 was undetectable in three. DNA concentrations of pfhrp2-negative samples were low (< 0.001 ng/μL). These findings suggest that PfHRP2-based RDTs remain effective tools for malaria diagnosis in Nchelenge District, but further study is warranted to understand the potential for pfhrp2/3 deletions in southern Zambia where malaria transmission declined over the past decade.
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Toward Mass Drug Administration Stopping Criteria for Schistosoma mansoni Control Programs
Available online: 04 February 2019More LessToward Mass Drug Administration Stopping Criteria for Schistosoma mansoni Control Programs
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Risk Factors for Undernutrition and Diarrhea Prevalence in an Urban Slum in Indonesia: Focus on Water, Sanitation, and Hygiene
Available online: 28 January 2019More LessUnsafe drinking water and poor sanitation and hygiene lead to deterioration of the child health condition in low- and middle-income countries. This study aimed to evaluate the nutritional and health status of children living in an urban slum and to clarify the factors contributing to undernutrition and diarrhea prevalence by focusing on water, sanitation, and hygiene from three viewpoints: household environments, child personal hygiene practices, and knowledge and awareness. The study was conducted at a preschool and two elementary schools in the densely populated area of Bandung, Indonesia. Participants were 228 pairs of children and their caretakers. The survey involved 1) anthropometric measurements (height and weight), 2) handwashing observation using a checklist, and 3) questionnaires. On multivariate logistic regression analysis, not using a towel for handwashing practices (adjusted odds ratio [AOR] = 2.37; 95% confidence interval [CI] = 1.13–4.96) was significantly associated with an increased risk of stunting. Regarding household environments, children from households using tap water as drinking water were significantly associated with an increased risk of stunting and thinness compared with households using tank water (AOR = 2.26; 95% CI = 1.03–4.93; and AOR = 2.88; 95% CI = 1.13–7.35, respectively). Moreover, children from households using open containers for water storage were significantly associated with an increased risk of diarrhea (AOR = 5.01; 95% CI = 1.08–23.15). Therefore, drinking water management at home and proper personal hygiene practices of children are important for maintaining and promoting child health in urban Indonesian slums.
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Exposure to Livestock Feces and Water Quality, Sanitation, and Hygiene (WASH) Conditions among Caregivers and Young Children: Formative Research in Rural Burkina Faso
Available online: 28 January 2019More LessLivestock farming is common in low-income settings as a source of income and animal-sourced food. However, there is growing evidence of the harmful health effects of proximity of animals to infants and young children, especially through exposure to zoonotic pathogens. Poultry ownership is almost universal in rural Burkina Faso. Poultry feces are a significant risk factor for enteric diseases that are associated with child undernutrition. To investigate the extent of exposure to livestock feces among young children and caregivers, we conducted direct observations of 20 caregiver–child dyads for a total of 80 hours (4 hours per dyad) and recorded water quality, sanitation, and hygiene (WASH)-related behaviors. We also undertook in-depth interviews with these caregivers and focus group discussions with separate groups of men and women who were poultry farmers. Poultry and other livestock feces were visible in all 20 and 19 households, respectively, in both kitchen areas and in the household courtyards where children frequently sit or crawl. Direct soil ingestion by young children was observed in almost half of the households (45%). Poor handwashing practices were also common among caregivers and children. Although latrines were available in almost all households, child feces disposal practices were inadequate. This body of research suggests an urgent need to adapt conventional WASH and livestock interventions to reduce the exposure of infants and young children to livestock feces.
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Low Zika Virus Seroprevalence in Vientiane, Laos, 2003–2015
Available online: 28 January 2019More LessZika virus (ZIKV) has been presumed to be endemic in Southeast Asia (SEA), with a low rate of human infections. Although the first ZIKV evidence was obtained in the 1950s through serosurveys, the first laboratory-confirmed case was only detected in 2010 in Cambodia. The epidemiology of ZIKV in SEA remains uncertain because of the scarcity of available data. From 2016, subsequent to the large outbreaks in the Pacific and Latin America, several Asian countries started reporting increasing numbers of confirmed ZIKV patients, but no global epidemiological assessment is available to date. Here, with the aim of providing information on ZIKV circulation and population immunity, we conducted a seroprevalence study among blood donors in Vientiane, Laos. Sera from 359 asymptomatic consenting adult donors in 2003–2004 and 687 in 2015 were screened for anti-ZIKV IgG using NS1 ELISA assay (Euroimmun, Germany). Positive and equivocal samples were confirmed for anti-ZIKV–neutralizing antibodies by virus neutralization tests. Our findings suggest that ZIKV has been circulating in Vientiane over at least the last decade. Zika virus seroprevalence observed in the studied blood donors was low, 4.5% in 2003–2004 with an increase in 2015 to 9.9% (P = 0.002), possibly reflecting the increase of ZIKV incident cases reported over this period. We did not observe any significant difference in seroprevalence according to gender. With a low herd immunity in the Vientiane population, ZIKV represents a risk for future large-scale outbreaks. Implementation of a nationwide ZIKV surveillance network and epidemiological studies throughout the country is needed.
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Long-Term in vitro Cultivation of Plasmodium falciparum in a Novel Cell Culture Device
Available online: 28 January 2019More LessThe standard in vitro cultivation procedure for Plasmodium falciparum requires gas exchange and a microaerophilic atmosphere. A novel system using a commercially available cell culture device (Petaka G3™; Celartia Ltd., Powell, OH) was assessed for long-term cultivation of a P. falciparum reference laboratory clone in normal air. Parasite growth during 30 days was similar, or better, in Petaka G3 than that in the standard cultivation method with gas exchange in a CO2 incubator. The successful cultivation of P. falciparum in the Petaka G3 device suggests that low O2 content available in hemoglobin and dissolved gas in the blood is sufficient for long-term cultivation. This finding may open the way to novel methods to cultivate and adapt P. falciparum field isolates to in vitro conditions with more ease.
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The Cholera Phone: Diarrheal Disease Surveillance by Mobile Phone in Bangladesh
Available online: 28 January 2019More LessExisting methodologies to record diarrheal disease incidence in households have limitations due to a high-episode recall error outside a 48-hour window. Our objective was to use mobile phones for reporting diarrheal episodes in households to provide real-time incidence data with minimum resource consumption and low recall error. From June 2014 to June 2015, we enrolled 417 low-income households in Dhaka, Bangladesh, and asked them to report diarrheal episodes to a call center. A team of data collectors then visited persons reporting the episode to collect data. In addition, each month, the team conducted in-home surveys on diarrhea incidence for a preceding 48-hour period. The mobile phone surveillance reported an incidence of 0.16 cases per person-year (95% CI: 0.13–0.19), with 117 reported diarrhea cases, and the routine in-home survey detected an incidence of 0.33 cases per person-year (95% CI: 0.18–0.60), the incidence rate ratio was 2.11 (95% CI: 1.08–3.78). During focus group discussions, participants reported a lack in motivation to report diarrhea by phone because of the absence of provision of intervening treatment following reporting. Mobile phone technology can provide a unique tool for real-time disease reporting. The phone surveillance in this study reported a lower incidence of diarrhea than an in-home survey, possibly because of the absence of intervention and, therefore, a perceived lack of incentive to report. However, this study reports the untapped potential of mobile phones in monitoring infectious disease incidence in a low-income setting.
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Laboratory Parameters after Treatment for Loa loa and Mansonella perstans: The Experience of a Single Referral Center for Tropical Diseases in a Non-Endemic Area
Available online: 28 January 2019More LessInfections due to Loa loa and Mansonella perstans are common yet elusive neglected filariases. Parasitological cure after treatment is very difficult to assess, as adult parasites are not accessible. Therefore, outside transmission areas, patients require a long follow-up period to ascertain the therapeutic outcome, which is impractical for non-sedentary populations such as migrants. We studied the change over time of microfilaremia, eosinophil counts, and antifilarial antibodies tested with a commercial ELISA test (Bordier Affinity Products, Crissier, Switzerland), in a retrospective cohort of patients with confirmed L. loa and M. perstans infections, to evaluate the role of serology in clinical practice. After treatment, all 22 eligible patients diagnosed in our center between 2015 and 2017 reached amicrofilaremia, with microfilarial counts decreasing sharply within 2 months. Paralleling eosinophil counts, antibodies decreased in all patients, 36% of whom reached sero-reversion or near–sero-reversion in < 20 months. These findings suggest that positive serology is not just residual from a past infection, and may be used for diagnosis even when microfilaremia is negative or cannot be performed. Interestingly, antibodies and eosinophil counts increased following some, but not all, re-treatment courses. If the rise in these parameters reflects death of macrofilariae, caution is required in interpreting high eosinophil counts and antibody titers shortly after treatment, as these may reflect no need for further treatment. To optimize patients’ management, it is now pivotal to ascertain the interval between treatment and macrofilarial death and therefore whether re-treatments are required for complete clearance of parasites.
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