The American Journal of Tropical Medicine and Hygiene - Current Issue

World leaders gather to consolidate their commitment to ending tuberculosis (TB). Vital to the success of renewed efforts is an overdue recognition of the pervasive and pernicious influence of TB stigma. TB stigma is sustained in structures, policies, traditions, and norms. Innovative modifications to infection control, drug dispensing, and surveillance practices are required to increase demand for TB screening and effective therapeutic alliances among those diagnosed. The authors argue that reducing TB stigma requires a scientific and inclusive process, with prominent roles for TB survivors and a willingness to integrate and learn from other stigmatized conditions.

Antibodies directed against malaria parasites are easy and inexpensive to measure but remain an underused surveillance tool because of a lack of consensus on what to measure and how to interpret results. High-throughput screening of antibodies from well-characterized cohorts offers a means to substantially improve existing assays by rationally choosing the most informative sets of responses and analytical methods. Recent data suggest that high-resolution information on malaria exposure can be obtained from a small number of samples by measuring a handful of properly chosen antibody responses. In this review, we discuss how standardized multi-antibody assays can be developed and efficiently integrated into existing surveillance activities, with potential to greatly augment the breadth and quality of information available to direct and monitor malaria control and elimination efforts.

Although Plasmodium vivax has been assumed to be absent from sub-Saharan Africa because of the protective mutation conferring the Duffy-negative phenotype, recent evidence has suggested that P. vivax cases are prevalent in these regions. We selected 292 dried blood spots from children who participated in the 2013–2014 Demographic and Health Survey of the Democratic Republic of the Congo (DRC), to assess for P. vivax infection. Four P. vivax infections were identified by polymerase chain reaction, each in a geographically different survey cluster. Using these as index cases, we tested the remaining 73 samples from the four clusters. With this approach, 10 confirmed cases, three probable cases, and one possible case of P. vivax were identified. Among the 14 P. vivax cases, nine were coinfected with Plasmodium falciparum. All 14 individuals were confirmed to be Duffy-negative by sequencing for the single point mutation in the GATA motif that represses the expression of the Duffy antigen. This finding is consistent with a growing body of literature that suggests that P. vivax can infect Duffy-negative individuals in Africa. Future molecular and sequencing work is needed to understand the relationship of these isolates with other P. vivax samples from Asia and South America and discover variants linked to P. vivax virulence and erythrocyte invasion.

To confirm and investigate possible explanations for unusual trends in malaria indicators, a protocol for rapid, focal assessment of malaria transmission and control interventions was piloted in N’Zérékoré and Macenta Prefectures, which each reported surprisingly low incidence of malaria during the peak transmission months during 2017 in holoendemic Forested Guinea. In each prefecture, epidemiological and entomological cross-sectional surveys were conducted in two sub-prefectures reporting high incidence and one sub-prefecture reporting low incidence. Investigators visited six health facilities and 356 households, tested 476 children, performed 14 larval breeding site transects, and conducted 12 nights of human landing catches during the 2-week investigation. Rapid diagnostic test positivity in the community sample of children under five ranged from 23% to 68% by subprefecture. Only 38% of persons with fever reported seeking care in the public health sector; underutilization was confirmed by verification of health facility and community healthcare worker (CHW) registries. High numbers of Anopheles mosquitoes were collected in human landing collections in N’Zérékoré (38 per night in combined indoor and outdoor collections) and Macenta (87). Most of the detected breeding sites positive for Anopheles larvae (83%) were shallow roadside puddles. In the investigated prefectures, malaria rates remain high and the low reported incidence likely reflects low utilization of the public health-care sector. Strengthening the CHW program to rapidly identify and treat malaria cases and elimination of roadside puddles as part of routine cleanup campaigns should be considered. Systematic joint epidemiological/entomological investigations in areas reporting anomalous signals in routine data can allow control programs to respond with tailored local interventions.

Gametocytes are the malaria parasite stages responsible for transmission from humans to mosquitoes. Gametocytemia often follows drug treatment, especially as therapies start to fail. We examined Plasmodium falciparum gametocyte carriage and drug resistance profiles among 824 persons with uncomplicated malaria in Cambodia to determine whether prevalent drug resistance and antimalarial use has led to a concentration of drug-resistant parasites among gametocyte carriers. Although report of prior antimalarial use increased from 2008 to 2014, the prevalence of study participants presenting with microscopic gametocyte carriage declined. Gametocytemia was more common in those reporting antimalarial use within the past year, and prior antimalarial use was correlated with higher IC50s to piperaquine and mefloquine, as well as to increased pfmdr1 copy number. However, there was no association between microscopic gametocyte carriage and parasite drug resistance. Thus, we found no evidence that the infectious reservoir, marked by those carrying gametocytes, is enriched with drug-resistant parasites.

We describe the case of a 12-year-old boy from Sudan who presented with fever of 1-week duration, headache, cough, and vomiting. A set of diagnostic tests led to the diagnosis of three infectious diseases: visceral leishmaniasis (probable diagnosis based on positive direct agglutination test), enteric fever (blood culture grown with Salmonella Paratyphi), and brucellosis (blood culture grown with Brucella melitensis). The patient received specific treatment of the three infections and recovered. This case illustrates the occurrence and possible implications of coinfections in patients with persistent fever, including conditions that are hard to diagnose in field settings, such as brucellosis and enteric fever.

Bolivian cutaneous leishmaniasis due to Leishmania braziliensis was treated with the combination of miltefosine (150 mg/day for 28 days) plus intralesional pentamidine (120 μg/mm2 lesion area on days 1, 3, and 5). Ninety-two per cent of 50 patients cured. Comparison to historic controls at our site suggests that the efficacy of the two drugs was additive. Adverse effects and cost were also additive. This combination may be attractive when a prime consideration is efficacy (e.g., in rescue therapy), avoidance of parenteral therapy, or the desire to treat locally and also provide systemic protection against parasite dissemination.

Cutaneous leishmaniasis is endemic in Salta province, which belongs to the northwest of Argentina. Leishmania spp. DNA from Giemsa-stained slides of up to 12 years in storage of patients from Salta was characterized through polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). One hundred smears positive for microscopy, classified in a semiquantitative scale for amastigote density, were analyzed. Also, Leishmanin skin test (LST) results were included. DNA extraction was carried out applying lysis buffer with proteinase K, and then DNA was amplified with ribosomal internal transcribed spacer 1 primers. PCR products were digested with HaeIII enzyme. All PCR-positive smears (74/100) belonged to Viannia subgenus. A statistically significant, directly proportional relationship between semiquantitative microscopy and PCR results was detected. All patients had LST-positive results (induration ≥ 5 mm), and the smears of those with smaller induration (LST < 19 mm) gave a higher proportion of positive PCR results. This study determined that smear age did not affect PCR positivity, which allows retrospective analyzes and suggests smears might be useful for molecular complementary diagnosis. Because Leishmania (Viannia) braziliensis is the main circulating species in the study area, determining Viannia subgenus in all analyzed samples confirms previous findings. PCR positivity showed statistically significant differences according to semiquantitative microscopy, highlighting the importance of parasite burden in the diagnostic sensitivity of the method. Considering that smears of patients with smaller LST induration were more positive in PCR, a negative smear from patients with positive LST response, but < 19 mm, could actually represent a false-negative result.

The diagnosis of visceral leishmaniasis (VL) is one of the foremost barriers in the control of this disease, as demonstration of the parasite by splenic/bone marrow aspiration is relatively difficult and requires expertise and laboratory support. The aim of the present study was to find a noninvasive diagnostic approach using the existing recombinant kinesine-39 (rK-39) immunochromatographic nitrocellulose strips test (ICT) with a human sweat specimen for the diagnosis of VL. The investigation was carried out on specimens (blood, sweat, and urine) collected from 58 confirmed VL, 50 confirmed post kala-azar dermal leishmaniasis (PKDL), 36 healthy control, and 35 patients from other diseases. The data obtained from this study reveal that 96.6% clinically confirmed active VL participants were found to be positive when tested against a sweat specimen. Interestingly, the scenario was similar when tested against a blood specimen (96.6% positive by rK-39). Moreover, a test of both sweats and blood specimens from 50 PKDL participants resulted in 100% positivity, whereas no healthy control participants were found to be rK-39 positive. The sensitivity of the rK-39 ICT in sweat specimen was 94.7%, whereas the specificity was 100% in healthy controls from endemic, nonendemic, and other infectious diseases, respectively. No difference was observed in sweat specimen of VL and PKDL cases which signifies its reliability. However, further evaluation of this method on a larger scale could enhance the reliability of the proposed model so that it could be used efficiently in VL management and eradication.

The disseminated form of leishmaniasis is a serious and rare disease, being diagnosed in 2% of the cutaneous cases registered per year in Brazil. The main characteristic is the appearance of multiple pleomorphic lesions on the cutaneous surface. A 68-year-old male from the rural area of Tocantins, Brazil, presented atypical disseminated cutaneous leishmaniasis (ACL). The clinical course and histopathological and immunological findings presented a mixed pattern that hindered diagnosis and therapeutic management. Molecular typing revealed a mixed infection with Leishmania (V.) guyanensis and Leishmania (L.) amazonensis. Molecular identification of the agents responsible for ACL is important for adequate therapeutic planning, minimizing the possibility of sequellae that impact the quality of life of the patient.

Dientamoeba fragilis is an intestinal protozoan, usually considered nonpathogenic. However, in the last years, there has been an attempt to clarify its possible pathogenic role. We aim to evaluate the clinical and epidemiological characteristics of D. fragilis–infected patients. Adults with D. fragilis detection in feces who attended the Vall d’Hebron University Hospital (Barcelona, Spain) were evaluated retrospectively from April 2009 to March 2014. We classified the patients in asymptomatic, symptomatic without other causes except infection of D. fragilis, and symptomatic with another cause. Among symptomatic patients, treatment response was evaluated. One hundred eight patients were included. Sixty-three percent of the patients were immigrants, 29.6% were autochthonous, and 7.4% were travelers. Forty-nine (45.3%) patients presented symptoms, and eosinophilia was observed in 26 (24.1%) patients. Overall, 59 (54.7%) patients were asymptomatic, 15 (13.8%) presented symptoms which were attributable to other causes, and 34 (31.5%) patients presented symptoms with no other causes. In this last group, 29 patients received specific treatment and 65.5% of them presented a complete resolution of the symptoms. The group of symptomatic patients with no other cause had more proportion of women, more proportion of autochthonous people, and were older compared with the group of asymptomatic patients. Dientamoeba fragilis infection should be considered as pathogenic when other causes are ruled out.

The existence of an imperfect reference standard presents complications when evaluating the unbiased performance of novel diagnostic techniques. This is especially true in the absence of a gold standard, as is the case in chronic Chagas disease (CD) diagnosis. To circumvent this constraint, we elected to use latent class analysis (LCA). Previously, our group demonstrated the high performance of four Trypanosoma cruzi–chimeric proteins (Molecular Biology Institute of Paraná [IBMP]-8.1, -8.2, -8.3, and -8.4) for CD diagnosis using several distinct immunoassays. Although commercial tests had previously been established as a reference standard, the diagnostic performance of these chimeric antigens could present bias because these tests fail to produce 100% accurate results. Thus, we used LCA to assess the performance of these IBMP chimeric antigens in chronic CD diagnosis. Using the LCA model as a gold standard, sensitivity and specificity values ranged from 93.5% to 99.4% and 99.6% to 100%, respectively. The accuracy values were 96.2% for IBMP-8.2, approximately 98% for IBMP-8.1 and IBMP-8.3, and nearly 100% for IBMP-8.4. For IBMP-8.1 and IBMP-8.2, higher positive predictive values were associated with increases in hypothetical prevalence. Similarly, higher hypothetical prevalence resulted in lower negative predictive values for IBMP-8.1, IBMP-8.2, and IBMP-8.3. In addition, samples with serodiscordant results from commercial serological tests were analyzed using LCA. Molecular Biology Institute of Paraná -8.1 demonstrated potential for use in confirmatory testing with regard to samples with inconsistent results. Moreover, our findings further confirmed the remarkable performance of the IBMP-8.4 antigen to diagnose chronic CD in both endemic and non-endemic areas.

Fasciola hepatica is the most widely distributed trematode-affecting humans. The Andes Mountains are highly endemic for fascioliasis. We report results of a cross-sectional study evaluating the epidemiology of Fasciola among children in 26 agricultural communities in the Cusco region of Peru. Children 3 to 16 years old were enrolled in preschools and schools. Blood from participants was tested for complete blood counts, transaminases, and Fasciola antibodies. Stool samples were tested for Fasciola and other parasites. A total of 2,515 children were included in the analysis and the mean age was 9.6 years (±3.6). Ten percent (253) of the children had at least one positive test for Fasciola, 6% had chronic infection, and 0.4% acute infection. The rest of the subjects had only antibodies against Fasciola. The prevalence of infection varied from 0% to 20% between communities. Children with evidence of Fasciola exposure were older, lived at higher altitudes, and had a lower socioeconomic status than children without infection. The logistic regression analysis showed that children from Ancahuasi district, older children, and children with higher measures of poverty were more likely to have Fasciola exposure. Fascioliasis is common in the Cusco region and associated with poverty. However, the distribution varies markedly between communities.

Hookworm disease caused by Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum affects half a billion people worldwide. The prevalence and intensity of infection of individual hookworm species are vital for assessing morbidity and generating targeted intervention programs for their control. The present study aims to evaluate a multiplex real-time quantitative PCR (qPCR) assay to determine the prevalence and egg intensity of all three hookworm species and compare this with standard microscopy and published genus-based conventional and real-time multiplex qPCRs. Performance of the diagnostic assays was evaluated using DNA extracted from 192 fecal samples collected as part of a soil-transmitted helminth (STH) survey in northern Cambodia. The prevalence of hookworms as detected by the multiplex hookworm qPCR of 84/192 (43.8%) was significantly higher than that using microscopy of 49/192 (25.5%). The hookworm multiplex qPCR showed very good agreement for the detection of both N. americanus (Kappa 0.943) and Ancylostoma spp. (Kappa 0.936) with a multiplex STH qPCR. A strong and moderate quantitative correlation between cycle threshold and eggs per gram (EPG) feces was obtained for the hookworm qPCR for seeded DNA egg extracts (R 2 ≥ 0.9004) and naturally egg-infected individuals (R 2 = 0.6848), respectively. The newly developed hookworm quantitative multiplex qPCR has the potential for application in anthelmintic efficacy trials and for monitoring the success of mass deworming programs targeting individual species of anthroponotic and zoonotic hookworms.

Disseminated strongyloidiasis is often fatal, despite treatment with oral albendazole and parenteral ivermectin (IVM). Here, we report elevated plasma IVM and albendazole sulfoxide concentrations in the context of extracorporeal membrane oxygenation and continuous renal replacement therapy in a patient with disseminated strongyloidiasis treated with subcutaneous IVM and nasogastric albenzadole. Despite elevated drug plasma concentrations, live filariform larvae were detected in endotracheal aspirates after 2 weeks of treatment.

The aim of this study was to demonstrate the presence of Taenia solium eggs in beetles collected from sources within the natural environment through molecular techniques. Fifty-four pools of beetles were collected in three villages in Piura, Peru. DNA was extracted using the FastDNA spin kit for soil. Molecular identification of Taenia species was then performed through partial amplification of the mitochondrial cytochrome C oxidase subunit I gene. Finally, positive samples were sequenced to determine the tapeworm species. Seven positive samples were obtained through polymerase chain reaction amplification. Sequencing confirmed that two samples were from T. solium and three samples were from Taenia hydatigena. The other two samples could not be specifically identified. Our findings demonstrate that dung beetles ingest T. solium and T. hydatigena eggs under natural conditions and suggest that beetles may play a role in the dynamics of transmission of these cestodes.

Dipylidium caninum is a cosmopolitan cestode infecting dogs, cats, and humans. Praziquantel is a highly effective cestocidal drug and resistance in adult cestodes has not been reported. From 2016 to 2018, a population of dogs with cestode infections that could not be eliminated despite multiple treatments with praziquantel or epsiprantel was identified. Cases of D. caninum were clinically resistant to praziquantel and could not be resolved despite increasing the dose, frequency, and duration of treatment. Resistant isolates were identified and characterized by sequencing the 28S, 12S, and voltage-gated calcium channel beta subunit genes. Cases were only resolved following treatment with nitroscanate or a compounded pyrantel/praziquantel/oxantel product. Clinicians should be aware of this alarming development as treatment options for cestodes are limited in both human and veterinary medicine.

A 63-year-old woman who migrated from Nigeria to the United States was found to have an elevated total serum protein, anemia, and eosinophilia. Serum protein electrophoresis (SPEP) and serum protein immunofixation electrophoresis (SPIFE) demonstrated monoclonal immunoglobulin G (IgG) κ restricted bands (IgG 3,820 mg/dL; κ/λ ratio 4.47), indicative of monoclonal gammopathy of unknown significance (MGUS). A rapid diagnostic test (RDT) for malaria was positive for Plasmodium falciparum (BinaxNOW®; Alere Scarborough Inc., Scarborough, ME). Giemsa-stained blood smears were negative for malarial parasites, however, Loa loa microfilariae were identified. Reverse transcription polymerase chain reaction for P. falciparum, Plasmodium ovale, Plasmodium malariae, and Plasmodium vivax yielded a negative result. She was treated for loiasis with diethylcarbamazine and received no malaria medication. Treatment resulted in a resolution of the microfilaremia and eosinophilia, a negative RDT for malaria, and marked reduction in the monoclonal gammopathy. This is the first reported human case of MGUS associated with loiasis and its resolution after antiparasitic treatment.

Nodding syndrome (NS) is an encephalopathy characterized by the core symptom of epileptic head nodding seizures, affecting children at the age between 3 and 18 years in distinct areas of tropical Africa. A consistent correlation with onchocerciasis was found, but so far, the causation of NS has not been fully clarified. With a systematic analysis of features of a cohort of epilepsy patients examined in the Itwara onchocerciasis focus of western Uganda in 1994, we provide evidence that NS actually occurred in this area at this time, and we demonstrate a correlation between prevalence of NS and that of onchocerciasis in different villages. Following the elimination of onchocerciasis by community-directed treatment with ivermectin and ground larviciding, our data provide a baseline to examine the question whether NS will disappear once its putative cause has been removed.

We present a case of intussusception with complete small bowel obstruction caused by intestinal anisakidosis requiring surgical resection. A 30-year-old man presented with acute onset of severe abdominal pain 3 days after eating home-cured salmon gravlax. Despite surgery, the patient developed recurrent abdominal pain on two occasions with evidence of continued inflammation proximal to the surgical anastomosis. He was then treated with albendazole and prednisone, and symptoms improved. A decision was made to prophylactically treat two asymptomatic family members who also consumed home-cured gravlax with albendazole, resulting in one individual passing an intact Anisakis worm in her stool. We suggest that albendazole therapy could be considered as a therapy for continued symptoms of anisakidosis and postexposure prophylaxis of Anisakis larvae ingestion from a common source.

Burkholderia pseudomallei, the etiological agent of melioidosis, has been hypothesized to be endemic throughout the Caribbean, including the impoverished nation of Haiti. However, because of the protean clinical manifestations, presence of asymptomatic infections, and limited medical diagnostic capacity, the identification of active melioidosis cases remains challenging. A seroepidemiological study was conducted using a novel enzyme-linked immunosorbent assay (ELISA) to detect antibodies toward B. pseudomallei in the native population. The performance of an indirect ELISA with purified lipopolysaccharide (LPS) from B. pseudomallei was evaluated using serum collected from rhesus macaques exposed to aerosolized B. pseudomallei. After optimization, serum collected from asymptomatic population members (n = 756) was screened for polyvalent (immunoglobulin M [IgM]/ immunoglobulin G [IgG]/ immunoglobulin A) and monoclonal (IgG or IgM) immunoglobulins against B. pseudomallei LPS. The population seroprevalence was 11.5% (95% confidence interval [CI]: 9.2, 13.8) for polyvalent immunoglobulins, 9.8% (95% CI: 7.7, 11.9) for IgG, and 1.7% (95% CI: 0.8, 2.6%) for IgM. The seroprevalence was not significantly different by gender (P = 0.16), but increased significantly (P < 0.001) with age, yielding an estimated annual seroconversion rate of 1.05% (95% CI: 0.81, 1.3). The detection of both recent (IgM+) and previous (IgG+) exposure to B. pseudomallei provides serological evidence that melioidosis is endemic in Haiti.

Carrion’s disease is a neglected, vector-borne illness that affects Colombia, Ecuador, and especially Peru. The phlebotomine sand flies Lutzomyia verrucarum and Lutzomyia peruensis are the main illness vectors described, although other species may be implicated in endemic areas such as some northern Peruvian regions, in which Carrion’s disease vector has not been established. The aim of this study was to evaluate the presence of Bartonella bacilliformis DNA in Lutzomyia maranonensis from Cajamarca, northern Peru. This sand fly has not been defined as a vector yet. Centers for Disease Control and Prevention light traps were used to collect adult phlebotomine sand flies from 2007 to 2008 in the Cajamarca department. Female specimens were identified using morphological keys and were grouped into pools of five sand flies, taking into account district and sampling site (intradomicile or peridomicile). DNA was extracted, and then conventional and real-time polymerase chain reaction (RT-PCR) were performed to detect B. bacilliformis and subsequently confirmed by sequencing. A total of 383 specimens of L. maranonensis species were analyzed. Two of 76 pools were positive for B. bacilliformis by sequencing; all positives pools were from Querocotillo district. In addition, Mesorhizobium spp. were identified in two pools of sand flies, which is an α-proteobacteria phylogenetically very close to B. bacilliformis. This study presents molecular evidence that suggests L. maranonensis is naturally infected by B. bacilliformis in the Cajamarca department. Further research should determine if L. maranonensis is a vector and could transmit B. bacilliformis.

Tetanus, a vaccine-preventable and potentially fatal disease, continues to remain prevalent in low- and middle-income countries. Furthermore, physicians are often unfamiliar with management of severe tetanus without ventilator support. Therefore, we proposed a modified treatment protocol that provides a low-cost and effective solution for the management of severe tetanus in resource-constrained settings. This is an observational study of 42 patients with severe tetanus treated during 2015–2016 at Surya Kanta Hospital, Bangladesh. This facility does not have an intensive care unit (ICU), and patients admitted here were provided treatment with the modified protocol. A total number of 42 patients with severe tetanus were treated with the modified protocol. Among them, 24 (57.1%) recovered completely, six (14.3%) recovered with the sequela, and 12 (28.6%) died. Among those who recovered with the sequela, four needed mechanical support during walking and two had a visual impairment. No significant adverse event was recorded during the treatment period. The results gathered during this case series provide a sustainable, low-cost, and effective solution to management of severe tetanus in resource-constrained settings where ICUs are unavailable.

The escalating burden of infections attributable to methicillin-resistant Staphylococcus aureus (MRSA) in East African countries is calling for interventional strategies to control the spread of this strain. The present study aimed at determining the prevalence, antimicrobial profiles, and staphylococcal cassette chromosome mec (SCCmec) typing of MRSA strains. This was a cross-sectional laboratory-based study involving 226 non-duplicated S. aureus isolates from different clinical samples of patients attending a referral hospital in Kigali. Kirby–Bauer disk diffusion method was used for drug susceptibility testing. Methicillin-resistant S. aureus were confirmed using polymerase chain reaction (PCR) assay for the mecA gene and SCCmec type PCR assay was used for genotyping. Of 138 S. aureus, 39 (31.2%) were found to be MRSA strains. The mean age of the patients was 21.9 years. The incidence of MRSA increases with age and was 27.1% in patient age group younger than 18 years, 33.3% in the age group between 19 and 65 years, and 66.7% in patient age group older than 65 years. There was a significant association between geographic regions and incidence of MRSA (P = 0.02) with the high MRSA isolates from Northern (61.5%) and Western (50%) provinces. Methicillin-resistant S. aureus strains were found to be mostly susceptible to linezolid (93.5%). Among the MRSA strains, SCCmec type I and SCCmec type IV were the most prevalent at 56.4% and 17.9%, respectively. A high prevalence of MRSA was found in Rwanda. Staphylococcal cassette chromosome mec type I (52.2%) was the most predominant. A continuous surveillance of MRSA strains, particularly in the hospital settings, should be an enduring exercise in Rwanda.

Febrile illnesses are a major cause of mortality in sub-Saharan Africa. Early identification of patients at increased risk of death may avert adverse outcomes. We aimed to independently evaluate the performance of the Modified Early Warning Score, quick Sequential Organ Failure Assessment (qSOFA) score, and Integrated Management of Adolescent and Adult Illness (IMAI) emergency signs and severity criteria to predict in-hospital mortality among a prospective cohort of febrile patients in Tanzania. We evaluated 419 patients aged ≥ 10 years in the period 2007–2008. Of the 44 patients who died, 31 (70.5%) were human immunodeficiency virus (HIV) infected. On univariate analysis, in-hospital mortality was associated with HIV infection, oxygen saturation < 90%, respiratory distress, Glasgow Coma Scale < 15, neck stiffness, unconsciousness, convulsions, hemoglobin < 9 g/dL, absence of a systemic syndrome, and neurologic syndrome. A qSOFA score ≥ 2, the presence of at least one, two, or three IMAI emergency signs, and IMAI severe respiratory distress syndrome without shock were significantly associated with in-hospital mortality. The criterion “presence of at least one IMAI emergency sign” showed a good diagnostic accuracy, as highlighted by the high sensitivity, low negative likelihood ratio, and wide area under the receiver operating characteristics curve. The remaining scores showed a poor performance in predicting fatal outcomes in our study population. Further studies are needed to validate our findings and to derive early warning scores that have good clinical performance in settings throughout sub-Saharan Africa.

Different health-care management guidelines by the World Health Organization exist to help health workers in resource-limited settings treat patients. However, for children with unclassified fever and no danger signs, management guidelines are less clear and follow-up recommendations differ. Both a “universal follow-up” for all children, irrespective of health status, and a “conditional follow-up” only for children whose fever persists are recommended in different guidelines. It is unclear how feasible and acceptable these two different follow-up guidelines are among community health workers and caregivers of the sick child. This qualitative study was conducted in Ethiopia and was nested within a cluster-randomized controlled trial (cRCT). It aimed to determine health extension workers’ (HEWs’) and caregivers’ experiences of the management of febrile children and their perceptions of universal versus conditional follow-up recommendations. Seventeen HEWs and 20 caregivers were interviewed. The interviews revealed that HEWs’ understanding of how to handle an unclassified fever diagnosis increased with the implementation of the cRCT in both study arms (universal versus conditional follow-up). This enabled HEWs to withhold medicines from children with this condition and avoid referral to health centers. Both follow-up recommendations had perceived advantages, while the universal follow-up provided an opportunity to see the child’s health progress, the conditional follow-up advice allowed saving time and costs. The findings suggest that improved awareness of the unclassified fever condition can make HEWs feel more comfortable in managing these febrile children themselves and omitting unnecessary medication. Future community-level management guidelines should provide clearer instructions on managing fever where no malaria, pneumonia, diarrhea, or danger signs are present.

The transmission pattern of hemorrhagic fever with renal syndrome (HFRS) is associated with environmental conditions, including meteorological factors and land-cover. In the present study, the association between HFRS and environmental factors (including maximum temperature, relative humidity, rainfall, and normalized difference vegetation index) were explored in two typical counties in Northeast and two counties in Northwest China with severe HFRS outbreaks by using seasonal autoregressive integrated moving average model with exogenous variables (SARIMAX). The results showed that rainfall with 3- to 4-month lag was closely associated with HFRS in the two counties in Northeast China, whereas relative humidity with 1- or 5-month lag significantly impacts HFRS transmission in the two counties in Northwest China. Moreover, the SARIMAX models exhibit accurate forecasting ability of HFRS cases. Our findings provide scientific support for local HFRS monitoring and control, and the development of a HFRS early warning system.

Travelers to developing regions are at risk for development of influenza-like illness (ILI). Little is known of traveler and trip characteristics associated with the development of ILI. TravMil is a prospective observational study, enrolling subjects presenting to six military travel clinics or predeployment-screening sites. We analyzed pre- and post-travel surveys from travelers visiting regions outside of the continental United States, Western or Northern Europe, Canada, Australia, or New Zealand between January 2010 and March 2016. Influenza-like illness was defined as a self-reported fever associated with either sore throat or cough. Trip and traveler characteristics were analyzed to determine risk factors for the development of ILI. Two thousand nine hundred and thirty-two trips were recorded (55% male, median age 45 years, 69% white, 51% on vacation, median travel duration 17 days). The 2,337 trips included the number of self-reported influenza vaccinations in the preceding 5 years (median 5). Eleven percent of the trips were complicated by an ILI lasting a median of 5 days; 70% and 17% of these reported upper and lower respiratory tract infection, respectively, and 12% reported both. On multivariate analysis, increased risk of ILI was associated with female gender (odds ratio [OR]: 1.60 [confidence interval (CI): 1.25–2.05], P < 0.01), age (years) (OR: 1.01 [CI: 1.01–1.02], P < 0.01); and duration of travel (days) (OR: 1.01 [CI: 1.00–1.01], P < 0.01). Influenza-like illness is common in travelers, regardless of traveler characteristics, purpose of travel, destination, or season of year. Female gender, older age, and longer duration of travel were associated with an increased risk of ILI. Additional tools and strategies are needed to prevent ILI in international travelers.

Both social media use and the popularity of global health electives (GHEs) have increased in recent years. Social media use during GHE is commonplace and has benefits, yet sharers may not consider the ramifications of these posts, including privacy violations. Social media policies—which have become more common in residency programs—may aid in providing clear expectations to trainees abroad. The authors aimed to determine the prevalence of social media policies among pediatric residency programs that offer GHE. The authors used a cross-sectional survey design in which educators at pediatric residency programs that offer GHE were surveyed using REDCap®. For all quantitative data, proportions of responses were calculated and analyzed using Microsoft Excel 2013®. The authors analyzed qualitative data using a conventional content analysis approach. The survey was sent to 74 educators; 39 (53%) responses were received. Most (62%; n = 24) of the pediatric residency programs that offer GHE reported that their institution had a social media policy. About one-third (34%; n = 13) of respondents stated that their programs had social media guidelines that pertained specifically to GHE and fewer indicated that social media guidelines were included in their programs’ GHE predeparture curricula (32%; n = 12). This study found that most of the residency programs surveyed had social media guidelines, but few had guidelines applicable or specific to GHE. Informed by this study and a literature review, the authors propose template language for a social media guideline with considerations for social media use in the context of GHE.

Longitudinal and collaborative global health research curricula to train a well-versed global health corps through skills building in assessment and evaluation are lacking. A without-walls research curriculum was offered to medical and public health students between 2007 and 2015. Mentored cross-disciplinary research projects were developed and implemented in partnership with communities. A multilevel mixed methods design, including semi-structured interviews, post-curriculum surveys, presentations, publications, postgraduation metrics, and feedback from project sites, evaluated educational outcomes. Students (N = 25; aged 27 ± 1.9 years; 90.5% female) participated in the studies in 12 countries, resulting in 26 national-level presentations and 24 peer-reviewed publications, including per student average and range of Institutional Review Board submission (0.95; 0–3), poster presentation (0.85; 0–3), oral presentation (0.65; 0–2), and peer-reviewed submission (1.05; 0–4). On average, the studies (40% mixed methods) lasted 2 years. Analyses and manuscript writing were the most challenging; data collection and presentations were the most rewarding. Majority of the participants strongly agreed with achieving skills in community engagement, interviewing techniques, research design and implementation, research dissemination, and career development. Interview themes included expectations and learning goals, effective mentorship, impact on career goals, and ethical learning. Mentorship qualities were accessibility, real-time problem solving, research expertise, advocate, and balancing guidance with independence. Project sites’ feedback was overwhelmingly positive regarding the projects’ impact. Postgraduation participants hold positions in humanitarian organizations, research programs serving the underserved, and primary care residencies, fellowships, and faculty. This experience illustrates the feasibility and effectiveness of mentored global health research and underlines the crucial link between community collaboration and scholarship for effective global health practice.

Dengue encephalitis and dengue encephalopathy are frequent neurological complications of systemic dengue virus infection. Neuroimaging is normal in approximately 50% of patients. Common imaging abnormalities involve periventricular structures, including the basal ganglion, thalamus, and periventricular white matter. We describe an unusual case of dengue encephalopathy with unilateral imaging abnormalities involving the right cerebral hemisphere and mimicking the involvement of the right middle cerebral artery.

The management of dengue fever (DF) has been suggested to be categorized into decision groups A, B, and C; however, its usefulness in predicting mortality is still unclear, and hence we conducted this study to clarify this issue. We conducted a study by recruiting 2,358 patients with DF from the 2015 outbreak in the Chi-Mei Medical Center. Demographic data, vital signs, clinical symptoms and signs, coexisting morbidities, laboratory data, decision groups categorized according to World Health Organization for clinical management of dengue in 2012, and 30-day mortality rates were included for analysis. The overall 30-day mortality rate was 1.4%. The 30-day mortality rates in decision groups A, B, and C were 0%, 0.5%, and 46.2%, respectively. Compared with Group A, there was a higher mortality risk in Group C (odds ratio [OR]: 1,480, 95% confidence interval [CI]: 195–11,200). The area under the curve of the variable of Group C was excellent (OR: 0.92, 95% CI: 0.85–0.99). The sensitivity, specificity, positive predictive value, and negative predictive value for predicting 30-day mortality in Group C were 88.2%, 98.5%, 46.2%, and 99.8%, respectively. This study showed that decision Group C has a good predictive value for 30-day mortality. Further studies including validation in other nations are warranted.

Dengue is endemic in Indonesia. Here, we describe the epidemiology of dengue in the city of Yogyakarta, Central Java, as a prelude to implementation of a cluster-randomized trial of Wolbachia for the biocontrol of arboviral transmission. Surveillance records from 2006 to 2016 demonstrate seasonal oscillations of dengue incidence with varying magnitude. Two lines of evidence demonstrate a high force of infection; the hospitalized case burden of patients diagnosed with dengue hemorrhagic fever or dengue shock syndrome over the last decade consisted predominantly of children/adolescents, and a serosurvey of 314 healthy children aged 1–10 years found 68% possessed dengue virus–neutralizing antibodies. Finally, a mobility survey indicated children aged 1–10 years, and particularly 1–5 year-olds, spent most of their daytime hours at home. These findings inform the design of clinical trials to measure the impact of novel vector control methods such as Wolbachia introgression into Aedes aegypti mosquitoes, by providing baseline data on disease incidence and identifying subpopulations for recruitment into prospective studies of dengue virus infection and disease. The mobility survey findings indicate that in cluster trials of interventions applied at the community level, young children can reasonably be expected to spend most of their exposure time, in epidemiological terms, within the treatment arm to which they were randomized.

A clinical, serological, and molecular investigation was performed to determine the presence of dengue virus (DENV) and other flaviviruses among residents of the city of Reynosa, Tamaulipas, on the Mexico–U.S. border in 2014–2016. The sample population consisted of 2,355 patients with suspected dengue, in addition to 346 asymptomatic individuals recruited during a household-based epidemiological investigation designed to identify flavivirus seroconversions. Sera were collected from patients with suspected dengue in the acute phase of illness and from asymptomatic individuals at enrollment and every 5–7 months for 19 months. Sera from suspected dengue patients were tested for DENV antigen by enzyme-linked immunosorbent assay (ELISA), and select antigen-positive sera were further tested using a serotype-specific, quantitative reverse transcription–polymerase chain reaction. Sera from the household cohort were tested for flavivirus-reactive antibodies by immunoglobulin (Ig) M and IgG ELISAs using DENV antigen. A total of 418 (17.7%) patients with suspected dengue had laboratory-confirmed DENV infections, including 82 patients who were positive for DENV RNA. The most frequently detected serotype was DENV-1 (61 patients), followed by DENV-2 (16 patients) and DENV-3 (five patients). A total of 217 (62.7%) asymptomatic individuals had flavivirus-reactive antibodies at enrollment, and nine flavivirus-naïve individuals seroconverted. Sera from a subset of dengue patients and household participants, including all those who seroconverted, were further tested by plaque reduction neutralization test, resulting in the detection of antibodies to DENV-1, DENV-2, and West Nile virus. In summary, we provide evidence for the co-circulation of multiple flaviviruses in Reynosa, Tamaulipas, on the Mexico–U.S. border.

Zika virus (ZIKV) was first detected in the Americas in Brazil in 2015, with a rapid spread to surrounding countries. In Panama, the outbreak began in November 2015 in an indigenous community located on the Caribbean side of the country. Zika virus is typically associated with a diffuse rash, fever, and conjunctivitis. It can rarely cause neurologic manifestations, most commonly microcephaly and Guillain–Barré syndrome. Encephalitis and acute encephalomyelitis are known complications, but ZIKV-associated cerebellitis has yet to be reported in the literature. Herein, we report a case of cerebellitis in a patient infected with ZIKV. This patient developed severe frontal headache and vertigo on the third day of illness, and dysarthria and ataxia on the fifth day. After 1 week of hospitalization, the patient completely recovered. The laboratory serological diagnosis was complicated because of the detection of antibodies against dengue, suggesting a secondary flavivirus infection.

When introduced into a naïve population, chikungunya virus generally spreads rapidly, causing large outbreaks of fever and severe polyarthralgia. We randomly selected households in the U.S. Virgin Islands (USVI) to estimate seroprevalence and symptomatic attack rate for chikungunya virus infection at approximately 1 year following the introduction of the virus. Eligible household members were administered a questionnaire and tested for chikungunya virus antibodies. Estimated proportions were calibrated to age and gender of the population. We enrolled 509 participants. The weighted infection rate was 31% (95% confidence interval [CI]: 26–36%). Among those with evidence of chikungunya virus infection, 72% (95% CI: 65–80%) reported symptomatic illness and 31% (95% CI: 23–38%) reported joint pain at least once per week approximately 1 year following the introduction of the virus to USVI. Comparing rates from infected and noninfected study participants, 70% (95% CI: 62–79%) of fever and polyarthralgia and 23% (95% CI: 9–37%) of continuing joint pain in patients infected with chikungunya virus were due to their infection. Overall, an estimated 43% (95% CI: 33–52%) of the febrile illness and polyarthralgia in the USVI population during the outbreak was attributable to chikungunya virus and only 12% (95% CI: 7–17%) of longer term joint pains were attributed to chikungunya virus. Although the rates of infection, symptomatic disease, and longer term joint symptoms identified in USVI are similar to other outbreaks of the disease, a lower proportion of acute fever and joint pain was found to be attributable to chikungunya virus.

The northeastern region of Brazil has faced in the last 2 years the largest outbreak of chikungunya virus (CHIKV) infection in its history. There are still few studies on kidney involvement in CHIKV. The aim of this study is to describe the impact of chronic kidney disease (CKD) on CHIKV clinical manifestations and outcome. This is a cross-sectional study conducted in the State of Ceara, northeastern Brazil, including all registered cases of CHIKV infection in the period from January 2016 to December 2017. Clinical manifestations were collected from the notification reports from official data bank from the State Secretary of Health of Ceara: National System of Diseases Notification and Laboratory Manager. A total of 182,731 cases were notified. Patients’ mean age was 32.4 ± 14.6 years, and 62.2% were female. The most common clinical manifestations were fever (88.6%), headache (72.9%), intense arthralgia (69.5%), and myalgia (65.6%). Hospital admission was required for 3,080 cases (3.3%), and death occurred in 383 cases (0.2%). Chronic kidney disease was reported in 691 cases (0.3%). Patients with CKD had a higher frequency of almost all clinical manifestations, including fever, myalgia, exanthema, vomiting, nausea, back pain, conjunctivitis, arthritis, severe arthralgia, petechiae, and retro-orbital pain. They also had a significantly higher frequency of diabetes, hematological disorders, liver diseases, hypertension, peptic ulcer disease, and autoimmune diseases. Mortality was significantly higher among CKD patients than patients without CKD (3.0% versus 0.2%, P < 0.0001).

Late presentation to healthcare by HIV infected patients’ is common in India despite access to free combination antiretroviral therapy (cART). We assessed risk factors for late presentation among patients with a recent HIV diagnosis in an academic university–based antiretroviral treatment center. This retrospective study included 474 recently diagnosed HIV-infected patients registered for cART between 2012 and 2013. Subjects with CD4+ T-lymphocyte (CD4) count ≤ 350 cells/μL or with an AIDS defining event were defined as late presenters (LP) and patients with CD4 count ≤ 200 cells/μL or with an AIDS defining event were defined as LP with advanced HIV disease (LPAD). Multivariable logistic regression analysis was used to investigate factors associated with late presentation. Of the 474 patients, 356 (75.1%) were LP. Of these, 299 (83.99%) were LPAD and 57 (16.01%) LP were AIDS-free. Median CD4 count among LP was 134 cells/μL (interquartile range 72.25–219). Mean age of LP was 42.50 ± 8.88 years; 256 (71.9%) were males. Increasing age (> 51 years; Adjusted odds ratio [aOR] 4.19; P = 0.014) and rural residence (aOR 3.19; P = < 0.001) were independently associated with late presentation. HIV-positive housewives (aOR 0.34; P = 0.027), HIV-positive individuals with negative partners (aOR 0.48; P = 0.006), and partners with unknown HIV status (aOR 0.43; P = 0.007) were less likely to present late compared with positive partners of people living with HIV/AIDS (PLWHA). Most patients were LP despite free access to cART. Rural population and older PLWHA should be targeted while implementing HIV care. There is a need to strengthen the HIV care cascade by linking PLWHA to cART immediately after diagnosis.

HIV-positive adults on treatment for multi drug-resistant tuberculosis (MDR-TB) experience high mortality. Biomarkers of HIV/MDR-TB treatment response may enable earlier treatment modifications that improve outcomes. To determine whether changes in C-reactive protein (CRP), D-dimer, and fibrinogen were associated with treatment outcome among those with HIV/MDR-TB coinfection, we studied 20 HIV-positive participants for the first 16 weeks of MDR-TB therapy. Serum CRP, fibrinogen, and D-dimer were measured at baseline and serially while on treatment. At baseline, all biomarkers were elevated above normal levels, with median CRP 86.15 mg/L (interquartile range [IQR] 29.25–149.32), D-dimer 0.85 µg/mL (IQR 0.34–1.80), and fibrinogen 4.11 g/L (IQR 3.75–6.31). C-reactive protein decreased significantly within 10 days of treatment initiation and fibrinogen within 28 days; D-dimer did not change significantly. Five (25%) participants died after a median of 32 days. Older age (median age of 38y among survivors and 54y among deceased, P = 0.008) and higher baseline fibrinogen (3.86 g/L among survivors and 6.37 g/L among deceased, P = 0.02) were significantly associated with death. After adjusting for other measured variables, higher CRP concentrations at the beginning of each measurement interval were significantly associated with a higher risk of death during that interval. Trends in fibrinogen and CRP may be useful for evaluating early response to treatment among individuals with HIV/MDR-TB coinfection.

We sought to compare seroprevalence of protective measles and rubella-specific antibody in mother–infant pairs across two populations: a pre-disease elimination Nepal population with recently introduced rubella vaccine and post-disease elimination U.S. population. Qualitative measles and rubella immunoglobulin G was assessed in maternal serum and cord blood from 258 pairs in Nepal, 2012–2013 and 49 pairs in Seattle, WA, 2014–2015. High rates of protective antibody were observed in both populations. Two hundred and forty-four (95%) pregnant women in Nepal had protective measles antibody versus 44 (92%) in Seattle (P = 0.42). Ninety-six percent of infants in Nepal (N = 246) and Seattle (N = 43) had protective measles antibody (P = 0.75). Ninety-four percentage of pregnant women in Nepal (N = 242) and Seattle (N = 45) had protective rubella antibody (P = 0.23). Two hundred and thirty-eight (93%) infants in Nepal had protective rubella antibody versus 44 (98%) in Seattle (P = 0.12). Continued surveillance will be necessary to ensure protective immunity, inform progress toward disease elimination in Nepal and avoid reemergence in the United States.

Heartland virus (HRTV) is a North American phlebovirus suspected to be transmitted by the lone star tick Amblyomma americanum. White-tailed deer (WTD) have been shown to develop HRTV-neutralizing antibodies following experimental infection. To further define the geographic distribution of HRTV through retrospective sampling of WTD, sera from the WTD herd health serum archive at the Southeastern Cooperative Wildlife Disease Study between 2001 and 2015 were analyzed using serum neutralization. Of 783 serum samples tested, 57 (7.3%) were positive for HRTV-neutralizing antibodies. Deer with moderate to heavy tick burdens were more likely seropositive. Seropositive samples were obtained from deer originating from states with documented human cases of HRTV-associated disease. Seropositive samples were identified from years before the recognition of the first human case in 2009. Overall, this study indicates that WTD in the southeastern United States have been exposed to HRTV as early as 2001 and that the presence of seropositive animals corresponds roughly with reported human HRTV-associated disease.

Bothrops lanceolatus is an endemic Crotalidae species in Martinique, where approximately 30 cases of envenoming are managed yearly. Envenoming characteristics from Bothrops species include local tissue damage, systemic bleeding, and hemodynamic alterations. We hereby report a case of severe envenomation following B. lanceolatus snakebite to the right calf. Severe local manifestations developed progressively up to the lower limb despite adequate antivenom therapy. Systemic manifestations of venom also occurred, resulting in intensive care therapy. Surgery exploration revealed soft tissue necrosis, friability of the deep fascia, and myonecrosis. The patient needed multiple debridement procedures and fasciotomy of all leg compartments and anterior compartment of the thigh. Diagnosis of necrotizing fasciitis was confirmed by positive Aeromonas hydrophila blood cultures. This clinical case illustrates that major soft tissue infection, including necrotizing fasciitis may occur after snakebite. Abnormal coagulation tests should not delay surgical management, as severe envenoming is a life-threatening condition.