The American Journal of Tropical Medicine and Hygiene - Current Issue

Melioidosis, a disease caused by the pathogen Burkholderia pseudomallei, is a significant underreported endemic disease found in tropical countries worldwide. Recent studies have demonstrated that human melioidosis cases have been increasingly recognized in the Americas. Therefore, the first Scientific Reunion of Melioidosis in the Americas was organized in Colombia, with the participation of health authorities of 11 Latin American countries and the United States. This report summarizes the topics reviewed during the meeting, including how to identify human infections and properly diagnose them, with the goal of increasing recognition of the disease in the Americas.

Mentoring is a critical component of career development for research scientists and is related to mentee success both in terms of career selection and advancement. However, there are limited data on the role of mentoring in low- and middle-income countries (LMICs). Cross-cultural mentorship programs have the potential to foster the transfer of knowledge and the development of capacity to resource-poor settings. This formative evaluation explores the cultural context of mentoring in the countries of Georgia and Ethiopia. Results were used to build culturally relevant mentor training programs for two Global Infectious Disease Research Training Programs focused on tuberculosis funded by the Fogarty International Center at the US National Institutes of Health. Four focus group discussions were conducted with research trainees and mentors to explore the perceptions of mentorship, identify obstacles for successful mentoring, and generate recommendations to strengthen mentoring in each program situated in a LMIC. Data revealed the barriers to mentoring in Ethiopia and Georgia included gaps in knowledge about mentoring roles and responsibilities, lack of knowledge about the responsibilities of the trainee in a mentoring relationship, and the need to set clear expectations between mentors and trainees. All of the focus group participants desired formal mentor training. These data informed six key components of the development and implementation of the mentor training programs in both countries. The topics included the following: a foundation in mentoring, establishing expectations between mentees and mentors, increasing interactions between mentees and mentors, additional mentor training, a case study curriculum, and methods of evaluating mentoring relationships.

Gram-negative bacilli Vibrio spp., Aeromonas spp., and Shewanella spp. are a major cause of severe waterborne infection. The aim of this study was to assess the clinical and microbiological characteristics and prognosis of patients hospitalized in Reunion Island for a waterborne infection. This retrospective study was conducted in the two university hospitals of Reunion Island between January 2010 and March 2017. Patients diagnosed with a Vibrio, Aeromonas, or Shewanella infection were evaluated. Over the study period, 112 aquatic strains were isolated at Reunion Island: Aeromonas spp. were found in 91 patients (81.3%), Shewanella spp. in 13 patients (11.6%), and Vibrio spp. in eight patients (7.2%). The in-hospital mortality rate was 11.6%. The main sites of infection were skin and soft tissue (44.6%) and the abdomen (19.6%). Infections were polymicrobial in 70 cases (62.5%). The most commonly prescribed empiric antibiotic regimen was amoxicillin–clavulanate (34.8%). Eighty-four percent of the aquatic strains were resistant to amoxicillin–clavulanate and more than > 95% were susceptible to third or fourth generation cephalosporins and fluoroquinolones. After multivariate analysis, the only independent risk factor of in-hospital mortality was the presence of sepsis (P < 0.0001). In Reunion Island, the most commonly isolated aquatic microorganisms were Aeromonas spp. Sepsis caused by aquatic microorganisms was frequent (> 50%) and associated with higher in-hospital mortality. This study suggests that empiric antibiotic regimens in patients with sepsis or septic shock caused by suspected aquatic microorganisms (tropical climate, skin lesion exposed to seawater…) should include broad-spectrum antibiotics (third or fourth generation cephalosporins).

A retrospective study was conducted to identify the risk factors associated with Salmonella enterica bacteremia in infants and children in Guadeloupe, French West Indies. The 171 patients with S. enterica infection seen between 2010 and 2014 included 155 (90.6%) with acute gastroenteritis, of whom 42 (27.1%) had concomitant bacteremia, and 16 (9.4%) with primary bacteremia. Most cases (97.7%) were in infants and children with no underlying health condition. Two subspecies were recovered: enterica (N = 161, 94.2%) and houtenae (N = 10, 5.8%). All but one (serovar Typhi) were non-typhoidal Salmonella. The most common serovars were Panama (N = 57, 33.3% of isolates) and Arechavaleta (N = 28, 16.4%). Univariate analysis showed a strong association only between age > 6 months and infection with the Panama or Arechavaleta serovar (P = 0.002). The rate of resistance to all classes of antibiotics during the study period was low (< 15%); however, the detection of one extended-spectrum beta-lactamase–producing S. enterica strain highlights the need for continued monitoring of antimicrobial drug susceptibility. Infection with Panama (P < 0.001) or Arechavaleta (P < 0.001) serovar was significantly associated with bacteremia in a multivariate analysis. These serovars are probably poorly adapted to humans or are more virulent. A delay between onset of symptoms and hospital admission > 5 days (P = 0.01), vomiting (P = 0.001), and increased respiratory rate (P = 0.001) contributed independently to bacteremia in the multivariate analysis. Thus, if non-typhoidal infection is suspected, blood should be cultured and antibiotic treatment initiated in all patients who meet these criteria.

Leptospirosis is a worldwide zoonotic bacterial infection with a rising incidence. French Guiana is mostly covered by Amazonian rain forest. Despite a potentially favorable environment, leptospirosis has been barely studied in French Guiana. The objective of this study was to describe the current trends of leptospirosis epidemiology in French Guiana. A cross-sectional study was performed in the two main hospitals of French Guiana. Cases of leptospirosis from 2007 to 2014 were retrospectively identified with a systematic screening of serological and polymerase chain reaction results to classify them as confirmed, probable, or excluded cases. Medical files were reviewed to collect epidemiological data. Among the 72 included patients, 55 (76.4%) cases were confirmed and 17 (23.6%) were probable. The median age was 39 years (range: 16–82 years) and the M/F sex ratio 6.2. Sixty-two (86.1%) patients required hospitalization, including 12 (16.7%) in the intensive care unit. Three (4.2%) patients died. The monthly distribution of cases was correlated with rainfall (P = 0.004) and moisture (P = 0.038). Professional exposure was frequently identified (especially gold mining and construction). Among 16 different serogroups identified by microagglutination test, Icterohaemorrhagiae was the most frequent (38.0%). This study revealed an epidemiology close to that observed in Brazilian regions, and professional and climatic risk factors. The high diversity of serogroups may reveal a complex environmental reservoir requiring further investigations. Only 20% of leptospirosis patients were suspected as such on hospital admission, thus emphasizing the need to inform local physicians.

Melioidosis has a high case fatality rate and is more common in patients with chronic kidney disease. Some authors recommended trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis for all hemodialysis (HD) patients during the wet season in melioidosis-endemic regions. Historical data were reviewed to determine if TMP/SMX prophylaxis was warranted in the HD population of Far North Queensland, Australia. Between 1997 and 2017, there were 242 culture-confirmed cases of melioidosis in the region, three (1.2%) occurred in HD patients; all survived without intensive care support. During the study period, there were 843 HD patients in the region with 3,024 cumulative patient years of risk. Even assuming 100% efficacy, it would have been necessary to prescribe TMP/SMX for 1,008 patient years to prevent one case of melioidosis. Given the significant additional cost and potentially life-threatening side effects of TMP/SMX therapy, clinicians should review the local epidemiology of melioidosis before the implementation of universal TMP/SMX prophylaxis in their HD population.

Pediatric tuberculosis (TB) represents a major barrier to reducing global TB mortality, especially in countries confronting dual TB and human immunodeficiency virus (HIV) epidemics. Our study aimed to characterize pediatric TB epidemiology in the high-burden setting of Harare, Zimbabwe, both to fill the current knowledge gap around the epidemiology of pediatric TB and to indicate areas for future research and interventions. We analyzed de-identified data of 1,051 pediatric TB cases (0–14 years) found among a total of 11,607 TB cases reported in Harare, Zimbabwe, during 2011–2012. We performed Pearson’s χ2 test and multivariate logistic regression analysis to characterize pediatric TB and to assess predictors of HIV coinfection. Pediatric TB cases accounted for 9.1% of all TB cases reported during 2011–2012. Approximately 50% of pediatric TB cases were children younger than 5 years. Almost 60% of the under-5 age group were male, whereas almost 60% of the 10–14 age group were female. The overall HIV coinfection rate was 58.3%. Odds for HIV coinfection was higher for the 5–9 age group (adjusted odds ratio [AOR]: 2.77, 95% confidence interval [CI]: 1.97–3.94), the 10–14 group (AOR: 3.57, 95% CI: 2.52–5.11), retreatment cases (AOR: 6.17, 95% CI: 2.13, 26.16), and pulmonary TB cases (AOR: 2.39, 95% CI: 1.52, 3.75). In conclusion, our study generated evidence that pediatric TB, compounded by HIV coinfection, significantly impacts children in high-burden settings. The findings of our study indicate a critical need for targeted interventions.

Wolbachia bacteria are known to cause deviations from random mating and affect sperm competition (SC) in some of their arthropod hosts. Because these effects could influence the effectiveness of Wolbachia in mosquito population replacement and suppression programs, we developed a theoretical framework to investigate them and we collected relevant data for the wMel infection in Aedes aegypti. Using incompatibility patterns as a measure of mating success of infected versus uninfected mosquitoes, we found some evidence that uninfected males sire more offspring than infected males. However, our theoretical framework suggests that this effect is unlikely to hamper Wolbachia invasion and has only minor effects on population suppression programs. Nevertheless, we suggest that mating effects and SC need to be monitored in an ongoing manner in release programs, given the possibility of ongoing selection for altered mating patterns.

We report a case of human cutaneous myiasis by Hypoderma lineatum, contracted by a farmer who never traveled outside Italy. Identification at species level has been performed by both morphological examination and sequencing of cytochrome c oxidase subunit I gene. This is the first description of human hypodermosis by H. lineatum contracted in Europe.

Congenital malaria (CM) is uncommon in both malaria-endemic and non-endemic countries. It may be caused by any Plasmodium spp., although Plasmodium falciparum and Plasmodium vivax are the more frequent etiologic agents. We report a case of delayed diagnosis of CM by P. vivax in a newborn of an Eritrean primigravida. The mother developed pregnancy-related immunodepression and varicella-zoster viral infection 9 days before natural delivery; therefore, the child was admitted in the neonatal intensive care unit (NICU) to administer specific varicella-zoster immunoglobulin prophylaxis and for clinical monitoring. During the NICU stay, the newborn presented a febrile syndrome with vomiting, anemia, and thrombocytopenia. A P. vivax severe malaria diagnosis was made by detecting trophozoites in the thick and thin blood smears. The infant was successfully treated with intravenous artesunate and clindamycin. Our experience suggests that malaria diagnostic tests need to be included in routine blood analyses in newborns with febrile syndrome from mothers with an epidemiologic link to malaria-endemic areas.

Although falciparum malaria is an important risk among travelers to sub-Saharan Africa, many travelers remain unaware of this risk. In October 2015, we found a cluster of imported Plasmodium falciparum malaria cases among Thai gem mine workers in Nigeria; none had received malaria chemoprophylaxis or information regarding malaria risk. The index case developed fever and visited our hospital on arrival day in Thailand after his 3-week stay in Nigeria. Plasmodium falciparum was found in his blood. He recovered completely 3 days post-admission. After we requested he contact his colleagues in Nigeria regarding malaria risk, we found that three of his five colleagues currently had fever, were diagnosed with malaria, and were being treated in a local hospital. Two were successfully treated in Nigeria. Although their blood films were negative for malaria, we could confirm that they recently had malaria because the polymerase chain reaction (PCR) was still positive for P. falciparum. Tragically, the last febrile case died in Nigeria 6 days post-admission, after developing jaundice and alteration of consciousness. The two colleagues without fever symptoms were also tested by PCR, which was negative for malaria. In conclusion, we found that four of six workers had malaria in this cluster, which was equal to 66.7% attack rate. There is an urgent need to raise awareness of malaria among workers in highly endemic areas. Clinical practice for travelers who are ill on their return should not only focus on individual cases but also consider potential disease clusters.

Using a decision-tree approach, we examined the cost-effectiveness of indoor residual spraying (IRS) of households with insecticide combined with insecticide-treated bed net (ITN) distribution (IRS + ITN), compared with ITN distribution alone in the programmatic context of mainland Tanzania. The primary outcome of our model was the expected economic cost to society per case of malaria averted in children ≤ 5 years of age. Indoor residual spraying of households with insecticide data came from a program implemented in northwest Tanzania from 2008 to 2012; all other data originated from the published literature. Through sensitivity and scenario analyses, the model also examined the effects of variations in insecticide resistance, malaria prevalence, and different IRS modalities. In the base case, IRS + ITN is expected to be more expensive and more effective than the ITN-only intervention (incremental cost-effectiveness ratio [ICER]: $152.36). The number of IRS rounds, IRS insecticide costs, ITN use, malaria prevalence, and the probability that a child develops symptoms following infection drove the interventions’ cost-effectiveness. Compared with universal spraying, targeted spraying is expected to lead to a higher number of malaria cases per person targeted (0.211–0.256 versus 0.050–0.076), but the incremental cost per case of malaria averted is expected to be lower (ICER: $41.70). In a scenario of increasing pyrethroid resistance, the incremental expected cost per case of malaria averted is expected to increase compared with the base case (ICER: $192.12). Tanzania should pursue universal IRS only in those regions that report high malaria prevalence. If the cost per case of malaria averted of universal IRS exceeds the willingness to pay, targeted spraying could provide an alternative, but may result in higher malaria prevalence.

Mefloquine (Lariam®; Roche Holding AG, Basel, Switzerland) has been linked to acute neuropsychiatric side effects. This is a concern for U.S. veterans who may have used mefloquine during recent Southwest Asia deployments. Using data from the National Health Study for a New Generation of U.S. Veterans, a population-based study of U.S. veterans who served between 2001 and 2008, we investigated associations between self-reported use of antimalarial medications and overall physical and mental health (MH) using the twelve-item short form, and with other MH outcomes using the post-traumatic stress disorder Checklist-17 and the Patient Health Questionnaire (anxiety, major depression, and self-harm). Multivariable logistic regression was performed to examine associations between health measures and seven antimalarial drug categories: any antimalarial, mefloquine, chloroquine, doxycycline, primaquine, mefloquine plus any other antimalarial, and any other antimalarial or antimalarial combination while adjusting for the effects of deployment and combat exposure. Data from 19,487 veterans showed that although antimalarial use was generally associated with higher odds of negative health outcomes, once deployment and combat exposure were added to the multivariable models, the associations with each of the MH outcomes became attenuated. A positive trend was observed between combat exposure intensity and prevalence of the five MH outcomes. No significant associations were found between mefloquine and MH measures. These data suggest that the poor physical and MH outcomes reported in this study population are largely because of combat deployment exposure.

The efficacies of 3-day regimens of artemether–lumefantrine (AL), artesunate–amodiaquine (AA), and dihydroartemisinin–piperaquine (DHP) were evaluated in 910 children < 5 years old with uncomplicated malaria from six geographical areas of Nigeria. Parasite positivity 1 day and Kaplan–Meier estimated risk of persistent parasitemia 3 days after therapy initiation were both significantly higher, and geometric mean parasite reduction ratio 1 day after treatment initiation (PRRD1) was significantly lower in AL-treated children than in AA- and DHP-treated children. No history of fever, temperature > 38°C, enrollment parasitemia > 75,000 μL−1, and PRRD1 < 5,000 independently predicted persistent parasitemia 1 day after treatment initiation. Parasite clearance was significantly faster and risk of reappearance of asexual parasitemia after initial clearance was significantly lower in DHP-treated children. Overall, day 42 polymerase chain reaction–corrected efficacy was 98.3% (95% confidence interval [CI]: 96.1–100) and was similar for all treatments. In a non-compartment model, declines of parasitemias were monoexponential with mean terminal elimination half-life of 1.3 hours and unimodal frequency distribution of half-lives. All treatments were well tolerated. In summary, all three treatments evaluated remain efficacious treatments of uncomplicated malaria in young Nigerian children, but DHP appears more efficacious than AL or AA.

The complex relationship between malnutrition and malaria affects morbidity and mortality in children younger than 5 years, particularly in parts of sub-Saharan Africa where these conditions occur together seasonally. Previous research on this relationship has been inconclusive. Here, we examine the association between anthropometric indicators and malaria infection in a population-based sample of children younger than 5 years in Niger. This cross-sectional study is a secondary analysis of a cluster-randomized trial comparing treatment strategies for trachoma in Niger. We included children aged 6–60 months residing in the 48 communities enrolled in the trial who completed anthropometric and malaria infection assessments at the final study visit. We evaluated the association between anthropometric indicators, including height-for-age z-score (HAZ) and weight-for-age z-score (WAZ) and indicators of malaria infection, including malaria parasitemia and clinical malaria. In May 2013, we collected data from 1,649 children. Of these, 780 (47.3%) were positive for malaria parasitemia and 401 (24.3%) had clinical malaria. In models of malaria parasitemia, the adjusted odds ratio (aOR) was 1.05 (95% confidence interval [CI]: 1.00–1.10) for HAZ and 1.07 (95% CI: 0.99, 1.15) for WAZ. In models of clinical malaria, the aOR was 1.07 (95% CI: 1.02–1.11) for HAZ and 1.09 (95% CI: 1.01–1.19) for WAZ. Overall, we did not find evidence of an association between most anthropometric indicators and malaria infection. Greater height may be associated with an increased risk of clinical malaria.

Universal malaria diagnostic testing of all fever cases is the first step in correct malaria case management. However, monitoring adherence to universal testing is complicated by unreliable recording and reporting of the true number of fever cases. We searched the literature to obtain gold-standard estimates for the proportion of patients attending outpatient clinics in sub-Saharan Africa with malarial and non-malarial febrile illness. To correct for differences in malaria transmission, we calculated the proportion of patients with fever after excluding confirmed malaria cases. Next, we analyzed routine data from Guinea and Senegal to calculate the proportion of outpatients tested after exclusion of confirmed malaria cases from the numerator and denominator. From 12 health facility surveys in sub-Saharan Africa with gold-standard fever screening, the median proportion of febrile illness among outpatients after exclusion of confirmed malaria fevers was 57% (range: 46–80%). Analysis of routine data after exclusion of confirmed malaria cases demonstrated much lower testing proportions of 23% (Guinea) and 13% (Senegal). There was substantial spatial and temporal heterogeneity in this testing proportion, and testing in Senegal was correlated with malaria season. Given the evidence from gold-standard surveys that at least 50% of non-malaria consultations in sub-Saharan Africa are for febrile illness, it appears that a substantial proportion of patients with fever are not tested for malaria in health facilities when considering routine data. Tracking the proportion of patients tested for malaria after exclusion of the confirmed malaria cases could allow programs to make inferences about malaria testing practices using routine data.

Malaria is endemic in the southern plain of Nepal which shares a porous border with India. More than 80% cases of malaria in Nepal are caused by Plasmodium vivax. The main objective of this study was to review the epidemiology of P. vivax malaria infections as recorded by the national malaria control program of Nepal between 1963 and 2016. National malaria data were retrieved from the National Malaria program in the Ministry of Health, Government of Nepal. The epidemiological trends and malariometric indicators were analyzed. Vivax malaria has predominated over falciparum malaria in the past 53 years, with P. vivax malaria comprising 70–95% of the annual malaria infections. In 1985, a malaria epidemic occurred with 42,321 cases (82% P. vivax and 17% Plasmodium falciparum). Nepal had experienced further outbreaks of malaria in 1991 and 2002. Plasmodium falciparum cases increased from 2005 to 2010 but since then declined. Analyzing the overall trend between 2002 (12,786 cases) until 2016 (1,009 cases) shows a case reduction by 92%. The proportion of imported malaria cases has increased from 18% of cases in 2001 to 50% in 2016. The current trends of malariometric indices indicate that Nepal is making a significant progress toward achieving the goal of malaria elimination by 2025. Most of the cases are caused by P. vivax with imported malaria comprising an increasing proportion of cases. The malaria control program in Nepal needs to counter importation of malaria at high risk areas with collaborative cross border malaria control activities.

It has been believed that concomitant bacteremia is uncommon in adults hospitalized with falciparum malaria. Accordingly, the World Health Organization treatment guidelines presently only recommended additional antibacterial therapy in these patients if they have a clinical syndrome compatible with serious bacterial infection. Admission blood cultures were collected from 20 consecutive adults in Myanmar, hospitalized with a positive immunochromatographic test and blood film, suggesting a diagnosis of falciparum malaria; four (20%) had bacteremia with a clinically significant pathogen. These case series’ data were pooled with a previously published multicenter study from Myanmar which had also collected blood cultures in adults hospitalized with a diagnosis of falciparum malaria. Among 87 patients in the two studies, 13 (15%) had clinically significant bacteremia on admission, with Gram-negative organisms in 10 (77%) and Staphylococcus aureus in the remaining three (23%). Bacteremic patients had more severe disease than non-bacteremic patients (median [interquartile range] respiratory coma acidosis malaria score 2 [1–4] versus 1 [1–2], P = 0.02) and were more likely to die (2/13 [15%] versus 1/74 [1%], P = 0.01). However, bacterial coinfection was suspected clinically in a minority of bacteremic patients (5/13 [38%] compared with 13/70 [19%] of non-bacteremic patients, P = 0.11). Concomitant bacteremia in adults diagnosed with falciparum malaria may be more common than previously believed and is difficult to identify clinically in resource-poor settings. Death is more common in these patients, suggesting that clinicians should have a lower threshold for commencing empirical antibacterial therapy in adults diagnosed with falciparum malaria in these locations than is presently recommended.

Histidine-rich protein 2 of Plasmodium falciparum (PfHRP2) forms the basis of many current malaria rapid diagnostic tests (RDTs). It is concerning that there are parasites that lack part or all of the pfhrp2 gene, and thus do not express the PfHRP2 protein; such parasites are not identifiable by PfHRP2-detecting RDTs. Very limited information is available regarding pfhrp2 genetic variation in Papua New Guinea (PNG). In the present study, this gene variation was evaluated using 169 samples previously collected from the Wosera area in East Sepik Province of PNG. Molecular diagnosis of these samples showed that 81% were infected, and P. falciparum was present in 91% of those infected samples. One hundred and twenty samples were amplified for pfhrp2 exon-2, from which 12 randomly selected amplicons were sequenced, yielding 18 sequences, all of which were unique. Baker repeat type 2 × type 7 numbers ranged from 0 to 108. Epitope mapping analysis revealed that three major epitopes, DAHHAHHA, AHHAADAHHA, and AHHAADAHH, were present in high prevalence and frequencies. These major epitopes have been shown to be recognized by the monoclonal antibodies 3A4 and PTL-3 (DAHHAHHA), C1-13 (AHHAADAHHA), and S2-5 and C2-3 (AHHAADAHH). This study provides further information on the high genetic variation of pfhrp2 and its unclear relationship with prediction of RDT detection sensitivity, and identifies major epitopes in this gene from PNG. These results could be relevant and useful to understand the genetic diversity of this gene and the performance of current and future RDTs in this malarious region of the world.

The present study aims to develop a method for rapid diagnosis of malaria using loop-mediated isothermal amplification (LAMP) combined with a lateral flow device (LFD). By adding the biotin-labeled and fluorescein amidite-labeled loop primers to the LAMP reaction solution, the end product can be visualized on a LFD. The entire procedure takes approximately 42 minutes to complete, LAMP assay exhibited high sensitivity, as the detection limit was 0.01 pg/μL for all five Plasmodium species. It was demonstrated that all Plasmodium knowlesi (N = 90) and Plasmodium vivax (N = 56) were positively amplified by LAMP-LFD assay, whereas healthy donor samples (N = 8) were negative. However, not all mixed infections were positive, and other infected nonmalaria samples were negative. Loop-mediated isothermal amplification-LFD represents a robust approach with potential suitability for use in resource-constrained laboratories. We believe that LAMP-LFD has a potential to be developed as point-of-care diagnostic tool in future.

Controlled human malaria infections (CHMIs) with Plasmodium falciparum (Pf) parasites are well established. Exposure to five Pf (NF54)-infected Anopheles mosquitoes results in 100% infection rates in malaria-naïve volunteers. Recently Pf clones NF135.C10 and NF166.C8 were generated for application in CHMIs. Here, we tested the clinical infection rates of these clones, using graded numbers of Pf-infected mosquitoes. In a double-blind randomized trial, we exposed 24 malaria-naïve volunteers to bites from one, two, or five mosquitoes infected with NF135.C10 or NF166.C8. The primary endpoint was parasitemia by quantitative polymerase chain reaction. For both strains, bites by five infected mosquitoes resulted in parasitemia in 4/4 volunteers; 3/4 volunteers developed parasitemia after exposure to one or two infected mosquitoes infected with either clone. The prepatent period was 7.25 ± 4.0 days (median ± range). There were no serious adverse events and comparable clinical symptoms between all groups. These data confirm the eligibility of NF135.C10 and NF166.C8 for use in CHMI studies.

Because anemia is one of the markers of morbidity associated with schistosomiasis, it has been proposed as a potential measure to evaluate the impact of control programs. However, anemia is also a common consequence of malaria, and schistosomiasis and malaria are often co-endemic. To estimate the attributable fraction of anemia due to Schistosoma mansoni and Plasmodium falciparum infections, we applied a log-binomial model to four studies measuring these parameters of a combined 5,849 children in western Kenya. In our studies, malaria contributed 23.3%, schistosomiasis contributed 6.6%, and co-infection contributed 27.6% of the anemia. We conclude that in areas where S. mansoni and P. falciparum are co-endemic, the contribution of schistosomiasis to anemia is masked by anemia resulting from malaria, thus limiting anemia as a useful measure for schistosomiasis control programs in these settings.

In rural areas in Morocco, diagnosing cutaneous leishmaniasis (CL) can be challenging. We evaluated the accuracy of a rapid diagnostic test (RDT) based on antigen detection, CL Detect Rapid Test™ (Inbios International Inc., Seattle, WA), in this setting. We consecutively recruited patients with new skin ulcers in nine primary health centers. We took a dental broach sample for the RDT and two other tissue samples by scraping the border and center of the lesion with a scalpel and smearing it on a slide. We duplicated each smear by pressing a clean slide against it and processed the slides by microscopy, polymerase chain reaction (PCR) internal transcribed spacer 1, and kDNA minicircle PCR. In a subgroup with positive PCR, the Leishmania species was identified using PCR-restriction fragment length polymorphism and PCR-sequencing of hsp70 genes. A participant with positive microscopy and/or PCR was considered a confirmed CL case. We computed sensitivity (Se) and specificity (Sp) of the RDT compared with this reference standard (ClinicalTrials.gov registration: NCT02979002). Between December 2016 and July 2017, we included 219 patients, 50% of them were under 18 years old. Rapid diagnostic test Se was 68% [95% confidence interval (CI): 61–74], Sp 94% [95% CI: 91–97], positive predictive value 95% [95% CI: 92–98], and negative predictive value 64% [95% CI: 58–70]. Despite its low Se, this novel RDT is a useful addition to clinical management of CL in Morocco, especially in isolated localities. Rapid diagnostic test–positive lesions can be treated as CL; but when RDT negative, microscopy should be done in a second step. The Se of the RDT can probably be optimized by improving the sampling procedure.

In the Americas, 8 million people are infected with Chagas disease, and an additional 90 million people are at risk for infection. Little is known about the role bats play in the sylvatic transmission cycle of Trypanosoma cruzi, the parasite causing Chagas disease. Here, we captured bats in the villages of Palmiche, Pachacutec, Nuevo San Martin, and Mayuriaga located in the Datem del Marañon Province in Loreto, Peru. Venous blood samples were collected by cardiac puncture or from the upper extremities, and trypanosomatids were identified by microscopy and molecularly. We collected blood samples from 121 bats on filter paper for molecular studies and 111 slides for microscopic examination of thin and thick blood smears from 16 different bat species. The prevalence of trypanosomatids in all bats species was 34.7% (42/121) and the prevalence of T. cruzi was 4.1% (5/121). In hematophagous bat species, the prevalence of trypanosomatids and T. cruzi was 36.9% (27/73) and 2.7% (2/73), respectively. In non-hematophagous bats, the prevalences of trypanosomatids and T. cruzi were 31.2% (15/48) and 6.2% (3/48), respectively. Also, we confirm the presence of T. cruzi in salivary glands of hematophagous bats Diaemus youngi. These results suggest a sylvatic cycle of trypanosomatid transmission in which bats may harbor infectious T. cruzi parasites that could be transmitted to humans via hematophagous bat bites or salivary contamination by non-hematophagous bats of vegetables consumed by humans.

Headache in patients with calcified neurocysticercosis (NCC) is probably common but has been largely overlooked. We aimed to assess the presence, characteristics, and diagnosis of headache across patients with calcified NCC and their matched controls. In this case–control study nested to a population-based cohort, Atahualpa residents aged ≥ 20 years with calcified NCC were identified as case patients and paired 1:1 to age- and gender-matched randomly selected controls. A culturally adapted questionnaire was derived from the EUROLIGHT. Headache diagnosis was established according to the International Classification of Headache Disorders, 3rd edition. Conditional logistic regression models for matched paired data were fitted to assess the independent association between calcified NCC (as the exposure) and headache variables, after adjusting for education, alcohol intake, depression, and epilepsy. The selection process generated 106 case patients and their matched controls. Lifetime headache prevalence (odds ratio [OR]: 4.18; 95% Confidence Interval [CI]: 1.79–9.75; P = 0.001), current headaches (OR: 4.19; 95% CI: 1.92–9.16; P < 0.001), and intense headaches (OR: 9.47; 95% CI: 2.88–31.19; P < 0.001) were more frequent among cases than in controls. In addition, migraine (but not other forms of headache) was more frequent among subjects with calcified NCC (OR: 4.89; 95% CI: 2.36–11.39; P < 0.001). This study shows a robust epidemiological association between headache—particularly migraine—and calcified NCC.

The Sri Lankan Anti-Filariasis campaign distributed five rounds of mass drug administration (MDA with diethylcarbamazine plus albendazole) to some 10 million people in eight districts between 2002 and 2006. Sri Lanka was recognized by the WHO for having eliminated lymphatic filariasis (LF) as a public health problem in 2016. However, recent studies by our group documented pockets with persistent LF in coastal Sri Lanka, especially in Galle district. The present study was performed to reexamine an area previously identified as a potential hotspot for persistent LF (Balapitiya Public Health Inspector area, population 17,500). A community survey documented high rates for circulating filarial antigenemia (3%, confidence interval [CI]: 1.8–4.9) and microfilaremia (1%, CI: 0.5–2.5%). Circulating filarial antigenemia rates were 2.8-fold higher in males than females. High prevalence was also observed for anti-filarial antibodies in young children (5.7%, CI: 3.7–8.4%) and for filarial DNA in vector mosquitoes (5.2%, CI: 4.2–6.3%). Spatial data showed that persistent LF was dispersed across the entire study area. Other studies showed that persistent LF was not limited to Balapitiya and not solved by additional rounds of MDA. Molecular xenomonitoring studies conducted in 2016 in 22 of 168 Public Health Midwife areas in the coastal Galle evaluation unit (approximate population 600,000) found that 179 of 660 (27%) pools of Culex collected from all areas were positive for Wuchereria bancrofti DNA by quantitative polymerase chain reaction; the estimated infection rate in mosquitoes was 1.26%, CI: 1.0–1.5%. Interventions other than routine MDA will be required to remove LF hotspots in Balapitiya and in other areas in coastal Sri Lanka.

Angiostrongyliasis is a food-borne parasitic disease caused by the nematode Angiostrongylus cantonensis that can lead to eosinophilic meningitis (EM) or meningoencephalitis in humans. Angiostrongylus cantonensis is prevalent in the Pacific Islands. In recent years, a large number of outbreaks and severe cases have occurred. Several species of mollusk, such as snails and slugs, act as intermediate and paratenic hosts of A. cantonensis. In this study, two cases of EM were found to have been caused by infection with A. cantonensis due to consumption of raw centipedes. To survey the A. cantonensis infections acquired through centipedes that the patients had bought at a vegetable market, we performed etiological examinations and polymerase chain reaction amplification of A. cantonensis genes. Third-instar larvae of A. cantonensis were detected in the centipedes, and specific genes from A. cantonensis were detected in all the specimens. This indicates that the centipede may act as a competent host for the transmission of A. cantonensis. To our knowledge, this is the first report of A. cantonensis infection through the consumption of centipedes.

Onchocerciasis is a neglected tropical disease targeted for elimination. The World Health Organization (WHO) has developed guidelines for the verification of onchocerciasis elimination that include entomological and epidemiological criteria. The latter require demonstrating with statistical confidence that the infection prevalence in children is less than 0.1%, necessitating an assay with a high degree of specificity. We present an analysis of the performance of the Onchocerciasis Elimination Program for the Americas (OEPA) version of the Ov16 enzyme-linked immunosorbant assay (ELISA) when used under operational conditions. In Africa and Latin America, the assay demonstrated 99.98% specificity in 69,888 children in 20 foci where transmission was believed to be interrupted. The assay produced a prevalence estimate equal to that of skin snip microscopy when applied in putatively hypo-endemic zones of Ethiopia. The OEPA Ov16 ELISA demonstrated the specificity required to be effectively deployed to verify transmission elimination under the WHO guidelines, while exhibiting a sensitivity equivalent to skin snip microscopy to identify hypo-endemic areas.

Protobothrops mucrosquamatus (Trimeresurus mucrosquamatus) is a medically important species of pit viper with a wide geographic distribution in Southeast Asia. Bites by P. mucrosquamatus mostly involve the extremities. Little is known about the toxic effects of P. mucrosquamatus envenoming to the head because of the infrequency of such occurrence. To better delineate the clinical manifestations of envenoming to the head, we report three patients who suffered from P. mucrosquamatus bites to the head and were treated successfully. All three patients developed progressive soft tissue swelling extending from head to neck, with two patients expanding further onto the anterior chest wall. Mild thrombocytopenia was noted in two patients. One patient had transient acute renal impairment and airway obstruction, necessitating emergent intubation. All three patients received high doses of species-specific antivenom with recovery within 1 week. No adverse reactions to antivenom were observed.

Flaviviruses such as Zika, dengue, and yellow fever cause epidemics throughout the tropics and account for substantial global morbidity and mortality. Although malaria and other vector-borne diseases have long been appreciated in Africa, flavivirus epidemiology is incompletely understood. Despite the existence of an effective vaccine, yellow fever continues to cause outbreaks and deaths, including at least 42 fatalities in the Democratic Republic of the Congo (DRC) in 2016. Here, we leveraged biospecimens collected as part of the nationally representative 2013–2014 Demographic and Health Survey in the DRC to examine serological evidence of flavivirus infection or vaccination in children aged 6 months to 5 years. Even in this young stratum of the Congolese population, we find evidence of infection by dengue and Zika viruses based on results from enzyme-linked immunosorbent assay and neutralization assay. Surprisingly, there was remarkable discordance between reported yellow fever vaccination status and results of serological assays. The estimated seroprevalences of neutralizing antibodies against each virus are yellow fever, 6.0% (95% confidence interval [CI] = 4.6–7.5%); dengue, 0.4% (0.1–0.9%); and Zika, 0.1% (0.0–0.5%). These results merit targeted, prospective studies to assess effectiveness of yellow fever vaccination programs, determine flavivirus seroprevalence across a broader age range, and investigate how these emerging diseases contribute to the burden of acute febrile illness in the DRC.

Bangladesh introduced hepatitis B vaccine in a phased manner during 2003–2005 into the routine childhood vaccination schedule. This study was designed to evaluate the impact of the introduction of hepatitis B vaccine in Bangladesh by comparing hepatitis B surface antigen (HBsAg) prevalence among children born before and after vaccine introduction and to estimate the risk of vertical transmission of chronic hepatitis B virus (HBV) infection from mother to infant. We also evaluated the field sensitivity and specificity of an HBsAg point-of-care test strip. We selected a nationally representative sample of 2,100 prevaccine era and 2,100 vaccine era children. We collected a 5-mL blood sample from each child. One drop of blood was used to perform rapid HBsAg testing. If a child had a positive HBsAg test result with the rapid test, a blood sample was collected from the mother of the HBsAg-positive child and from the mothers of two subsequently enrolled HBsAg-negative children. All samples were tested for serologic markers of HBV infection using standard enzyme-linked immunosorbent assay. One (0.05%) child in the vaccine era group and 27 (1.2%; 95% confidence interval [CI]: 0.8–1.7%) children in the prevaccine era group were HBsAg positive. Mothers of HBsAg-positive children were more likely to be HBsAg positive than mothers of HBsAg-negative children (odds ratios = 4.7; 95% CI: 1.0–21.7%). Sensitivity of the HBsAg rapid test was 91.2% (95% CI: 76.6–98.1%) and specificity was 100% (95% CI: 99.9–100%). The study results suggest that even without a birth dose, the hepatitis B vaccine program in Bangladesh was highly effective in preventing chronic HBV infection among children.

Data on the epidemiology of severe acute respiratory illness (SARI) in adults from low-income, high human immunodeficiency virus (HIV) prevalence African settings are scarce. We conducted adult SARI surveillance in Blantyre, Malawi. From January 2011 to December 2013, individuals aged ≥ 15 years with SARI (both inpatients and outpatients) were enrolled at a large teaching hospital in Blantyre, Malawi. Nasopharyngeal aspirates were tested for influenza and other respiratory viruses by polymerase chain reaction. We estimated hospital-attended influenza-positive SARI incidence rates and assessed factors associated with influenza positivity and clinical severity (Modified Early Warning Score > 4). We enrolled 1,126 SARI cases; 163 (14.5%) were positive for influenza. Human immunodeficiency virus prevalence was 50.3%. Annual incidence of hospital-attended influenza-associated SARI was 9.7–16.8 cases per 100,000 population. Human immunodeficiency virus was associated with a 5-fold greater incidence (incidence rate ratio 4.91, 95% confidence interval [CI]: 3.83–6.32). On multivariable analysis, female gender, as well as recruitment in hot, rainy season (December to March; adjusted odds ratios (aOR): 2.82, 95% CI: 1.57–5.06) and cool, dry season (April to August; aOR: 2.47, 95% CI: 1.35–4.15), was associated with influenza positivity, whereas influenza-positive patients were less likely to be HIV-infected (aOR: 0.59, 95% CI: 0.43–0.80) or have viral coinfection (aOR: 0.51, 95% CI: 0.36–0.73). Human immunodeficiency virus infection (aOR: 1.86; 95% CI: 1.35–2.56) and recruitment in hot, rainy season (aOR: 4.98, 95% CI: 3.17–7.81) were independently associated with clinical severity. In this high HIV prevalence population, influenza was associated with nearly 15% of hospital-attended SARI. Human immunodeficiency virus infection is an important risk factor for clinical severity in all-cause and influenza-associated SARI. Expanded access to HIV testing and antiretroviral treatment, as well as targeted influenza vaccination, may reduce the burden of SARI in Malawi and other high HIV prevalence settings.

The recent Zika virus (ZIKV) epidemic swept across Latin America and the Caribbean, where dengue virus (DENV) is endemic. The antigenic similarities of these closely related flaviviruses left researchers and clinicians with challenges to interpret serological tests. Thirty-six women attending a prenatal clinic in Honduras and with positive DENV IgM enzyme-linked immunoabsorbent assays (ELISAs) were screened with a ZIKV immunoglobulin M ELISA, reverse transcription polymerase chain reaction for ZIKV and DENV 1–4, and plaque reduction neutralization tests (PRNTs) for ZIKV and DENV-2. Plaque reduction neutralization test results were interpreted using the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Using the WHO criteria of a PRNT90 titer ≥ 20 and a 4-fold difference between ZIKV and DENV titers, we determined that 69.4% of samples had a recent ZIKV infection, compared with 5.6% using CDC criteria. The interpretation of ZIKV PRNTs in a DENV-endemic region is highly dependent on the choice of interpretation criteria.

Acute febrile illnesses (AFIs) in children from the developing world can have varying etiologies. Awareness of local epidemiology helps in prioritizing investigations and empiric treatment. This prospective study was carried out in a tertiary care center in North India, aiming to determine the burden, etiology, and outcome of AFI other than pneumonia and diarrhea in hospitalized children. A total of 613 consecutive children aged 3 months to 12 years with febrile illness of < 7 days during four selected months of 2014 representing different seasons were screened for eligibility. Those with acute respiratory diseases (N = 175, 28.5%) and diarrheal illness (N = 46, 7.5%) were excluded and 217 children were enrolled. Mean (standard deviation) age was 4.8 (3.4) years. Nearly half (N = 91, 41.9%) presented in post-monsoon season. Diagnosis could be established in 187 (86.2%) children. Acute central nervous system infections were the most common (N = 54, 24.8%). Among specific infections, scrub typhus was the most frequent (N = 23, 10.5%) followed by malaria (N = 14, 6.4%), typhoid (N = 14, 6.5%), and viral hepatitis (N = 13, 6.0%). Blood culture had a low (6.5%) yield; Salmonella typhi (N = 6) and Staphylococcus aureus (N = 5) were the common isolates. Serological tests were helpful in 50 (23%) cases. In multivariate analysis, hepatomegaly and/or splenomegaly independently predicted scrub typhus. Mortality rate was 10.1%. We conclude that AFI other than pneumonia and diarrhea are a significant burden and follow a seasonal trend. Scrub typhus has emerged as an important etiology of childhood AFIs in northern India. Periodic review of regional epidemiology will help in understanding the changing pattern of infectious diseases.

Antibiotics improve both weight and height gain in randomized trials of preschool children with preexisting morbidity. Here, we assess the effect of a short course of three different antibiotics (amoxicillin, azithromycin, and cotrimoxazole) on short-term linear and ponderal growth in a population-based sample of preschool children in rural Burkina Faso. We randomized households with at least two children in the Nouna district, Burkina Faso, to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic-randomized household, one child was randomly assigned to receive the antibiotic and the other to receive the placebo. Weight and height measurements were taken at baseline and 30 days following the last study medication dose. Weight-for-height Z (WHZ), height-for-age Z (HAZ), and weight-for-age Z (WAZ) scoreswere calculated based on the 2006 World Health Organization standards. Of the 124 households and 248 children enrolled, 229 had anthropometry measurements at 1 month and were analyzed. Children randomized to amoxicillin gained significantly more weight compared with both the placebo household (mean difference 317 g, 95% confidence interval [CI]: 115–519 g) and placebo sibling (mean difference 315 g, 95% CI: 147–482 g) controls. Growth velocity in g/kg/day, and WHZ and WAZ scores were higher in amoxicillin-treated children compared with placebo households and siblings. There were no differences in weight gain in children randomized to azithromycin or cotrimoxazole compared with placebo households or placebo siblings. There were no differences in height gain or HAZ across any of the study arms. Amoxicillin may have short-term growth-promoting effects in healthy children.

Devices to safely transfer fixed amounts of finger prick blood to rapid diagnostic tests (RDTs) pose a significant challenge, especially in non-laboratory settings. Following the success of an “inverted cup device” for transfer of 5 μL blood, a prototype with a conical cup shape was developed for transfer of 20 μL blood, the amount needed for human immunodeficiency virus or human African trypanosomiasis (HAT) RDTs. This study determined the volume of blood transferred by this new blood transfer device (BTD) and compared its ease of use, safety, and acceptability with that of a plastic pipette when used by health workers (HWs) for HAT RDTs in northwestern Uganda. After a half-day training, 48 HWs had used the two BTDs with at least 10 patients. The conical cup BTD effectively transferred a mean of 22.76 μL of blood (standard deviation 3.31 μL). A significantly higher proportion of HWs were able to collect the full amount of blood using the conical cup BTD, as compared with the pipette (92.4% versus 74.2%, P < 0.001). In HW questionnaires, the conical cup BTD scored higher than the pipette in various aspects of ease of use and safety. In addition, HWs preferred the conical cup BTD (79%), indicating that it was easy to handle, made work faster, and increased their confidence in front of the patient. These findings suggest that the design of the conical cup BTD may be adapted for RDTs requiring 20 μL of blood to facilitate safe and accurate blood transfer.

We report two cases of corneal coinfection with Acanthamoeba and Fusarium sp. along with the review of published literature. A 35-year-old woman and 65-year-old man presented to the institute with corneal ulcer refractory for treatment with topical antibiotics. Microbiological examination revealed the presence of Acanthamoeba cysts along with septate, hyaline fungal filaments. After emergency therapeutic penetrating keratoplasty (TPK) in both, the corneal tissue was sent for histopathologic examination, which confirmed the presence of Acanthamoeba and fungal coinfection. One patient had a recurrence of fungal infection after TPK. In subjects with a rapid progression of mycotic ulcer, coinfection with other microorganisms including Acanthamoeba should be suspected. The two cases presented here emphasize the importance of microbiology in making prompt diagnosis and appropriate management of these cases at an early stage.