The American Journal of Tropical Medicine and Hygiene - Volume 99, Issue 3, 2018

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.