The American Journal of Tropical Medicine and Hygiene - Current Issue

The American Committee on Immunization Practices recommends the use of the oral cholera vaccine (OCV) in international travelers aged 18–64 years who visit areas of active cholera transmission. CDC Travelers’ Health Branch currently tracks areas of active cholera transmission and posts this information on their country-specific destination web pages at https://wwwnc.cdc.gov/travel/destinations/list. Lessons learned from a webinar conducted among health care providers have led to improvements in how CDC shares information on the OCV. Here, we summarize the major considerations for providers offering the OCV to U.S. travelers and indicate where they can find more information.

The brain drain of professionals from low- and middle-income countries (LMICs) to developed countries is well documented and partially due to the challenges faced by biomedical researchers to establish themselves back at home, after training abroad. These challenges may result in the loss of highly trained individuals from LMICs and reduce the availability of local expertise to develop/inform best practices in health care and to direct locally relevant research. The path of training of LMIC researchers in high-income countries is well documented. However, strategies for a successful reintegration of biomedical researchers back to their home research institutions in LMICs are less clear. We report observations of workshops addressing repatriation needs of researchers returning to their home countries after training abroad during the American Society of Tropical Medicine and Hygiene (ASTMH) 2017 and 2018 annual meetings. Strategies proposed include maintaining connections with the home research institution, ideally through collaborations, planning 18 months ahead before returning with grants applications submitted, and engaging in networking throughout the training period. In addition to presenting our observations, we hope to build a network to facilitate this process, compile resources, and identify expertise within the ASTMH to develop robust strategies to allow young biomedical researchers to flourish in LMICs.

Sustainable and low-cost methods for delivery of safe drinking water in resource-limited settings remain suboptimal, which contributes to global diarrhea morbidity. We aimed to assess whether delivery of riverbank filtration-treated water to newly installed water storage tanks (improved quality and access, intervention condition) reduced reported diarrhea in comparison to delivery of unfiltered river water (improved access alone, control condition) in rural Indian villages. We used a stepped wedge cluster-randomized trial (SW-CRT) design involving four clusters (villages). Selection criteria included village size, proximity to a river, and lack of existing or planned community-level safe water sources. All adults and children were eligible for enrollment. All villages started in the control condition and were sequentially randomized to receive the intervention at 3-month intervals. Our primary outcome was 7-day-period prevalence of self- or caregiver-reported diarrhea, measured at 3-month intervals (five time points). Analysis was by intention to treat. Because blinding was not possible, we incorporated questions about symptoms unrelated to water consumption to check response validity (negative control symptoms). We measured outcomes in 2,222 households (9,836 participants). We did not find a measurable reduction in diarrhea post-intervention (RR: 0.98 [95% CI: 0.24–4.09]); possible explanations include low intervention uptake, availability of other safe water sources, low baseline diarrheal prevalence, and reporting fatigue. Our study highlights both the difficulties in evaluating the impact of real-world interventions and the potential for an optimized SW-CRT design to address budgetary, funding, and logistical constraints inherent in such evaluations.

Consumption of unsafe drinking water contributes to the global disease burden, necessitating identification and implementation of effective, acceptable, and sustainable water interventions in resource-limited settings. In a quantitative stepped-wedge cluster randomized trial of a community-based water intervention in rural India, we identified low rates of intervention uptake and reported diarrhea. To better understand and explain these findings, we performed a qualitative study examining barriers and enablers to intervention uptake and health reporting using the COM-B model, where capabilities, opportunities, and motivators interact to generate behavior. We conducted 20 focus groups and one semi-structured interview with participants and four focus groups with data collectors. Multifactorial barriers to intervention uptake included distorted perceptions of water-related health effects, implementation issues that reduced treated water availability; convenience of, and preference for, alternative drinking water sources; delivery of water to plastic storage tanks (perceived as affecting water quality and taste); and resistance to change. Enablers included knowledge of water-related health risks, proximity to tanks, and social opportunity. Barriers to health reporting included variability in interpretation of illness, suspicion regarding the consequences of reporting disease, weariness with repeated questions, and perceived inaction on health data already provided; low survey implementation fidelity was also important. Enablers included surveyor initiatives to encourage reporting and a sense of social responsibility. This qualitative explanatory study allowed better understanding of our quantitative results. It also identified obstacles and facilitators to implementing and evaluating community water interventions, providing insight on how to achieve better intervention uptake and health reporting in future studies.

A cluster, randomized control trial was conducted to assess the effects of social marketing approach on purchase rates and water treatment behavior of Klorfasil, a chlorine-based household water treatment product among seven villages in Thomassique, Haiti, from May to December 2016. Villages were randomized to the free-trial (257 households) or cost-sharing (240 households) group. Households in the free-trial group were allowed 30 days of free Klorfasil use before purchase decision. Households who purchased Klorfasil were then followed up for 30, 60, and 180 days. At the last follow-up, respondents were asked if they would like to repurchase Klorfasil. Questionnaire survey and water quality assessment by residual-free chlorine were conducted in each survey. Chi-square test, t-test, and logistic regression were applied. The first purchase rate of the cost-sharing group was significantly higher than that of the free-trial group (79.2% versus 67.3%). By contrast, the repurchase rate of the free-trial group was higher (82.9% versus 66.3%). However, the overall repurchase rate was 71.6% and the proportion of long-term users was significantly higher in the cost-sharing group (56% versus 47%). Water treatment rates in the cost-sharing group were significantly higher than those in the free-trial group in the first and final surveys (odds ratio [OR] = 0.15, OR = 0.32). Households with high and medium economic status both had significantly higher purchase rates than low economic status households (OR = 4.40, OR = 1.94). Households with higher educated respondents had significantly better water treatment practices (OR = 2.15). The free-trial approach did not increase the first purchase rate but increased the repurchase rate later. The cost-sharing approach significantly encouraged long-term usage.

Domestic animals have been associated with enteric infections in young children and can also be carriers of respiratory viruses. We conducted a cross-sectional assessment of health outcomes in children aged < 5 years associated with animal presence among 793 rural households in Uganda. We recorded the 2-week prevalence of diarrhea and respiratory infections in children, and the number of cows, poultry, sheep/goats, and pigs in the household. We used generalized linear models with robust standard errors to estimate the prevalence ratio (PR) for diarrhea and respiratory infections associated with households owning the above- versus below-median number of animals. We conducted unadjusted and adjusted analyses controlling for socioeconomic, water, sanitation, and hygiene indicators. Children in households with the above-median number (> 5) of poultry had 83% higher diarrhea prevalence than those with ≤ 5 poultry (adjusted PR = 1.83 [1.04, 3.23], P = 0.04). Children in households with the above-median number (> 2) of cows had 48% lower prevalence of respiratory infection than those with ≤ 2 cows (adjusted PR = 0.52 [0.35, 0.76], P < 0.005). There were no other significant associations between domestic animals and child health. Studies should assess if barring chickens from indoor living quarters and sanitary disposal of chicken and other animal feces can reduce childhood zoonotic infections.

The Republic of Zambia declared a cholera outbreak in Lusaka, the capital, on October 6, 2017. By mid-December, 20 of 661 reported cases had died (case fatality rate 3%), prompting the CDC and the Zambian Ministry of Health through the Zambia National Public Health Institute to investigate risk factors for cholera mortality. We conducted a study of cases (cholera deaths from October 2017 to January 2018) matched by age-group and onset date to controls (persons admitted to a cholera treatment center [CTC] and discharged alive). A questionnaire was administered to each survivor (or relative) and to a family member of each decedent. We used univariable exact conditional logistic regression to calculate matched odds ratios (mORs) and 95% CIs. In the analysis, 38 decedents and 76 survivors were included. Median ages for decedents and survivors were 38 (range: 0.5–95) and 25 (range: 1–82) years, respectively. Patients aged > 55 years and those who did not complete primary school had higher odds of being decedents (matched odds ratio [mOR] 6.3, 95% CI: 1.2–63.0, P = 0.03; mOR 8.6, 95% CI: 1.8–81.7, P < 0.01, respectively). Patients who received immediate oral rehydration solution (ORS) at the CTC had lower odds of dying than those who did not receive immediate ORS (mOR 0.1, 95% CI: 0.0–0.6, P = 0.02). Cholera prevention and outbreak response should include efforts focused on ensuring access to timely, appropriate care for older adults and less educated populations at home and in health facilities.

Helicobacter pylori (H. pylori), a gram-negative pathogen, has been shown to colonize multiple organs and cause various forms of extra-gastrointestinal diseases. The association of H. pylori infection with vitamin D status in apparently healthy children remained unclear; therefore, we investigated the relationship between vitamin D and H. pylori infection among apparently healthy infants and toddlers. In this large cross-sectional study, the examination data of children were collected from January 2013 to September 2017 in the Center for Children’s Health Care. Among these children, 6,896 infants and toddlers were screened for our study. Helicobacter pylori infection and vitamin D status were the main indicators, and micronutrients (zinc, iron, copper, magnesium), and growth parameters (height, weight, and weight for age Z score [WAZ], height for age Z score [HAZ]) were also analyzed in this study. Among the 6,896 infants and toddlers, the detection rate of H. pylori seropositivity was 30.6%. The prevalence of vitamin D deficiency in H. pylori seropositive and seronegative groups was 20.7% and 12.1%, respectively (P < 0.001). The logistic regression analysis suggested children with H. pylori–positive antibody were 2.06 times more likely to be vitamin D deficient compared with children who had negative H. pylori antibody (odds ratio: 2.06; 95% CI: 1.77, 2.38) after controlling for confounding factors. These data suggested that there was a significant association between H. pylori seropositivity and vitamin D deficiency in children aged 6–36 months, which would make a contribution to the treatment and monitoring of vitamin D deficiency and H. pylori infection.

Resistance to anti-leprosy drugs is on the rise. Several studies have documented resistance to rifampicin, dapsone, and ofloxacin in patients with leprosy. We looked for point mutations within the folP1, rpoB, and gyrA gene regions of the Mycobacterium leprae genome predominantly in the neural form of leprosy. DNA samples from 77 nerve tissue samples were polymerase chain reaction (PCR)-amplified for M leprae DNA and sequenced for drug resistance–determining regions of genes rpoB, folP1, and gyrA. The mean age at presentation and onset was 38.2 ± 13.4 (range 14–71) years and 34.9 ± 12.6 years (range 10–63) years, respectively. The majority had borderline tuberculoid leprosy (53 [68.8%]). Mutations associated with resistance were identified in 6/77 (7.8%) specimens. Mutations seen were those associated with resistance to rifampicin, ofloxacin, and dapsone. All the six patients were drug-naive. The clinical and pathological manifestations in this group did not differ from the drug-sensitive group. This study highlights the occurrence of resistance to the standard multidrug therapy and ofloxacin in leprosy. Among the entire cohort, 1/77 (1.3%) showed resistance to rifampicin, 2/77 (2.6%) to dapsone, and 5/77 (6.4%) to ofloxacin. Six new patients showing infection by mutant strains indicated the emergence of primary resistance. Resistance to ofloxacin could be due to frequent use of quinolones for many bacterial infections. The results of the study indicate the need for development of a robust and strict surveillance system for detecting drug resistance in leprosy in India.

Pulmonary tuberculosis (TB) is a major global public health problem. Thailand is listed as one of the countries with a high burden of pulmonary TB. Various factors are known to contribute to unsuccessful pulmonary TB treatment. However, studies in Thailand remain limited, especially in rural settings. This study aimed to identify the prevalence and associated factors of unsuccessful pulmonary TB treatment in community hospitals. A cross-sectional study was conducted from June–July 2019. We enrolled all patients receiving treatments in four community hospitals in central Thailand. The collected data included baseline characteristics, comorbid illnesses, a history of directly observed treatment—short course (DOTS), sputum acid-fast bacilli smear results, and chest radiography and treatment outcomes. Univariate and multivariate analyses were used to identify factors associated with unsuccessful pulmonary TB treatment. A total of 786 patients were enrolled in the study. Prevalence of unsuccessful treatment was 18.7%. Associated factors of unsuccessful pulmonary TB treatment were previously treated TB (adjusted odds ratio [AOR]: 2.1, 95% CI: 1.2–3.7), existence of comorbid illnesses (AOR: 2.8, 95% CI: 1.5–5.0), DOTS not performed (AOR: 2.5, 95% CI: 1.4–4.5), chest radiography showing multiple lung lesions at first diagnosis (AOR: 3.0, 95% CI: 1.7–5.2), no chest radiography improvement in the first follow-up (AOR: 17.7, 95% CI: 8.2–38.0), and unknown status of chest radiography in the first follow-up (AOR: 48.1, 95% CI: 22.3–103.5). Health promotion and primary care should be implemented in the communities to achieve ultimate successful treatment.

Point-of-care urine-lipoarabinomannan (LAM) Alere Determine TB-LAM assay has shown utility diagnosing tuberculosis (TB) in HIV-positive, severely immunocompromised, TB-symptomatic patients. We assessed LAM results in severely immunocompromised patients, who had LAM systematically performed at new or follow-up HIV consultations. This was a prospective, observational study on consecutive ambulatory, > 15-year-old HIV-positive patients with CD4 < 100 cells/µL in Mozambique. Clinical assessments and LAM were performed for all and microscopy, Xpert, sputum culture, and chest X-ray for LAM-positive participants. Patients were followed up for 6 months. Of 360 patients, half were ART-naive. Lipoarabinomannan positivity was 11.9% (43/360), higher among symptomatic patients compared with asymptomatic: 18.5% (30/162), and 6.6% (13/198), respectively, P = 0.001. Tuberculosis was bacteriologically confirmed in 6/35 LAM-positive patients (2 of them asymptomatic). Lipoarabinomannan positivity was associated with higher risk of mortality (adjusted odds ratio [aOR]: 4.6, 95% CI: 1.3–15.6, P = 0.015). Systematic urine-LAM allows for rapid TB treatment initiation in severely immunocompromised HIV ambulatory patients and identifies patients at a higher risk of death.

Cystic echinococcosis (CE) is an important health problem in northwest non-Qinghai Tibetan Plateau regions of China. Understanding CE risk factors may help in formulating effective prevention and control measures. In the current study, negative binomial regression was used to analyze CE-related factors using prevalence data from 147 counties (cities, districts, and banners) in northwest non-Qinghai Tibetan Plateau regions of China gathered from a national survey conducted in 2012, county economic data, and livestock production data for 2012. The negative binomial regression models indicated Echinococcus granulosus infection rate in livestock (odds ratio [OR]: 1.0471, 95% CI: 1.0128–1.0825, P = 0.0067), the mean number of dogs per family (OR: 3.0589, 95% CI: 1.5116–6.1900, P = 0.0019), the mean number of sheep per family (OR: 1.0431, 95% CI: 1.0027–1.0852, P = 0.0365), and the source of drinking water (OR: 0.9808, 95% CI: 0.9627–0.9992, P = 0.0413) were correlated with human CE prevalence, whereas altitude, surface temperature, economy, and mean number of cattle per family had a negative association. We found that the positive rate of dog stool coproantigen of Echinococcus was associated with human CE prevalence using the univariate analysis but not after controlling for covariates including the number of dogs per family. This might be partially due to the deworming campaigns that were carried out in most of the researched areas. Therefore, the positive rate of dog stool coproantigen of Echinococcus could not reflect the dog infection rate under natural conditions. These findings indicate that dogs and livestock play the most important role in CE transmission. Further studies should be carried out at the township or village level.

Human infection with the trematode Fasciola occurs with a worldwide prevalence of up to 17 million. Sheep and cattle are the normal host. Infection typically results in hepatobiliary disease, but extrahepatic manifestations are occasionally reported. Here, we present the case of a previously healthy 31-year-old Kurdish woman, admitted to hospital with a subarachnoid hemorrhage, eosinophilic meningitis, and lung and liver disease. A diagnosis of Fasciola infection was made based on strongly positive serology in blood and cerebrospinal fluid. The patient improved following treatment with triclabendazole and prednisolone.

This study investigated the applications of recombinant monoclonal antibodies (rmAbs) produced against two recombinant filarial proteins of diagnostic value. Ab5B and Ab3A were produced against recombinant BmSXP, and Ab4 and Ab4-fragment crystallizable (Fc) against recombinant BmR1. Ab5B and Ab4-Fc were found to be useful as quality control (QC) reagents for two commercial rapid test kits, such as Brugia RapidTM and BLF Rapid® (Reszon Diagnostics International Sdn. Bhd., 47600 Subang Jaya, Selangor, Malaysia), respectively. The two rmAbs reacted positively with the corresponding recombinant proteins lined on the nitrocellulose strips of the cassette tests, thus may replace or reduce the need for patient serum samples as positive controls for QC of the commercial kits. They were also successfully conjugated to gold nanoparticles and reacted positively with the test lines containing the corresponding recombinant proteins when directly applied to the cassette tests. The gold-conjugated reagents can be used to confirm the antigenicity of test lines after the storage of the rapid tests for a prolonged period or under unfavorable conditions. Furthermore, Ab5B and Ab3A were shown to be able to capture the target recombinant proteins through immunoaffinity purification, enabling their use for applications that need very highly purified proteins. In conclusion, this study demonstrated several potential uses of rmAb proteins produced against recombinant filarial proteins.

Plateau and Nasarawa states in central Nigeria were endemic for onchocerciasis. The rural populations of these two states received annual ivermectin mass drug administration (MDA) for a period of 8–26 years (1992–2017). Ivermectin combined with albendazole was given for 8–13 of these years for lymphatic filariasis (LF); the LF MDA program successfully concluded in 2012, but ivermectin MDA continued in areas known to have a baseline meso-/hyperendemic onchocerciasis. In 2017, serological and entomological assessments were undertaken to determine if MDA for onchocerciasis could be stopped in accordance with the current WHO guidelines. Surveys were conducted in 39 sites that included testing 5- to < 10-year-old resident children by using ELISA for OV16 IgG4 antibodies, and Onchocerca volvulus O150 pooled polymerase chain reaction (PCR) testing of Simulium damnosum s.l. vector heads. Only two of 6,262 children were OV16 positive, and none of 19,056 vector heads were positive for parasite DNA. Therefore, both states were able to meet WHO stop-MDA thresholds of an infection rate in children of < 0.1% and a rate of infective blackflies of <1/2,000, with 95% statistical confidence. Transmission of onchocerciasis was declared interrupted in Plateau and Nasarawa states by the Federal Ministry of Health, and 2.2 million ivermectin treatments/year were stopped in 2018. Post-treatment Surveillance was launched focusing on entomological monitoring on borders with neighboring onchocerciasis-endemic states. An apparent positive impact of the LF MDA program on eliminating hypo-endemic onchocerciasis was observed. This is the first stop-MDA decision for onchocerciasis in Nigeria and the largest single stop-MDA decision for onchocerciasis yet reported. This achievement, along with the process used in adapting and implementing the 2016 WHO stop-MDA guidelines, will be important as a potential model for decision makers and national onchocerciasis elimination committees in other African countries that are charged with advancing their programs.

Endemic cutaneous leishmaniasis (CL) in northern Argentina has traditionally been caused by Leishmania braziliensis. This study aims to describe an outbreak of Leishmania infantum–caused human CL in the Department Capital of Corrientes Province, Argentina. We retrospectively analyzed the reported cases of CL in this area from May 2015 to December 2016. Eighty cases of CL were clinically and analytically diagnosed, and there was one case of visceral leishmaniasis in a boy who also had CL. Patients’ median age was 33.6 years (range 1–89 years), and 18.5% were younger than 15 years; the male:female ratio was 3.5:1. Cases lived mostly in the municipality of Corrientes (72.8%), whereas 27.2% resided in Riachuelo. Although 67.9% had a single lesion, 32.1% had several. Molecular analyses showed that L. infantum was the causative species in all cases. Our results show that for the first time, there was an outbreak of CL by L. infantum in an urban area of Argentina.

The emergence of artemisinin-resistant Plasmodium falciparum in the Greater Mekong Subregion threatens both the efficacy of artemisinin-based combination therapy (ACT), the first-line treatment for malaria, and prospects for malaria elimination. Monitoring of ACT efficacy is essential for ensuring timely updates to elimination policies and treatment recommendations. In 2014–2015, we assessed the therapeutic efficacies of artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DP) for the treatment of uncomplicated P. falciparum at three study sites in Rakhine, Shan, and Kachin states in Myanmar. Patients presenting with uncomplicated P. falciparum malaria were enrolled, treated, and followed up for 28 days for AL or 42 days for DP. Both AL and DP demonstrated good therapeutic efficacy at all three study sites. The 28-day cure rate for AL was > 96% across all study sites, and the 42-day cure rate for DP was 100%. Parasitemia on day 3 was detected in 0%, 3.3%, and 3.6% of participants treated with AL at the Rakhine, Shan, and Kachin sites, respectively. No participants treated with DP were parasitemic on day 3. No evidence of P. falciparum k13 mutations was found at the Rakhine study site. A high prevalence of k13 mutations associated with artemisinin resistance was observed at the Kachin and Shan state study sites. These results confirm that ACT efficacy has been resilient in therapeutic efficacy study (TES) sentinel sites in Myanmar, despite the presence at some sites of k13 mutations associated with resistance. Studies are ongoing to assess whether this resilience persists.