The American Journal of Tropical Medicine and Hygiene - Current Issue

At the 2018 ASTMH Annual Meeting, October 28 through November 1, N. Regina Rabinovich, MD, FASTMH, wrapped up her term as ASTMH President. She recently talked with science writer Matthew Davis about the highlights of her year, the current state of the fight against major threats, including malaria and Ebola, and her advice for the new Society president, Chandy C. John, MD, MS, FASTMH.

Data are the basis for all scientific output. The sharing of data supporting that output is an important aspect of scientific communication, and is increasingly required by funders and publishers. Yet, academic advancement seldom recognizes or rewards data sharing. This article argues that although mandating data sharing will increase the amount of data available, this will not necessarily enable or encourage the secondary analyses needed to achieve its purported public good. We, therefore, need to build models that maximize the efficiency of processes for data collation and curation, and genuinely reward those engaged in data sharing and reuse. The WorldWide Antimalarial Resistance Network has 10 years of experience as a data platform, and its study group approach provides an example of how some of the challenges in equitable and impactful data-sharing and secondary use can be addressed, with a focus on the priorities of researchers in resource-limited settings.

Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV) is endemic in numerous countries, but the epidemiology and epizoology of Crimean-Congo hemorrhagic fever (CCHF) remain to be defined for most regions of the world. Using a broad database search approach, we reviewed the literature on CCHF and CCHFV in Southern and Western Asia to better define the disease burden in these areas. We used a One Health approach, moving beyond a focus solely on human disease burden to more comprehensively define this burden by reviewing CCHF case reports, human and animal CCHFV seroprevalence studies, and human and animal CCHFV isolations. In addition, we used published literature to estimate the distribution of Hyalomma ticks and infection of these ticks by CCHFV. Using these data, we propose a new classification scheme for organizing the evaluated countries into five categories by level of evidence for CCHF endemicity. Twelve countries have reported CCHF cases, five from Southern Asia and seven from Western Asia. These were assigned to level 1 or 2. Eleven countries that have evidence of vector circulation but did not report confirmed CCHF cases were assigned to level 3 or 4. This classification scheme was developed to inform policy toward strengthening CCHF disease surveillance in the Southern and Western Asia regions. In particular, the goal of this review was to inform international organizations, local governments, and health-care professionals about current shortcomings in CCHFV surveillance in these two high-prevalence regions.

A subset of multibacillary (MB) leprosy patients manifest with clinical “nonresponsiveness” to the fixed-duration, World Health Organization multidrug therapy MB regimen (WHO-MDT-MBR). The aim of this retrospective study was to assess the effectiveness and safety of alternate anti-leprosy therapy (ALT) in such patients. This is an analysis of patients’ records, registered in the leprosy clinic of our institute over a period of 6 years (2010–2015). The criteria for inadequate response/nonresponsiveness to treatment were as follows: 1) persistent/new lesions after completing ≥ 12 months of WHO-MDT-MBR (isolated reactions were ruled out histopathologically) and 2) persistent positive/increasing value of the morphological index (MI) and a 2 log increase in the bacteriological index (BI) after ≥ 12 months of WHO-MDT-MBR. Such cases were treated with ALT consisting of minocycline, clofazimine, and ofloxacin (24 months). Of 556 patients registered during the study period, 40.3% (224) were slit-skin smear (SSS) positive and 59.7% (332) were SSS negative. Of all, 35 patients (6.3%) satisfied the criteria for clinical nonresponsiveness. Of 224 SSS-positive patients, these 35 patients amounted to 15.6%. The mean BI and MI of these patients after completion of ≥ 12 months of WHO-MDT-MBR were 5.3 ± 0.6 and 14 ± 6.8%, respectively. After 6 months of treatment with ALT, MI became negative (0) in all these patients. After completion of ALT, the mean BI and MI became 1.7 ± 0.7 and 0%, respectively (P < 0.0001). There were 16 patients with corticosteroid-dependent recurrent/chronic erythema nodosum leprosum, who had excellent response with significant reduction in the number of reactional episodes and mean dose of prednisolone required (P < 0.0001). No serious adverse effects were noted. We conclude that ALT is safe and effective in the management of MB leprosy patients who are nonresponsive to 12 months of WHO-MDT-MBR.

Stigma has been associated with health-related outcomes such as medication adherence and quality of life (QOL) in patients with tuberculosis (TB); however, the mechanisms via which TB-related stigma interferes with specific outcomes are unclear. This study aimed to determine whether depressive symptoms were one of the mechanisms that mediated the associations between TB-related stigma and both medication adherence and QOL in patients with TB. A cross-sectional survey was conducted between October 1, 2013, and March 31, 2014, in Hubei Province, central China, and data were collected from 1,342 patients with TB, using a structured questionnaire that measured TB-related stigma, depressive symptoms, medication adherence, and QOL. Multiple imputation was used to account for missing data. Structural equation modeling was performed to assess the mediating effect of depressive symptoms on the associations of TB-related stigma with medication adherence and QOL. Mediation analyses showed that depressive symptoms partially mediated the association between TB-related stigma and medication adherence (standardized indirect effect = −0.16, 95% bias-corrected confidence interval [CI] [−0.19, −0.13], P < 0.01). Moreover, depressive symptoms fully mediated the association between TB-related stigma and QOL (standardized indirect effect = −0.17, 95% bias-corrected CI [−0.21, −0.14], P < 0.01). The results suggest that depressive symptoms played a key role in the relationships among TB-related stigma, medication adherence, and QOL in patients with TB. Therefore, the alleviation of depressive symptoms could be an important strategy for improving medication adherence and QOL in patients with TB.

Globally, pneumonia is the leading cause of death among children younger than 5 years old, with most deaths occurring in low-income countries. Rapid bedside tools to assist practitioners to accurately triage and risk-stratify these patients may improve clinical care and patient outcomes. We conducted a prospective cohort study of children with pneumonia admitted to two Ugandan hospitals to examine the predictive value of a single point-of-care lactate measurement using a commercially available handheld device, the Lactate Scout Analyzer. One hundred and fifty-five children were included, 90 (58%) male, with a median (interquartile range [IQR]) age of 11 (1.4–20) months. One hundred and twenty-five (81%) patients had chest indrawing, 133 (86%) were hypoxemic, and 75 (68%) had a chest x-ray abnormality. In-hospital mortality was 22/155 (14%). Median (IQR) admission lactate level was 2.4 (1.8–3.6) mmol/L among children who survived versus 7.2 (2.6–9.7) mmol/L among those who died (P < 0.001). Lactate was a better prognostic marker of mortality (area under receiver operator characteristic 0.76, 95% confidence interval: 0.69–0.87, P ≤ 0.001), than any single clinical sign or composite clinical risk score. Lactate level at admission of < 2.0, 2.0–4.0, and > 4.0 mmol/L accurately risk-stratified children, with 5-day mortality of 2%, 11% and 26%, respectively (P < 0.001). Slow lactate clearance also predicted subsequent mortality in children with repeated lactate measurements. Hand-held lactate measurement is a clinically informative and convenient tool in low-resource settings for triage and risk stratification of pediatric pneumonia.

With prequalification of a typhoid conjugate vaccine by the World Health Organization, countries are deciding whether and at what geographic scale to provide the vaccine. Optimal local data to clarify typhoid risk are expensive and often unavailable. To determine whether quantitative polymerase chain reaction (qPCR) can be used as a tool to detect typhoidal Salmonella DNA in the environment and approximate the burden of enteric fever, we tested water samples from urban Dhaka, where enteric fever burden is high, and rural Mirzapur, where enteric fever burden is low and sporadic. Sixty-six percent (38/59) of the water sources of Dhaka were contaminated with typhoidal Salmonella DNA, in contrast to none of 33 samples of Mirzapur. If these results can be replicated in larger scale in Bangladesh and other enteric fever endemic areas, drinking water testing could become a low-cost approach to determine the presence of typhoidal Salmonella in the environment that can, in turn, guide informed-design of blood culture-based surveillance and thus assist policy decisions on investing to control typhoid.

Matrix-assisted desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a clinical microbiology tool for the systematic identification of microorganisms. It has recently been presented as an innovative tool for the rapid and accurate identification of mosquitoes and their blood meal. To evaluate the capacity of this tool to identify mosquitoes collected in a tropical environment and preserved with silica gel, we analyzed 188 mosquitoes of different species collected in Chad, which were preserved with silica gel for 2 months. The MALDI-TOF MS analysis correctly identified 96% of the mosquitoes and 37.5% of their blood meals. Using MALDI-TOF MS and molecular biology, eight mosquito species were identified, including Anopheles gambiae s.l., Anopheles rufipes, Culex quinquefasciatus, Culex neavei, Culex pipiens, Culex perexiguus, Culex rima, and Culex watti. Blood meal identification revealed that mosquitoes fed mainly on humans, birds, and cows. Matrix-assisted desorption/ionization time-of-flight mass spectrometry appears to be a promising, fast, and reliable tool to identify mosquitoes and the origin of their blood meal for samples stored with silica gel.

The burden of Plasmodium falciparum (Pf) malaria in Kenya is decreasing; however, it is still one of the top 10 causes of morbidity, particularly in regions of western Kenya. Between April 2015 and June 2016, we enrolled 965 apparently healthy children aged 0–15 years in former Nyanza and Western Provinces in Kenya to characterize the demographic, geographic, and household risk factors of asymptomatic malaria as part of an epidemiologic study to investigate the risk factors for endemic Burkitt lymphoma. The children were sampled using a stratified, multistage cluster sampling survey design. Malaria was assessed by rapid diagnostic test (RDT) and thick-film microscopy (TFM). Primary analyses of Pf malaria prevalence (pfPR) are based on RDT. Associations between weighted pfPR and potential risk factors were evaluated using logistic regression, accounting for the survey design. Plasmodium falciparum malaria prevalence was 36.0% (27.5%, 44.5%) by RDT and 22.3% (16.0%, 28.6%) by TFM. Plasmodium falciparum malaria prevalence was positively associated with living in the lake-endemic area (adjusted odds ratio [aOR] 3.46; 95% confidence interval [95% CI] 1.63, 7.37), paternal occupation as peasant farmer (aOR 1.87; 1.08, 3.26) or manual laborer (aOR 1.83; 1.00, 3.37), and keeping dogs (aOR 1.62; 0.98–2.69) or cows (aOR 1.52; 0.96–2.40) inside or near the household. Plasmodium falciparum malaria prevalence was inversely associated with indoor residual insecticide spraying (IRS) (aOR 0.44; 0.19, 1.01), having a household connected to electricity (aOR 0.47; 0.22, 0.98), and a household with two (aOR 0.45; 0.22, 0.93) or ≥ three rooms (aOR 0.41; 0.18, 0.93). We report high but geographically heterogeneous pfPR in children in western Kenya and significant associations with IRS and household-level socioeconomic factors.

Self-medication with antimalarial drugs is a major factor in the development of drug resistance, exerting subtherapeutic drug pressure on circulating parasite populations. Data on self-medication with antimalarials from the Southern Pacific coast region of Colombia, where 4-aminoquinolines resistance and political instability prevail, are vital to elimination strategies. We present results of an exploratory study of 254 individuals having malaria symptoms who sought malaria diagnosis in two hospitals in Tumaco, Department of Nariño, Colombia. Thirty-two percent (82/254) of participants had positive Saker–Solomons urine tests, indicating self-medication with chloroquine (CQ) before consultation for diagnosis. Notably, among 30 pregnant women participating in the study, 43% were Saker-–Solomons positive. Molecular analysis of the K76T position encoded by the pfcrt gene revealed the mutant allele in all four samples that were both positive for Plasmodium falciparum and positive for the Saker–Solomons test, suggesting persistent CQ pressure. The high frequency of self-medication, particularly among pregnant women merits attention by public health authorities and comprehensive investigation.

In Colombia, published studies for the treatment of uncomplicated Plasmodium vivax malaria with chloroquine–primaquine (CQ-PQ) are scarce. The aim of the study was to evaluate the therapeutic efficacy and safety profile of this combination. A clinical trial was performed in adults with uncomplicated P. vivax malaria using the 28-day World Health Organization validated protocol. Patients received supervised antimalarial treatment and the primary efficacy end point was the clinical and parasitological response. Safety was assessed through adverse events surveillance, and plasma levels of antimalarial drugs were measured. A total of 77 patients were included. Adequate clinical and parasitological response rate diagnosed by thick blood smear examination was achieved in 72 of 73 patients (98.6%) with a complete 28-day follow-up. There were two parasitological therapeutic failures (TFs) (2.9%) on day 28, established by polymerase chain reaction among 68 patients, one of them with a positive film. No adverse events were detected. After completing the antimalarial treatment, all patients reached adequate plasma concentrations of CQ and desethylchloroquine (DECQ), with medians of 302.9 and 104.0 ng/mL, respectively. Uncomplicated P. vivax malaria treatment with CQ–PQ standard treatment was effective and safe in the study population; TFs were not associated with low plasma levels of CQ and DECQ.

In high prevalence settings, cryptosporidiosis is commonly implicated as a cause of a gastroenteritis syndrome in the organ transplant population. Stool microscopy is predominant diagnostic modality. Therapeutic options in this group of patients are limited, making their management exceptionally challenging. We describe a case of a renal transplant recipient with cryptosporidiosis confirmed by the stool FilmArray gastrointestinal panel (GIP) nucleic acid-based assay and stool microscopy, describe our institutional experience in diagnosing cryptosporidiosis in a low-prevalence setting, and review the available literature on management of this condition in the organ transplant population. In a low-prevalence setting, the GIP can serve as a rapid screening tool in the diagnosis of cryptosporidiosis.

Microscopic examination of stool samples has been considered to be the “gold standard” for diagnosis of intestinal parasites. Recently, polymerase chain reaction (PCR) has been approved by the World Health Organization as the method of choice for the diagnosis of Entamoeba histolytica. Of the 106 stool samples collected from the Esmeraldas and Pichincha provinces of Ecuador, all (100%) were positive for E. histolytica/Entamoeba dispar by light microscopy, whereas using real-time PCR (RT-PCR) DNA amplification, 74 (69.8%) were positive for E. dispar and only three (2.8%) were positive for E. histolytica. Some 29 (27.4%) samples were negative for the presence of either E. histolytica or E. dispar, this may be due the presence of Entamoeba mosksvskii, which is morphologically identical to E. histolytica/E. dispar and not specifically targeted by the RT-PCR used. These results indicate the necessity of reevaluating the epidemiology of amebiasis in Ecuador as the prominent species found are nonpathogenic.

Quantitative polymerase chain reaction (qPCR) for Toxoplasma gondii multicopy genes has emerged as a promising strategy for sensitive detection of parasite DNA. qPCR can be performed from blood samples, which are minimally invasive to collect. However, there is no consensus about what type of blood specimen yields the best sensitivity. The development of a novel protocol for qPCR detection of T. gondii using blood clot, involving an appropriate DNA extraction method and the use of an internal amplification control to monitor the reaction is presented in the current study. Assays directed to the B1 and REP529 genes were performed in spiked specimens of whole blood, guanidine–ethylenediaminetetraacetic acid blood, and clot. The clot-based qPCR was shown to be more sensitive when compared with other types of specimens, detecting five and 0.05 T. gondii genomes, using B1 and REP529 targets, respectively. Finally, a comparative analysis with samples from HIV patients with clinical suspicion of toxoplasmosis was performed, demonstrating the detection of four positive suspected cases with clots compared with only one using guanidine–ethylenediaminetetraacetic acid blood. The high analytical sensitivity and the cost-effective advantages offered by clot supports this methodology as a good laboratory tool to monitor parasite burden.

The rupestrian Triatoma costalimai species has been found infected by Trypanosoma cruzi in wild, peridomicile, and intradomicile environments in the municipality of Aurora do Tocantins, Tocantins, Brazil. Proximity between rock outcrops increases the risk of vector transmission of Chagas disease via this species. This work describes a focus of colonization by T. costalimai specimens infected by T. cruzi in rock outcrops located in an urban area in this municipality. Parasitological examination of feces from the collected specimens, axenic cultivation of T. cruzi–positive samples, and genetic characterization of the isolates were performed. Nymph and adult specimens were collected with a high infection prevalence (64.5%) for T. cruzi discrete type unit (DTU I). Participation of the T. costalimai species in the wild cycle of T. cruzi in rock outcrops located in an urban area demonstrates the need for entomological surveillance and control of vector transmission of Chagas disease in the municipality of Aurora do Tocantins, Tocantins.