The American Journal of Tropical Medicine and Hygiene - Current Issue

The American Society for Tropical Medicine and Hygiene recently inaugurated an award for the best clinical research article published in the society’s journal in the previous year. This article summarizes both the process of selecting the winner and several themes that stood out in those articles which rose to the top for consideration. Themes of note included the importance of doing clinical research outside of referral centers, the complexity that must be considered when implementing interventions, incorporation of both ends of the age spectrum into studies, and considering cost-effectiveness and opportunity cost of interventions.

Breast tuberculosis (TB) is rarely reported and poorly described. This review aims to update the existing literature on risk factors, clinical presentations, constitutional symptoms, diagnostic procedures, and medical and surgical treatments for breast TB. In all, 1,478 cases of breast TB were collected. Previous history of TB was reported in 19% of cases. The most common clinical appearance of the lesion was breast lump (75%). The most common associated finding was axillary lymphadenitis (33%) followed by sinus or fistula (24%). The most common symptoms were pain and fever, reported in 42% and 28% of cases, respectively. The most used diagnostic method was fine-needle aspiration cytology (32%), followed by biopsy (27%), acid-fast bacteria Ziehl–Neelsen stain (26%), culture (13%), and polymerase chain reaction (2%). These tested positive in 64%, 93%, 27%, 26%, and 58% of cases, respectively. The majority (69%) of patients received a 6-month anti-TB treatment (isoniazid, rifampicin, pyrazinamide, and ethambutol). Surgery consisted of excision in 39% of cases, drainage in 23%, and mastectomy in 5%. The great majority of patients had a positive outcome. It often mimics breast cancer, which makes it difficult to diagnose. Most patients, when diagnosed in time, respond to antitubercular therapy alone.

An epidemic of Rocky Mountain spotted fever (RMSF) is ongoing in Mexicali, México. We visited 100 neighborhoods with diagnosed human cases and 100 control neighborhoods to evaluate knowledge of the epidemic; obtain data on the spatial distribution of dogs, canine seroprevalence and active infection, tick infestations, and presence of rickettsial DNA in ticks; and evaluate risk factors for human cases, seropositivity, and tick infestation within an unbiased study design. The majority (80%) of residents had heard of RMSF, but only 48% used acaricides in the home or on dogs. Case neighborhoods and those with high canine seroprevalence tended to be on the city periphery or in the agricultural valley. No dogs were polymerase chain reaction (PCR) positive for Rickettsia rickettsii, and the overall seroprevalence was 65% (titers from 64 to 1,024). PCR prevalence in ticks was 0.70%, confirmed by DNA sequencing as R. rickettsii; neighborhood prevalence ranged from 0.7% to 6.1%. Twelve percent of dogs had high tick burdens, and all ticks were Rhipicephalus sanguineus. Epidemiologically significant risk factors were ground covering for a neighborhood having a human case; dogs having poor body condition and weighing < 10 kg for canine seropositivity; dogs living at the home for the number of ticks in the environment; and being near canals, having trash on the patio, and a dog being thin for tick burdens on dogs. A One Health approach is crucial to understanding RMSF and brown dog ticks.

Query fever (Q fever), caused by Coxiella burnetii, was first described in southern California in 1947. It was found to be endemic and enzoonotic to the region and associated with exposure to livestock. We describe a series of 20 patients diagnosed with Q fever at a Veterans Affairs hospital in southern California, with the aim of contributing toward the understanding of Q fever in this region. Demographics, laboratory data, diagnostic imaging, risk factors, and treatment regimens were collected via a retrospective chart review of patients diagnosed with Q fever at our institution between 2000 and 2016. Cases were categorized as acute or chronic and confirmed or probable. The majority presented with an acute febrile illness (90%). There was a delay in ordering diagnostic serology from the time of symptom onset (acute cases, average 31.9 days; chronic cases, average 63 days), and 15% progressed from acute to chronic infection. Of the chronic cases, 22.2% had endocarditis, 22.2% had endovascular infection, and 11.1% had both endocarditis and endovascular infection. The geographic distribution revealed that 20% resided in rural areas. Of the cases of Q fever that died, death attributed to Q fever was associated with an average diagnostic delay of 65.5 days. Acute Q fever is underreported in this region largely because of its often nonspecific clinical presentation.

This is the first cross-sectional study of the seroprevalence and risk factors for Coxiella burnetii in Jordan. A total of 781 individuals from 11 governorates of Jordan were tested by SERION ELISA classic C. burnetii IgG Phase 2. A validated and pretested questionnaire was used to collect risk factors and demographic data. The overall seroprevalence for C. burnetii was 24.2% (95% CI; 21.3–27.3%). Unadjusted odds ratios showed that governorate of residence, consumption of raw milk, and ownership of sheep, goats, and dogs were significantly (P ≤ 0.05) associated with C. burnetii seropositivity. The multivariate logistic regression showed that individuals who own small ruminants had three times greater odds of seropositivity than those who do not own a small ruminant, after controlling for age, gender, raw milk consumption, and ownership of dogs. In addition, individuals who live in Al-Karak, Az-Zarqa, and Al-Tafilah had significantly greater odds of seropositivity compared with individuals who live in the capital city, Amman (OR = 3.6, 4.8, and 2.7, respectively). This study suggests that preventive measures should be practiced in ruminant farms in Jordan to avoid C. burnetii infection. Coxiella burnetii should also be considered in the differential diagnosis of febrile-like illnesses in Jordan, especially among farmers and veterinarians.

Waterborne pathogens, associated with poverty and poor sanitary conditions, are a major cause of morbidity and mortality worldwide. There are limited data on the epidemiology of waterborne pathogens in indigenous populations living in the Amazon region. We did a cross-sectional survey in two indigenous Shuar communities in the Amazon region of Ecuador in which we documented the presence of pathogens representing different sources of environmental contamination of water. We detected protozoa and soil-transmitted helminths by microscopy of fecal samples and the presence of IgG antibodies to hepatitis A and Leptospira spp. in blood samples from individuals older than 2 years and collected data by questionnaire on sociodemographic factors and knowledge of infectious diseases. Seroprevalence for hepatitis A and Leptospira spp. were 98.1% (95% CI: 97.0–99.8) and 50.0% (95% CI: 43.3–56.6), respectively, whereas 62.6% (95% CI: 55.8–69.4) had enteric parasites in stool samples. In participants older than 6 years, eight of 10 had evidence of infection with or exposure to at least one of the pathogens studied. Although prevalence of pathogens varied by age, it did not vary significantly by gender, temporal migration, illiteracy, perceived morbidity, receipt of conditional cash transfers, water boiling practices, poor housing conditions, and anthropometric status. These findings indicate a high level of contamination of drinking water by human pathogens in these indigenous communities and the need for interventions to improve access to and use of clean drinking water in these marginalized communities.

To explore the consistency in impact evaluation based on reported diarrhea, we compared diarrhea data collected through two different surveys and with observed diarrhea-associated hospitalization for children aged ≤ 5 years from a non-blinded cluster-randomized trial conducted over 2 years in urban Dhaka. We have previously reported that the interventions did not reduce diarrhea-associated hospitalization for children aged ≤ 5 years in this trial. We randomly allocated 90 geographic clusters comprising > 60,000 low-income households into three groups: cholera vaccine only, vaccine plus behavior change (cholera vaccine and handwashing plus drinking water chlorination promotion), and control. We calculated reported diarrhea prevalence within the last 2 days using data collected from two different survey methods. The “census” data were collected from each household every 6 months for updating household demographic information. The “monthly survey” data were collected every month from a subset of randomly selected study households for monitoring the uptake of behavior change interventions. We used binomial regression with a logarithmic link accounting for clustering to compare diarrhea prevalence across intervention and control groups separately for both census and monthly survey data. No intervention impact was detected in the census (vaccine only versus control: 2.32% versus 2.53%; P = 0.49; vaccine plus behavior change versus control: 2.44% versus 2.53%; P = 0.78) or in the vaccine only versus control in the monthly survey (3.39% versus 3.80%; P = 0.69). However, diarrhea prevalence was lower in the vaccine-plus-behavior-change group than control in the monthly survey (2.08% versus 3.80%; P = 0.02). Although the reasons for different observed treatment effects in the census and monthly survey data in this study are unclear, these findings emphasize the importance of assessing objective outcomes along with reported outcomes from non-blinded trials.

We compared the diagnostic performance of the standard method (Kato-Katz) with two recently developed methods (Mini-FLOTAC and Flukefinder) for the detection and quantification of Fasciola hepatica eggs in human stool. Uninfected human stool samples were artificially spiked with F. hepatica eggs to reach final concentrations of 14, 28, 41, or 96 eggs per gram of stool (epg). Only Flukefinder showed 100% sensitivity in all but the samples with the lowest concentration of eggs (14 epg), in which it had a sensitivity of 60%. Each of the methods underestimated the true fecal egg counts (FECs), Flukefinder resulting in the most biased egg counts (egg counts 0.18 times lower than the expected FECs). Only the Flukefinder resulted in more precise results (coefficient of variance < 30%) from FECs of 96 epg onward. The outcome of this study indicates that the Flukefinder is a useful alternative diagnostic method for human fascioliasis in stool.

We report an unusual case of paragonimiasis in a Nepali patient presenting with massive pericardial effusion and pericardial tamponade. The patient reported neither the consumption of crabs or crayfish nor the consumption of wild animal meat, which are the usual sources of infection. It is suspected that the source of infection was instead the ingestion of raw live slugs as part of a traditional medicine treatment.

Following a 4-year annual praziquantel (PZQ) treatment campaign, the resulting prevalence of Schistosoma mansoni was seen to differ among individual villages along the Kenyan shore of Lake Victoria. We have investigated possible inherent differences in snail-related aspects of transmission among such 10 villages, including six persistent hotspot (PHS) villages (≤ 30% reduction in prevalence following repeated treatments) located along the west-facing shore of the lake and four PZQ-responding (RESP) villages (> 30% prevalence reduction following repeated treatment) along the Winam Gulf. When taking into account all sampling sites, times, and water hyacinth presence/absence, shoreline-associated Biomphalaria sudanica from PHS and RESP villages did not differ in relative abundance or prevalence of S. mansoni infection. Water hyacinth intrusions were associated with increased B. sudanica abundance. The deeper water snail Biomphalaria choanomphala was significantly more abundant in the PHS villages, and prevalence of S. mansoni among villages both before and after control was positively correlated with B. choanomphala abundance. Worm recoveries from sentinel mice did not differ between PHS and RESP villages, and abundance of non-schistosome trematode species was not associated with S. mansoni abundance. Biomphalaria choanomphala provides an alternative, deepwater mode of transmission that may favor greater persistence of S. mansoni in PHS villages. As we found evidence for ongoing S. mansoni transmission in all 10 villages, we conclude that conditions conducive for transmission and reinfection occur ubiquitously. This argues for an integrated, basin-wide plan for schistosomiasis control to counteract rapid reinfections facilitated by large snail populations and movements of infected people around the lake.

Schistosomiasis is a blood parasitic disease caused by trematode parasites of the genus Schistosoma. Schistosoma mansoni is one of the main contributors of the disease and 90% of the global burden of schistosomiasis is in Africa. Mass drug administration (MDA) has been implemented to reduce the disease burden in endemic areas. Because of MDA, the diagnostic sensitivity and specificity for classical diagnostic tests are reduced. In any disease situation, diagnosis is vital in determining asymptomatic, concurrent, current, new, and reinfection cases to evaluate the efficacy of any control program. We have evaluated the positive infection for S. mansoni from filtered urine samples collected from Zambian school children after MDA using loop-mediated isothermal amplification (LAMP) and compared its sensitivity and specificity with polymerase chain reaction (PCR). One hundred eleven urine samples collected from school children aged between 7 and 15 years from Siavonga district in southern Zambia were evaluated by PCR and LAMP for DNA extracted by two different protocols (filter-based versus crude extraction). The infection prevalence was 77% with PCR and almost 94% with mansoni-LAMP. Also, LAMP detected 16% (Qiagen extraction) and 10% (LAMP-Procedure for Ultra Rapid Extraction) more positive S. mansoni infection than PCR. We have demonstrated the efficacy of LAMP in a laboratory setup after MDA. The possible inclusion of LAMP as a field-based point-of-care test for surveillance can provide reliable prevalence of schistosomiasis after MDA and help in determining the efficacy of a control program.

Treating Mansonella perstans is challenged by the low efficacy of registered antihelminthics. Wolbachia endobacteria provide an alternative treatment target because depletion results in amicrofilaremia in filarial infections with Wuchereria bancrofti and Onchocerca volvulus infections. This open-label, randomized study sought to confirm that i) Wolbachia are present in M. perstans in Ghana and ii) doxycycline treatment will deplete Wolbachia and cause a slow, sustained decline in microfilariae (MF). Two hundred and two Ghanaians with M. perstans infection were randomized into early (immediate) and delayed (6 months deferred) treatment groups, given doxycycline 200 mg/day for 6 weeks, and monitored for MF and Wolbachia levels at baseline, 4, 12, and 24 months after the study onset (= time of randomization and start of treatment for the early group). Per protocol analysis revealed that the median MF/mL in the early group declined from 138 at baseline to 64 at month 4 and further to 0 at month 12. In the delayed group, MF load did not change from a baseline median of 97 to 102 at month 4 but declined to 42 at month 12, that is, 6 months after receiving treatment, trailing the early group as expected. By month 24, both treatment groups had reached a median MF level of 0. After treatment, Wolbachia were depleted from MF by ≥ 1-log drop compared with baseline levels. We conclude that M. perstans in Ghana harbor Wolbachia that are effectively depleted by doxycycline with subsequent reduction in MF loads, most likely because of interruption of fertility of adult worms.

The large number of activities contributing to zoonoses surveillance and control capability, on both human and animal domains, and their likely heterogeneous implementation across administrative units make assessment and comparisons of capability performance between such units a complex task. Such comparisons are important to identify gaps in capability development, which could lead to clusters of vulnerable areas, and to rank and subsequently prioritize resource allocation toward the least capable administrative units. Area-level preparedness is a multidimensional entity and, to the best of our knowledge, there is no consensus on a single comprehensive indicator, or combination of indicators, in a summary metric. We use Bayesian spatial factor analysis models to jointly estimate and rank disease control and surveillance capabilities against visceral leishmaniasis (VL) at the municipality level in Brazil. The latent level of joint capability is informed by four variables at each municipality, three reflecting efforts to monitor and control the disease in humans, and one variable informing surveillance capability on the reservoir, the domestic dog. Because of the large volume of missing data, we applied imputation techniques to allow production of comprehensive rankings. We were able to show the application of these models to this sparse dataset and present a ranked list of municipalities based on their overall VL capability. We discuss improvements to our models, and additional applications.

Cutaneous leishmaniasis (CL) remains one of the world’s most prevalent neglected diseases, particularly in developing countries. Identification of the involved Leishmania species is an important step in the diagnosis and case management process. In this study, we tested simple, rapid, and highly sensitive loop-mediated isothermal amplification (LAMP) assays for Leishmania DNA species-specific detection from cutaneous lesions. Two LAMP assays, targeting cysteine protease B (cpb) gene, were developed to detect and identify Leishmania major and Leishmania tropica species. Loop-mediated isothermal amplification specificity was examined using DNA samples from other Leishmania species and Trypanosoma species. No cross-reactions were detected. The developed LAMP assays exhibited sensitivity with a detection limit of 20 fg and 200 fg for L. major and L. tropica, respectively. Both tests were applied on clinical samples of CL suspected patients living in endemic Tunisian regions and compared with kinetoplast DNA quantitative PCR (qPCR), microscopic, and conventional cpb-based polymerase chain reaction (PCR) assays. Our LAMP tests were able to discriminate between L. major and L. tropica species and showed a sensitivity of 84% and a specificity of 100%. However, when compared with the performance of the diagnostic tests with latent class analysis (LCA), our LAMP assays show a sensitivity of 100%. These assays can be used as a first-line molecular test for early diagnosis and prompt management of CL cases in public health programs.

War provides ideal grounds for the outbreak of infectious diseases, and the Syrian war is not an exception to this rule. Following the civil crisis, Syria and refugee camps of neighboring countries witnessed an outbreak of leishmaniasis. We accessed the database of the central leishmaniasis registry in Latakia city and obtained the leishmaniasis data of the period 2008–2016. Our data showed that the years 2013 and 2014 recorded a surge in the number of both cutaneous leishmaniases (CL) and visceral leishmaniasis (VL) cases. This surge coincided with the massive internal displacement waves that struck Latakia governorate during that time. Subsequently, after 2015, the number of recorded CL and VL cases gradually decreased. This drop coincided with a reduced influx of internally displaced persons into Latakia governorate. Our report depicts the effects of the Syrian crisis on the epidemiology of leishmaniasis by outlining the experience of Latakia governorate. Similar results may have occurred in other refugee-hosting Syrian governorates.

Chagas disease is caused by the protozoan Trypanosoma cruzi. This disease is distributed in 21 Latin American countries, where it is mostly vector-borne. In Brazil, there are 68 triatomine species. To date, the epidemiological surveys indicate that the state of São Paulo presents 11 species of triatomines, and most of these species have already been collected in a home environment and found to be infected with T. cruzi. Problems in correctly identifying species can lead to incorrect panorama of distribution of Chagas disease vectors. Thus, we developed an identification key for the triatomines of the state of São Paulo, based on cytogenetic data. With the exception of Panstrongylus diasi that does not present cytogenetic data available in the literature, all species were differentiated by cytogenetic characteristics. We emphasize the importance of using this key as a simple and objective tool in the entoepidemiological surveys conducted by the vector control programs.