The American Journal of Tropical Medicine and Hygiene - Current Issue

In August 2017, the National Institute of Allergy and Infectious Diseases convened a meeting, entitled “Understanding the Liver-Stage Biology of Malaria Parasites to Enable and Accelerate the Development of a Highly Efficacious Vaccine,” to discuss the needs and strategies to develop a highly efficacious, whole organism–based vaccine targeting the liver stage of malaria parasites. It was concluded that attenuated sporozoite platforms have proven to be promising approaches, and that late-arresting sporozoites could potentially offer greater vaccine performance than early-arresting sporozoites against malaria. New knowledge and emerging technologies have made the development of late-arresting sporozoites feasible. Highly integrated approaches involving liver-stage research, “omics” studies, and cutting-edge genetic editing technologies, combined with in vitro culture systems or unique animal models, are needed to accelerate the discovery of candidates for a late-arresting, genetically attenuated parasite vaccine.

Epidemiologic data indicate a global distribution of anthrax outbreaks associated with certain ecosystems that promote survival and viability of Bacillus anthracis spores. Here, we characterized three anthrax outbreaks involving humans, livestock, and wildlife that occurred in the same locality in Kenya between 2014 and 2017. Clinical and epidemiologic data on the outbreaks were collected using active case finding and review of human, livestock, and wildlife health records. Information on temporal and spatial distribution of prior outbreaks in the area was collected using participatory epidemiology. The 2014–2017 outbreaks in Nakuru West subcounty affected 15 of 71 people who had contact with infected cattle (attack rate = 21.1%), including seven with gastrointestinal, six with cutaneous, and two with oropharyngeal forms of the disease. Two (13.3%) gastrointestinal human anthrax cases died. No human cases were associated with infected wildlife. Of the 54 cattle owned in 11 households affected, 20 died (attack rate = 37%). The 2015 outbreak resulted in death of 10.5% of the affected herbivorous wildlife at Lake Nakuru National Park, including 745 of 4,500 African buffaloes (species-specific mortality rate = 17%) and three of 18 endangered white rhinos (species-specific mortality rate = 16%). The species mortality rate ranged from 1% to 5% for the other affected wildlife species. Participatory epidemiology identified prior outbreaks between 1973 and 2011 in the same area. The frequency and severity of outbreaks in this area suggests that it is an anthrax hotspot ideal for investigating risk factors associated with long-term survival of anthrax spores and outbreak occurrence.

Bartonella rochalimae is an emerging zoonotic pathogen present in the United States, South America, and Europe. The molecular detection of B. rochalimae frequently relies on polymerase chain reaction (PCR) assays that target the genus Bartonella coupled with DNA sequencing for species determination. However, the presence of other Bartonella spp. in the sample being tested may result in false-negative results for B. rochalimae, especially when Sanger sequencing is used. We developed a sensitive and specific quantitative PCR platform for B. rochalimae by targeting the intergenic transcribed spacer, gltA, and rpoB genes, which are recommended for subtyping characterization. This PCR platform achieved the limit of detection between five and 10 genomic equivalents per reaction and did not amplify DNA from other Bartonella species or selected hosts. This PCR platform is a fast and cost-effective option to be used in epidemiological evaluations of reservoirs and vectors and in detecting and quantifying B. rochalimae infection in humans.

In many parts of the world, the case-fatality rate of Chromobacterium violaceum infection approaches 60%. To evaluate the spectrum of disease associated with C. violaceum in Far North Queensland (FNQ), Australia, we reviewed all culture-confirmed isolates from 1997 to 2017. There were 28 isolates, 15 represented infection, 11 were contaminants, and two charts were destroyed preventing detailed evaluation of these cases. The most common sites of infection were the skin and soft tissue and the urinary tract; there were two cases of bacteremia without focus. There were no deaths attributable to C. violaceum during the study period and only two cases required intensive care unit support, although in both patients this was not for the C. violaceum infection, but for the management of other health issues. Globally, C. violaceum has a reputation as a deadly pathogen, but in FNQ, Australia, infections usually follow a relatively benign course.

Severe flooding has been linked to outbreaks of leptospirosis. Two sequential extreme flood events in Western Fiji caused the largest outbreak of leptospirosis recorded in the South Pacific, with 1,217 total suspected cases, of which 314 were probable and confirmed. Most (83%) cases occurred within 6 weeks of the flood events, displaying a biphasic epidemic curve associated with the floods. Given the temporal proximity of cases to flooding events, most of the transmission appeared to occur during or immediately after the floods; therefore, prevention of exposure to contaminated environments is a priority in the immediate flood and post-flood period. In addition, genotyping studies suggest that multiple animal reservoirs were implicated in the outbreak, reaffirming the importance of integrated human and animal health strategies for leptospirosis control.

Among pyogenic liver abscesses, melioid etiology is considered in endemic regions in the presence of known health or occupational risk factors. “Honeycomb sign,” used to describe an abscess with multiple internal septations dividing the abscess cavity into multiple loculations of comparable sizes on imaging, is a sensitive sign for melioid liver abscess. This is a retrospective case–control study investigating incidence, sensitivity, and specificity of “honeycomb sign” in melioid liver abscess, in a cohort of patients with culture-proven melioidosis infection. Abscesses ≥ 2 cm were analyzed for the honeycomb sign. P value < 0.05 was taken as statistically significant. Interobserver agreement was calculated between two radiologists for the presence of the sign, sensitivity, and specificity. A total of 40 abscesses were analyzed. Thirty-four abscesses (85%) manifested the honeycomb sign with interobserver agreement (kappa = 0.70 and 0.92). Sensitivity of the sign is 85% (95% confidence interval [CI]: 70–94%), specificity is 75% (95% CI: 59–87%), positive predictive value is 77% (95% CI: 62–88%), and negative predictive value is 83% (95% CI: 67–94%). If abscess size is ≥ 3 cm, the sensitivity is 91% (95% CI: 77–98%), specificity is 75% (95% CI: 59–87%), positive predictive value is 76% (95% CI: 61–88%), and negative predictive value is 91% (95% CI: 76–98%). Honeycomb sign is a novel imaging marker for melioid liver abscess. Increased awareness and recognition of this imaging feature has the potential to affect patient management.

In collaboration with the health ministries that we serve and other partners, we set out to complete the multiple-country Global Trachoma Mapping Project. To maximize the accuracy and reliability of its outputs, we needed in-built, practical mechanisms for quality assurance and quality control. This article describes how those mechanisms were created and deployed. Using expert opinion, computer simulation, working groups, field trials, progressively accumulated in-project experience, and external evaluations, we developed 1) criteria for where and where not to undertake population-based prevalence surveys for trachoma; 2) three iterations of a standardized training and certification system for field teams; 3) a customized Android phone–based data collection app; 4) comprehensive support systems; and 5) a secure end-to-end pipeline for data upload, storage, cleaning by objective data managers, analysis, health ministry review and approval, and online display. We are now supporting peer-reviewed publication. Our experience shows that it is possible to quality control and quality assure prevalence surveys in such a way as to maximize comparability of prevalence estimates between countries and permit high-speed, high-fidelity data processing and storage, while protecting the interests of health ministries.

We present a rare case of an Indian immigrant suffering from concomitant infection of Salmonella typhi and spotted fever group Rickettsia. We discuss the scarce reports of dual infections from the developing world and the related diagnostic challenges.

We used whole-genome sequencing to investigate a tuberculosis outbreak involving U.S.-born persons in the prison system and both U.S.- and foreign-born persons in the community in Florida over a 7-year period (2009–2015). Genotyping by spacer oligonucleotide typing and 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat suggested that the outbreak might be clonal in origin. However, contact tracing could not link the two populations. Through a multidisciplinary approach, we showed that the cluster involved distinct bacterial transmission networks segregated by country of birth. The source strain is of foreign origin and circulated in the local Florida community for more than 20 years before introduction into the prison system. We also identified novel transmission links involving foreign and U.S.-born cases not discovered during contact investigation. Our data highlight the potential for spread of strains originating from outside the United States into U.S. “high-risk” populations, such as prisoners, with subsequent movement back to the general community.

Pulmonary tuberculosis (PTB) is associated with modulation of levels of adipokines, specifically adiponectin and leptin, but the effect of standard antituberculosis treatment (ATT) on the systemic levels of adiponectin, resistin, and leptin has not been well explored. To identify the association of adipokines with PTB and their relationship with disease severity and bacterial burden, we measured the levels of adiponectin, resistin, and leptin in PTB individuals and compared them with latent tuberculosis (LTB) and healthy control (HC) individuals. Pulmonary tuberculosis was characterized by diminished circulating levels of adiponectin and leptin and heightened circulating levels of resistin in comparison to that in LTB and HC individuals. However, PTB with bilateral or cavitary disease did not exhibit any increased systemic levels of these adipokines in comparison with those with unilateral or non-cavitary disease, respectively. In addition, none of the adipokines exhibited a positive correlation with bacterial burdens, but adiponectin alone exhibited a negative correlation with body mass index in PTB individuals. Finally, on successful completion of ATT, PTB individuals exhibited significantly increased levels of adiponectin and leptin and significantly decreased levels of resistin. Therefore, our data identify an important association of systemic adipokine levels with PTB disease and its alteration following ATT.

This is the first study to document the reduction of turbidity and Escherichia coli throughout the processes of full-scale gravity-fed drinking water plants (GFWTPs) and their downstream distribution systems in rural Honduras. The GFWTPs, which in these cases were designed by AguaClara, use standard treatment processes: coagulation, sedimentation, filtration, and chlorination. During the dry season, we measured E. coli, turbidity, and chlorine residual at five GFWTPs with < 1,000 connections and at three alternative piped-water systems in neighboring communities. Samples were evaluated from the raw water, settled water, filtered water, post-chlorination in the distribution tank, and at a distant-piped household connection. During the dry season, the treated water and household connections serviced by the GFWTPs met World Health Organization (WHO) recommendations for E. coli (< 1 most probable number [MPN]/100 mL). Alternative plants with the same water sources had comparable or higher E. coli and turbidity measurements posttreatment. We examined the performance robustness of two GFWTPs during the transition into the rainy season. The turbidity of the filtered water met WHO recommendations (< 1 nephelometric turbidity units). Escherichia coli was not detected in treated water, indicating that the two GFWTPs can consistently remove particulates and E. coli from source waters containing varying levels of turbidity. During two sampling events during the rainy season, E. coli was detected at the household connection of a GFWTP system with intermittent service and a substandard chlorine residual (geometric mean = 1.0 MPN/100 mL). Strategies to avoid contamination or inactivate E. coli in the distribution system are needed to ensure safe drinking water at the points of delivery, especially for systems with intermittent service.

Poor drinking water quality is one of the main causes of acute diarrheal disease in developing countries. The study investigated the relationship between fecal contamination of hands, stored drinking water, and source waters in India. We further evaluated the environmental and behavioral factors associated with recontamination of water between collection and consumption. The bacterial contamination, that is, Escherichia coli (log10 most probable number per two hands), found on mothers’ hands (mean = 1.11, standard deviation [SD] = 1.2, N = 152) was substantially higher than that on their children younger than 5 years (mean = 0.64, SD = 1.0, and N = 152). We found a low level of E. coli (< 1 per 100 mL) in the source water samples; however, E. coli contamination in stored drinking water was above the recommended guidelines of the World Health Organization. The study also found that E. coli on hands was significantly associated with E. coli in the stored drinking water (P < 0.001). Moreover, E. coli was positively associated with gastrointestinal symptoms (odds ratio 1.42, P < 0.05). In the households with elevated levels (> 100 E. coli/100 mL) of fecal contamination, we found that 43.5% had unimproved sanitation facilities, poor water handling practices, and higher diarrheal incidences. The water quality deterioration from the source to the point of consumption is significant. This necessitates effective interventions in collection, transport, storage, and extraction practices when hand–water contact is likely to occur. These findings support the role of hands in the contamination of stored drinking water and suggest that clean source water does not guarantee safe water at the point of consumption.

Available measures of handwashing are prone to bias. We tested the feasibility and reliability of weighing soap at repeated visits and subtracting the measured weight from the prior weight to assess daily per capita soap consumption in a low-income community in Dhaka, Bangladesh. Fieldworkers approached 220 households twice weekly over 2 months. They interviewed participants, weighed soap, and assessed hand cleanliness and the presence of a handwashing station. Respondents used bar soap (91% [201]) and laundry detergent cakes (39% [85]) for handwashing as well as for bathing and laundry. Ninety-eight percent of households had bar soap present on at least one visit, although only 50% had bar soap at every visit during the 2-month period. Fieldworkers observed a soap fragment on the wall near the latrine in 27% (470) of visits. Households consumed a mean 1.5 g of bar soap and 3.2 g detergent cake per person per day. Daily per capita soap consumption was similar in households visited by fieldworkers after different intervals (2, 3, 4, or 5 days). Soap consumption was not associated with household wealth, education of the household head, the presence of a handwashing station, the presence of water or soap at a handwashing station, or palm inspections of the mother or child. Soap weight measurements were an objective, reliable measure of soap consumption that provided different information from other handwashing indicators. The frequent use of a soap product for purposes other than handwashing complicates using soap consumption as a handwashing measure.

Diarrheal illness, a common occurrence among people living with human immunodeficiency virus (PLHIV), is largely preventable through access to safe drinking water quality, sanitation, and hygiene (WASH) facilities. We examined WASH characteristics among households with and without HIV-positive residents enrolled in the Global Enteric Multicenter Study (GEMS) in rural Western Kenya. Using univariable logistic regression, we examined differences between HIV-positive and HIV-negative households in regard to WASH practices. Among HIV-positive households, we explored the relationship between the length of time knowing their HIV status and GEMS enrollment. No statistically significant differences were apparent in the WASH characteristics among HIV-positive and HIV-negative households. However, we found differences in the WASH characteristics among HIV-positive households who were aware of their HIV status ≥ 30 days before enrollment compared with HIV-positive households who found out their status < 30 days before enrollment or thereafter. Significantly more households aware of their HIV-positive status before enrollment reported treating their drinking water (odds ratio [OR] confidence interval [CI]: 2.34 [1.12, 4.86]) and using effective water treatment methods (OR [CI]: 9.6 [3.09, 29.86]), and had better drinking water storage practices. This suggests that within this region of Kenya, HIV programs are effective in promoting the importance of practicing positive WASH-related behaviors among PLHIV.