The American Journal of Tropical Medicine and Hygiene - Current Issue

Strongyloidiasis is caused by a soil-transmitted helminth that is endemic in tropical and subtropical countries. The parasite can complete its life cycle without leaving the host, allowing autoinfection and persistence. The risk of infection in travelers is low, but the disease may become lethal following immunosuppression. In case of solid organ transplantation, the risk of donor transmission has been suspected for several years. However, the management of live donors in this context has only recently been considered, and no guidelines exist for the management of deceased donors. To highlight the complexity of diagnosing, treating, and preventing strongyloidiasis donor transmission, we describe a case of possible transmission of severe strongyloidiasis to a kidney transplant recipient with limited travel history. Taking into account the difficulty of diagnosing chronic strongyloidiasis infection and the increase in travel and immunosuppressive treatments, we recommend pragmatic management guidelines to limit the risks of infection.

We conducted a cross sectional study to assess 1) the association between access to basic sanitation and fecal contamination of sentinel toy balls and 2) if other sanitation factors such as shared use and cleanliness are associated with fecal contamination of sentinel toy balls. We assessed sanitation facilities in 454 households with a child aged 6–24 months in rural Bangladesh. We defined “basic” sanitation as access to improved sanitation facilities (pit latrine with a slab or better) not shared with other households. In each household, an identical toy ball was given to the target child. After 24 hours, the balls were rinsed to enumerate fecal coliforms as an indicator of household fecal contamination. Households with basic sanitation had lower fecal coliform contamination than households with no access to basic sanitation (adjusted difference in means: −0.31 log10 colony forming units [CFU]/toy ball; 95% confidence interval [CI]: −0.61, −0.01). Shared sanitation facilities of otherwise improved type were more likely to have visible feces on the latrine slab compared with private facilities. Among households with access to improved sanitation, households with no visible feces on the latrine slab had less toy ball contamination than households with visible feces on the latrine slab (adjusted difference in means: −0.38 log10 CFU/toy ball; 95% CI: −0.77, 0.02). Access to basic sanitation may prevent fecal contamination of the household environment. An Improved sanitation facility used by an individual household may be better in preventing household fecal contamination compared with improved facilities shared with other households.

We assessed the ability of sodium dichloroisocyanurate (NaDCC) to provide adequate chlorine residual when used to treat groundwater with variable iron concentration. We randomly selected 654 tube wells from nine subdistricts in central Bangladesh to measure groundwater iron concentration and corresponding residual-free chlorine after treating 10 L of groundwater with a 33-mg-NaDCC tablet. We assessed geographical variations of iron concentration using the Kruskal–Wallis test and examined the relationships between the iron concentrations and chlorine residual by quantile regression. We also assessed whether user-reported iron taste in water and staining of storage vessels can capture the presence of iron greater than 3 mg/L (the World Health Organization threshold). The median iron concentration among measured wells was 0.91 (interquartile range [IQR]: 0.36–2.01) mg/L and free residual chlorine was 1.3 (IQR: 0.6–1.7) mg/L. The groundwater iron content varied even within small geographical regions. The median free residual chlorine decreased by 0.29 mg/L (95% confidence interval: 0.27, 0.33, P < 0.001) for every 1 mg/L increase in iron concentration. Owner-reported iron staining of the storage vessel had a sensitivity of 92%, specificity of 75%, positive predictive value of 41%, and negative predictive value of 98% for detecting > 3 mg/L iron in water. Similar findings were observed for user-reported iron taste in water. Our findings reconfirm that chlorination of groundwater that contains iron may result in low-level or no residual. User reports of no iron taste or no staining of storage containers can be used to identify low-iron tube wells suitable for chlorination. Furthermore, research is needed to develop a color-graded visual scale for iron staining that corresponds to different iron concentrations in water.

Community-led total sanitation (CLTS) is a common method for promoting sanitation in low-income settings. This cluster-randomized trial evaluated an intervention to improve inclusion of people with disability in CLTS through training facilitators. A qualitative study examined intervention acceptability. The trial included 171 people with disabilities (78 control and 93 intervention) living in 15 intervention and 15 control communities. In the intervention arm, respondents were more likely to participate in a community meeting about sanitation (+18.7%, 95% confidence interval [CI]: 3.2, 34.2) and to have been visited to discuss sanitation (+19.7, 95% CI: 0.6, 37.8). More intervention households improved latrine access for the disabled member (+9%, CI: −3.1, 21.0). Inclusive CLTS could improve sanitation access for people with disability but requires support to households beyond that provided in this trial.

Poor child gut health, resulting from a lack of access to an improved toilet or clean water, has been proposed as a biological mechanism underlying child stunting and oral vaccine failure. Characteristics related to household sanitation, water use, and hygiene were measured among a birth cohort of 270 children from peri-urban Iquitos Peru. These children had monthly stool samples and urine samples at four time points and serum samples at (2–4) time points analyzed for biomarkers related to intestinal inflammation and permeability. We found that less storage of fecal matter near the household along with a reliable water connection were associated with reduced inflammation, most prominently the fecal biomarker myeloperoxidase (MPO) (no sanitation facility compared with those with an onsite toilet had −0.43 log MPO, 95% confidence interval [CI]: −0.74, −0.13; and households with an intermittent connection versus those with a continuous supply had +0.36 log MPO, 95% CI: 0.08, 0.63). These results provide preliminary evidence for the hypothesis that children less than 24 months of age living in unsanitary conditions will have elevated gut inflammation.

Water, sanitation and hygiene (WASH) interventions have a small but measurable benefit on stunting, but not on wasting. Our objective was to assess the effectiveness of a household WASH package on the performance of an Outpatient Therapeutic feeding Program (OTP) for severe acute malnutrition (SAM). We conducted a cluster-randomized controlled trial embedded in a routine OTP. The study population included 20 health centers (clusters) from Mao and Mondo districts in Chad. Both arms received the OTP. The intervention arm received an additional household WASH package (chlorine, soap, water storage container, and promotion on its use). The primary objective measures were the relapse rates to SAM at 2 and 6 months post-recovery. The secondary objectives included the recovery rate from SAM, the time-to-recovery, the weight gain, and the diarrhea longitudinal prevalence in OTP. The study lasted from April 2015 to May 2016. Among the 1,603 recruited children, 845 were in the intervention arm and 758 in the control arm. No differences in the relapse rates were noticed at 2 (−0.4%; P = 0.911) and 6 (−1.0%; P = 0.532) months. The intervention decreased the time-to-recovery (−4.4 days; P = 0.038), improved the recovery rate (10.5%; P = 0.034), and the absolute weight gain (3.0 g/d; P = 0.014). No statistical differences were noticed for the diarrhea longitudinal prevalence (−1.7%; P = 0.223) and the weight gain velocity (0.4 g/kg/d; P = 0.086). Our results showed that adding a household WASH package did not decrease post-recovery relapse rates but increased the recovery rate among children admitted in OTP. We recommend further robust trials in other settings to confirm our results.

Diarrhea is a leading cause of death among children aged less than five years globally. Most studies of pediatric diarrhea rely on caregiver-reported stool consistency and frequency to define the disease. Research on the validity of caregiver-reported diarrhea is sparse. We collected stool samples from 2,398 children participating in two clinical trials in the Amhara region of Ethiopia. The consistency of each stool sample was graded by the child’s caregiver and two trained laboratory technicians according to an illustrated stool consistency scale. We assessed the reliability of graded stool consistency among the technicians, and then compared the caregiver’s grade with the technician’s grade. We also tested if the illustrated stool consistency scale could improve the validity of caregiver’s report. The weighted kappa measuring the agreement between the two laboratory technicians reached 0.90 after 500 stool samples were graded. The sensitivity of caregiver-reported loose or watery stool was 15.5% (95% confidence interval [CI]: 9.7, 24.2) and the specificity was 98.4% (95% CI 97.1, 99.1). With the illustrated scale, the sensitivity was 68.5% (95% CI: 58.5, 77.1) and the specificity was 86.1% (95% CI: 79.3, 90.9). The results indicate that caregiver-reported stool consistency using the terms “loose or watery” does not accurately describe stool consistency as graded by trained laboratory technicians. Given the predominance of using caregiver-reported stool consistency to define diarrheal disease, the low sensitivity identified in this study suggests that the burden of diarrheal disease may be underestimated and intervention effects could be biased. The illustrated scale is a potential low-lost tool to improve the validity of caregiver-reported stool consistency.

During 2014, Africa reported more than half of the global suspected cholera cases. Based on the data collected from seven countries in the African Cholera Surveillance Network (Africhol), we assessed the sensitivity, specificity, and positive and negative predictive values of clinical cholera case definitions, including that recommended by the World Health Organization (WHO) using culture confirmation as the gold standard. The study was designed to assess results in real-world field situations in settings with recent cholera outbreaks or endemicity. From June 2011 to July 2015, a total of 5,084 persons with suspected cholera were tested for Vibrio cholerae in seven different countries of which 35.7% had culture confirmation. For all countries combined, the WHO case definition had a sensitivity = 92.7%, specificity = 8.1%, positive predictive value = 36.1%, and negative predictive value = 66.6%. Adding dehydration, vomiting, or rice water stools to the case definition could increase the specificity without a substantial decrease in sensitivity. Future studies could further refine our findings primarily by using more sensitive methods for cholera confirmation.

Consumption of contaminated stored food can cause childhood diarrhea. Flies carry enteropathogens, although their contribution to food contamination remains unclear. We investigated the role of flies in contaminating stored food by collecting food and flies from the same households in rural Bangladesh. We selected 182 households with children ≤ 24 months old that had stored foods for later feeding at room temperature for ≥ 3 hours. We collected food samples and captured flies with fly tapes hung by the kitchen. We used the IDEXX Quanti-Tray System (Colilert-18 media; IDEXX Laboratories, Inc., Westbrook, ME) to enumerate Escherichia coli with the most probable number (MPN) method. Escherichia coli–positive IDEXX wells were analyzed by polymerase chain reaction for pathogenic E. coli genes (eae, ial, bfp, ipaH, st, lt, aat, aaiC, stx 1 , and stx 2 ). Escherichia coli was detected in 61% (111/182) of food samples, with a mean of 1.1 log10 MPN/dry g. Fifteen samples (8%) contained pathogenic E. coli; seven (4%) had enteropathogenic E. coli (EPEC) genes (eae and/or bfp); and 10 (5%) had enteroaggregative E. coli genes (aat and/or aaiC). Of flies captured in 68 (37%) households, E. coli was detected in 41 (60%, mean 2.9 log10 MPN/fly), and one fly (1%) had an EPEC gene (eae). For paired fly-food samples, each log10 MPN E. coli increase in flies was associated with a 0.31 log10 MPN E. coli increase in stored food (95% confidence interval: 0.07, 0.55). In rural Bangladesh, flies possibly a likely route for fecal contamination of stored food. Controlling fly populations may reduce contamination of food stored for young children.

Burkholderia pseudomallei, the etiologic agent of melioidosis, is predicted to be ubiquitous in tropical regions of the world with areas of highest endemicity throughout Southeast Asia (SEA). Nevertheless, the distribution of B. pseudomallei and the burden of melioidosis in many SEA countries remain unclear. In Cambodia, only two human endemic cases of melioidosis were reported through 2008 and since then only a few hundred cases have been described in the literature. This is in sharp contrast to the annual burden of thousands of cases in surrounding areas. To further investigate the prevalence of melioidosis in Cambodia, we used a recently developed O-polysaccharide–based rapid enzyme-linked immunosorbent assay to detect B. pseudomallei–specific antibodies in serum samples obtained from 1,316 febrile illness or sepsis patients from 10 different provinces. Based on a cutoff value derived through culture-confirmed melioidosis cases, the proportion of positive samples in our cohort was approximately 12%. Regression analysis indicated that the odds of obtaining a positive result were 2.2 times higher for males than females controlling for age and province (95% confidence interval: 1.6–3.2, P < 0.001). Consistent with this, 9.2% of females were positive versus 18.2% of males (P < 0.001). Notably, 22.5% of grain or rice farmers were positive versus 10.1% of subjects with occupations not involving regular contact with soil. Positive results varied significantly by province. Collectively, the results of this study suggest that the true burden of melioidosis in Cambodia is greater than has previously been reported.

Streptococcus pneumoniae (SP) is a leading cause of child mortality globally, killing around half a million children aged 5 years and less per year. Nasopharyngeal carriage of SP is a prerequisite to disease, and the prevalence of colonization reaches 100% within the first few years of life. Serotype prevalence varies geographically, impacting the serotype coverage of pneumococcal vaccines, and serotype prevalence data are limited from large regions of the world, including sub-Saharan Africa. We enrolled 323 unvaccinated children, aged 4–7 years from coastal Kenya and obtained nasopharyngeal swab samples before and after vaccination with the 10-valent pneumococcal vaccine. Vaccination did not reduce the overall prevalence of pneumococcal carriage in our cohort, with 65 (20%) children colonized before vaccination and 63 (19.4%) colonized postvaccination. However, the prevalence of vaccine-included serotypes (vaccine strains) declined from 43% to 19% of positive swabs, whereas non-vaccine serotypes increased from 46% to 73%. This study contributes to the few data available regarding pneumococcal carriage and serotype prevalence in Kenya and is in concordance with reports of dynamic serotype replacement, driven by vaccine pressure.

The treatment of Helicobacter pylori infection is complicated by antibiotic resistance. A high levofloxacin (LVX) resistance rate was previously demonstrated in H. pylori isolates from gastric mucosa (40%) and esophagus (19%) in individual hosts of a Venezuelan population. We aimed to assess the molecular mechanisms of LVX resistance and susceptibility in isolates from the gastroesophageal mucosa, by studying point mutations in the quinolone resistance–determining region of gyrA and gyrB genes. Sequencing of gyrA and gyrB genes (N = 120) helped to identify point mutations in 60 isolates (30 from antrum and 30 from esophagus) of five dyspeptic patients. Double (Asn87Thr and Asp91Asn) and single (Asn87Ile or Asn87Thr) mutations in the gyrA gene were identified in the esophageal mucosa. These mutations have been commonly found in the stomach. Occurrence of a single (Asn87Ile) mutation was associated with high resistance (minimum inhibitory concentration ≥ 32 μg/mL) to LVX. Only a single (Ser479Gly) mutation was found in the gyrB gene in both mucosae. One patient presented isolates with no mutations in the two genes studied. Isolates with the same mutation pattern in individual hosts revealed identical genetic profiles for these genes, confirming that isolates identified in the esophageal mucosa come from isolates colonizing the stomach. Helicobacter pylori resistance to LVX in the esophagus is related to double- and single-point mutations in gyrA and gyrB genes, such as those found in the stomach. Levofloxacin should be applied with caution, because its antibiotic effect on H. pylori is decreasing in Latin America, perhaps owing to high prescription rates.

Leptospirosis is a globally important cause of acute febrile illness, and a common cause of non-malarial fever in Asia, Africa, and Latin America. Simple rapid diagnostic tests (RDTs) are needed to enable health-care workers, particularly in low resource settings, to diagnose leptospirosis early and give timely targeted treatment. This study compared four commercially available RDTs to detect human IgM against Leptospira spp. in a head-to-head prospective evaluation in Mahosot Hospital, Lao PDR. Patients with an acute febrile illness consistent with leptospirosis (N = 695) were included in the study during the 2014 rainy season. Samples were tested with four RDTs: (“Test-it” [Life Assay, Cape Town, South Africa; N = 418]; “Leptorapide” [Linnodee, Ballyclare, Northern Ireland; N = 492]; “Dual Path Platform” [DPP] [Chembio, Medford, NY; N = 530]; and “SD-IgM” [Standard Diagnostics, Yongin, South Korea; N = 481]). Diagnostic performance characteristics were calculated and compared with a composite reference standard combining polymerase chain reaction (PCR) (rrs), microscopic agglutination tests (MATs), and culture. Of all patients investigated, 39/695 (5.6%) were positive by culture, PCR, or MAT. The sensitivity and specificity of the RDTs ranged greatly from 17.9% to 63.6% and 62.1% to 96.8%, respectively. None of the investigated RDTs reached a sensitivity or specificity of > 90% for detecting Leptospira infections on admission. In conclusion, our investigation highlights the challenges associated with Leptospira diagnostics, particularly in populations with multiple exposures. These findings emphasize the need for extensive prospective evaluations in multiple endemic settings to establish the value of rapid tools for diagnosing fevers to allow targeting of antibiotics.

Anaplasmosis, cat-scratch disease, and Lyme disease are emerging vector-borne infectious diseases in Korea. Although the prevalence of vector-borne pathogens (VBPs) in domestic animals and vector arthropods has been documented, there is limited information on the presence of VBPs in wild animals. The raccoon dog (Nyctereutes procyonoides), a wild canid found in East Asia and Europe, represents a potential wildlife reservoir for zoonotic diseases. To investigate the prevalence of VBPs in raccoon dogs, 142 carcasses and 51 blood samples from captured raccoon dogs were collected from 2003 to 2010 and from 2008 to 2009, respectively, in Korea. In addition, 105 Haemaphysalis flava (14 larvae, 43 nymphs, 32 males, and 16 females) and nine Haemaphysalis longicornis (all female) were collected from three raccoon dogs. Samples of the spleen and blood were tested for the presence of VBPs by using nested polymerase chain reaction. Among the samples collected from 193 raccoon dogs and 114 ticks, two samples were positive for Anaplasma phagocytophilum, four for Anaplasma bovis, two for Borrelia theileri, and two for Bartonella henselae. To the best of our knowledge, this study is the largest survey of raccoon dogs aimed at the analysis of VBPs in this species. Moreover, the present study represents the first identification of A. phagocytophilum, B. henselae, and B. theileri in raccoon dogs in their native habitat (East Asia).

In 2004, there existed limited tuberculosis (TB) research capacity in the country of Georgia. In response, a collaborative research training program (RTP) supported by a National Institutes of Health Fogarty International Center Global Infectious Diseases grant was formed between a U.S. academic institution and the National Center for Tuberculosis and Lung Disease (NCTLD) and other institutions in Georgia. We sought to assess outcomes of this RTP. The TB RTP combined didactic and mentored research training for Georgian trainees. Long-term trainees were supported for a 2-year period and with posttrainee career development mentoring. Metrics used to measure program performance included publications, grants received, and career advancement. From 2004 to 2015, 20 trainees participated in the program with 15 (75%) authoring a total of 65 publications in PubMed-listed journals. The median number of publications per trainee was six (interquartile range 2–14). A total of 16 (80%) trainees remain working in the area of TB; nine were promoted to leadership positions and three to lead research units at Georgian institutions. Ten (50%) trainees were the principal investigator (PI) of a peer-reviewed external grant after Fogarty-supported training, and 40% served as research mentors. Annual TB-related research funding at the NCTLD increased from $5,000 in 2005 to ∼$1.5 million in 2017. A Georgian Fogarty trainee was either PI, site PI, or coinvestigator on > 90% of all research funding. We believe that the NIH Fogarty-funded TB research training grant has made critical contributions to increasing the TB-related research infrastructure and capacity in Georgia, particularly at the NCTLD.

Leprosy and podoconiosis (podo) are neglected tropical diseases that cause severe disfigurement and disability, and may lead to catastrophic health expenditure and hinder economic development of affected persons and households. This study compared economic costs of both diseases on affected households with unaffected neighboring households in the Northwest Region (N.W.R.) of Cameroon. A matched comparative cross-sectional design was used enrolling 170 households (43 podo case households, 41 podo control households, 43 leprosy case households, and 43 leprosy control households) from three health districts in the N.W.R. Direct treatment costs for podo averaged 142 United State dollar (USD), compared with zero for leprosy (P < 0.001). This was also reflected in the proportion of annual household income consumed (0.4 versus 0.0, respectively, P < 0.001). Both diseases caused considerable reductions in working days (leprosy 115 versus podo 135 days. P for comparison < 0.001). The average household income was considerably lower in podo-affected households than unaffected households (410 versus 913 USD, P = 0.01), whereas income of leprosy-affected households was comparable to unaffected households (329 versus 399 USD, P = 0.23). Both leprosy and podo cause financial burdens on affected households, but those on podo-affected families are much greater. These burdens occur through direct treatment costs and reduced ability to work. Improved access to public health interventions for podo including prevention, morbidity management and disability prevention are likely to result in economic returns to affected families. In Cameroon, one approach to this would be through subsidized health insurance for these economically vulnerable households.

Negative results in serological routine screening of patients with microbiologically proven Paracoccidioidomycosis (PCM) are occasionally reported. Failure in detecting anti-Paracoccidioides antibodies has been ascribed to factors either related to serological techniques or to the status of the host immune reactivity. Recently, this issue has been renewed by the recognition that the Paracoccidioides genera comprises two species, lutzii and brasiliensis, which have distinct antigenic profiles and, therefore, may elicit different host antibody responses. We describe a patient with the acute form PCM due to Paracoccidioides brasiliensis with negative results on two reference centers’ routine screening for P. brasiliensis antibodies, but positive results with Paracoccidioides lutzii antigens. The present case report suggests that antibodies elicited during P. brasiliensis infection recognize antigenic fractions shared by both species, highlighting the difficulties in distinguishing the two infections by means of the currently available routine serological assays.