The American Journal of Tropical Medicine and Hygiene - Current Issue

Despite the availability of proven measures to prevent the disease, rabies now kills more people in Myanmar than malaria. Although there are challenges in controlling rabies in such a large and culturally diverse country, Myanmar’s successful National Malaria Control Program demonstrates what can be achieved with sufficient political, financial, and scientific commitment. Presently, however, Myanmar lacks a comparable program to coordinate the multifaceted approach that is necessary to control rabies. The national government has invested heavily in improving access to postexposure prophylaxis, but there should also be an emphasis on other, more cost-effective strategies, particularly mass canine vaccination, which has been an essential component of successful rabies elimination programs in other countries. Continued health system strengthening is also required to improve primary health care, while decentralization of laboratory diagnostic services is needed to facilitate more timely, rational, and cost-effective use of postexposure prophylaxis.

Severe fever with thrombocytopenia syndrome (SFTS) is a newly recognized hemorrhagic fever disease found throughout Asia with a case fatality rate between 12% and 30%. Since 2009, SFTS has been reported in China throughout 14 Chinese Provinces. In addition, SFTS has been recognized in South Korea and Japan with the first confirmed cases reported in 2012. A similar disease, caused by the closely related Heartland virus, was also reported in the United States in 2009. SFTS is caused by SFTS virus, a novel tick-borne virus in the family Bunyaviridae, genus Phlebovirus. Unlike other mosquito- and sandfly-borne bunyaviruses, SFTS virus has not been extensively studied due to its recent emergence and many unknowns regarding its pathogenesis, life cycle, transmission, and options for therapeutics remains. In this review, we report the most current findings in SFTS virus research.

Enteroaggregative Escherichia coli (EAEC) cause acute and persistent diarrhea, mostly in children worldwide. Outbreaks of diarrhea caused by EAEC have been described, including a large outbreak caused by a Shiga toxin expressing strain. This study investigated the association of EAEC virulence factors with diarrhea in children less than 5 years. We characterized 428 EAEC strains isolated from stool samples obtained from moderate-to-severe diarrhea cases (157) and healthy controls (217) children aged 0–59 months recruited over 3 years as part of the Global Enteric Multicenter Study (GEMS) in The Gambia. Four sets of multiplex polymerase chain reaction were applied to detect 21 EAEC-virulence genes from confirmed EAEC strains that target pCVD432 (aatA) and AAIC (aaiC). In addition, Kirby-Bauer disc diffusion antimicrobial susceptibility testing was performed on 88 EAEC strains following Clinical Laboratory Standard Institute guidelines. We observed that the plasmid-encoded enterotoxin [odds ratio (OR): 6.9, 95% confidence interval (CI): 2.06–29.20, P < 0.001], aggregative adherence fimbriae/I fimbriae (aggA) [OR: 2.2, 95% CI: 1.16–4.29, P = 0.008], and hexosyltransferase (capU) [OR: 1.9, 95% CI 1.02–3.51, P = 0.028] were associated with moderate-to-severe diarrhea among children < 12 months old but not in the older age strata (> 12 months). Our data suggest that some EAEC-virulent factors have age-specific associations with moderate-to-severe diarrhea in infants. Furthermore, our study showed that 85% and 72% of EAEC strains tested were resistant to sulphamethoxazole-trimethoprim and ampicillin, respectively. Sulphamethoxazole-trimethoprim and ampicillin are among the first-line antibiotics used for the treatment of diarrhea in The Gambia.

We compared the concentrations of Escherichia coli quantified with Colilert™ and the compartment bag test (CBT) in the source water and household stored drinking water (SDW) of 35 households in western Kenya. We also investigated the associations of the perceptions of organoleptic properties and overall quality with ≥ 1 MPN/100 mL E. coli in SDW. Participants who rated the taste or smell of their SDW “< 5” on a 1 = “poor” to 5 = “excellent” Likert scale were 8.71 or 7.04 times more likely, respectively, to have ≥ 1 MPN/100 mL E. coli. Organoleptic properties are innate, albeit imperfect, indicators of fecal pollution in water. Within their shared quantification range, concentrations of E. coli enumerated with Colilert and CBT were similar and had a significant correlation coefficient, 0.896 (95% confidence interval = 0.691–1.101). The methods had moderate agreement within the World Health Organization’s health risk levels (Cohen’s Kappa coefficient = 0.640). In low-resource settings, CBT provides comparable assessments of E. coli concentrations to Colilert.

Lack of adequate sanitation results in fecal contamination of the environment and poses a risk of disease transmission via multiple exposure pathways. To better understand how eight different sources contribute to overall exposure to fecal contamination, we quantified exposure through multiple pathways for children under 5 years old in four high-density, low-income, urban neighborhoods in Accra, Ghana. We collected more than 500 hours of structured observation of behaviors of 156 children, 800 household surveys, and 1,855 environmental samples. Data were analyzed using Bayesian models, estimating the environmental and behavioral factors associated with exposure to fecal contamination. These estimates were applied in exposure models simulating sequences of behaviors and transfers of fecal indicators. This approach allows us to identify the contribution of any sources of fecal contamination in the environment to child exposure and use dynamic fecal microbe transfer networks to track fecal indicators from the environment to oral ingestion. The contributions of different sources to exposure were categorized into four types (high/low by dose and frequency), as a basis for ranking pathways by the potential to reduce exposure. Although we observed variation in estimated exposure (108–1016 CFU/day for Escherichia coli) between different age groups and neighborhoods, the greatest contribution was consistently from food (contributing > 99.9% to total exposure). Hands played a pivotal role in fecal microbe transfer, linking environmental sources to oral ingestion. The fecal microbe transfer network constructed here provides a systematic approach to study the complex interaction between contaminated environment and human behavior on exposure to fecal contamination.

Rapid urbanization has contributed to an urban sanitation crisis in low-income countries. Residents in low-income, urban neighborhoods often have poor sanitation infrastructure and services and may experience frequent exposure to fecal contamination through a range of pathways. There are little data to prioritize strategies to decrease exposure to fecal contamination in these complex and highly contaminated environments, and public health priorities are rarely considered when planning urban sanitation investments. The SaniPath Study addresses this need by characterizing pathways of exposure to fecal contamination. Over a 16 month period, an in-depth, interdisciplinary exposure assessment was conducted in both public and private domains of four neighborhoods in Accra, Ghana. Microbiological analyses of environmental samples and behavioral data collection techniques were used to quantify fecal contamination in the environment and characterize the behaviors of adults and children associated with exposure to fecal contamination. Environmental samples (n = 1,855) were collected and analyzed for fecal indicators and enteric pathogens. A household survey with 800 respondents and over 500 hours of structured observation of young children were conducted. Approximately 25% of environmental samples were collected in conjunction with structured observations (n = 441 samples). The results of the study highlight widespread and often high levels of fecal contamination in both public and private domains and the food supply. The dominant fecal exposure pathway for young children in the household was through consumption of uncooked produce. The SaniPath Study provides critical information on exposure to fecal contamination in low-income, urban environments and ultimately can inform investments and policies to reduce these public health risks.

Safe and sufficient water, sanitation, and hygiene (WaSH) prevent the spread of disease in health-care facilities (HCFs). Little research has been conducted on WaSH in HCF in sub-Saharan Africa. We carried out a cross-sectional study of WaSH in 1,318 randomly selected rural HCF (hospitals, health centers, health posts, and clinics) in regions throughout Ethiopia, Kenya, Mozambique, Rwanda, Uganda, and Zambia. Methods included questionnaires with head doctors and nurses to document WaSH access, continuity, quality, quantity and reliability, and analysis of drinking water samples for Escherichia coli. We found that fewer than 50% of rural HCFs had access to improved water sources on premises, improved sanitation, and consistent access to water and soap for handwashing (Ethiopia [7%), Kenya [30%], Mozambique [29%], Rwanda [50%], Uganda [30%], and Zambia [21%]). Adequate hand hygiene reduces disease transmission and health-care-acquired infections, but fewer than 25% of HCF in each country reported that a combination of water, soap, and hand-drying materials were always available. Our research points to a lack of basic WaSH services in rural HCFs in regions of sub-Saharan Africa, which poses a threat to the health of patients and health-care workers in these settings.

Marine microorganisms such as Shewanella spp., Vibrio spp., and Aeromonas spp. can cause sepsis secondary to a wound infection in the context of swimming. These microorganisms are most often susceptible to fluoroquinolones. Here, we report a unique case of Shewanella algae bacteremia associated with meningoencephalitis and disseminated via hematogenous spread secondary to a skin injury. The patient suffered the injury while swimming in saline water during a cruise holiday in Madagascar, and she was initially treated with amoxicillin. The neurological evolution was unsatisfactory. Better knowledge of such infections (and especially of the context in which they occur), as well as greater familiarity with the susceptibility profile of different marine microorganisms would have allowed health professionals to provide presumptive microbiological diagnosis and effective treatment earlier.

Multidrug-resistant organism (MDRO) infections cause high morbidity and mortality, and high costs to patients and hospitals. The study aims were to determine the frequency of MDRO colonization and associated factors in patients with lower-extremity wounds with colonization. A cross-sectional study was designed during November 2015 to July 2016 in a tertiary care hospital in Lima, Peru. A wound swab was obtained for culture and susceptibility testing. MDRO colonization was defined if the culture grew with methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and/or extended spectrum beta-lactamase (ESBL) microorganisms. The frequency of MDRO wound colonization was 26.8% among the 97 patients enrolled. The most frequent MDRO obtained was ESBL-producing Escherichia coli, which was significantly more frequent in chronic wounds versus acute wounds (17.2% versus 0%, P < 0.05). Infection control measures should be implemented when patients with chronic lower-extremity wounds are admitted.

Dengue virus (DENV) circulates in tropical and subtropical areas around the world, where it causes high morbidity and mortality. There is no effective treatment of infection, with supportive care being the only option. Furthermore, early detection and diagnosis are important to facilitate clinical decisions. In this study, seven monoclonal antibodies (mAbs) recognizing nonstructural protein 1 (NS1) of DENV were generated by hybridoma techniques. These antibodies can be divided into two groups: serotype-specific (DB6-1, DB12-3, and DB38-1) and nonspecific (consisting of antibodies DB16-1, DB20-6, DB29-1, and DB41-2). The B-cell epitopes of DB20-6 and DB29-1 were identified by phage display and site-directed mutagenesis, and its binding motif, WXXWGK, was revealed to correspond to amino acid residues 115–120 of the DENV-2 NS1 protein. A diagnostic platform, consisting of a serotype-specific capture antibody and a complex detection antibody, exhibited a detection limit of about 1 ng/mL, which is sufficient to detect NS1 in clinical serum samples from dengue patients. This diagnostic platform displayed better specificity and sensitivity than two examined commercial NS1 diagnostic platforms. In summary, our results indicate that these newly generated mAbs are suitable for detection of NS1 protein of DENV-2 in clinical samples.

Dengue virus (DENV) is expanding toward previously nonendemic areas. DENV has recently been introduced in Nepal with limited information. We report the clinical features and serotype distribution of DENV in Nepal during the 2010 outbreaks. A total of 1,215 clinical dengue cases at two major hospitals of central and western Nepal were investigated. Demographic, clinical, and laboratory parameters were recorded. Serum specimens were tested for DENV by IgM/IgG enzyme-linked immunosorbent assays (ELISAs) and reverse transcription polymerase chain reaction (RT-PCR). We confirmed DENV infection in 403 (33%) patients from 12 districts with an estimated case fatality rate of 1.5%. DENV infection was more common in adults (87%) and urban settings (74%). We detected all four serotypes but DENV-1 and -2 were mainly responsible for major outbreaks (92%). Overall, 60% of all DENV infections were secondary and 17% were severe dengue; both being more frequent among the DENV-2 infections. Rash, bleeding, abdominal pain, hepatomegaly, elevated liver enzymes, and thrombocytopenia were significantly more common in severe dengue compared with nonsevere infections. We also confirmed the expansion of dengue to hill urban areas (DENV-1 and -2), including the capital Kathmandu (altitude, 1,300 m) though > 90% cases were from southern plains. Differential clinical and laboratory features probably help in clinical decisions. Multiple serotypes circulation and elevated secondary infections pose potential risk of severe outbreaks and deaths in the future. Therefore, a country with recent dengue introduction, like Nepal, urgently requires a systematic surveillance and appropriate control measures in place to respond to any disastrous outbreaks.

With the Zika virus outbreak in South America starting in 2015 and its potential to cause malformation of the fetus in infected women, the need for diagnostic methods became obvious. Until now, only limited data are available on the diagnostic performance of commercial kits. Here, we present data comparing the RealStar® Zika Virus RT-PCR Kit 1.0 for detection of Zika virus from 208 serum and urine samples collected in French Guiana with a reference method. Of these, 114 samples tested positive with the RealStar® Kit and 111 with the reference method.

Immune reconstitution inflammatory syndrome (IRIS) includes a group of potentially serious inflammatory processes that may be present in HIV-infected patients after initiating highly active antiretroviral therapy (HAART). Paradoxical IRIS is a worsening of symptoms, after an overwhelming response to a previously diagnosed opportunistic infection (OI); unmasking IRIS reveals a previously occult OI. The main objective of the study was to describe the epidemiological, clinical, and outcome data of HIV-infected immigrants, stratified according to high- or low-income countries of origin, who developed IRIS and to compare them with native-born Spanish patients. This retrospective study reviewed all patients with HIV infection admitted to the Unit of Infectious Diseases and Tropical Medicine between 1998 and 2014. IRIS was identified in 25/138 (18%) immigrant patients and 24/473 (5%) native-born Spanish patients infected with HIV. Most cases, 19/25 (76%), were of unmasking IRIS. The time elapsed between initiation of HAART and development of IRIS was significantly longer in patients with unmasking versus paradoxical IRIS. OIs, in particular due to mycobacteria, were the most frequently involved processes. Twenty percent of patients died. The comparison of immigrant and native-born patients found significant differences for both IRIS type (higher incidence of paradoxical forms among immigrants) and for the absence of malignancies in native-born patients. No significant differences were found when the data of immigrants from low- and high-income countries were compared.

The number of new syphilis cases in Brazil has risen alarmingly in recent years. However, there is limited data regarding syphilis prevalence in the Brazilian prison population. To facilitate the development of effective interventions, a cross-sectional study was undertaken to determine the prevalence of Treponema pallidum infection, active syphilis, and associated risk factors among Brazilian prisoners. We administered a questionnaire to a population-based sample of prisoners from 12 prisons in Central-West Brazil and collected sera for syphilis testing, from January to December 2013. Univariable and multivariable regression analyses were performed to assess associations with active syphilis. We recruited 3,363 prisoners (men: 84.6%; women: 15.4%). The overall lifetime and active syphilis prevalences were 10.5% (9.4% among men; 17% among women, P < 0.001) and 3.8% (2% among men; 9% among women, P < 0.001), respectively. The variables associated with active syphilis in men prisoners were homosexual preference, history of sexually transmitted infections, and human immunodeficiency virus status. Among women, the factors were sex with intravenous drug users, genital ulcer disease, and previous incarceration. Despite the high prevalence of active syphilis, 88.5% reported unawareness of their serological status and 67% reported unprotected sexual practices. Women had the highest rates of infection, including them in a high-risk group for the development of syphilis during pregnancy. Thus, implementing screening programs to enable continuous measures of control and prevention of T. pallidum infection in the prison environment, mainly in women institutions, is important to prevent severe forms of this disease and congenital infections.

Coinfection with pathogens that cause acute febrile illness (AFI) can complicate patient diagnosis and management. This report describes a fatal case of Leptospira spp./Zika virus (ZIKV) coinfection in Puerto Rico. The patient presented with a 5-day history of AFI; reported behavioral risk factors for leptospirosis; was diagnosed with possible leptospirosis, dengue, chikungunya, or ZIKV disease; and received appropriate treatment for leptospirosis and dengue. Following a 3-day hospitalization, the patient died due to acute gastrointestinal hemorrhage, and kidney and liver failure. Serologic diagnostic testing for leptospirosis and ZIKV disease was negative; however, molecular diagnostic testing performed postmortem was positive for detection of Leptospira spp. and ZIKV nucleic acid. This case demonstrates the need for continued clinical awareness of leptospirosis in areas experiencing outbreaks of pathogens that cause AFI and the need for evaluation of coinfection with AFI-causing pathogens as a risk factor for increased severity of disease.

Rodents are the main reservoir animals of leptospirosis. In this study, we characterized and quantified the urinary excretion dynamics of Leptospira by Mus musculus infected with 2 × 108 virulent Leptospira borgpetersenii serogroup Ballum. Each micturition was collected separately in metabolic cages, at 12 time points from 7 to 117 days post-infection (dpi). We detected Leptospira in all urine samples collected (up to 8 per time point per mouse) proving that Leptospira excretion is continuous with ca. 90% live L. borgpetersenii Ballum, revealed by viability quantitative polymerase chain reaction. Microscopic visualization by Live/Dead fluorescence confirmed this high proportion of live bacteria and demonstrated that L. borgpetersenii Ballum are excreted, at least partly, as bacterial aggregates. We observed two distinct phases in the excretion dynamics, first an increase in Leptospira concentration shed in the urine between 7 and 63 dpi followed by a plateau phase from 63 dpi onward, with up to 3 × 107 Leptospira per mL of urine. These two phases seem to correspond to progressive colonization of renal tubules first, then to stable cell survival and maintenance in kidneys. Therefore, chronically infected adult mice are able to contaminate the environment via urine at each micturition event throughout their lifetime. Because Leptospira excretion reached its maximum 2 months after infection, older rodents have a greater risk of contaminating their surrounding environment.

Orientia tsutsugamushi is a major cause of vector-borne infection in Asia. Prompt recognition and appropriate treatment are crucial because of its potentially fatal complications and lack of response to beta-lactam antibiotics. The present study retrospectively evaluated the clinical characteristics and laboratory findings of 16 patients with scrub typhus-related central nervous system (CNS) infections. Single titers ≥ 1:40 of total serum antibodies against O. tsutsugamushi detected by an indirect immunofluorescent assay were considered as positive results. The median age was 35.5 (range, 14–72) years, and 10 (62.5%) patients were female. The most common symptoms were headache (81.3%) and fever (81.3%). Eschar formation was found in three (18.8%) patients. Among patients with encephalitis, seizures and altered consciousness occurred in five (83.3%) and four (66.7%) patients, respectively. An abnormal liver function was noted in seven (43.8%) patients. The median antibody titer was 1:120 (range, 1:40–1:2,560). Typical cerebrospinal fluid profiles were lymphocytic pleocytosis, mild protein elevations, and normal glucose levels. All patients received an empirical treatment with doxycycline and most (93.8%) of them recovered without neurological sequelae. None of the patients reported side effects of the doxycycline treatment. An empirical treatment with doxycycline is needed in patients with CNS infections in scrub typhus endemic areas.

Individuals with newly diagnosed tuberculosis (TB) were screened for diabetes (DM) with fasting plasma glucose (FPG) in Pakistan. A significant decrease in FPG was observed when TB was treated. Of those with newly diagnosed DM, 46% and 62% no longer had hyperglycemia after 3 and 6 months, respectively. Individuals with known DM also showed a significant decrease in fasting plasma levels when treated for TB, but after 3 months none had normoglycemia, and after 6 months 9.2% were normoglycemic. Thus, TB-related DM may abate when the stress terminates, as is the case in gestational DM. However, because stress hyperglycemia may be associated with subsequent risk of developing DM, follow-up is recommended.