The American Journal of Tropical Medicine and Hygiene - Volume 101, Issue 2, 2019

Detection of acute HIV infection is a unique problem that fourth-generation HIV assays were expected to alleviate. In this commentary, we draw attention to the limitations and challenges with use of currently available rapid antigen–antibody (Ag/Ab) combination tests for detection of acute HIV infection in sub-Saharan Africa. Laboratory-based HIV-1 Ag/Ab immunoassays are complex, requiring specialized equipment and handling that are currently not affordable in many settings in Africa. The point-of-care Ag/Ab platform on the other hand is easier to deploy and potentially more accessible in resource-limited settings. However, available fourth-generation HIV-1 rapid diagnostic tests have demonstrated poor performance characteristics in field studies where non-B subtypes of HIV-1 dominate. The potential for point-of-care HIV-1 Ag/Ab diagnostics to significantly improve detection of acute HIV infection remains yet to be realized in sub-Saharan Africa. Assay platforms need to be optimized to identify local circulating subtypes, and optimal algorithms need to be determined.

Early trials of killed, whole-cell typhoid vaccine indicated a paradoxical, positive effect on malaria infections. British soldiers in India in 1898 reported > 90% decrease in malaria recurrences after receiving an investigational typhoid vaccine despite no intention or expectation to observe such an outcome. In the 1940s, multiple doses of intravenous typhoid vaccine appeared to control parasitemia and limit reinfection in three syphilis patients purposefully infected with Plasmodium vivax. Several modern vaccines (against human papillomavirus, hepatitis B virus, and malaria) use a detoxified lipid A derived from Salmonella as an immune adjuvant. Early typhoid vaccines could have plausibly functioned as an innate immune stimulus, leading to some protection against malaria.

Providencia alcalifaciens is a member of the family Enterobacteriaceae that has been commonly implicated as a causative agent of diarrheal infection in humans and animals. Recent outbreaks of P. alcalifaciens in both developing and developed countries have raised public health concerns. Several studies have suggested that P. alcalifaciens can cause diarrhea by invading the intestinal mucosa, although its pathogenicity has not been well established. Often routine laboratory investigations that seek etiological agents of diarrhea do not actively pursue P. alcalifaciens detection. Therefore, routine laboratory diagnosis should be given more attention for better understanding the epidemiology and pathogenicity of P. alcalifaciens.

Despite being preventable, foodborne diseases remain a global health challenge. Poor food hygiene practices such as improper handling of kitchen utensils are among the major causes of diarrhea transmission. A formative study was conducted in Malawi to inform an intervention design to promote complementary food hygiene practices. An assessment of contextual and psychosocial factors for behavior change was conducted using Risk, Attitude, Norms, Ability, and Self-regulation model. We conducted 323 household surveys with caregivers of children aged 6 to 24 months. Analysis of variance was used to estimate difference between doers and non-doers of three targeted behaviors: washing utensils with soap, keeping utensils on a raised place, and handwashing with soap. Analysis of variance analyses revealed that literacy level, ownership of animals, and presence of handwashing facility and dish racks were contextual factors predicting storage of utensils on an elevated place and handwashing frequencies. Psychosocial factors, such as time spent to wash utensils with soap, distance to the handwashing facility, and cost for soap, had an influence on washing utensils and handwashing practices. Perceived vulnerability determined effective handwashing and storage of utensils. Perceived social norms and ability estimates were favorable for the three targeted behaviors. Promotion of already existing targeted beneficial behaviors should be encouraged among caregivers. Risk perceptions on storage of utensils and handwashing practices should be increased with motivational exercises such as paint games. Caregivers’ technical know-how of local dish rack and tippy tap construction is essential.

Diarrheal disease is a leading cause of childhood morbidity and mortality worldwide, but particularly in low-income countries in sub-Saharan Africa and South Asia. The Global Enteric Multicenter Study (GEMS) examined the infectious etiologies as well as associated demographics, socioeconomic markers, health-care–seeking behaviors, and handwashing practices of the households of children with diarrhea and their age- and gender-matched controls in seven countries over a 3-year period (December 2007–December 2010). Stool studies to determine diarrheal etiologies and anthropometry were performed at baseline and at 60-day follow-up visits, along with surveys to record demographics and living conditions of the children. We performed secondary analyses of the GEMS data derived from the Bangladesh portion of the study in children with diarrhea associated with viral enteropathogens and explored pathogen-specific features of disease burden. Rotavirus and norovirus were the most prevalent pathogens (39.3% and 35%, respectively). Disease due to rotavirus and adenovirus was more common in infants than in older children (P < 0.001 and P = 0.001, respectively). Height for age decreased from baseline to follow-up in children with diarrhea associated with rotavirus, norovirus, and adenovirus (P < 0.001). Based on these analyses, preventive measures targeted at rotavirus, norovirus, and adenovirus will be expected to have meaningful clinical impact. Cost of treatment was highest for rotavirus as well, making it an obvious target for intervention. Association of specific viruses with stunting is particularly notable, as stunting is an attributable risk factor for poor cognitive development and future productivity and economic potential.

Acute diarrhea is an important public health issue. Here, we focused on the differences of enteropathogens in acute diarrhea between urban and rural areas in southeast China. Laboratory- and sentinel-based surveillance of acute diarrhea (≥ 3 loose or liquid stools/24 hours) was conducted at 16 hospitals. Fecal specimens were tested for bacterial (Aeromonas sp., Campylobacter sp., diarrheagenic Escherichia coli, Plesiomonas shigelloides, non-typhoidal Salmonella, Shigella sp., Vibrio sp., and Yersinia sp.) and viral (adenovirus, astrovirus, Norovirus, Rotavirus, and Sapovirus) pathogens. Descriptive statistics were used. Between January 1, 2010, and December 31, 2014, 4,548 outpatients with acute diarrhea were enrolled (urban, n = 3,220; rural, n = 1,328). Pathogens were identified in 2,074 (45.6%) patients. Norovirus (25.7%), Vibrio parahaemolyticus (10.2%), enteroaggregative Escherichia coli (EAEC) (8.8%), group A Rotavirus (7.0%), and enterotoxigenic Escherichia coli (ETEC) (5.6%) were the most common pathogens. Enteropathogens were less common in urban than in rural areas (42.0% versus 54.4%, P < 0.001). In urban areas, EAEC and ETEC were more common in high-income than in middle-income regions. Interventions targeting the most common enteropathogens can substantially reduce the burden of acute diarrhea in southeast China.

Acute respiratory distress syndrome (ARDS) is seldom described as a complication of typhoid fever (TF). Only 13 cases have hitherto been reported in the English and non-English literature since 1990. We report an 8-year-old boy with TF after return from India who developed pediatric ARDS (pARDS) despite adequate antibiotic treatment. Among patients with available information including this case, we noted that most not born or raised in a TF-endemic country (4/6) compared with none (0/6) of the domestic cases in a TF-endemic country developed ARDS within 48 hours of starting the antibiotic treatment. Our case raises important questions regarding the frequency, pathophysiology, and appropriate management of ARDS and pARDS in patients with TF.

Melioidosis is a bacterial infection caused by exposure to water or soil that contains Burkholderia pseudomallei (Bp). Burkholderia pseudomallei is endemic to many tropical and subtropical areas of the world. In 2013, the first case of melioidosis was recognized in Yap, the Federated States of Micronesia. Six additional cases were identified in the subsequent 3 years. An investigation was initiated to understand the epidemiology of melioidosis in Yap. Serum from family and community members of the identified cases were tested for antibodies to Bp. Archived serum from a 2007 Zika serosurvey were also tested for antibodies to Bp. Sequencing of bacterial isolates was performed to understand bacterial phylogeny. Soil and water were tested for the presence of Bp in the environment by culture and PCR. None of the affected patients had a history of travel to melioidosis-endemic countries. Two of the 34 (5.8%) samples from the field investigation and 67 (11.7%) of the historical samples demonstrated serologic evidence of prior Bp exposure. No Bp were detected from 30 soil or water samples. Genotype analysis showed highly related Bp isolates that were unique to Yap. Melioidosis is likely to be endemic to Yap; however, it has only recently been recognized by the clinical community in country. Further investigation is needed to understand the local sites that harbor Bp and represent the highest risk to the community.

Although the in-hospital mortality of Australian patients with melioidosis continues to decline, the ensuing clinical course of survivors is poorly described. Between January 1, 1998, and January 31, 2019, 228 patients in Cairns, tropical Australia, survived their hospitalization with melioidosis; however, 52 (23%) subsequently died. Death occurred at a median of 3.8 years after discharge, with patients dying at a mean age of 59 years. Only 1/27 (4%) without predisposing conditions for melioidosis died during follow-up, versus 51/201 (25%) with these comorbidities (P = 0.01). Death during follow-up was more likely in patients with chronic lung disease (OR [95% CI]: 4.05 (1.84–8.93, P = 0.001) and chronic kidney disease (OR [95% CI]: 2.87 [1.33–6.20], P = 0.007), and was most commonly due to infection and macrovascular disease. A significant proportion of Australians surviving hospitalization with melioidosis will die soon after discharge, usually prematurely and frequently from preventable conditions. A more holistic approach is required to their care.

Rickettsia monacensis and Orientia tsutsugamushi are bacteria of the family Rickettsiaceae, which causes fever, rash, and eschar formation; outdoor activities are a risk factor for Rickettsiaceae infection. A 75-year-old woman presented with fever, rash, and eschar and was confirmed as being scrub typhus based on a nested-polymerase chain reaction (N-PCR) test for a 56-kDa gene of O. tsutsugamushi; the genome was identified as the Boryong genotype. In addition, a pan-Rickettsia real-time PCR test was positive and a N-PCR test using a Rickettsia-specific partial outer membrane protein A (rOmpA) confirmed R. monacensis. This is the first case wherein a patient suspected of having scrub typhus owing to the presence of rash and eschar was also found to be coinfected with O. tsutsugamushi and R. monacensis based on molecular testing.

Rocky Mountain spotted fever (RMSF) has been reported in Colombia since 1937. Most recent outbreaks were in 2006–2008, followed by the absence of recognized cases. This report describes new clinical cases of RMSF and epidemiologic investigations. Medical records were reviewed, and fieldwork, serological and molecular diagnostic testing, and bacterial isolation were performed. Fever, hypotension, abdominal discomfort, and rash accompanied by thrombocytopenia and leukopenia were the most characteristic manifestations. Two convalescent sera from the index case and sera from two dogs revealed high anti-spotted fever group Rickettsia antibody titers. Rickettsia rickettsii was isolated from case 4. Cases 2 and 3 were identified by epidemiological connection with the index case. Thus, a new cluster of cases of RMSF was identified in Antioquia, Colombia, with the occurrence of fatal cases, which indicates the active circulation of the bacteria and a potential risk for the population.

In this study, we investigated the diagnostic utility of the cytokine profile of the cerebrospinal fluid (CSF) and enzyme-linked immunospot (ELISPOT) assays of patients with suspected tuberculous meningitis (TBM). We prospectively enrolled adult patients with suspected TBM, and CSF specimens were analyzed for 18 cytokines/chemokines and soluble programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1). Enzyme-linked immunospot assays were performed on mononuclear cells from the CSF (CSF-MCs) and peripheral blood (PBMCs). A total of 87 patients with meningitis, including 42 TBM-suspected patients and 45 non-TBM patients, were enrolled. Excluding the 32 patients with possible TBM, 10 patients with TBM and 45 patients with non-TBM were finally analyzed. Levels of adenosine deaminase (ADA), interleukin 12 subunit β (IL-12p40), IL-13, macrophage inflammatory protein α (MIP-1α), and soluble PD-1 and PD-L1 in the CSF were significantly higher in the TBM group than in the non-TBM group (P < 0.05). The optimal cutoff values for the sensitivities and specificities of the test methods for diagnosing TBM with small samples of 10 cases of definite or probable TBM were as follows: ADA > 6.95 U/L, 70% and 81%; IL-12p40 > 52.04 pg/mL, 80% and 73%; IL-13 > 0.44 pg/mL, 90% and 47%; MIP-1α > 8.83 pg/mL, 80% and 62%; soluble PD-1 > 35.87 pg/mL, 80% and 63%; soluble PD-L1 > 24.19 pg/mL, 80% and 61%; CSF-MC ELISPOT > 13.5 spots/250,000 CSF-MC, 30% and 91%; and PBMC ELISPOT > 14 spots/250,000 PBMCs, 50% and 78%, respectively. Therefore, CSF IL-12p40, IL-13, MIP-1α, and soluble PD-1 and PD-L1 concentrations appear to be useful adjuncts for diagnosing TBM.

Statins have anti-inflammatory and immunomodulatory properties that may affect the development of tuberculosis (TB). We assessed the association between use of statins and the risk of active TB by propensity score matching. Furthermore, we analyzed the impact of statins on TB in patients according to the presence or absence of diabetes. The study was based on the National Health Insurance database and its subset database of the “medical checkup” population of South Korea. We identified 123,468 statin users and 439,546 non–statin users. After propensity score matching, 28,018 statin users and the same number of non–statin users were finally analyzed. The development of active TB was monitored in these matched pairs over 11 years. In the propensity score–matching analysis, the number of active TB cases was 30 in 30,303 person-years (0.99 per 1,000 person-years; 95% CI, 0.64–1.35) in the statin users and 235 in 167,857 person-years (1.40 per 1,000 person-years; 95% CI, 1.22–1.58) in the non–statin users. Statin users had a significantly lower risk of TB than non–statin users: hazard ratio (HR) 0.67 (95% CI, 0.46–0.98) (P = 0.04). A subgroup analysis showed that statin use reduced the risk of TB in subjects without diabetes, but not in patients with diabetes: HRs were, respectively, 0.28 (95% CI, 0.13–0.60) (P = 0.001) and 1.05 (95% CI, 0.66–1.67) (P = 0.84). There is epidemiologic evidence that statin decreases the risk of active TB. However, the protective effect of statins against TB is attenuated by diabetes.

Most deaths in tuberculous meningitis occur in the early part of the illness. We assessed the determinants of early deaths, occurring within 2 months of intensive therapy. We prospectively included consecutive newly diagnosed adults with HIV-negative tuberculous meningitis. Patients were given WHO-recommended antituberculosis treatment and were followed up for 9 months. We enrolled 152 patients. A total of 26 deaths were recorded during 2 months. The logistic regression analysis revealed that papilledema (P = 0.029, odds ratio (OR) = 4.8 [1.2–19.8]), increasing age (P = 0.001, OR = 1.07 [1.03–1.1]), stage-III disease (Glasgow coma scale score ≤ 10; P = 0.01, OR = 4.2 [1.4–12.3]), and hydrocephalus (P = 0.003, OR = 8.4 [2.1–33.6]) were independently associated with death. In addition, cerebral infarcts (P = 0.012, OR = 5.6 [1.5–21.3]), paraparesis (P = 0.004, OR = 8.8 [2.02–38.1]), and age (P = 0.005, OR = 1.05 [1.02–1.09]) were associated with poor functional outcome. In conclusion, disease severity predicts early deaths in tuberculous meningitis.

The Asian tiger mosquito, Aedes albopictus, transmits several arboviruses of public health importance, including chikungunya and dengue. Since its introduction to the United States in 1985, the species has invaded more than 40 states, including temperate areas not previously at risk of Aedes-transmitted arboviruses. Mathematical models incorporate climatic variables in predictions of site-specific Ae. albopictus abundances to identify human populations at risk of disease. However, these models rely on coarse resolutions of environmental data that may not accurately represent the climatic profile experienced by mosquitoes in the field, particularly in climatically heterogeneous urban areas. In this study, we pair field surveys of larval and adult Ae. albopictus mosquitoes with site-specific microclimate data across a range of land use types to investigate the relationships between microclimate, density of larval habitat, and adult mosquito abundance and determine whether these relationships change across an urban gradient. We find no evidence for a difference in larval habitat density or adult abundance between rural, suburban, and urban land classes. Adult abundance increases with increasing larval habitat density, which itself is dependent on microclimate. Adult abundance is strongly explained by microclimate variables, demonstrating that theoretically derived, laboratory-parameterized relationships in ectotherm physiology apply to the field. Our results support the continued use of temperature-dependent models to predict Ae. albopictus abundance in urban areas.

Seasonal variation in the proportion of the population using an insecticide-treated net (ITN) is well documented and is widely believed to be dependent on mosquito abundance and heat, driven by rainfall and temperature. However, seasonal variation in ITN use has not been quantified controlling for ITN access. Demographic and Health Survey and Malaria Indicator Survey datasets, their georeferenced data, and public rainfall and climate layers were pooled for 21 countries. Nine rainfall typologies were developed from rainfall patterns in Köppen climate zones. For each typology, the odds of ITN use among individuals with access to an ITN within their households (“ITN use given access”) were estimated for each month of the year, controlling for region, wealth quintile, residence, year, temperature, and malaria parasitemia level. Seasonality of ITN use given access was observed over all nine rainfall typologies and was most pronounced in arid climates and less pronounced where rainfall was relatively constant throughout the year. Peak ITN use occurred 1–3 months after peak rainfall and corresponded with peak malaria incidence and average malaria transmission season. The observed lags between peak rainfall and peak ITN use given access suggest that net use is triggered by mosquito density. In equatorial areas, ITN use is likely to be high year-round, given the presence of mosquitoes and an associated year-round perceived malaria risk. These results can be used to inform behavior change interventions to improve ITN use in specific times of the year and to inform geospatial models of the impact of ITNs on transmission.

Trypanosoma cruzi is the etiologic agent of Chagas disease (CD), which can result in severe cardiomyopathy. Trypanosoma cruzi is endemic to the Americas, and of particular importance in Latin America. In the United States and other non-endemic countries, rising case numbers have also been observed. The currently used drugs are benznidazole (BNZ) and nifurtimox, which have limited efficacy during chronic infection. We repurposed itraconazole (ICZ), originally an antifungal, in combination with amiodarone (AMD), an antiarrhythmic, with the goal of interfering with T. cruzi infection. Human pluripotent stem cells (hiPSCs) were differentiated into cardiomyocytes (hiPSC-CMs). Vero cells or hiPSC-CMs were infected with T. cruzi trypomastigotes of the II or I strain in the presence of ICZ and/or AMD. After 48 hours, cells were Giemsa stained, and infection and multiplication were evaluated microscopically. Trypanosoma cruzi infection and multiplication were evalutated also by electron microscopy. BNZ was used as a reference compound. Cell metabolism in the presence of test substances was assessed. Itraconazole and AMD showed strain- and dose-dependent interference with T. cruzi infection and multiplication in Vero cells or hiPSC-CMs. Combinations of ICZ and AMD were more effective against T. cruzi than the single substances, or BNZ, without affecting host cell metabolism, and better preserving host cell integrity during infection. Our in vitro data in hiPSC-CMs suggest that a combination of ICZ and AMD might serve as a treatment option for CD in patients, but that different responses due to T. cruzi strain differences have to be taken into account.

Mucosal leishmaniasis (ML) is characterized by high production of inflammatory cytokines. Administration of pentoxifylline (PTX), an inhibitor of TNF-alpha, with pentavalent antimony (Sbv), has been successfully used as alternative treatment for refractory ML. Our study aims to investigate the in situ cellular response underlying the effectiveness of this therapy, by evaluating the intensity of the inflammatory infiltrate, cellular composition, and expression of cytokines and granzyme A in lesions from ML before and after treatment with Sbv alone or in combination with PTX. Our data showed no differences in the intensity of inflammatory infiltrate comparing before and after treatment, and comparing between different treatments. However, although the number and frequency of CD4+ and CD8+ cells were not different before and after treatments or comparing different treatments, frequency of CD68+ cells decreased after treatment with Sbv + PTX, but not with Sbv. This was due to a reduction in CD68+ TNF-alpha+ and not in CD68+ IL-10+ cells. The frequency of TNF-alpha+ cells was correlated with the intensity of the inflammatory infiltrate before treatment, but this correlation was lost after treatment with Sbv + PTX. Although the total expression of granzyme A did not significantly change after treatments, a clear trend of decrease was observed after treatment with Sbv + PTX. Interestingly, patients who took longer to heal, regardless of the treatment, displayed a higher frequency of granzyme A+ cells. Our data suggest that treatment with Sbv + PTX acts in CD68+ cells reducing the expression of TNF-alpha but not IL-10, resulting in more efficient modulation of the inflammatory response, accelerating the healing process.

Immunosuppressive treatments for rheumatic diseases present special problems in areas endemic for chronic infectious diseases because of the possibility of reactivation. Leishmaniasis is a significant neglected tropical disease caused by different species of protozoan parasites within the genus Leishmania. Amastigotes live as intracellular parasites in a variety of mammalian cells, most notably within phagocytes such as macrophages, and residual parasites can persist even after treatment and healing of the lesions. We herein report a case of relapsing mucosal leishmaniasis after aggressive immunotherapy for ankylosing spondylitis, with requirement for secondary prophylaxis with amphotericin B to prevent reactivation. This approach can be necessary for patients from endemic areas of tegumentary leishmaniasis, who will undergo aggressive immunotherapy.

Long-lasting insecticide-treated bednets are widely used and promoted for malaria control. Limitations in measurement methods have resulted in a poor understanding of how bednets are used in practice. We deployed a novel remote monitoring tool in Uganda to obtain, for the first time, a comprehensive characterization of bednet use in households at risk for malaria. Ten households each used one SmartNet adherence monitor over a commonly used sleeping area for 6 weeks. SmartNet continuously measures and records bednet use every 15 minutes. Bednet use was monitored for a total of 9,258 hours overall, with an average of 42 nights per household (SD: 3.5). Average duration of bednet use was 9 hours 49 minutes per night (SD: 1 hour 56 minutes), and adherence was 85–90% from 2100 to 0600. Bednets were not used at all on 4.5% (19/418) of observation nights. Overall, the average clock time that bednets were unfurled was 2034 (SD: 1 hour 25 minutes) and they were folded up at 0743 (SD: 43 minutes). The rate of interruptions per night observed in all households was 0.23 (86/369), with an average duration of 48 minutes (SD: 49 minutes). There was substantial heterogeneity between households, and some households had consistently poorer adherence relative to others. Variations in bednet use behaviors are a potentially important, and under-researched, component of long-lasting insecticide-treated bednet effectiveness. Remote bednet use monitors can provide novel insights into how bednets are used in practice, helping identify both households at risk of malaria due to poor adherence and also potentially novel targets for improving malaria prevention.

Multiplicity of infection (MOI), the number of unique Plasmodium falciparum parasite genotypes found in one infected individual, may contribute to the development of clinical malaria disease. However, the independent contribution of MOI and parasite density to clinical disease has not been well characterized. We conducted a two-year longitudinal cohort study of adults and children in a high-transmission setting in Malawi to test the hypothesis that increased MOI was independently associated with clinical disease, after accounting for parasite density. Of 1,062 episodes of infection, 477 (44.9%) were associated with symptoms. After controlling for repeated measures within an individual, key demographic factors, and parasite density, there was no association between MOI and clinical disease (OR = 1.02, 95% CI: 0.70–1.51). Although the limited ability to discern MOI in low-density asymptomatic infections may have impacted our results, we conclude that MOI is not an independent risk factor for clinical disease.

India accounts for approximately half of the global Plasmodium vivax cases, but information as to the presence of chloroquine (CQ) resistance is scarce. In an observational study in Mangaluru, south-western India, of 116 vivax malaria patients analyzed, 89.5% (102/114) had cleared parasitemia on days two or three of CQ treatment. Two remaining patients presented on days four and five without parasitemia. One hundred eight isolates of these 116 patients were successfully sequenced for pvmdr1 polymorphisms. Eight non-synonymous polymorphisms but no wild-type isolate were detected. Ten pvmdr1 haplotypes were observed with mutations T958M and F1076L occurring in all isolates, whereas the candidate CQ resistance marker Y976F was present in one isolate only. Pvmdr1 polymorphisms were not associated with early parasite clearance. The high proportion of early parasite clearance and the virtual absence of pvmdr1 Y976F and of sextuple pvmdr1 mutants suggest that CQ in the study area is still sufficiently effective. However, the abundance of pvmdr1 mutations in the local parasite population warrants monitoring.

We report two unusual cases of clinical strongyloidiasis that present as extensive thrombosis: a case of hyperinfection with concurrent eosinophilia and a case of disseminated infection as a complication of immunosuppression. We discuss risk factors for the development of Strongyloides stercoralis infection and thromboembolism, and the recommended management.

Strongyloides stercoralis affects 30–100 million people worldwide. The burden is underestimated because of the paucity of studies, limited geographical areas surveyed, and poor quality of diagnostic tests. This study aimed at determining the epidemiology of strongyloidiasis using sensitive microscopy testing in rural populations living at different altitudes in Cusco, Peru. Data were collected from subjects aged > 3 years living in Quellouno (elevation 2,600 ft) and Limatambo (elevation 8,379 ft) districts. Subjects provided one fresh stool sample and answer a standardized questionnaire. Fresh stool was tested on site using the Baermann’s test and agar plate culture. Formalin-preserved stool was tested by rapid sedimentation. Eighty percent (585/715) of eligible subjects consented to participate; after excluding subjects with missing data, 65% (462/715) were included. Fifty-five percentage were female; the median age was 33 years (interquartile range 13–52), and 72% had government health insurance. Half had intestinal parasites, and Strongyloides was the most common (24.5%) followed by Giardia (15.5%), Blastocystis (14.9%), and hookworm (11.5%). The agar plate culture detected more cases of Strongyloides than Baermann’s or sedimentation tests. Strongyloides infection was more common at low altitude (26.4%) than at high altitude (18.6%), but the difference was not statistically significant (P = 0.08). Older age, walking barefoot, bathing in rivers/streams, and using municipal sewage were associated with strongyloidiasis. Strongyloides was the most prevalent parasite in the areas studied and was associated with demographic, socioeconomic, and sanitary factors.

This study describes the clinical features of a cohort of imported cases of strongyloidiasis and the performance of standard diagnostic techniques for this condition. A total of 413 cases were identified, of whom 86 had microscopically proven infection. In proven cases, 23% had normal eosinophil counts, 19% had negative Strongyloides-specific serology, and 9.3% had normal blood counts and were seronegative. Serological testing was less sensitive for returning travelers (46.2%) than for migrants (89.7%). Immunosuppression, including human T-cell lymphotropic virus 1, was significantly associated with proven infection after controlling for age, presence of symptoms, duration of infection, and eosinophilia (OR 5.60, 95% CI 1.54–20.4). Patients with proven infection had lower serology values than those diagnosed with strongyloidiasis on the basis of positive serology and eosinophilia alone (P = 0.016). Symptomatic patients were significantly younger, had a shorter presumed duration of infection, and lower serology values. These data suggest a correlation between immunologic control of strongyloidiasis and the amplitude of the humoral response.

The conventional method of detecting Strongyloides stercoralis in fecal samples has poor diagnostic sensitivity. Detection of Strongyloides-specific antibodies increases the sensitivity; however, most tests are ELISAs that use parasite extract which may cross-react with the sera of other helminth infections. To improve the serological diagnosis of strongyloidiasis, this study aimed at developing a sensitive and specific lateral flow rapid dipstick test. Two recombinant proteins, recombinant NIE (rNIE) and recombinant Ss1a (rSs1a), were used in preparing the dipstick, with gold-conjugated antihuman IgG4 as detector reagent. In parallel, the corresponding ELISA was performed. Both assays demonstrated diagnostic sensitivity of 91.3% (21/23) when tested with serum samples of patients with Strongyloides infection, and 100% specificity with 82 sera of asymptomatic (healthy) and those with other parasitic infections. The ELISA and dipstick test results were positively correlated to each other (r = 0.6114, P = 0.0019). The developed lateral flow dipstick test may improve the serodiagnosis of strongyloidiasis and merit further validation studies.

Lymphatic filariasis is a mosquito-borne parasitic disease responsible for morbidity and disability that affects 1.2 billion people worldwide, mainly the poor communities. Currently, filarial antigen testing is the method of choice for the detection of bancroftian filariasis, and to date, there are two commonly used tests. In the present study, a recently reported recombinant monoclonal antibody (5B) specific to BmSXP filarial antigen was used in developing an ELISA for the detection of circulating filarial antigen in sera of patients with bancroftian filariasis. The performance of the ELISA was evaluated using 124 serum samples. The ELISA was positive with all sera from microfilaremic bancroftian filariasis patients (n = 34). It also showed 100% diagnostic specificity when tested with sera from 50 healthy individuals and 40 patients with other parasitic diseases. The developed assay using the novel 5B recombinant monoclonal antibody could potentially be a promising alternative antigen detection test for bancroftian filariasis.

Arboviral diseases are responsible for a high burden of disease in humans, and a significant part of disease risk reduction efforts relies on vector control methods. The elimination of potential breeding sites for the mosquito vectors and a higher level of literacy by the populations at risk could present a sustainable and environmentally friendly solution. This review aims to assess the efficacy of educational interventions for arboviral diseases on knowledge and self-reported behavior. A systematic literature search was performed using Cochrane, EMBASE, Global Health, and PubMed. References of articles retrieved were searched manually for further studies. Critical appraisal of the selected articles was performed using the Effective Public Health Practice Project tool, and studies with a control group were further assessed through the Cochrane’s risk of bias tool. A summary narrative of the results and a meta-analysis was conducted. Fourteen studies fulfilling the inclusion criteria were analyzed. Overall, there was an increase in knowledge and in self-reported adoption of protective measures. No effect was found using solely printed material. A meta-analysis was performed separately for the two outcomes measured, which produced a mean standardized difference of 1.86 (95% CI: 1.33–2.39) in knowledge scores compared with the control groups. Regarding the self-reported protective behavior, the results show a summary value of odds ratio of 5.23 (95% CI: 3.09–7.36). Most of the educational interventions had a positive impact on knowledge and self-reported adoption of protective measures. More research producing stronger evidence and evaluating long-term impact is needed.

Dengue hemorrhagic fever is one of the most commonly encountered mosquito-borne viral infections of humans worldwide with multiple reported outbreaks. Cardiac involvement is a known manifestation of the disease usually presenting as rhythm abnormalities, myocarditis, or pericardial effusion, which may be clinically asymptomatic. We describe a case of a 30-year-old woman who presented to us with high-grade fever, headache, retro-orbital pain, generalized maculopapular rash with bilateral pleural effusion, and hypotension. Dengue non-structural protein 1 (NS1) antigen and IgM antibodies were positive on admission, supporting a diagnosis of dengue hemorrhagic fever. Cardiac troponin-I was elevated on admission (65 ng/L) with diffuse convex ST segment elevations on electrocardiogram, suggestive of possible myopericarditis. Echocardiogram on admission revealed minimal pericardial effusion with preserved ejection fraction. Despite administration of fluids and inotrope use, the patient’s hypotension progressively deteriorated over the next 6 hours, associated with decreased urine output and worsening sensorium. Clinical examination revealed muffled heart sounds and raised jugular venous pressure. A repeat echocardiogram confirmed an increase in the pericardial effusion manifesting as cardiac tamponade. Ultrasound-guided pigtail catheter insertion led to a prompt removal of the excessive pericardial fluid and correction of hypotension. Early identification of this uncommon but important complication of dengue hemorrhagic fever led to a good outcome in our case.

Molecular epidemiological data are key for dengue outbreak characterization and preparedness. However, sparse Dengue virus (DENV) molecular information is available in Laos because of limited resources. In this proof-of-concept study, we evaluated whether DENV1 RNA extracted from rapid diagnostic tests (RDTs) could be amplified and sequenced. The protocol for envelope gene amplification from RNA purified from RDTs was first assessed using viral isolate dilutions then conducted using 14 dengue patient sera. Envelope gene amplification was successful from patient sera with high virus titer, as was sequencing but with lower efficiency. Hence, based on our results, RDTs can be a source of DENV1 RNA for subsequent envelope gene amplification and sequencing. This is a promising tool for collecting molecular epidemiology data from rural dengue-endemic areas. However, further investigations are needed to improve assay efficiency and to assess this tool’s level of efficacy on a larger scale in the field.

Although sera are most commonly used in serological diagnostic tests for dengue, sometimes only plasma containing ethylenediaminetetraacetic acid (EDTA) may be available. When we studied the performance of a widely used noncommercial dengue ELISA in the detection of reactive IgG in sera and plasma from the same individuals, we found no significant differences in the diagnostic performance of the assay. The inter-specimen coefficient of variation (CV) of the optical density was 0.081 and the concordance correlation coefficient (CCC) was 0.92, showing a very strong agreement between the two matrix specimens. The intra-specimen CV and CCC were higher for plasma than for serum at low dilutions, but similar at high dilutions. Overall, our results show that the performance of a widely used in-house ELISA using plasma containing EDTA is equivalent to serum with the recommendation to assay the plasma specimens in duplicate to reduce variability of results at lower dilutions.

Tanzania is one of the sub-Saharan countries that have experienced a number of Rift Valley fever (RVF) outbreaks at intervals of 10–20 years since the first isolation of the virus during the early 1930s. Recent studies have reported serological evidence of inter epizootic/epidemic period circulation of RVF virus (RVFV) in livestock and humans. The aim of this study was to conduct a cross-sectional survey in Tanzania during 2015/16 to further explore the possibility that RVFV was circulating among cattle during the Inter epizootic/epidemic period. A total of 443 cattle samples were collected in Manyara, Dodoma, Singida, and Mbeya regions of Tanzania. The samples were tested for RVFV antibodies using a commercial ELISA kit and a plaque reduction neutralization test. Serum samples were also tested for RVFV viral RNA by an reverse transcription polymerase chain reaction (RT-PCR) assay. An overall RVFV seroprevalence rate of 7.7% (34/443) was detected by ELISA among cattle in all four regions. The Mbeya region cattle had the highest seroprevalence of 26.4% (23/87), followed by Dodoma 5.9% (10/171) and lastly Singida 0.9% (1/101). Of 33 ELISA antibody-positive samples, only 0.2% (1/443) had IgM antibody. Of 36 ELISA antibody-positive and doubtful samples, 32 were positive for neutralizing antibody with titers between 10 and > 10,240. None of the samples were positive for RVFV viral RNA by RT-PCR. The detection of RVFV antibodies in cattle suggested that these animals were involved in an enzootic cycle during the interepidemic period and that the high antibody titers may confer protection of cattle against RVFV.

Deer tick virus (DTV) is a genetic variant of Powassan virus (POWV) that circulates in North America in an enzootic cycle involving the blacklegged or “deer tick,” Ixodes scapularis, and small rodents such as the white-footed mouse. The number of reported human cases with neuroinvasive disease has increased substantially over the past few years, indicating that POWV may be of increasing public health importance. To this end, we sought to estimate POWV infection rates in questing I. scapularis collected from four health districts in Maine (York, Cumberland, Midcoast, and Central Maine). Infection rates were 1.6%, 1.7%, 0.7%, and 0%, respectively, for adults collected from April to November in 2016. Adults collected in October and November in 2017 from York and Cumberland counties had slightly higher rates of 2.3% and 3.5%, respectively. There was no difference in the number of males verses the number of females infected. All positive samples were of the DTV (lineage II) variant. Phylogenetic analysis was performed on 8 of the 15 DTV sequences obtained in 2016. Deer tick virus from the coastal regions were genetically similar and clustered with virus strains isolated from I. scapularis from New York State and Bridgeport, CT. The two inland viruses were genetically nearly identical and grouped with viruses from Massachusetts, Connecticut, and New York. These results are the first reported infection rates and sequences for POWV in questing ticks collected in Maine and will provide a reference point for future POWV studies.