The American Journal of Tropical Medicine and Hygiene - Current Issue

Household food and water insecurity often co-occur, and both can lead to malnutrition, psycho-emotional stress, and increased risk of infectious and chronic diseases. This can occur through multiple pathways including poor diet and inadequate sanitation. In this perspective, we discuss the potential advantages of a syndemic approach to understanding the consequences of food and water insecurity, that is, one that makes possible the assessment of their mutually enhancing effects on health. Syndemic theory considers the concerted, deleterious interaction of two or more diseases or other health conditions, such as psycho-emotional stress, that result from structural inequities. We therefore call for an approach that links localized morbidity of individual- or household-level experiences of concurrent food and water insecurity to larger structural and contextual forces/risk environments. Such an approach permits the investigation of food and water insecurity as suites of risk, such that certain disease outcomes serve as signals for interlinked stressors. For example, the use of a syndemic perspective could help explain the persistence of conditions like diarrhea or stunting after food or water interventions; that is, existing approaches may be too narrow in scope to protect individuals from multiple and overlapping environmental and biopsychosocial stressors.

The Walter Reed Army Institute of Research (WRAIR) supports more than 350,000 people on lifesaving HIV treatment in Kenya, Nigeria, Tanzania, and Uganda through funding from the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR). Here, we review and synthesize the range of impacts WRAIR’s implementation science portfolio has had on PEPFAR service delivery for military and civilian populations since 2003. We also explore how investments in implementation science create institutional synergies within the U.S. Department of Defense, contributing to broad global health engagements and improving health outcomes for populations served. Finally, we discuss WRAIR’s contributions to PEPFAR priorities through use of data to drive and improve programming in real time in the era of HIV epidemic control and public health messaging that includes prevention, the 95-95-95 goals, and comorbidities.

Malaria remains a major global health burden, killing hundreds of thousands annually, especially in sub-Saharan Africa. In December 2019, a novel illness termed COVID-19, caused by SARS-CoV-2, was reported in China. This disease soon spread around the world and was declared a pandemic by the WHO on March 11, 2020. Considering that the malaria burden is high in many low-income tropical countries with little capacity to fund malaria control and eradication programs, the fight against malaria in these regions is likely to be hindered by COVID-19. Indeed, access to health care has generally been limited during the pandemic, whereas malaria interventions, such as seasonal malaria chemoprevention, and distribution of long-lasting insecticide-treated bed nets, have been suspended because of lockdowns. Likewise, the repurposing of antimalarials for the treatment of COVID-19 and a shift in focus from the production of malaria rapid diagnostic tests to COVID-19 rapid diagnostic tests are causes for concern in malaria-endemic regions. COVID-19 has disproportionately affected developed countries, threatening their capacity to aid in malaria control efforts. Here, we address impacts of the COVID-19 pandemic on the management and control of malaria in Africa.

The WHO recently expressed concern at the potential impact of COVID-19 on hunger, which is likely to exacerbate the already considerable burden of malnutrition of Africa. The impact of the disease is expected to be greater among those grappling with malnutrition, whereas widespread hunger and malnutrition will likely increase because of movement restrictions. COVID-19 is unfolding in Africa against a backdrop of worrying levels of hunger and undernourishment which could worsen as the virus threatens livelihoods and household economies. The perspective piece addresses the crisis within crisis of COVID-19 and hunger on the well-being of children in Africa.

Minority communities have borne the brunt of COVID-19 disease in the United States. Nonwhites have contracted most of the SARS-CoV-2 infections; COVID-19 mortality rates for Black Americans are more than twice those for whites. Given this, studying the most effective ways to prevent and treat SARS-CoV-2 in these populations should be a research priority, particularly with respect to vaccine trials. Federal guidelines from the National Institutes of Health and Food and Drug Administration emphasize the need for inclusion of minority groups in these trials, but none of the publicly available SARS-CoV-2 vaccine trial protocols requires representative sampling of minorities. This piece emphasizes the importance of adequate inclusion of minority communities in SARS-CoV-2 vaccine trials, and the implications of this inclusion for SARS-CoV-2 vaccine distribution.

The efficacy and safety of hydroxychloroquine (HCQ) for the prevention and treatment of COVID-19 has received great attention, and most notably, the enthusiasm for HCQ has been one of politicization rather than science. Laboratory studies and case series published early in the pandemic supported its efficacy. The scientific community raced to conduct observational and randomized evaluations of the drug in all stages of the disease, including prophylaxis, early treatment, and advanced disease. Yet a divisive media response affected recruitment, funding, and subsequent enthusiasm for continuing scientific investigations. Of the more than 300 HCQ trials registered, fewer than 50% report having recruited any patients, and most trials might fail to achieve any useful portions of their intended sample size. Multiple observational studies and two large randomized trials have demonstrated HCQ does not offer efficacy against COVID-19 in hospitalized patients. Prophylaxis studies and early treatment studies provided heterogeneous results and are plagued by low event rates and poor study outcome monitoring. Emerging high-quality evaluations of prophylaxis and early treatment do not support a role for HCQ in these populations. The story of HCQ for COVID-19 has followed a pattern of initial enthusiasm supported by poor quality evidence, followed by disappointment based on more rigorous evaluations. The experience of HCQ in the COVID-19 era calls for the depoliticization of science away from media glare.

Since 1999, the CORE Group Polio Project (CGPP) has developed, refined, and deployed effective strategies to mobilize communities to improve vaccine uptake for polio (and other vaccine-preventable diseases such as measles) and conduct surveillance for infectious disease threats in high-risk, border, and hard-to-reach locations. CORE Group Polio Project teams have been called upon to address the COVID-19 pandemic, and, like with polio, the pandemic response is impacted by stigma in all areas of response, from health education, testing, contact tracing, and even treatment for infected individuals. The CGPP has reached back into its polio experience and is redeploying successful community engagement activities to address stigma as part of the COVID-19 response. Across country programs, community health volunteers communicate risk and behavior change at the household level by integrating health education and promotion activities with a focus on practical measures of COVID-19 prevention. Moreover, leveraging established and trusted partnerships with community networks and community leaders are providing lessons that can be adopted by the global community. The CGPP offers three overarching recommendations to curb stigma: 1) facilitating inclusive community engagement, 2) leveraging existing community networks and 3) cocreating with community leaders.

Dengue fever (DF) is a viral infection that is common in tropical countries and represents a significant cause of global morbidity and mortality. Despite its prevalence and severity, treatment options for DF remain limited and consist primarily of supportive measures. Several recent studies have concluded that micronutrient supplementation may improve clinical outcomes in patients with DF, but no review has summarized and synthesized these findings. We conducted a literature review to identify articles investigating the effect of micronutrient supplementation on clinical outcomes among patients with DF. We found several studies which indicated that supplemental vitamin C, vitamin D, vitamin E, and zinc may be useful adjuncts in DF treatment. Folic acid supplementation did not appear to affect clinical outcomes. The reviewed studies have significant limitations including small sample sizes and limited data about the baseline nutritional status of study subjects. We identify a need for additional high-quality randomized trials to elucidate the role of micronutrient supplementation in DF treatment.

Dengue infections are increasing globally and account for significant morbidity and mortality. Severe dengue results in microvascular changes and coagulopathy that may make surgical intervention risky and the overall surgical management challenging. We outline the potential surgical manifestations and complications following dengue infections and describe the clinical, pathogenetic, diagnostic, and treatment aspects of dengue and surgical patients. The main surgical presentations were acute cholecystitis, acute pancreatitis, acute appendicitis, splenic rupture, bowel perforation, gastrointestinal bleeding, and hematomas. Dengue may also mimic an acute abdomen without any true surgical complications. A majority were treated nonoperatively. Misdiagnosis and unnecessary surgical intervention resulted in poor outcomes. Better knowledge of the potential surgical complications would help in early diagnosis, treatment, and referral to specialized centers and thus improve outcomes. A high degree of suspicion of dengue fever is necessary when patients in a dengue-epidemic area present with acute abdomen or bleeding manifestations. In endemic areas, early dengue antigen testing and abdominal imaging before surgical intervention may help in the diagnoses. Multidisciplinary team involvement with case-by-case decision-making is needed for optimal care.

COVID-19 is an infectious disease caused by SARS-CoV-2. This enveloped RNA coronavirus primarily has tropism for the respiratory tract. However, it has also been shown to have various extrapulmonary manifestations such as pulmonary embolism, ischemic strokes, deep venous thrombosis, or arterial thrombosis. We present a case of a 34-year-old woman who had severe COVID-19 infection with no respiratory symptoms and developed strokes in multiple vascular territories and digital ischemia due to thrombosis formation in the brachial circulation of her arm despite receiving therapeutic anticoagulation.

Clinical manifestations and complications of SARS-CoV-2 are still emerging and variant. Gastrointestinal (GI) manifestations and complications are hugely under-recognized. The presence of angiotensin converting enzyme-2 receptors in the intestinal enterocytes, the receptors primarily involved in the pathogenesis of COVID-19 pneumonia, maybe the key factor contributing to the pathogenesis of GI manifestations. Ischemic colitis, although the most common ischemic pathology of the GI tract, is relatively rare, occurring as a result of colonic hypoperfusion. The innumerable causes of colonic ischemia are categorized into occlusive and nonocclusive pathologies. Here, we have discussed a case of severe COVID-19 pneumonia, developing ischemic colitis, as a rare GI complication. The cause of ischemia in COVID-19 pneumonia is multifactorial, including hypercoagulable state, coagulopathy leading to thromboembolic complications, and use of vasopressors in severely ill patients with hemodynamic compromise.

The COVID-19 pandemic has spread globally. Only three cases in Bangladesh were reported on March 8, 2020. Here, we aim to predict the epidemic progression for 1 year under different scenarios in Bangladesh. We extracted the number of daily confirmed cases from March 8 to July 20, 2020. We considered the suspected-infected-removed (SIR) model and performed a maximum likelihood-based grid search to determine the removal rate (ɣ). The transmission was modeled as a stochastic random walk process, and sequential Monte Carlo simulation was run 100 times with bootstrap fits to infer the transmission rate (β) and R t . According to the simulation, the (real) peak daily incidence of 3,600 would be followed by a steady decline, reaching below 1,000 in late January 2021. Thus, the model predicted that there would still be more than 300 cases/day even after a year. However, with proper interventions, a much steeper decline would be achieved following the peak. If we apply a combined (0.8β, 1.2ɣ) intervention, there would be less than 100 cases by mid-October, only around five odd cases at the beginning of the year 2021, and zero cases in early March 2021. The predicted total number of deaths (in status quo) after 1 year would be 8,533 which would reduce to 3,577 if combined (0.8β, 1.2ɣ) intervention is applied. We have also predicted the ideal number of tests that Bangladesh should perform and based on that redid the whole simulation. The outcome, though worse, would be manageable with interventions according to the simulation.

The unprecedented coronavirus pandemic is hitting the whole world, including the United Arab Emirates. Public awareness and adherence to the recommendations play a major role in managing a crisis of this magnitude which is largely affected by knowledge, attitudes, and practices (KAP). Hence, the aim of this study was to assess COVID-19–related KAP of the University of Sharjah (UOS) students and compare between health-related (HR) and non-HR (NHR) majors. A cross-sectional study was conducted in May 2020 in which 1,012 (481 health-related and 531 NHR) students participated via an online KAP questionnaire. The students’ sociodemographic characteristics and sources of information were also recorded, and data were analyzed. Students were aged 20–25 years, with an overall knowledge score of 72.4%, and the main source of their information was the Internet and social media (85.2%). Those in HR majors had a higher knowledge score (76%) than those in NHR students (69%). Regarding attitudes, both HR and NHR students demonstrated comparable and positive attitudes to curb the spread. With respect to practices, more NHR students used masks (92.3%), almost all the time than HR students (88.4%). HR students (99.4%) avoided crowded places and practiced social distancing more than NHR students (99.4% versus 97.4% and 97.7% versus 93.2%, respectively). In conclusion, UOS students demonstrated adequate knowledge, and possessed good attitudes and low-risk practices toward prevention of COVID-19. It is recommended that universities including UOS continue to use digital university communication platforms to regularly disseminate vital information in such emergencies.

Globally, India has reported the third highest number of COVID-19 cases. Chennai, the capital of Tamil Nadu state, witnessed a huge surge in COVID-19 cases, resulting in the establishment of isolation facilities named COVID Care Center (CCC). In our study, we describe the demographic, epidemiological, and clinical characteristics; clinical progression; and outcome of 1,263 asymptomatic/mildly symptomatic COVID-19 patients isolated in one such CCC between May 4, 2020 and June 4, 2020. Around 10.5% of the patients progressed to moderate/severe illness, requiring referral for tertiary care, and three died. Nearly half (49.5%) of the patients were symptomatic at the time of admission, 2.2% of the patients developed symptoms post-testing, and 48.5% patients remained asymptomatic during the entire course of illness. Most common presenting symptoms were fever (69.9%) and cough (29.6%), followed by generalized body pain, breathlessness, and loss of smell and taste. On multivariate analysis, we identified that symptomatic patients with comorbidities and higher neutrophil–lymphocyte ratio (NLR) were more likely to progress to severe illness warranting referral for tertiary care. COVID Care Center ensured case isolation and monitoring of asymptomatic/mildly symptomatic patients, thereby providing hospital beds for sick patients. COVID Care Center isolation facilities are safe alternatives for medical institutions to isolate and monitor COVID-19 patients. Older symptomatic patients with comorbidities and a high NLR admitted in an isolation facility must be frequently monitored for prompt identification of clinical progression and referral to higher center for advanced medical care.

Global health has been thrown into turmoil by the COVID-19 pandemic, which has caused devastating morbidity and unprecedented loss of life in almost all continents of the world. It was predicted that the magnitude of the pandemic in Africa will be high because of poor health structure and intensely poor living condition, but that has not happened, surprisingly. It was hypothesized that the youthful population and a vastly primed immune system were protective, and many people may have been exposed without coming down with the severe disease. Most of them would have presented in hospitals with other medical conditions and possibly transmit COVID-19 to health workers inadvertently. This study is designed to measure serum SARS-CoV-2 IgG levels in health workers as a marker of latent exposure. Asymptomatic frontline health workers were randomly selected from the University College Hospital Ibadan, Nigeria; venous blood samples were obtained from them, and the serum SARS-CoV-2 IgG level was determined using ELISA techniques. A proportion of participants with seropositivity were obtained, and factors associated with seropositivity were determined. A total of 133 participants were recruited for this study, and 60 (45.1%) of them were seropositive for SARS-CoV-2. Among the seropositive participants were doctors, nurses, health assistants, laboratory scientists and technicians, and nonmedical staff. Obstetrics, gynecology, and emergency departments had higher odds of seropositivity. Seroprevalence of SARS-CoV-2 is very high among frontline health workers, though asymptomatic. This calls for a more stringent precaution against further spread within the hospital environment.

The COVID-19 pandemic has great consequences on mental health. We aimed to assess medical students’ psychological condition and influencing factors as a baseline evidence for interventions promoting their mental wellbeing. We conducted an online survey from April 8 to April 18, 2020 to examine the mental health of medical students by the nine-item Patient Health Questionnaire, seven-item Generalized Anxiety Disorder Scale, seven-item Insomnia Severity Index, and six-item Kessler psychological distress scale. Factors associated with mental health outcomes were identified by multivariable logistic regression analysis. Five hundred forty-nine students completed the survey; 341 (62.3%), 410 (74.6%), 344 (62.6%), and 379 (69%) reported anxiety, depression, insomnia, and distress, respectively. Female students, living in high COVID-19 prevalence locations, more than 25 days confinement, psychiatric consult history, and being in a preclinical level of studies had higher median scores and severe symptom levels. Multivariable logistic regression showed female gender as a risk factor for severe symptoms of anxiety (odds ratio [OR]: 1.653; 95% CI: 1.020–2.679; P = 0.042), depression (OR: 2.167; 95% CI: 1.435–3.271; P < 0.001), insomnia (OR: 1.830; 95% CI: 1.176–2.847; P = 0.007), and distress (OR: 1.994; 95% CI: 1.338–2.972; P = 0.001); preclinical level of enrollment as a risk factor for depression (OR: 0.679; 95% CI: 0.521–0.885; P = 0.004), insomnia (OR: 0.720; 95% CI: 0.545–0.949; P = 0.02), and distress (OR: 0.650; 95% CI: 0.499–0.847; P = 0.001), whereas living in high COVID-19 prevalence locations was a risk factor for severe anxiety (OR: 1.628; 95% CI: 1.090–2.432; P = 0.017) and depression (OR: 1.438; 95% CI: 1.002–2.097; P = 0.05). Currently, medical students experience high levels of mental health symptoms, especially female students, those at a preclinical level and living in regions with a high prevalence of COVID-19 cases. Screening for mental health issues, psychological support, and long-term follow-up could alleviate the burden and protect future physicians.

Information on the risk factors for COVID-19 mortality in low- and middle-income countries is still scarce. In this retrospective cohort study, we analyzed the factors associated with COVID-19 mortality in hospitalized patients in a poor area of Brazil. Logistic regression was used to identify factors independently associated with mortality, including gender, age, and the presence of underlying medical conditions. A total of 1,207 patients were included in the analysis, and a 1.5-fold increase in COVID-19 mortality was found among patients aged > 65 years with hypertension and diabetes (odds ratio [OR]: 1.50, 95% CI: 1.02–2.19). Moreover, infectious disease (OR: 4.31, 95% CI: 1.39–13.39), kidney disease (OR: 2.59, 95% CI: 1.27–5.27), and heart disease (OR: 2.00, 95% CI: 1.31–3.04) were also predictive for COVID-19 in-hospital death. This large cohort provides important data on potential factors associated with COVID-19 mortality in Brazil.

The WHO defined three clinical forms for chikungunya virus infection (CHIKV, namely, acute, atypical, and severe cases) and a chronic form. These definitions seemed inappropriate for the elderly. So, we propose an adapted definition for elderly people. A cross-sectional analysis was performed including patients aged ≥ 65 years, who attended the emergency department with a positive biological diagnosis of CHIKV in 2014. A total of 267 elderly patients (80 ± 8 years) were included. When using the 2015 WHO definitions, 114 patients could not be classified (42.7%) in any of the category, of whom 43 (37.7%) reported absence of fever, 85 (74.6%) reported absence of joint pain, and 14 (12.3%) reported absence of both fever and joint pain. After adaptation of the WHO definitions, the 114 unclassifiable patients were reclassified as follows: eight as typical cases, 50 as atypical cases, 42 as severe cases, and 14 remained unclassifiable. The atypical clinical form was the most common form. The 2015 WHO definitions of the clinical forms at the acute phase of CHIKV are ill suited to the elderly. The adapted definition we propose here appears to be more appropriate and could help improved management of older patients with CHIKV.

We describe a case of dengue fever–associated foveolitis that presented initially to the ophthalmologists with complaints of unilateral diminution of vision. A 30-year-old Indian woman had presented with sudden onset diminution of vision in the left eye (LE) for the past 2 days. It was also associated with low-grade fever and myalgia, which started few days before visual deterioration. Fundus showed few retinal hemorrhages and tiny subretinal yellowish lesions at the fovea in the LE. Optical coherence tomography and fluorescein angiography were indicative of foveolitis. Amsler charting showed a central scotoma in the LE. She was treated with oral steroids along with supportive treatments. A near-complete anatomical and functional recovery was noted. Our case depicts the significance of awareness of the ophthalmic complications of dengue fever among both ophthalmologists and physicians, and also highlights the key clinical and multimodal imaging findings in a case of dengue foveolitis.

Dengue virus (DENV) is the cause of one of the most prevalent neglected tropical diseases, and up to half of the world’s population is at risk for infection. Recent results from clinical trials have shown that DENV vaccination can induce the development of severe dengue disease and/or prolong hospitalization after natural infection in certain naive populations. Thus, it is crucial that vaccine development takes into account the history of DENV exposure in the targeted population. In Nepal, DENV infection was first documented in 2004, and despite the increasing prevalence of DENV infection, the population remains relatively naive. However, it is not known which of the four DENV serotypes circulate in Nepal or whether there is evidence of repeated exposure to DENV in the Nepali population. To address this, we studied 112 patients who presented with symptomology suspicious for DENV infection at clinics throughout Nepal during late 2015 and early 2016. Of the 112 patients examined, 39 showed serological and/or genetic evidence of primary or secondary DENV infection: 30 were positive for DENV exposure by IgM/IgG ELISA, two by real-time reverse-transcription PCR (RT-PCR), and seven by both methods. Dengue virus 1–3, but not DENV4, serotypes were detected by RT-PCR. Whole genome sequencing of two DENV2 strains isolated from patients with primary and secondary infections suggests that DENV was introduced into Nepal through India, with which it shares a porous border. Further study is needed to better define the DENV epidemic in Nepal, a country with limited scientific resources and infrastructure.

Under-recognition of dengue infection may lead to increased morbidity and mortality, whereas early detection is shown to help improve patient outcomes. Recent incidence and outbreak reports of dengue virus in the United States and other temperate regions where dengue was not typically seen have raised concerns regarding appropriate diagnosis and management by healthcare providers unfamiliar with the disease. This study aimed to describe self-reported clinical symptoms of dengue fever in a non-endemic cohort and to establish a clinically useful predictive algorithm based on presenting features that can assist in the early evaluation of potential dengue infection. Volunteers who experienced febrile illness while traveling in dengue-endemic countries were recruited for this study. History of illness and blood samples were collected at enrollment. Participants were classified as dengue naive or dengue exposed based on neutralizing antibody titers. Statistical analysis was performed to compare characteristics between the two groups. A regression model including joint/muscle/bone pain, rash, dyspnea, and rhinorrhea predicts dengue infection with 78% sensitivity, 63% specificity, 80% positive predictive value, and 61% negative predictive value. A decision tree model including joint/muscle/bone pain, dyspnea, and rash yields 77% sensitivity and 67% specificity. Diagnosis of dengue fever is challenging because of the nonspecific nature of clinical presentation. A sensitive predicting model can be helpful to triage suspected dengue infection in the non-endemic setting, but specificity requires additional testing including laboratory evaluation.

Dengue seroprevalence data are useful for understanding epidemiologic trends and transmission dynamics, and for making decisions about implementation of dengue control programs. A logistical challenge to seroprevalence surveys is the collection and transport of serum samples. For conducting large and repeated dengue serosurveys, dried blood spots (DBS) would allow easier sample collection, shipment, transport, and storage than standard serum collection methods. Further evidence is needed to understand how well DBS performs compared with standard serum collection methods in laboratory assays. We evaluated the detection of anti-dengue antibodies by IgG indirect ELISA when using DBS compared with sera. Specimens were collected from healthy children in Cebu, Philippines, who would be 9–14 years of age at the time of a mass dengue vaccination program. Using an ELISA index value cutoff of 0.9, 1,285/1,488 (86.4%) of the DBS were seropositive and 203 (13.6%) were seronegative, compared with 1,292/1,488 (86.8%) seropositive and 196 (13.2%) seronegative serum samples. Compared with sera, the DBS method had a 98.3% sensitivity, 92.4% specificity, 98.9% positive predictive value, and 89.2% negative predictive value. Considering the advantages in terms of sample collection, shipment, and storage, DBS sampling may be appropriate for dengue population serosurveys.

A phase III dengue vaccine trial including 9- to 16-year-olds in Latin America (NCT01374516) was ongoing at the time of a Zika outbreak. We explored interactions between dengue and Zika, in the context of dengue vaccination. Symptomatic virologically confirmed Zika (VCZ) was evaluated using acute-phase sera from febrile participants (January 2013–March 2018). Neutralizing antibody geometric mean titers (GMTs) were evaluated pre- and post-Zika outbreak (months 25 and 72) in 2,000 randomly selected participants. Baseline dengue serostatus was determined using the plaque reduction neutralization test or inferred post hoc using nonstructural protein 1 IgG ELISA at M13 (case–cohort analysis). Vaccine efficacy against VCZ and serologically suspected Zika (SSZ) was estimated. Overall, 239/10,157 (2.4%) acute-phase samples were VCZ positive during the study. Dengue vaccine efficacy against VCZ was 27.8% (95% CI: 0.3; 47.7) among baseline dengue-seropositive participants. No vaccine effect was evident against SSZ. Zika antibody GMTs increased from pre- to post-Zika epidemic, with smaller increases observed for participants who were dengue seropositive at baseline than for those who were dengue seronegative: post-/pre-Zika GMT ratios for baseline dengue-seropositive participants were 21.5 (vaccine group) and 30.8 (placebo); and for dengue seronegatives, 88.1 and 89.5, respectively. Dengue antibody GMTs post-Zika were higher in dengue vaccine and placebo recipients with SSZ than those without SSZ in both dengue seropositives and seronegatives. Dengue vaccine did not enhance symptomatic Zika illness in dengue-seropositive individuals, rather it reduced the risk of VCZ. Zika infection boosted preexisting vaccine-induced or naturally occurring dengue-neutralizing antibodies.

The control of container Aedes species by house inspections usually achieves insufficient coverage and impact because a percentage of residents are absent and some residents refuse inspections and treatments. In addition, another fraction of the buildings may be uninhabited, such as those for rent or sale, or abandoned. Although the productivity of Aedes aegypti has been investigated in abandoned lots, less is known about the importance of uninhabited buildings. We investigated Ae. aegypti pupal productivity in inhabited, vacant, and abandoned houses and its interaction with socioeconomic levels (SELs). We found pupae in containers of 386 houses (66 abandoned, 62 vacant, and 258 inhabited) in 19 neighborhoods in southern Puerto Rico from May to August 2017. Using a generalized linear model, we found a significant interaction between the status of the house (abandoned, vacant, and inhabited) and SELs (low, medium) on Ae. aegypti pupal abundance. More pupae were found in abandoned and inhabited houses of low SELs. The lowest productivity was found in vacant houses, regardless of the SEL. Most containers producing Ae. aegypti in low-SEL houses were discarded on backyards, whereas in medium SELs, most productivity came from containers in use. Septic tanks producing Ae. aegypti were found only in houses of low SELs, where most emerging mosquitoes came from inhabited houses. We did not find any pupae of Ae. aegypti on roofs. These results indicate that proper yard management could significantly reduce the production of Ae. aegypti and the risk of dengue infections in low-SEL neighborhoods.

Modeling vector-borne diseases is best conducted when heterogeneity among interacting biotic and abiotic processes is captured. However, the successful integration of these complex processes is difficult, hindered by a lack of understanding of how these relationships influence disease transmission across varying scales. West Nile virus (WNV) is the most important mosquito-borne disease in the United States. Vectored by Culex mosquitoes and maintained in the environment by avian hosts, the virus can spill over into humans and horses, sometimes causing severe neuroinvasive illness. Several modeling studies have evaluated drivers of WNV disease risk, but nearly all have done so at broad scales and have reported mixed results of the effects of common explanatory variables. As a result, fine-scale relationships with common explanatory variables, particularly climatic, socioeconomic, and human demographic, remain uncertain across varying spatial extents. Using an interdisciplinary approach and an ongoing 12-year study of the Chicago region, this study evaluated the factors explaining WNV disease risk at high spatiotemporal resolution, comparing the human WNV model and covariate performance across three increasing spatial extents: ultrafine, local, and county scales. Our results demonstrate that as spatial extent increased, model performance increased. In addition, only six of the 23 assessed covariates were included in best-fit models of at least two scales. These results suggest that the mechanisms driving WNV ecology are scale-dependent and covariate importance increases as extent decreases. These tools may be particularly helpful for public health, mosquito, and disease control personnel in predicting and preventing disease within local and fine-scale jurisdictions, before spillover occurs.

Rubella occurs worldwide, causing approximately 100,000 cases annually of congenital rubella syndrome, leading to severe birth defects. Better targeting of public health interventions is needed to achieve rubella elimination goals. To that end, we measured the epidemiological characteristics and seasonal dynamic patterns of rubella and determined its association with meteorological factors in Shaanxi Province, China. Data on rubella cases in Shaanxi Province from 2005 to 2018 were obtained from the Chinese National Notifiable Disease Reporting System. The Morlet wavelet analysis was used to estimate temporal periodicity of rubella incidence. Mixed generalized additive models were used to measure associations between meteorological variables (temperature and relative humidity) and rubella incidence. A total of 17,185 rubella cases were reported in Shaanxi during the study period, for an annual incidence of 3.27 cases per 100,000 population. Interannual oscillations in rubella incidence of 0.8–1.4 years, 3.8–4.8 years, and 0.5 years were detected. Both temperature and relative humidity exhibited nonlinear associations with the incidence of rubella. The accumulative relative risk of transmission for the overall pooled estimates was maximized at a temperature of 0.23°C and relative humidity of 41.6%. This study found that seasonality and meteorological factors have impact on the transmission of rubella; public health interventions to eliminate rubella must consider periodic and seasonal fluctuations as well as meteorological factors.

In many regions where ticks negatively impact public health or economic production, multiple medically important tick species may have overlapping geographic distribution, and in North America, this includes members of Ixodes, Dermacentor, and Amblyomma genera. Acquired tick resistance is the process by which some animals develop an immune response against feeding ticks after one or more exposures. This form of immunity can restrict the ability of ticks to feed and may inhibit transmission of pathogens. Likewise, many proteins present in tick saliva are conserved among tick species, and prior studies have reported cross-protective host immunity against certain combinations of ticks. In this study, we used a guinea pig model to assess whether host resistance against Ixodes scapularis could confer protection against two other medically important tick vectors, Dermacentor variabilis and Amblyomma americanum. Tick challenges using nymphs were used to induce host resistance against a primary species, followed by additional challenge using a secondary tick species. Tick attachment to hosts and engorgement weights were reduced significantly for D. variabilis and A. americanum feeding on I. scapularis–sensitized hosts. Reciprocally, I. scapularis engorgement weights were reduced to a lesser extent, and attachment was unaffected when feeding on hosts sensitized with either D. variabilis or A. americanum. These results indicate that immunity against I. scapularis could potentially be exploited for use in an anti-tick vaccine targeting multiple tick species and their associated pathogens.

Rocky Mountain spotted fever (RMSF) is a serious disease in northwest Mexico, particularly in low-income communities. This study aimed to evaluate RMSF-related knowledge, attitudes, and practices in an endemic urban area with a high burden of the disease. A cross-sectional study design using a non-probabilistic household survey was conducted with 400 residents in Hermosillo, Mexico. Primary themes assessed included dog and tick-related exposure, RMSF knowledge, healthcare-seeking behavior, sociodemographic data, and household information. The majority (59%) of those surveyed had heard about RMSF, although only 36% of RMSF-aware respondents knew any RMSF symptoms. Among RMSF-aware respondents, 26% did not know or were unsure of prevention strategies. Individuals in the low socioeconomic status (SES) stratum were less likely to have heard about RMSF (odds ratio [OR]: 0.39; 95% CI: 0.25–0.59), use dog collars or any other product to avoid ticks (OR: 0.40; 95% CI: 0.17–0.99), or check their dogs for ticks (OR: 0.25; 95% CI: 0.09–0.74). The likelihood of observing high numbers of free-roaming dogs in their neighborhood was four times higher in the low SES stratum (OR: 4.19; 95% CI: 2.10–8.38) than in the high SES stratum. These findings emphasize the need for an integrative community approach to improve early recognition of symptoms and knowledge of prevention strategies, particularly in low SES neighborhoods.

Rocky Mountain spotted fever (RMSF), caused by Rickettsia rickettsii, is a severe and potentially fatal tick-borne disease. In 2015, Mexico issued a declaration of epidemiologic emergency in response to ongoing outbreaks of RMSF in northern Mexico. Sonora state is one of the most heavily impacted states in Mexico, with historic case fatality rates (CFRs) of 18%. We summarized data from enhanced surveillance to understand demographic, clinical, and treatment factors associated with the high mortality. We conducted a retrospective review of confirmed and probable RMSF cases reported to the General Directorate of Health Promotion and Disease Prevention in Sonora. A case of RMSF is defined as fever (> 38.5°C), plus two symptoms, and epidemiologic criteria. A confirmed case requires laboratory evidence. During 2015–2018, a total of 510 cases of RMSF were reported; 252 (49%) were in persons aged ≤ 18 years. Case fatality rate was 44% (n = 222). Older age and being confirmed by PCR were associated with fatal outcome (P-value < 0.01). The mean time from onset of symptoms to treatment with doxycycline was 7.9 days (SD ± 5.5). Hot spot analysis revealed neither areas of inordinately high nor low incidence, rather clusters of disease in population centers. The CFR for RMSF in Sonora remains high, and a large proportion of cases are seen in persons aged ≤ 18 years. Whereas previously children experienced a disproportionately high CFR, interventions have reversed this trend. Disease clusters in urban nuclei, but location remains a predictor of fatal outcome.

Bartonella henselae is a zoonotic Gram-negative Bacillus associated with self-limited regional lymphadenopathy. In recent decades, an expanding spectrum of clinical manifestations has been described, in part, due to improved diagnostics. However, updated epidemiological data are sparse. We retrospectively reviewed the clinical features of 31 patients with B. henselae infection over 15 years from 2005 to 2019, in the tropical Top End of Australia. Our annual disease incidence of 1.3 cases per 100,000 population is lower than that in the national database surveillances in the United States, but the hospitalization incidence of 0.9 per 100,000 population in our region is higher than those reported in the literature, with an average length of stay of 9 days. Patients were more commonly male, aboriginal, and aged less than 14 years (median age: 7 years), living in a rural setting with presentation during our monsoon season. The disease spectrum included lymph node disease (74%), organ peliosis, endocarditis, cutaneous lesions, parapharyngeal abscess, parotitis, and neurologic and ocular syndromes. Lymph node disease was far commoner in children than the more serious systemic B. henselae infections associated with adults (P = 0.074). Although no deaths were reported, significant morbidities were observed. Two endocarditis cases presented with glomerulonephritis, and hematological and neurological features mimicking vasculitis, and consequently received immunosuppressants. One case was only diagnosed after representation with serial embolic strokes. Given the heterogeneity of disease manifestations with nonspecific symptoms and significant consequences, a timely and accurate diagnosis is needed to avoid unnecessary treatments or interventions.

The Trachoma Control Program in Amhara region, Ethiopia, scaled up the surgery, antibiotics, facial cleanliness, and environmental improvement (SAFE) strategy in all districts starting in 2007. Despite these efforts, many districts still require additional years of SAFE. In 2017, four districts were selected for the assessment of antibody responses against Chlamydia trachomatis antigens and C. trachomatis infection to better understand transmission. Districts with differing endemicity were chosen, whereby one had a previous trachomatous inflammation-follicular (TF) prevalence of ≥ 30% (Andabet), one had a prevalence between 10% and 29.9% (Dera), one had a prevalence between 5% and 10% (Woreta town), and one had a previous TF prevalence of < 5% (Alefa) and had not received antibiotic intervention for 2 years. Survey teams assessed trachoma clinical signs and took conjunctival swabs and dried blood spots (DBS) to measure infection and antibody responses. Trachomatous inflammation-follicular prevalence among children aged 1–9 years was 37.0% (95% CI: 31.1–43.3) for Andabet, 14.7% (95% CI: 10.0–20.5) for Dera, and < 5% for Woreta town and Alefa. Chlamydia trachomatis infection was only detected in Andabet (11.3%). Within these districts, 2,195 children provided DBS. The prevalence of antibody responses to the antigen Pgp3 was 36.9% (95% CI: 29.0–45.6%) for Andabet, 11.3% (95% CI: 5.9–20.6%) for Dera, and < 5% for Woreta town and Alefa. Seroconversion rate for Pgp3 in Andabet was 0.094 (95% CI: 0.069–0.128) events per year. In Andabet district, where SAFE implementation has occurred for 11 years, the antibody data support the finding of persistently high levels of trachoma transmission.

Leptospirosis is an important zoonotic disease with worldwide distribution and nonspecific clinical manifestation. We report a case of fatal leptospirosis in a previously healthy woman with a causative agent. A young adult Indian woman was brought in dead to the forensic department. Ten days before, she developed fever, dizziness with headache, myalgia, diarrhea, and vomiting. Routine inquest and autopsy were performed on the deceased, revealing hemorrhagic lungs with extensive intra-alveolar hemorrhages, pale liver with dissociation and separation of hepatocyte plates, and edematous brain with histiocyte and lymphocyte infiltration in the parenchyma and meninges. Heart tissue depicts myocarditis and pericarditis inflammatory changes. Cerebrospinal fluid (CSF) was turbid in appearance with mildly elevated leukocytes, predominantly lymphocytes. Real-time PCR targeting lipL32 gene of pathogenic Leptospira was detected in the blood, CSF, brain, kidney, heart, and liver. The genetic profile of the causative agent was ST149 (multi-locus sequence typing Scheme 3). This study illustrates the usefulness of Leptospira PCR assay in postmortem diagnosis and addresses the need for further surveillance to identify the epidemiological link of the disease.

Because pediatric leprosy strongly indicates continuous disease transmission in the community, knowing the profiles of pediatric leprosy is of great value for a leprosy-free world. We conducted this study to assess the clinical profiles of pediatric leprosy in Nepal. This retrospective study analyzed the 7-year record from 2011 to 2017. There were a total of 68 pediatric leprosy cases. Male (63.2%) cases outnumbered female cases. The minimum age of the leprosy-affected children was 6 years, with the mean age 12.17 (±1.95) years. Contact history was present in 26 (38.2%) children. Most of them (83.8%) had positive slit-skin smear. Lepra reaction was present in 14.7%. Nine had disability, with 4/9 (44.4%) of them having grade 2 disability. More than two-thirds (70.6%) were multi-bacillary cases. Some (2.9%) even had lepromatous leprosy. Leprosy continues to be a disease of concern in the post-elimination era even in the pediatric population.

Abdominal tuberculosis (ATB) is uncommon and not very well known by clinicians. We describe the characteristics, evolution, and treatment of patients with ATB in two large hospitals in the Paris region. We reviewed all records of patients treated for ATB, from January 01, 2010 to December 01, 2016, diagnosed by bacteriological and/or histological methods or highly suspected because of clinical/radiological features. We included 80 patients, with a median (IQR) age of 39 (29–50) years, with 56.2% being males. Among them, 63.7% had African origins, 15% Asian, and 11.2% European. Twenty-nine had a cause of immunosuppression (n = 21 HIV infection). The main abdominal localizations were lymph nodes (72.5%), peritoneum (62.5%), and solid organs (25%). Extra-abdominal localizations were recorded in 65 (81.2%) patients. Tuberculosis was proven bacteriologically in 71%, histologically in 50%, and solely clinical/radiological in 10% of cases. Patients received standard therapy for a median duration of 9 months, with a favorable outcome. Corticosteroid therapy was used in 15 cases, either for paradoxical reaction or to prevent complications. Abdominal TB was mainly represented by lymphatic and peritoneal localizations, proven bacteriologically, and associated with extra-abdominal localizations in most cases. The use of steroids remains controversial, but it does not seem systematically needed in case of abdominal involvement.

Cryptosporidiosis is common in early childhood, and both diarrheal and subclinical infections are associated with adverse developmental outcomes. Improved therapeutic medications may help reduce the burden of cryptosporidial diarrhea; however, an effective vaccine would be better able to prevent the detrimental impact of both diarrheal and subclinical disease. A more complete understanding of naturally occurring immunity may further inform strategies to develop an effective vaccine. In this prospective cohort study of Bangladeshi children, greater fecal IgA at 12 months, but not plasma IgG, directed against two sporozoite-expressed, immunodominant and vaccine candidate antigens was associated with delayed time to subsequent cryptosporidiosis to 3 years of life. These findings extend prior work and further support the role of mucosal antibody responses in naturally developing protective immunity to Cryptosporidium.

Leishmania RNA virus (LRV) is a double-stranded RNA virus belonging to the Totiviridae family detected as cytoplasmic inclusions in some strains of the human parasite Leishmania spp. Experimental evidence supports the hypothesis that human coinfection with Leishmania spp.–LRV triggers an exacerbated immune response in the host that can be responsible for the observed complicated outcomes in cutaneous leishmaniasis (CL), such as mucosal leishmaniasis (ML) and treatment failure of CL. However, the reported frequencies of LRV associated with complicated outcomes in patient’s series are highly variable, diminishing the relevance on the virus presence in the pathogenesis of the disease. To assess whether or not the inconsistent information about the frequency of LRV associated with CL complicated outcomes could be related to the virus detection approach, the present study evaluated the LRV presence in clinical samples using a diagnostic algorithm according to the type of the sample. In 36 samples with diagnosis of complicated forms of CL (15 of ML and 21 of CL antimony treatment failure) and six samples with non–Leishmania spp. infection, the LRV presence was assessed by RT-PCR, RT-qPCR, and nested RT-PCR. Viral load was estimated in parasite clinical isolates. By combining the methods, LRV1 presence was confirmed in 45% (9/20) of isolates and 37.5% (6/16) of the incisional biopsies. Remarkably, in some cases (4/8), LRV1 was undetectable in the isolates but present in their respective biopsies, and less frequently, the opposite was observed (1/8), suggesting the possibility of loss of parasites harboring LRV1 during the in vitro growth.

Postexposure prophylaxis using artemisinin-based combination therapy (ACT) was prescribed to a malaria-naive nurse who experienced an injury with a hollow needle previously used on a patient admitted for severe imported Plasmodium falciparum malaria (blood parasitemia 10.8%). Artemether–lumefantrine, four tablets twice daily for 3 days, was started 12 hours after exposure, and no side effects were reported. During the six following months, she only developed one episode of fever that was associated with pyelonephritis. Biological follow-up, based on blood smears, molecular biology, and serology, did not evidence P. falciparum malaria. This case suggests that ACT can prevent occupational P. falciparum malaria following needle-stick injury. We found evidence of only one other unpublished similar case where a Turkish resident doctor did not develop malaria after postexposure prophylaxis using ACT. Such a prophylaxis could be prescribed not only in case of occupational exposure to Plasmodium spp. in nonvector-borne laboratory-acquired infections but also following blood exposure in healthcare setting.

Malaria and malnutrition remain primary causes of morbidity and mortality among children younger than 5 years in Africa. Studies investigating the association between malnutrition and subsequent malaria outcomes are inconsistent. We studied the effects of malnutrition on incidence and prevalence of malaria parasitemia in data from a cohort studied in the 1990s. Data came from the Asembo Bay cohort study, which collected malaria and health information on children from 1992 to 1996 in western Kenya. Infants were enrolled at birth and followed up until loss to follow-up, death, end of study, or 5 years old. Anthropometric measures and blood specimens were obtained monthly. Nutritional exposures included categorized Z-scores for height-for-age, weight-for-age, and weight-for-height. Febrile parasitemia and afebrile parasitemia were assessed with thick and thin blood films. Multiply imputed and weighted multinomial generalized estimating equation models estimated odds ratios (OR) for the association between exposures and outcomes. The sample included 1,182 children aged 0–30 months who contributed 18,028 follow-up visits. There was no significant association between malnutrition and either incident febrile parasitemia or prevalent febrile parasitemia. Prevalence ORs for afebrile parasitemia increased from 1.07 (95% CI: 0.89, 1.29) to 1.35 (1.03, 1.76) as stunting severity increased from mild to severe, and from 1.16 (1.02, 1.33) to 1.35 (1.09, 1.66) as underweight increased from mild to moderate. Stunting and underweight did not show a significant association with subsequent febrile parasitemia infections, but they did show a modest association with subsequent afebrile parasitemia. Consideration should be given to testing malnourished children for malaria, even if they present without fever.

The occurrence of malaria resurgences could threaten progress toward elimination of the disease. This study investigated the impact of repeated renewal of long-lasting insecticide-treated net (LLIN) universal coverage on malaria resurgence over a period of 10 years of net implementation in Dielmo (Senegal). A longitudinal study was carried out in Dielmo between August 2007 and July 2018. In July 2008, LLINs were offered to all villagers through universal campaign distribution which was renewed in July 2011, August 2014, and May 2016. Malaria cases were treated with artemisinin-based combination therapy. Two resurgences of malaria occurred during the 10 years in which LLINs have been in use. Since the third renewal of the nets, malaria decreased significantly compared with the first year the nets were implemented (adjusted incidence rate ratio) (95% CI) = 0.35 (0.15–0.85), during the ninth year after net implementation). During the tenth year of net implementation, no cases of malaria were observed among the study population. The use of nets increased significantly after the third time the nets were renewed when compared with the year after the first and the second times the nets were renewed (P < 0.001). The third renewal of nets, which took place after 2 years instead of 3 years together with a higher use of LLINs especially among the young, probably prevented the occurrence of a third malaria upsurge in this village.

Delayed parasite clearance time observed in Southeast Asia provided the first evidence of Plasmodium falciparum resistance to artemisinins. The ex vivo ring-stage survival assay (RSA) mimics parasite exposure to pharmacologically relevant artemisinin concentrations. Mutations in the C-terminal propeller domain of the putative kelch protein Pf3D7_1343700 (K13) are associated with artemisinin resistance. Variations in the pfmdr1 gene are associated with reduced susceptibility to the artemisinin partner drugs mefloquine (MQ) and lumefantrine (LF). To clarify the unknown landscape of artemisinin resistance in Colombia, 71 patients with uncomplicated P. falciparum malaria were enrolled in a non-randomized observational study in three endemic localities in 2014–2015. Each patient’s parasite isolate was assessed for ex vivo RSA, K13-propeller mutations, pfmdr1 copy number, and pfmdr1 mutations at codons 86, 184, 1034, 1042, and 1246, associated with reduced susceptibility, and 50% inhibitory concentration (IC50) for other antimalarial drugs. Ex vivo RSAs were successful in 56% (40/71) of samples, and nine isolates showed survival rates > 1%. All isolates had wild-type K13-propeller sequences. All isolates harbored either of two pfmdr1 haplotypes, NFSDD (79.3%) and NFSDY (20.7%), and 7.1% of isolates had > 1 pfmdr1 gene. In vitro IC50 assays showed that variable proportions of isolates had decreased susceptibility to chloroquine (52.4%, > 100 nM), amodiaquine (31.2%, > 30 nM), MQ (34.3%, > 30 nM), and LF (3.2%, > 10 nM). In this study, we report ex vivo RSA and K13 data on P. falciparum isolates from Colombia. The identification of isolates with increased ex vivo RSA rates in the absence of K13-propeller mutations and no positivity at day three requires further investigation.

Artemisinin combination therapies are the current frontline therapy for falciparum malaria. Artemisinin is activated by heme iron, and the consequent production of reactive oxygen species and carbon-centered radicals results in rapid parasite clearance. Red blood cells (RBCs) from anemic iron-deficient individuals have decreased levels of heme, and such deficiencies are highly prevalent among children and pregnant women in malaria-endemic countries. We, therefore, investigated the possibility that host anemia could impair artemisinin activity and alter the drug sensitivity of artemisinin-resistant strains of Plasmodium falciparum. We collected RBCs from anemic (n = 35) and nonanemic (n = 11) Gambian children between the ages of 2 and 24 months. Parasites grown in RBCs from both groups were assessed in vitro using the ring-stage survival assay with artemisinin-resistant and artemisinin-sensitive strains of P. falciparum. No differences were found in artemisinin sensitivity (P > 0.05), and there was no correlation between artemisinin activity and host hemoglobin levels. Standard antimalarial drug activity assays for representatives of the major classes of antimalarial drugs found no differences in the IC50 values against P. falciparum between anemic and nonanemic RBCs. We conclude that host anemia does not influence artemisinin activity.

The control of malaria, in terms of drug resistance, remains a significant global challenge, with Bangladesh, a malaria-endemic country, being no exception. The aim of this study was to explore antimalarial resistance in Bangladesh by molecular analysis of Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance transporter 1 (pfmdr1) genetic markers of P. falciparum. Samples were obtained from uncomplicated malaria patients between 2009 and 2014 from six malaria-endemic districts. Based on parasite transmission intensity, the endemic districts were divided into high-transmission (Chittagong Hill Tracts [CHT]) and low-transmission (non-CHT) regions. Falciparum malaria-positive isolates were genotyped for K76T of the pfcrt gene, and N86Y and Y184F of the pfmdr1 gene: in total, 262 P. falciparum clinical isolates were analyzed. In CHT areas, the prevalence of polymorphisms was 70.6% for 76T, 14.4% for 86Y, and 7.8% for 184F. In non-CHT areas, 76T and 86Y mutations were found in 78.0% and 19.5% of the samples, respectively, whereas no 184F mutations were observed. We compared our data with previous similar molecular observations, which shows a significant decrease in pfcrt 76T mutation prevalence. No pfmdr1 amplification was observed in any of the samples suggesting an unaltered susceptibility to amino alcohol drugs such as mefloquine and lumefantrine. This study provides an updated assessment of the current status of pfcrt and pfmdr1 gene mutations in Bangladesh, and suggests there is persistent high prevalence of markers of resistance to aminoquinoline drugs.

Plasmodium falciparum sporozoite (PfSPZ) Vaccine (radiation-attenuated, aseptic, purified, cryopreserved PfSPZ) and PfSPZ-CVac (infectious, aseptic, purified, cryopreserved PfSPZ administered to subjects taking weekly chloroquine chemoprophylaxis) have shown vaccine efficacies (VEs) of 100% against homologous controlled human malaria infection (CHMI) in nonimmune adults. Plasmodium falciparum sporozoite-CVac has never been assessed against CHMI in African vaccinees. We assessed the safety, immunogenicity, and VE against homologous CHMI of three doses of 2.7 × 106 PfSPZ of PfSPZ Vaccine at 8-week intervals and three doses of 1.0 × 105 PfSPZ of PfSPZ-CVac at 4-week intervals with each arm randomized, double-blind, placebo-controlled, and conducted in parallel. There were no differences in solicited adverse events between vaccinees and normal saline controls, or between PfSPZ Vaccine and PfSPZ-CVac recipients during the 6 days after administration of investigational product. However, from days 7–13, PfSPZ-CVac recipients had significantly more AEs, probably because of Pf parasitemia. Antibody responses were 2.9 times higher in PfSPZ Vaccine recipients than PfSPZ-CVac recipients at time of CHMI. Vaccine efficacy at a median of 14 weeks after last PfSPZ-CVac dose was 55% (8 of 13, P = 0.051) and at a median of 15 weeks after last PfSPZ Vaccine dose was 27% (5 of 15, P = 0.32). The higher VE in PfSPZ-CVac recipients of 55% with a 27-fold lower dose was likely a result of later stage parasite maturation in the liver, leading to induction of cellular immunity against a greater quantity and broader array of antigens.

Village health workers (VHWs) in Bugoye subcounty, Uganda, provide integrated community case management (iCCM) care to children younger than 5 years for malaria, pneumonia, and diarrhea. We assessed the longevity of VHWs’ skills in performing and reading malaria rapid diagnostic tests (RDTs) 4 years after initial training, comparing VHWs who had completed initial iCCM training 1 year before the study with VHWs who had completed training 4 years before the study. Both groups received quarterly refresher trainings. Trained interviewers observed 36 VHWs reading six mock RDTs each and performing an RDT as part of a larger skills assessment exercise. VHWs read 97% of mock RDTs correctly; of the 36 VHWs, 86% read all six mock RDTs correctly. Most VHWs scored either 12/13 or 13/13 on the RDT checklist (39% and 36%, respectively), with 25% scoring 11/13 or lower. For reading mock RDTs, VHWs in the first group (initial training 4 years before study) read 97% of mock RDTs correctly, whereas those in the second group (initial training 1 year before study) read 96% of mock RDTs correctly; the first group had a mean of 5.83 RDTs read correctly, compared with 5.77 RDTs read correctly in the second group (P = 0.83). For performing an RDT, the first group completed a mean of 12.0 steps correctly, compared with a mean of 12.2 correct steps in the second group (P = 0.60). Overall, VHWs demonstrated proficiency in reading RDTs accurately and performing RDTs according to protocol at least 4 years after initial iCCM training.

Spinal sparganosis of the cauda equina has been rarely reported. A 54-year-old man presented at the hospital after having experienced lower back pain for 10 months, progressive weakness and numbness of the left leg for 4 months, and urinary incontinence for 3 weeks. Magnetic resonance imaging of the lumbosacral spine revealed a heterogeneous enhancing mass at the T12-S1 level. Spinal sparganosis was diagnosed by histological examination and molecular identification of the parasite in the tissue section. The patient was treated with a high dose of praziquantel because the parasitic mass was only partially removed and symptoms worsened following surgery.

Increased levels of guinea worm (GW) disease transmission among dogs in villages along the Chari River in Chad threaten the gains made by the GW Eradication Program. Infected dogs with preemergent worm blisters are difficult to proactively identify. If these dogs are not contained, blisters can burst upon submersion in water, leading to the contamination of the water supply with L1 larvae. Guinea worm antigens previously identified using sera from human dracunculiasis patients were coupled to polystyrene beads for multiplex bead assay analysis of 41 non-endemic (presumed negative) dog sera and 39 sera from GW-positive dogs from Chad. Because commercially available anti-dog IgG secondary antibodies did not perform well in the multiplex assay, dog IgGs were partially purified, and a new anti-dog IgG monoclonal antibody was developed. Using the new 4E3D9 monoclonal secondary antibody, the thioredoxin-like protein 1–glutathione-S-transferase (GST), heat shock protein (HSP1)–GST, and HSP2–GST antigen multiplex assays had sensitivities of 69–74% and specificities of 73–83%. The domain of unknown function protein 148 (DUF148)–GST antigen multiplex assay had a sensitivity of 89.7% and a specificity of 85.4%. When testing samples collected within 1 year of GW emergence (n = 20), the DUF148–GST assay had a sensitivity of 90.0% and a specificity of 97.6% with a receiver-operating characteristic area under the curve of 0.94. Using sera from two experimentally infected dogs, antibodies to GW antigens were detected within 6 months of exposure. Our results suggest that, when used to analyze paired, longitudinal samples collected 1–2 months apart, the DUF148/GST multiplex assay could identify infected dogs 4–8 months before GW emergence.

Non–plaque-induced lesions may occur on the gingiva as medical disorders or manifestations of systemic conditions. Scabies is a parasitic infection caused by Sarcoptes scabiei. Here, we present the first case of oral scabies reported in the literature located on the gingiva in a 43-year-old woman. She was admitted to the hospital complaining of an ulcerative lesion on the gingiva with unknown duration, with a suggestive diagnosis of pemphigoid. A diagnosis of scabies infestation was made based on the visualization of eggs and larvae/nymph forms. The treatment consisted of 100 mg of ivermectin (three times per day for 15 days), supplemental oral hygiene with chlorhexidine, and extensive cleaning. The follow-up was made 30 days after treatment with ivermectin. The patient did not report side effects, with skin and oral lesions completely healed. Based on this, we need to perform a thoughtful ectoscopy examination and be alert to signs that indicate unusual causes to diagnose correctly and choose the appropriate treatment.

Snakebite envenomation (SBE) is a neglected One Health issue that overwhelmingly affects people living in rural and impoverished regions of Africa and Asia. Information on SBE is scarce in Rwanda; thus, our objectives were to 1) describe the demographics of SBE patients seeking hospital care, 2) evaluate physician adherence to national treatment guidelines, and 3) assess availability of snake antivenom at hospitals in Rwanda. To achieve these goals, we obtained national data on animal bites/stings and visited every district and provincial hospital in Rwanda to obtain physical records of SBE patients treated in 2017 and 2018. Hospital pharmacies were assessed for antivenom availability. We identified snakes as the second leading cause of animal bites, after dogs, among patients who sought hospital care in 2017 and 2018. Of 363 SBE patients, the highest number of cases occurred among children (< 18 years; 32%) and young adults (18–30 years; 33%), females (61%), farmers (82%), and those living in Eastern Province (37%). Overall, physician adherence to treatment guidelines was 63%. Prescriptions of vitamin K and antivenom were low (4% and 13%, respectively), and only 8% of hospital pharmacies had antivenom in stock throughout the study period. The antivenom stocked was an Indian generic suited for Asian snakes. This minimum estimate of hospitalization cases does not include individuals who died in communities or sought care outside the formal sector. Our study highlights the need to map incidence, risk factors, and patient experiences to mitigate human–snake conflicts and improve patient outcomes.

Protobothrops mucrosquamatus is one of the common venomous snakes in Southeast Asia. This retrospective cohort study conducted in six medical institutions in Taiwan aimed to obtain information on the optimal management strategies for P. mucrosquamatus snakebite envenomation. Data were extracted from the Chang Gung Research Database from January 2006 to December 2016. The association between early antivenom administration and patient demographics, pain requiring treatment with analgesic injections, and hospital length of stay was analyzed. A total of 195 patients were enrolled; 130 were administered antivenom within 1 hour after emergency department arrival (early group), whereas 65 were treated later than 1 hour after arrival (late group). No in-hospital mortality was identified. The difference in surgical intervention rates between the early and late groups was statistically insignificant (P = 0.417). Compared with the early group, the late group showed a higher rate of antivenom skin test performance (46.9% versus 63.1%, respectively, P = 0.033), longer hospital stay (42 ± 62 hours versus 99 ± 70 hours, respectively, P = 0.016), and higher rate of incidences of pain requiring treatment with analgesic injections (29.2% versus 46.2%, respectively, P = 0.019). After adjusting for confounding factors, early antivenom administration was associated with decreased pain requiring treatment with analgesic injections (adjusted odds ratio: 0.51, 95% CI: 0.260–0.985). Antivenom administration within 1 hour of arrival was associated with a decreased likelihood of experiencing pain and hospital length of stay in patients with P. mucrosquamatus snakebites. Antivenom skin testing was associated with delays in antivenom administration.

The Swat district, a conflict-hit territory due to Taliban militancy, had a damaged local health infrastructure. Animal-bite injuries leading to rabies is one of the major health concerns in developing countries, especially within conflict zones. The current prospective epidemiological study was conducted to estimate the cumulative incidence of animal-bite injuries, to summarize characteristics of bite victims and biting animals, and to collect information about post-exposure prophylaxis (PEP) practices in Swat district, Pakistan, during 2014. A questionnaire was designed to collect data about the sociodemography of the patients, bite incident situation (provoked or unprovoked), injury pattern, animal type, PEP, and vaccination. Descriptive analyses were conducted using bar graphs, frequency tables, and chi-square tests were used to determine associations. The cumulative incidence of animal-bite injuries was 39 per 100,000 people during the study period (May–August 2014). The majority of incidents were reported from rural regions (77.7%) and were males (76.6%) younger than 10 years (37.3%). Dogs were the most frequent biting animal (86.8%) followed by rats (4.7%). About 77.7% patients washed their wound before arrival at hospital. After an eclipse phase of 10 days, 44 (10.1%) animals developed sign of rabies. The current study has highlighted a topic of interest for health, education, veterinary, and local government policy makers regarding prevention of animal bites, benefits of PEP, vaccination of human and domestic animals, control of stray dogs, and eradication of rabies in developing countries with damaged healthcare structures.

Access to safe water and basic sanitation and hygiene facilities (WASH) are important for childhood health globally. However, inequalities in WASH access persist, and local governments need to better understand the potential impact of scaling up WASH services on childhood health. Using 2011 Peru Demographic and Health Survey data as a case study, we applied a modified substitution estimator approach to assess the impact of scaling up access (20–100%) to WASH on diarrhea prevalence among children < 5 years. The modified substitution estimator approach can help identify population subgroups or areas where WASH interventions and sustained implementation could be most beneficial and reduce existing disparities. Using findings from a recent meta-analysis and computing bootstrapped estimates and 95% CIs, we examined inequalities in the effect of WASH on self-reported diarrhea by urbanicity, maternal education level, household wealth, and district of residence. Increasing access (100% change) to improved water sources, sanitation, and hygiene facilities reduced population-level prevalence of childhood diarrhea by 8.2% (95% CI: 4.1, 12.3), 5.5% (95% CI: 0.7, 9.8), and 5.2% (95% CI: 2.2, 8.1), respectively. In stratified analyses, increased access to improved water sources and hygiene facilities was associated with decreased prevalence of diarrhea, with the largest reduction in rural areas and households with lower maternal education and lower wealth. Our findings suggest targeted WASH implementation in Peru is needed in rural areas and among lower socioeconomic-status households. In addition, even low levels of change in overall WASH access may decrease diarrhea prevalence.

The persistence and pervasiveness of growth stunting in low- and middle-income countries spur reexamination of disease transmission pathways related to water, sanitation, and hygiene. Animal feces constitute a more important reservoir of enteric pathogens in homes in low-income countries than previously recognized, and exploratory object mouthing and direct ingestion of soil and animal feces represent underexplored exposure pathways. The effectiveness, adoption, constraints, and scale-up potential of measures for reducing infant and young children’s exposure to fecal pathogens are recently beginning to be systematically explored. This mixed methods study tested the feasibility and appeal of using playpens to establish a hygienic “safe zone” for infants in rural Ethiopia. We conducted home trials of three playpen designs, including two models made from locally available materials through user-centered design. After using playpens for several weeks, caregivers reported extensive benefits, ranging from perceived safety to developmental and hygiene benefits for infants and relief from physical stress and worry for caregivers. We observed many playpens contaminated with Escherichia coli after weeks of use, though at concentrations below those of the common room floor on which infants might otherwise have played. Caregivers reported daily playpen use, but for intervals likely insufficient to protect infants from pathogen exposure affecting growth. We determine that playpens alone cannot plausibly protect infants from environmental contamination, but our results support further exploration of the potential benefits and commercial viability of scaling up use of playpens in rural, agricultural households as part of a comprehensive approach to child development and women’s empowerment.

Poor food hygiene practices, child feces not being disposed of in a latrine, child mouthing of contaminated fomites, and poor hand hygiene of caregivers have been associated with diarrheal diseases, environmental enteropathy, and impaired growth in young children. Mobile health (mHealth) programs present a low-cost approach to delivering water, sanitation, and hygiene (WASH) programs. We conducted a theory-driven and evidence-based approach to formative research and intervention development to design and pilot test a Baby WASH mHealth program targeting food hygiene, child mouthing, and child feces disposal behaviors in urban Dhaka, Bangladesh. Formative research activities included 31 semi-structured interviews, five group discussions, six mHealth workshops, and a three-phase iterative pilot study among 102 households. Findings from semi-structured interviews and group discussions indicate that caregivers of young children have relatively high awareness of the need for safer food hygiene, child mouthing, and child feces disposal practices, but are limited by existing household responsibilities and restricted access to enabling technology that would facilitate practicing recommended behaviors. The piloted Baby WASH mHealth program was well-received by households. This study presents a theory-driven and evidence-based approach for intervention development that can be implemented for the development of future WASH mHealth programs in low-resource settings.

Using previously validated microbial source tracking markers, we detected and quantified fecal contamination from avian species and avian exposure, dogs, and humans on household cooking tables and floors. The association among contamination, infrastructure, and socioeconomic covariates was assessed using simple and multiple ordinal logistic regressions. The presence of Campylobacter spp. in surface samples was linked to avian markers. Using molecular methods, animal feces were detected in 75.0% and human feces in 20.2% of 104 households. Floors were more contaminated than tables as detected by the avian marker Av4143, dog marker Bactcan, and human marker Bachum. Wood tables were consistently more contaminated than non-wood surfaces, specifically with the mitochondrial avian markers ND5 and CytB, fecal marker Av4143, and canine marker Bactcan. Final multivariable models with socioeconomic and infrastructure characteristics included as covariates indicate that detection of avian feces and avian exposure was associated with the presence of chickens, maternal age, and length of tenancy, whereas detection of human markers was associated with unimproved water source. Detection of Campylobacter in surface samples was associated with the avian fecal marker Av4143. We highlight the critical need to detect and measure the burden of animal fecal waste when evaluating household water, hygiene, and sanitation interventions, and the possibility of decreasing risk of exposure through the modification of surfaces to permit more effective household disinfection practices. Animals may be a more important source of household fecal contamination than humans in many low-resource settings, although interventions have historically focused almost exclusively on managing human waste.

Despite multiple studies demonstrating the effectiveness of household water treatment with chlorine in disinfecting water and preventing diarrhea, social marketing of this intervention in low- and middle-income countries has resulted in only modest uptake. In a cluster randomized trial in Vihiga district, western Kenya, we compared uptake of household water treatment with chlorine among six villages served by community vendors trained in standard social marketing plus education through listening (ETL), an innovative behavior change method, and six villages served by community vendors trained in standard social marketing only. Water treatment uptake, water quality, and childhood diarrhea were measured over 6 months and compared between the two groups of villages. During the 6-month period, we found no association between ETL exposure and reported and confirmed household water treatment with chlorine. In both groups (ETL and comparison), reported use of water treatment was low and did not change during our 6-month follow-up. However, persons confirmed to have chlorinated water had improved bacteriologic water quality. Study findings suggest that ETL implementation was suboptimal, which, along with unexpected changes in the supply and price of chlorine, may have prevented an accurate assessment of the potential impact of ETL on water treatment behavior. Taken together, these observations exemplify the complexities of habits, practices, attitudes, and external factors that can create challenging conditions for implementing behavioral interventions. As a consequence, in this trial, ETL had no measurable impact on water treatment behavior.

We sought to determine whether a shortened version of the 12-item Household Water Insecurity Experiences (HWISE) Scale, which measures water insecurity equivalently in low- and middle-income countries (LMICs), is valid for broad use. Using data from 9,261 households in 25 LMICs, subsets of candidate items were evaluated on their predictive accuracy, criterion validity, and sensitivity–specificity. A subset with items assessing “worry,” “changing plans,” “limited drinking water,” and “inability to wash hands” because of problems with water (range: 0–12) were highly correlated with full HWISE Scale scores (correlation coefficient: 0.949–0.980) and introduced minimal additional error (root mean square error: 2.13–2.68). Criterion validity was demonstrated, and a cut point of ≥ 4 correctly classified more than 91% of households as water secure or insecure. The brief HWISE-4 can be used in LMICs to inform decisions about how to most effectively target resources and evaluate public health interventions.

Advances in sepsis resuscitation have significantly improved shock control; however, many patients still die after septic shock reversal. We conducted a retrospective review to examine in-hospital death in whom shock was reversed and vasopressor was discontinued for 72 hours or longer. Factors independently associated with death were determined. Medical records of septic shock survivors from the medical intensive care unit of the Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, during January 2012–January 2019 were analyzed. A total of 350 septic shock patients were enrolled. Of these, 280 survived initial resuscitation. Eighty of 280 patients died, 45 died by 28 days (16.1%), and 35 (12.5%) died thereafter during their hospital stay. Multi-organ failure and hospital-acquired pneumonia (HAP) were the leading causes of death, followed by other infection and noninfectious complication. Although the death group had more laboratory derangement and required more organ support, there were four factors associated with mortality from multivariate analysis. Hospital-acquired pneumonia was the leading factor, followed by sequential organ failure assessment score and serum albumin at 72 hours after discontinuation of vasopressors, and total intravenous fluid during 72 hours after discontinuation of vasopressors. In-hospital mortality after hemodynamic restoration in patients with septic shock was substantial. Causes and contributing factors were identified. Measures to mitigate these risks would be beneficial for rendering more favorable patient outcomes.

Since 2011, considerable amounts of Sargassum algae regularly end up on beaches in the Gulf of Mexico, the Caribbean, and in the French overseas departments. We report observations of two bilateral keratoconjunctivitis associated with important functional symptomatology. There was a conjunctival hyperemia and superficial punctate keratitis. The ocular impairment would repeat at every algae ashore landing. Clinical examination, history, and time line of symptomatology onset allowed us to eliminate the classic etiologies of bilateral keratoconjunctivitis and to suggest an irritant toxic origin tied to hydrogen sulfide. This is the first description of ocular impairment tied to Sargassum algae decomposition. Their decomposition, through H2S emission, can be at the origin of bilateral keratoconjunctivitis. Ocular impairment is often at the forefront of complaints made by individuals exposed to H2S.