The American Journal of Tropical Medicine and Hygiene - Current Issue

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.