The American Journal of Tropical Medicine and Hygiene - Current Issue

The American Society for Tropical Medicine and Hygiene recently inaugurated an award for the best clinical research article published in the society’s journal in the previous year. This article summarizes both the process of selecting the winner and several themes that stood out in those articles which rose to the top for consideration. Themes of note included the importance of doing clinical research outside of referral centers, the complexity that must be considered when implementing interventions, incorporation of both ends of the age spectrum into studies, and considering cost-effectiveness and opportunity cost of interventions.

Breast tuberculosis (TB) is rarely reported and poorly described. This review aims to update the existing literature on risk factors, clinical presentations, constitutional symptoms, diagnostic procedures, and medical and surgical treatments for breast TB. In all, 1,478 cases of breast TB were collected. Previous history of TB was reported in 19% of cases. The most common clinical appearance of the lesion was breast lump (75%). The most common associated finding was axillary lymphadenitis (33%) followed by sinus or fistula (24%). The most common symptoms were pain and fever, reported in 42% and 28% of cases, respectively. The most used diagnostic method was fine-needle aspiration cytology (32%), followed by biopsy (27%), acid-fast bacteria Ziehl–Neelsen stain (26%), culture (13%), and polymerase chain reaction (2%). These tested positive in 64%, 93%, 27%, 26%, and 58% of cases, respectively. The majority (69%) of patients received a 6-month anti-TB treatment (isoniazid, rifampicin, pyrazinamide, and ethambutol). Surgery consisted of excision in 39% of cases, drainage in 23%, and mastectomy in 5%. The great majority of patients had a positive outcome. It often mimics breast cancer, which makes it difficult to diagnose. Most patients, when diagnosed in time, respond to antitubercular therapy alone.

An epidemic of Rocky Mountain spotted fever (RMSF) is ongoing in Mexicali, México. We visited 100 neighborhoods with diagnosed human cases and 100 control neighborhoods to evaluate knowledge of the epidemic; obtain data on the spatial distribution of dogs, canine seroprevalence and active infection, tick infestations, and presence of rickettsial DNA in ticks; and evaluate risk factors for human cases, seropositivity, and tick infestation within an unbiased study design. The majority (80%) of residents had heard of RMSF, but only 48% used acaricides in the home or on dogs. Case neighborhoods and those with high canine seroprevalence tended to be on the city periphery or in the agricultural valley. No dogs were polymerase chain reaction (PCR) positive for Rickettsia rickettsii, and the overall seroprevalence was 65% (titers from 64 to 1,024). PCR prevalence in ticks was 0.70%, confirmed by DNA sequencing as R. rickettsii; neighborhood prevalence ranged from 0.7% to 6.1%. Twelve percent of dogs had high tick burdens, and all ticks were Rhipicephalus sanguineus. Epidemiologically significant risk factors were ground covering for a neighborhood having a human case; dogs having poor body condition and weighing < 10 kg for canine seropositivity; dogs living at the home for the number of ticks in the environment; and being near canals, having trash on the patio, and a dog being thin for tick burdens on dogs. A One Health approach is crucial to understanding RMSF and brown dog ticks.

Query fever (Q fever), caused by Coxiella burnetii, was first described in southern California in 1947. It was found to be endemic and enzoonotic to the region and associated with exposure to livestock. We describe a series of 20 patients diagnosed with Q fever at a Veterans Affairs hospital in southern California, with the aim of contributing toward the understanding of Q fever in this region. Demographics, laboratory data, diagnostic imaging, risk factors, and treatment regimens were collected via a retrospective chart review of patients diagnosed with Q fever at our institution between 2000 and 2016. Cases were categorized as acute or chronic and confirmed or probable. The majority presented with an acute febrile illness (90%). There was a delay in ordering diagnostic serology from the time of symptom onset (acute cases, average 31.9 days; chronic cases, average 63 days), and 15% progressed from acute to chronic infection. Of the chronic cases, 22.2% had endocarditis, 22.2% had endovascular infection, and 11.1% had both endocarditis and endovascular infection. The geographic distribution revealed that 20% resided in rural areas. Of the cases of Q fever that died, death attributed to Q fever was associated with an average diagnostic delay of 65.5 days. Acute Q fever is underreported in this region largely because of its often nonspecific clinical presentation.

This is the first cross-sectional study of the seroprevalence and risk factors for Coxiella burnetii in Jordan. A total of 781 individuals from 11 governorates of Jordan were tested by SERION ELISA classic C. burnetii IgG Phase 2. A validated and pretested questionnaire was used to collect risk factors and demographic data. The overall seroprevalence for C. burnetii was 24.2% (95% CI; 21.3–27.3%). Unadjusted odds ratios showed that governorate of residence, consumption of raw milk, and ownership of sheep, goats, and dogs were significantly (P ≤ 0.05) associated with C. burnetii seropositivity. The multivariate logistic regression showed that individuals who own small ruminants had three times greater odds of seropositivity than those who do not own a small ruminant, after controlling for age, gender, raw milk consumption, and ownership of dogs. In addition, individuals who live in Al-Karak, Az-Zarqa, and Al-Tafilah had significantly greater odds of seropositivity compared with individuals who live in the capital city, Amman (OR = 3.6, 4.8, and 2.7, respectively). This study suggests that preventive measures should be practiced in ruminant farms in Jordan to avoid C. burnetii infection. Coxiella burnetii should also be considered in the differential diagnosis of febrile-like illnesses in Jordan, especially among farmers and veterinarians.

Waterborne pathogens, associated with poverty and poor sanitary conditions, are a major cause of morbidity and mortality worldwide. There are limited data on the epidemiology of waterborne pathogens in indigenous populations living in the Amazon region. We did a cross-sectional survey in two indigenous Shuar communities in the Amazon region of Ecuador in which we documented the presence of pathogens representing different sources of environmental contamination of water. We detected protozoa and soil-transmitted helminths by microscopy of fecal samples and the presence of IgG antibodies to hepatitis A and Leptospira spp. in blood samples from individuals older than 2 years and collected data by questionnaire on sociodemographic factors and knowledge of infectious diseases. Seroprevalence for hepatitis A and Leptospira spp. were 98.1% (95% CI: 97.0–99.8) and 50.0% (95% CI: 43.3–56.6), respectively, whereas 62.6% (95% CI: 55.8–69.4) had enteric parasites in stool samples. In participants older than 6 years, eight of 10 had evidence of infection with or exposure to at least one of the pathogens studied. Although prevalence of pathogens varied by age, it did not vary significantly by gender, temporal migration, illiteracy, perceived morbidity, receipt of conditional cash transfers, water boiling practices, poor housing conditions, and anthropometric status. These findings indicate a high level of contamination of drinking water by human pathogens in these indigenous communities and the need for interventions to improve access to and use of clean drinking water in these marginalized communities.

To explore the consistency in impact evaluation based on reported diarrhea, we compared diarrhea data collected through two different surveys and with observed diarrhea-associated hospitalization for children aged ≤ 5 years from a non-blinded cluster-randomized trial conducted over 2 years in urban Dhaka. We have previously reported that the interventions did not reduce diarrhea-associated hospitalization for children aged ≤ 5 years in this trial. We randomly allocated 90 geographic clusters comprising > 60,000 low-income households into three groups: cholera vaccine only, vaccine plus behavior change (cholera vaccine and handwashing plus drinking water chlorination promotion), and control. We calculated reported diarrhea prevalence within the last 2 days using data collected from two different survey methods. The “census” data were collected from each household every 6 months for updating household demographic information. The “monthly survey” data were collected every month from a subset of randomly selected study households for monitoring the uptake of behavior change interventions. We used binomial regression with a logarithmic link accounting for clustering to compare diarrhea prevalence across intervention and control groups separately for both census and monthly survey data. No intervention impact was detected in the census (vaccine only versus control: 2.32% versus 2.53%; P = 0.49; vaccine plus behavior change versus control: 2.44% versus 2.53%; P = 0.78) or in the vaccine only versus control in the monthly survey (3.39% versus 3.80%; P = 0.69). However, diarrhea prevalence was lower in the vaccine-plus-behavior-change group than control in the monthly survey (2.08% versus 3.80%; P = 0.02). Although the reasons for different observed treatment effects in the census and monthly survey data in this study are unclear, these findings emphasize the importance of assessing objective outcomes along with reported outcomes from non-blinded trials.

We compared the diagnostic performance of the standard method (Kato-Katz) with two recently developed methods (Mini-FLOTAC and Flukefinder) for the detection and quantification of Fasciola hepatica eggs in human stool. Uninfected human stool samples were artificially spiked with F. hepatica eggs to reach final concentrations of 14, 28, 41, or 96 eggs per gram of stool (epg). Only Flukefinder showed 100% sensitivity in all but the samples with the lowest concentration of eggs (14 epg), in which it had a sensitivity of 60%. Each of the methods underestimated the true fecal egg counts (FECs), Flukefinder resulting in the most biased egg counts (egg counts 0.18 times lower than the expected FECs). Only the Flukefinder resulted in more precise results (coefficient of variance < 30%) from FECs of 96 epg onward. The outcome of this study indicates that the Flukefinder is a useful alternative diagnostic method for human fascioliasis in stool.

We report an unusual case of paragonimiasis in a Nepali patient presenting with massive pericardial effusion and pericardial tamponade. The patient reported neither the consumption of crabs or crayfish nor the consumption of wild animal meat, which are the usual sources of infection. It is suspected that the source of infection was instead the ingestion of raw live slugs as part of a traditional medicine treatment.

Following a 4-year annual praziquantel (PZQ) treatment campaign, the resulting prevalence of Schistosoma mansoni was seen to differ among individual villages along the Kenyan shore of Lake Victoria. We have investigated possible inherent differences in snail-related aspects of transmission among such 10 villages, including six persistent hotspot (PHS) villages (≤ 30% reduction in prevalence following repeated treatments) located along the west-facing shore of the lake and four PZQ-responding (RESP) villages (> 30% prevalence reduction following repeated treatment) along the Winam Gulf. When taking into account all sampling sites, times, and water hyacinth presence/absence, shoreline-associated Biomphalaria sudanica from PHS and RESP villages did not differ in relative abundance or prevalence of S. mansoni infection. Water hyacinth intrusions were associated with increased B. sudanica abundance. The deeper water snail Biomphalaria choanomphala was significantly more abundant in the PHS villages, and prevalence of S. mansoni among villages both before and after control was positively correlated with B. choanomphala abundance. Worm recoveries from sentinel mice did not differ between PHS and RESP villages, and abundance of non-schistosome trematode species was not associated with S. mansoni abundance. Biomphalaria choanomphala provides an alternative, deepwater mode of transmission that may favor greater persistence of S. mansoni in PHS villages. As we found evidence for ongoing S. mansoni transmission in all 10 villages, we conclude that conditions conducive for transmission and reinfection occur ubiquitously. This argues for an integrated, basin-wide plan for schistosomiasis control to counteract rapid reinfections facilitated by large snail populations and movements of infected people around the lake.

Schistosomiasis is a blood parasitic disease caused by trematode parasites of the genus Schistosoma. Schistosoma mansoni is one of the main contributors of the disease and 90% of the global burden of schistosomiasis is in Africa. Mass drug administration (MDA) has been implemented to reduce the disease burden in endemic areas. Because of MDA, the diagnostic sensitivity and specificity for classical diagnostic tests are reduced. In any disease situation, diagnosis is vital in determining asymptomatic, concurrent, current, new, and reinfection cases to evaluate the efficacy of any control program. We have evaluated the positive infection for S. mansoni from filtered urine samples collected from Zambian school children after MDA using loop-mediated isothermal amplification (LAMP) and compared its sensitivity and specificity with polymerase chain reaction (PCR). One hundred eleven urine samples collected from school children aged between 7 and 15 years from Siavonga district in southern Zambia were evaluated by PCR and LAMP for DNA extracted by two different protocols (filter-based versus crude extraction). The infection prevalence was 77% with PCR and almost 94% with mansoni-LAMP. Also, LAMP detected 16% (Qiagen extraction) and 10% (LAMP-Procedure for Ultra Rapid Extraction) more positive S. mansoni infection than PCR. We have demonstrated the efficacy of LAMP in a laboratory setup after MDA. The possible inclusion of LAMP as a field-based point-of-care test for surveillance can provide reliable prevalence of schistosomiasis after MDA and help in determining the efficacy of a control program.

Treating Mansonella perstans is challenged by the low efficacy of registered antihelminthics. Wolbachia endobacteria provide an alternative treatment target because depletion results in amicrofilaremia in filarial infections with Wuchereria bancrofti and Onchocerca volvulus infections. This open-label, randomized study sought to confirm that i) Wolbachia are present in M. perstans in Ghana and ii) doxycycline treatment will deplete Wolbachia and cause a slow, sustained decline in microfilariae (MF). Two hundred and two Ghanaians with M. perstans infection were randomized into early (immediate) and delayed (6 months deferred) treatment groups, given doxycycline 200 mg/day for 6 weeks, and monitored for MF and Wolbachia levels at baseline, 4, 12, and 24 months after the study onset (= time of randomization and start of treatment for the early group). Per protocol analysis revealed that the median MF/mL in the early group declined from 138 at baseline to 64 at month 4 and further to 0 at month 12. In the delayed group, MF load did not change from a baseline median of 97 to 102 at month 4 but declined to 42 at month 12, that is, 6 months after receiving treatment, trailing the early group as expected. By month 24, both treatment groups had reached a median MF level of 0. After treatment, Wolbachia were depleted from MF by ≥ 1-log drop compared with baseline levels. We conclude that M. perstans in Ghana harbor Wolbachia that are effectively depleted by doxycycline with subsequent reduction in MF loads, most likely because of interruption of fertility of adult worms.

The large number of activities contributing to zoonoses surveillance and control capability, on both human and animal domains, and their likely heterogeneous implementation across administrative units make assessment and comparisons of capability performance between such units a complex task. Such comparisons are important to identify gaps in capability development, which could lead to clusters of vulnerable areas, and to rank and subsequently prioritize resource allocation toward the least capable administrative units. Area-level preparedness is a multidimensional entity and, to the best of our knowledge, there is no consensus on a single comprehensive indicator, or combination of indicators, in a summary metric. We use Bayesian spatial factor analysis models to jointly estimate and rank disease control and surveillance capabilities against visceral leishmaniasis (VL) at the municipality level in Brazil. The latent level of joint capability is informed by four variables at each municipality, three reflecting efforts to monitor and control the disease in humans, and one variable informing surveillance capability on the reservoir, the domestic dog. Because of the large volume of missing data, we applied imputation techniques to allow production of comprehensive rankings. We were able to show the application of these models to this sparse dataset and present a ranked list of municipalities based on their overall VL capability. We discuss improvements to our models, and additional applications.

Cutaneous leishmaniasis (CL) remains one of the world’s most prevalent neglected diseases, particularly in developing countries. Identification of the involved Leishmania species is an important step in the diagnosis and case management process. In this study, we tested simple, rapid, and highly sensitive loop-mediated isothermal amplification (LAMP) assays for Leishmania DNA species-specific detection from cutaneous lesions. Two LAMP assays, targeting cysteine protease B (cpb) gene, were developed to detect and identify Leishmania major and Leishmania tropica species. Loop-mediated isothermal amplification specificity was examined using DNA samples from other Leishmania species and Trypanosoma species. No cross-reactions were detected. The developed LAMP assays exhibited sensitivity with a detection limit of 20 fg and 200 fg for L. major and L. tropica, respectively. Both tests were applied on clinical samples of CL suspected patients living in endemic Tunisian regions and compared with kinetoplast DNA quantitative PCR (qPCR), microscopic, and conventional cpb-based polymerase chain reaction (PCR) assays. Our LAMP tests were able to discriminate between L. major and L. tropica species and showed a sensitivity of 84% and a specificity of 100%. However, when compared with the performance of the diagnostic tests with latent class analysis (LCA), our LAMP assays show a sensitivity of 100%. These assays can be used as a first-line molecular test for early diagnosis and prompt management of CL cases in public health programs.

War provides ideal grounds for the outbreak of infectious diseases, and the Syrian war is not an exception to this rule. Following the civil crisis, Syria and refugee camps of neighboring countries witnessed an outbreak of leishmaniasis. We accessed the database of the central leishmaniasis registry in Latakia city and obtained the leishmaniasis data of the period 2008–2016. Our data showed that the years 2013 and 2014 recorded a surge in the number of both cutaneous leishmaniases (CL) and visceral leishmaniasis (VL) cases. This surge coincided with the massive internal displacement waves that struck Latakia governorate during that time. Subsequently, after 2015, the number of recorded CL and VL cases gradually decreased. This drop coincided with a reduced influx of internally displaced persons into Latakia governorate. Our report depicts the effects of the Syrian crisis on the epidemiology of leishmaniasis by outlining the experience of Latakia governorate. Similar results may have occurred in other refugee-hosting Syrian governorates.

Chagas disease is caused by the protozoan Trypanosoma cruzi. This disease is distributed in 21 Latin American countries, where it is mostly vector-borne. In Brazil, there are 68 triatomine species. To date, the epidemiological surveys indicate that the state of São Paulo presents 11 species of triatomines, and most of these species have already been collected in a home environment and found to be infected with T. cruzi. Problems in correctly identifying species can lead to incorrect panorama of distribution of Chagas disease vectors. Thus, we developed an identification key for the triatomines of the state of São Paulo, based on cytogenetic data. With the exception of Panstrongylus diasi that does not present cytogenetic data available in the literature, all species were differentiated by cytogenetic characteristics. We emphasize the importance of using this key as a simple and objective tool in the entoepidemiological surveys conducted by the vector control programs.

Medication adherence is critical to the effectiveness of benznidazole (BZ) therapy for the treatment of Chagas disease. Assessing BZ adherence using traditional plasma sampling methods presents numerous challenges in resource-limited settings. Dried blood spot (DBS) sampling of BZ can be used to overcome logistical barriers and provides a less invasive method for assessing BZ levels. A BZ DBS assay using liquid chromatography-tandem mass spectrometry was developed and applied to a clinical study of infants and children being treated with BZ for Trypanosoma cruzi infection in Argentina. The assay was validated over a concentration range of 9.8–5,000 ng/mL. Inter-assay and intra-assay measures ranged from −2.9% to 2.7% and 0.5% to 8.3% for accuracy and from 3.5% to 12% and 1.6% to 13.6% for precision, respectively. The mean recovery of BZ was greater than 91%. Partitioning ratios for DBSs/plasma ranged from 0.95 to 1.02. A cohort of 10 infants and six children with T. cruzi infection being treated with BZ had median BZ concentrations of 1.2 (IQR 0.29, 2.14) µg/mL with seven of 65 (11%) samples above the BZ treatment goal of 3 μg/mL for adults. The reported DBS assay is a simple and accurate method for the quantitative measurement of BZ that can be applied to facilitate urgently needed clinical studies of BZ for the treatment of Chagas disease and assess BZ adherence in resource-limited settings.

We report the case of a 64-year-old woman found to have urban-acquired Trypanosoma brucei (T.b.) gambiense human African trypanosomiasis (HAT) as the cause of sustained fever starting 9 months after returning to Canada from Democratic Republic of the Congo, in the context of concomitant multiple myeloma and HIV-1 coinfection. Approaches for the management of both clinical stages of T.b. gambiense HAT are well defined for endemic settings using current diagnostics and treatments. However, few data inform the diagnosis and management of patients with bone marrow suppression from active malignancy, recent anticancer therapy, or HIV coinfection. We discuss the implications of immunosuppression for diagnosis and management of T.b. gambiense HAT.

Malaria transmission is dependent on the density and distribution of mosquito vectors, but drivers of vector abundance have not been adequately studied across a range of transmission settings. To inform intervention strategies for high-burden areas, further investigation is needed to identify predictors of vector abundance. Active household (HH) surveillance was conducted in Nchelenge district, Luapula Province, northern Zambia, a high-transmission setting with limited impact of malaria control. Between April 2012 and July 2017, mosquitoes were collected indoors during HH visits using CDC light traps. Demographic, environmental, and climatological correlates of vector abundance were identified using log-binomial regression models with robust standard errors. The primary malaria vectors in this setting were Anopheles funestus sensu stricto (s.s.) and Anopheles gambiae s.s. Anopheles funestus predominated in both seasons, with a peak in the dry season. Anopheles gambiae peaked at lower numbers in the rainy season. Environmental, climatic, and demographic factors were correlated with HH vector abundance. Higher vector counts were found in rural areas with low population density and among HHs close to roads and small streams. Vector counts were lower with increasing elevation and slope. Anopheles funestus was negatively associated with rainfall at lags of 2–6 weeks, and An. gambiae was positively associated with rainfall at lags of 3–10 weeks. Both vectors had varying relationships with temperature. These results suggest that malaria vector control in Nchelenge district should occur throughout the year, with an increased focus on dry-season transmission and rural areas.

Test positivity rate (TPR)—confirmed cases per 100 suspected cases tested, and test-confirmed malaria case rate (IR)—cases per 1,000 population, are common indicators used routinely for malaria surveillance. However, few studies have explored relationships between these indicators over time and space. We studied the relationship between these indicators in children aged < 11 years presenting with suspected malaria to the outpatient departments of level IV health centers in Nagongera, Kihihi, and Walukuba in Uganda from October 2011 to June 2016. We evaluated trends in indicators over time and space, and explored associations using multivariable regression models. Overall, 65,710 participants visited the three clinics. Pairwise comparisons of TPR and IR by month showed similar trends, particularly for TPRs < 50% and during low-transmission seasons, but by village, the relationship was complex. Village mean annual TPRs remained constant, whereas IRs drastically declined with increasing distance from the health center. Villages that were furthest away from the health centers (fourth quartile for distance) had significantly lower IRs than nearby villages (first quartile), with an incidence rate ratio of 0.40 in Nagongera (95% CI: 0.23–0.63; P = 0.001), 0.55 in Kihihi (0.40–0.75; P < 0.001), and 0.25 in Walukuba (0.12–0.51; P < 0.001). Regression analysis results emphasized a nonlinear (cubic) relationship between TPR and IR, after accounting for month, village, season, and demographic factors. Results show that the two indicators are highly relevant for monitoring malaria burden. However, interpretation differs with TPR primarily indicating demand for malaria treatment resources and IR indicating malaria risk among health facility catchment populations.

Data on fever and malaria cases reported by health facilities are used for tracking incidence and quantification of malaria commodity needs in Guinea. Periodic assessments of the quality of malaria case management and routine data are a critical activity for the malaria program. In May–June 2018, survey teams visited 126 health facilities in six health districts purposefully selected to represent a spectrum (Stratum 1—high, Stratum 2—intermediate, and Stratum 3—low) of perceived quality of case management and reporting, as assessed from an a priori analysis of routine data. Surveyors performed exit interviews with 939 outpatients and compared results with registry data for interviewed patients. Availability of rapid diagnostic tests (RDTs) and artemisinin-based combination therapies (ACTs) was 100% in Strata 1 and 2, compared with 82% (95% CI: 63–92%) for RDTs and 86% (68–95%) for any formulation of ACT in Stratum 3. Correct case management for suspect malaria cases was 85% in both Stratum 1 (95% CI: 78–90%) and Stratum 2 (79–89%), but only 52% (37–67%) in Stratum 3. Concordance between exit interviews and registry entries for key malaria indicators was significantly higher in Strata 1 and 2 than in Stratum 3. Both adherence to national guidelines for testing and treatment and data quality were high in Strata 1 and 2, but substandard in Stratum 3. The survey results reflected the trends seen in the routine data, suggesting that analysis of routine data can identify areas requiring more attention to improve malaria case management and reporting.

Intrahepatic pseudoaneurysm (IHPA) is generally iatrogenic, and it warrants urgent management because of its reportedly significant risk of rupture leading to considerable mortality. Intrahepatic pseudoaneurysm caused by amebic liver abscess (ALA) is exceedingly rare with fewer than seven published reports. All reported symptomatic cases have been treated with hepatic artery embolization; therefore, little is known about its natural course and effect of abscess drainage on its outcome. We report the first case of symptomatic intracavitary IHPA caused by ALA in which ultrasound-guided percutaneous catheter drainage of the abscess resulted in the spontaneous resolution of the IHPA.

Cryptosporidium is a parasite that causes watery diarrhea among both children and adults. However, because many physicians do not routinely ask for Cryptosporidium diagnostic test, cryptosporidiosis prevalence is likely underestimated. The current study investigated the prevalence of cryptosporidiosis among children admitted to the hospital with gastrointestinal symptoms. Stool sample was collected from each child and subjected to routine microbiological culture. Cryptosporidium presence was tested by three different methods: real-time PCR (RT-PCR), quick antigen, and microscopic examination with acid-fast staining. Each positive specimen was further tested with BioFire FilmArray Multiplex PCR (bioMérieux SA, Marcy-l'Etoile, France) to determine that Cryptosporidium is the only pathogen in the sample. Demographic and epidemiological data were collected from the patients’ medical records. Of 291 patient stool samples, nine were positive for Cryptosporidium hominis or Cryptosporidium parvum. The average age of the nine Cryptosporidium-positive cases was 2.3 years, lower than the average age of the study population (4.2 years). Of the positive cases, 66.7% were Arabs and 33.3% were Jews. The main complaint of children with Cryptosporidium was diarrhea. Regarding the laboratory methods for Cryptosporidium identification, of the positive samples, 100% (9/9) were identified by RT-PCR, 88% (8/9) were positive by antigen test, and only 67% (6/9) were positive by microscopic examination with acid-fast staining. Because of the low incidence of Cryptosporidium among patients in our facility, the prevalence of cryptosporidiosis still cannot be established. Nevertheless, among the other pathogens found in stool samples, Cryptosporidium is the second leading cause of hospitalization due to gastrointestinal disease in children in our area.

The CYD-TDV vaccine is licensed in multiple endemic countries based on vaccine efficacy (VE) against symptomatic, virologically confirmed dengue demonstrated in two phase 3 trials (CYD14, 2- to 14-year-olds, Asia; CYD15, 9- to 16-year-olds, Latin America). 50% plaque reduction neutralization test (PRNT50) titers at baseline and month 13 (post-vaccination) were associated with VE and may enable bridging VE to adults. Two phase 2 trials of CYD-TDV measured baseline and month 13 PRNT50 titers: CYD22 (9- to 45-year-olds, Vietnam) and CYD47 (18- to 45-year-olds, India). 50% plaque reduction neutralization test distributions were compared between age cohorts, and four versions of an epidemiological bridging method were used to estimate VE against any serotype (dengue virus [DENV]-Any) and against each serotype over 25 months post first vaccination in a hypothetical CYD14 + CYD15 18- to 45-year-old cohort (bridging population 1) and in the actual CYD47 18- to 45-year-old cohort (bridging population 2). Baseline and month 13 geometric mean PRNT50 titers to each serotype were significantly greater in 18- to 45-year-olds than 9- to 16-year-olds for all comparisons. The four methods estimated VE against DENV-Any at 75.3–86.0% (95% CIs spanning 52.5–100%) for bridging population 1 and 68.4–77.5% (95% CIs spanning 42.3–88.5%) for bridging population 2. The vaccine efficacy against serotype 1, 2, 3, and 4 was estimated at 56.9–76.9%, 68.3–85.8%, 91.4–95.0%, and 93.2–100% (bridging population 1) and 44.5–66.9%, 53.2–69.2%, 79.8–92.0%, and 90.6–95.0% (bridging population 2), respectively; thus, CYD-TDV would likely confer improved efficacy in adults than 9- to 16-year-olds. Using the same methods, we predicted VE against hospitalized DENV-Any over 72 months of follow-up, with estimates 59.1–73.5% (95% CIs spanning 40.9–92.2%) for bridging population 1 and 50.9–65.9% (95% CIs spanning 38.1–82.1%) for bridging population 2.

Faced with the reemergence of yellow fever (YF) in the metropolitan region of São Paulo, Brazil, we developed a retrospective study to describe the cases of YF attended at the Institute of Infectology Emilio Ribas from January to March 2018 and analyze the factors associated with death, from the information obtained in the hospital epidemiological investigation. A total of 72 cases of sylvatic YF were confirmed, with 21 deaths (29.2% lethality rate). Cases were concentrated in males (80.6%) and in the age group of 30 to 59 years (56.9%). Two logistic regression models were performed, with continuous variables adjusted for the time between onset of symptoms and hospitalization. The first model indicated age (odds ratiosadjusted [ORadj]: 1.038; CI 95%: 1.008–1.212), aspartate aminotransferase (AST) (ORadj: 1.038; CI 95%: 1.005–1.072), and creatinine (ORadj: 2.343; CI 95%: 1.205–4.553) were independent factors associated with mortality. The second model indicated age (ORadj: 1.136; CI 95%: 1.013–1.275), alanine aminotransferase (ALT) (ORadj: 1.118; CI 95%: 1.018–1.228), and creatinine (ORadj: 2.835; CI 95%: 1.352–5,941). The risk of death in the model with continuous variables was calculated from the increase of 1 year (age), 1 mg/dL (creatinine), and 100 U/L for AST and ALT. Another logistic regression analysis with dichotomous variables indicated AST > 1,841 IU/L (ORadj: 12.92; CI 95%: 1.50–111.37) and creatinine > 1.2 mg/dL (ORadj: 81.47; CI 95%: 11.33–585.71) as independent factors associated with death. These results may contribute to the appropriate clinical management of patients with YF in health-care services and improve the response to outbreaks and public health emergencies.

Tick-borne encephalitis (TBE) is a viral infectious disease and has become a reemerging public health threat in recent years in northeastern China. However, no studies has characterized the epidemiologic features and explored the spatial dynamics and environmental factors of TBE cases in Jilin Province. In this study, we have described the epidemiological features of 846 reported human TBE cases from 2006 to 2016 in Jilin Province. There was an obvious single peak pattern of TBE cases from May to July in Jilin Province. More than 60% of TBE cases occurred in farmers, and the people in 50- to 59-year-old group had the high incidence of the disease. The results of Getis-Ord Gi* statistics demonstrated that the human TBE cases were more clustered in the northeastern border including Dunhua and Yanji cities and Antu and Wangqing counties, and southern areas including Huinan, Jingyu, Jiangyuan, and Liuhe counties in Jilin Province. We demonstrated that the temporal dynamics of TBE in Jilin was significantly associated with the dynamics of meteorological factors especially after 2009. The results from the auto-logistic regression analysis showed that the percentage coverage of forest, temperature, and autoregressive term were significantly associated with the occurrence of human TBE cases in Jilin Province. Our findings will provide a scientific evidence for the targeted prevention and control programs.

Filoviruses, which include ebolaviruses and marburgvirus, can cause outbreaks of highly lethal hemorrhagic fever. This disease causes significant morbidity and mortality in humans and non-human primates, with human fatality rates reaching 90% during some outbreaks. Currently, there is lack of licensed vaccines or antivirals for these viruses. Since early symptoms of filovirus infection mimic more common diseases, there is a strong unmet public health and biodefense need for broad-spectrum filovirus rapid diagnostics. We have generated a panel of mouse single-chain Fv-antibodies (scFvs) to filovirus glycoproteins (GPs) using cell-free ribosome display and determined their cross-reactivity profiles to all known filovirus species. Two scFvs (4-2 and 22-1) were able to detect all known Ebolavirus and Marburgvirus species. This is the first report on ribosome display scFvs that can detect a broad set of filovirus GPs, which demonstrates the potential for use in diagnostics.

rVSVΔG-ZEBOV-GP vaccine is a live recombinant (r) vesicular stomatitis virus (VSV), where the VSV G protein is replaced with the Zaire Ebola virus (ZEBOV) glycoprotein (GP). For vaccine immunogenicity testing, clinical trial sera collected during an active ZEBOV outbreak underwent gamma irradiation (GI) before testing in biosafety level 2 laboratories to inactivate possible wild-type ZEBOV. Before irradiating pivotal trial samples, two independent studies evaluated the impact of GI (50 kGy) on binding ZEBOV-GP (ELISA) antibodies against rVSVΔG-ZEBOV-GP, using sera from a North American phase 1 study. Gamma irradiation was associated with slightly higher antibody concentrations in pre-vaccination samples and slightly lower concentrations postvaccination. Results indicate that GI is a viable method for treating samples from regions where filoviruses are endemic, with minor effects on antibody titers. The impact of GI on immunogenicity analyses should be considered when interpreting data from irradiated specimens.

In 2016, the World Health Assembly endorsed the Global Health Sector Strategy on Viral Hepatitis, which calls for elimination of hepatitis B virus (HBV) by 2030 (definition: ≤ 0.1% hepatitis B surface antigen [HBsAg] prevalence among children aged 5 years). The burden of chronic HBV infection among children in Haiti is unknown. We conducted a nationally representative cross-sectional serological survey among 5- to 7-year-old children based on a two-stage cluster design with two strata: West (includes metropolitan Port-au-Prince) and non-West (all other departments). We collected demographic, socioeconomic, and vaccination history data and tested for HBsAg using a rapid point-of-care test. We estimated HBsAg prevalence and evaluated the association of HBV infection with vaccination history, demographics, and socioeconomic characteristics. Of the 1,152 children, seven (0.5%, 95% CI: 0.2–1.2) were HBsAg positive. The HBsAg prevalence varied by region (West: 0.1%, 95% CI: 0.01–0.9; non-West: 0.7%, 95% CI: 0.2–1.9) (P = 0.1), gender (males: 0.7%, 95% CI: 0.2–2.4; females: 0.2%, 95% CI: 0.05–1.1) (P = 0.3), and caregiver’s education level (none: 0.8%, 95% CI: 0.2–3.1; some or completed primary: 0.5%, 95% CI: 0.1–1.8; some secondary: 0.4%, 95% CI: 0.1–1.8; secondary and higher: 0.0%, 95% CI: 0–0), although the differences were not statistically significant. None of the HBsAg-positive children had documented vaccination with hepatitis B vaccine (HepB). Haiti’s chronic HBV infection prevalence among children is low; however, it is above the elimination target. To reach elimination, Haiti needs to achieve high coverage with the three HepB doses and introduce a HepB birth dose.

The albumin–bilirubin (ALBI) score was originally established to stratify prognosis in patients with cirrhosis. The diagnostic accuracy of ALBI score in liver fibrosis staging in patients with chronic hepatitis B remains to be investigated. The present retrospective study, therefore, aimed to evaluate the ability of this score to stage liver fibrosis in these patients. Briefly, consecutive patients with hepatitis B virus (HBV) infection who underwent liver biopsy examinations in Kagawa University Hospital were enrolled. Liver fibrosis stage was assessed using a modified Meta-Analysis of Histological Data in Viral Hepatitis score. Albumin–bilirubin scores were calculated according to the following equation: (log10 total bilirubin [T-Bil] × 0.66) + (albumin [Alb] × −0.085). A total of 91 patients were enrolled in this study. Albumin–bilirubin score was able to differentiate stage 4 from stage 3 fibrosis (P < 0.05). When an ALBI score of −2.190 was adopted as the cutoff value for differentiating stage 4 from stages 1–3, the sensitivity, specificity, and positive likelihood ratio were 85.7%, 74.0%, and 3.300, respectively. Kaplan–Meier analysis showed that baseline ALBI scores < −2.190 correlated with better hepatocellular carcinoma (HCC)–free survival (P < 0.05). In conclusion, ALBI score can be used for liver fibrosis staging in Japanese chronic hepatitis B patients and can help distinguish cirrhotic from non-cirrhotic status. Furthermore, ALBI score was useful as a prognosis biomarker in our patients, with smaller ALBI scores predicting better HCC-free survival. Because calculating ALBI score is easy using serum T-Bil and Alb alone, ALBI score will help clinicians with decision-making in management of HBV-infected patients.

Hepatitis B virus (HBV) is endemic throughout Africa, but its prevalence in the Democratic Republic of the Congo (DRC) is incompletely understood. We used dried blood spot (DBS) samples from the 2013 to 2014 Demographic and Health Survey in the DRC to measure the prevalence of HBV using the Abbott ARCHITECT HBV surface antigen (HBsAg) qualitative assay. We then attempted to sequence and genotype HBsAg-positive samples. The weighted national prevalence of HBV was 3.3% (95% CI: 1.8–4.7%), with a prevalence of 2.2% (95% CI: 0.3–4.1%) among children. Hepatitis B virus cases occurred countrywide and across age strata. Genotype E predominated (60%), and we found a unique cluster of genotype A isolates (30%). In conclusion, DBS-based HBsAg testing from a nationally representative survey found that HBV is common and widely distributed among Congolese adults and children. The distribution of cases across ages suggests ongoing transmission and underscores the need for additional interventions to prevent HBV infection.

Hepatitis E virus (HEV) infection is associated with a high fatality rate among pregnant women, and gestational complications have been reported among pregnant women infected with hepatitis A virus (HAV). The aim of this study was to determine the seroprevalence of HAV and HEV infections among pregnant women in Haiti. We stratified the population (n = 1,307) between West and non-West regions. Specimens were tested for total HAV antibody (anti-HAV), and IgM and IgG HEV antibody (anti-HEV). Overall, 96.8% pregnant women were positive for total anti-HAV, 10.3% for IgG anti-HEV, and 0.3% for IgM anti-HEV. The prevalence of IgG anti-HEV in the non-West region (12.3%) was significantly greater than that in the West region (5.3%) (P < 0.0001). Most pregnant women in Haiti had evidence of past exposure and immunity to HAV. The non-West region had a higher prevalence of HEV. Improvement in water and sanitation will help in the prevention and control of these infections in Haiti.

Japanese encephalitis virus (JEV) is the most common cause of viral encephalitis in Asia, and it is increasingly a global public health concern because of its recent geographic expansion. Although commercial vaccines are available and used in some endemic countries, JEV continues to cause illness, with more than 60,000 cases reported annually. To develop a reproducible positive control antibody useable in diagnosis of JEV infections, murine hybridomas were developed from mice inoculated with a combination of IXIARO JEV vaccine and JEV domain III of the envelope protein (E-DIII). Monoclonal antibodies (MAbs) were characterized for their ability to neutralize virus in vitro. Monoclonal antibody 17BD3-2 was found to be JEV specific and highly neutralizing, with a plaque reduction neutralization test (PRNT)90 endpoint titer of 1.25 μg/mL. The functional epitopes were mapped using virus neutralization escape variants to amino acid residues S309, K312, and G333 in E-DIII. This MAb may be substituted for human immune sera used as a positive control in PRNT for distribution to public health laboratories worldwide in potential future outbreaks of JEV.

Endemic transmission of measles has been reestablished in Venezuela, and outbreaks of diphtheria remain ongoing across Latin America (LA). Hence, a large cross-sectional population-based serosurveillance study was conducted on Bonaire, one of the Dutch Leeward Antilles, to assess specific age and population groups at risk. Participants (aged 0–90 years) donated a blood sample and completed a questionnaire (n = 1,129). Antibodies against measles and diphtheria were tested using bead-based multiplex immunoassays. Our data revealed that immunity against measles is suboptimal, especially for those aged less than 5 years from Suriname, Aruba, and former Dutch Antilles (SADA), and adolescents from LA; and against diphtheria for persons aged more than 30 years, particularly among females and residents from SADA and LA. As refugees arrive persistently, health authorities on the Dutch Leeward Antilles should be on alert to detect early cases and prevent subsequent transmission. Ultimately, there is an urgent need for serosurveillance studies in the Caribbean region.

Anemia is known to impact a child’s growth and development, but not all anemias are caused by iron deficiency, and the CDC and WHO have emphasized investigating other contributors to anemia. This cross-sectional sub-study of a 2012–2016 maternal-child cohort in coastal Kenya evaluated 244 children and found 185 (76%) to have been anemic on at least one time point since birth. At the time of assessment in 2016, evaluation included a complete blood count, nutritional assessment, and testing for parasitic infections, focusing on the primary outcome of anemia, defined as hemoglobin (Hb) < 11 g/dL. The average age at assessment was 20.5 ± 7 months. Ninety-five percent had a lifetime average Hb in the anemic range. Adjusting for age and gender, prior or current malaria infection (prior: Hb β = −0.99, 95% CI: −1.49 to −0.49, P = 0.01), or having any current infection with hookworm, Trichuris, Strongyloides, Ascaris, and/or malaria (β = −0.84, 95% CI: −1.36 to −0.33, P = 0.01) was associated with decreased current Hb. Nutritional evaluation revealed that children with a declining Hb ate fewer vitamin-A–rich vegetables per week (P = 0.01) or eggs (P = 0.01), drank more milk (P = 0.07), and ate more bread (P = 0.01), and were more likely to live in a household that experienced food shortage (P = 0.05). The high prevalence of anemia, polyparasitism, and dietary insufficiency among children in rural coastal Kenya suggests that remedial interventions will need to address both diet and parasitic infections to effectively combat this significant health threat.

The etiology of infections of the central nervous system (CNS) in Nepal often remains unrecognized because of underdeveloped laboratory facilities. The aim of this study was to investigate the etiology of CNS infections in a rural area of Nepal using molecular methods. From November 2014 to February 2016, cerebrospinal fluid (CSF) was collected from 176 consecutive patients presenting at United Mission Hospital in Tansen, Nepal, with symptoms of possible CNS infection. After the CSF samples were stored and transported frozen, polymerase chain reaction (PCR) was performed in Sweden, targeting a total of 26 pathogens using the FilmArray® ME panel (BioFire, bioMerieux, Salt Lake City, UT), the MeningoFinder® 2SMART (PathoFinder, Maastricht, The Netherlands), and an in-house PCR test for dengue virus (DENV), Japanese encephalitis virus (JEV), and Nipah virus (NiV). The etiology could be determined in 23%. The bacteria detected were Haemophilus influenzae (n = 5), Streptococcus pneumoniae (n = 4), and Neisseria meningitidis (n = 1). The most common virus was enterovirus detected in eight samples, all during the monsoon season. Other viruses detected were cytomegalovirus (n = 6), varicella zoster virus (n = 5), Epstein–Barr virus (n = 3), herpes simplex virus (HSV) type 1 (HSV-1) (n = 3), HSV-2 (n = 3), human herpes virus (HHV) type 6 (HHV-6) (n = 3), and HHV-7 (n = 2). Cryptococcus neoformans/gatti was found in four samples. None of the samples were positive for DENV, JEV, or NiV. Of the patients, 67% had been exposed to antibiotics before lumbar puncture. In conclusion, the etiology could not be found in 77% of the samples, indicating that the commercial PCR panels used are not suitable in this setting. Future studies on the etiology of CNS infections in Nepal could include metagenomic techniques.

Subacute sclerosing panencephalitis (SSPE) is still a common disease in India which is characterized by a progressive mental decline, myoclonus, periodic encephalographic abnormalities, and raised anti-measles antibody titter in the cerebrospinal fluid. Acute fulminant SSPE is characterized by a rapid course of disease culminating in death, within 6 months. We report of a 10-year-old boy, who came with a 14-day history of continuous involuntary jerky movements of the left half of the body, including the head. There was a highly increased anti-measles IgG antibody titer, both in the cerebrospinal fluid and serum. We conclude that acute rapidly progressive SSPE can present as acute encephalitis syndrome.

This qualitative study assessed the knowledge and beliefs surrounding fever syndrome among adult febrile patients seeking health care in Kilombero, Tanzania. From June 11 to July 13, 2014, 10% of all adult (≥ 15 years) febrile patients enrolled in the larger syndromic study, who presented with an axillary temperature ≥ 37.5°C and symptom onset ≤ 5 days prior, were randomly selected to participate in an in-depth physician–patient interview, informed by Health Belief Model constructs. Interviews were audio recorded, translated, and transcribed. Transcripts were coded using NVivo Version 11.1, and the thematic content was analyzed by two separate researchers. Blood and nasopharyngeal/oralpharyngeal specimens were collected and analyzed using both acute febrile illness and respiratory TaqMan Array Cards for multipathogen detection of 56 potential causative agents. A total of 18 participants provided 188 discrete comments. When asked to speculate the causative agent of febrile illness, 33.3% cited malaria and the other 66.6% offered nonbiomedical responses, such as “mosquitoes” and “weather.” Major themes emerging related to severity and susceptibility to health hazards included lack of bed net use, misconceptions about bed nets, and mosquito infestation. Certain barriers to treatment were cited, including dependence on traditional healers, high cost of drugs, and poor dispensary services. Overall, we demonstrate low concurrence in speculations of fever etiology according to patients, clinicians, and laboratory testing. Our findings contribute to the important, yet limited, base of knowledge surrounding patient risk perceptions of febrile illness and underscore the potential utility of community-based participatory research to inform disease control programs.

The transmission assessment survey (TAS) is recommended to determine whether cessation of mass drug administration (MDA) for lymphatic filariasis (LF) is warranted. Ministries of health typically implement TASs in evaluation units (EUs) that have had more than five rounds of annual MDA. Under TAS guidelines, sample size calculations determine a decision value: if the number of individuals testing positive exceeds this threshold, then MDA continues in the EU. The objective of this study was to determine whether fine scale geospatial covariates could be used to identify predictors of TAS failure. We geo-referenced 746 TAS EUs, of which 65 failed and extracted geospatial covariates using R to estimate odds of failure. We implemented stepwise backward elimination to select covariates for inclusion in a logistic regression to estimate the odds of TAS failure. Covariates included environmental predictors (aridity, distance to fresh water, elevation, and enhanced vegetation index), cumulative rounds of MDA, measures of urbanicity and access, LF species, and baseline prevalence. Presence of Brugia was significantly associated with TAS failure (odds ratio [OR]: 4.79, 95% CI: 2.52–9.07), as was population density (OR: 2.91, 95% CI: 1.06–7.98). The presence of nighttime lights was highly protective against failure (OR: 0.22, 95% CI: 0.10–0.50), as was an increase in elevation (OR: 0.36, 95% CI: 0.18–0.732). This work identifies predictors associated with TAS failure at the EU areal level, given the data presently available, and also identifies the need for more granular data to conduct a more robust assessment of these predictors.