The American Journal of Tropical Medicine and Hygiene - Volume 92, Issue 5, May 2015

We evaluated the monthly distribution of rotavirus diarrhea in a cohort of children 12–24 months of age followed as part of a diarrhea clinical trial in a peri-urban community of Lima. We observed a peak of rotavirus diarrhea in the winter months and a decrease in rotavirus prevalence after the introduction of the rotavirus vaccine in Peru.

We have previously shown that anti–dengue virus nonstructural protein 1 (anti-DENV NS1) antibodies cross-react with endothelial cells, and several autoantigens have been identified. This study shows that the antibody levels against these self-proteins are higher in sera from patients with dengue hemorrhagic fever (DHF) than those in control sera. Anti–protein disulfide isomerase (PDI) and anti–heat shock protein 60 (anti-HSP60) IgM levels correlated with both anti–endothelial cells and anti-DENV NS1 IgM titers. A cross-reactive epitope on the NS1 amino acid residues 311–330 (P311–330) had been predicted. We further found that there were higher IgM and IgG levels against P311–330 in DHF patients' sera than those in the control sera. In addition, correlations were observed between anti-PDI with anti-P311–330 IgM and IgG levels, respectively. Therefore, our results indicate that DENV NS1 P311–330 is a major epitope for cross-reactive antibodies to PDI on the endothelial cell surface, which may play an important role in DENV infection–induced autoimmunity.

Autochthonous dengue virus transmission has occurred in the continental United States with increased frequency during the last decade; the principal vector, Aedes aegypti, has expanded its geographic distribution in the southern United States. Dengue, a potentially fatal arboviral disease, is underreported, and US clinicians encountering patients with acute febrile illness consistent with dengue are likely to not be fully familiar with dengue diagnosis and management. Recently, investigators suggested that an outbreak of dengue likely occurred in Houston during 2003 based on retrospective laboratory testing of hospitalized cases with encephalitis and aseptic meningitis. Although certain aspects of the Houston testing results and argument for local transmission are doubtful, the report highlights the importance of prospective surveillance for dengue in Aedes-infested areas of the United States, the need for clinical training on dengue and its severe manifestations, and the need for laboratory testing in domestic patients presenting with febrile neurologic illness in these regions to include dengue.

Studies on serotype-specific features of dengue and disease severity on adults are limited. We prospectively recruited adult febrile patients without alternate diagnosis to dengue from April 2005 to December 2011. Outcomes were defined using both the World Health Organization (WHO) 1997 and 2009 criteria; Dengue hemorrhagic fever (DHF) and severe dengue (SD). Infecting serotype was identified in 469 dengue-confirmed patients comprising 22.0% dengue virus serotype 1 (DENV-1), 57.1% DENV-2, 17.1% DENV-3, and 3.8% DENV-4. Cases infected with DENV-1 were more likely to present with red eyes whereas presence of joint pain and lower platelet count was associated with DENV-2 cases. After adjusting for potential confounders, DENV-1 was associated with both DHF (adjusted Relative Risk [aRR] = 1.74) and SD (aRR = 2.1) whereas DENV-2 had a lower risk of DHF (aRR = 0.5). DENV-1 genotype 1 and DENV-2 cosmopolitan were the predominant genotypes identified. Infecting dengue serotype and possibly genotype may play an important role in disease severity among adult dengue patients in Singapore.

The Houston West Nile Cohort (HWNC) was founded in 2002 when West Nile virus (WNV) reached Houston, TX. The long-term outcomes following WNV infection are still mostly unknown, though neurological abnormalities up to 1 year postinfection have been documented. We report an observational study of neurological abnormalities at 1–3 and 8–11 years following WNV infection in the HWNC. We conducted standard neurological examinations at two separate time points to assess changes in neurological status over time. The majority of patients (86%, 30/35) with encephalitis had abnormal neurological exam findings at the time of the first assessment compared with uncomplicated fever (27%, 3/11) and meningitis (36%, 5/14) cases. At the time of the second assessment, 57% (4/7) of West Nile fever (WNF), 33% (2/6) of West Nile meningitis (WNM), and 36% (5/14) of West Nile encephalitis (WNE) had developed new neurological complications. The most common abnormalities noted were tandem gait, hearing loss, abnormal reflexes, and muscle weakness. Long-term neurological abnormalities were most commonly found in patients who experienced primary WNV encephalitis. New abnormalities may develop over time regardless of initial clinical infection. Future studies should aim to differentiate neurological consequences due to WNV neuroinvasive infection versus neurological decline related to comorbid conditions.

West Nile virus (WNV) is a leading cause of mosquito-borne disease in the United States. Annual seasonal outbreaks vary in size and location. Predicting where and when higher than normal WNV transmission will occur can help direct limited public health resources. We developed models for the contiguous United States to identify meteorological anomalies associated with above average incidence of WNV neuroinvasive disease from 2004 to 2012. We used county-level WNV data reported to ArboNET and meteorological data from the North American Land Data Assimilation System. As a result of geographic differences in WNV transmission, we divided the United States into East and West, and 10 climate regions. Above average annual temperature was associated with increased likelihood of higher than normal WNV disease incidence, nationally and in most regions. Lower than average annual total precipitation was associated with higher disease incidence in the eastern United States, but the opposite was true in most western regions. Although multiple factors influence WNV transmission, these findings show that anomalies in temperature and precipitation are associated with above average WNV disease incidence. Readily accessible meteorological data may be used to develop predictive models to forecast geographic areas with elevated WNV disease risk before the coming season.

Influenza accounts for a large burden of acute respiratory tract infections in high-income countries; data from lower-income settings are limited due to lack of confirmatory testing. Consecutive outpatients presenting to the largest tertiary care hospital in southern Sri Lanka were surveyed for influenza-like illness (ILI), defined as acute onset of fever ≥ 38.0°C and cough. Patients were administered a questionnaire and nasal/nasopharyngeal sampling for rapid influenza A/B testing. We enrolled 311 patients with ILI from March to November 2013: 170 (54.7%) children and 172 (55.3%) males. Approximately half (147, 47.3%) tested positive for influenza, but 253 (81.4%) were prescribed antibiotics. On bivariable analysis, symptoms associated with influenza included pain with breathing (P < 0.001), headache (P = 0.005), fatigue (P = 0.003), arthralgias (P = 0.003), and myalgias (P = 0.006) in children and pain with breathing (P = 0.01), vomiting (P = 0.03), and arthralgias (P = 0.03) in adults. Our final clinical predictive models had low sensitivity and fair specificity—50.0% (95% CI: 38.6–61.4%) and 83.2% (95% CI: 73.4–90.0%), respectively, in children and 52.2% (95% CI: 39.9–64.2%) and 81.4% (95% CI: 70.0–89.4%), respectively, in adults. Our study confirms the ability of rapid influenza testing to identify an influenza epidemic in a setting in which testing is not routinely available.

In Kenya, more than 10 million episodes of acute febrile illness are treated annually among children under 5 years. Most are clinically managed as malaria without parasitological confirmation. There is an unmet need to describe pathogen-specific etiologies of fever. We enrolled 370 febrile children and 184 healthy controls. We report demographic and clinical characteristics of patients with Plasmodium falciparum, group A streptococcal (GAS) pharyngitis, and respiratory viruses (influenza A and B, respiratory syncytial virus [RSV], parainfluenza [PIV] types 1–3, adenovirus, human metapneumovirus [hMPV]), as well as those with undifferentiated fever. Of febrile children, 79.7% were treated for malaria. However, P. falciparum was detected infrequently in both cases and controls (14/268 [5.2%] versus 3/133 [2.3%], P = 0.165), whereas 41% (117/282) of febrile children had a respiratory viral infection, compared with 24.8% (29/117) of controls (P = 0.002). Only 9/515 (1.7%) children had streptococcal infection. Of febrile children, 22/269 (8.2%) were infected with > 1 pathogen, and 102/275 (37.1%) had fevers of unknown etiology. Respiratory viruses were common in both groups, but only influenza or parainfluenza was more likely to be associated with symptomatic disease (attributable fraction [AF] 67.5% and 59%, respectively). Malaria was overdiagnosed and overtreated. Few children presented to the hospital with GAS pharyngitis. An enhanced understanding of carriage of common pathogens, improved diagnostic capacity, and better-informed clinical algorithms for febrile illness are needed.

We assessed changes in the effect size of risk factors for infant mortality comparing a birth cohort from 2005 to 2010 with a birth cohort from 1993 to 1999 in the Nouna Health and Demographic Surveillance System (HDSS) in Burkina Faso. Single- and three-level Cox proportional hazards regression models were used for analysis. Independent variables among others included year of birth, ethnicity, religion, age of the mother, birth order, death of the mother, being a twin, and distance to the closest health facility. We observed an infant mortality rate of about 51/1,000 person-years. The strongest risk factors were death of the mother and being a twin, which were also the strongest risk factors from the previous analysis period. Compared with the period 1993–1999, the effect of most risk factors decreased, notably ethnicity, religious affiliation, distance to the closest health facility, birth order, and season of birth. The strongest reduction in mortality occurred in the groups with the previously highest infant mortality rates in 1993–1999.

We performed a prospective multicenter study to address the lack of data on the etiology, clinical and demographic features of hospitalized pediatric diarrhea in Ho Chi Minh City (HCMC), Vietnam. Over 2,000 (1,419 symptomatic and 609 non-diarrheal control) children were enrolled in three hospitals over a 1-year period in 2009–2010. Aiming to detect a panel of pathogens, we identified a known diarrheal pathogen in stool samples from 1,067/1,419 (75.2%) children with diarrhea and from 81/609 (13.3%) children without diarrhea. Rotavirus predominated in the symptomatic children (664/1,419; 46.8%), followed by norovirus (293/1,419; 20.6%). The bacterial pathogens Salmonella, Campylobacter, and Shigella were cumulatively isolated from 204/1,419 (14.4%) diarrheal children and exhibited extensive antimicrobial resistance, most notably to fluoroquinolones and third-generation cephalosporins. We suggest renewed efforts in generation and implementation of policies to control the sale and prescription of antimicrobials to curb bacterial resistance and advise consideration of a subsidized rotavirus vaccination policy to limit the morbidity due to diarrheal disease in Vietnam.

We designed and evaluated the accuracy and usability of a device to regulate the volume of fluid dispensed during intravenous drip therapy. The mechanical system was developed in response to a pressing need articulated by clinicians in pediatric wards throughout sub-Saharan Africa, who require a tool to prevent overhydration in children receiving intravenous fluid in settings that lack burettes or electronic infusion pumps. The device is compatible with most intravenous bags and limits the volume dispensed to a preset amount that can be adjusted in 50 mL increments. Laboratory accuracy over a range of clinically-relevant flow rates, initial bag volumes, and target volumes was within 12.0 mL of the target volume. The ease of use is “excellent,” with a mean system usability score of 84.4 out of 100. Use of the device limits the volume of fluid dispensed during intravenous therapy and could potentially reduce the morbidity and mortality associated with overhydration in children receiving intravenous therapy.

The increasing intensification of pork production in southeast Asia necessitates an urgent requirement to better understand the dual impact of pig-associated zoonotic disease on both pig production and human health in the region. Sharing porous borders with five countries and representing many regional ethnicities and agricultural practices, the Lao People's Democratic Republic (Lao PDR) appears well placed to gauge the levels of pig-associated zoonoses circulating in the wider region. Despite this, little is known about the true impact of zoonotic pathogens such as leptospirosis, Trichinella, hepatitis E virus (HEV), Japanese encephalitis (JE), and Taenia solium on human health and livestock production in the country. A comprehensive review of the published prevalences of these five pig-associated zoonoses in Lao PDR has demonstrated that although suspicion remains high of their existence in pig reservoirs across the country, epidemiological data are scarce; only 31 epidemiological studies have been undertaken on these diseases in the past 25 years. A greater understanding of the zoonoses prevalence and subsequent risks associated with pork production in the southeast Asian region could help focus public health and food safety interventions at key points along the value chain, benefiting both livestock producers and the broader animal and human health systems in the region.

The Pediatric Health Information System (PHIS) database collects admission, diagnostic, and treatment data among 44 children's hospitals across the United States (U.S.) and presents an opportunity for travel-associated infectious disease (TAID) surveillance. We calculated cumulative incidence rates among children admitted to 16 PHIS hospitals for dengue, malaria, and typhoid, and pooled TAID using discharge codes from 1999 to 2012. We compared incidence rates before, during, and after the 2007–2009 economic recession. Among 16 PHIS hospitals during the study period (1999–2012), incidence of dengue and pooled TAID (malaria, dengue, typhoid fever) increased significantly, and rates of malaria and typhoid trended upward. Admissions for dengue and pooled TAIDs increased significantly among 16 children's hospitals across the United States from 1999 to 2012. The PHIS database may provide a useful surveillance tool for TAIDs among children in the United States.

Interventions targeting adult mosquitoes are used to combat transmission of vector-borne diseases, including dengue. Without available vaccines, targeting the primary vector, Aedes aegypti, is essential to prevent transmission. Older mosquitoes (≥ 7 days) are of greatest epidemiological significance due to the 7-day extrinsic incubation period of the virus. Age-grading of female mosquitoes is necessary to identify post-intervention changes in mosquito population age structure. We developed models using near-infrared spectroscopy (NIRS) to age-grade adult female Ae. aegypti. To determine if diet affects the ability of NIRS models to predict age, two identical larval groups were fed either fish food or infant cereal. Adult females were separated and fed sugar water ± blood, resulting in four experimental groups. Females were killed 1, 4, 7, 10, 13, or 16 days postemergence. The head/thorax of each mosquito was scanned using a near-infrared spectrometer. Scans from each group were analyzed, and multiple models were developed using partial least squares regression. The best model included all experimental groups, and positively predicted the age group (< or ≥ 7 days) of 90.2% mosquitoes. These results suggest both larval and adult diets can affect the ability of NIRS models to accurately assign age categories to female Ae. aegypti.

Triatomine surveillance in rural areas, artificial ecotypes, and natural ecotopes of the cities of Caturama, Ibipitanga, Macaúbas, and Seabra in the south-central region of the Brazilian state of Bahia was carried out between 2008 and 2013. Natural infection by Trypanosoma cruzi was evaluated in the specimens collected to monitor vectors of Chagas disease. A total of 1,357 specimens were collected, and four species were identified: Triatoma sordida (83%), Triatoma lenti (16.4%), Triatoma pseudomaculata (0.5%), and Panstrongylus geniculatus (0.1%). Triatoma sordida was found in four cities, only 0.7% in intradomiciliary environments. Triatoma lenti was found only in Macaúbas; 8.5% were found in intradomiciliary environments, 88.3% in peridomiciliary environments, and 3.1% in sylvatic environments. Natural infection by T. cruzi was 0.5% for T. sordida and 3.1% T. lenti. All of these cases were found in peridomiciliary environments of Macaúbas. As the results show, triatomines were found in intradomiciliary environments in three cities that were surveyed in the south-central region of the state of Bahia. Thus, an epidemiologic survey should be performed to avoid the risk of transmission to the population.