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Dengue endemicity varies but comparative, multicountry data are extremely limited. An improved understanding is needed to prioritize prevention, including vaccination, which is currently recommended only under specific epidemiological conditions. We used serological study data from 46 geographical sites in 13 countries to estimate dengue force of infection (FOI, the proportion of children seroconverting per year) under assumptions of either age-constant or age-varying FOI, and the age at which 50% and 80% of children had been infected. After exclusions, 13 661 subjects were included. Estimated constant FOI varied widely, from 1.7% (Singapore) to 24.1% (the Philippines). In the site-level analysis 44 sites (96%) reached 50% seroconversion and 35 sites (75%) reached 80% seroconversion by age 18 years, with significant heterogeneity. These findings confirm that children living in dengue-endemic countries receive intense early dengue exposure, increasing risk of secondary infection, and imply serosurveys at fine spatial resolutions are needed to inform vaccination campaigns. [ABSTRACT FROM AUTHOR]

Background: Japanese encephalitis virus (JEV) is a zoonotic, mosquito-borne flavivirus, distributed across Asia. Infections are mostly mild or asymptomatic, but symptoms include neurological disorders, sequelae, and fatalities. Data to inform control strategies are limited due to incomplete case reporting.Methods: We used JEV serological data from a multicountry Asian dengue vaccine study in children aged 2-14 years to describe JEV endemicity, measuring antibodies by plaque reduction neutralization test (PRNT50).Results: A total 1479 unvaccinated subjects were included. A minimal estimate of pediatric JEV seroprevalence in dengue-naive individuals was 8.1% in Indonesia, 5.8% in Malaysia, 10.8% in the Philippines, and 30.7% in Vietnam, translating to annual infection risks varying from 0.8% (in Malaysia) to 5.2% (in Vietnam). JEV seroprevalence and annual infection estimates were much higher in children with history of dengue infection, indicating cross-neutralization within the JEV PRNT50 assay.Conclusions: These data confirm JEV transmission across predominantly urban areas and support a greater emphasis on JEV case finding, diagnosis, and prevention. [ABSTRACT FROM AUTHOR]

Dengue seroprevalence data in the literature is limited and the available information is difficult to compare between studies because of the varying survey designs and methods used. We assessed dengue seropositivity across 14 countries using data from 15 trials conducted during the development of a tetravalent dengue vaccine between October 2005 and February 2014. Participants' dengue seropositivity (n=8592) was determined from baseline (before vaccination) serum samples at two centralized laboratories with the plaque reduction neutralization test (PRNT50). Seropositivity rates generally increased with age in endemic settings. Although seropositivity rates varied across geographical areas, between countries, and within countries by region, no major differences were observed for given age groups between the two endemic regions, Latin America and Asia-Pacific. Seropositivity rates were generally stable over time. The proportion of participants who had only experienced primary infection tended to be higher in younger children than adolescents/adults. These results will help inform and guide dengue control strategies in the participating countries. [ABSTRACT FROM AUTHOR]

Clinical Trials Registration: NCT01190228. [ABSTRACT FROM AUTHOR]

Background: We assessed replication and excretion of the live attenuated tetravalent dengue vaccine (CYD-TDV) into biological fluids following vaccination in dengue-naive adults in Australia.Methods: Vaccinal viremia/shedding was assessed in a subset of participants enrolled in a lot-to-lot consistency study; 95 participants received 3 subcutaneous doses of CYD-TDV from phase 2/3 lots of the vaccine, and 8 received placebo; doses were administered 6 months apart. Quantitative reverse-transcription polymerase chain reaction (qR-PCR) analysis was used to initially detect the yellow fever virus (YFV) core protein gene in the backbone of CYD-TDV in serum, saliva and urine, followed by serotype-specific qRT-PCR analysis of samples positive for YFV by qRT-PCR (lower limit of detection, 5.16 GEq/mL).Results: YFV viremia was detected by qRT-PCR in 69.5% of participants (66 of 95) who received CYD-TDV, mainly 6-14 days after injection 1. The serotypes detected were serotype 4 (in 68.2% of participants [45 of 95]), serotype 3 (in 19.7% [13 of 95]), and serotype 1 (in 12.1% [8 of 95]); serotype 2 was not detected. None of the placebo recipients had vaccinal viremia/shedding. No participants had detectable viral shedding into saliva at levels above the lower limit of quantitation. Two participants had low-level viral shedding (serotype 3) in urine (5.47 and 5.77 GEq/mL). None of the participants with viremia or shedding experienced concomitant fever.Conclusions: Low-level vaccinal viremia may occur following vaccination with CYD-TDV, but this is not associated with any symptom or adverse event.Clinical Trials Registration: NCT01134263. [ABSTRACT FROM AUTHOR]

Background: The live-attenuated Japanese encephalitis (JE) vaccine (JE-CV; IMOJEV) induces a protective response in children. A shift in circulating JE virus strains suggests that a genotype shift phenomenon may occur throughout Southeast Asia. We assessed the neutralization of wild-type (WT) JE virus isolates at distal time points after vaccination.Methods: We analyzed serum samples from a subset of 47 children who had received a JE-CV booster after an inactivated JE vaccine primary immunization. We measured antibody titers (50% plaque reduction neutralization test) using a panel of WT JE strains at baseline, then after the booster at 28 days and 6 months in all subjects present at the time points and in a subset at year 5. Three additional recent isolates were tested at year 5.Results: Of 47 subjects, 43 (91.5%) subjects had JE neutralizing antibody titers ≥10 (reciprocal serum dilution) against the homologous strain before JE-CV boost; all were seroprotected up to year 5 after the JE-CV boost. Baseline WT seroprotection ranged between 78.7% and 87.2%; all subjects were seroprotected against the 4 WT strains at 28 days and 6 months; year 5 seroprotection ranged between 95.7% and 97.9%. Similar rates of protection against 3 additional WT isolates were observed at year 5.Conclusions: The long-term immune responses induced after a JE-CV booster dose in toddlers were able to neutralize WT viruses from various genotypes circulating in Southeast Asia and India.Clinical Trials Registration: NCT00621764. [ABSTRACT FROM AUTHOR]

Diarrhea caused by infection with rotavirus annually results in an estimated 611,000 deaths among infants and young children <5 years of age worldwide, and these deaths primarily occur in developing countries. Infection with human immunodeficiency virus (HIV) is also common among young children in many developing countries, particularly in sub-Saharan Africa and Asia. The need for a vaccine to reduce the number of deaths caused by rotavirus infection among children in developing countries is substantial, but current rotavirus vaccines comprise live attenuated oral viruses, the behaviors of which are unknown in HIV-infected children. Therefore, we reviewed available data on natural rotavirus infection in HIV-infected children and examined unpublished data on a small group of HIV-infected infants in South Africa who were given a live rotavirus vaccine. Together, these data suggest that vaccination programs against rotavirus infection could include HIV-infected populations. However, studies addressing the safety, reactogenicity, and immunogenicity of rotavirus vaccines in an HIV-infected population are urgently needed. [ABSTRACT FROM AUTHOR]

The effect of nutritional status on protective efficacy of a live attenuated human rotavirus vaccine (RIX4414) was studied. Vaccine protection was evaluated through a secondary analysis of data from an efficacy study conducted in Brazil, Mexico, and Venezuela. Vaccine efficacy against rotavirus gastroenteritis (RVGE) was similar in well-nourished and malnourished infants: 74.1% (95% confidence interval [CI], 52.2%–86.2%) and 73% (95% CI, 11.2%–92.3%) for severe RVGE and 60.9% (95% CI, 37.4%–75.4%) and 61.2% (95% CI, 10.4%–83.1%) for RVGE of any severity, respectively. RIX4414 significantly decreased the rate of RVGE regardless of nutritional status, which suggests that this patient group can also benefit from rotavirus vaccination. [ABSTRACT FROM AUTHOR]

Conclusion: ETEC is the most common pathogen among travelers and Mexican residents in this study. The duration of untreated diarrhea due to ETEC was significantly shorter among Mexicans (49 hours in Mexican, 94 hours in US adults; p = .0004), as was the average number of unformed stools passed over 4 days (Mexicans 8.8 versus travelers 17.9 stools; p = .0009) [ABSTRACT FROM AUTHOR]

Background: Enterotoxigenic Escherichia coli (ETEC) is the most common pathogen identified in travelers to Mexico with diarrhea. There have been few recent studies looking at the etiology of diarrhea in travelers compared with the local resident population.Methods: We compared enteric pathogens isolated in two populations experiencing acute diarrhea acquired in Guadalajara, Mexico and also compared clinical illness caused by the principal pathogen, ETEC.Results: A single and 2 enteropathogens were detected in 107 (23%) and 8 (2%), respectively, of 457 Mexicans in 1995 and 1997, and 37 (29%) and 2 (2%), respectively, of 127 US adults in 1997. The most common pathogen was ETEC in both groups (11% of Mexican, 19% of US adults), although more common in the US travelers group (p =.0017). Shigella spp and Cryptosporidium spp were less common in the Mexican (<1% and <1%, respectively) than in the travelers group (6% and 3%, respectively) (p <.001 and p =.002, respectively). Entamoeba histolytica was more often found in the Mexican group (4% Mexican, 0% US adults; p =.027).Conclusion: ETEC is the most common pathogen among travelers and Mexican residents in this study. The duration of untreated diarrhea due to ETEC was significantly shorter among Mexicans (49 hours in Mexican, 94 hours in US adults; p =.0004), as was the average number of unformed stools passed over 4 days (Mexicans 8.8 versus travelers 17.9 stools; p =.0009 [ABSTRACT FROM AUTHOR]