iHuman sapovirus has been shown to be one of the most important etiologies in pediatric patients with acute diarrhea. However, very limited data are available about the causative roles and epidemiology of sapovirus in community settings. A nested matched case-control study within a birth cohort study of acute diarrhea in a peri-urban community in Peru from 2007 to 2010 was conducted to investigate the attributable fraction (AF) and genetic diversity of sapovirus. By quantitative reverse transcription-realtime PCR (qPCR) sapovirus was detected in 12.4% (37/299) of diarrheal and 5.7% (17/300) of nondiarrheal stools (P ‫؍‬ 0.004). The sapovirus AF (7.1%) was higher in the second year (13.2%) than in the first year (1.4%) of life of children. Ten known genotypes and one novel cluster (n ‫؍‬ 5) within four genogroups (GI, GII, GIV, and GV) were identified by phylogenetic analysis of a partial VP1 gene. Further sequence analysis of the full VP1 gene revealed a possible novel genotype, tentatively named GII.8. Notably, symptomatic reinfections with different genotypes within the same (n ‫؍‬ 3) or different (n ‫؍‬ 5) genogroups were observed in eight children. Sapovirus exhibited a high attributable burden for acute gastroenteritis, especially in the second year of life, of children in a Peruvian community. Further large-scale studies are needed to understand better the global burden, genetic diversity, and repeated infections of sapovirus. Acute diarrhea is one of the most important causes of morbidity and mortality in pediatric populations, especially in developing countries. Rotavirus, norovirus, and other viruses are common causative etiological agents, and rotavirus accounts for about 440,000 child deaths annually (1), while norovirus is a leading cause of epidemic and sporadic acute diarrhea (2). Currently a rotavirus vaccination program has been implemented in 80 countries as a part of national immunization programs (http://sites.path.org /rotavirusvaccine/rotavirus-vaccines/#global-intro). It successfully reduced the number of hospitalizations and deaths due to acute gastroenteritis (3, 4) and is cost-effective (5). Norovirus has now replaced rotavirus as the leading cause of medically attended acute diarrhea in pediatric populations (6, 7), and sapovirus, belonging to a separate genus of the Caliciviridae family, has been reported as the second most commonly detected virus after norovirus in children with acute diarrhea where rotavirus vaccination was implemented (8, 9). In addition, reports on sapovirus outbreaks across all age groups have increased in South Asia, Europe, and North America recently (10)(11)(12)(13)(14).The genome of sapovirus consists of a positive-sense, singlestranded RNA with two open reading frames (ORFs) (12). ORF1 encodes the nonstructural proteins and a major capsid protein, VP1, and ORF2 encodes a protein whose function is still unknown (12). Like for norovirus, multiple genetic clusters of human sapovirus have been reported, including four genogroups (GI, GII, GIV, and GV) with 17 gen...

This was the first birth cohort study with active surveillance of sapovirus infection in a developing country. High incidences of sapovirus infection and associated diarrhea during the first 2 years of life were reported. Sapovirus reinfection is common but rare with the same genotype.

Acute P. falciparum malaria coinfection impacts virus-host dynamics in HIV-1-infected persons at the cellular level, notably showing a reversible induction of HIV-1 replication in CD14 macrophages that is associated with changes in immune activation.

BackgroundOutdoor malaria transmission hinders malaria elimination efforts in the Amazon region and novel vector control tools are needed. Ivermectin mass drug administration (MDA) to humans kills wild Anopheles, targets outdoor-feeding vectors, and can suppress malaria parasite transmission. Laboratory investigations were performed to determine ivermectin susceptibility, sporontocidal effect and inhibition of time to re-feed for the primary Amazonian malaria vector, Anopheles darlingi.MethodsTo assess ivermectin susceptibility, various concentrations of ivermectin were mixed in human blood and fed to An. darlingi. Mosquito survival was monitored daily for 7 days and a non-linear mixed effects model with Probit analysis was used to calculate lethal concentrations of ivermectin that killed 50% (LC50), 25% (LC25) and 5% (LC5) of mosquitoes. To examine ivermectin sporonticidal effect, Plasmodium vivax blood samples were collected from malaria patients and offered to mosquitoes without or with ivermectin at the LC50, LC25 or LC5. To assess ivermectin inhibition of mosquito time to re-feed, concentrations of ivermectin predicted to occur after a single oral dose of 200 μg/kg ivermectin were fed to An. darlingi. Every day for 12 days thereafter, individual mosquitoes were given the opportunity to re-feed on a volunteer. Any mosquitoes that re-blood fed or died were removed from the study.ResultsIvermectin significantly reduced An. darlingi survivorship: 7-day-LC50 = 43.2 ng/ml [37.5, 48.6], -LC25 = 27.8 ng/ml [20.4, 32.9] and -LC5 = 14.8 ng/ml [7.9, 20.2]. Ivermectin compound was sporontocidal to P. vivax in An. darlingi at the LC50 and LC25 concentrations reducing prevalence by 22.6 and 17.1%, respectively, but not at the LC5. Oocyst intensity was not altered at any concentration. Ivermectin significantly delayed time to re-feed at the 4-h (48.7 ng/ml) and 12-h (26.9 ng/ml) concentrations but not 36-h (10.6 ng/ml) or 60-h (6.3 ng/ml).ConclusionsIvermectin is lethal to An. darlingi, modestly inhibits sporogony of P. vivax, and delays time to re-feed at concentrations found in humans up to 12 h post drug ingestion. The LC50 value suggests that a higher than standard dose (400-μg/kg) is necessary to target An. darlingi. These results suggest that ivermectin MDA has potential in the Amazon region to aid malaria elimination efforts.