Abstract. Estimates of malaria transmission intensity (MTI) typically rely upon microscopy or rapid diagnostic testing (RDT). However, these methods are less sensitive than nucleic acid amplification techniques and may underestimate parasite prevalence. We compared microscopy, RDT, and polymerase chain reaction (PCR) for the diagnosis of Plasmodium falciparum parasitemia as part of an MTI study of 800 children and adults conducted in Lilongwe, Malawi. PCR detected more cases of parasitemia than microscopy or RDT. Age less than 5 years predicted parasitemia detected by PCR alone (adjusted odds ratio = 1.61, 95% confidence interval = 1.09-2.38, Wald P = 0.02). In addition, we identified one P. falciparum parasite with a false-negative RDT result due to a suspected deletion of the histidinerich protein 2 (hrp2) gene and used a novel, ultrasensitive PCR assay to detect low-level parasitemia missed by traditional PCR. Molecular methods should be considered for use in future transmission studies as a supplement to RDT or microscopy.Plasmodium falciparum infects hundreds of millions of individuals and kills 600,000 persons every year.1 A recently completed phase three trial of the RTS,S/ASO1 malaria vaccine demonstrated moderate and varying efficacy in different transmission settings.2 Study sites conducted annual malaria transmission intensity (MTI) studies during the trial using microscopy and rapid diagnostic test (RDT) parasite prevalence as a surrogate for transmission intensity.Both microscopy and RDT are known to produce negative results in Africa when parasitemia levels are beneath their limits of detection, 50 and 200 parasites/μL blood, respectively. [3][4][5] Infections not detected by microscopy or RDT, often referred to as subpatent infections, can often be detected by nucleic acid detection methods. 6 Though infections detected by microscopy and RDT are likely responsible for the majority of transmission, further studies are needed to assess the impact of subpatent infections on the transmission reservoir. 7,8 In the context of vaccine trials, these low-level, subpatent parasitemias may confound estimates of transmission intensity used to study vaccine efficacy.To evaluate the impact of subpatent parasitemias on parasite prevalence estimates, we collected dried blood spots from all participants during the final year of the 3-year MTI study in Lilongwe, Malawi, to allow for nucleic acid detection of parasitemia. Using clinical data and a spatial database to evaluate ecological factors that may influence transmission, we attempted to identify risk factors for subpatent parasitemia. We also investigated the impact of other factors on discordances between polymerase chain reaction (PCR) and other assays (RDT and microscopy) including 1) nonfalciparum parasitemia, 2) the occurrence of histidine-rich protein 2 (hrp2) gene deletions on false-negative RDTs, and 3) low-level parasitemia detectable by ultrasensitive PCR targeting high copy number genes. 9 This work adds to the growing literature concerning the rela...

Norovirus is a leading cause of pediatric gastroenteritis. Understanding norovirus epidemiology is essential for reducing disease burden. We conducted a case-control study to describe the distribution, clinical features, and risk factors of norovirus gastroenteritis among children < 5 years of age in León, Nicaragua. Cases were children testing positive for norovirus and controls were children living in the cases' communities. Study staff interviewed mothers of enrolled cases and controls to obtain detailed exposure information including food, water, and sanitation sources; recent exposures; household characteristics; and handwashing practices. In addition, study staff requested stool samples to be tested for norovirus from select household members. We used descriptive statistics to understand the epidemiologic and clinical features of gastroenteritis episodes. To analyze potential risk factors, we used Firth's penalized logistic regression to estimate crude and adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs). There were 102 children with gastroenteritis, 18 cases of norovirus and 31 controls. Norovirus cases occurred later in the year, corresponding to a delay in the rainy season. Cases were more likely to have a household member with norovirus in their stool as compared with controls [crude OR: 13.3 (95% CI: 2.5, 136.2) and adjusted OR: 11.5 (95% CI: 1.6, 223.2)]. In addition, alcohol-based hand sanitizer use among household members was reported for 10 (32%) of controls and but never for cases. Further research is needed to understand household transmission of norovirus in low- and middle-income countries and the potential impact of hand sanitizer use.

Accelerated iTBS treatment in depressed patients differentially modulates reward system activity based on anhedonia.