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Item The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya(BMC, 2021-09-17) Salgado, Christina; Ayodo, George; Macklin, Michael D.; Gould, Meetha P.; Nallandhighal, Srinivas; Odhiambo, Eliud O.; Obala, Andrew; Prudhomme O’Meara, Wendy; John, Chandy C.; Tran, Tuan M.; Medicine, School of MedicineBackground: Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitaemia and gametocytaemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections with sensitive molecular methods can adequately detect the majority of infected individuals who are potentially capable of onward transmission. Methods: In a cross-sectional survey of 1354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa-Kipsamoite), asymptomatic P. falciparum infections were screened by rapid diagnostic tests, blood smear, and quantitative PCR of dried blood spots targeting the varATS gene in genomic DNA. A multiplex quantitative reverse-transcriptase PCR assay targeting female and male gametocyte genes (pfs25, pfs230p), a gene with a transcriptional pattern restricted to asexual blood stages (piesp2), and human GAPDH was also developed to determine total parasite and gametocyte densities among parasitaemic individuals. Results: The prevalence of varATS-detectable asymptomatic infections was greatest in Ajigo (42%), followed by Webuye (10%). Only two infections were detected in Kapsisywa. No infections were detected in Kipsamoite. Across all communities, children aged 11-15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults (> 21 years old) had sub-microscopic parasitaemia. Piesp2-derived parasite densities correlated poorly with microscopy-determined parasite densities in patent infections relative to varATS-based detection. In general, both male and female gametocytaemia increased with increasing varATS-derived total parasitaemia. A substantial proportion (41.7%) of individuals with potential for onward transmission had qPCR-estimated parasite densities below the limit of microscopic detection, but above the detectable limit of varATS qPCR. Conclusions: This assessment of parasitaemia and gametocytaemia in three communities with different transmission intensities revealed evidence of a substantial sub-patent infectious reservoir among asymptomatic carriers of P. falciparum. Experimental studies are needed to definitively determine whether the low-density infections in communities such as Ajigo and Webuye contribute significantly to malaria transmission.Item SARS-CoV-2 reinfections in a US university setting, Fall 2020 to Spring 2021(BMC, 2022-07-04) Rosenberg, Molly; Chen, Chen; Golzarri‑Arroyo, Lilian; Carroll, Aaron; Menachemi, Nir; Ludema, Christina; Health Policy and Management, School of Public HealthBackground: SARS-CoV-2 reinfections are a public health concern because of the potential for transmission and clinical disease, and because of our limited understanding of whether and how well an infection confers protection against subsequent infections. Despite the public health importance, few studies have reported rigorous estimates of reinfection risk. Methods: Leveraging Indiana University's comprehensive testing program to identify both asymptomatic and symptomatic SARS-CoV-2 cases, we estimated the incidence of SARS-CoV-2 reinfection among students, faculty, and staff across the 2020-2021 academic year. We contextualized the reinfection data with information on key covariates: age, sex, Greek organization membership, student vs faculty/staff affiliation, and testing type. Results: Among 12,272 people with primary infections, we found a low level of SARS-CoV-2 reinfections (0.6%; 0.4 per 10,000 person-days). We observed higher risk for SARS-CoV-2 reinfections in Greek-affiliated students. Conclusions: We found evidence for low levels of SARS-CoV-2 reinfection in a large multi-campus university population during a time-period prior to widespread COVID-19 vaccination.Item Subclinical Inflammation in Asymptomatic Schoolchildren With Plasmodium falciparum Parasitemia Correlates With Impaired Cognition(Oxford University Press, 2024) Johnson, Alexander E.; Upadhye, Aditi; Knight, Veronicah; Gaskin, Erik L.; Turnbull, Lindsey B.; Ayuku, David; Nyalumbe, Mark; Abuonji, Emily; John, Chandy C.; McHenry, Megan S.; Tran, Tuan M.; Ayodo, George; Medicine, School of MedicineBackground: Subclinical inflammation and cognitive deficits have been separately associated with asymptomatic Plasmodium falciparum infections in schoolchildren. However, whether parasite-induced inflammation is associated with worse cognition has not been addressed. We conducted a cross-sectional pilot study to better assess the effect of asymptomatic P. falciparum parasitemia and inflammation on cognition in Kenyan schoolchildren. Methods: We enrolled 240 children aged 7-14 years residing in high malaria transmission in Western Kenya. Children performed five fluid cognition tests from a culturally adapted NIH toolbox and provided blood samples for blood smears and laboratory testing. Parasite densities and plasma concentrations of 14 cytokines were determined by quantitative PCR and multiplex immunoassay, respectively. Linear regression models were used to determine the effects of parasitemia and plasma cytokine concentrations on each of the cognitive scores as well as a composite cognitive score while controlling for age, gender, maternal education, and an interaction between age and P. falciparum infection status. Results: Plasma concentrations of TNF, IL-6, IL-8, and IL-10 negatively correlated with the composite score and at least one of the individual cognitive tests. Parasite density in parasitemic children negatively correlated with the composite score and measures of cognitive flexibility and attention. In the adjusted model, parasite density and TNF, but not P. falciparum infection status, independently predicted lower cognitive composite scores. By mediation analysis, TNF significantly mediated ~29% of the negative effect of parasitemia on cognition. Conclusions: Among schoolchildren with PCR-confirmed asymptomatic P. falciparum infections, the negative effect of parasitemia on cognition could be mediated, in part, by subclinical inflammation. Additional studies are needed to validate our findings in settings of lower malaria transmission and address potential confounders that could affect both inflammation and cognitive performance.Item What is the burden of asymptomatic coronavirus infections?(Elsevier, 2023) Al-Tawfiq, Jaffar A.; Memish, Ziad A.; Altawfi, Kauthar J.; Pan, Qiuwei; Schlagenhauf, Patricia; Medicine, School of Medicine