Exploration of mosquito behavior, anopheline diversity, and human malaria risk in holoendemic and hypoendemic transmission settings in Zambia

This thesis examines mosquito behavior, anopheline diversity, and human malaria risk in two transmission settings in Zambia. Choma District in southern Zambia experiences seasonal hypoendemic transmission, while Nchelenge District in northern Zambia experiences holoendemic malaria transmission. In Choma District, anophelines were collected using CDC light traps in index case and neighboring households from 2015-2018. Outdoor collections captured more anophelines than indoor traps, and ten different species were molecularly identified. Four species (Anopheles arabiensis, An. rufipes, An. squamosus, and An. coustani) were positive for Plasmodium falciparum CSP by ELISA, and 61% of those were captured outdoors. Blood meal assays confirmed plasticity in An. arabiensis host preference, while An. rufipes, An. squamosus and An. coustani were largely zoophilic and exophagic. Linear regression of count data for indoor traps revealed rainy season, using a stream or pond as a water source and households with at least one parasitemic resident by PCR were associated with higher female anopheline counts. Overall, the composite data suggest that anophelines with behavioral plasticity or exophagic tendencies are responsible for residual transmission in Choma District, and are likely not affected by indoor vector control interventions. In Nchelenge District, malaria remains holoendemic despite a decade of intensive interventions leading to the hypothesis that vectors may feed outdoors and before people go to sleep. Entomological collections were performed in 2019 during the dry season using CDC light traps indoors, outdoors where people gather, and near animal pens from 16:00-22:00, before most participants retired to bed. Fifteen species of Anopheles were identified including An. gibbinsi which had not been previously reported in Zambia. Molecular analyses revealed high zoophilic tendencies in this species and >99% identity to “An. sp.6”. Anopheles funestus and An. gambiae captured both indoors and outdoors were positive for P. falciparum, suggesting that infection may not be limited to indoor, overnight exposure. Exposure also varied spatially with the highest calculated EIR among indoor An. funestus collected from inland households. These findings provide a potential explanation for the refractoriness to ongoing interventions and underscore the necessity to continue development and evaluation of vector control tools that are effective outdoors

The first genome sequence of Anopheles squamous from Macha, Zambia [version 1; peer review: 2 approved]

Despite efforts to minimize the impacts of malaria and reduce the number of primary vectors, malaria has yet to be eliminated in Zambia. Understudied vector species may perpetuate malaria transmission in pre-elimination settings. Anopheles squamosus is one of the most abundantly caught mosquito species in southern Zambia and has previously been found with Plasmodium falciparum sporozoites, a causal agent of human malaria. This species may be a critical vector of malaria transmission, however, there is a lack of genetic information available for An. squamosus. We report the first genome data and the first complete mitogenome (Mt) sequence of An. squamosus. The sequence was extracted from one individual mosquito from the Chidakwa area in Macha, Zambia. The raw reads were obtained using Illumina Novaseq 6000 and assembled through NOVOplasty alignment with related species. The length of the An. squamosus Mt was 15,351 bp, with 77.9 % AT content. The closest match to the whole mitochondrial genome in the phylogenetic tree is the African malaria mosquito, Anopheles gambiae. Its genome data is available through National Center for Biotechnology Information (NCBI) Sequencing Reads Archive (SRA) with accession number SRR22114392. The mitochondrial genome was deposited in NCBI GenBank with the accession number OP776919. The ITS2 containing contig sequence was deposited in GenBank with the accession number OQ241725. Mitogenome annotation and a phylogenetic tree with related Anopheles mosquito species are provided

Predicted contribution of folic acid fortification of corn masa flour to the usual folic acid intake for the US population: National Health and Nutrition Examination Survey 2001–2004

Background: Folic acid can prevent up to 70% of neural tube defects (NTDs) if taken before pregnancy. Compared with other race-ethnicities, Hispanic women have higher rates of NTDs, lower rates of folic acid supplement use, and lower total folic acid intakes. Objective: The objective was to assess potential effects of fortifying corn masa flour with folic acid on Mexican American women and other segments of the US population. Design: A model was developed by using data from the National Health and Nutrition Examination Survey 2001-2004 to estimate the folic acid content in foods containing corn masa flour if fortified at a level of 140 ug folic acid/100 g corn masa flour. Results: Had corn masa flour fortification occurred, we estimated that Mexican American women aged 15-44 y could have increased their total usual daily folic acid intake by 19.9% and non-Hispanic white women by 4.2%. Among the US population, estimated relative percentage increases in total usual daily folic acid intake with corn masa flour fortification were greatest among Mexican Americans (16.8%) and lowest among children aged 1-3 y (2%) and adults aged \u3e51 y (0-0.5%). Conclusion: Analyses suggest that corn masa flour fortification would have effectively targeted Mexican Americans, specifically, Mexican American women, without substantially increasing folic acid intake among other segments of the population. Such increases could reduce the disparity in total folic acid intake between Mexican American and non-Hispanic white women of childbearing age and implies that an additional NTD preventive benefit would be observed for Mexican American women

Optical Trapping with High Forces Reveals Unexpected Behaviors of Prion Fibrils

Amyloid fibrils are important in diverse cellular functions, feature in many human diseases and have potential applications in nanotechnology. Here we describe methods that combine optical trapping and fluorescent imaging to characterize the forces that govern the integrity of amyloid fibrils formed by a yeast prion protein. A crucial advance was to use the self-templating properties of amyloidogenic proteins to tether prion fibrils, enabling their manipulation in the optical trap. At normal pulling forces the fibrils were impervious to disruption. At much higher forces (up to 250 pN), discontinuities occurred in force-extension traces before fibril rupture. Experiments with selective amyloid-disrupting agents and mutations demonstrated that such discontinuities were caused by the unfolding of individual subdomains. Thus, our results reveal unusually strong noncovalent intermolecular contacts that maintain fibril integrity even when individual monomers partially unfold and extend fibril length.National Institutes of Health (U.S.) (Grant GM025874)National Science Foundation (U.S.). CAREER (Award 0643745

sj-docx-1-wem-10.1177_10806032241245093 - Supplemental material for Acute Gastroenteritis Outbreak Among Colorado River Rafters and Backpackers in the Grand Canyon, 2022

Supplemental material, sj-docx-1-wem-10.1177_10806032241245093 for Acute Gastroenteritis Outbreak Among Colorado River Rafters and Backpackers in the Grand Canyon, 2022 by Shanna Miko, Laura Calderwood, Ariella P. Dale, Ronan F. King, Matthew B. Maurer, Maria A. Said, Marette Gebhardt, Laurie P. Dyer, Wendy Maurer, Mary E. Wikswo, and Sara A. Mirza in Wilderness & Environmental Medicine</p