Background malaria incidence and parasitemia during the three-dose RTS,S/AS01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria.

BACKGROUND: RTS,S/AS01 has been recommended by WHO for widespread implementation in medium to high malaria transmission settings. Previous analyses have noted lower vaccine efficacies in higher transmission settings, possibly due to the more rapid development of naturally acquired immunity in the control group. METHODS: To investigate a reduced immune response to vaccination as a potential mechanism behind lower efficacy in high transmission areas, we examine initial vaccine antibody (anti-CSP IgG) response and vaccine efficacy against the first case of malaria (to exclude the effect of naturally acquired immunity) using data from three study areas (Kintampo, Ghana; Lilongwe, Malawi; Lambaréné, Gabon) from the 2009-2014 phase III trial (NCT00866619). Our key exposures are parasitemia during the vaccination series and background malaria incidence. We calculate vaccine efficacy (one minus hazard ratio) using a cox-proportional hazards model and allowing for the time-varying effect of RTS,S/AS01. RESULTS: We find that antibody responses to the primary three-dose vaccination series were higher in Ghana than in Malawi and Gabon, but that neither antibody levels nor vaccine efficacy against the first case of malaria varied by background incidence or parasitemia during the primary vaccination series. CONCLUSIONS: We find that vaccine efficacy is unrelated to infections during vaccination. Contributing to a conflicting literature, our results suggest that vaccine efficacy is also unrelated to infections before vaccination, meaning that control-group immunity is likely a major reason for lower efficacy in high transmission settings, not reduced immune responses to RTS,S/AS01. This may be reassuring for implementation in high transmission settings, though further studies are needed.

Malaria Transmission Intensity and Parasitemia during the Three-Dose RTS,S/AS01 Vaccination Series do not Reduce Magnitude of Antibody Response nor Efficacy Against the First Case of Malaria.

Background: RTS,S/AS01 has been recommended by WHO for widespread implementation in medium to high malaria transmission settings. Previous analyses have noted lower vaccine efficacies in higher transmission settings, possibly due to the more rapid development of naturally acquired immunity in the control group. Methods: To investigate a reduced immune response to vaccination as a potential mechanism behind lower efficacy in high transmission areas, we examine initial vaccine antibody (anti-CSP IgG) response and vaccine efficacy against the first case of malaria to exclude the delayed malaria effect using data from three study areas (Kintampo, Ghana; Lilongwe, Malawi; Lambaréné, Gabon) from the 2009-2014 phase III trial (NCT00866619). Our key exposures are parasitemia during the vaccination series and malaria transmission intensity. We calculate vaccine efficacy (one minus hazard ratio) using a cox-proportional hazards model and allowing for the time-varying effect of RTS,S/AS01. Results: We find that antibody responses to the primary three-dose vaccination series were higher in Ghana than in Malawi and Gabon, but that neither antibody levels nor vaccine efficacy against the first case of malaria varied by transmission intensity or parasitemia during the primary vaccination series. Conclusions: We find that vaccine efficacy is unrelated to infections during vaccination. Contributing to a conflicting literature, our results suggest that vaccine efficacy is also unrelated to infections before vaccination, meaning that delayed malaria is likely the main reason for lower efficacy in high transmission settings, not reduced immune responses. This may be reassuring for implementation in high transmission settings, though further studies are needed.

Association between domesticated animal ownership and Plasmodium falciparum parasite prevalence in the Democratic Republic of the Congo: a national cross-sectional study.

BACKGROUND: Domesticated animal ownership is an understudied aspect of the human environment that influences mosquito biting behaviour and malaria transmission, and is a key part of national economies and livelihoods in malaria-endemic regions. In this study, we aimed to understand differences in Plasmodium falciparum prevalence by ownership status of common domesticated animals in DR Congo, where 12% of the world's malaria cases occur and anthropophilic Anopheles gambiae vectors predominate. METHODS: In this cross-sectional study, we used survey data from individuals aged 15-59 years in the most recent (2013-14) DR Congo Demographic and Health Survey and previously performed Plasmodium quantitative real-time PCR (qPCR) to estimate P falciparum prevalence differences by household ownership of cattle; chickens; donkeys, horses, or mules; ducks; goats; sheep; and pigs. We used directed acyclic graphs to consider confounding by age, gender, wealth, modern housing, treated bednet use, agricultural land ownership, province, and rural location. FINDINGS: Of 17 701 participants who had qPCR results and covariate data, 8917 (50·4%) of whom owned a domesticated animal, we observed large differences in malaria prevalence across types of animals owned in both crude and adjusted models. Household chicken ownership was associated with 3·9 (95% CI 0·6 to 7·1) more P falciparum infections per 100 people, whereas cattle ownership was associated with 9·6 (-15·8 to -3·5) fewer P falciparum infections per 100 people, even after accounting for bednet use, wealth, and housing structure. INTERPRETATION: Our finding of a protective association conferred by cattle ownership suggests that zooprophylaxis interventions might have a role in DR Congo, possibly by drawing An gambiae feeding away from humans. Studies of animal husbandry practices and associated mosquito behaviours could reveal opportunities for new malaria interventions. FUNDING: The National Institutes of Health and the Bill & Melinda Gates Foundation. TRANSLATIONS: For the French and Lingala translations of the abstract see Supplementary Materials section.

Spatial distribution of incident pediatric Burkitt lymphoma in central and northern Malawi and association with malaria prevalence.

BACKGROUND: Burkitt lymphoma (BL) accounts for 90% of pediatric lymphomas in sub-Saharan Africa. Plasmodium falciparum malaria is considered an etiological factor of BL. We describe the geographic distribution of pediatric BL in Malawi and association with P. falciparum malaria prevalence rate (PfPR). METHODS: We enrolled 220 pathologically confirmed incident pediatric BL cases (2013-2018) into an observational clinical cohort at Kamuzu Central Hospital (KCH) in Lilongwe district. KCH is the main tertiary cancer referral center serving the central and northern regions of Malawi. Using an ecological study design, we calculated district-level annual BL incidence rate using census population estimates. District-level PfPR was extracted from the National Malaria Control Program 2010 report. BL incidence and PfPR maps were constructed in QGIS. Moran's I  test was used to identify BL spatial clusters. Pearson's correlation and multiple linear regression analyses were used to statistically examine the relationship between PfPR and BL. RESULTS: BL incidence was higher in central region districts (8.2 cases per million) than northern districts (2.9 cases per million) and was elevated in lakeshore districts. Districts with elevated PfPR tended to have elevated BL incidence. A low-risk BL cluster was detected in the north. Statistically, BL incidence was positively correlated with PfPR (r = .77, p < .01). A 1% increase in PfPR predicted an increase in BL incidence of 0.2 cases per million (p = .03), when controlling for travel time from referral district hospital to KCH. CONCLUSION: Our study supports evidence for an association between P. falciparum and BL and highlights a need to improve geographic accessibility to tertiary cancer services in Malawi's northern region.

Ethnoracial Disparities in SARS-CoV-2 Seroprevalence in a Large Cohort of Individuals in Central North Carolina from April to December 2020.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths around the world within the past 2 years. Transmission within the United States has been heterogeneously distributed by geography and social factors with little data from North Carolina. Here, we describe results from a weekly cross-sectional study of 12,471 unique hospital remnant samples from 19 April to 26 December 2020 collected by four clinical sites within the University of North Carolina Health system, with a majority of samples from urban, outpatient populations in central North Carolina. We employed a Bayesian inference model to calculate SARS-CoV-2 spike protein immunoglobulin prevalence estimates and conditional odds ratios for seropositivity. Furthermore, we analyzed a subset of these seropositive samples for neutralizing antibodies. We observed an increase in seroprevalence from 2.9 (95% confidence interval [CI], 1.8 to 4.5) to 12.8 (95% CI, 10.6 to 15.2) over the course of the study. Latinx individuals had the highest odds ratio of SARS-CoV-2 exposure at 6.56 (95% CI, 4.66 to 9.44). Our findings aid in quantifying the degree of asymmetric SARS-CoV-2 exposure by ethnoracial grouping. We also find that 49% of a subset of seropositive individuals had detectable neutralizing antibodies, which was skewed toward those with recent respiratory infection symptoms. IMPORTANCE PCR-confirmed SARS-CoV-2 cases underestimate true prevalence. Few robust community-level SARS-CoV-2 ethnoracial and overall prevalence estimates have been published for North Carolina in 2020. Mortality has been concentrated among ethnoracial minorities and may result from a high likelihood of SARS-CoV-2 exposure, which we observe was particularly high among Latinx individuals in North Carolina. Additionally, neutralizing antibody titers are a known correlate of protection. Our observation that development of SARS-CoV-2 neutralizing antibodies may be inconsistent and dependent on severity of symptoms makes vaccination a high priority despite prior exposure.

Effectiveness of a national mass distribution campaign of long-lasting insecticide-treated nets and indoor residual spraying on clinical malaria in Malawi, 2018-2020.

INTRODUCTION: Malawi's malaria burden is primarily assessed via cross-sectional national household surveys. However, malaria is spatially and temporally heterogenous and no analyses have been performed at a subdistrict level throughout the course of a year. The WHO recommends mass distribution of long-lasting insecticide-treated bed nets (LLINs) every 3 years, but a national longitudinal evaluation has never been conducted in Malawi to determine LLIN effectiveness lifespans. METHODS: Using District Health Information Software 2 (DHIS2) health facility data, available from January 2018 to June 2020, we assessed malaria risk before and after a mass distribution campaign, stratifying by age group and comparing risk differences (RDs) by LLIN type or annual application of indoor residual spraying (IRS). RESULTS: 711 health facilities contributed 20 962 facility reports over 30 months. After national distribution of 10.7 million LLINs and IRS in limited settings, malaria risk decreased from 25.6 to 16.7 cases per 100 people from 2018 to 2019 high transmission seasons, and rebounded to 23.2 in 2020, resulting in significant RDs of -8.9 in 2019 and -2.4 in 2020 as compared with 2018. Piperonyl butoxide (PBO)-treated LLINs were more effective than pyrethroid-treated LLINs, with adjusted RDs of -2.3 (95% CI -2.7 to -1.9) and -1.5 (95% CI -2.0 to -1.0) comparing 2019 and 2020 high transmission seasons to 2018. Use of IRS sustained protection with adjusted RDs of -1.4 (95% CI -2.0 to -0.9) and -2.8% (95% CI -3.5 to -2.2) relative to pyrethroid-treated LLINs. Overall, 12 of 28 districts (42.9%) experienced increases in malaria risk in from 2018 to 2020. CONCLUSION: LLINs in Malawi have a limited effectiveness lifespan and IRS and PBO-treated LLINs perform better than pyrethroid-treated LLINs, perhaps due to net repurposing and insecticide-resistance. DHIS2 provides a compelling framework in which to examine localised malaria trends and evaluate ongoing interventions.

Disparities in SARS-CoV-2 seroprevalence among individuals presenting for care in central North Carolina over a six-month period.

Background: Robust community-level SARS-CoV-2 prevalence estimates have been difficult to obtain in the American South and outside of major metropolitan areas. Furthermore, though some previous studies have investigated the association of demographic factors such as race with SARS-CoV-2 exposure risk, fewer have correlated exposure risk to surrogates for socioeconomic status such as health insurance coverage. Methods: We used a highly specific serological assay utilizing the receptor binding domain of the SARS-CoV-2 spike-protein to identify SARS-CoV-2 antibodies in remnant blood samples collected by the University of North Carolina Health system. We estimated the prevalence of SARS-CoV-2 in this cohort with Bayesian regression, as well as the association of critical demographic factors with higher prevalence odds. Findings: Between April 21st and October 3rd of 2020, a total of 9,624 unique samples were collected from clinical sites in central NC and we observed a seroprevalence increase from 2·9 (1·7, 4·3) to 9·1 (7·2, 11·1) over the study period. Individuals who identified as Latinx were associated with the highest odds ratio of SARS-CoV-2 exposure at 7·77 overall (5·20, 12·10). Increased odds were also observed among Black individuals and individuals without public or private health insurance. Interpretation: Our data suggests that for this care-accessing cohort, SARS-CoV-2 seroprevalence was significantly higher than cumulative total cases reported for the study geographical area six months into the COVID-19 pandemic in North Carolina. The increased odds of seropositivity by ethnoracial grouping as well as health insurance highlights the urgent and ongoing need to address underlying health and social disparities in these populations.

SARS-CoV-2 testing in North Carolina: Racial, ethnic, and geographic disparities.

SARS-CoV-2 testing data in North Carolina during the first three months of the state's COVID-19 pandemic were analyzed to determine if there were disparities among intersecting axes of identity including race, Latinx ethnicity, age, urban-rural residence, and residence in a medically underserved area. Demographic and residential data were used to reconstruct patterns of testing metrics (including tests per capita, positive tests per capita, and test positivity rate which is an indicator of sufficient testing) across race-ethnicity groups and urban-rural populations separately. Across the entire sample, 13.1% (38,750 of 295,642) of tests were positive. Within racial-ethnic groups, 11.5% of all tests were positive among non-Latinx (NL) Whites, 22.0% for NL Blacks, and 66.5% for people of Latinx ethnicity. The test positivity rate was higher among people living in rural areas across all racial-ethnic groups. These results suggest that in the first three months of the COVID-19 pandemic, access to COVID-19 testing in North Carolina was not evenly distributed across racial-ethnic groups, especially in Latinx, NL Black and other historically marginalized populations, and further disparities existed within these groups by gender, age, urban-rural status, and residence in a medically underserved area.

Considering Alternate Pathways of Drinking-Water Contamination: Evidence of Risk Substitution from Arsenic Mitigation Programs in Rural Bangladesh.

Deep tubewells are a key component of arsenic mitigation programs in rural Bangladesh. Compared to widely prevalent shallow tubewells, deep tubewells reduce ground-water arsenic exposure and provide better microbial water quality at source. However, the benefits of clean drinking-water at these more distant sources may be abated by higher levels of microbial contamination at point-of-use. One such potential pathway is the use of contaminated surface water for washing drinking-water storage containers. The aim of this study is to compare the prevalence of surface water use for washing drinking-water storage containers among deep and shallow tubewell users in a cohort of 499 rural residents in Matlab, Bangladesh. We employ a multi-level logistic regression model to measure the effect of tubewell type and ownership status on the odds of washing storage containers with surface water. Results show that deep tubewell users who do not own their drinking-water tubewell, have 6.53 times the odds [95% CI: 3.56, 12.00] of using surface water for cleaning storage containers compared to shallow tubewell users, who own their drinking-water source. Even deep tubewell users who own a private well within walking distance have 2.53 [95% CI: 1.36, 4.71] times the odds of using surface water compared to their shallow tubewell counterparts. These results highlight the need for interventions to limit risk substitution, particularly the increased use of contaminated surface water when access to drinking water is reduced. Increasing ownership of and proximity to deep tubewells, although crucial, is insufficient to achieve equity in safe drinking-water access across rural Bangladesh.