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Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria2, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%.

I. INTRODUCTION 343 II. OVERVIEW OF COMMUNITY COLLEGES & THEIR ROLE IN 344 ECONOMIC MOBILITY A. Who Attends Community Colleges--Demographics of 345 Community College Students B. Community College as a [...], Community colleges have the potential to be a powerful force to alleviate poverty in the United States. However, the persistent underfunding of community colleges inhibits their ability to meet the aspiration of economic mobility for all students as they serve students who have more significant needs with fewer resources than public or private four-year institutions of higher education. The challenges faced by community colleges mirror the circumstances faced by many K-12 schools in low-income communities and communities of color in the United States where limited school funding has contributed to inequitable access to opportunity and inhibited student outcomes. However, unlike the community college context, decades of litigation and strategic advocacy have contributed to improvements in K-12 school funding. This Note argues that key lessons from the K-12 school funding litigation can be applied to the community college context to both increase funding available to community colleges and improve the funding pipeline so that it better accounts for the unique needs in the community college context. This would be achieved through a dual-pronged strategy. The first prong centers on litigation advancing the argument that states have a constitutional obligation to adequately fund community colleges. The second prong requires political advocacy at the state and federal levels. By taking a multi-pronged approach advancing both litigation and advocacy efforts, those seeking to achieve more adequate community college funding amplify their power and reach. Community colleges have the ability to promote economic mobility and alleviate poverty. Through collective legal and advocacy efforts, this potential can be realized.

Background: Environmental enteric dysfunction (EED) is an acquired subclinical condition of the small intestine with lasting health implications for nutritional status, linear growth and development among children. EED is characterised by structural and functional changes to the gut barrier. There are no standardised diagnostic criteria, however, a number of biomarkers have been evaluated to capture EED domains. While the causes of EED are not fully understood, risk factors include poor water, sanitation and hygiene conditions and exposure to enteric pathogens. Very few studies have evaluated the impact of schistosomiasis on EED despite repeated intestinal damage from parasite eggs passing across the gut barrier. Methods: In a cohort of 354 preschool‐aged children aged 12–47 months with Schistosoma mansoni infection recruited from the Lake Albert region of Uganda, we assessed exposure to water, sanitation and hygiene conditions and measured markers from each EED domain: intestinal inflammation (faecal calprotectin), epithelial damage (serum intestinal fatty‐acid binding‐protein), increased permeability (urine lactulose to mannitol ratio and faecal alpha‐1 antitrypsin) and microbial translocation (serum endotoxin core antibody). Results: In multivariable linear regression models, we found that children whose drinking water was sourced from Lake Albert had higher concentrations of intestinal fatty‐acid binding‐protein (β = 0.48, 95% CI 0.20–0.76, p < 0.001), and lack of toilet/latrine access was associated with higher concentrations of calprotectin (β = 0.48, 95% CI 0.18–0.78, p < 0.01). Higher schistosomiasis intensity (eggs per gram of stool) was associated with higher calprotectin (β = 0.10, 95% CI 0.02–0.17, p = 0.01), but not with other EED markers. Conclusions: Few studies have investigated schistosomiasis‐related morbidities in very young children infected with schistosomiasis. Our findings from Uganda show that poor water, sanitation and hygiene conditions and heavier schistosomiasis burden are associated with intestinal inflammation and damage, contributing to EED. Improved treatment coverage for preschool‐aged children infected with schistosomiasis may reduce the burden from EED and associated long‐term morbidities. [ABSTRACT FROM AUTHOR]

Global attention on early child development, inclusive of those with disability, has the potential to translate into improved action for the millions of children with developmental disability living in low- and middle-income countries. Nurturing care is crucial for all children, arguably even more so for children with developmental disability. A high proportion of survivors of neonatal conditions such as prematurity and neonatal encephalopathy are affected by early child developmental disability. The first thousand days of life is a critical period for neuroplasticity and an important window of opportunity for interventions, which maximize developmental potential and other outcomes. Since 2010, our group has been examining predictors, outcomes, and experiences of neonatal encephalopathy in Uganda. The need for an early child intervention program to maximize participation and improve the quality of life for children and families became apparent. In response, the "ABAaNA early intervention program," (now re-branding as 'Baby Ubuntu') a group participatory early intervention program for young children with developmental disability and their families, was developed and piloted. Piloting has provided early evidence of feasibility, acceptability, and impact and a feasibility trial is underway. Future research aims to develop programmatic capacity across diverse settings and evaluate its impact at scale.

Introduction: Tight junctions (TJs) serve as permeability filters between the internal and external cellular environment. A large number of proteins have been identified to be localized at the TJs. Due to limitations in tissue collection, TJs in the male genital tract have been understudied. Methods: We analysed the transcriptomics of 132 TJ genes in foreskin tissue of men requesting voluntary medical male circumcision (VMMC) and enrolled in the Combined HIV Adolescent Prevention Study (CHAPS) trial conducted in South Africa and Uganda (NCT03986970). The trial evaluated the dose requirements for event-driven HIV pre-exposure prophylaxis (PrEP) with emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during insertive sex. A total of 144 participants were randomized to either control arm or one of 8 PrEP arms (n=16/arm), receiving oral FTC-TDF or FTC-TAF over one or two days. Following in vivo oral PrEP dosing and VMMC, the expression level of three important TJ proteins (CLDN-1, OCN and ZO-1) was measured ex vivo in foreskin tissue by Western blot. The expression of cytokine genes implicated in TJ regulation was determined. Non-parametric Kruskal-Wallis tests were used to compare TJ gene expression and protein levels by type of PrEP received, and Spearman's correlation coefficients were calculated to assess whether TJ gene expression levels were related to cytokine gene levels or to PrEP drug concentrations and their active intracellularly phosphorylated metabolites. Results: A high level of expression in foreskin tissue was found for 118 (of 132) TJ genes analysed; this finding contributed to create a map of TJ components within the male genital tract. Importantly, PrEP regimens tested in the CHAPS trial did not affect the expression of TJ genes and the analysed proteins in the foreskin; thus, further supporting the safety of this prevention strategy against HIV-1 transmission during insertive sex. Additionally, we identified the level of several cytokines' genes to be correlated to TJ gene expression: among them, IL-18, IL-33 and VEGF. Discussion: TJs can limit viral entry into target cells; to affect this biological function viruses can reduce the expression of TJ proteins. Our study, on the expression and regulation of TJs in the foreskin, contribute important knowledge for PrEP safety and further design of HIV-1 prophylaxis. [ABSTRACT FROM AUTHOR]

Vaccine efficacy varies globally, often showing reduced immune responses in low‐ and middle‐income countries, possibly due to the immunomodulatory effects of parasitic infections like malaria. This systematic review evaluates the impact of malaria on immune responses to unrelated vaccines in humans and animals. We systematically searched five databases—MEDLINE, Web of Science, Global Health, Scopus and Embase—up to 5th December 2023. Eligible studies compared immune responses to WHO‐approved vaccines between malaria‐infected and uninfected groups, or between antimalarial‐treated and untreated groups. Meta‐analysis was performed using random‐effects models with standardised mean differences (SMDs) as summary statistics. The study is registered with PROSPERO (CRD42022298053). Twenty‐four articles (17 human, 7 animal) met the inclusion criteria, with 13 human articles contributing data for the meta‐analysis. Significant heterogeneity was observed. Vaccine responses were higher in malaria uninfected individuals (SMD 0.34, 95% CI 0.07 to 0.60, I2 = 87.15%) with weaker differences between antimalarial‐treated and untreated groups (SMD 0.07, 95% CI −0.01 to 0.16, I2 = 85.01%). The overall SMD for malaria uninfected/treated vs. infected/untreated was 0.15, 95% CI 0.05–0.26, I2 = 90.91. Narrative analysis suggested malaria's adverse impact on vaccine responses in animals. Malaria infection may impair vaccines responses; with preventive treatment of malaria partially reversing these effects, highlighting the need for targeted public health interventions. [ABSTRACT FROM AUTHOR]

Background: Variations in vaccine responses have been observed between populations. A role for helminth infections has been proposed due to their immunomodulatory properties. In a secondary analysis of data from a randomised trial assessing effects of anthelminthic treatment on vaccine responses, we examined associations between helminth infections at baseline prior to vaccine administration, and vaccine responses among adolescents (9-17 years) in Koome Islands, Lake Victoria, Uganda. Methods: Participants received BCG [week 0], yellow fever (YF-17D), oral typhoid (Ty21a), HPV-prime [week 4], and HPV-boost, tetanus/diphtheria [week 28]. Outcomes were BCG-specific interferon-g ELISpot responses and antibody responses to yellow-fever-, typhoid-, HPV-, tetanus- and diphtheria-specific antigens measured at two time points post vaccination. S. mansoni infection was determined as positive if either the plasma Circulating Anodic Antigen (CAA) assay or stool PCR were positive. Hookworm and Strongyloides were determined by stool PCR. Linear mixed effects regression was used to assess associations. Results: Among 478 adolescents, 70% were Schistosoma mansoni (Sm) infected and 23% hookworm infected at baseline. Sm was associated with lower Salmonella Typhi O:LPS-specific IgG responses (adjusted geometric mean ratio (aGMR) 0.69 (0.57-0.83)), and hookworm with higher diphtheria-specific IgG (aGMR 1.16 (1.02, 1.31)) and lower HPV-16-specific IgG (aGMR 0.70 (0.55, 0.90)) post-vaccination. High Sm intensity was associated with lower BCG-specific interferon-g and S. Typhi O:LPS-specific IgG. Conclusions: We found inverse associations between Sm and responses to two live vaccines, whereas hookworm was positively associated with diphtheriaspecific IgG. These findings support the hypothesis that helminth infections can modulate vaccine responses, while also highlighting potential heterogeneity in the direction of these effects. [ABSTRACT FROM AUTHOR]

BackgroundPopulation size estimates (PSEs) for hidden populations at increased risk of HIV, including female sex workers (FSWs), are important to inform public health policy and resource allocation. The service multiplier method (SMM) is commonly used to estimate the sizes of hidden populations. We used this method to obtain PSEs for FSWs at 9 sites in Zimbabwe and explored methods for assessing potential biases that could arise in using this approach. ObjectiveThis study aimed to guide the assessment of biases that arise when estimating the population sizes of hidden populations using the SMM combined with respondent-driven sampling (RDS) surveys. MethodsWe conducted RDS surveys at 9 sites in late 2013, where the Sisters with a Voice program (the program), which collects program visit data of FSWs, was also present. Using the SMM, we obtained PSEs for FSWs at each site by dividing the number of FSWs who attended the program, based on program records, by the RDS-II weighted proportion of FSWs who reported attending this program in the previous 6 months in the RDS surveys. Both the RDS weighting and SMM make a number of assumptions, potentially leading to biases if the assumptions are not met. To test these assumptions, we used convergence and bottleneck plots to assess seed dependence of RDS-II proportion estimates, chi-square tests to assess if there was an association between the characteristics of FSWs and their knowledge of program existence, and logistic regression to compare the characteristics of FSWs attending the program with those recruited to RDS surveys. ResultsThe PSEs ranged from 194 (95% CI 62-325) to 805 (95% CI 456-1142) across 9 sites from May to November 2013. The 95% CIs for the majority of sites were wide. In some sites, the RDS-II proportion of women who reported program use in the RDS surveys may have been influenced by the characteristics of selected seeds, and we also observed bottlenecks in some sites. There was no evidence of association between characteristics of FSWs and knowledge of program existence, and in the majority of sites, there was no evidence that the characteristics of the populations differed between RDS and program data. ConclusionsWe used a series of rigorous methods to explore potential biases in our PSEs. We were able to identify the biases and their potential direction, but we could not determine the ultimate direction of these biases in our PSEs. We have evidence that the PSEs in most sites may be biased and a suggestion that the bias is toward underestimation, and this should be considered if the PSEs are to be used. These tests for bias should be included when undertaking population size estimation using the SMM combined with RDS surveys.

Objectives: Schistosomiasis is persistent in Lake Albert, Uganda, but local data are limited. This study aims to describe the local burden of moderate‐to‐heavy infection and associated morbidity in all ages and identify factors associated with these outcomes to guide further research. Methods: This cross‐sectional pilot study was conducted in July–August, 2022 in four village sites (Walukuba, Rwentale, Kyabarangwa and Runga) of the Praziquantel in Preschoolers (PIP) trial. Residents (approximately four per household) of any age of households of PIP participants were eligible, but individuals <10 years were only enrolled if no older individuals were available. Socio‐demographic information, household location, single stool Kato‐Katz and hepatic ultrasound results were obtained for a convenience sampled subset of trial households. The primary outcome, moderate‐to‐heavy infection (≥100 eggs per gram of faeces), was analysed using mixed‐effects logistic regression, with a household random effect. Univariate analyses were used for the secondary outcome, periportal fibrosis (Niamey protocol ultrasound image pattern C–F). Results: Of 243 participants with a median age of 22 (interquartile range 12–33) years from 66 households, 49.8% (103/207 with a Kato‐Katz result) had moderate‐to‐heavy infection and 11.2% (25/224 with ultrasound data) had periportal fibrosis. Moderate‐to‐heavy infection clustered by household (intraclass correlation coefficient = 0.11) and, in multivariable analysis, varied by village (Walukuba vs. Kyabarangwa adjusted odds ratio [aOR] 0.11, 95% CI 0.02–0.71), was highest in participants aged 10–15 years (vs. 5–9 years aOR 6.14, 95% CI 1.61–23.38) and lower in those reporting praziquantel treatment in the past year (aOR 0.39, 95% CI 0.18–0.88). Conclusions: In this setting, schistosome infection and morbidity are pervasive in all age groups. More intensive interventions are needed, for example more frequent praziquantel treatment, under investigation in the PIP trial and improved water and sanitation. More research is needed to understand local treatment barriers and optimal control strategies. [ABSTRACT FROM AUTHOR]

Author(s): Peter MacPherson 1,2,3,*, Emily L. Webb 4, Wala Kamchedzera 2, Elizabeth Joekes 1, Gugu Mjoli 5, David G. Lalloo 1, Titus H. Divala 2,3,6, Augustine T. Choko 1,2, Rachael [...], Background Suboptimal tuberculosis (TB) diagnostics and HIV contribute to the high global burden of TB. We investigated costs and yield from systematic HIV-TB screening, including computer-aided digital chest X-ray (DCXR-CAD). Methods and findings In this open, three-arm randomised trial, adults ([greater than or equal to]18 years) with cough attending acute primary services in Malawi were randomised (1:1:1) to standard of care (SOC); oral HIV testing (HIV screening) and linkage to care; or HIV testing and linkage to care plus DCXR-CAD with sputum Xpert for high CAD4TBv5 scores (HIV-TB screening). Participants and study staff were not blinded to intervention allocation, but investigator blinding was maintained until final analysis. The primary outcome was time to TB treatment. Secondary outcomes included proportion with same-day TB treatment; prevalence of undiagnosed/untreated bacteriologically confirmed TB on day 56; and undiagnosed/untreated HIV. Analysis was done on an intention-to-treat basis. Cost-effectiveness analysis used a health-provider perspective. Between 15 November 2018 and 27 November 2019, 8,236 were screened for eligibility, with 473, 492, and 497 randomly allocated to SOC, HIV, and HIV-TB screening arms; 53 (11%), 52 (9%), and 47 (9%) were lost to follow-up, respectively. At 56 days, TB treatment had been started in 5 (1.1%) SOC, 8 (1.6%) HIV screening, and 15 (3.0%) HIV-TB screening participants. Median (IQR) time to TB treatment was 11 (6.5 to 38), 6 (1 to 22), and 1 (0 to 3) days (hazard ratio for HIV-TB versus SOC: 2.86, 1.04 to 7.87), with same-day treatment of 0/5 (0%) SOC, 1/8 (12.5%) HIV, and 6/15 (40.0%) HIV-TB screening arm TB patients (p = 0.03). At day 56, 2 SOC (0.5%), 4 HIV (1.0%), and 2 HIV-TB (0.5%) participants had undiagnosed microbiologically confirmed TB. HIV screening reduced the proportion with undiagnosed or untreated HIV from 10 (2.7%) in the SOC arm to 2 (0.5%) in the HIV screening arm (risk ratio [RR]: 0.18, 0.04 to 0.83), and 1 (0.2%) in the HIV-TB screening arm (RR: 0.09, 0.01 to 0.71). Incremental costs were US$3.58 and US$19.92 per participant screened for HIV and HIV-TB; the probability of cost-effectiveness at a US$1,200/quality-adjusted life year (QALY) threshold was 83.9% and 0%. Main limitations were the lower than anticipated prevalence of TB and short participant follow-up period; cost and quality of life benefits of this screening approach may accrue over a longer time horizon. Conclusions DCXR-CAD with universal HIV screening significantly increased the timeliness and completeness of HIV and TB diagnosis. If implemented at scale, this has potential to rapidly and efficiently improve TB and HIV diagnosis and treatment. Trial registration clinicaltrials.gov NCT03519425.