BackgroundProtective immunity against cholera is serogroup specific. Serogroup specificity in Vibrio cholerae is determined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). Generally, polysaccharides are poorly immunogenic, especially in young children.MethodologyHere we report the evaluation in mice of a conjugate vaccine for cholera (OSP:TThc) made from V. cholerae O1 Ogawa O-Specific Polysaccharide–core (OSP) and recombinant tetanus toxoid heavy chain fragment (TThc). We immunized mice intramuscularly on days 0, 21, and 42 with OSP:TThc or OSP only, with or without dmLT, a non-toxigenic immunoadjuvant derived from heat labile toxin of Escherichia coli.Principal FindingsWe detected significant serum IgG antibody responses targeting OSP following a single immunization in mice receiving OSP:TThc with or without adjuvant. Anti-LPS IgG responses were detected following a second immunization in these cohorts. No anti-OSP or anti-LPS IgG responses were detected at any time in animals receiving un-conjugated OSP with or without immunoadjuvant, and in animals receiving immunoadjuvant alone. Responses were highest following immunization with adjuvant. Serum anti-OSP IgM responses were detected in mice receiving OSP:TThc with or without immunoadjuvant, and in mice receiving unconjugated OSP. Serum anti-LPS IgM and vibriocidal responses were detected in all vaccine cohorts except in mice receiving immunoadjuvant alone. No significant IgA anti-OSP or anti-LPS responses developed in any group. Administration of OSP:TThc and adjuvant also induced memory B cell responses targeting OSP and resulted in 95% protective efficacy in a mouse lethality cholera challenge model.ConclusionWe describe a protectively immunogenic cholera conjugate in mice. Development of a cholera conjugate vaccine could assist in inducing long-term protective immunity, especially in young children who respond poorly to polysaccharide antigens.

The advent of antiretroviral therapy (ART) in 1996 brought with it an urgent need to develop models of health care delivery that could enable its effective and equitable delivery, especially to patients living in poverty. Community-based care, which stretches from patient homes and communities—where chronic infectious diseases are often best managed—to modern health centers and hospitals, offers such a model, providing access to proximate HIV care and minimizing structural barriers to retention. We first review the recent literature on community-based ART programs in low- and low-to-middle-income country settings and document two key principles that guide effective programs: decentralization of ART services and long-term retention of patients in care. We then discuss the evolution of the community-based programs of Partners In Health (PIH), a nongovernmental organization committed to providing a preferential option for the poor in health care, in Haiti and several countries in sub-Saharan Africa, Latin America, Russia and Kazakhstan. As one of the first organizations to treat patients with HIV in low-income settings and a pioneer of the community-based approach to ART delivery, PIH has achieved both decentralization and excellent retention through the application of an accompaniment model that engages community health workers in the delivery of medicines, the provision of social support and education, and the linkage between communities and clinics. We conclude by showing how PIH has leveraged its HIV care delivery platforms to simultaneously strengthen health systems and address the broader burden of disease in the places in which it works.

Aerobic fitness has been shown to have several beneficial effects on child health. However, research on its relationship with academic performance has been limited, particularly in developing countries and among undernourished populations. This study examined the association between aerobic fitness and academic achievement in clinically healthy but nutritionally compromised Indian school-aged children and assessed whether micronutrient status affects this association. 273 participants, aged 7 to 10.5 years, were enrolled from three primary schools in Bangalore, India. Data on participants’ aerobic fitness (20-m shuttle test), demographics, anthropometry, diet, physical activity, and micronutrient status were abstracted. School-wide exam scores in mathematics and Kannada language served as indicators of academic performance and were standardized by grade level. The strength of the fitness/achievement association was analyzed using Spearman’s rank correlation, multiple variable logistic regression, and multi-level models. Significant positive correlations between aerobic capacity (VO2 peak) and academic scores in math and Kannada were observed (P < 0.05). After standardizing scores across grade levels and adjusting for school, gender, socioeconomic status, and weight status (BMI Z-score), children with greater aerobic capacities (mL * kg-1 * min-1) had greater odds of scoring above average on math and Kannada exams (OR=1.08, 95% CI: 1.02 to 1.15 and OR=1.11, 95% CI: 1.04 to 1.18, respectively). This association remained significant after adjusting for micronutrient deficiencies. These findings provide preliminary evidence of a fitness/achievement association in Indian children. While the mechanisms by which aerobic fitness may be linked to academic achievement require further investigation, the results suggest that educators and policymakers should consider the adequacy of opportunities for physical activity and fitness in schools for both their physical and potential academic benefits.