Action to protect the independence and integrity of global health research

Storeng KT, Abimbola S, Balabanova D, et al. Action to protect the independence and integrity of global health research. BMJ GLOBAL HEALTH. 2019;4(3): e001746

Effect of a 'diagonal' intervention on uptake of HIV and reproductive health services by female sex workers in three sub-Saharan African cities

Objectives: To enhance uptake of sexual and reproductive health (SRH) services by female sex workers (FSWs), we conducted an implementation study in which we piloted and tested context-specific diagonal' interventions, combining vertical, targeted interventions with horizontally improved access to the general health services, in three cities in sub-Saharan Africa. Methods: We collected indicators of SRH service uptake through face-to-face interviews with approximately 400 FSWs, pre- and post-intervention, in Durban, South Africa; Tete, Mozambique; and Mombasa, Kenya, recruited by respondent-driven sampling. Changes in uptake were tested for their statistical significance using multivariate logistic regression models. Results: In all cities, overall uptake of services increased. Having used all services for contraception, STI care, HIV testing, HIV care, cervical cancer screening and sexual violence, if needed, increased from 12.5% to 41.5% in Durban, 25.0% to 40.1% in Tete and 44.9% to 69.1% in Mombasa. Across cities, the effect was greatest in having been tested for HIV in the past six months which increased from 40.9% to 83.2% in Durban, 56.0% to 76.6% in Tete and 70.9% to 87.6% in Mombasa. In Tete and Mombasa, rise in SRH service use was almost entirely due to a greater uptake of targeted services. Only in Durban was there additionally an increase in the utilisation of general health services. Conclusion: SRH service utilisation improved in the short-term in three different sub-Saharan African contexts, primarily through vertical, targeted components. The long-term effectiveness of diagonal approaches, in particular on the use of general, horizontal health services, needs further investigation

Table_1_An optimized Factor H-Fc fusion protein against multidrug-resistant Neisseria gonorrhoeae.docx

Novel therapeutics against the global threat of multidrug-resistant Neisseria gonorrhoeae are urgently needed. Gonococci evade killing by complement by binding factor H (FH), a key inhibitor of the alternative pathway. FH comprises 20 short consensus repeat (SCR) domains organized as a single chain. Gonococci bind FH through domains 6 and 7, and C-terminal domains 18 through 20. Previously, we showed that a chimeric protein comprising (from the N- to C-terminus) FH domains 18-20 (containing a point mutation in domain 19 to prevent lysis of host cells) fused to human IgG1 Fc (called FH*/Fc1) killed gonococci in a complement-dependent manner and reduced the duration and bacterial burden in the mouse vaginal colonization model of gonorrhea. Considering the N. gonorrhoeae-binding FH domains 18-20 are C-terminal in native FH, we reasoned that positioning Fc N-terminal to FH* (Fc1/FH*) would improve binding and bactericidal activity. Although both molecules bound gonococci similarly, Fc1/FH* displayed a 5-fold lower IC50 (the concentration required for 50% killing in complement-dependent bactericidal assays) than FH*/Fc1. To further increase complement activation, we replaced human IgG1 Fc in Fc1/FH* with Fc from human IgG3, the most potent complement-activating IgG subclass, to obtain Fc3/FH*. Bactericidal activity was further increased ~2.3-fold in Fc3/FH* compared to Fc1/FH*. Fc3/FH* killed (defined by <50% survival) 45/45 (100%) diverse PorB1B-expessing gonococci, but only 2/15 PorB1A-expressing isolates, in a complement-dependent manner. Decreased Fc3/FH* binding accounted for the limited activity against PorB1A strains. Fc3/FH* was efficacious against all four tested PorB1B gonococcal strains in the mouse vaginal colonization model when administered at a dose of 5 µg intravaginally, daily. Furthermore, Fc3/FH* retained bactericidal activity when reconstituted following lyophilization or spray-drying, suggesting feasibility for formulation into intravaginal rings. In conclusion, Fc3/FH* represents a promising prophylactic immunotherapeutic against multidrug-resistant gonococci.</p