Mapping the impact of the expanded Mexico City Policy for HIV/ family planning service integration in PEPFAR-supported countries: a risk index.

BACKGROUND: The previously-named Mexico City Policy (MCP) - which prohibited non U.S.-based non-governmental organizations (NGOs) from receiving U.S. family planning (FP) funding if they advocated, provided, counseled, or referred clients for abortions, even with non-U.S. funds - was reinstated and expanded in 2017. For the first time, the expanded MCP (EMCP) applies to HIV funding through the President's Emergency Plan for AIDS Relief (PEPFAR) in addition to FP funding. Previous, and more limited, iterations of the policy forced clinic closures and decreased contraceptive access, prompting the need to examine where and how the EMCP may impact FP/HIV service integration. METHODS: The likelihood of FP/HIV service de-integration under the EMCP was quantified using a composite risk index for 31 PEPFAR-funded countries. The index combines six standardized indicators from publically available sources organized into three sub-indexes: 1) The importance of PEPFAR for in-country service delivery of HIV and FP services; 2) The susceptibility of implementing partners to the EMCP; and 3) The integration of FP/HIV funds and programming through PEPFAR and USAID. RESULTS: Countries with the highest overall risk scores included Zambia (3.3) Cambodia (3.2), Uganda (3.1), South Africa (2.9), Haiti (2.8), Lesotho (2.8), Swaziland (2.1), and Burundi (1.5). Zambia's risk score is driven by sub-index 1, having a high proportion of country HIV expenditures provided by PEPFAR (86.3%). Cambodia and Uganda's scores are driven sub-index 3, with both countries reporting 100% of PEPFAR supported HIV delivery sites were providing integrated FP services in 2017. South Africa's risk score is driven by sub-index 2, where roughly 60% of PEPFAR funding is to non U.S.-based NGOs. Of the countries with the highest risk scores, Swaziland, Lesotho, and South Africa, are also in the top quartile of PEPFAR countries for HIV prevalence and unintended pregnancies among young women. CONCLUSION: This analysis highlights where and why the EMCP may have the greatest impact on FP/HIV service integration. The possible disruption of service integration in countries with generalized HIV epidemics highlights significant risks. Researchers, national governments, and non-U.S. funders can consider these risk factors to help target their responses to the EMCP and mitigate potential harms of the policy.

Comparative molecular profiling of multidrug-resistant Pseudomonas aeruginosa identifies novel mutations in regional clinical isolates from South India.

Objectives: We sought to analyse the antibiotic susceptibility profiles and molecular epidemiology of MDR clinical Pseudomonas aeruginosa isolates from South India using non-MDR isolates as a reference. Methods: We established a comprehensive clinical strain library consisting of 58 isolates collected from patients across the South Indian state of Kerala from March 2017 to July 2019. The strains were subject to antibiotic susceptibility testing, modified carbapenem inactivation method assay for carbapenemase production, PCR sequencing, comparative sequence analysis and quantitative PCR of MDR determinants associated with antibiotic efflux pump systems, fluoroquinolone resistance and carbapenem resistance. We performed in silico modelling of MDR-specific SNPs. Results: Of our collection of South Indian P. aeruginosa clinical isolates, 74.1% were MDR and 55.8% were resistant to the entire panel of antibiotics tested. All MDR isolates were resistant to levofloxacin and 93% were resistant to meropenem. We identified seven distinct, MDR-specific mutations in nalD, three of which are novel. mexA was significantly overexpressed in strains that were resistant to the entire test antibiotic panel while gyrA and gyrB were overexpressed in MDR isolates. Mutations in fluoroquinolone determinants were significantly associated with MDR phenotype and a novel GyrA Y100C substitution was observed. Carbapenem resistance in MDR isolates was associated with loss-of-function mutations in oprD and high prevalence of NDM (blaNDM-1) within our sample. Conclusions: This study provides insight into MDR mechanisms adopted by P. aeruginosa clinical isolates, which may guide the potential development of therapeutic regimens to improve clinical outcomes.

A Novel N4-Like Bacteriophage Isolated from a Wastewater Source in South India with Activity against Several Multidrug-Resistant Clinical Pseudomonas aeruginosa Isolates.

Multidrug-resistant community-acquired infections caused by the opportunistic human pathogen Pseudomonas aeruginosa are increasingly reported in India and other locations globally. Since this organism is ubiquitous in the environment, samples such as sewage and wastewater are rich reservoirs of P. aeruginosa bacteriophages. In this study, we report the isolation and characterization of a novel P. aeruginosa N4-like lytic bacteriophage, vB_Pae_AM.P2 (AM.P2), from wastewater in Kerala, India. AM.P2 is a double-stranded DNA podovirus that efficiently lyses the model strain, PAO1, at a multiplicity of infection as low as 0.1 phage per bacterium and resistance frequency of 6.59 × 10-4 Synergy in bactericidal activity was observed between AM.P2 and subinhibitory concentrations of the antibiotic ciprofloxacin. Genome sequencing of AM.P2 revealed features similar to those of the N4-like P. aeruginosa phages LUZ7 and KPP21. As judged by two independent assay methods, spot tests and growth inhibition, AM.P2 successfully inhibited the growth of almost 30% of strains from a contemporary collection of multidrug-resistant P. aeruginosa clinical isolates from South India. Thus, AM.P2 may represent an intriguing candidate for inclusion in bacteriophage cocktails developed for various applications, including water decontamination and clinical bacteriophage therapy.IMPORTANCE In India, multidrug resistance determinants are much more abundant in community-associated bacterial pathogens due to the improper treatment of domestic and industrial effluents. In particular, a high bacterial load of the opportunistic pathogen P. aeruginosa in sewage and water bodies in India is well documented. The isolation and characterization of bacteriophages that could target emerging P. aeruginosa strains, representing possible epicenters for community-acquired infections, could serve as a useful alternative tool for various applications, such as phage therapy and environmental treatment. Continuing to supplement the repertoire of broad-spectrum bacteriophages is an essential tool in confronting this problem.