Key factors to facilitate locally driven family planning programming: a qualitative analysis of urban stakeholder perspectives in Africa and Asia.

BACKGROUND: There has been greater recognition of the importance of country ownership in global health and development. However, operationalising country ownership to ensure the scale up and sustainability of proven interventions remains elusive at best. To address this challenge, we undertook a thematic analysis of interviews collected from representatives of local governments, public health systems, and communities in poor urban areas of East Africa, Francophone West Africa, India, and Nigeria, supported by The Challenge Initiative (TCI), aiming to rapidly and sustainably scale up evidence-based reproductive health and family planning solutions. METHODS: The main objective of this study was to explore critical elements needed for implementing and scaling evidence-based family planning interventions. The research team conducted thematic analysis of 96 stories collected using the Most Significant Change (MSC) technique between July 2018 and September 2019. After generating 55 unique codes, the codes were grouped into related themes, using TCI's model as a general analytical framework. RESULTS: Five key themes emerged: (1) strengthening local capacity and improving broader health systems, (2) shifting mindsets of government and community toward local ownership, (3) institutionalising the interventions within existing government structures, (4) improving data demand and use for better planning of health services, and (5) enhancing coordination of partners. CONCLUSION: While some themes feature more prominently in a particular region than others, taken together they represent what stakeholders perceive to be essential elements for scaling up locally-driven health programmes in urban areas in Africa and Asia.

Genetic diversity of Plasmodium vivax metacaspase 1 and Plasmodium vivax multi-drug resistance 1 genes of field isolates from Mauritania, Sudan and Oman.

BACKGROUND: Plasmodium vivax is the second most important human malaria parasite, widely spread across the world. This parasite is associated with important issues in the process toward malaria elimination, including potential for relapse and increased resistance to chloroquine. Plasmodium vivax multi-drug resistant (pvmdr1) is suspected to be a marker of resistance although definitive evidence is lacking. Progress has been made in knowledge of biological factors affecting parasite growth, including mechanisms of regulated cell death and the suspected role of metacaspase. Plasmodium vivax metacaspase1 (PvMCA1-cd) has been described with a catalytic domain composed of histidine (H372) and cysteine (C428) residues. The aim of this study was to test for a link between the conserved histidine and cysteine residues in PvMCA1-cd, and the polymorphism of the P. vivax multi-drug resistant gene (pvmdr1). RESULTS: Thirty P. vivax isolates were collected from Mauritania, Sudan, and Oman. Among the 28 P. vivax isolates successfully sequenced, only 4 samples showed the conserved His (372)-Cys (428) residues in PvMCA1-cd. Single nucleotide polymorphisms observed were H372T (46.4%), H372D (39.3%), and C428R (85.7%). A new polymorphic catalytic domain was observed at His (282)-Cys (305) residues. Sequences alignment analysis of pvmdr1 showed SNP in the three codons 958, 976 and 1076. A single SNP was identified at the codon M958Y (60%), 2 SNPs were found at the position 976: Y976F (13%) and Y976V (57%), and 3 SNPs were identified at the position 1076: F1076L (40%), F1076T (53%) and F1076I (3%). Only one isolate was wildtype in all three codons (MYF), 27% were single MYL mutants, and 10% were double MFL mutants. Three new haplotypes were also identified: the triple mutant YVT was most prevalent (53.3%) distributed in the three countries, while triple YFL and YVI mutants (3%), were only found in samples from Sudan and Mauritania. CONCLUSIONS: Triple or quadruple mutants for metacaspase genes and double or triple mutants for Pvmdr1 were observed in 24/28 and 19/28 samples. There was no difference in the frequency of mutations between PvMCA1-cd and Pvmdr1 (P > 0.2). Histidine and cysteine residues in PvMCA1-cd are highly polymorphic and linkage disequilibrium with SNPs of Pvmdr1 gene may be expected from these three areas with different patterns of P. vivax transmission.

Drying anti-malarial drugs in vitro tests to outsource SYBR green assays.

BACKGROUND: Measurement of anti-malarial drug efficacy and resistance relies mainly on in vivo clinical trials, in vitro/ex vivo assays and molecular markers detection. The existing in vitro/ex vivo assays, in particular those that are using non-radioactive devices, need to be standardized and adapted to field conditions. SYBR Green assay offers a rapid and cheap alternative to other in vitro assays, but it requires tools not commonly available in field laboratories. Here is described a modified SYBR green I protocol to perform the parasite growth test with blood samples in endemic areas, followed later by the SYBR green fluorescence assay performed at a specialized laboratory level. METHODS: In vitro susceptibility of Plasmodium falciparum clones HB3, 3D7, W2 and 7G8 to chloroquine (CQ), dihydroartemisinin (DHA), pyronaridine (PYD) and piperaquine (PPQ) was tested. Fresh isolates of P. falciparum from imported malaria cases were collected for ex vivo assays. The parasite suspension was added in 96-well plates predosed with anti-malarial drugs and incubated for 72 hours at 37°C, 5% CO2. SYBR green I protocol was modified to dry the plates after freeze-thawed process to mimic storage and shipping conditions. The plates were rehydrated with 200 µl of complete RPMI medium for fluorescence assay. RESULTS: There were no significant differences in IC50 values of CQ, DHA, PYD and PPQ, determined by the modified protocol, compared to standard protocol. Longer storage did not affect the IC50 values. CONCLUSION: The SYBR green I modified protocol produced reliable results and could be a suitable method for in vitro/ex vivo assays in field.

Increasing Contraceptive Use Through Free Family Planning Special Days in Poor Urban Areas in Francophone West Africa.

INTRODUCTION: In francophone West Africa (FWA), contraceptive uptake remains limited, often due to geographic, economic, and social barriers. With technical support from The Challenge Initiative (TCI), municipalities and health systems implemented Family Planning Special Days (FPSDs) to improve family planning (FP) uptake and reduce high unmet need. The FPSD intervention consisted of organizing free FP services on a monthly or quarterly basis over 2 to 5 consecutive days within health facilities or sites close to the population. These events helped to educate, inform, and mobilize the community around FP and improve geographic and financial access to FP services. We describe the process of implementing FPSDs in FWA countries and analyze the results. METHODS: We used several techniques and data sources in our descriptive analysis, including document review of activity reports, analysis of health management information system data, and retrospective data collection on the profile of FPSD users and implementation costs. RESULTS: Between July 2020 and June 2021, municipalities and health systems collaborated to hold 1,046 FPSDs in 452 health facilities in 10 FWA cities. This collaboration was made possible through the establishment of city-level management and coordination units composed of municipal, health system, and TCI focal points. In the 10 FWA cities, 181,792 people were made aware of the FPSDs and 71,669 contraceptive users were served. The overall cost of organizing the FPSDs was about 145382501 Central African CFA francs (US$252839), 35% of which came from the municipalities' local financial contribution. DISCUSSION: Results from our analysis showed that, with appropriate financial support from municipalities, the health system could offer high-quality free FP services. Nonetheless, there are still challenges to the sustainability of conducting FPSDs, including the availability of contraceptive products and continued financing of the strategy during system shocks such as the COVID-19 pandemic.

Implementing Quality Improvement Initiatives to Improve the Use of Adolescent- and Youth-Friendly Health Services in Zou, Benin.

INTRODUCTION: In Benin, the unmet need for family planning services is especially high for adolescent girls and youth aged 15-24 years. The Challenge Initiative (TCI) supported the health system to assess and improve the quality of adolescent and youth sexual reproductive health services and enhance contraceptive uptake in 65 service delivery points (SDPs) of the Zou department. PROGRAM DESCRIPTION: Between June 2019 and March 2021, TCI supported the health districts in Zou to train an assessment team to complete 3 cycles of quality assessments (QAs) using a QA checklist adapted to the local context. Based on assessment scores, the SDPs were categorized into poor, moderate, or good to excellent quality. The SDP managers developed remedial action plans after each cycle and for each SDP and followed up with supportive supervision. RESULTS: The first QA cycle showed that 52% of assessed SDPs achieved a good to excellent classification; by the second QA cycle, this reached 74%. However, the quality of adolescent- and youth-friendly health services regressed during the third QA cycle (during COVID-19 pandemic disruptions), when only 40% of SDPs achieved the good to excellent category. Between the first and second QA cycles, contraceptive uptake for adolescents and youth improved in the SDPs that had good or excellent quality of services, compared to the ones that were of lower quality (established significance level of 5% with a P value of .031). CONCLUSION: Further assessments could deepen our understanding of the internal and external factors that can affect service quality. The findings reinforce the importance of investing in quality improvement strategies to maximize the use of sexual and reproductive health services among adolescents and youth. They also underscore the need for a contextual and nuanced approach to ensure enduring results.

An outbreak of locally acquired Plasmodium vivax malaria among migrant workers in Oman.

Plasmodium vivax is the most widely distributed human malaria parasite. Outside sub-Saharan Africa, the proportion of P. vivax malaria is rising. A major cause for concern is the re-emergence of Plasmodium vivax in malaria-free areas. Oman, situated in the south-eastern corner of the Arabian Peninsula, has long been an area of vivax malaria transmission but no locally acquired cases were reported in 2004. However, local transmission has been registered in small outbreaks since 2007. In this study, a local outbreak of 54 cases over 50 days in 2014 was analyzed retrospectively and stained blood slides have been obtained for parasite identification and genotyping. The aim of this study was to identify the geographical origin of these cases, in an attempt to differentiate between imported cases and local transmission. Using circumsporozoite protein (csp), merozoite surface protein 1 (msp1), and merozoite surface protein 3 (msp3) markers for genotyping of parasite DNA obtained by scrapping off the surface of smears, genetic diversity and phylogenetic analysis were performed. The study found that the samples had very low genetic diversity, a temperate genotype, and a high genetic distance, with most of the reference strains coming from endemic countries. We conclude that a small outbreak of imported malaria is not associated with re-emergence of malaria transmission in Oman, as no new cases have been seen since the outbreak ended.

Diagnostic accuracy of loop-mediated isothermal amplification (LAMP) for screening patients with imported malaria in a non-endemic setting.

BACKGROUND: Sensitive and easy-to-perform methods for the diagnosis of malaria are not yet available. Improving the limit of detection and following the requirements for certification are issues to be addressed in both endemic and non-endemic settings. The aim of this study was to test whether loop-mediated isothermal amplification of DNA (LAMP) may be an alternative to microscopy or real-time PCR for the screening of imported malaria cases in non-endemic area. RESULTS: 310 blood samples associated with 829 suspected cases of imported malaria were tested during a one year period. Microscopy (thin and thick stained blood slides, reference standard) was used for the diagnosis. Real-time PCR was used as a standard of truth, and LAMP (Meridian Malaria Plus) was used as an index test in a prospective study conducted following the Standards for Reporting Diagnosis Accuracy Studies. In the 83 positive samples, species identification was P. falciparum (n = 66), P. ovale (n = 9), P. vivax (n = 3) P. malariae (n = 3) and 2 co-infections with P. falciparum + P.malariae. Using LAMP methods, 93 samples gave positive results, including 4 false-positives. Sensitivity, specificity, positive predictive value and negative predictive value for LAMP tests were 100%, 98.13%, 95.51%, and 100% compared to PCR. CONCLUSION: High negative predictive value, and limit of detection suggest that LAMP can be used for screening of imported malaria cases in non-endemic countries when expert microscopists are not immediately available. However, the rare occurrence of non-valid results and the need for species identification and quantification of positive samples preclude the use of LAMP as a single reference method.

Wanted Plasmodium falciparum, dead or alive.

Mechanisms of cell death in unicellular parasites have been subjects of debate for the last decade, with studies demonstrating evidence of apoptosis or non-apoptosis like mechanisms, including necrosis, and autophagy. Recent clarifications on the definition of regulated or accidental cell death by The Nomenclature Committee on Cell Death provides an opportunity to reanalyze some data, re-evaluate conclusions in the light of parasite diversity, and to propose alternative arguments in the context of malaria drug resistance, considering lack of really new drugs in the pipeline. Deciphering the mechanisms of death may help in detection of new drug targets and the design of innovative drugs. However, classifications have been evolving rapidly since initial description of "programmed cell death", leading to some uncertainty as to whether Plasmodium cell death is accidental or regulated.