High levels of genetic diversity in Plasmodium falciparum populations are an obstacle to malaria control. Here, we investigate the relationship between local variation in malaria epidemiology and parasite genetic diversity in Papua New Guinea (PNG). Cross-sectional malaria surveys were performed in 14 villages spanning four distinct malaria-endemic areas on the north coast, including one area that was sampled during the dry season. High-resolution msp2 genotyping of 2,147 blood samples identified 761 P. falciparum infections containing a total of 1,392 clones whose genotypes were used to measure genetic diversity. Considerable variability in infection prevalence and mean multiplicity of infection was observed at all of the study sites, with the area sampled during the dry season showing particularly striking local variability. Genetic diversity was strongly associated with multiplicity of infection but not with infection prevalence. In highly endemic areas, differences in infection prevalence may not translate into a decrease in parasite population diversity.
Background: The medical field causes significant environmental impact. Reduction of the primary care practice carbon footprint could contribute to decreasing global carbon emissions. This study aims to quantify the average carbon footprint of a primary care consultation, describe differences between primary care practices (best, worst and average performing) in western Switzerland and identify opportunities for mitigation. Methods: We conducted a retrospective carbon footprint analysis of ten private practices over the year 2018. We used life-cycle analysis to estimate carbon emissions of each sector, from manufacture to disposal, expressing results as CO2 equivalents per average consultation and practice. We then modelled an average and theoretical best- case and worst-case practices. Collected data included invoices, medical and furniture inventories, heating and power supply, staff and patient transport, laboratory analyses (in/out-house) waste quantities and management costs. Results: An average medical consultation generated 4.8 kg of CO2eq and overall, an average practice produced 30 tons of CO2eq per year, with 45.7% for staff and patient transport and 29.8% for heating. Medical consumables produced 5.5% of CO2eq emissions, while in-house laboratory and X-rays contributed less than 1% each. Emergency analyses requiring courier transport caused 5.8% of all emissions. Support activities generated 82.6% of the total CO2eq. Simulation of best- and worst-case scenarios resulted in a ten-fold variation in CO2eq emissions. Conclusion: Optimizing structural and organisational aspects of practice work could have a major impact on the carbon footprint of primary care practices without large-scale changes in medical activities.
There is a need to investigate the effectiveness and appropriateness of antibiotics prescription within the Integrated Management of Childhood Illness (IMCI) strategy in the context of routine outpatient clinics. Making use of a passive case detection system established for a malaria prevention trial in outpatient clinics in Papua New Guinea, the appropriateness and effectiveness of the use of antibiotics within the IMCI was assessed in 1605 young children. Main outcomes were prescription of antibiotics and re-attendances within 14 days for mild pneumonia, mild diarrhoea and uncomplicated malaria whether they were managed with or without antibiotics (proxy of effectiveness). Appropriateness was assessed for both mild and severe cases, while effectiveness was assessed only for mild diseases. A total of 6975 illness episodes out of 8944 fulfilled inclusion criteria (no previous attendance <14 days+full medical records). Clinical incidence rates (episodes/child/year; 95% CI) were 0.85 (0.81–0.90) for pneumonia, 0.62 (0.58–0.66) for malaria and 0.72 (0.65–0.93) for diarrhoea. Fifty three percent of 6975 sick children were treated with antibiotics, 11% were not treated with antibiotics when they should have been and in 29% antibiotics were prescribed when they should not have been. Re-attendance rates within 14 days following clinical diagnosis of mild pneumonia were 9% (126/1401) when managed with antibiotics compared to 8% (56/701) when managed without (adjusted Hazard Ratio (aHR) = 1.00 (0.57–1.76), p = 0.98). Rates for mild diarrhoea were 8% (73/874) and 9% (79/866) respectively (aHR = 0.8 (0.42–1.57), p = 0.53). Non-adherence to IMCI recommendations for prescription of antibiotics is common in routine settings in Papua New Guinea. Although recommended, the use of antibiotics in young children with mild pneumonia as defined by IMCI criteria did not impact on their outcome. Better tools and new strategies for the identification of bacterial infections that require antibiotics are urgently needed.
Polymorphism in antigens is a common mechanism for immune evasion used by many important pathogens, and presents major challenges in vaccine development. In malaria, many key immune targets and vaccine candidates show substantial polymorphism. However, knowledge on antigenic diversity of key antigens, the impact of polymorphism on potential vaccine escape, and how sequence polymorphism relates to antigenic differences is very limited, yet crucial for vaccine development. Plasmodium falciparum apical membrane antigen 1 (AMA1) is an important target of naturally-acquired antibodies in malaria immunity and a leading vaccine candidate. However, AMA1 has extensive allelic diversity with more than 60 polymorphic amino acid residues and more than 200 haplotypes in a single population. Therefore, AMA1 serves as an excellent model to assess antigenic diversity in malaria vaccine antigens and the feasibility of multi-allele vaccine approaches. While most previous research has focused on sequence diversity and antibody responses in laboratory animals, little has been done on the cross-reactivity of human antibodies. We aimed to determine the extent of antigenic diversity of AMA1, defined by reactivity with human antibodies, and to aid the identification of specific alleles for potential inclusion in a multi-allele vaccine. We developed an approach using a multiple-antigen-competition enzyme-linked immunosorbent assay (ELISA) to examine cross-reactivity of naturally-acquired antibodies in Papua New Guinea and Kenya, and related this to differences in AMA1 sequence. We found that adults had greater cross-reactivity of antibodies than children, although the patterns of cross-reactivity to alleles were the same. Patterns of antibody cross-reactivity were very similar between populations (Papua New Guinea and Kenya), and over time. Further, our results show that antigenic diversity of AMA1 alleles is surprisingly restricted, despite extensive sequence polymorphism. Our findings suggest that a combination of three different alleles, if selected appropriately, may be sufficient to cover the majority of antigenic diversity in polymorphic AMA1 antigens. Antigenic properties were not strongly related to existing haplotype groupings based on sequence analysis. Antigenic diversity of AMA1 is limited and a vaccine including a small number of alleles might be sufficient for coverage against naturally-circulating strains, supporting a multi-allele approach for developing polymorphic antigens as malaria vaccines.
Purpose: General practitioners (GPs) could play a role in mitigating climate change by raising awareness of its impact on human health and implementing changes to improve population health and decreasing environmental footprints. The aim of this study was to assess GPs’ knowledge and perspectives about the health impacts of climate change. Method: A questionnaire was sent to 1972 GPs in the French-speaking part of Switzerland. Knowledge of the impact of environmental degradations and climate change on health and willingness to address climate change with patients, to be exemplary and to act as role models were surveyed as well as demographic characteristics of GPs. Results: Respondents (N = 497) expressed a high level of self-reported knowledge regarding climate change, although it was lower for more specific topics, such as planetary health or health–environment co-benefits. Participants mostly agreed that it is necessary to adapt clinical practice to the health impacts of climate change and that they have a role in providing information on climate change and its links to human health. Conclusion: Most of the GPs were concerned about environmental and climate degradation. However, this study revealed a gap between the willingness of GPs to integrate the impact of climate change on health into their clinical activities and their lack of overall knowledge and scientific evidence on effective interventions. A promising way forward may be to develop co-benefit interventions adapted to the clinical setting on diet, active mobility and connecting with nature.