The impact of home-based management of malaria on clinical outcomes in sub-Saharan African populations: a systematic review and meta-analysis.

BACKGROUND: Malaria remains a significant cause of morbidity and mortality globally and continues to disproportionately afflict the African population. We aimed to evaluate the effect of home management of malaria intervention on health outcomes. METHODS: In our systematic review and meta-analysis, six databases (Pubmed, Cochrane CENTRAL, EMBASE, CAB Abstracts and Global Health, CINAHL Complete, and BIOSIS) were searched for studies of home management of malaria from inception until November 15, 2023. We included before-after studies, observational studies, and randomised controlled trials of home management intervention delivered in community settings. The primary outcomes were malaria mortality and all-cause mortality. The risk of bias in individual observational studies was assessed using the ROBINS-I tool, whilst randomised controlled trials were judged using a revised Cochrane risk of bias tool and cluster-randomised controlled trials were evaluated using an adapted Cochrane risk of bias tool for cluster-randomised trials. We computed risk ratios with accompanying 95% confidence intervals for health-related outcomes reported in the studies and subsequently pooled the results by using a random-effects model (DerSimonian-Laird method). RESULTS: We identified 1203 citations through database and hand searches, from which 56 articles from 47 studies encompassing 234,002 participants were included in the systematic review. All studies were conducted in people living in sub-Saharan Africa and were rated to have a low or moderate risk of bias. Pooled analyses showed that mortality rates due to malaria (RR = 0.40, 95% CI = 0.29-0.54, P = 0.00001, I2 = 0%) and all-cause mortality rates (RR = 0.62, 95% CI = 0.53-0.72, P = 0.00001, I2 = 0%) were significantly lower among participants receiving home management intervention compared to the control group. However, in children under 5 years of age, there was no significant difference in mortality rates before and after implementation of home management of malaria. In terms of secondary outcomes, home management of malaria was associated with a reduction in the risk of febrile episodes (RR = 1.27, 95% CI = 1.09-1.47, P = 0.002, I2 = 97%) and higher effective rates of antimalarial treatments (RR = 2.72, 95% CI = 1.90-3.88, P < 0.00001, I2 = 96%) compared to standard care. Home malaria management combined with intermittent preventive treatment showed a significantly lower incidence risk of malaria than home management intervention that exclusively provided treatment to individuals with febrile illness suggestive of malaria. The risks for adverse events were found to be similar for home management intervention using different antimalarial drugs. Cost-effectiveness findings depicted that home malaria management merited special preferential scale-up. CONCLUSIONS: Home management of malaria intervention was associated with significant reductions in malaria mortality and all-cause mortality. The intervention could help decrease health and economic burden attributable to malaria. Further clinical studies are warranted to enable more meaningful interpretations with regard to wide-scale implementation of the intervention, settings of differing transmission intensity, and new antimalarial drugs.

Triple artemisinin-based combination therapy (TACT): advancing malaria control and eradication efforts.

This paper examines the far-reaching implications of Triple Artemisinin-Based Combination Therapy (TACT) in the global battle against malaria. Artemisinin-Based Combination Therapy (ACT) is recognized for its cost-effectiveness, lower likelihood of adverse events, and widespread acceptance by patients and healthcare providers. However, TACT introduces novel dimensions to the fight against malaria that make them a superior choice in several aspects. TACT has been demonstrated to address resistance, offer a broader spectrum of action, reduce the risk of treatment failure, and can be tailored to meet regional needs, strengthening the global effort to combat malaria. However, maximizing these benefits of TACT depends on accessibility, particularly in resource-limited regions where malaria is most prevalent. Collaborative efforts among stakeholders, sustainable pricing strategies, efficient supply chains, and public-private partnerships are essential to ensure that TACT reaches needy populations. Moreover, dispelling prevalent malaria myths through health education campaigns is critical in this endeavour. The paper underscores the significance of collaborative initiatives and partnerships among governments, international organizations, research institutions, acadaemia, pharmaceutical companies, and local communities. Together, these efforts can pave the way for the acceptance, adoption, and success of TACT, ultimately advancing the global goal of a malaria-free world.

Plasmodium knowlesi: the game changer for malaria eradication.

Plasmodium knowlesi is a zoonotic malaria parasite that has gained increasing medical interest over the past two decades. This zoonotic parasitic infection is prevalent in Southeast Asia and causes many cases with fulminant pathology. Despite several biogeographical restrictions that limit its distribution, knowlesi malaria cases have been reported in different parts of the world due to travelling and tourism activities. Here, breakthroughs and key information generated from recent (over the past five years, but not limited to) studies conducted on P. knowlesi were reviewed, and the knowledge gap in various research aspects that need to be filled was discussed. Besides, challenges and strategies required to control and eradicate human malaria with this emerging and potentially fatal zoonosis were described.

Protecting future antimalarials from the trap of resistance: Lessons from artemisinin-based combination therapy (ACT) failures.

Having faced increased clinical treatment failures with dihydroartemisinin-piperaquine (DHA-PPQ), Cambodia swapped the first line artemisinin-based combination therapy (ACT) from DHA-PPQ to artesunate-mefloquine given that parasites resistant to piperaquine are susceptible to mefloquine. However, triple mutants have now emerged, suggesting that drug rotations may not be adequate to keep resistance at bay. There is, therefore, an urgent need for alternative treatment strategies to tackle resistance and prevent its spread. A proper understanding of all contributors to artemisinin resistance may help us identify novel strategies to keep artemisinins effective until new drugs become available for their replacement. This review highlights the role of the key players in artemisinin resistance, the current strategies to deal with it and suggests ways of protecting future antimalarial drugs from bowing to resistance as their predecessors did.

Climate-proofing a malaria eradication strategy.

Two recent initiatives, the World Health Organization (WHO) Strategic Advisory Group on Malaria Eradication and the Lancet Commission on Malaria Eradication, have assessed the feasibility of achieving global malaria eradication and proposed strategies to achieve it. Both reports rely on a climate-driven model of malaria transmission to conclude that long-term trends in climate will assist eradication efforts overall and, consequently, neither prioritize strategies to manage the effects of climate variability and change on malaria programming. This review discusses the pathways via which climate affects malaria and reviews the suitability of climate-driven models of malaria transmission to inform long-term strategies such as an eradication programme. Climate can influence malaria directly, through transmission dynamics, or indirectly, through myriad pathways including the many socioeconomic factors that underpin malaria risk. These indirect effects are largely unpredictable and so are not included in climate-driven disease models. Such models have been effective at predicting transmission from weeks to months ahead. However, due to several well-documented limitations, climate projections cannot accurately predict the medium- or long-term effects of climate change on malaria, especially on local scales. Long-term climate trends are shifting disease patterns, but climate shocks (extreme weather and climate events) and variability from sub-seasonal to decadal timeframes have a much greater influence than trends and are also more easily integrated into control programmes. In light of these conclusions, a pragmatic approach is proposed to assessing and managing the effects of climate variability and change on long-term malaria risk and on programmes to control, eliminate and ultimately eradicate the disease. A range of practical measures are proposed to climate-proof a malaria eradication strategy, which can be implemented today and will ensure that climate variability and change do not derail progress towards eradication.

The Molecular Basis of Evolution and Disease: A Cold War Alliance.

This paper extends previous arguments against the assumption that the study of variation at the molecular level was instigated with a view to solving an internal conflict between the balance and classical schools of population genetics. It does so by focusing on the intersection of basic research in protein chemistry and the molecular approach to disease with the enactment of global health campaigns during the Cold War period. The paper connects advances in research on protein structure and function as reflected in Christian Anfinsen's The molecular basis of evolution, with a political reading of Emilé Zuckerkandl and Linus Pauling's identification of molecular disease and evolution. Beyond atomic fallout, these advances constituted a rationale for the promotion of genetic surveys of human populations in the Third World, in connection with international health programs. Light is shed not only on the experimental roots of the molecular challenge but on the broader geopolitical context where the rising role of biomedicine and public health (particularly the malaria eradication campaigns) had an impact on evolutionary biology.

Long-term impacts of early-life exposure to malaria: Evidence from Taiwan's Eradication Campaign in the 1950s.

This paper utilizes the eradication campaign in Taiwan in the 1950s to estimate the long-term impacts of early-life (in utero and postnatal) exposure to malaria. Matching adults in the 1992-2012 Taiwan Social Change Survey to the malaria intensity in their individual place and year of birth, difference-in-difference estimation shows strong evidence that the eradication increased men's own educational attainment as well as their family income in adulthood. We also use the 1980 census data to show there was a sharp education increase after the eradication. Furthermore, the eradication increased the educational attainment of married men's spouses. Finally, quantile regressions show that the effect concentrated on the lower percentile of the income distribution. Overall, our results suggest negative effects of early-life exposure to malaria.

Multistage inhibitors of the malaria parasite: Emerging hope for chemoprotection and malaria eradication.

Over time, several exciting advances have been made in the treatment and prevention of malaria; however, this devastating disease continues to be a major global health problem and affects millions of people every year. Notably, the paucity of new efficient drug molecules and the inevitable drug resistance of the malaria parasite, Plasmodium falciparum, against frontline therapeutics are the foremost struggles facing malaria eradication initiatives. According to the malaria eradication agenda, the discovery of new chemical entities that can destroy the parasite at the liver stage, the asexual blood stage, the gametocyte stage, and the insect ookinete stage of the parasite life cycle (i.e., compounds exhibiting multistage activity) are in high demand, preferably with novel and multiple modes of action. Phenotypic screening of chemical libraries against the malaria parasite is certainly a crucial step toward overcoming these crises. In the last few years, various research groups, including industrial research laboratories, have performed large-scale phenotypic screenings that have identified a wealth of chemical entities active against multiple life stages of the malaria parasite. Vital scientific and technological developments have led to the discovery of multistage inhibitors of the malaria parasite; these compounds, considered highly valuable starting points for subsequent drug discovery and eradication of malaria, are reviewed.

Humanized mouse models infected with human Plasmodium species for antimalarial drug discovery.

INTRODUCTION: Efforts on malaria drug discovery are expected to increase in the coming years to achieve malaria eradication. Owing to the increasing number of new potential candidates together with the actual limitations of the primate models, humanized mouse models infected with human Plasmodium spp. (HmHP) now appear as an alternative to the primate model. Areas covered: The authors review the progress obtained in the HmHP in the last two decades, with a special emphasis of their input on the drug discovery pathway. The authors discuss the methodologies and strategies used in these models to obtain an accurate assessment of the compound activity and a reliable prediction of the human efficacious regimen. Expert opinion: Research efforts have led us to an era in which HmHP can successfully be infected with P. falciparum, P vivax and P. ovale. Furthermore, it is now a reality that the complete human cycle of P. falciparum can be obtained in HmHP. The HmHP has shown a real input mainly in the preclinical evaluation of new compounds against the erythrocytic stages of P. falciparum. However, further technical improvements are needed before HmHP may replace the primate model.