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Objective Nigeria ranks highest globally in malaria burden, disproportionately affecting children. This study investigated trends in the incidence and outcomes of 948 children with cases of severe malaria in a tertiary hospital in northwestern Nigeria. Methods We conducted a retrospective cross-sectional study of children with severe malaria between January 1, 2019, and December 31, 2022. We extracted relevant data, including sociodemographics, clinical features, as well as hospitalization outcomes (death or discharge), and the trends analyzed over the period. Results Of the 8,295 pediatric admissions during the study period, 948 (11.4%) were cases of severe malaria. The trends of severe malaria (incidence) showed a surge of 17.3% in 2020 from 11.4% in 2019 and subsequently declined to 9.9% in 2022 (p < 0.001). There was a decline in the proportion of under-fives with severe malaria from 47.5% observed in 2019 to 43.7% in 2022 (p = 0.019). The overall mortality rate (malaria specific) was 7.2% (68/948) which rose from 2.3% in 2019 to 10.3% in 2020 and declined to 8.5% in 2022, p = 0.003. The proportion of malaria-specific deaths (from all-cause mortality) increased from 4.6% in 2019 to 17.3% in 2020 and declined to 9.3% in 2022 (p = 0.004). Among under-fives, there was no significant change in the malaria-specific mortality rate (from 3.2% in 2019 to 10.2% in 2020, 6.4% in 2021 and 10.3% in 2022, p = 0.104) and the proportion of malaria-specific deaths in under-fives among malaria deaths (from 66.7% in 2019 to 52.9% in 2022, p = 0.653). Among the clinical features, the presence of cerebral malaria and acute kidney injury had the highest case fatality rate (57.1%). Conclusion Despite the initial surge in severe malaria cases during the coronavirus disease 2019 era, there has been an overall progressive decline in childhood severe malaria. However, among those under-fives, the trends in malaria deaths remained unchanged. [ABSTRACT FROM AUTHOR]

Nigeria accounts for 39% of global malaria deaths in children under 5 years of age and the effective management of severe malaria is a health priority. The Annual Nigeria Severe Malaria Stakeholders Workshop, held on the 5–6th of July 2023 in Abuja, Nigeria brought together representatives from 36 States, the Federal Capital Territory, and other key stakeholders to address the management of severe malaria across all levels of the health service. Aims were to provide updates and review progress on severe malaria activities, the burden of disease, commodity logistics management, and pre-referral national policy implementation as well as to disseminate research findings. Two roundtable discussions were conducted to identify the challenges, barriers, and facilitators to the effective management of severe malaria in Nigeria. A key challenge was the limited awareness of updated guidelines and strategic documents among frontline health workers, leading to the misuse of non-recommended medications, like α-β-arteether. Further to this, the need to ensure appropriate treatments during pregnancy and the adoption of the WHO directive on the use of rectal artesunate were highlighted. To address these issues, innovative dissemination channels for guideline awareness were recommended and collaboration with professional organizations to enrich training materials emphasized. Other areas for improvement considered the processes involved in severe malaria management, with insufficient coordination among government agencies, inadequate referral linkages, and inadequate human resources identified as barriers. Recommendations focused on practical measures to minimize wastage of injectable artesunate, enhance data management through scaling up electronic medical records, and strengthen referral systems. The extension of severe malaria surveillance to patients older than 5 years was also proposed. To deliver these changes, actionable plans for sustained recruitment and training are needed, as well as committed advocacy at all levels to ensure timely fund disbursement and institutional support. A key overarching theme from the workshop was that a multifaceted approach was needed to address severe malaria in Nigeria, emphasizing collaborative efforts, evidence-based practices, and strategic resource allocation. With the largest malaria burden globally, the potential impact of addressing the challenges of severe malaria management in Nigeria cannot be understated and must be urgently addressed. [ABSTRACT FROM AUTHOR]

Background: Recent reports of artemisinin partial resistance from Rwanda and Uganda are worrisome and suggest a future policy change to adopt new anti-malarials. This is a case study on the evolution, adoption, and implementation of new anti-malarial treatment policies in Nigeria. The main objective is to provide perspectives to enhance the future uptake of new anti-malarials, with an emphasis on stakeholder engagement strategies. Methods: This case study is based on an analysis of policy documents and stakeholders' perspectives drawn from an empirical study conducted in Nigeria, 2019–2020. A mixed methods approach was adopted, including historical accounts, review of programme and policy documents, and 33 qualitative in-depth interviews and 6 focus group discussions. Results: Based on policy documents reviewed, the adoption of artemisinin-based combination therapy (ACT) in Nigeria was swift due to political will, funding and support from global developmental partners. However, the implementation of ACT was met with resistance from suppliers, distributors, prescribers, and end-users, attributed to market dynamics, costs and inadequate stakeholder engagement. Deployment of ACT in Nigeria witnessed increased developmental partner support, robust data generation, ACT case-management strengthening and evidence on anti-malarial use in severe malaria and antenatal care management. A framework for effective stakeholder engagement for the future adoption of new anti-malarial treatment strategies was proposed. The framework covers the pathway from generating evidence on drug efficacy, safety and uptake; to making treatment accessible and affordable to end-users. It addresses which stakeholders to engage with and the content of engagement strategies with key stakeholders at different levels of the transition process. Conclusion: Early and staged engagement of stakeholders from global bodies to community level end-users is critical to the successful adoption and uptake of new anti-malarial treatment policies. A framework for these engagements was proposed as a contribution to enhancing the uptake of future anti-malarial strategies. [ABSTRACT FROM AUTHOR]

In non-anaemic children with malaria, early-appearing anaemia (EAA) is common following artemisinin-based combination treatments (ACTs) and it may become persistent (PEAA). The factors contributing to and kinetics of resolution of the deficit in haematocrit from baseline (DIHFB) characteristic of ACTs-related PEAA were evaluated in 540 consecutive children with malaria treated with artemether-lumefantrine, artesunate-amodiaquine or dihydroartemisinin-piperaquine. Asymptomatic PEAA occurred in 62 children. In a multiple logistic regression model, a duration of illness ≤3 days before presentation, haematocrit

Objective To explore the cost-effectiveness of parenteral artesunate for the treatment of severe malaria in children and its potential impact on hospital budgets. Methods The costs of inpatient care of children with severe malaria were assessed in four of the 11 sites included in the African Quinine Artesunate Malaria Treatment trial, conducted with over 5400 children. The drugs, laboratory tests and intravenous fluids provided to 2300 patients from admission to discharge were recorded, as was the length of inpatient stay, to calculate the cost of inpatient care. The data were matched with pooled clinical outcomes and entered into a decision model to calculate the cost per disability-adjusted life year (DALY) averted and the cost per death averted. Findings The mean cost of treating severe malaria patients was similar in the two study groups: 63.5 United States dollars (US$) (95% confidence interval, Cl: 61.7-65.2) in the quinine arm and US$ 66.5 (95% Cl: 63.7-69.2) in the artesunate arm. Children treated with artesunate had 22.5% lower mortality than those treated with quinine and the same rate of neurological sequelae: (artesunate arm: 2.3 DALYs per patient; quinine arm: 3.0 DALYs per patient). Compared with quinine as a baseline, artesunate showed an incremental cost per DALY averted and an incremental cost per death averted of US$ 3.8 and US$ 123, respectively. Conclusion Artesunate is a highly cost-effective and affordable alternative to quinine for treating children with severe malaria. The budgetary implications of adopting artesunate for routine use in hospital-based care are negligible. Objectif Etudier la rentabilite de l'artesunate parenteral dans le cadre du traitement d'enfants gravement atteints de paludisme et son impact potentiel sur les budgets hospitaliers. Methodes Les couts des soins administres aux patients hospitalises gravement atteints de paludisme ont ete evalues dans 4 des 11 sites participant a l'essai Traitement quinine/artesunate contre le paludisme en Afrique, realise sur plus de 5400 enfants. Afin de calculer le cout de l'hospitalisation, les medicaments, les essais en laboratoire et les liquides intraveineux administres a 2300 patients entre leur admission et leur sortie ont ete enregistres, ainsi que la duree de l'hospitalisation. Les donnees ont ete comparees avec les resultats cliniques regroupes et integres a un modele de decision afin de calculer le cout par annee de vie corrigee du facteur invalidite (AVCI) evite et le cout par deces evite. Resultats Le cout moyen du traitement des patients gravement atteints du paludisme s'est revele similaire dans les deux groupes experimentaux: 63,5 dollars americains (US$) (intervalle de confiance 95% IC: 61,7-65,2) pour le bras recevant la quinine et 66,5 US$ (95% IC: 63,7-69,2) pour le bras recevant l'artesunate. Les enfants traites par artesunate affichaient un taux de mortalite inferieur de 22,5% a ceux recevant de la quinine, et un taux de sequelles neurologiques identique: (bras recevant l'artesunate: 2,3 AVCI par patient; bras recevant la quinine: 3,0 AVCI par patient). En comparaison avec la quinine en tant que ligne de base, l'artesunate a demontre un cout incremental par AVCI evitee et un cout incremental par deces evite de 3,8 US$ et 123 US$, respectivement. Conclusion Dans le cadre du traitement des enfants gravement atteints de paludisme, rartesunate constitue une alternative extremement rentable et abordable par rapport a la quinine. Les implications budgetaires liees a l'adoption de l'artesunate pour une utilisation habituelle Iors des soins hospitaliers sont negligeables. Objetivo Analizar la relacion coste-eficacia del artesunato parenteral en el tratamiento de la malaria grave infantil y su posible impacto en los presupuestos hospitalarios. Metodos En cuatro de los 11 centros incluidos en el Estudio comparativo de los tratamientos de la malaria con artesunato y quinina en Africa participaron mas de 5400 ninos. Para calcular el coste de la hospitalizacion se registraron los farmacos, las pruebas clinicas y los liquidos endovenosos suministrados a 2300 pacientes, desde su ingreso hasta el alta, segun la duracion del ingreso del paciente. Los datos se compararon con los resultados clinicos agrupados e introducidos en un modelo de decision para calcular el coste por ano de vida ajustada por discapacidad (AVAD) evitada y el coste por muerte evitada. Resultados El coste medio del tratamiento de los pacientes con malaria grave fue similar en los dos grupos del estudio: 63,5 dolares estadounidenses (US$) (intervalo de confianza del 95%, IC: 61,7-65,2) en el grupo de quinina y US$ 66,5 (IC del 95%: 63,7-69,2) en el grupo de artesunato. Los ninos tratados con artesunato presentaron una mortalidad un 22,5% inferior que los tratados con quinina y la misma tasa de secuelas neurologicas: (grupo de artesunato: 2,3 AVAD por paciente; grupo de quinina: 3,0 AVAD por paciente). En comparacion con la quinina como referencia, el artesunato ha mostrado un coste incremental por AVAD evitado y un coste incremental por muerte evitada de US$ 3,8 y US$ 123, respectivamente. Conclusion El artesunato es una alternativa a la quinina muy rentable y con una excelente relacion coste-eficacia para el tratamiento de ninos con malaria grave. Las implicaciones presupuestarias de la adopcion del artesunato para su uso sistematico en la asistencia hospitalaria son insignificantes., Introduction Despite reported falling transmission in much of sub-Saharan Africa, (1-3) malaria remains a leading cause of inpatient admissions and mortality in paediatric wards. (4-6) The policy for first-line treatment [...]

Introduction: Understanding the human immune response to Plasmodium falciparum gametocytes and its association with gametocytemia is essential for understanding the transmission of malaria as well as progressing transmission blocking vaccine candidates. Methods: In a multi-national clinical efficacy trial of artemisinin therapies (13 sites of varying transmission over South-East Asia and Africa), we measured Immunoglobulin G (IgG) responses to recombinant P. falciparum gametocyte antigens expressed on the gametocyte plasma membrane and leading transmission blocking vaccine candidates Pf s230 (Pf s230c and Pf s230D1M) and Pf s48/45 at enrolment in 1,114 participants with clinical falciparum malaria. Mixed effects linear and logistic regression were used to determine the association between gametocyte measures (gametocytemia and gametocyte density) and antibody outcomes at enrolment. Results: Microscopy detectable gametocytemia was observed in 11% (127/1,114) of participants at enrolment, and an additional 9% (95/1,114) over the follow-up period (up to day 42) (total 20% of participants [222/1,114]). IgG levels in response to Pf s230c, Pf s48/45 and Pf s230D1M varied across study sites at enrolment (p < 0.001), as did IgG seroprevalence for anti- Pf s230c and D1M IgG (p < 0.001), but not for anti- Pf s48/45 IgG (p = 0.159). In adjusted analyses, microscopy detectable gametocytemia at enrolment was associated with an increase in the odds of IgG seropositivity to the three gametocyte antigens (Pf s230c OR [95% CI], p : 1.70 [1.10, 2.62], 0.017 ; Pf s48/45: 1.45 [0.85, 2.46], 0.174 ; Pf s230D1M: 1.70 [1.03, 2.80], 0.037), as was higher gametocyte density at enrolment (per two-fold change in gametocyte density Pf s230c OR [95% CI], p : 1.09 [1.02, 1.17], 0.008 ; Pf s48/45: 1.05 [0.98, 1.13], 0.185 ; Pf s230D1M: 1.07 [0.99, 1.14], 0.071). Conclusion: Pf s230 and Pf s48/45 antibodies are naturally immunogenic targets associated with patent gametocytemia and increasing gametocyte density across multiple malaria endemic settings, including regions with emerging artemisinin-resistant P. falciparum. [ABSTRACT FROM AUTHOR]