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The Asia-Pacific region faces significant challenges in eliminating malaria. More than 2 billion people are at risk of malaria, with multiple species of the parasite and various vectors transmitting the disease. The World Health Organization (WHO) and the Asia Pacific Leaders Malaria Alliance (APLMA) are working towards malaria elimination by 2030, with Australia providing financial and technical support. However, progress has been variable, and recent factors such as the COVID-19 pandemic, climate change, and armed conflict have hindered efforts. Challenges include the need for more sensitive tools to detect malaria, the inadequacy of current prevention methods, drug resistance, and the complexity of treating P. vivax infections. To achieve malaria elimination, innovative tools and strategies must be developed and implemented, with collaboration, community engagement, and political commitment. [Extracted from the article]

Objective To determine household and health-care provider costs associated with Plasmodium vivax infection across a range of endemic settings. Methods We collected cost data alongside three multicentre clinical trials of P vivax treatment in Afghanistan, Brazil, Colombia, Ethiopia, Indonesia, Philippines, Peru, Thailand and Viet Nam conducted between April 2014 to December 2017. We derived household costs from trial participant surveys administered at enrolment and again 2 weeks later to determine the costs of treatment and transportation, and the number of days that patients and their household caregivers were unable to undertake their usual activities. We determined costs of routine care by health-care providers by micro-costing the resources used to diagnose and treat P vivax at the study sites. Findings The mean total household costs ranged from 8.7 United States dollars (US$; standard deviation, SD: 4.3) in Afghanistan to US$ 254.7 (SD: 148.4) in Colombia. Across all countries, productivity losses were the largest household cost component, resulting in mean indirect costs ranging from US$ 5.3 (SD: 3.0) to US$ 220.8 (SD: 158.40). The range of health-care provider costs for routine care was US$ 3.6-6.6. The cost of administering a glucose-6-phosphate-dehydrogenase rapid diagnostic test, ranged from US$ 0.9 to 13.5, consistently lower than the costs of the widely-used fluorescent spot test (US$ 6.3 to 17.4). Conclusion An episode of P vivax malaria results in high costs to households. The costs of diagnosing and treating P vivax are important inputs for future cost-effectiveness analyses to ensure optimal allocation of resources for malaria elimination. Objectif Determiner les couts, pour les menages et les prestataires de soins, associes a l'infection par Plasmodium vivax dans differentes zones endemiques. Methodes Nous avons recueilli des donnees sur les couts a l'occasion de trois essais cliniques multicentres relatifs au traitement contre P vivax menes en Afghanistan, au Bresil, en Colombie, en Ethiopie, en Indonesie, aux Philippines, au Perou, en Thailande et au Viet Nam entre avril 2014 et decembre 2017. Nous avons calcule les couts pour les menages a partir d'enquetes realisees aupres des participants aux essais, lors de leur admission puis 2 semaines plus tard, afin de determiner les couts de traitement et de transport ainsi que le nombre de jours ou les patients et leurs aidants familiaux n'avaient pu accomplir leurs activites habituelles. Nous avons determine le cout des soins courants par les prestataires de soins en calculant le cout individuel des ressources utilisees pour diagnostiquer et traiter P vivax sur le site des etudes. Resultats Les couts totaux moyens pour les menages allaient de 8.7 dollars des Etats-Unis ($ US; ecart type, ET: 4,3) en Afghanistan a 254.7 $ US (ET: 148,4) en Colombie. Tous pays confondus, les pertes de productivity etaient la principale composante des couts pour les menages, puisqu'elles entrainaient des couts indirects moyens allant de 5,3 $ US (ET: 3,0) a 220,8 $ US (ET: 158,40). En ce qui concerne les prestataires de soins, le cout des soins courants allait de 3,6 a 6,6 $ US. Le cout de realisation d'un test de diagnostic rapide base sur le glucose6- phosphate-deshydrogenase variait de 0,9 $ US a 13,5 $ US, un cout toujours inferieur a celui du tres repandu test par fluorescence (6,3 $ US a 17,4 $ US). Conclusion Un episode de paludisme a P vivax entraine des couts eleves pour les menages. Connaitre les couts du diagnostic et du traitement de P vivax sera fort utile aux futures analyses cout-efficacite. Cela permettra d'affecter les ressources de maniere optimale en vue d'eradiquer le paludisme. Objetivo Determinar los costos del hogar y de los proveedores de atencion de la salud asociados con la infeccion por Plasmodium vivax en una variedad de ambitos endemicos. Metodos Se recopilaron datos de costos junto con tres ensayos clinicos multicentricos del tratamiento con P. vivax en Afganistan, Brasil, Colombia, Etiopia, Filipinas, Indonesia, Peru, Tailandia y Vietnam realizados entre abril de 2014 y diciembre de 2017. Los costos del hogar se derivaron de las encuestas de los participantes del ensayo administradas en el momento de la inscripcion y de nuevo dos semanas despues para determinar los costos del tratamiento y del transporte, asi como el numero de dias en que los pacientes y los cuidadores en el hogar no pudieron llevar a cabo sus actividades habituales. Se determinaron los costos de la atencion de rutina por parte de los proveedores de atencion de la salud mediante el microcosto de los recursos utilizados para diagnosticar y tratar el P. vivax en los centros de estudio. Resultados Los costos totales promedio de los hogares oscilaron entre 8,7 dolares estadounidenses (USD; desviacion estandar, DE: 4,3) en Afganistan y 254,7 USD (DE: 148,4) en Colombia. En todos los paises, las perdidas de productividad fueron el mayor componente del costo del hogar, lo que dio lugar a costos indirectos promedios que oscilaron entre 5,3 y 220,8 USD. El rango de los costos de los proveedores de atencion de la salud para la atencion de rutina fue de 3,6 a 6,6 USD. El costo por administrar una prueba de diagnostico rapido de la glucosa-6- fosfatodeshidrogenasa, vario de 0,9 a 13,5 USD, consistentemente mas bajo que los costos de la prueba de fluorescencia aleatoria ampliamente utilizada (6,3 a 17,4 USD). Conclusion Un episodio de malaria por P. vivax tiene como resultado un alto costo para el hogar. Los costos del diagnostico y tratamiento de P. vivax son insumos importantes para futuros analisis de costoefectividad que aseguren una asignacion optima de recursos para la eliminacion de la malaria., Introduction Outside Sub-Saharan Africa, Plasmodium vivax is now the predominant cause of malaria, affecting 14.0 million patients in 2016. (1) While cost-effectiveness analyses can inform the efficient provision of health-care [...]

Author(s): Kamala Thriemer 1, Benedikt Ley 1, Lorenz von Seidlein 2,3,* Summary points Efforts to control Plasmodium vivax malaria have been less successful than for Plasmodium falciparum , resulting in [...]

Background Glucose-6-phosphate dehydrogenase (G6PD) activity is dependent upon G6PD genotype and age of the red blood cell (RBC) population, with younger RBCs having higher activity. Peripheral parasitemia with Plasmodium spp. induces hemolysis, replacing older RBCs with younger cells with higher G6PD activity. This study aimed to assess whether G6PD activity varies between individuals with and without malaria or a history of malaria. Methods and findings Individuals living in the Chittagong Hill Tracts of Bangladesh were enrolled into 3 complementary studies: (i) a prospective, single-arm clinical efficacy trial of patients (n = 175) with uncomplicated malaria done between 2014 and 2015, (ii) a cross-sectional survey done between 2015 and 2016 (n = 999), and (iii) a matched case-control study of aparasitemic individuals with and without a history of malaria done in 2020 (n = 506). G6PD activity was compared between individuals with and without malaria diagnosed by microscopy, rapid diagnostic test (RDT), or polymerase chain reaction (PCR), and in aparasitemic participants with and without a history of malaria. In the cross-sectional survey and clinical trial, 15.5% (182/1,174) of participants had peripheral parasitemia detected by microscopy or RDT, 3.1% (36/1,174) were positive by PCR only, and 81.4% (956/1,174) were aparasitemic. Aparasitemic individuals had significantly lower G6PD activity (median 6.9 U/g Hb, IQR 5.2-8.6) than those with peripheral parasitemia detected by microscopy or RDT (7.9 U/g Hb, IQR 6.6-9.8, p < 0.001), but G6PD activity similar to those with parasitemia detected by PCR alone (submicroscopic parasitemia) (6.1 U/g Hb, IQR 4.8-8.6, p = 0.312). In total, 7.7% (14/182) of patients with malaria had G6PD activity < 70% compared to 25.0% (248/992) of participants with submicroscopic or no parasitemia (odds ratio [OR] 0.25, 95% CI 0.14-0.44, p < 0.001). In the case-control study, the median G6PD activity was 10.3 U/g Hb (IQR 8.8-12.2) in 253 patients with a history of malaria and 10.2 U/g Hb (IQR 8.7-11.8) in 253 individuals without a history of malaria (p = 0.323). The proportion of individuals with G6PD activity < 70% was 11.5% (29/253) in the cases and 15.4% (39/253) in the controls (OR 0.7, 95% CI 0.41-1.23, p = 0.192). Limitations of the study included the non-contemporaneous nature of the clinical trial and cross-sectional survey. Conclusions Patients with acute malaria had significantly higher G6PD activity than individuals without malaria, and this could not be accounted for by a protective effect of G6PD deficiency. G6PD-deficient patients with malaria may have higher than expected G6PD enzyme activity and an attenuated risk of primaquine-induced hemolysis compared to the risk when not infected., Author(s): Benedikt Ley 1,*, Mohammad Shafiul Alam 2, Mohammad Golam Kibria 2, Jutta Marfurt 1, Ching Swe Phru 2, Jenifar Quaiyum Ami 2, Kamala Thriemer 1, Sarah Auburn 1, Nusrat [...]

Background There is a high risk of Plasmodium vivax parasitaemia following treatment of falciparum malaria. Our study aimed to quantify this risk and the associated determinants using an individual patient data meta-analysis in order to identify populations in which a policy of universal radical cure, combining artemisinin-based combination therapy (ACT) with a hypnozoitocidal antimalarial drug, would be beneficial. Methods and findings A systematic review of Medline, Embase, Web of Science, and the Cochrane Database of Systematic Reviews identified efficacy studies of uncomplicated falciparum malaria treated with ACT that were undertaken in regions coendemic for P. vivax between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of P. vivax parasitaemia at days 42 and 63 and associated risk factors were investigated by multivariable Cox regression analyses. Study quality was assessed using a tool developed by the Joanna Briggs Institute. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42018097400). In total, 42 studies enrolling 15,341 patients were included in the analysis, including 30 randomised controlled trials and 12 cohort studies. Overall, 14,146 (92.2%) patients had P. falciparum monoinfection and 1,195 (7.8%) mixed infection with P. falciparum and P. vivax. The median age was 17.0 years (interquartile range [IQR] = 9.0-29.0 years; range = 0-80 years), with 1,584 (10.3%) patients younger than 5 years. 2,711 (17.7%) patients were treated with artemether-lumefantrine (AL, 13 studies), 651 (4.2%) with artesunate-amodiaquine (AA, 6 studies), 7,340 (47.8%) with artesunate-mefloquine (AM, 25 studies), and 4,639 (30.2%) with dihydroartemisinin-piperaquine (DP, 16 studies). 14,537 patients (94.8%) were enrolled from the Asia-Pacific region, 684 (4.5%) from the Americas, and 120 (0.8%) from Africa. At day 42, the cumulative risk of vivax parasitaemia following treatment of P. falciparum was 31.1% (95% CI 28.9-33.4) after AL, 14.1% (95% CI 10.8-18.3) after AA, 7.4% (95% CI 6.7-8.1) after AM, and 4.5% (95% CI 3.9-5.3) after DP. By day 63, the risks had risen to 39.9% (95% CI 36.6-43.3), 42.4% (95% CI 34.7-51.2), 22.8% (95% CI 21.2-24.4), and 12.8% (95% CI 11.4-14.5), respectively. In multivariable analyses, the highest rate of P. vivax parasitaemia over 42 days of follow-up was in patients residing in areas of short relapse periodicity (adjusted hazard ratio [AHR] = 6.2, 95% CI 2.0-19.5; p = 0.002); patients treated with AL (AHR = 6.2, 95% CI 4.6-8.5; p < 0.001), AA (AHR = 2.3, 95% CI 1.4-3.7; p = 0.001), or AM (AHR = 1.4, 95% CI 1.0-1.9; p = 0.028) compared with DP; and patients who did not clear their initial parasitaemia within 2 days (AHR = 1.8, 95% CI 1.4-2.3; p < 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high. Conclusions In this meta-analysis, we found a high risk of P. vivax parasitaemia after treatment of P. falciparum malaria that varied significantly between studies. These P. vivax infections are likely attributable to relapses that could be prevented with radical cure including a hypnozoitocidal agent; however, the benefits of such a novel strategy will vary considerably between geographical areas., Author(s): Mohammad S. Hossain 1,2,3,4, Robert J. Commons 1,2,5, Nicholas M. Douglas 2,3, Kamala Thriemer 2, Bereket H. Alemayehu 6, Chanaki Amaratunga 7, Anupkumar R. Anvikar 8, Elizabeth A. Ashley [...]

Background Artemisinin-based combination therapy (ACT) is recommended for uncomplicated Plasmodium vivax malaria in areas of emerging chloroquine resistance. We undertook a systematic review and individual patient data meta-analysis to compare the efficacies of dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL) with or without primaquine (PQ) on the risk of recurrent P. vivax. Methods and findings Clinical efficacy studies of uncomplicated P. vivax treated with DP or AL and published between January 1, 2000, and January 31, 2018, were identified by conducting a systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42016053310. Investigators of eligible studies were invited to contribute individual patient data that were pooled using standardised methodology. The effect of mg/kg dose of piperaquine/lumefantrine, ACT administered, and PQ on the rate of P. vivax recurrence between days 7 and 42 after starting treatment were investigated by Cox regression analyses according to an a priori analysis plan. Secondary outcomes were the risk of recurrence assessed on days 28 and 63. Nineteen studies enrolling 2,017 patients were included in the analysis. The risk of recurrent P. vivax at day 42 was significantly higher in the 384 patients treated with AL alone (44.0%, 95% confidence interval [CI] 38.7-49.8) compared with the 812 patients treated with DP alone (9.3%, 95% CI 7.1-12.2): adjusted hazard ratio (AHR) 12.63 (95% CI 6.40-24.92), p < 0.001. The rates of recurrence assessed at days 42 and 63 were associated inversely with the dose of piperaquine: AHRs (95% CI) for every 5-mg/kg increase 0.63 (0.48-0.84), p = 0.0013 and 0.83 (0.73-0.94), p = 0.0033, respectively. The dose of lumefantrine was not significantly associated with the rate of recurrence (1.07 for every 5-mg/kg increase, 95% CI 0.99-1.16, p = 0.0869). In a post hoc analysis, in patients with symptomatic recurrence after AL, the mean haemoglobin increased 0.13 g/dL (95% CI 0.01-0.26) for every 5 days that recurrence was delayed, p = 0.0407. Coadministration of PQ reduced substantially the rate of recurrence assessed at day 42 after AL (AHR = 0.20, 95% CI 0.10-0.41, p < 0.001) and at day 63 after DP (AHR = 0.08, 95% CI 0.01-0.70, p = 0.0233). Results were limited by follow-up of patients to 63 days or less and nonrandomised treatment groups. Conclusions In this study, we observed the risk of P. vivax recurrence at day 42 to be significantly lower following treatment with DP compared with AL, reflecting the longer period of post-treatment prophylaxis; this risk was reduced substantially by coadministration with PQ. We found that delaying P. vivax recurrence was associated with a small but significant improvement in haemoglobin. These results highlight the benefits of PQ radical cure and also the provision of blood-stage antimalarial agents with prolonged post-treatment prophylaxis., Author(s): Robert J. Commons 1,2,*, Julie A. Simpson 3, Kamala Thriemer 1, Tesfay Abreha 4, Ishag Adam 5, Nicholas M. Anstey 1, Ashenafi Assefa 6, Ghulam R. Awab 7,8, J. [...]