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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 [...]

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. [...]

Introduction: Soil-transmitted helminths (STHs) are the most common nematodes that infect human, especially children who live in tropical climates, particularly Indonesia. The frequency of anthelmintics administration depends on the burden of STHs in each area. Several studies showed residual infections despite twice yearly antihelmintic administration. Objective: To compare STH residual infection after treatment with albendazole for two and three times a year in primary school children. Methods: This was an open-label randomized clinical trial. The children were divided into two groups receiving either two or three times albendazole a year. All subjects were followed longitudinally for one year. Chi-squared statistical analysis was done to compare residual infections, whereas paired t-test was used to compare eggs per gram (epg). Result: There were 330 from 834 children with STH infections. There was a decrease in infection rate from 38.2% to 21.8% after the administration of albendazole as a single dose for three times a year with reduce A. lumbricoides, T. trichiura and hookworms infection. However, there were no significant differences in residual infections of the two groups post-albendazole treatment with P value 0.129. Conclusion: Albendazole treatment two times a year shows similar efficacy to three times a year treatment for residual infection. [ABSTRACT FROM AUTHOR]

In 2017, diphtheria outbreaks occurred in several provinces in Indonesia; however, the epidemiological data in the country is limited. The aim of this study was to determine the association between clinical findings and laboratory parameters associated with mortality of children with diphtheria. A retrospective cohort study was conducted at Haji Adam Malik General Hospital, Medan, Indonesia, covering diphtheria patients from January 2020 to December 2023. All patients aged 1-18 years clinically diagnosed with diphtheria were considered eligible. The associations between demographic characteristics, clinical features, immunization status, complications, and laboratory profiles with mortality were determined using Fisher's exact test, and the odds ratio (OR) with a 95% confidence interval (95%CI) was calculated. Our data indicated that the clinical characteristics of myocarditis ( p =0.005) and airway obstruction ( p =0.003) were associated with mortality. There was also a significant association between thrombocytopenia ( p =0.020) and mortality in diphtheria patients. Patients with airway obstruction were 13 times more likely to have an increase in mortality compared to patients without airway obstruction. This study highlights that clinical and laboratory characteristics could be associated with in-hospital mortality of diphtheria cases, and therefore, pediatricians should be aware of the presence of those characteristics to prevent the mortality of the patients., Competing Interests: All authors affirm that they have no conflicts of interest., (© 2024 The Author(s).)

This study investigated indicators of the severity and mortality of COVID-19 in children in Medan, Sumatera Utara Province, Indonesia. The aim of this study was to identify determinants of severity and outcome of children with COVID-19 as the lesson learned from the COVID-19 pandemic, particularly the limited health facilities in Indonesia. This retrospective cohort study was conducted in 2020, 2021, and 2022 at multiple centers. Inpatient and outpatient children confirmed to be SARS-CoV-2 positive were randomly recruited in the selected hospitals. Baseline data (demographic, clinical, laboratory and radiological data) were collected, and outcomes were classified as recovered/deceased (for the inpatient group) or returned to the hospital (for the outpatient group). Severity status was identified based on the Indonesia COVID-19 guidelines. The laboratory data were categorized according to international standards and data were analyzed using univariate analyzes followed by multivariate logistic regression. A total of 303 inpatient and 114 outpatient children were included in the analysis. Out of the total inpatient cases, nine patients died, with 2.9 mortality rate. Our final multivariate indicated that the presence of shortness of breath (SOB), anemia, and abnormal C-reactive protein (CRP) levels were significantly associated with the severity or the presence of emergency signs, while the presence of SOB and comorbidities were significantly associated with mortality in inpatient children with COVID-19. The presence of fever, cough, SOB, muscle ache and diarrhea were the reasons why the children were returned to the hospital from self-isolation at home among outpatient COVID-19 cases; however, the cough was the only significant factor in the final multivariate mode. This study highlights important determinants of COVID-19 severity and mortality in children, which should be considered during clinical decision-making in low-resource settings of healthcare centers in Indonesia., Competing Interests: All the authors declare that there are no conflicts of interest, (© 2024 The Author(s).)

Background: Primaquine is used to eliminate Plasmodium vivax hypnozoites, but its optimal dosing regimen remains unclear. We undertook a systematic review and individual patient data meta-analysis to investigate the efficacy and tolerability of different primaquine dosing regimens to prevent P vivax recurrence., Methods: For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, and if they included a treatment group with daily primaquine given over multiple days, where primaquine was commenced within 7 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, or dihydroartemisinin-piperaquine). We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. We assessed the effects of total dose and duration of primaquine regimens on the rate of first P vivax recurrence between day 7 and day 180 by Cox's proportional hazards regression (efficacy analysis). The effect of primaquine daily dose on gastrointestinal symptoms on days 5-7 was assessed by modified Poisson regression (tolerability analysis). The study was registered with PROSPERO, CRD42019154470., Findings: Of 226 identified studies, 23 studies with patient-level data from 6879 patients from 16 countries were included in the efficacy analysis. At day 180, the risk of recurrence was 51·0% (95% CI 48·2-53·9) in 1470 patients treated without primaquine, 19·3% (16·9-21·9) in 2569 patients treated with a low total dose of primaquine (approximately 3·5 mg/kg), and 8·1% (7·0-9·4) in 2811 patients treated with a high total dose of primaquine (approximately 7 mg/kg), regardless of primaquine treatment duration. Compared with treatment without primaquine, the rate of P vivax recurrence was lower after treatment with low-dose primaquine (adjusted hazard ratio 0·21, 95% CI 0·17-0·27; p<0·0001) and high-dose primaquine (0·10, 0·08-0·12; p<0·0001). High-dose primaquine had greater efficacy than low-dose primaquine in regions with high and low relapse periodicity (ie, the time from initial infection to vivax relapse). 16 studies with patient-level data from 5609 patients from ten countries were included in the tolerability analysis. Gastrointestinal symptoms on days 5-7 were reported by 4·0% (95% CI 0·0-8·7) of 893 patients treated without primaquine, 6·2% (0·5-12·0) of 737 patients treated with a low daily dose of primaquine (approximately 0·25 mg/kg per day), 5·9% (1·8-10·1) of 1123 patients treated with an intermediate daily dose (approximately 0·5 mg/kg per day) and 10·9% (5·7-16·1) of 1178 patients treated with a high daily dose (approximately 1 mg/kg per day). 20 of 23 studies included in the efficacy analysis and 15 of 16 in the tolerability analysis had a low or unclear risk of bias., Interpretation: Increasing the total dose of primaquine from 3·5 mg/kg to 7 mg/kg can reduce P vivax recurrences by more than 50% in most endemic regions, with a small associated increase in gastrointestinal symptoms., Funding: Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture., Competing Interests: Declaration of interests JAG and GCKWK are former employees of GSK and hold shares in GSK and AstraZeneca. GCKWK reports travel support from AstraZeneca. JKB reports institutional research funding from Medicines for Malaria Venture, GSK, Wellcome Trust, and Sanaria; participation on the US National Institutes of Health data safety monitoring board; and membership of the editorial board of Travel Medicine and Infectious Disease and the guidelines development group for malaria control and elimination, Global Malaria Programme, WHO. RJC, JKB, and RNP report contributions to Up-to-Date. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)