Implementation of a Randomized, Placebo-Controlled Trial of Live Attenuated Malaria Sporozoite Vaccines in an Indonesian Military Study Population.

Malaria eradication efforts prioritize safe and efficient vaccination strategies, although none with high-level efficacy against malaria infection are yet available. Among several vaccine candidates, Sanaria® PfSPZ Vaccine and Sanaria PfSPZ-CVac are, respectively, live radiation- and chemo-attenuated sporozoite vaccines designed to prevent infection with Plasmodium falciparum, the leading cause of malaria-related morbidity and mortality. We are conducting a randomized normal saline placebo-controlled trial called IDSPZV1 that will analyze the safety, tolerability, immunogenicity, and efficacy of PfSPZ Vaccine and PfSPZ-CVac administered pre-deployment to malaria-naive Indonesian soldiers assigned to temporary duties in a high malaria transmission area.

Primaquine radical cure in patients with Plasmodium falciparum malaria in areas co-endemic for P falciparum and Plasmodium vivax (PRIMA): a multicentre, open-label, superiority randomised controlled trial.

Background: In areas co-endemic for Plasmodium vivax and Plasmodium falciparum there is an increased risk of P vivax parasitaemia following P falciparum malaria. Radical cure is currently only recommended for patients presenting with P vivax malaria. Expanding the indication for radical cure to patients presenting with P falciparum malaria could reduce their risk of subsequent P vivax parasitaemia.

Weekly primaquine for radical cure of patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase deficiency.

Background: The World Health Organization recommends that primaquine should be given once weekly for 8-weeks to patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but data on its antirelapse efficacy and safety are limited.

Methods: Within the context of a multicentre, randomised clinical trial of two primaquine regimens in P. vivax malaria, patients with G6PD deficiency were excluded and enrolled into a separate 12-month observational study.

The heterogeneity of symptom reporting across study sites: a secondary analysis of a randomised placebo-controlled multicentre antimalarial trial.

Introduction: Symptoms reported following the administration of investigational drugs play an important role in decisions for registration and treatment guidelines. However, symptoms are subjective, and interview methods to quantify them are difficult to standardise. We explored differences in symptom reporting across study sites of a multicentre antimalarial trial, with the aim of informing trial design and the interpretation of safety and tolerability data.

Quantifying spatial heterogeneity of malaria in the endemic Papua region of Indonesia: Analysis of epidemiological surveillance data.

Background: As control efforts progress towards elimination, malaria is likely to become more spatially concentrated in few local areas. The purpose of this study was to quantify and characterise spatial heterogeneity in malaria transmission-intensity across highly endemic Indonesian Papua.

Methods: We analysed individual-level malaria surveillance data for nearly half a million cases (2019-2020) reported in the Papua and West Papua provinces and adapted the Gini index approach to quantify spatial heterogeneity at the district and health-unit levels.

Hypnozoite depletion in successive Plasmodium vivax relapses.

Genotyping Plasmodium vivax relapses can provide insights into hypnozoite biology. We performed targeted amplicon sequencing of 127 relapses occurring in Indonesian soldiers returning to malaria-free Java after yearlong deployment in malarious Eastern Indonesia. Hepatic carriage of multiple hypnozoite clones was evident in three-quarters of soldiers with two successive relapses, yet the majority of relapse episodes only displayed one clonal population.

Pandemic inequity in a megacity: a multilevel analysis of individual, community and healthcare vulnerability risks for COVID-19 mortality in Jakarta, Indonesia.

Introduction: Worldwide, the 33 recognised megacities comprise approximately 7% of the global population, yet account for 20% COVID-19 deaths. The specific inequities and other factors within megacities that affect vulnerability to COVID-19 mortality remain poorly defined. We assessed individual, community-level and healthcare factors associated with COVID-19-related mortality in a megacity of Jakarta, Indonesia, during two epidemic waves spanning 2 March 2020 to 31 August 2021.

Using syndromic measures of mortality to capture the dynamics of COVID-19 in Java, Indonesia, in the context of vaccination rollout.

Background: As in many countries, quantifying COVID-19 spread in Indonesia remains challenging due to testing limitations. In Java, non-pharmaceutical interventions (NPIs) were implemented throughout 2020. However, as a vaccination campaign launches, cases and deaths are rising across the island.

Clinical characteristics and mortality associated with COVID-19 in Jakarta, Indonesia: A hospital-based retrospective cohort study.

Background: Data on COVID-19-related mortality and associated factors from low-resource settings are scarce. This study examined clinical characteristics and factors associated with in-hospital mortality of COVID-19 patients in Jakarta, Indonesia, from March 2 to July 31, 2020.

Methods: This retrospective cohort included all hospitalised patients with PCR-confirmed COVID-19 in 55 hospitals.

Defining malaria risks among forest workers in Aceh, Indonesia: a formative assessment.

Background: Following a dramatic decline of malaria cases in Aceh province, geographically-based reactive case detection (RACD) was recently evaluated as a tool to improve surveillance with the goal of malaria elimination. While RACD detected few cases in households surrounding index cases, engaging in forest work was identified as a risk factor for malaria and infections from Plasmodium knowlesi-a non-human primate malaria parasite-were more common than expected. This qualitative formative assessment was conducted to improve understanding of malaria risk from forest work and identify strategies for targeted surveillance among forest workers, including adapting reactive case detection.

Towards harmonization of microscopy methods for malaria clinical research studies.

Microscopy performed on stained films of peripheral blood for detection, identification and quantification of malaria parasites is an essential reference standard for clinical trials of drugs, vaccines and diagnostic tests for malaria. The value of data from such research is greatly enhanced if this reference standard is consistent across time and geography. Adherence to common standards and practices is a prerequisite to achieve this.

Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial.

Background: Primaquine is the only widely used drug that prevents Plasmodium vivax malaria relapses, but adherence to the standard 14-day regimen is poor. We aimed to assess the efficacy of a shorter course (7 days) of primaquine for radical cure of vivax malaria.

Methods: We did a randomised, double-blind, placebo-controlled, non-inferiority trial in eight health-care clinics (two each in Afghanistan, Ethiopia, Indonesia, and Vietnam).

Association of Impaired Cytochrome P450 2D6 Activity Genotype and Phenotype With Therapeutic Efficacy of Primaquine Treatment for Latent Plasmodium vivax Malaria.

Importance: Latent hepatic Plasmodium vivax hypnozoites provoke repeated clinical attacks called relapses. Only primaquine phosphate kills hypnozoites, and its therapeutic activity may depend on naturally polymorphic cytochrome P450 2D6 isotype (CYP2D6) activity.

Objective: To examine the association of impaired CYP2D6 genotypes and CYP2D6 metabolic phenotypes with therapeutic failure of directly observed high-dose primaquine treatment for P vivax malaria relapse.

Accurate light microscopic diagnosis of South-East Asian ovalocytosis.

Introduction: South-East Asian ovalocytosis (SAO) is a common inherited red blood cell polymorphism in South-East Asian and Melanesian populations, coinciding with areas of malaria endemicity. Validation of light microscopy as a diagnostic alternative to molecular genotyping may allow for its cost-effective use either prospectively or retrospectively by analysis of archived blood smears.

Methods: We assessed light microscopic diagnosis of SAO compared to standard PCR genotyping.

Randomized trial of primaquine hypnozoitocidal efficacy when administered with artemisinin-combined blood schizontocides for radical cure of Plasmodium vivax in Indonesia.

Background: Safety and efficacy of primaquine against repeated attacks of Plasmodium vivax depends upon co-administered blood schizontocidal therapy in radical cure. We assessed primaquine (PQ) as hypnozoitocide when administered with dihydroartemisinin-piperaquine (Eurartesim®, DHA-PP) or artesunate-pyronaridine (Pyramax®, AS-PYR) to affirm its good tolerability and efficacy. A third arm, artesunate followed by primaquine, was not intended as therapy for practice, but addressed a hypothesis concerning primaquine efficacy without co-administration of blood schizontocide.

A comprehensive assessment of the malaria microscopy system of Aceh, Indonesia, in preparation for malaria elimination.

Background: The Health Office of Aceh aims to eliminate malaria from Aceh Province, Indonesia by 2015. Malaria was formerly common in Aceh (population 4.5 million), but has declined dramatically in recent years consequent to post-tsunami control efforts.

Randomized, open-label trial of primaquine against vivax malaria relapse in Indonesia.

Radical cure of Plasmodium vivax infection applies blood schizontocidal therapy against the acute attack and hypnozoitocidal therapy against later relapse. Chloroquine and primaquine have been used for 60 years in this manner. Resistance to chloroquine by the parasite now requires partnering other blood schizontocides with primaquine.