21st International Congress for Tropical Medicine and Malaria (ICTMM) – 2024: Day 2

MESA Correspondents bring you cutting-edge coverage from the ICTMM 2024 Congress “Global Responses and Interdisciplinary Research Towards Eliminating Tropical Diseases”.

Malaria – Diagnostics 1

Himanshu Gupta (GLA University, India) presented a study that investigated the role of miR-3158-3p which is released upon organ damage as a biomarker for the diagnosis of severe malaria. He pointed out that the increase in fatality due to severe malaria is associated with sequestration of P. falciparum-infected erythrocytes that leads to organ dysfunction. Using quantitative reverse transcriptase PCRs, the study validated the potential of miR-3158-3p as a biomarker in severe malaria cases as well as its correlation with the severity in patients. Gupta revealed the observation of high levels of miRNA in patients with cerebral malaria compared to patients with non-severe malaria. Change in the micro-RNA levels suggests its potential as a new tool and a cheaper alternative to neuroimaging techniques in the diagnosis of severe malaria.  

Mohammad Shoyaib Khazi (London School of Hygiene and Tropical Medicine – LSHTM, United Kingdom) presented a study that assessed factors affecting non-usage of bed nets by women of the reproductive age group in India. Khazi highlighted the role of bed nets in the fight against malaria which led to their study on factors affecting usage among women within the reproductive age in the country. The study utilized data from the National Family Health Survey that assessed annual parasite index at a community level and demographics at individual levels of over 700,000 participants. He stated that the study found a correlation between bed-net usage with age, education status, and annual parasite index.  According to him the high non-usage in urban areas, in regions with high API, and in women with low levels of formal education is of concern. Mohammad emphasized the need for continued enlightenment on the importance of using bed nets through informal education, mass media, and social media among populations in India to maximally harness the benefits of the bed nets in the fight against malaria in the country.  

Chiging Tupe (ICMR National Institute of Malaria Research, India) presented a study on the mosquito protein ferritin’s effect on Plasmodium survival in malaria vectors. The protein which plays a crucial role in iron metabolism is reported in the study to exhibit a diet-dependent expression in Anopheles mosquitoes used in the study. Tupe added that the study targeted various stages of the mosquito life cycle using ferritin selective and broad iron chelators. Iron chelators in their study were interestingly found not only to have an inhibitory effect on Plasmodium survival but also to cause larvicidal effect and decrease in oocytes in female mosquitoes owing to its role in the transport of iron to ovaries. Tupe highlighted the importance of iron chelators and suggested their use in new drug development for malaria control.

Huai Chang (Nagasaki University, Japan) presented on the development of a system that will evaluate expression of an exogenously introduced Schizont Infected Cell Agglutination (SICA) protein on red blood cell surface caused by Plasmodium knowlesi infection. He highlighted the importance of understanding the molecular basis of Plasmodium knowlesi pathogenicity and virulence owing to its increasing cases and associated mortality in Southeast Asia for an effective intervention strategy. Chang reported an observed sequestration of P. knowlesi-infected red blood cells that is associated with disease severity in patients. They interestingly discovered a protein, which mediated the adhesion of P. knowlesi to infected red blood cells in human umbilical vein endothelial cells, and named it SICA-HUVEC. He added that the discovery could be useful for screening of chemicals that can be used in inhibiting the expression of parasite-derived molecules on infected red blood cell surfaces with the aim of reducing the parasite’s virulence in patients. 

Davinder Kaur (Postgraduate Institute of Medical Education and Research, India) presented a study that investigated Toll-Like Receptors (TLR) polymorphism from 65 clinical blood samples positive for Plasmodium vivax using PCR-RFLP. The study further identified levels of cytokines from serum of the samples using ELISA to investigate the association between TLR polymorphism and cytokine levels. The study not only detected 4 types of polymorphisms from the samples but also revealed an association between the polymorphism and cytokine levels. Kaur described this relationship as an indicator that could be used in vaccine development and in designing new tools for the control of malaria.

Rahul Pasupureddy (ICMR National Institute of Malaria Research, India) expressed the importance of malaria protease in the degradation of host’s red blood cells (RBC) during the erythrocytic phase of Plasmodium infection. Pasupureddy presented a study that investigated the interactions of malarial proteases, falcipains, with their natural substrate haemoglobin and their inhibitor using a combination of bioinformatics and mutagenesis analysis. The study revealed the role of a single amino acid in mediating interaction of the malarial protein falcipain with haemoglobin in RBCs. He revealed how their study characterised novel interactions of FP2 with haemoglobin and also described this phenomenon as potential chemotherapeutic applications in the future.

Peeyush (ICMR National Institute of Malaria Research, India) addressed the challenges of mosquito identification that often required expert knowledge and an ample amount of time. Peeyush presented a study that focused on creating an AI-powered application that can easily be used to identify mosquitoes. Peeyush’s study used 950 laboratory-reared mosquitoes of different species. Peeyush added that quality data images and optimized model configurations are key to the development of the AI application. One of the limitations of the current development of the application is the requirement of in-depth morphology for species-specific identification. Peeyush indicated that source, resolution, and model complexity are critical to achieving higher accuracy. Future work will focus on expanding the dataset and refining model configurations to enhance accuracy, providing practical applications in mosquito surveillance and vector control.

Parsakorn Tapaopong (Mahidol University, Thailand) presented a study that investigated the trend in Plasmodium knowlesi surface protein polymorphism in Thailand over a span of 20 years. Samples at different time periods from the study were compared for the polymorphism which  revealed that samples from recent years expressed fewer haplotypes than samples from previous years after sequencing the 42-kDa region of pkmsp1. He linked the observed reduction to mutation which was mediated by adaptive response of the parasite to evade host immunity caused by its increased widespread transmission across the country and beyond. He concluded that findings in their study will contribute to understanding  the evolutionary changes of the parasite which could pose a significant threat for malaria control strategies.

Jing Wen Hang (National University of Singapore – NUS, Singapore) presented a study discovering malaria’s complexity via volume electron microscopy (vEM). Hang noted the role of parasite-host interaction for diagnostic methods and treatment of malaria. Their study investigated the application of vEM in studying different developmental stages of Plasmodium falciparum and Plasmodium knowlesi. The presented method is expected to provide a 3D visualisation of the parasite’s structures with high resolution and identification of ultrastructural features. Weng added that the technique helped in a better understanding of parasites morphology, host-parasite interaction, drug development as well as malaria treatment and prevention. Despite its potentials, she also pointed out the pitfalls of the method which include it being sluggish and the difficulty in interpreting data of complex 3Ds and the requirement of specialised skills and advanced computational tools.

Symposium P03 –  At the Cusp of Malaria Elimination: What are the Lessons Asia can Share with Africa?

Kimberly Fornace (National University of Singapore – NUS, Singapore) reviewed the factors that drive and distribute simian malaria. In doing so she identified priorities for surveillance and control,  further discussing the implications for global malaria control and elimination policies. Non-human primates play a significant role in zoonotic malaria in Malaysia, particularly in Sabah and Sarawak. It is known that Plasmodium knowlesi is the most prevalent among non-human primates. She conducted a literature review of 148 unique surveys, which included 6,322 non-human primates (mostly long-tailed macaques and some pig-tailed macaques) tested for P. knowlesi using molecular methods. Human-mosquito-human transmission was demonstrated experimentally once, but there was no evidence of widespread non-zoonotic transmission of P. knowlesi based on systematic reviews and mathematical modelling. However, there remains a possibility for this to occur in the future. Environmental changes, shifting levels of immunity, and the absence of current control measures present challenges to the elimination of zoonotic malaria. Fornace reiterated the need for innovative surveillance and robust control measures to be implemented globally.

Lieven Vernaeve (Malaria Consortium, United Kingdom) presented a success story from his project on reducing residual malaria cases in Cambodia. Cambodia has a strategic plan for malaria elimination for 2015-2028. As part of this, Village Malaria Workers (VMWs) and Mobile Malaria Workers (MMWs) were established in 2001 and 2009, respectively, to provide preventive tools, diagnose malaria early, and provide treatment to hard-to-reach populations. The MMWs are locally recruited members of the community who are well-known by their peers and have knowledge of mobility patterns, local culture, and language. As of June 2024, there are 95 active MMWs in six northern provinces. Diversified activities have been conducted, offering quality mobile malaria services, such as screening co-travelers, active fever screening, passive case detection at the MMWs’ homes, empowering communities through community dialogues, and distributing long-lasting insecticidal nets (LLINs). Vernaeve highlighted MMWs in the six northern provinces of Cambodia who significantly contributed to malaria case screening, as part of provincial malaria data. He concluded by drawing attention to its possible integration with other public health issues which could contribute to a more sustainable impact from the MMWs and stressed on  the importance of robust surveillance, and community contributions to the objectives of the National Malaria Program.

Muhammad Mukhtar (Ministry of National Health Services, Regulations, and Coordination, Pakistan) explained the steps Pakistan has taken in an effort to eliminate malaria by 2035. Anopheles stephensi has posed a significant burden in Pakistan as a vector of malaria, with its impact starting in the early 2000s. It is known that An. Stephensi has undergone behavioural changes (resting, biting, feeding, breeding, and seasonality). Rising temperatures have also contributed to the distribution of An. stephensi between 2000 and 2020. In response, the government of Pakistan has developed new strategies to manage this species and has offered to assist Africa in malaria elimination by sharing knowledge and expertise. The efforts include robust vector surveillance, capacity strengthening, policy consultancy, institutional support, innovative technologies like drones and AI, and joint research initiatives.

Poe Poe Aung (Malaria Consortium, United Kingdom) shared her activities in addressing the spread of arboviruses in African and Southeast Asian countries pointing out Resilience Against Future Threats (RAFT) which was launched to help address capacity shortfalls in arbovirus preparedness. They have partners in countries including Thailand and Cameroon, which serve as host countries. They work on new research, decision-making frameworks, provide accessible state-of-knowledge evidence reviews, promote South-to-South exchanges, and conduct country case studies. During exchange meetings, they share new ideas and surveillance strategies, along with laboratory and field visits. Lessons learned highlight deficiencies in arbovirus outbreak preparedness, surveillance, and control across Africa. Prioritizing community engagement, robust surveillance systems, and translating research into practice will strengthen national programs. She concluded by acknowledging future challenges that included the need for capacity strengthening and the use of context-appropriate tools in Sub-Saharan Africa.

Plenary 1 – Malaria in India: How Shifting Epidemiology and Changes in Parasite Transmission are Challenging the Road to Elimination

Jane Carlton (Johns Hopkins Malaria Research Institute – JHMRI, United States) highlighted her research and discoveries during the 14 years of achievement with continuous, long-term funding, and underscored the importance of continuing basic and translational research on malaria elimination in India. Malaria in India is complex and historically had a high burden from 2005 to 2022, with P. falciparum and P. vivax being the dominant species. Malaria elimination efforts began in 2015, utilizing methods such as Rapid Diagnostic Tests (RDT), PCR, and microscopy. Due to the high number of asymptomatic and submicroscopic malaria cases, a new elimination initiative called Durgama Anchalare Malaria Nirakaran (DAMaN) Camps, a malaria control initiative in inaccessible areas was launched in 2017, delivering malaria control services to remote villages across the state. To evaluate the effectiveness of DAMaN in reducing malaria prevalence, three arms were deployed to compare malaria prevalence in different villages. The evaluations revealed a high failure rate (70%) in RDTs, primarily due to Pfhrp2 gene deletions in P. falciparum, posing a significant threat to malaria elimination efforts. To address these issues, Carlton’s team is developing the Vector-Cam app for mosquito recognition using AI algorithms, creating portable labs for sample processing and sequencing with MinION, continuing to assess DAMaN’s effectiveness, and identifying better RDT targets in P. falciparum. With these efforts, new research and surveillance tools are on the horizon, aiming to enhance vector control and improve malaria diagnosis.

Sponsored session – Advancing malaria research: Innovative solutions from QIAGEN®️

Khor Yee Min (QIAGEN, Malaysia) presented the benefits of digital PCR (dPCR) for the detection of microorganisms using QIAcuity. This is a third generation and most advanced PCR technology designed for the detection and quantification of nucleic acids using nanoplates. The technology works based on the real-time PCR chemistry and workflow with the same reagents with added benefit of end-point detection, higher precision, and reproducibility, absolute quantification, binary signal from low abundant molecules as well as end-point detection. Khor outlined four key benefits of the new method which include; specificity in detecting target sequence, sensitivity in detecting genes in small number of targets, 2 hour rapid detection, and ability to carry out multiplex of 5 targets per reaction with an interesting ability to combine both viral and bacterial DNA. 

Iara Silman (QIAGEN, Germany) presented a novel approach for Plasmodium species detection using a direct multiplex qPCR technology with QIAprep&amp. Silman outlined the limitations of the various tools used in malaria diagnosis such as the need for expertise, low sensitivity, storage issues, and time consumption. The proposed new technology can be used for the detection of P. falciparum for as low as 1 parasite/4uL. The technology is equipped with high sensitivity, compatibility, quickness, and simple workflow to detect DNA from large samples without the need for separate DNA extraction formerly used in other protocols. external and internal laboratory trials revealed high sensitivity in detecting Plasmodium parasites. Silman highlighted the special thing about the new technology to differentiate three different Plasmodium species with an internal control to monitor internal workflow and one hour result processing time. 

Bienvenu Nsengimaana (Infectious Diseases Research Collaboration – IDRC, Uganda) presented the performance of the nanoplate digital PCR technology in genotyping and surveillance of pfhrp2/pfrp3 gene deletion in Uganda. Bienvenu recalled Uganda as the 3rd country with the worst malaria cases in the world. Limitations on the use of previous methods of PCR, qPCR and ELISA in cases of mixed infection and low parasite counts and limitation of the most widely used and cost-effective Rapid Diagnostic Test (RDT) of possible false positive due to pfhrp2/pfrhp mutations lead to the investigation into the presence of the mutation that could have affected reported RDT positive reported cases in the country. Interestingly their study found effectiveness of the technology in detecting the mutation and at the same time reported negligible mutation in the country. He shed light on the importance of rapid diagnostic kits in the detection of malaria, especially in developing countries such as Uganda. Although he described the mutation as uncommon in Uganda, he recommended continuous surveillance of the mutation in the country.

Malaria – Epidemiology 1

Daniel Reegan (ICMR-Vector Control Research Centre, India) discussed the malaria epidemiological data of two endemic coastal localities in India: Besant Nagar (urban) and Pamban (rural), covering the period from 2004 to 2023, and correlated it with the highest recorded maximum temperatures. Malaria prevalence in these two areas was analyzed over the same period. Reegan’s analysis showed that malaria cases (Plasmodium vivax and P. falciparum) increased proportionally as temperatures rose in both areas, particularly during the summer seasons from 2004 to 2011, and subsequently decreased by 2023. Mixed infections of P. vivax and P. falciparum were detected only in Besant Nagar. Additionally, there was no recorded resistance in P. falciparum to artemisinin-based antimalarials in these coastal areas. Effective control measures and surveillance contributed to the successful elimination of malaria. The implementation of the new National Drug Policy successfully reduced the malaria parasite load in the community. Larval control activities and Indoor Residual Spray (IRS) also helped in reducing vector populations.

Alfredo Mayor (Manhiça Health Research Centre – CISM, Mozambique) spoke about the benefits of using malaria genomic surveillance for decision-making in Mozambique. The GenMoz project includes the Plasmodium falciparum genomic intelligence initiative in Mozambique. The database builds next-generation sequencing (NGS) capacities, generates data (sampling and sequencing), and promotes the use of malaria molecular surveillance (MMS) data at CISM. In May 2011, GenMoz was initiated, involving ethical approval, field activities, training, MiSeq implementation, the first NGS run, and the creation of the dashboard. GenMoz detected 0.1% hrp2/3 deletions, helped in detecting resistance to artemisinin combination therapy (ACT) related to the kelch 13 gene and piperaquine, detected mutations in pfdhfr/pfdhps for sulfadoxine/pyrimethamine chemoprevention, analyzes the sources of malaria, and is used in antenatal care (ANC) surveillance, aiding in malaria transmission interventions. The data collected were used to create a genetic dashboard and trimestral brochure. He finished the presentation by highlighting that genomic data has the potential to be also used in future vaccine development.

Md. Hasanuzzaman’s (Bangladesh Atomic Energy Commission, Bangladesh) topic aimed at exploring harmala alkaloids as novel antimalarial agents against Plasmodium falciparum through bioinformatics approaches. Unfortunately, the speaker could not attend the oral session.

Kinley Wangdi (The University of Canberra, Australia) explained how imported cases drive local transmission in Bhutan. Data from Bhutan’s Vector-borne Disease Control Program (VDCP) from 2016 to 2020 were analyzed using Hawkes processes to study the role of imported malaria in local transmission. According to the data, 87.4% of the malaria cases were male, 71.1% were infected by Plasmodium vivax, and 73.6% of the cases came from India. The models showed that P. vivax remains infectious for over 19 days, while P. falciparum is infectious for 8 days. The study also suggested that P. falciparum transmission was mainly caused by importation, whereas P. vivax transmission was driven by relapses. Wangdi recommended that the Hawkes process can serve as an alternative surveillance tool for low-case settings and can be strengthened by incorporating factors such as climate, environment, and control measures, as well as investigating the drivers of P. vivax transmission.

Angela Ogechukwu Ugwu (University of Nigeria Nsukka, Nigeria) explained the role of immune-inflammatory markers in children with complicated and uncomplicated malaria in Enugu, Nigeria. The study adopted a case-control design, and eligible children were categorized into three groups: those with complicated malaria, uncomplicated malaria, and healthy children, during the period from June 2023 to November 2023. The immune-inflammatory markers studied were IFN-γ, TNF-α, IL-10, NLR, and MLR. The mean age of the participants was 7.3 ± 3.4 years, and the male-to-female ratio was 1:1. They found that the mean level of IL-10 was higher in cases of uncomplicated malaria, and there was a positive correlation between NLR and IFN-γ. She concluded by stating that complicated malaria was associated with higher levels of pro-inflammatory cytokines, while uncomplicated malaria was linked to higher levels of anti-inflammatory cytokines. Furthermore, NLR correlated positively with pro-inflammatory cytokines and could be useful in evaluating the severity of malaria infection.

Win Htike (Burnet Institute, Australia) discussed the health system needs for malaria control in the Greater Mekong Subregion through a qualitative study. This study was conducted through 39 semi-structured interviews in Laos, Myanmar, Thailand, and Vietnam. It focused on high-level policymakers, decision-makers, and managers from the National Malaria Control Program (NMCP) and technical agencies, as well as field managers and supervisors from NMCPs or the Ministry of Health’s Infectious Disease Institute. The study participants were purposively recruited, and the data were analyzed using reflexive thematic analysis. Stakeholders highlighted the importance of continuous funding support for malaria elimination to avoid interruptions in malaria elimination activities and the need for strengthening malaria microscopy. Additionally, he emphasized the necessity of tailored interventions for high-risk groups, dedicated staff, highly sensitive surveillance systems, and political commitment and support for a successful malaria elimination program. It is important to assess whether these requirements are already in place before initiating malaria elimination activities.

Geetika Narang (ICMR-National Institute of Malaria Research, India) explained the longitudinal population analysis and natural selection of the Apical Membrane Antigen-1 (AMA-1) gene in Indian Plasmodium falciparum isolates. A total of 173 samples were collected from 14 Indian states between 1993 and 2021. The polymorphic profile, structure, and natural selection of the gene were assessed to explore longitudinal variation in Pfama-1 in Indian P. falciparum isolates. The results showed 70 haplotypes arising from 52 polymorphic sites, along with two previously unreported mutations: S498C/G and F505Y. However, no significant positive Tajima’s D value was observed, and no distinct genetic pattern in the Pfama-1 gene structure was detected. Thus, Narang underlined that the genetic structure of Pfama-1 in Indian isolates is complex, exhibiting a high degree of genetic polymorphism. Also, the extensive antigenic repertoire observed in the gene, both in India and globally, could pose challenges for vaccine design. Finally, since allele-specific immunity has been observed in the gene, Domain II, which showed relative conservation both globally and across all Indian states, could have implications for vaccine design.

Annisa Rahmalia (Menzies School of Health Research, Australia) discusses the barriers to primaquine safety monitoring by community health workers (CHWs) in Timika, Papua, Indonesia. To set the scene, Rahmalia presented several important points. P. vivax forms hypnozoites in the liver, which can cause relapse. Artemisinin treatment only targets the blood stage of the malaria parasite. Primaquine is used to target the hypnozoites and the treatment with primaquine takes longer than the duration of the malaria symptoms. This treatment can hemolyze red blood cells, causing the urine to become dark. The results of trial settings showed that the probability of a six-month recurrence of P. vivax is lower with supervised compared to unsupervised treatment with primaquine. However, several barriers exist to implementing the supervision, such as a lower number of CHWs compared to the number of patients, difficulties in locating patients, misconceptions about urine color and malaria, and the fact that direct inquiries about urine color can be considered offensive. She concluded that treatment adherence and primaquine safety monitoring require multiple differentiated strategies to reach patients, along with cultural sensitivity and social embeddedness.

Rita Reyburn (World Health Organization – WHO, Lao P.D.R.) initiated a strategy of Plasmodium vivax serological-testing-and-treatment (PvSeroTAT) and genomic analysis for an unusual P. vivax malaria outbreak in a malaria-free district of Lao PDR. The Nakai district in Khammuane Province has been considered malaria-free; however, there were 222 P. vivax cases reported between July 1 and August 16, 2023. Reyburn conducted a serological and genomic survey in early November 2023, targeting all individuals aged over 18 months. The results revealed that 4% were positive by PCR, 17% by serology, 4% by both PCR and serology, and 17% by either PCR or serology. It was noted that 56% had no previous malaria diagnosis. Through genotyping, the diversity and relatedness between the outbreak infections and those from other sites could be determined. The study concluded that the outbreak in Nakai was unusual in that a large number of P. vivax cases were detected suddenly in a previously malaria-free area.

Symposium P21 –  Emerging Data on the Latest Available Treatments for the Radical Cure of Plasmodium Vivax 

Prayuth Sudathip (Ministry of Public Health, Thailand) presented an assessment of the appropriate use and non-use of tafenoquine (TQ) / daily primaquine based on Glucose-6-phosphate dehydrogenase (G6PD) activity for patients greater than 16 year old with uncomplicated P. vivax malaria in Yala and Mae Hong Son provinces. They found high follow-up rates on Day 5 and 14 with four patients hospitalized due to non-drug related causes. No cases of acute hemolytic anemia were detected and no patients with possible signs of hemolysis had autoimmune hemolytic anemia (AHA). Four patients were hospitalized but it was due to non-drug related causes. From this, it was concluded that TQ was correctly used in 100% of the cases based on G6PD activity. Sudathip ended the talk by stating the feasibility of using TQ with G6PD testing at different levels of the health system based on this study.

Ayodhia Pitaloka Pasaribu (Universitas Sumatera Utara, Indonesia) Pasaribu presented a study that investigated the use of a higher dose of primaquine (PQ) with shorter course of 1 mg/kg/day administered in 7 days (PQ7) to improve adherence to the treatment regimen among patients. While this regimen had good efficacy under trial settings, it was with increased risk of gastrointestinal intolerability and hemolysis. To mitigate this effect, a point-of-care G6PD test was used to screen patients prior to PQ administration. A case management package was developed with improved patient counselling tools and processes, community-based clinical review on day 3, and improved malariometric surveillance and pharmacovigilance. She concluded by highlighting that the combination of point-of-care G6PD testing and high dose short course PQ has potential to be safe and effective if implemented with patient education and early clinical review. As such, more evidence is needed on safety feasibility and cost-effectiveness.

Moses Laman (Papua New Guinea Institute of Medical Research – PNG-IMR, Papua New Guinea) presented on the feasibility of implementing a revised case management package for patients with P. vivax malaria at 10 health facilities in Indonesia and Papua New Guinea. The package included a point-of-care G6PD activity test prior to treatment with Primaquine (PQ), and subsequent prescription of high dose (7mg/kg total) PQ over 7 or 14 days to eligible patients. Education before treatment and a community-based clinical review on day 3 to encourage treatment adherence and facilitate early detection and management of adverse events were also implemented. Health workers felt that the effort put in has reduced the risks associated with PQ administration in patients. Moses mentioned that PQ7 treatment was received well by the participants and reported a reduced risk of subsequent illness. The day 3 follow-up was seen as an opportunity for PQ education and patients appreciated the visit. The revised case management package was seen as a positive perception of the study’s impact on personal health care experience.

Brice Campo (Medicines for Malaria Venture – MMV, Switzerland) presented a study that assessed the use of Tafenoquine (TQ) as a single-dose treatment administered with chloroquine (CQ) for the treatment of P. vivax. The combination strategy of TQ-CQ already showed TQ to be active and to synergize well at 300 mg. In a previous study, TQ was tested with dihydroartemisinin-piperaquine (DHA-PQP) instead of CQ but failed to confirm radical cure. Subsequent pre-clinical studies replicated the trial’s results and found that although CQ and PQP synergized with PQ, DHA interfered with this synergy. The basis of reduction in efficacy appears to be pharmacodynamic. Campo concluded that this study showed the importance of synergies and understanding their mechanisms which might prompt the use of in vitro and in vivo assays for investigation and validation in the interactions of TQ with other potential drugs.

Gonzalo Domingo (PATH, United States) stood in for Emily Gerth-Guyette and doubled down on the safe use of TQ and PQ through G6PD deficiency testing. Domingo then introduced point-of-care G6PD tests that had been integrated into malaria case management to expand and optimize provision of radical cure for P. vivax. One such example was the STANDARD G6PD test which underwent operations and implementation research in 21 countries. The test was found to be generally acceptable to use and feasible to implement among both providers and patients at multiple levels of the health care system provided with proper training and supervision. Domingo underlined some implementation challenges such as the need for a referral to a health facility which might impact access, the need for quality control for decentralized testing, the overestimation of G6PD activity as testing is expanded to more users, and gaps between policies. Moreover, he mentioned context-specific implementation challenges that will require contextually specific solutions and mitigations for every country.