Research Highlights

Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry

Posted 08/06/2020. Safe and effective radical cure of malaria will require better ways of testing for G6PD deficiency. In a large collaborative study a paper in PLoS Medicine, Daniel Pfeffer, Ric Price and colleagues highlight substantial variation between research laboratories using the current gold standard method (spectrophotometry). The study highlights challenges but also opportunities for new point of care tests.

Causes of fever in primary care in Southeast Asia and the performance of C-reactive protein in discriminating bacterial from viral pathogens

Posted 02/06/2020. Thomas Althaus and colleagues identified Influenza and dengue viruses as key pathogens in febrile children and adults attending primary care in Thailand and Myanmar. CRP performance for distinguishing bacterial from viral pathogens was average while patients recovered regardless of antibiotic prescription. This suggests that most primary care infections do not require an antibiotic.

Barriers and facilitators to healthcare workers’ adherence with infection prevention and control guidelines for respiratory infectious diseases

Posted 05/05/2020. In this Cochrane qualitative review to inform the 2020 COVID19 pandemic, Xin Hui Chan and colleagues identify key barriers and facilitators to healthcare workers’ adherence to infection prevention and control (IPC) guidelines for respiratory infectious diseases to support policymakers and healthcare leaders in designing and implementing IPC guidelines. These include organisational factors (safety climate, design & communication of consistent PPE guidelines, availability of training programmes), physical environment (space, facility design, administrative controls, personal protective equipment availability), and individual factors (knowledge, beliefs, attitudes).

Efficacy and tolerability of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy

Posted 01/05/2020. Although effective treatment for malaria in pregnancy is needed for preventing adverse impact on both mother and fetus, quinine is still widely used in pregnancy. Makoto Saito and 41 other collaborators worldwide put their individual patient data together to summarise the currently available evidence showing that quinine is inferior to ACT and further research on dose optimization of ACT is warranted.

Plasmodium falciparum ATP4 inhibitors to treat malaria: worthy successors to artemisinin?

Posted 28/04/2020. In this comment Elizabeth Ashley and Aung Pyae Phyo discuss two recent studies of SJ733, a PFATP4 inhibitor. Compounds from this promising novel class of antimalarials kill parasites rapidly, a property previously unique to the artemisinin derivatives among antimalarials in use, and one that underpins their enormous success.

The estimated burden of scrub typhus in Thailand from national surveillance data (2003-2018)

Posted 24/04/2020. Scrub typhus is a major cause of fever in the tropics. Tri Wangrangsimakul and colleagues estimated the disease burden in Thailand and showed that the number of cases rose significantly over the last two decades. Age, sex and occupation along with meteorological and geographical factors may be important determinants of disease incidence.

Longevity of the insecticidal effect of three pyrethroid formulations applied to outdoor vegetation on a laboratory-adapted colony of the Southeast Asian malaria vector Anopheles dirus

Posted 21/04/2020. This study by Victor Chaumeau and colleagues was carried out in order to assess the longevity of insecticide mists applied to outdoor vegetation. Insecticidal effect of sprayed plant material against malaria mosquitoes lasted for several weeks. These results provide a strong rationale for using outdoor residual spraying against the mosquito vectors that rest outside premises.

COVID-19 and risks to the supply and quality of tests, drugs, and vaccines

Posted 14/04/2020. Enormous emergency efforts are underway to find optimal medical products, to prevent, diagnose, and treat COVID-19, that 7.8 billion people will depend on. With dire disruption of pharmaceutical production and supply and increasing falsified and substandard products, we need strategic planning now to ensure global access to quality-assured medical products and monitoring of supply chains

Parenting interventions to prevent violence against children in low- and middle-income countries in East and Southeast Asia

Posted 17/03/2020. This systematic review and meta-analysis by Amalee McCoy and colleagues synthesizes available evidence on the effectiveness of parenting interventions in preventing violence against children in the East and Southeast Asian region. The results suggest that parenting interventions can reduce rates of particular forms of violence against children, as well as promote positive parent-child interactions.

Mapping the travel patterns of people with malaria in Bangladesh

Posted 13/03/2020. New research by Ipsita Sinha and colleagues provides a framework for identifying key traveler groups and their origins and destinations of travel combination with knowledge of local epidemiology to inform malaria control and elimination efforts. This publication is based on travel information collected from over 2000 patients from 57 study sites in South-East Bangladesh, in collaboration with the National Malaria Elimination Control programme of Bangladesh.

Estimation of incidence of typhoid and paratyphoid fever in Vientiane, Lao People’s Democratic Republic

Posted 10/03/2020. Incidence data about infectious diseases are needed to inform decisions about vaccine introduction. Using data from health-seeking behaviour survey for fever and data from hospital bloodstream infection, Mayfong Mayxay and colleagues estimated typhoid and paratyphoid fever incidence in Vientiane, the capital of Laos, and found that the incidence is low, with an annual incidence of 4.7 and 0.5 per 100,000 persons, for typhoid and paratyphoid fever, respectively.

Factors affecting the electrocardiographic QT interval in malaria

Posted 06/03/2020. Prolongation of the electrocardiographic QT interval is a widely-used marker of the risk of developing abnormal heart rhythms. Several antimalarial drugs are associated with QT interval prolongation. Xin Hui Chan and colleagues found that malaria and fever also affect QT interval. To improve cardiac safety assessments, adjustment for QT interval prolongation occurring after recovery is needed. This would prevent unnecessary withdrawal of lifesaving antimalarial treatment.

Prevalence of group A Streptococcus in primary care patients and the utility of C-reactive protein and clinical scores for its identification in Thailand

Posted 03/03/2020. It is challenging to know who needs antibiotics for a sore throat and fever. In Thailand, Rachel Greer and colleagues found a bacteria (group A Streptococcus) in less than 1 out 10 patients. These patients had a raised C-reactive protein blood test but it was not able to predict who had the bacteria.

Performance of the Access Bio/CareStart rapid diagnostic test for the detection of glucose-6-phosphate dehydrogenase deficiency

Posted 04/02/2020. Primaquine radical cure for treatment of Plasmodium vivax is contraindicated in patients with G6PD deficiency. Ric Price, Benedikt Ley and colleagues review evidence from 11 studies of a novel point of care diagnostic (CareStart RDT) and show overall good performance under research conditions. Further feasibility studies are under way to assess its reliability under field conditions.

Transmission dynamics and control of multidrug-resistant Klebsiella pneumoniae in neonates in a developing country

Posted 31/01/2020. Drug-resistant strains of the bacterial pathogen Klebsiella pneumoniae are an important and increasing cause of infant mortality in developing countries. In this study led by Professor Ben Cooper, researchers used mathematical modelling and whole genome sequencing to quantify the effects of antibiotics and other factors in driving the hidden transmission of this pathogen within a Cambodian neonatal unit.

Economic considerations support C-reactive protein testing alongside malaria rapid diagnostic tests to guide antimicrobial therapy for patients with febrile illness in settings with low malaria endemicity

Posted 17/01/2020. Malaria is no longer a common cause of febrile illness in many regions of the tropics. Yoel Lubell and colleagues consider the costs and benefits of multiplex malaria/CRP tests that are now commercially available in terms of (i) the improved health outcomes for patients with bacterial illnesses; (ii) the costs of antimicrobial resistance averted; or (iii) the economic benefits of better management of remaining malaria cases and shorter malaria elimination campaigns. They conclude that a multiplexed malaria/CRP test could be highly cost-effective and utilize the well-established funding and distribution systems already in place for malaria RDTs.

Sensitivity of C‐reactive protein for the identification of bacterial infections in northern Tanzania

Posted 07/01/2020. Identifying bacterial infections in sub-Saharan Africa is a challenge because of limited access to laboratory infrastructure. Thomas Althaus and colleagues measured high sensitivity of C-reactive protein (CRP) in detecting bacterial blood stream infections and zoonotic bacterial pathogens among febrile patients both in primary levels of care and hospitals in Moshi, northern Tanzania

Feeding practices and risk factors for chronic infant undernutrition among refugees and migrants along the Thailand-Myanmar border

Posted 20/12/2019. How do birth outcomes, a mother’s nutrition, and how a mother feeds her infant relate to chronic undernutrition among refugee and migrant infants along the Thailand-Myanmar border? Why do these mothers feed their infants as they do? Come learn more from a recent study by Ahmar Hashmi and colleagues at the Shoklo Malaria Research Unit.

Forest work and its implications for malaria elimination

Posted 03/12/2019. Malaria transmission in Cambodia is concentrated in forest foci. Nou Sannan, Tom Peto and MORU colleagues interviewed forest workers who had recently been infected with malaria to understand their behaviour and perception of risk, establish the efficacy and feasibility of malaria prophylaxis , and identify potential strategies for malaria elimination in these populations.

Genetic variation associated with infection and the environment in the accidental pathogen Burkholderia pseudomallei

Posted 26/11/2019. Claire Chewapreecha and colleagues combined 753 newly sequenced Thai Burkholderia pseudomallei (the bacteria causing melioidosis) isolates with 258 Australian isolates to identify genes associated with either clinical or environmental strains. They found 47 genes that may provide clues to the strategy used by this microbe to adapt to survive in wide range of ecological niches, including human hosts.

Microbiology Investigation Criteria for Reporting Objectively (MICRO): a framework for the reporting and interpretation of clinical microbiology data

Posted 07/05/2019. Developed by Paul Turner and fellow members of the Oxford Tropical Network, the MICRO framework provides the scientific community with clear guidance on reporting and interpretation of clinical microbiology and antimicrobial resistance (AMR) data. Use of the framework will result in publication of better quality data for use in the global fight against AMR. The MICRO guideline is also posted on the EQUATOR website www.equator-network.org/reporting-guidelines

Early life risk factors of motor, cognitive and language development

Posted 22/10/2019. Rose McGready and SMRU colleagues contributed RCT data from the Thailand-Myanmar border to this large review on low- and middle-income countries (21 studies in 20 882 children). The results suggests targeting parental, environmental and nutritional factors from pre-pregnancy through childhood, as a way forward to improve health and development of children in such settings.

Scrub typhus and the misconception of doxycycline resistance

Posted 18/10/2019. Scrub typhus is a major cause of fever across the Asia Pacific region. Doxycycline resistance, the main antibiotic used for treatment, was described in the 1990s but independent verification was neglected, leading to doubts regarding its efficacy. Assessment of historical evidence and recent reports by Tri Wangrangsimakul and colleagues suggest this finding was a misconception.

Short-course primaquine for the radical cure of Plasmodium vivax malaria

Posted 16/10/2019. Plasmodium vivax is particularly hard to eliminate because it can relapse from dormant liver stages, weeks to months after the initial infection. Bob Taylor and colleagues present a large multicentred clinical trial showing that a 7 day course with double the daily dose of primaquine is as effective as the traditional 14 day primaquine course, with acceptable tolerability in G6PD normal patients. The trial paves the way for safer and more effective treatment of this parasite.

Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam

Posted 08/10/2019. A rapidly evolving multi-drug resistant lineage of P. falciparum malaria parasites continues to spread in Southeast Asia, leading to alarmingly high treatment failure rates in Cambodia, Thailand and Vietnam for DHA-piperaquine, one of the world’s most important anti-malaria drugs. Rob van der Pluijm and colleagues say that accelerated elimination of P falciparum malaria in this region is urgently needed, to prevent further spread and avoid a potential global health emergency.

Quality of medical products for diabetes management

Posted 01/10/2019. In the light of the alarming global increase in diabetes, Kartika Saraswati and colleagues at the LOMWRU-IDDO Medicine Quality team found few investigations on the quality of antidiabetics and supplies for self-monitoring of blood glucose. However, poor quality medical products were identified on four continents. This important public health issue should thus be further investigated.

Investigating causal pathways in severe falciparum malaria

Posted 06/09/2019. A formal causal inference-based analysis of clinical and laboratory data from 9000+ severe falciparum malaria patients from Africa and Asia by James Watson and colleagues suggests that moderate anaemia may be protective against death in severe malaria. The severe anaemia threshold criteria for a definition of severe falciparum malaria should be reconsidered.

Improving the estimation of the global burden of antimicrobial resistant infections

Posted 03/09/2019. Estimating the global burden of antimicrobial resistance (AMR) is essential for resource allocation and to inform AMR action plans at national and global levels. Direk Limmathurotsakul and colleagues discuss the underlying assumptions, characteristics, limitations, and comparability of the approaches used to quantify mortality from AMR bacterial infections. We define key actions required and call for innovative thinking and solutions to address these problems.

Spatiotemporal epidemiology, environmental correlates, and demography of malaria in Tak Province, Thailand (2012–2015)

Posted 23/08/2019. Tak Province in western Thailand is a significant target area to help achieve nationwide malaria elimination by 2024, and in the Greater Mekong Subregion by 2030. Integrating routine surveillance and publicly available data, Chris Mercado and colleagues demonstrated Tak’s big decline in malaria from 2012 to 2015, a likely result of elimination activities as opposed to climate or forest change.

A population dynamic model to project the burden of undiagnosed diabetes in Thailand

Posted 20/08/2019. Demographics changes result in rapid transformation of population structure; together with other factors such as urbanization, household size decreasing and seasonal movement could greatly influence the prediction of disease burden. Wirichada Pan-ngum and colleagues demonstrated this trend using a mathematical modelling approach.

Nutrition in transition: historical cohort analysis among pregnant women along the Thailand–Myanmar border 1986 - 2016

Posted 16/07/2019. Worrying nutritional trends in possibly the longest and largest cohort of nearly 50,000 refugee and migrant pregnant women in a LMIC setting. Ahmar Hashmi and colleagues at SMRU summarise trends in under- and over-nutrition among pregnant women, and show a double burden of malnutrition in these marginalised and vulnerable communities from the Myanmar-Thailand border.

Antimicrobial resistance in Cambodia

Posted 09/07/2019. On behalf of the Cambodian Ministry of Health Technical Working Group on Antimicrobial Resistance, Paul Turner and colleagues at COMRU recently led a review of published data on AMR in Cambodia. Significant AMR was identified in a range of priority pathogens although data were limited. On-going national AMR surveillance will address this data gap.

“I can’t read and don’t understand”: Health literacy and messaging in a migrant population on the Myanmar-Thailand border

Posted 05/07/2019. Health information can be life-saving, but how can it be conveyed to those who could benefit most? Through analysis of an unsuccessful public health campaign, Mary Ellen Gilder and SMRU colleagues learned from migrant women valuable lessons about health messaging in communities where most women do not complete the fourth grade.

Optimal duration of follow-up antimalarial efficacy in pregnancy on the Thailand–Myanmar border

Posted 02/07/2019. Highly efficacious treatment can limit the cumulative deleterious impact of malaria during pregnancy on the mother and fetus. Correct assessment of treatment efficacy with an adequate length of follow up is required. Makoto Saito and colleagues at the Shoklo Malaria Research Unit (SMRU) on the Thailand-Myanmar border suggest that pregnant women need to be followed up longer than the currently recommended duration of follow-up to assess antimalarial drug efficacy.

‘Antibiotic footprint’ as a communication tool to aid reduction of antibiotic consumption

Posted 18/06/2019. How should we communicate to the public the magnitude of antibiotic use in humans and animals? Led by Direk Limmathurotsakul, our scientists and global partners propose the concept of ‘antibiotic footprint’. It could support individual, national and global actions against superbugs as 'carbon footprint' has done for climate change

Novel approaches to control malaria in forested areas of Southeast Asia

Posted 11/06/2019. Remaining foci of malaria transmission are often in forests, where vectors tend to bite during daytime and outdoors thus reducing the effectiveness of insecticide treated bednets. Limited periods of exposure suggest that chemoprophylaxis could be a promising strategy to protect forest workers against malaria. Lorenz Von Seidlein and colleagues discuss which antimalarial drug regimens are most appropriate, how frequently the chemoprophylaxis should be delivered, and how to motivate forest workers to use and adhere to malaria prophylaxis.

Malaria morbidity and mortality following introduction of a universal policy of artemisinin-based treatment for malaria in Papua, Indonesia

Posted 04/06/2019. In Papua, where multidrug resistant P. falciparum and P. vivax are coendemic, the introduction of a universal policy of ACT plus IV artesunate for all patients with malaria halved hospital admissions and malarial deaths. However the reduction in P. vivax was far less than that for P. falciparum. This study by Ric Price and colleagues emphasizes the need for better drug regimens to clear the liver stages of P. vivax.

Antimicrobial-resistant Gram-negative colonization in infants from a neonatal intensive care unit in Thailand

Posted 31/05/2019. Drug-resistant infections caused by Enterobacteriaceae, a family of Gram-negative bacteria, account for a high and increasing disease burden amongst hospitalised neonates in Southeast Asia; carbapenem-resistant strains are particularly important because of limited antibiotic treatment options. Tamalee Roberts and colleagues found that nearly two thirds of infants in a neonatal unit in Thailand became asymptomatic carriers with carbapenem-resistant Enterobacteriaceae during their hospital stays. This work indicates a critical need for interventions to reduce this usually hidden reservoir of drug-resistant bacteria.

Spatial heterogeneity and temporal trends in malaria on the Thai–Myanmar border (2012–2017)

Posted 21/05/2019. Wirichada Pan-ngum and colleagues explore how decreasing trends reflect the achievements of malaria control efforts on the Thai–Myanmar border. However, one of the main challenges facing elimination programs in this low transmission setting is maintaining a strong system for early diagnosis and treatment, even when malaria cases are very close to zero, whilst preventing re-importation of cases.

Microbiology Investigation Criteria for Reporting Objectively (MICRO): a framework for the reporting and interpretation of clinical microbiology data

Posted 07/05/2019. Developed by Paul Turner and fellow members of the Oxford Tropical Network, the MICRO framework provides the scientific community with clear guidance on reporting and interpretation of clinical microbiology and antimicrobial resistance (AMR) data. Use of the framework will result in publication of better quality data for use in the global fight against AMR. The MICRO guideline is also posted on the EQUATOR website www.equator-network.org/reporting-guidelines

Clinical characteristics and outcome of children hospitalized with scrub typhus in an area of endemicity

Posted 25/04/2019. It has been almost 30 years since clinicians from northern Thailand first raised the issue of severe scrub typhus and poor responses to treatment in patients. Tri Wangrangsimakul and colleagues show that paediatric scrub typhus is frequently severe, potentially fatal, and associated with high rates of treatment failure. A lack of awareness leading to delays in treatment may have contributed. Investigating the determinants of treatment failure and raising the awareness of this neglected disease remains a priority.

Human population movement and behavioural patterns in malaria hotspots on the Thai–Myanmar border: implications for malaria elimination

Posted 23/04/2019. Human population movement can lead to the persistence of malaria along the Thai–Myanmar border. Lisa White, Wirichada Pan-ngum and colleagues show that malaria risk is related to the number of days doing outdoor activities in the dry season, especially trips to Myanmar, to forest areas and overnight trips. Understanding movement patterns is important when considering targeted public health interventions, especially during the elimination phase.

Community engagement, social context and coverage of mass anti-malarial administration

Posted 16/04/2019. Lorenz Von Seidlein and colleagues in Thailand, Myanmar, Vietnam, Cambodia, and Laos explored what happens to malaria transmission when all people residing in a village are treated with antimalarials at the same time, whether they are sick or not. They demonstrated that providing the necessary information is important, but building trust between residents and the team providing the antimalarials is most critical for success.

The rise and fall of long-latency Plasmodium vivax

Posted 05/04/2019. Until World War II the only Plasmodium vivax malaria generally recognised had either a long (8–9 months) incubation period or a similarly long interval between initial illness and the first relapse. Long-latency P. vivax ‘strains’ were the first in which relapse, drug resistance and liver stage development were described, yet in recent years they have been largely forgotten.

How context can impact clinical trials

Posted 29/03/19. This qualitative study documents how clinical interventions are influenced by their local context. Factors like health policies or physicians’ fears of under-treating infectious diseases can influence adherence to the intervention and potentially hamper efforts to reduce antibiotic use in developing countries. The work was led by former CTMGH member Marco J Haenssgen, drawing on clinical trials in Southeast Asia by Yoel Lubell and Heiman Wertheim.

The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia

Posted 26/03/19. Lorenz Von Seidlein and colleagues wanted to know whether well-resourced mass drug administrations (MDA) can accelerate malaria elimination in the Greater Mekong Subregion. They randomised 16 villages in Myanmar, Vietnam, Cambodia, and Laos to receive MDAs with antimalarial drugs. The intervention had a substantial impact on the prevalence of P. falciparum infections by month 3 after the start of the MDAs. Over the subsequent 9 months, P. falciparum infections returned but stayed below baseline levels.

How can interventions that target forest-goers be tailored to accelerate malaria elimination in the Greater Mekong Subregion?

Posted 18/03/2019. Tailored interventions that specifically target at-risk populations, such as forest-goers, will be crucial for achieving malaria elimination in Southeast Asia. This review By Tom Peto and colleagues highlights the behaviours and attitudes of forest-goers towards malaria prevention and control interventions to identify what changes can be made to reduce the malaria incidence in this population.

Collider bias and the apparent protective effect of G6PD deficiency on cerebral malaria

Posted 12/03/2019. Large case-control studies have reported that glucose-6-phosphate dehydrogenase deficiency exists due to its opposing effects on falciparum malaria: protection against cerebral malaria but an increased propensity to develop severe malarial anaemia. A reanalysis of these claims by James Watson and colleagues shows they are likely explained by 'collider bias', as case definitions excluded patients with both anaemia and coma on presentation.

Optimal dosing of dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in young children

Posted 05/03/2019. Seasonal malaria is common in the Sahel, resulting in malaria-related morbidity and mortality, particularly in young children. Seasonal chemoprevention with the antimalarial drug dihydroartemisinin-piperaquine is effective and safe. However, results presented here by Palang Chotsiri and colleagues show that malaria incidence could be reduced substantially by using an increased and extended dosage in young children.

Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria

Posted 26/02/2019. In this multi-center randomized controlled trial, Cindy Chu and colleagues assess the safety of a single dose tafenoquine for Plasmodium vivax radical cure. With appropriate G6PD testing, the number of adverse events, frequency and severity of haemoglobin reduction are similar to primaquine. Anti-relapse efficacy of tafenoquine is similar to primaquine; 69.1% vs 73.2%, respectively.

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Research Highlights