Research Highlights

Molecular characterization and mapping of G6PD mutations in the Greater Mekong Subregion

Posted 19/02/2019. Germana Bancone and colleagues characterized glucose-6-phosphate dehydrogenase deficiency in over 10 thousand samples collected in 138 villages in Cambodia, Lao PDR, Myanmar, Thailand and Vietnam, showing a country-level prevalence in males ranging from 7.3% to 18.8%. Given this high prevalence, G6PD testing should be carried out in the Greater Mekong Subregion before P. vivax radical cure with 8-aminoquinolines.

Health care worker explaining malaria facts to villagers

Association of mutations in P. falciparum Kelch13 gene with parasite clearance rates after artemisinin-based treatments

Posted 05/02/2019. In this study, the WWARN K13 genotype-phenotype Study Group gathered 18 studies from Africa and Asia to explore the relationships between identified Kelch 13 mutant alleles and delayed parasite clearance. Results show one P. falciparum specific mutant and 20 pfk13 propeller region mutant alleles strongly associated with the slow clearance phenotype, including 15 mutations that have not been confirmed before. It was reassuring that no pfk13 alleles associated with slow parasite clearance were observed in the parasites from African studies gathered between 2000-2017.

Optimizing respiratory management in resource-limited settings

Posted 01/02/2019. In many low- and middle-income countries, putting a critically ill patient on a ventilator is associated with a high risk of the patient dying or developing additional problems. In this paper, Rebecca Inglis and colleagues explore measures avert to the need for a ventilator. They also look at ways to improve the safety of ventilators in low-resource settings.

Effect of point-of-care C-reactive protein testing on antibiotic prescription in febrile patients attending primary care in Thailand and Myanmar

Posted 15/01/2019. Dr Thomal Althaus and colleagues managed to reduce antibiotic prescription using the C-reactive protein (CRP) test among 2,410 children and adults presented with a fever in primary care centres in Thailand & Myanmar. The perspective of a rapid and affordable test for CRP, identifying febrile patients who really need an antibiotic, is now possible!

The double burden of diabetes and global infection in low and middle-income countries

Posted 08/01/19. Four out of five people in the world with diabetes now live in low and middle income countries. Professor Susanna Dunachie and her Thai collaborator Parinya Chamnan describe how diabetes leads to increased risk and worse outcomes for global infections such as TB, melioidosis and dengue, alongside discussing potential mechanisms and interventions.

Challenges arising when seeking broad consent for health research data sharing

Posted 11/12/2018. Phaik Yeong Cheah and colleagues report a qualitative study on how best to seek broad consent to sharing individual level health research data beyond research collaborations. Their findings demonstrated that research participants prioritise information about the potential benefits and harms of data sharing. The researchers also found that explaining data sharing to research participants was challenging.

Health care worker measuring circumference of a young patient's arm

Complex interactions between malaria and malnutrition

Posted 05/12/2018. A WWARN team recently completed a large systematic literature review to understand whether undernutrition places children at higher, lower, or no differential risk for getting malaria. We raise the concern whether an adapted antimalarial treatment strategy is needed in malnourished children. The results present the risks associated with chronic and severe acute malnutrition and the impact on sub-optimal drug exposure, poor patient outcomes and the potential contribution towards an increased risk of antimalarial drug resistance. Photo credit: Albert González Farran, UNAMID, 2013

The arrhythmogenic cardiotoxicity of the quinoline and structurally related antimalarial drugs

Posted 13/11/2018. Quinoline and related antimalarial drugs are vital tools in the fight against malaria. However, concerns about their possible effects on the heart rhythm may limit their use. Dr Ilsa Haeusler, Dr Xin Hui Chan, and colleagues found that these serious side effects are reassuringly rare in the treatment of malaria

Anaemia and malaria

Posted 06/11/18, review by Professor Nick White. Malaria, a parasitic infection of red blood cells, is a leading cause of anaemia in the tropics. Where malaria transmission is intense patients, typically children, may die from severe anaemia. However when falciparum malaria causes other vital organs to fail, moderate anaemia appears to protect against death.

Field detection devices for screening the quality of medicines

Posted 23/10/18. A plethora of innovative portable devices to screen for poor quality medicines has become available. In a review of the scientific evidence regarding their performances, Dr Celine Caillet and colleagues show that there is a vitally important lack of independent evaluation of the majority of the 41 devices (most being spectrophotometers) found in our search, particularly in field settings. Intensive research is needed in order to inform national medicines regulatory authorities of the optimal choice of device to combat poor quality medicines.

Valuing the unpaid contribution of community health volunteers to mass drug administration programs

Posted 10/10/2018. Community volunteers are used to deliver a number of healthcare interventions. Although these volunteers are not paid, their time still has an economic value, known as an opportunity cost. Dr Hugo Turner and colleagues found that this economic value is significant for mass drug administration programs: for the African Programme for Onchocerciasis Control alone it would be valued at US$60-90 million.

Enumerating the economic cost of antimicrobial resistance per antibiotic consumed to inform the evaluation of interventions affecting their use

Posted 18/09/2018. Let by Professor Yoel Lubell, researchers from MORU and IDDO estimated the economic costs of AMR associated with the consumption of a range of antibiotic classes in high and lower-middle income countries. These estimates are essential for economic evaluations of interventions that affect antibiotic consumption to reflect the full costs and benefits of their use.

Important antimalarial drug DHA-piperaquine safe to use

Posted 04/09/2018. DHA-piperaquine is an important antimalarial recommended by the WHO for the treatment of malaria, and an ideal candidate for mass use in malaria elimination. In a large meta-analysis of ~200,000 subjects, Dr Xin Hui Chan and colleagues find the risk of sudden unexplained death after DHA-piperaquine is extremely low and not higher than baseline, confirming the drug’s safety for the treatment and prevention of malaria.

Addressing challenges faced by insecticide spraying for the control of dengue fever

Posted 24/07/18. A study from Bangkok by Professor Wirichada Pan-Ngum and colleagues shows accessing households for proper spraying was a problem for control dengue outbreaks. In addition, inefficient communications among the sectors from hospital to district offices led to inaccurate or missing patient addresses for spraying. Involving community networks help to improve public engagement with and participation in the programmes.

Risk-based reboot for global lab biosafety

Posted 17/07/2018. This paper by Professor Stuart Blacksell and colleagues describes the first update to the WHO Laboratory Biosafety Manual in 15 years. The need to update international lab biosafety guidance is part of a broader initiative to globalize biosafety, emphasizing principles and approaches that are accessible to countries spanning a broad range of financial, technical and regulatory resources.

Comparison of the Cumulative Efficacy and Safety of Chloroquine, Artesunate, and Chloroquine-Primaquine in Plasmodium vivax Malaria

Posted 03/07/2018. Chloroquine, the recommended treatment for vivax malaria, delays but does not prevent relapses. Primaquine is the only widely available drug that prevents relapses but it can induce haemolysis in patients with G6PD deficiency. Cindy Chu and colleagues showed that added to chloroquine, primaquine is very effective for relapse prevention, but should be used alongside quantitative G6PD testing.

Small children and pregnant women may be underdosed with widely used antimalarial drug

Posted 27/06/2018. Current recommended treatment regimens for the most widely used medicine for uncomplicated Plasmodium falciparum malaria may be sub-optimal for small children and pregnant women according to a study led by Professor Joel Tarning.

Scrub typhus point-of-care testing

Posted 15/05/2018. Kartika Karaswati, Stuart Blacksell and colleagues reviewed the diagnostic accuracy of the available scrub typhus point-of-care tests, feasible to be used in resource limited settings. Although the available evidence is varied in methodology and quality, POCTs appear to have low false positive rates, thus confidence in interpreting a positive result can be high.

The ethics of using placebo in randomised controlled trials

Posted 08/05/2018. Is it ethical to withhold a recommended treatment from a patient in clinical trial? In this paper we evaluate whether exchanging placebo for an active drug is ethical. We use the example of a randomised control trial of primaquine to determine its anti-relapse efficacy against vivax malaria and conclude that in some cases a placebo arm is imperative.

Primaquine pharmacokinetics in lactating women and breastfed infant exposures

Posted 25/04/2018. Mary-Ellen Gilder and colleagues at SMRU demonstrate low levels of primaquine in breast milk, findings that should change treatment policy allowing more breastfeeding women to be cured of P.vivax. This will potentially reduce the global burden of this infection which has significant negative consequences for pregnant mothers and infants.

Malaria

Posted 17/04/2018. This new Lancet malaria seminar, by Elizabeth Ashley and Charlie Woodrow, is one of a series of clinically focused, structured, up-to-date reviews which are grouped together in The Lancet Clinic with other relevant content. The aim of the seminars is to give a comprehensive overview of diseases to practising clinicians, emphasising recent advances, controversies and uncertainties.

Study analyses antimicrobial resistance surveillance networks in LMICs

Posted 10/04/2018. Antimicrobial resistance (AMR) is a serious threat to public health. A new report by Elizabeth Ashley and colleagues describes the role of supranational networks in AMR surveillance in low- and middle-income countries (LMICs); Liz Ashley and colleagues analysed networks that were in existence between January 2000 and August 2017. This study reveals the challenges of establishing sustainable and effective networks to tackle resistance to antimicrobial medicines.

Acetaminophen as a renoprotective adjunctive treatment for patients with malaria

Posted 29/03/2018. This randomised controlled trial, by Katherine Plewes and colleagues, of acetaminophen (paracetamol) in Bangladeshi patients with severe and moderately severe malaria shows that acetaminophen reduces kidney dysfunction and risk of developing acute kidney injury, particularly in patients with significant haemolysis. This proof-of-principle study supports the underlying hypothesis that acetaminophen inhibits cell-free haemoglobin-mediated oxidative kidney damage.

Mass drug administration to stop multi drug resistant malaria in Cambodia

Posted 20/03/2018. A clinical trial in Cambodia evaluated the safety and effectiveness of mass drug administration (MDA) to interrupt multi-drug resistant falciparum malaria. Coverage with at least one round was 88%, no severe adverse events were reported, and MDA was associated with the absence of clinical P. falciparum cases for at least one year.

Promising approach to reducing Malaria transmission by ivermectin

Posted 14/03/2018. Blood from patients treated with ivermectin can kill mosquitos. Our results indicate that ivermectin mass drug administration to humans could be a potential malaria control tool to aid malaria elimination efforts in South America.

Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria

Posted 06/03/2018. Primaquine is being promoted actively to block the transmission of falciparum malaria parasites between humans and mosquitoes to reduce the spread of highly resistant malaria ‘superbugs.’ In response, Bob Taylor and colleagues developed a primaquine dosing scheme based on age. This will be useful where there are no functioning weighing scales and when primaquine mass drug treatment will be given.

Community participation in mass anti-malarial administrations in Cambodia

Posted 13/02/2018. Two mass drug administrations against falciparum malaria were conducted in 2015–16, one as operational research in northern Cambodia, and the other as a clinical trial in western Cambodia. During an April 2017 workshop in Phnom Penh the field teams from Médecins Sans Frontières and the Mahidol-Oxford Tropical Medicine Research Unit discussed lessons for future mass drug administrations.

Ethics, regulation, and beyond: the landscape of research with pregnant women

Posted 16/01/2018. Ethics guidelines have evolved to protect vulnerable groups such as pregnant women from research. This has resulted in a lack of research in these populations making them even more vulnerable because of the lack of evidence-based medical care. In this paper, Professor Phaik Yeong Cheah and her collaborators discuss how regulatory frameworks can sometimes lead to a generalized exclusion of pregnant women from research.

Estimating the burden of scrub typhus Estimating the burden of scrub typhus

Posted 21/11/2017. Scrub typhus is a serious mite-transmitted and difficult-to-diagnose infectious disease increasingly recognised as a major treatable cause of febrile illnesses with a wider distribution beyond Asia. Despite many limitations on the amount and quality of available reports to date, scrub typhus remains a severely underappreciated tropical disease, deserving more attention.

Quantification of the association between malaria in pregnancy and stillbirth

Posted 17/10/2017. Plasmodium falciparum and Plasmodium vivax malaria in pregnancy both increase stillbirth risk, which is likely to increase as endemicity declines. A study by SMRU and University of Melbourne researchers shows that better P. falciparum malaria control efforts could prevent up to 1 in 5 to 8 stillbirths in sub-Saharan Africa.

Infection with Burkholderia pseudomallei – immune correlates of survival in acute melioidosis

Posted 04/10/2017. Recruiting 183 acute melioidosis patients and 21 control subjects in order to explore immune factors associated with survival status and diabetes, this study identified two class I HLA alleles associated with increased risk of death during melioidosis. Stronger T cell responses to nine immunodominant antigens were observed in those who survived, with responses to one of these – GroEL – observed to be impaired in patients with diabetes.

Community engagement for the rapid elimination of malaria

Posted 26/09/2017. Professor Phaik Yeong Cheah and colleagues published a paper describing their experience and challenges engaging with communities involved in the Targeted Malaria Elimination initiative in Karen State, Myanmar. The report gives a detailed account of the activities conducted and challenges encountered which included difficulties explaining concepts like drug resistance and submicroscopic infection.

Geographic resource allocation based on cost effectiveness

Posted 05/09/2017. Can faster progress be made in the fight against malaria by targeting interventions to where they will have the most impact? Health economists and mathematical modellers from the Mahidol-Oxford Tropical Medicine Research Unit have developed an approach to use maps of disease risk together with models of the transmission of disease and the costs and effectiveness of malaria interventions to help local decision makers design more impactful malaria control and elimination programmes.

Influence of number and timing of malaria episodes during pregnancy on prematurity and birthweight

Posted 25/08/2017. In more than 50,000 pregnancies where 16% of women had malaria infection, the odds of small for gestational age and preterm birth following falciparum, and vivax malaria, were quantified. These newborn effects have life-long implications and efforts to effectively prevent malaria in pregnancy must be pursued.

Migration histories of multidrug-resistant tuberculosis patients from the Thailand-Myanmar border, 2012–2014

Posted 14/08/2017. Through history and attributes of migration of Multi Drug Resistant Tuberculosis patients before diagnosis and treatment, and spatial analysis of their travelling patterns, the study highlights links between human migration and dispersal of multi-drug resistant Tuberculosis across wide geographic areas. It confirms needs for interventions suited to migrants’ life circumstances.

First-trimester artemisinin derivatives and quinine treatments and the risk of adverse pregnancy outcomes in Africa and Asia

Posted 13/06/2017. It has been maintained for decades that quinine is the safest drug for treatment of malaria in the first trimester of pregnancy. In the largest analysis of data from Thailand and Africa, artemisinins are reported to be at least as safe as quinine. This will simplify treatment protocols worldwide.

An epidemic of dystonic reactions in central Africa

Posted 17/03/2017. An investigation conducted by the international medical organisation Médecins Sans Frontières revealed that over a thousand people in a remote area of the Democratic Republic of Congo suffered toxic effects after ingesting fake diazepam pills. The research was published in The Lancet Global Health with contribution from Prof Paul Newton from IDDO and LOMWRU.

Harmonised Zika virus research protocols published

Posted 03/11/2016. Six harmonised protocols to capture Zika-related data to help public health professionals, clinicians and clinical researchers to gain a better understanding of the disease has been published on the WHO website. A number of partners - under the leadership of Institut Pasteur and WHO, including ISARIC and CONSISE have contributed to the development of these protocols to address key public health concerns associated with the Zika virus outbreak. The Working Group on ZIKV Harmonized Research, which included Dr Gail Carson and Professor Peter Horby, published a commentary on the project in the Lancet Global Health yesterday.

Birth attendant training course may be global model for safer birth care in poor communities

Posted 17/10/2016. Training local Karen and Burman women as skilled birth attendants in refugee settings resulted in no adverse perinatal outcomes and many positive outcomes such as a drop in stillbirths and infant deaths and more babies being born in clinics rather than at home, says a new study, led by Professor Rose McGready and published in PLOS ONE.

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Research Highlights