Improving treatment, particularly in LMICs
BIOANALYSIS AND PHARMACOMETRICS
2018 findings influencing treatment and efficacy include:
- Co-administration of ivermectin plus dihydroartemisinin-piperaquine leads to increased concentrations of ivermectin, imparting a greater mosquito-lethal effect;
- In a study in Niger, malnutrition was significantly associated with decreased absorption of lumefantrine, leading to under-exposure and an increased risk of malaria reinfection;
- Chloroquine, dihydroartemisinin-piperaquine and artesunate-pyronaridine all significantly increase plasma primaquine concentrations; and
- In TB modelling and simulation showed inadequate rifampicin drug levels in children with the currently available dosing regimens, and the developed population pharmacokinetic model was used to suggest an optimised dose regimen.
During 2018 the Africa Asia Programme ran around 70 clinical studies – observational, case-control, pharmacokinetics/pharmacodynamic (PK/PD) and randomised controlled trial (RCTs) – at any one time. Highlights include:
- A large multinational trial testing triple artemisinin combination therapies (TACTs) for the treatment of drug resistant falciparum malaria (TRAC II) was completed in 2018, demonstrating that TACTs are well tolerated and effective at treating multi-drug resistant malaria prevalent in much of the GMS;
- These studies have been complemented by detailed drug-drug interaction studies of the components of the triple therapies in healthy volunteers. The most important finding to date – which allowed the multinational clinical trials to proceed – was to show that mefloquine did not potentiate the effects of piperaquine on ventricular repolarisation;
- A large study of the safety of single low dose primaquine, using a novel age-based dosing regimen, in G6PD deficient African children with uncomplicated falciparum malaria is underway in Kinshasa (KIMORU) and Uganda (Imperial-KEMRI-Wellcome);
- The largest ever multicentre study on primaquine radical treatment of vivax malaria (IMPROV) was completed in 2018 and offers an efficacious and tolerated double dose primaquine regimen over 7 days; and
- An RCT in Bangladesh showed a reno-protective effect of paracetamol in adult severe malaria through an anti-oxidative mechanism.
ETHICS OF RESEARCH IN RESOURCE-LIMITED COUNTRIES
Research on how to ethically involve children, pregnant women, migrants, refugees and other under-served groups in medical research continues, including initiation of the multi-centre study “In Their Own Voices: Vulnerabilities & Abilities of Women, Children, & Families in Health Research”.
Multiple publications arose from research on how to meaningfully engage communities in research, including the use of community advisory boards and innovative approaches (e.g. art and theatre) in order for the research to be responsive, ethical and ultimately to improve lives.
The LOMWRU-based medicine quality team play a global leadership role in medicine quality research. They continue to provide evidence to the Member State Mechanism of WHO on medicine quality issues, and in 2018 organised the first ever International Conference on Medicine Quality and Public Health. Accessible data on the quality of maternal health medicines, antibiotics, antidiabetics, anti-retrovirals, and anti-tuberculous drugs is being tabulated, and these are being mapped before expanding to other classes of essential medicines. A pilot WWARN/IDDO project to map national laws related to medicine quality and the definitions of different types of poor quality medicines has been completed.
The team are also evaluating multiple innovative medicine quality screening devices. With the current evidence, it is unlikely that any one device would be able to effectively monitor the quality of all medicines.
CRITICAL CARE MEDICINE IN LOW AND MIDDLE-INCOME COUNTRIES (LMIC)
The critical illness team continues to show global leadership in translating evidence-based Western Intensive Care Units (ICU) care to LMIC settings:
- The “surviving sepsis campaign” guidelines were adapted for se in resource-poor and tropical settings, in collaboration with an international group of experts;
- A low-cost registry was developed and tested in ICUs in Sri Lanka, which will be expanded to 42 ICUs across the region as part of the Wellcome Innovations critical illness flagship programme;
- Studies on improving ICU training in low and middle-income countries have been set up and are currently running in Lao PDR and Sri Lanka; and
- A study was published showing the improved performance and reduction in mortality of a large ICU training effort in India, Bangladesh and Nepal.