On 17 Nov, the Pakistan arm of COPCOV enrolled its first participant at Aga Khan University (AKU), Karachi, as COPCOV Pakistan PI Prof. M. Asim Beg looked on. Prof. Beg will be supported by AKU’s Drs Farah Qamar, Faisal Mahmood, Noshin Nasir, Momin Qazi, Sonia Qureshi and Najia Ghanchi as well as Prof. Saeed Hamid, director of AKU’s Clinical Trials Unit.
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.
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.
Posted 18/12/2020. Lorenz Von Seidlein and colleagues observed that poorest people in rural Tanzania were the oldest people and especially old people without children. This observation came as a surprise because generation, the baby boomers has accumulated wealth throughout life and ended up wealthier by the time they reached retirement. There is a need to provide more financial and housing security for older people in rural Africa. Currently for many older people in rural Africa the only security are their children.
Posted 30/03/2021. Reactive case detection has played a role in the elimination of malaria in China. The approach has been adapted and is used in the Greater Mekong Subregion. Because it requires considerable man power but only few cases are detected the approach is controversial. Jacqueline Deen, Lorenz Von Seidlein and colleagues included 8 articles in a meta-analysis that found the percentage of positive malaria cases among potential contacts using microscopy or rapid diagnostic test was 0.56%.
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.
Posted 18/09/2020. New findings by Ric Price and colleagues highlight that a remarkably high number of P. vivax infections arise from relapses (reactivation of dormant liver stages). This has important implications since almost 85% of recurrent infections could be prevented if more patients were treated with primaquine. The study emphasises the important of work done by the VxWG (Vivax Working Group for the Asia Pacific Malaria Eliminiation Network) in promoting wider access to safe and effective radical cure.
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.
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.
Posted 15/06/2021. Plasmodium vivax caused an estimated 14 million malaria cases in 2017. By collating economic and epidemiological data, Angela Devine and colleagues estimated an economic cost of $359 million associated with these episodes. A scenario analysis explored how costs might change with global access to safe radical cure, estimating cost savings of $17-93 million.
Posted 25/05/2021. Seeking treatment including antibiotics without prescription at drug shops is a common practice in Nepal which can contribute to rising antibiotic resistance. This may leave us without effective antibiotics for future infections. In this study, Bipin Adhikari and colleagues explore why people buy antibiotics over the counter in Nepal and implications for its control.
Posted 07/05/2021. Multidrug-resistant tuberculosis (MDR-TB) remains a significant burden in the Southeast Asia region. Using mathematical modelling approach, Wirichada Pan-Ngum and colleagues assessed the population-level impacts of short-course MDR-TB treatment compared to the conventional therapy. Early initiation of treatment and good level of treatment eligibility are identified to be important determinants to the success of MDR-TB control programmes.
Posted 30/04/2021. In many low- and middle-income countries febrile children are managed by health workers with limited training, in settings where referrals can confer substantial costs and risks. Spot Sepsis, a multi-centre study being implemented by MORU and MSF, aims to develop a practical prognostic tool to help community healthcare providers identify febrile children who may benefit from referral for facility-based medical care.
Posted 16/04/2021. This systematic review by Arjun Chandna and colleagues identified clinical and laboratory prognostic factors, measured at the point of presentation, that can help identify children at risk of severe febrile illness. Most studies included only hospitalised children and further work is required to identify the best predictors to build data-driven triage tools for use by community healthcare providers.
Posted 27/04/2021. The complete treatment of vivax malaria requires a radical cure with a course of 8-aminoquinolines. Bipin Adhikari and colleagues interviewed policymakers in Asia why the radical cure is currently so poorly implemented and what can be done to improve the uptake of the radical cure.
Posted 20/04/2021. Artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated falciparum malaria, but the ACT drugs are starting to fail. Triple artemisinin-based combination therapy (TACT) is being studied to replace ACTs. In this paper, Phaik Yeong Cheah and colleagues discuss the most important ethical and practical considerations in the potential deployment of TACT.
Posted 09/03/2021. X-linked glucose-6-phosphate dehydrogenase deficiency is the most common human enzymopathy. Ghulam Awab and colleagues analysed their clinical study and epidemiological data from Afghanistan gathered over the last decade and showed that the G6PD Mediterranean variant provided a marked gene dose proportional protection against P. vivax malaria.
Posted 02/03/2021. Direk Limmathurotsakul and colleagues show that a Sepsis Fast Track (SFT) programme, implemented in Thailand to screen, initiate sepsis care and fast-track them when applicable to ICU upon admission, are associated with higher chances of survival. We analyzed data of a prospective observational study, having control group from both pre and post-intervention periods.
Posted 09/02/2021. Wirichada Pan-ngum and colleagues address key knowledge gaps on human-animal-water-source interactions and leptospirosis in high-risk settings, Thailand. Water-source sharing networks and human–animal contact patterns are key information potentially involved in the epidemiology of leptospirosis. Occupations related to animals/environmental water and consuming water from more than two sources increased the risk exposure to leptospirosis.
Posted 11/12/2020. COVID-19 has hit informal urban settlements particularly hard. The control and prevention of COVID-19 in slums starts with organizing community infrastructure, provision of basic needs and protection of people at highest risk. Slums are a source for persistent transmission. In view of the constant risk that slums present to the entire population decisive steps need to be taken to rehabilitate and improve informal settlements, Lorenz Von Seidlein and colleagues provide suggestions.
Posted 08/10/2020. “No bacterial culture, no drug-resistant infections.” Cherry Lim, Direk Limmathurotsakul and colleagues show that the impact of low blood culture utilization on the observed proportions and incidences of drug-resistant infections could be high. This is likely happening in most of LMICs. A set of recommendations are proposed.
Following WHO recommendations against the use of hydroxychloroquine in the prevention of COVID-19, including its use in controlled trials, we are reviewing the guideline and available evidence. We are concerned that this judgement from the authors of the guideline is scientifically unsound.
As the world waits impatiently for a COVID-19 vaccine, an exhaustive review of hydroxychloroquine and chloroquine pharmacology suggests that the doses used in COVID-19 prevention trials are safe, say University of Oxford affiliated researchers in a study published in PLoS Medicine.
Hydroxychloroquine could still prevent COVID-19 and save tens of thousands of lives around the world, say leading scientific researchers. While it doesn’t work in treatment of hospitalised patients, it could still prevent infections. However, fraudulent data, unjustified extrapolation and exaggerated safety concerns together with intense politicisation and negative publicity may stop COPCOV, the only large, global clinical trial testing hydroxychloroquine in COVID-19 prevention, from ever finding out.
The UK regulator MHRA announced on 26 June that it would again permit recruitment to the COPCOV COVID-19 prevention clinical trial. The MHRA decision came 5 weeks after it reacted immediately to the now-discredited paper published in The Lancet suggesting harms with hydroxychloroquine, and paused recruitment of UK participants. But The Lancet paper was based on fabricated data and was swiftly retracted. After this interruption, recruitment around the globe to COPCOV can now resume.
Paper by NJ White et al, PLoS Medicine, in press. Using available pharmacokinetic information from healthy volunteers, the treatment of malaria, the chronic treatment of rheumatological conditions and the toxicokinetics of chloroquine in self-poisoning, the authors predict exposures and safety margins in the high dose chloroquine and hydroxychloroquine COVID-19 prevention and treatment regimens currently under evaluation. These regimens are predicted to have reasonable safety margins. Large, well conducted randomised clinical trials with appropriate monitoring are required to determine if chloroquine and hydroxychloroquine have preventive or treatment efficacy in COVID-19 and acceptable safety. Current recommendations for their use outside of clinical trials are not justified at this time.
On 4 June 2020, after a week of increasing scientific concern and scrutiny, first The Lancet, then the New England Journal of Medicine, retracted studies that were based on inaccessible data. The studies have been extremely damaging to chloroquine and hydroxychloroquine COVID-19 clinical trials around the globe. MORU researchers played a key role in bringing this scandal to light, whose consequences continue to play out.