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Primaquine and tafenoquine are the only licensed drugs with activity against Plasmodium vivax hypnozoites but cause haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Malaria also causes haemolysis, leading to the replacement of older erythrocytes with low G6PD activity by reticulocytes and young erythrocytes with higher activity. Aim of this study was to assess the impact of acute malaria on G6PD activity. Selected patients with uncomplicated malaria were recruited in Bangladesh (n = 87), Indonesia (n = 75), and Ethiopia (n = 173); G6PD activity was measured at the initial presentation with malaria and a median of 176 days later (range 140 to 998) in the absence of malaria. Among selected participants (deficient participants preferentially enrolled in Bangladesh but not at other sites) G6PD activity fell between malaria and follow up by 79.1% (95%CI: 40.4 to 117.8) in 6 participants classified as deficient (<30% activity), 43.7% (95%CI: 34.2 to 53.1) in 39 individuals with intermediate activity (30% to <70%), and by 4.5% (95%CI: 1.4 to 7.6) in 290 G6PD normal (≥70%) participants. In Bangladesh and Indonesia G6PD activity was significantly higher during acute malaria than when the same individuals were retested during follow up (40.9% (95%CI: 33.4-48.1) and 7.4% (95%CI: 0.2 to 14.6) respectively), whereas in Ethiopia G6PD activity was 3.6% (95%CI: -1.0 to -6.1) lower during acute malaria. The change in G6PD activity was apparent in patients presenting with either P. vivax or P. falciparum infection. Overall, 66.7% (4/6) severely deficient participants and 87.2% (34/39) with intermediate deficiency had normal activities when presenting with malaria. These findings suggest that G6PD activity rises significantly and at clinically relevant levels during acute malaria. Prospective case-control studies are warranted to confirm the degree to which the predicted population attributable risks of drug induced haemolysis is lower than would be predicted from cross sectional surveys., Competing Interests: The authors have declared that no competing interests exist.

Background: The COVID-19 pandemic and resulting restrictions, particularly travel restrictions, have had significant impact on the conduct of global clinical trials. Our clinical trials programme, which relied on in-person visits for training, monitoring and capacity building across nine low- and middle-income countries, had to adapt to those unprecedented operational challenges. We report the adaptation of our working model with a focus on the operational areas of training, monitoring and cross-site collaboration. The new working model: Adaptations include changing training strategies from in-person site visits with three or four team members to a multi-pronged virtual approach, with generic online training for good clinical practice, the development of a library of study-specific training videos, and interactive virtual training sessions, including practical laboratory-focused training sessions. We also report changes from in-person monitoring to remote monitoring as well as the development of a more localized network of clinical trial monitors to support hybrid models with in-person and remote monitoring depending on identified risks at each site. We established a virtual network across different trial and study sites with the objective to further build capacity for good clinical practice–compliant antimalarial trials and foster cross-country and cross-study site collaboration. Conclusion: The forced adaptation of these new strategies has come with advantages that we did not envisage initially. This includes improved, more frequent engagement through the established network with opportunities for increased south-to-south support and a substantially reduced carbon footprint and budget savings. Our new approach is challenging for study sites with limited prior experience but this can be overcome with hybrid models. Capacity building for laboratory-based work remains difficult using a virtual environment. The changes to our working model are likely to last, even after the end of the pandemic, providing a more sustainable and equitable approach to our research. [ABSTRACT FROM AUTHOR]

Background. Coinfection with malaria and typhoid fever is a major public health issue in developing countries. In endemic areas, including Ethiopia, people are at risk of acquiring both malaria and typhoid fever at the same time. Therefore, this study aimed to determine the magnitude of malaria-typhoid fever coinfection in febrile patients attending hospital at Southern Ethiopia. Methods. A hospital-based cross-sectional study was carried out on 416 febrile patients attending Arba Minch General Hospital from 1st October to 30th December 2021. The data was collected using a pretested structured questionnaire. Capillary and Venus blood samples were collected for assessing malaria and typhoid fever, respectively. Blood smear, culture, and biochemical tests were performed based on standard parasitological and microbiological methods. The P -value ≤ 0.05 was considered statistically significant. Results. The magnitude of malaria, typhoid fever, and their coinfections was 26.2% (109/416), 6.5% (27/416), and 3.1% (13/416), respectively. Among the confirmed malaria cases, about 66% of infections were Plasmodium falciparum. The malaria-typhoid fever coinfection showed a statistically significant association with a clinical presentation of a continuous pattern of fever (AOR = 5.84; 95% CI: 1.44–23.71, P = 0.014) and chills (AOR = 3.94; 95% CI: 1.04–14.89, P = 0.044). About 29.6% of Salmonella isolates were multidrug-resistant (MDR). Conclusion. The total rate of coinfection with malaria and typhoid fever was comparable to that of previous studies. With the consideration of higher prevalence of drug resistance of Salmonella spp. and higher prevalence of malaria‐typhoid fever coinfection, proper diagnostic procedure should be implemented for proper use of drugs. [ABSTRACT FROM AUTHOR]