Delay in receiving treatment for uncomplicated malaria (UM) is often reported to increase the risk of developing severe malaria (SM), but access to treatment remains low in most high-burden areas. Understanding the contribution of treatment delay on progression to severe disease is critical to determine how quickly patients need to receive treatment and to quantify the impact of widely implemented treatment interventions, such as ‘test-and-treat’ policies administered by community health workers (CHWs). We conducted a pooled individual-participant meta-analysis to estimate the association between treatment delay and presenting with SM. A search using Ovid MEDLINE and Embase was initially conducted to identify studies on severe Plasmodium falciparum malaria that included information on treatment delay, such as fever duration (inception to 22nd September 2017). Studies identified included 5 case–control and 8 other observational clinical studies of SM and UM cases. Risk of bias was assessed using the Newcastle–Ottawa scale, and all studies were ranked as ‘Good’, scoring ≥7/10. Individual-patient data (IPD) were pooled from 13 studies of 3,989 (94.1% aged <15 years) SM patients and 5,780 (79.6% aged 24 hours versus ≤24 hours; p = 0.009). Reported illness duration was a strong predictor of presenting with severe malarial anaemia (SMA) in children, with an OR of 2.79 (95% CI:1.92–4.06; p < 0.001) for a delay of 2–3 days and 5.46 (95% CI: 3.49–8.53; p < 0.001) for a delay of >7 days, compared with receiving treatment within 24 hours from symptom onset. We estimate that 42.8% of childhood SMA cases and 48.5% of adult SMA cases in the study areas would have been averted if all individuals were able to access treatment within the first day of symptom onset, if the association is fully causal. In studies specifically recording onset of nonsevere symptoms, long treatment delay was moderately associated with other SM phenotypes (OR [95% CI] >3 to ≤4 days versus ≤24 hours: cerebral malaria [CM] = 2.42 [1.24–4.72], p = 0.01; respiratory distress syndrome [RDS] = 4.09 [1.70–9.82], p = 0.002). In addition to unmeasured confounding, which is commonly present in observational studies, a key limitation is that many severe cases and deaths occur outside healthcare facilities in endemic countries, where the effect of delayed or no treatment is difficult to quantify. Our results quantify the relationship between rapid access to treatment and reduced risk of severe disease, which was particularly strong for SMA. There was some evidence to suggest that progression to other severe phenotypes may also be prevented by prompt treatment, though the association was not as strong, which may be explained by potential selection bias, sample size issues, or a difference in underlying pathology. These findings may help assess the impact of interventions that improve access to treatment.

Background: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focused on high-income settings.Methods: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys, we explored how contact characteristics (number, location, duration, and whether physical) vary across income settings.Results: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, with low-income settings characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income strata on the frequency, duration, and type of contacts individuals made.Conclusions: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens and the effectiveness of different non-pharmaceutical interventions.Funding: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

This study examined the association between resilience and psychological distress in healthcare workers, the general population, and patients during the COVID-19 pandemic. We searched the PubMed, Web of Science, PsycInfo, Science Direct, and Nursing and Allied Health databases. Included articles examined healthcare workers (e.g., physicians and nurses), the general population, and patients during the COVID-19 pandemic. Studies of exposure to other infectious diseases related to epidemics or pandemics (e.g., SARS and MERS) were excluded. This study was performed following the Cooper matrix review method and PRISMA guidelines, followed by a meta-analysis of study results using R version 4.1.2. A random effect model was used for the pooled analysis. This study was registered with PROSPERO (registration No. CRD42021261429). Based on the meta-analysis, we found a moderate negative relationship between overall resilience and psychological distress (r = −0.42, 95% confidence interval [CI]: −0.45 to −0.38, p < 0.001). For the subgroup analysis, a moderately significant negative relationship between overall resilience and psychological distress was found among healthcare workers (r = −0.39, 95% CI: −0.44 to −0.33, p < 0.001), which was weaker than in the general population (r = −0.45, 95% CI: −0.50 to −0.39, p < 0.001) and in patients (r = −0.43; 95% CI: −0.52 to −0.33; p < 0.001). This association was robust, although the heterogeneity among individual effect sizes was substantial (I² = 94%, 99%, and 74%, respectively). This study revealed a moderate negative relationship between resilience and psychological distress in healthcare workers, the general population, and patients. For all these populations, interventions and resources are needed to improve individuals’ resilience and ability to cope with psychological distress during the COVID-19 pandemic and in future disease outbreaks.

Partial artemisinin resistance, mediated by Plasmodium falciparum K13 (PfK13) mutations, has been confirmed in certain areas of East Africa that are historically associated with high-level antimalarial resistance. The Democratic Republic of Congo (DRC) borders these areas in the East. This study aimed to determine the prevalence of resistance markers in six National Malaria Control Program surveillance sites; Boende, Kabondo, Kapolowe, Kimpese, Mikalayi, and Rutshuru. The single nucleotide polymorphisms (SNPs) in P. falciparum genes PfK13, Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt were assessed using targeted next-generation sequencing of isolates collected at enrollment in therapeutic efficacy studies. PfK13 SNPs were detected in two samples: in Kabondo (R561H) and in Rutshuru (P441L), both areas near Uganda and Rwanda. The Pfdhps ISGEGA haplotype, associated with reduced sulfadoxine-pyrimethamine chemoprevention efficacy, ranged from 0.8% in Mikalayi (central DRC) to 42.2% in Rutshuru (East DRC). R561H and P441L observed in eastern DRC are a concern, as they are associated with delayed artemisinin-based combination therapies-clearance and candidate marker of resistance, respectively. This is consistent with previous observations of shared drug resistance profiles in parasites of that region with bordering areas of Rwanda and Uganda. The likely circulation of parasites has important implications for the ongoing surveillance of partial artemisinin-resistant P. falciparum and for future efforts to mitigate its dispersal.

Sulfadoxine-pyrimethamine (SP) is recommended for perennial malaria chemoprevention in young children in high burden areas across Africa. Mutations in the dihydropteroate synthase (dhps) gene (437 G/540E/581 G) associated with sulfadoxine resistance vary regionally, but their effect on SP protective efficacy is unclear. We retrospectively analyse time to microscopy and PCR-confirmed re-infection in seven efficacy trials including 1639 participants in 12 sites across Africa. We estimate the duration of SP protection against parasites with different genotypes using a Bayesian mathematical model that accounts for variation in transmission intensity and genotype frequencies. The longest duration of SP protection is >42 days against dhps sulfadoxine-susceptible parasites and 30.3 days (95%Credible Interval (CrI):17.1-45.1) against the West-African genotype dhps GKA (437G-K540-A581). A shorter duration of protection is estimated against parasites with additional mutations in the dhps gene, with 16.5 days (95%CrI:11.2-37.4) protection against parasites with the east-African genotype dhps GEA (437G-540E-A581) and 11.7 days (95%CrI:8.0-21.9) against highly resistant parasites carrying the dhps GEG (437G-540E−581G) genotype. Using these estimates and modelled genotype frequencies we map SP protection across Africa. This approach and our estimated parameters can be directly applied to any setting using local genomic surveillance data to inform decision-making on where to scale-up SP-based chemoprevention or consider alternatives.

Children recovering from severe malarial anaemia (SMA) remain at high risk of readmission and death after discharge from hospital. However, a recent trial found that post-discharge malaria chemoprevention (PDMC) with dihydroartemisinin-piperaquine reduces this risk. We developed a mathematical model describing the daily incidence of uncomplicated and severe malaria requiring readmission among 0–5-year old children after hospitalised SMA. We fitted the model to a multicentre clinical PDMC trial using Bayesian methods and modelled the potential impact of PDMC across malaria-endemic African countries. In the 20 highest-burden countries, we estimate that only 2–5 children need to be given PDMC to prevent one hospitalised malaria episode, and less than 100 to prevent one death. If all hospitalised SMA cases access PDMC in moderate-to-high transmission areas, 38,600 (range 16,900–88,400) malaria-associated readmissions could be prevented annually, depending on access to hospital care. We estimate that recurrent SMA post-discharge constitutes 19% of all SMA episodes in moderate-to-high transmission settings.