Plasmodium vivax (P. vivax) malaria was long considered to have low mortality. Severe malaria was classically associated with Plasmodium falciparum (P. falciparum). However, there is growing evidence that severe and complicated forms of vivax malaria may be more widespread than previously assumed. We report a case of a 32-year-old female patient with acute respiratory distress syndrome (ARDS) as a complication of P. vivax malaria who has recovered completely following starting intravenous antimalarial medications and noninvasive ventilation (NIV).

Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator of NF-ƙB ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL), and is increasingly recognised as a marker of poor prognosis in a number of diseases. Here we demonstrate that in Malaysian adults with falciparum and vivax malaria, OPG is increased, and its ligands TRAIL and RANKL decreased, in proportion to disease severity. In volunteers experimentally infected with P. falciparum and P. vivax, RANKL was suppressed, while TRAIL was unexpectedly increased, suggesting binding of OPG to RANKL prior to TRAIL. We also demonstrate that P. falciparum stimulates B cells to produce OPG in vitro, and that B cell OPG production is increased ex vivo in patients with falciparum, vivax and knowlesi malaria. Our findings provide further evidence of the importance of the OPG/RANKL/TRAIL pathway in pathogenesis of diseases involving systemic inflammation, and may have implications for adjunctive therapies. Further evaluation of the role of B cell production of OPG in host responses to malaria and other inflammatory diseases is warranted.

UNASSIGNED: Falciparum malaria remains a global health problem. Two vaccines, based on the circumsporozoite antigen, are available. RTS, S/AS01 was recommended for use in 2021 following the advice of the World Health Organisation (WHO) Strategic Advisory Group of Experts (SAGE) on Immunization and WHO Malaria Policy Advisory Group (MPAG). It has since been pre-qualified in 2022 by the WHO. R21 is similar to RTS, S/AS01, and recently licensed in Nigeria, Ghana and Burkina Faso following Phase 3 trial results.
UNASSIGNED: We conducted a Phase 1b age de-escalation, dose escalation bridging study after a change in the manufacturing process for R21. We recruited healthy adults and children and used a three dose primary vaccination series with a booster dose at 1-2 years. Variable doses of R21 and adjuvant (Matrix-M ™) were administered at 10µgR21/50 µg Matrix-M™, 5µgR21/25µg Matrix-M™ and 5µgR21/50µg Matrix-M™ to 20 adults, 20 children, and 51 infants.
UNASSIGNED: Self-limiting adverse events were reported relating to the injection site and mild systemic symptoms. Two serious adverse events were reported, neither linked to vaccination. High levels of IgG antibodies to the circumsporozoite antigen were induced, and geometric mean titres in infants, the target group, were 1.1 (0.9 to 1.3) EU/mL at day 0, 10175 (7724 to 13404) EU/mL at day 84 and (following a booster dose at day 421) 6792 (5310 to 8687) EU/mL at day 456.
UNASSIGNED: R21/Matrix-M™ is safe, and immunogenic when given at varied doses with the peak immune response seen in infants 28 days after a three dose primary vaccination series given four weeks apart. Antibody responses were restored 28 days after a 4 th dose given one year post a three dose primary series in the young children and infants.
UNASSIGNED: Clinicaltrials.gov (NCT03580824; 9 th of July 2018; Pan African Clinical Trials Registry (PACTR202105682956280; 17 th May 2021).

Monitoring antimalarial efficacy is important to detect the emergence of parasite drug resistance. Angola conducts in vivo therapeutic efficacy studies (TESs) every 2 years in its fixed sentinel sites in Benguela, Lunda Sul, and Zaire provinces. Children with uncomplicated Plasmodium falciparum malaria were treated with artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), dihydroartemisinin-piperaquine (DP), or artesunate-pyronaridine (ASPY) and followed for 28 (AL and ASAQ) or 42 days (DP and ASPY) to assess clinical and parasitological response to treatment. Two drugs were sequentially assessed in each site in February-July 2021. The primary indicator was the Kaplan-Meier estimate of the PCR-corrected efficacy at the end of the follow-up period. A total of 622 patients were enrolled in the study and 590 (95%) participants reached a study endpoint. By day 3, ≥98% of participants were slide-negative in all study sites and arms. After PCR correction, day 28 AL efficacy was 88.0% (95% CI: 82%-95%) in Zaire and 94.7% (95% CI: 90%-99%) in Lunda Sul. For ASAQ, day 28 efficacy was 92.0% (95% CI: 87%-98%) in Zaire and 100% in Lunda Sul. Corrected day 42 efficacy was 99.6% (95% CI: 99%-100%) for ASPY and 98.3% (95% CI: 96%-100%) for DP in Benguela. High day 3 clearance rates suggest no clinical evidence of artemisinin resistance. This was the fourth of five rounds of TES in Angola showing a corrected AL efficacy <90% in a site. For Zaire, AL has had an efficacy <90% in 2013, 2015, and 2021. ASAQ, DP, and ASPY are appropriate choices as artemisinin-based combination therapies in Angola.

UNASSIGNED: Malaria remains a major cause of morbidity in sub-Saharan Africa. Undetected asymptomatic falciparum malaria results in a large transmission reservoir and there is evidence of increasing non-falciparum malaria as malaria is controlled in Africa, both resulting in challenges for malaria control programs.
UNASSIGNED: We performed quantitative real time PCR for 4 malaria species in 4,596 individuals from the 2014-2015 Rwanda Demographic Health Survey. Bivariate models were used to determine species-specific associations with risk factors.
UNASSIGNED: Asymptomatic falciparum malaria, P. ovale spp., and P. malariae infection had broad spatial distribution across Rwanda. P. vivax infection was rare. Overall infection prevalence was 23.6% (95%CI [21.7%, 26.0%]), with falciparum and non-falciparum at 17.6% [15.9%, 19.0%] and 8.3% [7.0%, 10.0%], respectively. Parasitemias tended to be low and mixed species infections were common, especially where malaria transmission was the highest. Falciparum infection was associated with socio-econiomic status, rural residence and low altitude. Few risk factors were associated with non-falciparum malaria.
UNASSIGNED: Asymptomatic falciparum malaria and non-falciparum malaria are common and widely distributed across Rwanda. Continued molecular monitoring of Plasmodium spp. is needed to monitor these threats to malaria control in Africa.

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Malaria remains one of the most challenging tropical diseases. Since malaria cases are reportedly alarming in terms of infections and mortality, urgent attention is needed for addressing the issues of drug resistance in falciparum malaria. High throughput screening methods have paved the way for rapid identification of anti-malarial. Furthermore, drug repurposing helps in shortening the time required for drug safety approvals. Hence, the discovery of new antimalarials by drug repurposing is a promising approach for combating the disease. This article summarizes the recent computational approaches used for identifying novel antimalarials by using drug target interaction tools followed by pharmacokinetic studies.

Autoimmune hemolytic anemia (AIHA) has been rarely reported worldwide or from India as the underlying cause of anemia in malaria. We hereby present a case of complicated Plasmodium falciparum malaria with concomitant warm AIHA in a 31-year-old male. Direct Antiglobulin Test (DAT) was positive and elution studies showed pan-agglutination reaction. Clinico-hematological and serological follow-up of the patient was done post artesunate treatment until day 9. We suggest that it is important to establish the immune basis of anemia in malaria patients for guiding the treatment plan for the clinicians and providing packed red blood cell transfusion if required.

BACKGROUND: Malaria is the most deadly parasitic disease and continues to claim more than a half million of deaths across the world each year, mainly those of under-fives children in sub-Saharan Africa. The aim of this study was to determine the epidemiological, clinical and laboratory features of patients with severe malaria at the Centre Hospitalier Régional Amissa Bongo (CHRAB), a referral hospital in Franceville.
METHODS: It was an observational descriptive study conducted at CHRAB over 10 months. All admitted patients at the emergency ward of all ages presenting with positive test to falciparum malaria diagnosed by microscopy and rapid test with clinical signs of severe illness describe by World Health Organization were enrolled.
RESULTS: During this study, 1065 patients were tested positive for malaria, of them 220 had severe malaria. Three quarters (75.0%) were less than 5 years of age. The mean time to consultation was 3.5 ± 1 days. The most frequent signs of severity on admission were dominated by neurological disorders 92.27% (prostration 58.6% and convulsion 24.1%), followed by severe anemia 72.7%, hyperlactatemia 54.6%, jaundice 25% and respiratory distress 21.82%.The other forms such as hypoglycemia, haemoglobinuria, renal failure were found in low proportions < 10%. Twenty-one patients died, coma (aOR = 15.54, CI 5.43-44.41, p < 0.01), hypoglycemia (aOR = 15.37, CI 2.17-65.3, p < 0.01), respiratory distress (aOR = 3.85, CI 1.53-9.73, p = 0.004) and abnormal bleeding (aOR = 16.42, CI 3.57-104.73, p = 0.003) were identified as independent predictors of a fatal outcome. Anemia was associated with decreased mortality.
CONCLUSIONS: Severe malaria remains a public health problem affecting mostly children under 5 years. Classification of malaria helps identify the most severely ill patients and aids early and appropriate management of the severe malaria cases.

BACKGROUND: Countries of the Greater Mekong Sub-region aim to achieve malaria elimination by 2030. In the region, malaria is concentrated in high-risk areas and populations such as forest-going mobile and migrant populations (MMPs). However, routine protective measures such as long-lasting insecticidal nets do not prevent all infectious bites in these high-risk populations. Evidence for the effectiveness of a personal protection package tailored to forest-going MMPs which is acceptable, feasible, and cost-effective for reducing malaria transmission is required to inform the malaria elimination toolkit in the region.
METHODS: A personal protection package consisting of long-lasting insecticidal hammock net, insect repellent and health communication pamphlet was developed in consultation with relevant implementing partners from Cambodia and Lao PDR. An open stepped-wedge cluster-randomised controlled trial will be conducted over a period of 12 months in a minimum of 488 villages (~ 428 in Lao PDR and ~ 60 in Cambodia) to evaluate the effectiveness of the personal protection package. Villages will be randomised into 11 blocks, with blocks transitioned in random order from control to intervention states at monthly intervals, following a 1-month baseline period. The primary outcome of the trial is the prevalence of Plasmodium spp. infection diagnosed by rapid diagnostic test. Difference in prevalence of malaria infection will be estimated across intervention and control periods using generalized linear mixed modelling. Nested within the stepped-wedge cluster-randomised controlled trial is a mixed-methods study to explore the acceptability of the personal protection package, feasibility of implementing a personal protection package as a vector control intervention, and knowledge, attitude and practice of MMPs regarding malaria prevention; and cost-analysis to determine the cost-effectiveness of implementing a personal protection package.
CONCLUSIONS: This study, using a rigorous design and mixed-methods methodology, will evaluate whether a personal protection package can reduce residual malaria transmission among forest-going MMPs in Cambodia and Lao PDR. It will also measure implementation research outcomes such as effectiveness of the intervention package, cost-effectiveness, acceptability, and feasibility, in order to inform potential national and regional policy. Trial registration This trial was prospectively registered on ClinicalTrials.gov (NCT05117567) on 11th November 2021.