The Lancet | Malaria

Malaria 

Jeanne Rini Poespoprodjo, Nicholas M Douglas, Daniel Ansong, et al.
The Lancet 2023. Available online 2 November 2023
DOI: 10.1016/S0140-6736(23)01249-7

Summary

Malaria is resurging in many African and South American countries, exacerbated by COVID-19-related health service disruption. In 2021, there were an estimated 247 million malaria cases and 619 000 deaths in 84 endemic countries. Plasmodium falciparum strains partly resistant to artemisinins are entrenched in the Greater Mekong region and have emerged in Africa, while Anopheles mosquito vectors continue to evolve physiological and behavioural resistance to insecticides. Elimination of Plasmodium vivax malaria is hindered by impractical and potentially toxic antirelapse regimens. Parasitological diagnosis and treatment with oral or parenteral artemisinin-based therapy is the mainstay of patient management. Timely blood transfusion, renal replacement therapy, and restrictive fluid therapy can improve survival in severe malaria. Rigorous use of intermittent preventive treatment in pregnancy and infancy and seasonal chemoprevention, potentially combined with pre-erythrocytic vaccines endorsed by WHO in 2021 and 2023, can substantially reduce malaria morbidity. Improved surveillance, better access to effective treatment, more labour-efficient vector control, continued drug development, targeted mass drug administration, and sustained political commitment are required to achieve targets for malaria reduction by the end of this decade.

Section snippets

Epidemiology

Malaria is transmitted by female Anopheles mosquitoes that breed in freshwater bodies in warm and humid environments. Endemicity is determined by the geographical distribution of vector species, their proximity to humans, and the capacity of human populations to control vectors and effectively manage infection. Therefore, malaria flourishes in low-income tropical regions and is exacerbated by social disruption, such as war or natural disaster.
Of an estimated 247 million malaria cases…

Biology

Sporozoites from female Anopheles mosquitoes enter the human circulation following a blood meal and are transported to the liver to invade hepatocytes. After 5–8 days of pre-erythrocytic incubation (approximately 15 days for P malariae), merozoites are released from rupturing hepatic schizonts and enter circulation to invade red blood cells, initiating the intraerythrocytic lifecycle responsible for malaria symptoms. Asexual parasite development in erythrocytes occurs over 24–72 h…

P falciparum

Severe falciparum malaria is caused by microvascular sequestration and obstruction from parasitised red cells cytoadhering to activated and dysfunctional endothelial cells.5, 28 Sequestered parasite biomass and endothelial activation are each independently associated with impaired perfusion, severity of organ dysfunction, and mortality.29, 30 Cytoadherence is mediated by binding of the PfEMP1 family of proteins expressed on parasitised erythrocytes to receptors on endothelial cells and other…

Clinical presentation

Malaria is a non-specific febrile illness that cannot be differentiated from other infections on clinical grounds alone. Typical symptoms include fever, chills, headache, vomiting, diarrhoea, and cough. In highly endemic areas, parasitaemia is often coincidental to an alternative cause of illness. Parasitaemia, platelet count, and plasma HRP2 thresholds for falciparum malaria have been evaluated in regions of different endemicity to distinguish the likelihood of malaria causing symptoms and…

Laboratory diagnosis

Microscopy of thick and thin blood films remains the gold standard for diagnosing malaria. This method can differentiate Plasmodium species and quantify parasitaemia, both important for diagnosing and prognosticating severe malaria, targeting appropriate treatment, and monitoring therapeutic response. Unless performed by experienced technicians, microscopy results might not be reliable.
Malaria rapid diagnostic tests (RDTs) are used as an alternative or adjunct to microscopy, particularly in…

Case management

Comprehensive guidelines for management of severe and uncomplicated malaria are provided by WHO.5, 81…

Malaria in pregnancy

Malaria in pregnancy can be fatal to both the mother and fetus. In sub-Saharan Africa, maternal falciparum malaria contributes to 10–20% of maternal deaths and is indirectly responsible for 75 000–200 000 infant deaths. Non-immune pregnant women and semi-immune primigravidae are at particularly high risk of severe malaria.145 Maternal malaria impairs placental function, affecting fetal development and thereby increasing the risk of miscarriage, low birthweight, small for gestational age, …

Congenital and neonatal malaria

Congenital and neonatal malaria is defined as parasitaemia within the first 7–28 days of life. The estimated global prevalence of symptomatic congenital and neonatal malaria is 0·1–0·6%. Failure to include congenital and neonatal malaria as a differential diagnosis in sick neonates presenting with sepsis syndrome in endemic areas can lead to life-threatening treatment delay. Maternal-to-fetal malaria transmission can occur in utero or at delivery. Although most patients…

Antimalarial drug resistance

The recurrence of malaria following treatment can be because of incomplete clearance of parasitaemia (recrudescence), reinfection, or, in the case of P vivax and P ovale malaria, relapse. Recrudescence is more probable if there is initial hyperparasitaemia, suboptimal antimalarial drug dosing or absorption, use of substandard or fake antimalarial drugs, incomplete adherence to treatment, or parasite resistance to the antimalarial drugs used.
Antimalarial resistance has plagued efforts for…

Delayed complications of malaria

Long-term cognitive impairment arises from three of the major clinical syndromes associated with acute mortality in children with falciparum malaria: cerebral malaria, severe anaemia, and AKI. Other neurological sequelae of cerebral malaria include epilepsy, motor and visual deficits, and short-term developmental delay. A reversible, post-malaria neurological syndrome can develop rarely after recovery from severe and uncomplicated falciparum malaria. AKI can lead to…

Factors that modulate the risk of malaria

Both heritable and acquired factors modulate the risk of Plasmodium infection and malaria severity (appendix). Most heritable factors alter either the efficiency of parasite red-cell invasion or intraerythrocytic survival and collectively account for approximately a third of the variability in risk of severe disease. Heterozygotes for HbS (sickle trait) are afforded 85–90% protection against severe and fatal P falciparum malaria, but are not protected against asymptomatic parasitaemia…

Chemoprevention

Prompt diagnosis and effective treatment of malaria not only benefits individuals, but is also a cornerstone of malaria prevention. Clearance of parasitaemia with ACTs minimises the risk of onward mosquito transmission primarily by limiting development of further gametocytes. This risk is reduced further by administering a single dose of primaquine to sterilise mature gametocytes in P falciparum malaria.
Antimalarial drugs are also used for mass-chemoprevention or targeted-chemoprevention
The future of malaria control and elimination…
Launched in 1955, the Global Malaria Eradication Program ended without success 14 years later. Since 1969, there has been no further time-limited commitment to global malaria eradication and its feasibility continues to be debated. However, malaria elimination—defined by WHO as the interruption of local transmission of a specific malaria parasite species in a defined geographical area due to deliberate activities—is being pursued vigorously in multiple countries with unstable malaria…