Children under five, pregnant women, people living with HIV, and travelers without prior exposure are the most susceptible to malaria. In 2024, the disease caused an estimated 282 million cases and 610,000 deaths worldwide, with 95% of those deaths occurring in sub-Saharan Africa. Susceptibility depends on a mix of immune status, genetics, geography, and daily exposure to mosquitoes.
Children Under Five
Young children bear the heaviest toll. In the WHO African Region, children under five account for roughly 75% of all malaria deaths. Their immune systems have not yet encountered the parasite, so even a first infection can escalate quickly to life-threatening illness. In areas where malaria transmission is constant, children face repeated infections throughout early childhood. Each bout helps the immune system learn to recognize the parasite, but that learning process takes years, and many children don’t survive it.
To bridge this gap, the WHO recommends seasonal malaria chemoprevention (SMC), which involves giving children preventive doses of antimalarial medicine each month during the rainy season when transmission peaks. This approach was originally limited to children under six but has since been expanded to older children in high-risk areas.
Pregnant Women
Pregnancy creates a near-perfect storm for malaria susceptibility. The immune system naturally dials itself back during pregnancy to avoid rejecting the fetus, and that suppression also weakens the body’s defenses against the malaria parasite. On top of that, the placenta itself provides a favorable environment where the most dangerous species of malaria parasite can accumulate and multiply.
Women in their first pregnancy are especially vulnerable. The immune system has never had to manage malaria in the context of a placenta before, and first-time mothers consistently show higher infection rates than women who have been pregnant before. The consequences extend beyond the mother: infected placental tissue can restrict oxygen and nutrient delivery to the fetus, leading to low birth weight, growth restriction, preterm delivery, stillbirth, and long-term developmental problems in children who survive. Maternal anemia is common and can be severe.
Preventive treatment during pregnancy, known as IPTp, is now recommended by the WHO for all pregnant women in malaria-endemic areas regardless of how many prior pregnancies they’ve had. Earlier guidance limited this to first and second pregnancies, but updated evidence showed the risk persists.
People Living With HIV
HIV and malaria each make the other worse. HIV weakens the immune system’s ability to control malaria parasites, leading to more frequent infections, higher parasite levels in the blood, and more severe complications like cerebral malaria and dangerous anemia. People with both infections are twice as likely to develop severe anemia compared to those with malaria alone, and they’re also more likely to experience treatment failure, where the parasite returns after an apparently successful course of medication.
In children, the combination is particularly harsh. HIV-positive children experience more frequent episodes of clinical malaria, and those episodes tend to be more severe, with higher rates of respiratory distress, acidosis, and death. In pregnant women, the overlap is equally dangerous. A study in Zimbabwe found that HIV-positive pregnant women were about four times more likely to develop malaria symptoms than HIV-negative pregnant women. Unlike women without HIV, who gradually build placental immunity across multiple pregnancies, women living with HIV appear to remain as vulnerable in later pregnancies as they were in their first.
Travelers and People Without Prior Exposure
Anyone who grows up outside a malaria-endemic region and then visits one has essentially zero natural defense against the parasite. In people with no prior exposure, even a very small number of parasites in the blood can trigger symptoms like high fever, chills, and headache. The body doesn’t recognize the infection, so parasites multiply rapidly and can reach dangerous levels before the immune system mounts an effective response.
By contrast, people who grew up in endemic areas and later moved away retain some residual immunity. Studies comparing these “visiting friends and relatives” travelers to first-time visitors consistently show that people with childhood exposure develop less severe illness and lower parasite counts. Their immune memory isn’t perfect, and it fades over years spent in malaria-free settings, but it provides a meaningful buffer. For truly non-immune travelers, the disease can progress from mild symptoms to organ failure within days if untreated.
How Partial Immunity Develops
People who live in areas with constant malaria transmission do eventually develop partial protection, but it takes many years of repeated infections. This isn’t the kind of sterilizing immunity you get from a vaccine for measles, where one exposure prevents all future illness. Instead, it’s a gradual process where the immune system learns to keep parasite levels low enough to prevent severe disease, even if it can’t eliminate the parasite entirely. Adults in high-transmission areas often carry low-level infections with few or no symptoms.
This partial immunity is maintained only through ongoing exposure. Move away from an endemic area for several years, and it begins to erode. It also explains why malaria is deadliest in young children: they simply haven’t had enough infections yet for their immune systems to learn effective control.
Genetic Factors That Affect Susceptibility
Certain inherited blood cell traits offer natural protection against severe malaria. The most well-known is sickle cell trait, where a person carries one copy of the sickle cell gene (rather than two, which causes sickle cell disease). The malaria parasite grows and develops less effectively inside red blood cells that carry this trait. Infected cells are also more likely to be flagged and destroyed by the spleen before the parasite can multiply further. Research in Gambia found that the immune system’s ability to recognize and clear parasite-infected red blood cells was enhanced in children with sickle cell trait.
This protective effect is significant enough that sickle cell trait has persisted at high rates in populations from malaria-endemic regions through natural selection over thousands of years. Other inherited red blood cell variations, including certain forms of thalassemia, provide a similar though less dramatic level of protection through related mechanisms involving early destruction of infected cells. On the flip side, people without any of these genetic traits who live in or travel to endemic regions lack this extra layer of defense.
Occupational and Environmental Exposure
Where you live and what you do for work significantly affects your malaria risk. Rural agricultural communities in endemic areas face some of the highest exposure because farming activities create and sustain mosquito breeding habitat. Crops that require heavy irrigation, like rice, cotton, sugarcane, and maize, keep standing water on the landscape. Land clearing for new fields creates pooling on the soil surface. Poorly maintained irrigation channels stagnate. All of these conditions favor the mosquito species that transmit malaria.
Research among women in small-scale agriculture in South Africa found that those who worked on family-owned farms were 2.6 times more likely to report a history of malaria. Women who sprayed pesticides in the fields, which kept them outdoors for extended periods, were 2.3 times more likely. Starting work early in the morning, around 6:00 AM, overlapped with peak mosquito biting hours and increased contact. Living close to a water source, residing in the same house for more than four years (suggesting cumulative exposure), and the type of housing construction all independently raised risk.
Where Transmission Is Highest
Geography is one of the strongest predictors of who gets malaria. Over 92% of survey locations reporting the highest parasite prevalence rates are in sub-Saharan Africa, concentrated between 15 degrees north and south of the equator. This band corresponds to the range of the most efficient malaria-transmitting mosquito species. Eleven countries within this zone account for roughly two-thirds of all global cases and deaths.
Outside of Africa, transmission intensity drops substantially. In the Americas and the Eastern Mediterranean/European regions, 87% and 65% of surveyed areas respectively showed infection rates below 10%, classified as low-level transmission. Southeast Asia and the Western Pacific follow a similar pattern, with over 65% of surveys reporting low prevalence. Even in Africa, arid zones like the Sahel, the Horn of Africa, and parts of southern Africa see lower transmission because dry conditions limit mosquito breeding. Globally, about 42% of people exposed to some malaria risk live in areas with unstable, seasonal transmission rather than year-round exposure, meaning they build less natural immunity and remain more vulnerable when outbreaks do occur.