‘All Malaria Is Local’
The parasite-mosquito-human nexus spawns an incredibly complex disease challenge. Successes against malaria often don’t last, nor are they easily replicated. Yet.
In 2003, they came by the hundreds. By foot and by bicycle, subsistence farmers carried their feverish children to Macha Mission Hospital. These were children with malaria, some shaking with chills, others comatose, some convulsed by seizures, others listless. That year, the 200-bed hospital in southern Zambia admitted 1,100 children under 6 years old with malaria.
Thirty-three of them died.
This was nothing new. When Limonty Simubali was growing up near Macha in the 1980s, the entomologist lost two brothers to malaria before they turned 3. “Malaria used to be so abundant,” he recalls.
Then, after 2003, cases plunged and never resurged, according to scientists from the local Macha Research Trust and the Johns Hopkins Malaria Research Institute who have collaborated since that same year. In 2020, fewer than 50 Macha-area children with the mosquito-borne disease came to the hospital, which serves 56,000 people. And for three straight years, no child has died from malaria. Now, just 1%–2% of the population carries the Plasmodium falciparum parasite that causes the disease.
Roughly 800 miles to the north, the situation is starkly different. In Zambia’s densely populated Nchelenge District, where the Bloomberg School team has done similar research for a decade, half the children carry malaria parasites in their blood. Last year, 420 people died of malaria in the hospital there, which serves 300,000 people. Most who died were younger than 15.
The government malaria program in Nchelenge employs the same measures that seemingly succeeded in Macha— insecticide-treated bed nets, spraying the walls of houses with insecticide, and free treatment for people with the parasite—yet those efforts have barely dented transmission.
Why hasn’t Macha’s success been replicated in Nchelenge?
“All malaria is local,” says Matthew Ippolito, MD, PhD ’21, a JHMRI researcher and an assistant professor at the Johns Hopkins School of Medicine.
And all malaria is complicated. The disease proliferates through encounters among three organisms: the female Anopheles mosquito in search of human blood for dinner, the Plasmodium parasite infesting her saliva, and the bitten human. Complicating this triad are other factors like climate, income, human behavior, travel, politics, and even spirituality.
Phil Thuma, MD, didn’t focus much on malaria when he arrived at Macha Mission Hospital in 1976 with his wife, Elaine Nell Thuma, a nurse. The son of the hospital’s American founder, Thuma had grown up in Macha. As a newly graduated general practitioner, he wanted to address malnutrition, eliminate measles, and improve water quality and sanitation. Haunted by the fact that half of local children were dying by age 11, Thuma did a pediatrics residency at Johns Hopkins. When the Thuma family returned to Macha in 1983, the only form of malaria control was treating sick people with two old drugs, chloroquine and quinine.
“Malaria affected every single family I knew,” says Thuma. “Sometimes I’d see three kids die from malaria in one day, kids that had been healthy two weeks ago. We went to funerals frequently.”
Although adults develop some immunity after repeated exposure to infection, children are quite vulnerable. “You could lose a kid no matter how careful you were,” says Thuma.
After a surge of cases in 1988, Thuma began to give malaria his full attention. A year later, he established what is now called the Macha Research Trust. And in 2003, the Trust began to receive support from Bloomberg Philanthropies. Collaboration with JHMRI brought the School’s scientists and opportunities for educational exchange.
Researchers working in Macha have come to believe three interventions contributed to the area’s dramatic decline in malaria cases: drugs, nets, and spraying. Local people had access to new artemisinin combination medications years before they came onto the market in 2004 because Thuma had arranged for his hospital to take part in clinical trials for the drugs. “They worked crazy fast,” Thuma says, and without the side effects of quinine drugs. Starting in 2003, Zambia’s National Malaria Control Program began supplying insecticide-treated bed nets and spraying inside houses before the annual November-through-March rainy season.
In addition, the government initiated a methodical test-and-treat program that it still follows. A field team visits the home of anyone diagnosed with the parasite and treats other household members and nearby neighbors if they test positive for Plasmodium. The Hopkins team concluded that this does not eliminate transmission, however. The system may fail partly because the rapid tests are not nearly as accurate in areas where people have low parasitemia (levels of parasites in their blood), says JHMRI deputy director William Moss, MD, MPH. The researchers have proposed that their Zambian colleagues try a slightly different approach: treating everyone who shares a household with an infected person without any testing.
One elimination strategy—mass drug treatment—was thought to kill even hidden parasites, but it doesn’t work. The parasites can elude the medication by hiding out in the liver (and in mosquitoes, of course). In addition, studies in Zambia and elsewhere have found that even when optimally managed, mass treatment misses about 30% of the population.
Moss and some colleagues suspect that the sharp reduction in malaria in 2004 was at least partly a gift borne by drought, which locally killed off an efficient vector of the parasite, Anopheles funestus. But Kenya, without a drought, also saw sharp declines in malaria infections that year, so Moss only half trusts the theory. Meanwhile, the niche that Anopheles funestus occupied was filled by other little-studied anophelines, such as the rufipes, squamosus, and coustani.
What surely did help, says Ippolito, was the swift fivefold increase in Zambia’s GDP that began in 2000. That meant more people could install indoor plumbing and avoid going outdoors at night to relieve themselves, and more people had money to buy malaria medicine at local shops rather than trekking to the hospital.
Malaria control efforts also benefitted from community confidence in biomedicine, says Simubali, the Trust’s entomology coordinator. He remembers when parents would interpret a sick child’s convulsions and hallucinations as evidence of a spiritual disorder needing care from a traditional healer or a spiritualist. After that, the child usually arrived at the hospital too late. Nowadays, following workshops and person-to-person conversations, healers and spiritualists send feverish children directly to the hospital, with a referral note.
THE LOCAL FIGHT
Now the goal in Macha is to eliminate malaria. Driving down the numbers is not enough, because even low-level asymptomatic parasitemia has its costs, notes JHMRI director Peter Agre, MD. For the individual, he says, it means “an enormous burden on the body.” For the community, it poses a risk: A mosquito that bites an asymptomatic carrier can still spread infection.
Moss recommends two strategies for ridding Macha of malaria. First, use more sensitive rapid tests in the field, such as mobile PCR tests. Second, gain a better understanding of “outdoor biting.” Mosquitoes that feed outside after dark find plenty of human prey because people in Macha cook and socialize outdoors. Moss suspects that open-air bites come from Anopheles rufipes, squamosus, and coustani. To further complicate matters, research shows that when people move indoors earlier in the evening, mosquitoes adapt by biting earlier. Their brains may be smaller than a pencil point, but as Thuma puts it, “mosquitoes are smart little buggers.”
In Nchelenge, malaria fighters face an additional challenge: the mammoth Lake Mweru, fringed with swampy areas favored by breeding mosquitoes. And mosquitoes in the region bite during both the rainy and dry seasons.
Then there’s always the risk of parasite importation. For instance, some 15,000 refugees from high-transmission areas in neighboring Democratic Republic of the Congo settled in the Nchelenge District in 2018. Malaria rates are so high in Nchelenge that researchers cannot gauge how the new residents affected overall transmission.
The Bloomberg School research program—technically, the Southern and Central Africa International Center of Excellence for Malaria Research—has scoped out future priorities for Macha and Nchelenge. In Macha, they recommend testing of households near mosquito-friendly sites like streams; studying less-known vectors and evaluating outdoor mosquito controls; and using a new phone app that speeds the time to report, locate, and treat infected people. In Nchelenge, they suggest beefing up supply chains to avoid shortages of malaria drugs and blood products for treating malaria-induced anemia; expanding bed net use; and spraying insecticide in more houses. The government is already piloting another recommendation—moving indoor spraying of houses to April. This is the end of the rainy season, when A. funestus typically peaks.
Another promising development is the first-ever malaria vaccine for children, which WHO recommended last fall. Though the RTS,S vaccine reduces cases of severe disease only by 30% to 40%, Moss says it could have a big impact in places with high prevalence like Nchelenge.
Malaria researchers, he says, must continue working on interventions at both ends of the transmission spectrum. “We’ve got the Macha area, where we’ve seen transmission go downward and where there are hopes of eliminating malaria. That’s the optimistic side,” Moss says. “On the other hand, in the same country, and in other parts of sub-Saharan Africa, there are places like Nchelenge where, with our current tools, the problem seems intractable.”