Children infected with malaria can become “super spreaders” and pass the parasite on to flocks of local mosquitoes, even if the children never develop symptoms of the disease, according to a new study.
Since the disease is transmitted from humans to mosquitoes and back again, rather than from person to person, this finding is worrying.
If malaria is left untreated in these asymptomatic children, the parasites will continue to circulate among mosquitoes, even in places that have intensive malaria controls like insecticides, bed nets, and free diagnostic tests and treatments. According to a new study presented at the American Society for Tropical Medicine and Hygiene (ASTMH) annual meeting on Wednesday (November 18), even a small number of infected children can transmit malaria parasites to a lot of mosquitoes, which can then go away to more people to infect.
Based on their new research in Uganda, the researchers concluded that asymptomatic children between the ages of 5 and 15 are the main source of infection for local mosquitoes in the region they studied. Some of these children were so-called super-spreaders, which means that they infected far greater numbers of mosquitoes than others; In experiments in which mosquitoes were given blood samples from infected people, more than 60% of the resulting mosquito infections could be traced back to just four asymptomatic children, two of whom were of school age. The other two super spreaders were 3 and 4 years old.
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Although some children were infected with multiple malaria clones during the study, these children never got sick and continued to “live normal lives … somehow living with all these parasites,” said lead author Chiara Andolina, a PhD student and malaria expert the Radboud University Medical Center in the Netherlands. Malaria is well controlled in the region the team studied. However, should control efforts ever wane or stop, these children could potentially lead to disease recurrence in the area.
To prevent malaria cases from recovering, the control efforts could specifically target school-age children, senior author Teun Bousema, a malaria epidemiologist at Radboud, told Live Science. For example, regular malaria screenings and treatment campaigns in schools could have a “very significant impact” on malaria reservoir depletion and ultimately bring the number of cases to zero, he said.
Discover the superspreader
Asymptomatic malaria infections account for 80% or more of the cases discovered through extensive research in areas where the disease regularly circulates, Bousema said. Studies suggest that these asymptomatic infections are most common in school-age children.
While scientists believe that mosquitoes ingest malaria in both symptomatic and asymptomatic people, the question arises whether one type of infection is more or less contagious than the other. In search of the answer, the study’s authors traveled to the Tororo District in Uganda.
Malaria was once incredibly common in Tororo; As recently as 2011, each resident was bitten by malaria-infected mosquitoes about 310 times a year, Andolina said in her ASTMH presentation. Now, after years of intense malaria control, infection rates have dropped. In 2018, exposure to infectious mosquitoes dropped to just 0.43 bites per person per year.
“It’s kind of a blueprint for what to expect. If you really invest very heavily in malaria control, you can lower the burden of malaria,” Bousema said. But to completely eradicate malaria, scientists need to find and clean up any remaining hiding spots for the parasite, he added.
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To this end, the Tororo team recruited 531 adults and children from 80 households and monitored them for malaria for two years. Every month they performed diagnostic tests and collected blood samples from the participants; The blood was checked for malaria parasites and then used in mosquito feeding experiments.
(Photo credit: Teun Bousema and Chiara Andolina)
In order to pass from humans to mosquitoes, malaria parasites must first mature into “gametocytes”. As soon as the gametocytes are ingested by the blood-sucking insects, they divide into sex cells, fertilize each other and multiply. With this in mind, the team also analyzed the density of gametocytes in human blood samples, as the number can indicate how contagious this blood could be to mosquitoes.
During the course of the study, the team detected 148 malaria episodes – 38 symptomatic and 110 asymptomatic. They performed nearly 540 mosquito feeding experiments on blood from 107 infected people, using a device that keeps the blood warm with circulating water. In each experiment, dozens of mosquitoes were released into a container with the device, where they could access the blood through a membrane that mimicked human skin.
The team later dissected the fed mosquitoes to see how many became infected, and the vast majority of infections were associated with blood from asymptomatic people.
Total infected blood from symptomatic persons was only 0.6% of the total infected mosquitoes.
Aim for hidden reservoirs
This trend is likely due in part to symptomatic people who have easy access to malaria treatment, according to the authors.
“In our study, when children and adults got sick, often went to the clinic before they developed these transmissible gametocytes,” said Bousema. It takes nine to 12 days for the gametocytes to mature. By this time, most of the symptomatic people had already received treatment. “It actually shows that with very good access to care, you can prevent transmission of symptomatic individuals.”
The challenge then is to identify infected people with no symptoms so that their chains of transmission can also be broken, he said. Notably, some asymptomatic individuals in the study remained infectious for months, although their gametocyte counts fluctuated over time. For example, two children remained infectious for six months without ever developing symptoms of malaria.
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“Asymptomatic infections really dominated in children … and school children somehow have longer-lasting infections, higher gametocyte densities, so they were really the major source of mosquito infection,” said Bousema.
Overall, the researchers estimated that children ages 5 to 15 make up almost 57% of the infectious reservoir, which means they carry the most parasites that mosquitoes could infect with malaria. After school-age children, children under 5 make up 27.5% of the reservoir, while children 16 and over make up the remaining 15.7%.
Malaria control measures, like insecticide-treated nets to cover people’s beds, are often prioritized for toddlers under 5 and pregnant women, but school-age children may be overlooked, the authors noted. Beyond networks, test-and-treat campaigns in schools could help eradicate new cases of malaria before they are transmitted to local mosquitoes. Preventive drugs, many of which can also be used to treat malaria, could help children avoid picking the parasites in the first place.
Originally published on Live Science.