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Malaria-infected children can become “super diffusers” and transmit the parasite in droves of local mosquitoes, even if the children never develop symptoms of the disease, a new study suggests.
As this disease is transmitted from humans to mosquitoes and then again, rather than person-to-person, this finding is worrying.
Self malaria is not treated in these asymptomatic children, parasites will continue to circulate between mosquitoes, even in places that employ intensive malaria controls such as insecticides, bed nets, and free diagnostic tests and treatments. According to new research, presented Wednesday (November 18) at the American Society of Tropical Medicine and Hygiene (ASTMH) annual meeting, even a small number of infected children can transmit malaria parasites to a crowd of mosquitoes, which can then go to infect more humans.
From 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-diffusers, meaning that they infected far more mosquitoes than others; in experiments where mosquitoes were fed blood samples from infected people, more than 60% of the resulting mosquito infections could be traced to just four asymptomatic children, two of whom were of school age. The other two super speakers 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 lead “normal lives … somehow living with all these parasites,” said lead author. Chiara Andolina, a graduate student and malaria expert at Radboud University Medical Center in the Netherlands. Malaria is well-controlled in the region studied by the team, but if control efforts falter or cease, these children could potentially fuel a resurgence of the disease in the area.
To prevent the rebound of malaria cases, control efforts could specifically target school-age children, senior author Teun Bousema, a malaria epidemiologist in Radboud, told Live Science. For example, regular malaria checks and treatment campaigns in schools could have a “very significant impact” on depleting malaria reservoirs and ultimately bring the countdown to zero, he said.
Identification of super speakers
Asymptomatic malaria infections make up 80 percent or more of cases detected through comprehensive screening in areas where the disease circulates regularly, Bousema said. Education to suggest that these asymptomatic infections occur more often in school-age children.
While scientists agree that mosquitoes contract malaria from both symptomatic and asymptomatic people, there is a question as to whether one type of infection is more or less contagious than the other. In search of the answer, the study authors traveled to the Tororo district of Uganda.
Malaria was once incredibly common in Tororo; As recently as 2011, each resident was bitten about 310 times a year by malaria-infected mosquitoes, Andolina said in her ASTMH presentation. Now, after years of intensive malaria control, infection rates have plummeted. In 2018, exposure to infectious mosquitoes dropped to just 0.43 bites per person per year.
“It’s sort of a model for what you can expect: If you really invest a lot in malaria control, you can reduce the malaria burden,” Bousema said. But to completely eliminate malaria, scientists must find and eliminate all the parasite’s remaining hiding places, he added.
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To do this in Tororo, the team recruited 531 adults and children from 80 families and monitored them for malaria for two years. Each month they conducted diagnostic tests and collected blood samples from participants; the blood was screened for malaria parasites and then used in mosquito feeding experiments.
To pass from humans to mosquitoes, malaria parasites must first mature into “gametocytes”; once ingested by blood-sucking insects, gametocytes divide into sex cells, fertilize and multiply. With that in mind, the team also analyzed the gametocyte density in human blood samples, as the number can suggest how contagious that blood might be to mosquitoes.
Over the course of the study, the team found 148 episodes of malaria – 38 symptomatic and 110 asymptomatic. They conducted nearly 540 experiments of feeding mosquitoes with the blood of 107 infected people, using an apparatus that keeps blood warm with circulating water. In each experiment, dozens of mosquitoes were released into a container with the apparatus, where they could access blood through a membrane that mimicked human skin.
The team subsequently dissected the fed mosquitoes to see how many were infected, and the vast majority of infections were linked to the blood of asymptomatic people.
In all, the blood of symptomatic people infected only 0.6% of the total number of infected mosquitoes.
Targeting of hidden tanks
This trend is likely due, in part, to symptomatic people having easy access to malaria treatment, the authors said.
“In our study, children and adults if they got sick … they often went to the clinic before developing these transmissible gametocytes,” Bousema said. Gametocytes take 9 to 12 days to reach maturity, during which time most symptomatic people had already received treatment. “It actually shows that if your access to care is very good, you can prevent symptomatic people from passing on.”
The challenge then becomes to identify infected people without symptoms, so that their chains of transmission can be broken as well, he said. Notably, some asymptomatic people in the study remained contagious for months, although their gametocyte levels fluctuated over time. For example, two infants remained contagious for six months without ever developing symptoms of malaria.
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“Asymptomatic infections are really dominant in children … and schoolchildren somehow have longer-lasting infections, higher gametocyte densities, and so they were really the major source of mosquito infection,” Bousema said.
Overall, the researchers estimated that children ages 5 to 15 account for nearly 57 percent of the infectious reservoir, meaning they carry most of the parasites that could infect mosquitoes with malaria. After school-age children, children under the age of 5 account for 27.5% of the reservoir, while those aged 16 and above account for the remaining 15.7%.
Malaria control measures, such as insecticide-treated nets to cover people’s beds, are often a priority for children under 5 and pregnant women, but school-age children may be overlooked, the authors noted. Beyond the networks, test-and-treat campaigns in schools could help eliminate new cases of malaria before they are transmitted to local mosquitoes, they said, and preventive drugs, many of which can also be used to treat malaria, could help children avoid catching the parasites in the first place.
Originally published on LiveScience.
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