Tag Archives: malaria vaccine

The Global Experiment with Malaria Vaccine Starts in African States

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Thirty years in the making, RTS,S, the malaria vaccine, also known by its brand name, Mosquirix, targets Plasmodium falciparum, the most common and most lethal of four malaria parasite species. It is an answer to a dire need. After decades of declining numbers of cases and deaths, the fight against malaria has stalled. Parasites resistant to the most widely used treatment, called artemisinin-based combination therapy, are spreading, while malaria mosquitoes are increasingly resistant to insecticides. And yet the rollout in Malawi and in two other African countries, isn’t quite the breakthrough the field has been waiting for. Mosquirix’s efficacy and durability are mediocre: Four doses offer only 30% protection against severe malaria, for no more than 4 years. Some experts question whether that is worth the cost and effort. 

The biggest concerns, however, are about the vaccine’s safety. In the largest trial, children who received Mosquirix had a risk of meningitis 10 times higher than those who received a control vaccine. Mosquirix may not have triggered the meningitis cases—there are other possible explanations—but the possible risk worried the global health community so much that, rather than rolling out the vaccine across Africa, the World Health Organization (WHO) has decided to set up a pilot in Malawi, Ghana, and Kenya in which the vaccine will be given to hundreds of thousands of children.

The Malaria parasite  is a challenging target for a vaccine. It has a complex life cycle that begins when an infected female mosquito bites a human and spits Plasmodium cells called sporozoites into the bloodstream. They multiply in the liver, emerge as another cell type named merozoites, invade red blood cells, and continue to multiply. The blood cells burst, causing fever, headache, chills, muscle aches, and often anemia. (They also flood the blood with gametocytes—the parasite’s reproductive cells—ready to be picked up by the next mosquito.) Along the way, the parasite frequently changes its surface proteins. That makes it an elusive target for the immune system, and for a vaccine.

Mosquirix, developed in the 1980s by a team in Belgium at SmithKline-RIT, now part of GlaxoSmithKline (GSK), stimulates an immune response against a protein that occurs only on the sporozoites’ surface. To bolster the response, the research team fused the vaccine protein with a hepatitis B surface protein and added an adjuvant….

A relative outside, Danish anthropologist and vaccine researcher Peter Aaby of the Bandim Health Project in Guinea-Bissau, offered another argument against introduction. After reanalyzing the data from the biggest trial, Aaby discovered that although the vaccinated children had malaria less often, they did not die less often. Among girls, overall mortality was almost doubled, Aaby told his colleagues at the meeting. “This vaccine is killing girls,” he recalls saying. Whereas WHO expects the vaccine to save one life per 200 children vaccinated, Aaby believes one in 200 will die as a result of it; he predicts “a nightmare.”

Aaby and Christine Stabell Benn, a global health professor at the University of Southern Denmark, have an explanation. The married couple has studied routine vaccinations in Africa for decades and believes vaccines can “train” the immune system in ways that don’t affect just the target disease. Vaccines that contain a living, weakened pathogen—such as the vaccines against measles and tuberculosis—strengthen the immune system generally, Aaby and Stabell Benn say, making recipients better able to fight off other infections. But vaccines that contain a killed pathogen or only bits of it weaken the immune system, their theory goes—especially in girls, because their immune systems seem to respond more strongly to vaccines in general.

Excerpts from Jop de Vrieze, A Shot of Hope, Science Magazine, Nov. 29, 2019, at 1063

Imperfect Tools Used Imperfectly: 400 000 Malaria Deaths

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According to a report, published on December 4th, 2019 by the World Health Organization,  there were 228 million cases of malaria in 2018, which resulted in 400,000 deaths. Most victims were young children in Africa. That is a far cry from targets set in 2015 for the near-elimination of malaria by 2030.  These targets depended on a $6 billion a year being poured into malaria-control efforts. Funding in recent years, however, has been about $3 billion a year. More money would surely help. But substantial gains can be made by doing things more efficiently—something at which malaria programmes have been dismal.

Stopping malaria relies on three things: insecticide-treated bed nets to prevent nocturnal mosquito bites; the spraying of homes with insecticides; and the treating of pregnant women and children with rounds of preventive medication. These are all “imperfect tools, often used imperfectly”, says Pedro Alonso, head of the malaria programme at the World Health Organisation. Countries usually deploy the same package of measures everywhere, even though infection rates and their seasonal patterns vary a lot between regions, and particularly between cities and the countryside. Transmission reaches a peak in the rainy season, when mosquitoes are abundant, so preventive mass-treatment of children then can make a huge difference. Regional variations are particularly pronounced in large countries like Nigeria—a place that, by itself, accounts for a quarter of the world’s malaria cases.

The typical approach of a malaria-control programme is to bombard a country with bed nets and then use whatever cash remains for sporadic rounds of preventive medication. But in many big cities, such as Dar es Salaam and Nairobi, cases are few and far between, so deploying nets there is a waste. Overspending on nets at the expense of other things happens partly because nets are easy to count—a feature that aid programmes are particularly fond of. Results which cannot be attributed directly to money a donor spends tend to fall further down that donor’s list of priorities. This kind of reasoning tips the scales, because foreign aid accounts for two-thirds of the money spent on malaria.

Excerpts from Tropical disease: Malaria infections have stopped falling, Economist, Dec. 7, 2019

How Venom from Spiders Kills Malaria Mosquitoes

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In the 1980s, the village of Soumousso in Burkina Faso helped launch one of the most powerful weapons against malaria: insecticide-treated bed nets, which had early field trials there and went on to save millions of lives. But as mosquitoes developed resistance to widely used insecticides, the nets lost some of their power. Now, researchers are hoping the village can help make history again by testing a new countermeasure: a genetically modified (GM) fungus that kills malaria-carrying mosquitoes. In tests in a 600-square-meter structure in Soumousso called the MosquitoSphere—built like greenhouse but with mosquito netting instead of glass—the fungus eliminated 99% of the mosquitoes within a month, scientists report in the  magazine Science.

MosquitoSphere, Burkina Faso

The fungus also has clear advantages, however: It spares insects other than mosquitoes, and because it doesn’t survive long in sunlight, it’s unlikely to spread outside the building interiors where it would be applied.  Fungi naturally infect a variety of insects, consuming the host’s tissues in order to reproduce, and they have been used for decades to control a wide variety of crop pests….Researchers have tested dozens of different fungal strains against disease-carrying mosquitoes, but none was effective enough to pass muster. So researchers from the University of Maryland (UMD) in College Park and the Research Institute of Health Sciences & Centre Muraz in Bobo-Dioulasso, Burkina Faso, endowed a strain called M. pingshaense with a gene for a toxin isolated from spider venom that turns on when it contacts hemolymph, the insect version of blood. In the lab, the team showed its creation could kill mosquitoes faster and that just one or two spores could cause a lethal infection. 

Burkina Faso was a promising place for a field test: Unlike many countries in Africa, it has an established system to evaluate and approve the use of GM organisms. It also has one of the highest rates of malaria in the world, and insecticide-resistant mosquitoes are widespread. For those and other reasons, the U.S. National Institutes of Health funded the MosquitoSphere, which is specifically designed to test GM organisms.

Excerpts fromGretchen Vogel  Fungus with a venom gene could be new mosquito killer, Science, May 31, 2019