In Malawi I work simultaneously on two clinical trials. Clinical trials are studies in humans of interventions (a new medicine, a new surgical procedure, a new device such as a pacemaker) given to see if the new therapy is safe and will lead to better outcomes, things like lower death rates or less pain. Both the clinical trials I work on enroll children with cerebral malaria. Cerebral malaria is when someone infected with the malaria parasite falls into coma. It has the highest mortality rate of any malaria syndrome, 100% if untreated. Even with the best care available, one in six children dies. It is a major killer of African children less than 5 years old. Tens of thousands of children die from it every year.
Because it is such a major killer, many clinical trials have already been performed in pediatric cerebral malaria. Most test “adjunctive” therapies, medications given in addition to standard of care treatments such as intravenous antimalarials. Every one of these completed clinical trials failed to decrease death from this disease. A few made things worse. As researchers learn more about the cerebral malaria, though, new ideas for adjunctive therapies pop up. Both clinical trials I work on are testing new adjunctive therapies for pediatric cerebral malaria.
As in all medical research, money to perform clinical trials is extremely difficult to obtain. Usually, it takes several years to be awarded funding. Rejection follows rejection until finally someone says “Yes”. In the research world it is an adage that by the time one is finally able to begin a clinical trial, the disease under study disappears. Disease incidence falls off a cliff once you finally get the money to study it.
Many clinical trials have already been performed in pediatric cerebral malaria. Most test “adjunctive” therapies, medications given in addition to standard of care treatments such as intravenous antimalarials. Every one of these completed clinical trials failed to decrease death from this disease. A few made things worse…
Throughout Africa, beginning about 10 years ago malaria cases began to decrease. This went well for a few years with steady declines, but 5 years ago things levelled out. There are not as many cerebral malaria cases now as there were 20 years ago, but there were still too many. But in the last year, something drastic happened. In 2022, cerebral malaria in Malawi has nearly ceased to exist. Yes, a few cases trickle in 7 to 10 days after we have a big rain (rain means mosquitoes means malaria) but the number of cases this year has declined precipitously. Everyone has a personal theory but no one knows why.
On Friday I met a Malawian physician friend. She asked me how things were going with clinical trial recruitment. I explained what was happening. Her immediate reaction was “Great! The children aren’t dying like usual.” This is what I thought at first, too. But this reaction is only appropriate if malaria cases never come back. That, unfortunately, is very unlikely.
Malaria is not going away. The World Health Organization gave up on eliminating malaria from Africa many years ago. With infectious diseases that are transmitted by a vector (the mosquito), elimination is almost impossible. Though fewer children this year with cerebral malaria is great, this likely temporary lull harms future children who will get this disease. Why? Clinical trials run for a fixed period of time. Our studies will go through the next five years. If not enough children have the disease in the next years, we will never know if our new therapies work. If malaria comes roaring back (as it always has in the past), we will be forced to use the same treatments as we use now.
Obviously, if the current decrease in cases is permanent, that would be terrific. If the malaria parasites in Africa become resistant to our current antimalarial medications (as they already have done in Asia), all bets are off. Should that happen, I hope we have better options to offer the children of Africa than a one in six chance of dying.
