Earlier research showed Africans who had one or the other inherited trait were protected from malaria.
Those with sickle cell trait inherit a sickle-shaped hemoglobin gene from one parent as opposed to sickle cell anemia, in which they inherit abnormal hemoglobin genes from both parents.
"We've looked at these traits individually and we expected that if people had both of them, they would be really protected" against malaria, said Tom Williams of the Kenya Medical Research Institute.
"But it turns out that when you start combining the two, you can lose the effect of both," he said.
Williams said the 2,000-child study will help scientists learn more about the complex biological mechanisms at work in naturally acquired immunity.
He presented his findings at the Multilateral Initiative on Malaria Pan-African Malaria Conference in Yaounde, Cameroon.