Low-density asymptomatic parasitemia in southern Zambia does not lead to clinical malaria and is not associated with household transmission: results from a two-year cohort study

Background In low malaria transmission settings targeting elimination, the World Health Organization recommends a combination of mass (e.g., mass test-and-treat), targeted (e.g., chemoprophylaxis or treatment for travelers), and reactive (e.g., reactive drug administration) strategies. Most of these strategies would not identify and treat individuals with asymptomatic parasitemia. This study was conducted in a pre-elimination setting in Southern Province, Zambia to examine risk factors for asymptomatic parasitemia, its epidemiologic relationship to incident clinical malaria, and evidence of its contribution to ongoing transmission to inform policy on whether these parasitemic individuals need to be identified and treated to achieve malaria elimination. Methods An intensive longitudinal cohort study of 197 households within the catchment area of a single health center was designed to capture all clinical malaria cases and episodes of asymptomatic parasitemia between 2018 and 2020. During monthly collections, all household members and overnight visitors were administered a questionnaire and a blood sample was collected to identify Plasmodium falciparum parasitemia by qPCR. Passive surveillance was also established at the local health center to identify cases of clinical malaria. The statistical analysis examined risk factors for parasitemia and associations between asymptomatic parasitemia and subsequent episodes of clinical malaria within individuals and parasitemia in household members. Results Of the 1071 individuals enrolled in the cohort, 144 (13%) were positive by qPCR for P. falciparum at least once during the two-year study period. Monthly parasite prevalence by qPCR never exceeded 4% and parasite density was very low with a median of four parasites/µL. Incidence of self-reported clinical malaria was 46.7 cases per 1000 person-years. Low-density asymptomatic parasitemia was identified in all age groups, including young children. There was no association between asymptomatic parasitemia and clinical malaria within individuals, nor was there an association between asymptomatic parasitemia and subsequent parasitemia in household members beyond one month of the index case. Conclusion Low-level parasitemia was prevalent despite few cases of clinical malaria in this low transmission setting. There was no evidence that low-level asymptomatic parasitemia led to clinical cases of malaria or transmission to other household members.