Abstract
SummaryBackgroundA substantial proportion of Plasmodium species infections are asymptomatic with densities too low to be detectable with standard diagnostic techniques. The importance of such asymptomatic plasmodium infections in malaria transmission is probably related to their duration and density. To explore the duration of asymptomatic plasmodium infections and changes in parasite densities over time, a cohort of participants who were infected with Plasmodium parasites was observed over a 2-year follow-up period.MethodsIn this open cohort study, inhabitants of four villages in Vietnam were invited to participate in baseline and subsequent 3-monthly surveys up to 24 months, which included the collection of venous blood samples. Samples were batch-screened using ultra-sensitive (u)PCR (lower limit of detection of 22 parasites per mL). Participants found to be infected by uPCR during any of these surveys were invited to join a prospective cohort and provide monthly blood samples. We estimated the persistence of Plasmodium falciparum and Plasmodium vivax infections and changes in parasite densities over a study period of 24 months.FindingsBetween Dec 1, 2013, and Jan 8, 2016, 356 villagers participated in between one and 22 surveys. These study participants underwent 4248 uPCR evaluations (11·9 tests per participant). 1874 (32%) of 4248 uPCR tests indicated a plasmodium infection; 679 (36%) of 1874 tests were P falciparum monoinfections, 507 (27%) were P vivax monoinfections, 463 (25%) were co-infections with P falciparum and P vivax, and 225 (12%) were indeterminate species of Plasmodium. The median duration of P falciparum infection was 2 months (IQR 1–3); after accounting for censoring, participants had a 20% chance of having parasitaemia for 4 months or longer. The median duration of P vivax infection was 6 months (3–9), and participants had a 59% chance of having parasitaemia for 4 months or longer. The parasite densities of persistent infections oscillated; following ultralow-density infections, high-density infections developed frequently.InterpretationPersistent largely asymptomatic P vivax and P falciparum infections are common in this area of low seasonal malaria transmission. Infections with low-density parasitaemias can develop into much higher density infections at a later time, which are likely to sustain malaria endemicity.FundingThe Wellcome Trust, Bill & Melinda Gates Foundation.
Highlights
Estimating the submicroscopic plasmodium reservoir has become more accurate with the development of a high blood volume (1 mL), ultrasensitive, quantitative PCR method with a diagnostic sensitivity as low as 22 parasites per mL, allowing the detection of more than 85% of all Plasmodium vivax parasitaemias and more than 70% of all Plasmodium falciparum parasitaemias.[4]
Most low-density plasmodium infections detected by uPCR have low gametocyte densities, which could be insufficient to transmit the infection to mosquito vectors at that time because the mosquito has to ingest at least one male and one female gametocyte in a blood meal to propagate the infection.[6]
Our study reports on a cohort of asymptomatic participants infected with P falciparum, Plasmodium vivax, or both, who were followed up for 24 months and documents the frequent persistence of infections over extended periods
Summary
Persistent, asymptomatic plasmodium infections carry health risks for the infected individual including chronic anaemia, increased risks of maternal and neonatal mortality, impaired immune competence resulting in co-infections with invasive bacterial diseases, and cognitive impairment.[5] At the public health level, asymptomatic, submicroscopic infections provide a parasite reservoir for malaria transmission. In areas with low and seasonal transmission, persistent asymptomatic parasite carriage bridges the dry season, during which mosquito numbers are very low and malaria transmission is almost absent, sustaining endemicity. Most low-density plasmodium infections detected by uPCR have low gametocyte densities, which could be insufficient to transmit the infection to mosquito vectors at that time because the mosquito has to ingest at least one male and one female gametocyte in a blood meal to propagate the infection.[6] This observation has led some researchers to question the public health importance
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