Epidemiology of subpatent Plasmodium falciparum infection: implications for detection of hotspots with imperfect diagnostics

Abstract

BackgroundAt the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density.MethodsDried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA).ResultsPolymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated.ConclusionThe negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings.

Malaria Parasites in the Asymptomatic: Looking for the Hay in the Haystack

“…This is in line with studies showing a reduction in parasite densities with increasing transmission intensity at village level [89] or with increasing proximity to vector breeding sites [90]. Similarly, the performance of rapid tests has been shown to decline with increasing transmission intensity [89], suggesting that people living in high-transmission areas may acquire immunity and control infections to densities below the detection threshold of standard diagnostic techniques. However, the relationship between transmission and parasite density seen on smaller scales is not observed over larger geographical areas, where lower endemicity has been related to a larger proportion of submicroscopic infections [73].…”

“…At a microscale, several studies also show a higher prevalence of asymptomatic carriers in villages of high compared with low malaria incidence [88]. This is in line with studies showing a reduction in parasite densities with increasing transmission intensity at village level [89] or with increasing proximity to vector breeding sites [90]. Similarly, the performance of rapid tests has been shown to decline with increasing transmission intensity [89], suggesting that people living in high-transmission areas may acquire immunity and control infections to densities below the detection threshold of standard diagnostic techniques.…”

Pfmdr1 gene polymorphism of Plasmodium falciparum isolates from asymptomatic individuals of Dienga, southeastern Gabon

“…Moreover, in a study performed in Uganda, it has been documented that genotype 86Y was more important in asymptomatic carriers compared to febrile ones [36]. It has been previously documented that Pfmdr1 86Y and 1246Y mutations decrease chloroquine and amodiaquine sensitivity, but they increase lumefantrine, mefloquine and dihydroartemisin sensitivity according to Pickard [13,40,36,41].…”

High Levels of Asymptomatic and Subpatent Plasmodium falciparum Parasite Carriage at Health Facilities in an Area of Heterogeneous Malaria Transmission Intensity in the Kenyan Highlands

“…These findings align with the current theory that, in areas with stable transmission, older individuals will have sufficient immunity to tolerate infections and maintain parasite densities below the limit of detection of RDTs. 30,38 Also, reporting taking malaria drugs in the 2 weeks before the survey was associated with having a subpatent malaria infection. The increased odds of being subpatent in those reporting that they took antimalarial drugs may be associated with residual parasitemia shortly after treatment or the detection of DNA from persisting gametocytes.…”