A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting

Abstract

BackgroundMany countries are scaling up malaria interventions towards elimination. This transition changes demands on malaria diagnostics from diagnosing ill patients to detecting parasites in all carriers including asymptomatic infections and infections with low parasite densities. Detection methods suitable to local malaria epidemiology must be selected prior to transitioning a malaria control programme to elimination. A baseline malaria survey conducted in Temotu Province, Solomon Islands in late 2008, as the first step in a provincial malaria elimination programme, provided malaria epidemiology data and an opportunity to assess how well different diagnostic methods performed in this setting.MethodsDuring the survey, 9,491 blood samples were collected and examined by microscopy for Plasmodium species and density, with a subset also examined by polymerase chain reaction (PCR) and rapid diagnostic tests (RDTs). The performances of these diagnostic methods were compared.ResultsA total of 256 samples were positive by microscopy, giving a point prevalence of 2.7%. The species distribution was 17.5% Plasmodium falciparum and 82.4% Plasmodium vivax. In this low transmission setting, only 17.8% of the P. falciparum and 2.9% of P. vivax infected subjects were febrile (≥38°C) at the time of the survey. A significant proportion of infections detected by microscopy, 40% and 65.6% for P. falciparum and P. vivax respectively, had parasite density below 100/μL. There was an age correlation for the proportion of parasite density below 100/μL for P. vivax infections, but not for P. falciparum infections. PCR detected substantially more infections than microscopy (point prevalence of 8.71%), indicating a large number of subjects had sub-microscopic parasitemia. The concordance between PCR and microscopy in detecting single species was greater for P. vivax (135/162) compared to P. falciparum (36/118). The malaria RDT detected the 12 microscopy and PCR positive P. falciparum, but failed to detect 12/13 microscopy and PCR positive P. vivax infections.ConclusionAsymptomatic malaria infections and infections with low and sub-microscopic parasite densities are highly prevalent in Temotu province where malaria transmission is low. This presents a challenge for elimination since the large proportion of the parasite reservoir will not be detected by standard active and passive case detection. Therefore effective mass screening and treatment campaigns will most likely need more sensitive assays such as a field deployable molecular based assay.

Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies

“…These included individual-level data on location and timing of collection, RDT and microscopy test results, RDT brand 21 , age, sex, use of an ITN, fever and antimalarial use in the past two weeks. In addition, individual-level data sets from one unpublished and one published study were included 44 , as well as shared data sets of the RDT and PCR comparison that also included microscopy measurements (see below) [45][46][47][48][49] .…”

The silent threat: asymptomatic parasitemia and malaria transmission

“…Using microscopy to diagnose infections, a larger proportion of P. f alciparum infections (37.5%) compared with P. vivax infections (18.5%) in Brazil were asymptomatic (presenting with none of the 13 malarial symptoms) [50]. In comparison, a greater proportion of P. vivax infections (97.1%) in the Solomon Islands compared with P. falciparum infections (82.2%) were asymptomatic (axillary temperature: <38°C) [51]. Few studies have reported both the number of species-specific malaria cases and species-specific symptom rates, and diagnosed all infections by PCR; in Cambodia, 92% of the P. falciparum and 83% of the P. vivax infections were asymptomatic [52], whereas in Brazil, these proportions were 78 and 93%, respectively [53].…”

High Degree of Plasmodium vivax Diversity in the Peruvian Amazon Demonstrated by Tandem Repeat Polymorphism Analysis

“…Yet, in malaria-endemic regions, asymptomatic malaria parasitemia, with degrees of prevalence that are geographically variable, is common. [11][12][13][14][15][16][17][18] This observation has raised two important hypotheses: 1) that asymptomatic parasitemia may contribute significantly to maintaining malaria transmission in endemic regions; and 2) different Plasmodium falciparum or P. vivax clones may differ in virulence, some more likely than others to result in symptoms. Substantial data support the former hypothesis; few data to date support the latter.…”