Persistent Plasmodium falciparum and Plasmodium vivax infections in a western Cambodian population: implications for prevention, treatment and elimination strategies

Rupam Tripura, Thomas J Peto, Jeremy Chalk, Sue J Lee, Pasathorn Sirithiranont, Chea Nguon, Mehul Dhorda, Lorenz von Seidlein, Richard J Maude, Nicholas P J Day, Mallika Imwong, Nicholas J White, Arjen M Dondorp, Rupam Tripura, Thomas J Peto, Jeremy Chalk, Sue J Lee, Pasathorn Sirithiranont, Chea Nguon, Mehul Dhorda, Lorenz von Seidlein, Richard J Maude, Nicholas P J Day, Mallika Imwong, Nicholas J White, Arjen M Dondorp

Abstract

Background: Subclinical Plasmodium parasitaemia is an important reservoir for the transmission and persistence of malaria, particularly in low transmission areas.

Methods: Using ultrasensitive quantitative PCR (uPCR) for the detection of parasitaemia, the entire population of three Cambodian villages in Pailin province were followed for 1 year at three-monthly intervals. A cohort of adult participants found initially to have asymptomatic malaria parasitaemia was followed monthly over the same period.

Results: The initial cross sectional survey in June 2013 (M0) of 1447 asymptomatic residents found that 32 (2.2%) had Plasmodium falciparum, 48 (3.3%) had P. vivax, 4 (0.3%) had mixed infections and in 142/1447 (9.8%) malaria was detected but there was insufficient DNA to identify the species (Plasmodium. species). Polymorphisms in the 'K13-propeller' associated with reduced susceptibility to artemisinin derivatives (C580Y) were found in 17/32 (51%) P. falciparum strains. Monthly follow-up without treatment of 24 adult participants with asymptomatic mono or mixed P. falciparum infections found that 3/24 (13%) remained parasitaemic for 2-4 months, whereas the remaining 21/24 (87%) participants had cleared their parasitaemia after 1 month. In contrast, 12/34 (35%) adult participants with P. vivax mono-infection at M0 had malaria parasites (P. vivax or P. sp.) during four or more of the following 11 monthly surveys.

Conclusions: This longitudinal survey in a low transmission setting shows limited duration of P. falciparum carriage, but prolonged carriage of P. vivax infections. Radical treatment of P. vivax infections by 8-aminoquinoline regimens may be required to eliminate all malaria from Cambodia. Trial registration ClinicalTrials.gov NCT01872702.

Keywords: Artemisinins; Cambodia; Clearance; Cohort; Falciparum; Malaria; PCR; Pailin; Persistence; Plasmodium; Resistance; Vivax.

Figures

Fig. 1
Fig. 1
Parasite prevalence at 3-monthly surveys of the entire village
Fig. 2
Fig. 2
a, b, and c represent the prevalence of Plasmodium falciparum or mixed infections (a), Plasmodium vivax or mixed infections (b), and all species, including Plasmodium species which could not be determined (c). The figures represent a composite of uPCR data from cross-sectional surveys, clinical data collected by village malaria workers, and meteorological data collected by the Department of Meteorology, Ministry of Water Resources and Meteorology, Cambodia. The percentage of specimens found to be positive by uPCR is indicate by diamonds. The ambient min/max temperature range is indicated by dots. The daily rainfall in mm is shown as a blue line. uPCR data were collected during the study period June 2013 and June 2014 indicated by the red arrow. The clinical and meteorological data were collected between January 2013 and December 2014. Information on malaria episodes were collected by village malaria (VMW), mobile malaria workers (MMW) and primary health centres for 2013–14
Fig. 3
Fig. 3
The persistence and transitions of Plasmodium falciparum infections in an adult cohort (ordered by number of episodes)
Fig. 4
Fig. 4
The persistence and transitions of Plasmodium vivax infections in an adult cohort (ordered by number of episodes)
Fig. 5
Fig. 5
Log parasite densities (log parasites/mL) in three participants with persistent Plasmodium vivax infections

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