Submicroscopic carriage of Plasmodium falciparum and Plasmodium vivax in a low endemic area in Ethiopia where no parasitaemia was detected by microscopy or rapid diagnostic test

Abstract

BackgroundMotivated by the success in malaria control that was documented over the last decade Ethiopia is aiming at malaria elimination by 2020 in selected districts. It is currently unknown if asymptomatic, submicroscopic malaria parasite carriage may form a hurdle to achieve elimination. The elimination effort may further be complicated by possible glucose-6 phosphate dehydrogenase (G6PD) deficiency which would hinder the use of 8-aminoquinolines in the elimination efforts.MethodIn February 2014 a community-based cross-sectional survey was conducted in Malo, southwest Ethiopia. Finger-prick blood samples (n = 555) were tested for presence of Plasmodium falciparum and Plasmodium vivax with microscopy, rapid diagnostic test (RDT), and nested polymerase chain reaction (nPCR). Multiplicity of P. falciparum infections was determined based on genotyping the polymorphic merozoite surface protein-2 (MSP-2) gene. Individuals were also genotyped for mutations in the gene that produces G6PD.ResultsAll study participants were malaria infection negative by microscopy and RDT. Nested PCR revealed P. falciparum mono-infection in 5.2% (29/555), P. vivax mono-infection in 4.3% (24/555) and mixed infection in 0.2% (1/555) of individuals. All parasitemic individuals were afebrile (axillary temperature <37.5°C). None of the study participants carried mutations for the G6PD African A-(202GA) and Mediterranean (563CT) variants. All infections, except one, were single-clone infection by MSP-2 genotyping.ConclusionThe detection of a substantial number of subpatent malaria infections in an apparently asymptomatic population without evidence for malaria transmission by conventional diagnostics raises questions about the path to malaria elimination. It is currently unknown how important these infections are for sustaining malaria transmission in the study sites. The absence of G6PD deficiency indicates that 8-aminoquinolines may be safely deployed to accelerate elimination initiatives.

Assessment of subpatent Plasmodium infection in northwestern Ethiopia

“…Studies in Iran [37] and Sri Lanka [38] reported zero prevalence by the more sensitive methods, indicative of no local transmission and confirmation of malaria elimination. Golassa et al [14] and Tadesse et al [15] reported PCR prevalence ranging from 1.7 to 5.8% in southwest Ethiopia, comparable to the 3.3% prevalence reported in the current study.…”

“…A relatively high prevalence of subpatent or low parasite density infections, that are often missed by conventional diagnostic methods (microscopy and rapid diagnostic tests) are being reported especially from low transmission settings [7][8][9][10][11][12][13][14]. Such asymptomatic, subpatent infections could be explained by acquired immunity in higher transmission settings [15]. Even in low transmission settings, asymptomatic and subpatent infections might play a role in transmission dynamics, hindering the progress of malaria elimination [14][15][16][17][18][19].…”

“…Such asymptomatic, subpatent infections could be explained by acquired immunity in higher transmission settings [15]. Even in low transmission settings, asymptomatic and subpatent infections might play a role in transmission dynamics, hindering the progress of malaria elimination [14][15][16][17][18][19].…”

Epidemiology of Plasmodium vivax in Indonesia

“…In their sample of 1,509 people, 52 (3.4%) were diagnosed as having malaria by microscopic examination, whereas 399 (26%) were positive by PCR. These data, and others like it, consistently demonstrate that microscopically subpatent parasitemia is the rule in Indonesia, as elsewhere (Solomon Islands, the Mekong Region, Horn of Africa, and Amazonia) 16. The long-held presumption that natural immunity to malaria required sustained and intense transmission needs reconsideration.…”

The challenge of maintaining microscopist capacity at basic levels for malaria elimination in Jiangsu Province, China

“…In this province, the regular refresher training courses are organized by both provincial and prefecture level every year to maintain the microscopical test skills from the majority of the counties' level, and there are two mutual-checking microscopists meetings every year, in which the microscopists from all the 13 prefectures bring their positive and negative slides and checked by each other, in addition, the quality control system for the whole provincial microscopical test has been established, provincial reference lab for malaria diagnosis collect the slides quarterly and reviewed the reading accuracy and feedback the result to the administrative department. The number of rapid diagnostic tests (RDTs) that are available and the scale of their use for malaria detection has increased rapidly over the past few years; however, RDTs have a relatively poor detection rate for asymptomatic malaria cases with low parasite densities [10][11][12]. In addition, limited RDT products for malaria have been registered with the State Food and Drug Administration (SFDA) in China; therefore, microscopic examination is still the first choice for malaria diagnosis in most parts of China.…”