Avian Plasmodium
 infection in field-collected mosquitoes during 2012-2013 in Tarlac, Philippines

Abstract Background Malaria elimination requires targeting asymptomatic and low-density Plasmodium infections that largely remain undetected. Therefore we conducted a cross-sectional study to estimate the burden of asymptomatic and low-density Plasmodium infection using conventional and molecular diagnostics. Methods A total of 9118 participants, irrespective of age and sex, were screened for malaria using rapid diagnostic tests (RDTs), microscopy and polymerase chain reaction. Results Among the participants, 707 presented with symptoms and 8411 without symptoms, of which Plasmodium was present in 15.6% (110/707) and 8.1% (681/8411), respectively. Low-density infection was found in 5.1% (145/2818) of participants and 8327 of 9118 were Plasmodium negative. Endemicity was propotional to asymptomatic infections (high endemicity 11.1% [404/3633] vs low endemicity 5.8% [277/4778]; odds ratio [OR] 2.0 [95% confidence interval {CI} 1.7 to 2.4]) but inversely related to low-density infection (high endemicity 3.7% [57/1545] vs low endemicity 6.9% [88/1273]; OR 1.9 [95% CI 1.4 to 2.7]). The spleen rate in children 2–9 y of age was 17.9% (602/3368) and the enlarged spleen index was 1.6. Children between 8 and 14 y showed higher odds for asymptomatic (adjusted OR [aOR] 1.75 [95% CI 1.4 to 2.2]) and low-density infections (aOR 0.63 [95% CI 0.4 to 1.0)] than adults. Conclusions The prevalence of asymptomatic and low-density Plasmodium infection undermines the usefulness of standard diagnostic tools used by health agencies. This necessitates deploying molecular tools in areas where malaria microscopy/RDTs indicate a dearth of infection.

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The fibrinolytic system enables the onset of Plasmodium infection in the mosquito vector and the mammalian host

Science Advances ◽

10.1126/sciadv.abe3362 ◽

2021 ◽

Vol 7 (6) ◽

pp. eabe3362 ◽

Cited By ~ 1

Author(s):

Thiago Luiz Alves e Silva ◽

Andrea Radtke ◽

Amanda Balaban ◽

Tales Vicari Pascini ◽

Zarna Rajeshkumar Pala ◽

...

Keyword(s):

Plasminogen Activators ◽

Fibrinolytic System ◽

Matrix Proteins ◽

Parasite Development ◽

Mammalian Host ◽

Mosquito Vector ◽

Plasminogen Activation ◽

Plasmodium Infection ◽

Human Plasminogen ◽

Vertebrate Hosts

Plasmodium parasites must migrate across proteinaceous matrices to infect the mosquito and vertebrate hosts. Plasmin, a mammalian serine protease, degrades extracellular matrix proteins allowing cell migration through tissues. We report that Plasmodium gametes recruit human plasminogen to their surface where it is processed into plasmin by corecruited plasminogen activators. Inhibition of plasminogen activation arrests parasite development early during sexual reproduction, before ookinete formation. We show that increased fibrinogen and fibrin in the blood bolus, which are natural substrates of plasmin, inversely correlate with parasite infectivity of the mosquito. Furthermore, we show that sporozoites, the parasite form transmitted by the mosquito to humans, also bind plasminogen and plasminogen activators on their surface, where plasminogen is activated into plasmin. Surface-bound plasmin promotes sporozoite transmission by facilitating parasite migration across the extracellular matrices of the dermis and of the liver. The fibrinolytic system is a potential target to hamper Plasmodium transmission.

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