Dataset Information

Association between Subclinical Malaria Infection and Inflammatory Host Response in a Pre-Elimination Setting.

ABSTRACT: Subclinical infections in endemic areas of Southeast Asia sustain malaria transmission. These asymptomatic infections might sustain immunity against clinical malaria and have been considered benign for the host, but if they are associated with chronic low-grade inflammation this could be harmful. We conducted a case-control study to explore the association between subclinical malaria and C-reactive protein (CRP), an established biomarker of inflammation.Blood samples from asymptomatic villagers in Pailin, Western Cambodia were tested for malaria by high-volume ultra-sensitive polymerase chain reaction (uPCR) to determine the Plasmodium species. Plasma CRP concentration was measured in 328 individuals with parasitaemia (cases) and compared with: i) the same individual's value at the first time point when they had no detectable parasites (n = 282); and ii) age- sex- and village-matched controls (n = 328) free of Plasmodium infection. Plasma CRP concentrations were compared against thresholds of 3mg/L and 10mg/L. Subgroup analysis was carried out for cases with P vivax and P falciparum mono-infections.Median plasma CRP level for all samples was 0.59mg/L (interquartile range: 0.24-1.64mg/L). CRP concentrations were higher in parasitaemic individuals compared with same-person-controls (p = 0.050); and matched-controls (p = 0.025). 4.9% of samples had CRP concentrations above 10mg/L and 14.6% were above 3mg/L. Cases were more likely to have plasma CRP concentrations above these thresholds than age/sex matched controls, odds ratio 3.5 (95%CI 1.5-9.8) and 1.8 (95%CI 1.1-2.9), respectively. Amongst cases, parasite density and CRP were positively correlated (p<0.001), an association that remained significant when controlling for age and fever. Individuals with P.vivax mono-infections had the highest plasma CRP concentrations with the greatest association with parasitaemia.In this setting persistent malaria infections in asymptomatic individuals were associated with moderately elevated plasma CRP concentrations; chiefly evident in cases with P.vivax mono-infections. As well as interrupting malaria transmission within the community, treatment of asymptomatic malaria infections, in particular radical cure of vivax malaria, may benefit the health of infected individuals.

SUBMITTER: Peto TJ

PROVIDER: S-EPMC4936742 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Association between Subclinical Malaria Infection and Inflammatory Host Response in a Pre-Elimination Setting.

Peto Thomas J TJ Tripura Rupam R Lee Sue J SJ Althaus Thomas T Dunachie Susanna S Nguon Chea C Dhorda Mehul M Promnarate Cholrawee C Chalk Jeremy J Imwong Mallika M von Seidlein Lorenz L Day Nicholas P NP Dondorp Arjen M AM White Nicholas J NJ Lubell Yoel Y

PloS one 20160707 7

<h4>Background</h4>Subclinical infections in endemic areas of Southeast Asia sustain malaria transmission. These asymptomatic infections might sustain immunity against clinical malaria and have been considered benign for the host, but if they are associated with chronic low-grade inflammation this could be harmful. We conducted a case-control study to explore the association between subclinical malaria and C-reactive protein (CRP), an established biomarker of inflammation.<h4>Methods</h4>Blood s ...[more]

PMID: 27386859

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Project description:BackgroundThailand is committed to eliminating malaria by 2024. From 2013 to 2020, the total number of malaria cases have decreased, from 37,741 to 4474 (an 88.1% reduction). However, infections with Plasmodium knowlesi, a monkey malarial pathogen that can also infect humans, have been increasingly observed. This study focused on the molecular analysis of P. knowlesi parasites causing malaria in Thailand.MethodsUnder Thailand's integrated Drug Efficacy Surveillance (iDES), which includes drug-resistance monitoring as part of routine case-based surveillance and responses, specimens were collected from malaria patients (n = 966) between 2018 and 2020. Thirty-one mono P. knowlesi infections (3.1%), most of which were from eastern and southern Thailand, were observed and confirmed by nested PCR assay and DNA sequencing. To evaluate whether these pathogens were from different lineages, cluster analysis based on seven microsatellite genotyping markers and the merozoite surface protein 1 (pkmsp1) gene was carried out. The P. knowlesi pyrimethamine resistance gene dihydrofolate reductase (pkdhfr) was sequenced and homology modelling was constructed.ResultsThe results of analysing the seven microsatellite markers and pkmsp1 sequence demonstrated that P. knowlesi parasites from eastern Thailand were of the same lineage as those isolated in Cambodia, while the parasites causing malaria in southern Thailand were the same lineage as those isolated from Malaysia. The sequencing results for the pkdhfr genes indicated the presence of two mutations, Arg34Leu and a deletion at position 105. On analysis with homology modelling, the two mutations were not associated with anti-malarial drug resistance.ConclusionsThis report compared the genetic populations of P. knowlesi parasites in Thailand from 2018 to 2020 and have shown similar lineages as those isolated in Cambodia and Malaysia of P. knowlesi infection in Thailand and demonstrated that the P. knowlesi parasites were of the same lineages as those isolated in Cambodia and Malaysia. The parasites were also shown to be sensitive to pyrimethamine.

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Project description:Accurate diagnosis of malaria is vital for the effectiveness of parasite clearance interventions in elimination settings. Thus, evaluating the diagnostic performance of rapid diagnostic tests (RDTs) used in malaria parasite clearance interventions in elimination settings is essential. Therefore, this study aimed to evaluate the diagnostic performance of rapid diagnostic tests recently used in detecting malaria parasites in northwest Ethiopia. A facility-based cross-sectional study was conducted from November 2020 to February 2021 comparing PfHRP2/pLDH CareStart malaria RDTs with light microscopy and polymerase chain reaction (PCR). Blood samples were collected from 310 febrile patients who attended the outpatient department and examined using CareStart RDTs, light microscopy, and PCR. Statistical analyses were performed using STATA/SE version 17.0. The sensitivity of PfHRP2/pLDH CareStart malaria RDTs, regardless of species, was 81.0% [95% CI, 75.3, 86.7] and 75.8% [95% CI, 69.6, 82.0] compared to light microscopy and PCR, while the specificity was 96.8% [95% CI, 93.7, 99.9] and 93.2% [95% CI, 88.6, 97.8], respectively. The false-negative rate of CareStart malaria RDTs in comparison with light microscopy and PCR was 19.0% and 24.2%, respectively. The level of agreement beyond chance between tests was substantial, RDT versus microscopy was 75.0% and RDT versus PCR was 65.1%. The diagnostic performance of PfHRP2/pLDH CareStart RDTs in detecting malaria parasites among febrile patients in the study area was below the recommended WHO standard. The limited diagnostic performance of RDTs in the malaria elimination area undoubtedly affects the impact of malaria parasite clearance interventions. Therefore, parasite clearance intervention like targeted mass drug administration with antimalarial drugs is recommended to back up the limited diagnostic performance of the RDT or replace the existing malaria RDTs with more sensitive, field-deployable, and affordable diagnostic tests.

Dataset Information

Association between Subclinical Malaria Infection and Inflammatory Host Response in a Pre-Elimination Setting.

Publications

Association between Subclinical Malaria Infection and Inflammatory Host Response in a Pre-Elimination Setting.

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