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Ultrasensitive diagnostic test for asymptomatic malaria outperforms other rapid tests

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December 4, 2018

A recently developed ultrasensitive rapid diagnostic test outperformed regular rapid diagnostic tests in identifying asymptomatic malaria infections, but was still inferior to loop-mediated isothermal amplification, or LAMP, according to study findings.

Writing in Clinical Infectious Diseases, researchers said there is a growing need for accurate tests to identify asymptomatic malaria infections, which may aid in the elimination of the disease.

“The primary objective of the study was to determine the sensitivity and specificity of different diagnostic tests for malaria, including [rapid diagnostic tests (RDTs)], [ultrasensitive RDTs (uRDTs)], LAMP, microscopy and quantitative real-time PCR (qRT-PCR),” Dylan R. Pillai, MD, PhD, a clinician-scientist at the University of Calgary, and colleagues wrote. “The secondary objectives were to determine epidemiological characteristics for malaria and whether asymptomatic individuals harboring malaria were anemic compared to uninfected persons using highly accurate ultrasensitive diagnostics.”

In a cross-sectional study, Pillai and colleagues assessed 562 asymptomatic individuals in the Gambella region of southwest Ethiopia to establish epidemiological characteristics associated with asymptomatic malaria. Participants were tested for malaria by LAMP, ultrasensitive qRT-PCR and three RDTs, including the uRDT Alere Malaria Ag P.f (Abbott), CareStart (Accessbio) and SD Bioline Malaria Ag P.f (Abbott).

According to the findings, compared with qRT-PCR, LAMP had the highest sensitivity (92.6%; 95% CI, 86.4-96.5). The uRDT Alere test was next (33.9%; 95% CI, 25.5-43.1), followed by CareStart (14%; 95% CI, 8.4-21.5); microscopy (7.3%; 95% CI, 2.7-15.3) and SD Bioline (5%; 95% CI, 1.8-10.5).

Additionally, Pillai and colleagues compared the sensitivity of the tests for detecting Plasmodium falciparum specimens only and found the sensitivity for uRDT Alere was 50% (95% CI, 38.8-61.3), whereas SD Bioline was 7.3% (95% CI, 2.7-15.3).

According to the study, every 3.2% increase in the prevalence of asymptomatic malaria caused a decrease in hemoglobin by 1 g/dL when based on a multivariate regression analysis and compared with the gold standard, qRT-PCR. Furthermore, 4.8% deletions were observed in HRP2.

“These data show that uRDT is superior to traditional RDT in detecting asymptomatic individuals, but uRDT is still inferior to molecular techniques, with LAMP having the highest sensitivity to detect malaria compared to qRT-PCR,” Pillai and colleagues wrote. “Further studies are required to identify the optimal diagnostic test for interrupting malaria transmission in elimination studies. Longitudinal studies are also required to investigate the potential clinical benefits of treating asymptomatic malaria.” – by Marley Ghizzone

Disclosures : The authors report no relevant financial disclosures.

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The reported prevalence of malaria infections in a population is highly dependent upon the parasitemias most common in the population and the limit of detection of the diagnostic test used for the survey, as demonstrated in the present study. With the advent of ultrasensitive nucleic acid-based tests for the malaria parasite, it has become clear that parasitemias in active P. falciparum infections range as low as one to a few parasites per milliliter of blood, which remains far below the limit of detection of diagnostic tests in clinical use. Most individuals having infections with parasitemias below 100,000 parasites/ML are asymptomatic, and it is common to find in an endemic area in which more than 20% of all asymptomatic individuals carry parasites, as seen in the Gambella region of southwest Ethiopia. Here 40% of those with such infections were identified using uRDT Alere Malaria, making this a valuable improvement over microscopy and two other commonly used RDTs, which identified only between 5% and 17% of the asymptomatic infections. Unfortunately, a complication in the use of RDTs, such as uRDT Alere Malaria that are based upon detection of the HRP2/3 antigens, is the rise of parasite lineages in which one or both genes encoding these antigens has been deleted from the genome. Where these HRP2- lineages are prevalent, possibly as a result of “test-and-treat” selection against lineages with these antigens, these RDTs are of limited to no value for diagnosis. At this time, only the ultrasensitive tests based upon detecting the parasite’s 18S rRNA have limits of detection allowing determination of nearly all blood stage infections. For malaria elimination schemes to be successful, they must implement methods to eliminate this huge but difficult-to-identify asymptomatic reservoir of infection. Improved access to ultrasensitive tests including uRDT Alere Malaria and those detecting 18S rRNA of the parasite offers the basis for a test-and-treat strategy for elimination, which avoids antimalarial drug administration to large numbers of individuals who do not have malaria infections.

John B. Dame, PhD

Professor, department of infectious diseases and immunology
University of Florida

Disclosure: Dame reports no relevant financial disclosures.