Performance of highly sensitive and conventional rapid diagnostic tests for clinical and subclinical Plasmodium falciparum infections, and hrp2/3 deletion status in Burundi

Niyukuri, David; Sinzinkayo, Denis; Troth, Emma V.; Oduma, Colins O.; Barengayabo, Mediatrice; Ndereyimana, Mireille; Holzschuh, Aurel; Vera-Arias, Claudia A.; Gebre, Yilekal; Badu, Kingsley; Nyandwi, Joseph; Baza, Dismas; Juma, Elizabeth; Koepfli, Cristian

doi:10.1371/journal.pgph.0000828

Cited by 11 publications

(12 citation statements)

References 39 publications

(47 reference statements)

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“…Nearly two thirds of infections were submicroscopic, and thus might not be detected by mass screen-and-treat campaigns. A novel generation of highly sensitive rapid diagnostic tests detect ultra-low density infections [ 86 , 87 ]. Whether this increased sensitivity is sufficient to reduce transmission if used in mass test and treatment or reactive case detection campaigns remains to be shown.…”

Section: Discussionmentioning

confidence: 99%

Altitude, not potential larval habitat availability, explains pronounced variation in Plasmodium falciparum infection prevalence in the western Kenya highlands

Oduma

Ombok

Zhao

et al. 2023

PLOS Glob Public Health

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Progress in malaria control has stalled over the recent years. Knowledge on main drivers of transmission explaining small-scale variation in prevalence can inform targeted control measures. We collected finger-prick blood samples from 3061 individuals irrespective of clinical symptoms in 20 clusters in Busia in western Kenya and screened for Plasmodium falciparum parasites using qPCR and microscopy. Clusters spanned an altitude range of 207 meters (1077–1284 m). We mapped potential mosquito larval habitats and determined their number within 250 m of a household and distances to households using ArcMap. Across all clusters, P. falciparum parasites were detected in 49.8% (1524/3061) of individuals by qPCR and 19.5% (596/3061) by microscopy. Across the clusters, prevalence ranged from 26% to 70% by qPCR. Three to 34 larval habitats per cluster and 0–17 habitats within a 250m radius around households were observed. Using a generalized linear mixed effect model (GLMM), a 5% decrease in the odds of getting infected per each 10m increase in altitude was observed, while the number of larval habitats and their proximity to households were not statistically significant predictors for prevalence. Kitchen located indoors, open eaves, a lower level of education of the household head, older age, and being male were significantly associated with higher prevalence. Pronounced variation in prevalence at small scales was observed and needs to be taken into account for malaria surveillance and control. Potential larval habitat frequency had no direct impact on prevalence.

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Section: Discussionmentioning

confidence: 99%

Altitude, not potential larval habitat availability, explains pronounced variation in Plasmodium falciparum infection prevalence in the western Kenya highlands

Oduma

Ombok

Zhao

et al. 2023

PLOS Glob Public Health

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“…In this study, the sensitivity of LM and RDTs was 24% and 34%, respectively, as compared to the var ATS qPCR. Highly sensitive RDTs (55) or loop-mediated isothermal amplification (LAMP) (56) could be promising options to improve the diagnosis of asymptomatic and sub-patent infections in areas where they are common. In Northern Côte d’Ivoire, for example, LAMP has been shown to be a relevant field diagnostic alternative to standard RDTs for identifying asymptomatic infections with a sensibility and specificity of 93.3% (95% CI 85.7–100) and 95.4% (95% CI 92.2–100), respectively (56).…”

Section: Discussionmentioning

confidence: 99%

High prevalence of asymptomatic and sub-patentPlasmodium falciparuminfections in Urban Bouaké, Côte d’Ivoire, but nohrp2deletions: Implications for Malaria Control

Sagna,

Gebre,

Vera-Arias

et al. 2023

Preprint

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AsymptomaticPlasmodium falciparuminfections are common in endemic settings, yet diagnosing these infections remains challenging because they are often below the limit of detection of conventional light microscopy (LM) or rapid diagnostic tests (RDTs). Deletions of thehrp2/3gene, encoding the protein detected by the most sensitive class of RDTs, present a further threat. In this study, the prevalence of asymptomatic and sub-patentP. falciparuminfections was characterized in the rainy season in the city of Bouaké, Central Côte d’Ivoire. A cross-sectional survey was conducted in nine neighborhoods of Bouaké, Côte d’Ivoire, in 2016. Matched LM, RDTs, andvarATS qPCR, were used to determine the prevalence ofP. falciparuminfections and to compare the performance of the different diagnostic methods.P. falciparum hrp2/3deletions were typed by digital PCR. Among 2313 individuals, malaria prevalence was 10.8% by microscopy, 13.0% by RDT, 35.1% by qPCR, and 37.3% (863/2313) when all three methods were combined. 96.4% (832/863) of individuals withP. falciparuminfections did not report a recent fever. 57.1% (493/863) of infections were sub-patent. The prevalence was highly heterogeneous across the neighborhoods, ranging from 15% to 55.2%, and differed among age groups (<5 years: 17.7%, 5-14 years: 42.7%, ≥15 years: 35.9%). Compared tovarATS qPCR, LM and RDT had a low sensitivity of 24.3% and 34.2%, respectively, although both methods were highly specific (>96%). Sub-microscopic malaria infections were more prevalent in ≥15-year-olds (69.9%, 349/499) and in the neighborhood of Dar es Salam (75.9%, 44/58). No hrp2 deletions were observed, and two samples carriedhrp3deletion/wild-type mixed infections. The high prevalence of asymptomatic and sub-patent infections prompts the implementation of strategies targeting these parasite reservoirs to achieve reductions in malaria burden in this high-transmission city of Côte d’Ivoire.

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“…In Ghana, samples were screened with the Rapigen BIOCREDIT Malaria Ag Pf (pLDH/HRPII) RDT. This novel test has bands for HRP2 and LDH, and is more sensitive than RDTs that had been available previously (including the RDT used in Ethiopia) [ 5 ]. Expert microscopy has been considered the gold standard for parasite diagnosis and quantification for many decades [ 20 ].…”

Section: Study Population and Methodsmentioning

confidence: 99%

A digital microscope for the diagnosis of Plasmodium falciparum and Plasmodium vivax, including P. falciparum with hrp2/hrp3 deletion

Ewnetu,

Badu,

Carlier

et al. 2024

PLOS Glob Public Health

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Sensitive and accurate malaria diagnosis is required for case management to accelerate control efforts. Diagnosis is particularly challenging where multiple Plasmodium species are endemic, and where P. falciparum hrp2/3 deletions are frequent. The Noul miLab is a fully automated portable digital microscope that prepares a blood film from a droplet of blood, followed by staining and detection of parasites by an algorithm. Infected red blood cells are displayed on the screen of the instrument. Time-to-result is approximately 20 minutes, with less than two minutes hands-on time. We evaluated the miLab among 659 suspected malaria patients in Gondar, Ethiopia, where P. falciparum and P. vivax are endemic, and the frequency of hrp2/3 deletions is high, and 991 patients in Ghana, where P. falciparum transmission is intense. Across both countries combined, the sensitivity of the miLab for P. falciparum was 94.3% at densities >200 parasites/μL by qPCR, and 83% at densities >20 parasites/μL. The miLab was more sensitive than local microscopy, and comparable to RDT. In Ethiopia, the miLab diagnosed 51/52 (98.1%) of P. falciparum infections with hrp2 deletion at densities >20 parasites/μL. Specificity of the miLab was 94.0%. For P. vivax diagnosis in Ethiopia, the sensitivity of the miLab was 97.0% at densities >200 parasites/μL (RDT: 76.8%, microscopy: 67.0%), 93.9% at densities >20 parasites/μL, and specificity was 97.6%. In Ethiopia, where P. falciparum and P. vivax were frequent, the miLab assigned the wrong species to 15/195 mono-infections at densities >20 parasites/μL by qPCR, and identified only 5/18 mixed-species infections correctly. In conclusion, the miLab was more sensitive than microscopy and thus is a valuable addition to the toolkit for malaria diagnosis, particularly for areas with high frequencies of hrp2/3 deletions.

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Performance of highly sensitive and conventional rapid diagnostic tests for clinical and subclinical Plasmodium falciparum infections, and hrp2/3 deletion status in Burundi

Cited by 11 publications

References 39 publications

Altitude, not potential larval habitat availability, explains pronounced variation in Plasmodium falciparum infection prevalence in the western Kenya highlands

Altitude, not potential larval habitat availability, explains pronounced variation in Plasmodium falciparum infection prevalence in the western Kenya highlands

High prevalence of asymptomatic and sub-patentPlasmodium falciparuminfections in Urban Bouaké, Côte d’Ivoire, but nohrp2deletions: Implications for Malaria Control

A digital microscope for the diagnosis of Plasmodium falciparum and Plasmodium vivax, including P. falciparum with hrp2/hrp3 deletion

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