Accuracy of Two Malaria Rapid Diagnostic Tests (RDTS) for Initial Diagnosis and Treatment Monitoring in a High Transmission Setting in Uganda

Mbabazi, Phoebe; Hopkins, Heidi; Osilo, Emmanuel; Kalungu, Michael; Byakika-Kibwika, Pauline; Kamya, Moses R.

doi:10.4269/ajtmh.14-0180

Cited by 39 publications

(49 citation statements)

References 22 publications

(35 reference statements)

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“…While other studies have reported ranges of HRP2 specificity from 55% to 88% at high-transmission sites in Uganda (16)(17)(18)(19)(20), our results suggest that the specificity may be even lower than previously described. The most likely explanation for these findings is the persistence of HRP2 antigenemia following treatment of an acute infection.…”

Section: Discussioncontrasting

confidence: 55%

“…A recent study from southwestern Uganda demonstrated that the median time to a negative HRP2 RDT after treatment was between 35 and 42 days, with more than a quarter of individuals remaining positive at the end of the 6-week study period (21). Another study from eastern Uganda reported HRP2 persistence in approximately half of cases 1 month after treatment (18).…”

Section: Discussionmentioning

confidence: 99%

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Improving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm

et al. 2017

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Poor specificity may negatively impact rapid diagnostic test (RDT)-based diagnostic strategies for malaria. We performed real-time PCR on a subset of subjects who had undergone diagnostic testing with a multiple-antigen (histidine-rich protein 2 and pan-lactate dehydrogenase pLDH [HRP2/pLDH]) RDT and microscopy. We determined the sensitivity and specificity of the RDT in comparison to results of PCR for the detection of Plasmodium falciparum malaria. We developed and evaluated a two-step algorithm utilizing the multiple-antigen RDT to screen patients, followed by confirmatory microscopy for those individuals with HRP2-positive (HRP2 ϩ )/ pLDH-negative (pLDH Ϫ ) results. In total, dried blood spots (DBS) were collected from 276 individuals. There were 124 (44.9%) individuals with an HRP2 ϩ /pLDH ϩ result, 94 (34.1%) with an HRP2 ϩ /pLDH Ϫ result, and 58 (21%) with a negative RDT result. The sensitivity and specificity of the RDT compared to results with real-time PCR were 99.4% (95% confidence interval [CI], 95.9 to 100.0%) and 46.7% (95% CI, 37.7 to 55.9%), respectively. Of the 94 HRP2 ϩ /pLDH Ϫ results, only 32 (34.0%) and 35 (37.2%) were positive by microscopy and PCR, respectively. The sensitivity and specificity of the two-step algorithm compared to results with real-time PCR were 95.5% (95% CI, 90.5 to 98.0%) and 91.0% (95% CI, 84.1 to 95.2), respectively. HRP2 antigen bands demonstrated poor specificity for the diagnosis of malaria compared to that of realtime PCR in a high-transmission setting. The most likely explanation for this finding is the persistence of HRP2 antigenemia following treatment of an acute infection. The two-step diagnostic algorithm utilizing microscopy as a confirmatory test for indeterminate HRP2 ϩ /pLDH Ϫ results showed significantly improved specificity with little loss of sensitivity in a high-transmission setting.KEYWORDS Plasmodium falciparum, antigen specificity, diagnostics, epidemiology, malaria, rapid tests S ince 2010, the World Health Organization (WHO) has recommended that all suspected malaria cases have a parasite-based diagnosis, either by microscopy or a rapid diagnostic test (RDT), prior to treatment with artemisinin-based combination therapy (ACT) (1). While light microscopy is the traditional reference standard for the diagnosis of malaria, RDTs are increasingly employed because they require minimal Improving the specificity of Plasmodium falciparum malaria diagnosis in hightransmission settings with a two-step rapid diagnostic test and microscopy algorithm. J

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Improving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm

et al. 2017

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“…RDTs are increasingly being used independently or in combination to microscopy in surveys [ 8 ]. RDTs are attractive as diagnostic tools due to their higher sensitivity compared to microscopy, ease of use and rapid availability of results [ 14 , 26 ]. However, specificity of RDTs and parasite prevalence estimates were highly variable in this study.…”

Section: Discussionmentioning

confidence: 99%

Estimating malaria parasite prevalence from community surveys in Uganda: a comparison of microscopy, rapid diagnostic tests and polymerase chain reaction

Nankabirwa

Yeka

Arinaitwe

et al. 2015

Malar J

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BackgroundHousehold surveys are important tools for monitoring the malaria disease burden and measuring impact of malaria control interventions with parasite prevalence as the primary metric. However, estimates of parasite prevalence are dependent on a number of factors including the method used to detect parasites, age of the population sampled, and level of immunity. To better understand the influence of diagnostics, age, and endemicity on estimates of parasite prevalence and how these change over time, community-based surveys were performed for two consecutive years in three settings and the sensitivities of microscopy and immunochromatographic rapid diagnostic tests (RDTs) were assessed, considering polymerase chain reaction (PCR) as the gold standard.MethodsSurveys were conducted over the same two-month period in 2012 and 2013 in each of three sub-counties in Uganda: Nagongera in Tororo District (January–February), Walukuba in Jinja District (March–April), and Kihihi in Kanungu District (May–June). In each sub-county, 200 households were randomly enrolled and a household questionnaire capturing information on demographics, use of malaria prevention methods, and proxy indicators of wealth was administered to the head of the household. Finger-prick blood samples were obtained for RDTs, measurement of hemoglobin, thick and thin blood smears, and to store samples on filter paper.ResultsA total of 1200 households were surveyed and 4433 participants were included in the analysis. Compared to PCR, the sensitivity of microscopy was low (65.3 % in Nagongera, 49.6 % in Walukuba and 40.9 % in Kihihi) and decreased with increasing age. The specificity of microscopy was over 98 % at all sites and did not vary with age or year. Relative differences in parasite prevalence across different age groups, study sites, and years were similar for microscopy and PCR. The sensitivity of RDTs was similar across the three sites (range 77.2–82.8 %), was consistently higher than microscopy (p < 0.001 for all pairwise comparisons), and decreased with increasing age. The specificity of RDTs was lower than microscopy (76.3 % in Nagongera, 86.3 % in Walukuba, and 83.5 % in Kihihi) and varied significantly by year and age. Relative differences in parasite prevalence across age groups and study years differed for RDTs compared to microscopy and PCR.ConclusionMalaria prevalence estimates varied with diagnostic test, age, and transmission intensity. It is important to consider the effects of these parameters when designing and interpreting community-based surveys.

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“…Additional considerations include high rates of false positivity with certain formulations (i.e. histidine‐rich protein 2‐based RDTs), and a requirement for blood smears to confirm negative test results . While molecular testing is highly sensitive and specific, the required infrastructure and technical expertise preclude widespread implementation .…”

Section: Discussionmentioning

confidence: 99%

Pathogen reduction and blood transfusion safety in Africa: strengths, limitations and challenges of implementation in low‐resource settings

et al. 2017

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Transfusion‐transmitted infection risk remains an enduring challenge to blood safety in Africa. A high background incidence and prevalence of the major transfusion‐transmitted infections (TTIs), dependence on high‐risk donors to meet demand, suboptimal testing and quality assurance collectively contribute to the increased risk. With few exceptions, donor testing is confined to serological evaluation of human immunodeficiency virus (HIV), hepatitis B and C (HBV and HCV) and syphilis. Barriers to implementation of broader molecular methods include cost, limited infrastructure and lack of technical expertise. Pathogen reduction (PR), a term used to describe a variety of methods (e.g. solvent detergent treatment or photochemical activation) that may be applied to blood following collection, offers the means to diminish the infectious potential of multiple pathogens simultaneously. This is effective against different classes of pathogen, including the major TTIs where laboratory screening is already implemented (e.g. HIV, HBV and HCV) as well pathogens that are widely endemic yet remain unaddressed (e.g. malaria, bacterial contamination). We sought to review the available and emerging PR techniques and their potential application to resource‐constrained parts of Africa, focusing on the advantages and disadvantages of such technologies. PR has been slow to be adopted even in high‐income countries, primarily given the high costs of use. Logistical considerations, particularly in low‐resourced parts of Africa, also raise concerns about practicality. Nonetheless, PR offers a rational, innovative strategy to contend with TTIs; technologies in development may well present a viable complement or even alternative to targeted screening in the future.

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Accuracy of Two Malaria Rapid Diagnostic Tests (RDTS) for Initial Diagnosis and Treatment Monitoring in a High Transmission Setting in Uganda

Cited by 39 publications

References 22 publications

Improving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm

Improving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm

Estimating malaria parasite prevalence from community surveys in Uganda: a comparison of microscopy, rapid diagnostic tests and polymerase chain reaction

Pathogen reduction and blood transfusion safety in Africa: strengths, limitations and challenges of implementation in low‐resource settings

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