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How long do rapid diagnostic tests remain positive after anti-malarial treatment?

ABSTRACT: BACKGROUND:Rapid diagnostic tests (RDTs) are increasingly becoming a paradigm for both clinical diagnosis of malaria infections and for estimating community parasite prevalence in household malaria indicator surveys in malaria-endemic countries. The antigens detected by RDTs are known to persist in the blood after treatment with anti-malarials, but reports on the duration of persistence (and the effect this has on RDT positivity) of these antigens post-treatment have been variable. METHODS:In this review, published studies on the persistence of positivity of RDTs post-treatment are collated, and a bespoke Bayesian survival model is fit to estimate the number of days RDTs remain positive after treatment. RESULTS:Half of RDTs that detect the antigen histidine-rich protein II (HRP2) are still positive 15 (5-32) days post-treatment, 13 days longer than RDTs that detect the antigen Plasmodium lactate dehydrogenase, and that 5% of HRP2 RDTs are still positive 36 (21-61) days after treatment. The duration of persistent positivity for combination RDTs that detect both antigens falls between that for HRP2- or pLDH-only RDTs, with half of RDTs remaining positive at 7 (2-20) days post-treatment. This study shows that children display persistent RDT positivity for longer after treatment than adults, and that persistent positivity is more common when an individual is treated with artemisinin combination therapy than when treated with other anti-malarials. CONCLUSIONS:RDTs remain positive for a highly variable amount of time after treatment with anti-malarials, and the duration of positivity is highly dependent on the type of RDT used for diagnosis. Additionally, age and treatment both impact the duration of persistence of RDT positivity. The results presented here suggest that caution should be taken when using RDT-derived diagnostic outcomes from cross-sectional data where individuals have had a recent history of anti-malarial treatment.

SUBMITTER: Dalrymple U

PROVIDER: S-EPMC5994115 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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How long do rapid diagnostic tests remain positive after anti-malarial treatment?

Dalrymple Ursula U Arambepola Rohan R Gething Peter W PW Cameron Ewan E

Malaria journal 20180608 1

<h4>Background</h4>Rapid diagnostic tests (RDTs) are increasingly becoming a paradigm for both clinical diagnosis of malaria infections and for estimating community parasite prevalence in household malaria indicator surveys in malaria-endemic countries. The antigens detected by RDTs are known to persist in the blood after treatment with anti-malarials, but reports on the duration of persistence (and the effect this has on RDT positivity) of these antigens post-treatment have been variable.<h4>Me ...[more]

PMID: 29884184

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Project description:BACKGROUND: The World Health Organization recommends parasitological confirmation of all malaria cases. Tanzania is implementing a phased rollout of malaria rapid diagnostic tests (RDTs) for routine use in all levels of care as one strategy to increase parasitological confirmation of malaria diagnosis. This study was carried out to evaluated artemisinin combination therapy (ACT) prescribing patterns in febrile patients with and without uncomplicated malaria in one pre-RDT implementation and one post-RDT implementation area. METHODS: A cross-sectional health facility surveys was conducted during high and low malaria transmission seasons in 2010 in both areas. Clinical information and a reference blood film on all patients presenting for an initial illness consultation were collected. Malaria was defined as a history of fever in the past 48 h and microscopically confirmed parasitaemia. Routine diagnostic testing was defined as RDT or microscopy ordered by the health worker and performed at the health facility as part of the health worker-patient consultation. Correct diagnostic testing was defined as febrile patient tested with RDT or microscopy. Over-testing was defined as a non-febrile patient tested with RDT or microscopy. Correct treatment was defined as patient with malaria prescribed ACT. Over-treatment was defined as patient without malaria prescribed ACT. RESULTS: A total of 1,247 febrile patients (627 from pre-implementation area and 620 from post-implementation area) were included in the analysis. In the post-RDT implementation area, 80.9% (95% CI, 68.2-89.3) of patients with malaria received recommended treatment with ACT compared to 70.3% (95% CI, 54.7-82.2) of patients in the pre-RDT implementation area. Correct treatment was significantly higher in the post-implementation area during high transmission season (85.9% (95% CI, 72.0-93.6) compared to 58.3% (95% CI, 39.4-75.1) in pre-implementation area (p?=?0.01). Over-treatment with ACT of patients without malaria was less common in the post-RDT implementation area (20.9%; 95% CI, 14.7-28.8) compared to the pre-RDT implementation area (45.8%; 95% CI, 37.2-54.6) (p?<?0.01) in high transmission. The odds of overtreatment was significantly lower in post- RDT area (adjusted Odds Ratio (OR: 95% CI) 0.57(0.36-0.89); and much higher with clinical diagnosis adjusted OR (95% CI) 2.24(1.37-3.67) CONCLUSION: Implementation of RDTs increased use of RDTs for parasitological confirmation and reduced over-treatment with ACT during high malaria transmission season in one area in Tanzania. Continued monitoring of the national RDT rollout will be needed to assess whether these changes in case management practices will be replicated in other areas and sustained over time. Additional measures (such as refresher trainings, closer supervisions, etc.) may be needed to improve ACT targeting during low transmission seasons.

Project description:BackgroundRapid diagnostic tests (RDTs) are central to fulfilling the WHO's recommendation for parasitologic confirmation of all suspected cases of malaria. RDT performance may be compromised when exposed to the high temperature conditions typical of most malaria endemic regions. However, a systematic method to monitor RDT quality and performance in endemic countries is lacking at the present time. Current methods to monitor RDT performance in the field include comparing results from RDTs to diagnoses made by light microscopy and observing health workers perform tests. These methods are not substitutes for direct quality control. In this study, the suitability of dried Plasmodium falciparum-infected blood as quality control samples for malaria RDTs was evaluated.MethodsThree cultured strains of P. falciparum at 200 and 2,000 parasites/μl were tested on 10 brands of RDT. After baseline testing to determine initial reactivity, aliquots of parasite-infected blood were air dried, stored at 35°C, room temperature (~25°C) or 4°C for one, four and 12 weeks and were then tested on the 10 RDTs after rehydration. Extended stability testing of dried blood stored at 4°C was done using P. falciparum strain 3D7 at 1,000 and 2,000 parasites/μl.ResultsAll dried blood samples at 2,000 parasites/μl retained reactivity (100% sensitivity) at all three temperatures and time points for all nine RDT brands that detect histidine-rich protein-2 (HRP2). The dried blood samples with 200 parasites/μl were detected by six of the nine HRP2-based RDTs at all storage temperatures and time points. The sensitivity for two of the three remaining HRP2-based RDTs was 100% up to four weeks of storage at all temperatures but dropped to 87.5% at week 12. Of the four RDTs that detect plasmodium lactate dehydrogenase (pLDH) in a pan-specific manner, alone or in combination with HRP2, the detection of pLDH in samples with 2,000 parasites/μL was 100% for two RDTs and 80% for the other two RDTs. The mean level for detection of pLDH at 200 parasites/μl was low (29%), with a range of 0% to100%, which was partly attributable to weak initial baseline reactivity. Reactivity of dried 3D7 at 1,000 and 2,000 parasites/μl stored at 4°C was retained at 100% for up to 52 weeks for both HRP2 and pLDH.ConclusionsIn the absence of native or recombinant positive control antigens, well-standardized P. falciparum-infected dried blood samples can be used as positive control samples for monitoring RDT performance, particularly with HRP2-detecting tests.

Project description:BackgroundLarge-scale surveillance of molecular markers of anti-malarial drug resistance is an attractive method of resistance monitoring, to complement therapeutic efficacy studies in settings where the latter are logistically challenging.MethodsBetween 2014 and 2017, this study sampled malaria rapid diagnostic tests (RDTs), used in routine clinical care, from two health centres in Bissau, Guinea-Bissau. In order to obtain epidemiological insights, RDTs were collected together with patient data on age and sex. A subset of positive RDTs from one of the two sites (n?=?2184) were tested for Plasmodium DNA content. Those testing positive for Plasmodium DNA by PCR (n?=?1390) were used for library preparation, custom designed dual indexing and next generation Miseq targeted sequencing of Plasmodium falciparum genes pfcrt, pfmdr1, pfdhfr, pfdhps and pfk13.ResultsThe study found a high frequency of the pfmdr1 codon 86N at 88-97%, a significant decrease of the pfcrt wildtype CVMNK haplotype and elevated levels of the pfdhfr/pfdhps quadruple mutant ranging from 33 to 51% between 2014 and 2017. No polymorphisms indicating artemisinin tolerance were discovered. The demographic data indicate a large proportion of young adults (66%, interquartile range 11-28 years) presenting with P. falciparum infections. While a total of 5532 gene fragments were successfully analysed on a single Illumina Miseq flow cell, PCR-positivity from the library preparation varied considerably from 13 to 87% for different amplicons. Furthermore, pre-screening of samples for Plasmodium DNA content proved necessary prior to library preparation.ConclusionsThis study serves as a proof of concept for using leftover clinical material (used RDTs) for large-scale molecular surveillance, encompassing the inherent complications regarding to methodology and analysis when doing so. Factors such as RDT storage prior to DNA extraction and parasitaemia of the infection are likely to have an effect on whether or not parasite DNA can be successfully analysed, and are considered part of the reason the data yield is suboptimal. However, given the necessity of molecular surveillance of anti-malarial resistance in settings where poor infrastructure, poor economy, lack of educated staff and even surges of political instability remain major obstacles to performing clinical studies, obtaining the necessary data from used RDTs, despite suboptimal output, becomes a feasible, affordable and hence a justifiable method.

Project description:BackgroundThe World Health Organization (WHO) has targeted a reduction in viral hepatitis-related mortality by 65% and incidence by 90% by 2030, necessitating enhanced hepatitis B treatment and prevention programmes in low- and middle-income countries. Hepatitis B e antigen (HBeAg) status is used in the assessment of eligibility for antiviral treatment and for prevention of mother-to-child transmission (PMTCT). Accordingly, the WHO has classified HBeAg rapid diagnostic tests (RDTs) as essential medical devices.MethodsWe assessed the performance characteristics of three commercially available HBeAg RDTs (SD Bioline, Alere, South Africa; Creative Diagnostics, USA; and Biopanda Reagents, UK) in two hepatitis B surface antigen-positive cohorts in Blantyre, Malawi: participants of a community study (n = 100) and hospitalised patients with cirrhosis or hepatocellular carcinoma (n = 94). Two investigators, blinded to the reference test result, independently assessed each assay. We used an enzyme-linked immunoassay (Monolisa HBeAg, Bio-Rad, France) as a reference test and quantified HBeAg concentration using dilutions of the WHO HBeAg standard. We related the findings to HBV DNA levels, and evaluated treatment eligibility using the TREAT-B score.ResultsAmong 194 HBsAg positive patients, median age was 37 years, 42% were femaleand 26% were HIV co-infected. HBeAg prevalence was 47/194 (24%). The three RDTs showed diagnostic sensitivity of 28% (95% CI 16-43), 53% (38-68) and 72% (57-84) and specificity of 96-100% for detection of HBeAg. Overall inter-rater agreement κ statistic was high at 0.9-1.0. Sensitivity for identifying patients at the threshold where antiviral treatment is recommended for PMTCT, with HBV DNA > 200,000 IU/ml (39/194; 20%), was 22, 49 and 54% respectively. Using the RDTs in place of the reference HBeAg assay resulted in 3/43 (9%), 5/43 (12%) and 8/43 (19%) of patients meeting the TREAT-B treatment criteria being misclassified as ineligible for treatment. A relationship between HBeAg concentration and HBeAg detection by RDT was observed. A minimum HBeAg concentration of 2.2-3.1 log10IU/ml was required to yield a reactive RDT.ConclusionsCommercially available HBeAg RDTs lack sufficient sensitivity to accurately classify hepatitis B patients in Malawi. This has implications for hepatitis B public health programs in sub-Saharan Africa. Alternative diagnostic assays are recommended.

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How long do rapid diagnostic tests remain positive after anti-malarial treatment?

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How long do rapid diagnostic tests remain positive after anti-malarial treatment?

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