Performance of pfHRP2 versus pLDH antigen rapid diagnostic tests for the detection of Plasmodium falciparum: a systematic review and meta-analysis

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Abstract

Introduction

There have been many inconsistent reports about the performance of histidine-rich protein 2 (HRP2) and lactate dehydrogenase (LDH) antigens as rapid diagnostic tests (RDTs) for the diagnosis of past Plasmodium falciparum infections. This meta-analysis was performed to determine the performance of pfHRP2 versus pLDH antigen RDTs in the detection of P. falciparum.

Material and methods

After a systematic review of related studies, Meta-DiSc 1.4 software was used to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Forest plots and summary receiver operating characteristic curve (SROC) analysis were used to summarize the overall test performance.

Results

Fourteen studies which met the inclusion criteria were included in the meta-analysis. The summary performances for pfHRP2- and pLDH-based tests in the diagnosis of P. falciparum infections were as follows: pooled sensitivity, 96.3% (95.8–96.7%) vs. 82.6% (81.7–83.5%); specificity, 86.1% (85.3–86.8%) vs. 95.9% (95.4–96.3%); diagnostic odds ratio (DOR), 243.31 (97.679–606.08) vs. 230.59 (114.98–462.42); and area under ROCs, 0.9822 versus 0.9849 (all p < 0.001).

Conclusions

The two RDTs performed satisfactorily for the diagnosis of P. falciparum, but the pLDH tests had higher specificity, whereas the pfHRP2 tests had better sensitivity. The pfHRP2 tests had slightly greater accuracy compared to the pLDH tests. A combination of both antigens might be a more reliable approach for the diagnosis of malaria.

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Systematic review and meta-analysis: rapid diagnostic tests versus placental histology, microscopy and PCR for malaria in pregnant women

Johanna Kattenberg, Eleanor A Ochodo, Kimberly R. Boer … (2011)

Background During pregnancy, malaria infection with Plasmodium falciparum or Plasmodium vivax is related to adverse maternal health and poor birth outcomes. Diagnosis of malaria, during pregnancy, is complicated by the absence or low parasite densities in peripheral blood. Diagnostic methods, other than microscopy, are needed for detection of placental malaria. Therefore, the diagnostic accuracy of rapid diagnostic tests (RDTs), detecting antigen, and molecular techniques (PCR), detecting DNA, for the diagnosis of Plasmodium infections in pregnancy was systematically reviewed. Methods MEDLINE, EMBASE and Web of Science were searched for studies assessing the diagnostic accuracy of RDTs, PCR, microscopy of peripheral and placental blood and placental histology for the detection of malaria infection (all species) in pregnant women. Results The results of 49 studies were analysed in metandi (Stata), of which the majority described P. falciparum infections. Although both placental and peripheral blood microscopy cannot reliably replace histology as a reference standard for placental P. falciparum infection, many studies compared RDTs and PCR to these tests. The proportion of microscopy positives in placental blood (sensitivity) detected by peripheral blood microscopy, RDTs and PCR are respectively 72% [95% CI 62-80], 81% [95% CI 55-93] and 94% [95% CI 86-98]. The proportion of placental blood microscopy negative women that were negative in peripheral blood microscopy, RDTs and PCR (specificity) are 98% [95% CI 95-99], 94% [95% CI 76-99] and 77% [95% CI 71-82]. Based on the current data, it was not possible to determine if the false positives in RDTs and PCR are caused by sequestered parasites in the placenta that are not detected by placental microscopy. Conclusion The findings suggest that RDTs and PCR may have good performance characteristics to serve as alternatives for the diagnosis of malaria in pregnancy, besides any other limitations and practical considerations concerning the use of these tests. Nevertheless, more studies with placental histology as reference test are urgently required to reliably determine the accuracy of RDTs and PCR for the diagnosis of placental malaria. P. vivax-infections have been neglected in diagnostic test accuracy studies of malaria in pregnancy.

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Meta-analysis: accuracy of rapid tests for malaria in travelers returning from endemic areas.

Reto Nüesch, Blaise Genton, Matthias Egger … (2005)

Microscopic diagnosis of malaria is unreliable outside specialized centers. Rapid tests have become available in recent years, but their accuracy has not been assessed systematically. To determine the accuracy of rapid diagnostic tests for ruling out malaria in nonimmune travelers returning from malaria-endemic areas. The authors searched MEDLINE, EMBASE, CAB Health, and CINAHL (1988 to September 2004); hand-searched conference proceedings; checked reference lists; and contacted experts and manufacturers. Diagnostic accuracy studies in nonimmune individuals with suspected malaria were included if they compared rapid tests with expert microscopic examination or polymerase chain reaction tests. Data on study and patient characteristics and results were extracted in duplicate. The main outcome was the likelihood ratio for a negative test result (negative likelihood ratio) for Plasmodium falciparum malaria. Likelihood ratios were combined by using random-effects meta-analysis, stratified by the antigen targeted (histidine-rich protein-2 [HRP-2] or parasite lactate dehydrogenase [LDH]) and by test generation. Nomograms of post-test probabilities were constructed. The authors included 21 studies and 5747 individuals. For P. falciparum, HRP-2-based tests were more accurate than parasite LDH-based tests: Negative likelihood ratios were 0.08 and 0.13, respectively (P = 0.019 for difference). Three-band HRP-2 tests had similar negative likelihood ratios but higher positive likelihood ratios compared with 2-band tests (34.7 vs. 98.5; P = 0.003). For P. vivax, negative likelihood ratios tended to be closer to 1.0 for HRP-2-based tests than for parasite LDH-based tests (0.24 vs. 0.13; P = 0.22), but analyses were based on a few heterogeneous studies. Negative likelihood ratios for the diagnosis of P. malariae or P. ovale were close to 1.0 for both types of tests. In febrile travelers returning from sub-Saharan Africa, the typical probability of P. falciparum malaria is estimated at 1.1% (95% CI, 0.6% to 1.9%) after a negative 3-band HRP-2 test result and 97% (CI, 92% to 99%) after a positive test result. Few studies evaluated 3-band HRP-2 tests. The evidence is also limited for species other than P. falciparum because of the few available studies and their more heterogeneous results. Further studies are needed to determine whether the use of rapid diagnostic tests improves outcomes in returning travelers with suspected malaria. Rapid malaria tests may be a useful diagnostic adjunct to microscopy in centers without major expertise in tropical medicine. Initial decisions on treatment initiation and choice of antimalarial drugs can be based on travel history and post-test probabilities after rapid testing. Expert microscopy is still required for species identification and confirmation.

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Comparison of HRP2- and pLDH-based rapid diagnostic tests for malaria with longitudinal follow-up in Kampala, Uganda.

Sarah G. Staedke, Philip Rosenthal, Heidi Hopkins … (2007)

Presumptive treatment of malaria results in significant overuse of antimalarials. Malaria rapid diagnostic tests (RDTs) may offer a reliable alternative for case management, but the optimal RDT strategy is uncertain. We compared the diagnostic accuracy of histidine-rich protein 2 (HRP2)- and plasmodium lactate dehydrogenase (pLDH)-based RDTs, using expert microscopy as the gold standard, in a longitudinal study of 918 fever episodes over an 8-month period in a cohort of children in Kampala, Uganda. Sensitivity was 92% for HRP2 and 85% for pLDH, with differences primarily due to better detection with HRP2 at low parasite densities. Specificity was 93% for HRP2 and 100% for pLDH, with differences primarily due to rapid clearance of pLDH antigenemia after treatment of a previous malaria episode. RDTs may provide an effective strategy for improving rational delivery of antimalarial therapy; in Kampala, either test could dramatically decrease inappropriate presumptive treatments.

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Author and article information

Journal

Journal ID (nlm-ta): Arch Med Sci

Journal ID (iso-abbrev): Arch Med Sci

Journal ID (publisher-id): AMS

Title: Archives of Medical Science : AMS

Publisher: Termedia Publishing House

ISSN (Print): 1734-1922

ISSN (Electronic): 1896-9151

Publication date (Electronic): 20 April 2017

Publication date (Print): 01 April 2017

Volume: 13

Issue: 3

Pages: 541-549

Affiliations

[1 ]Center for Clinical Laboratory, 302 Hospital of PLA, Beijing, China

[2 ]Graduate Student Team, Medical University of PLA, Beijing, China

Author notes

Corresponding author: Prof. Yuanli Mao, Center for Clinical Laboratory, 302 Hospital of PLA, Beijing, China. Phone: +86 10 63879625, Fax: +86 10 63879625. E-mail: pipi780816@ 123456aliyun.com

Article

Publisher ID: 29827

DOI: 10.5114/aoms.2017.67279

PMC ID: 5420633

PubMed ID: 28507567

SO-VID: 8aa7b89f-80b3-4c9a-bc34-bc96ac473881

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

Performance of pfHRP2 versus pLDH antigen rapid diagnostic tests for the detection of Plasmodium falciparum: a systematic review and meta-analysis

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Abstract

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Most cited references 22

Systematic review and meta-analysis: rapid diagnostic tests versus placental histology, microscopy and PCR for malaria in pregnant women

Meta-analysis: accuracy of rapid tests for malaria in travelers returning from endemic areas.

Comparison of HRP2- and pLDH-based rapid diagnostic tests for malaria with longitudinal follow-up in Kampala, Uganda.

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