Placental Plasmodium falciparum malaria infection: Operational accuracy of HRP2 rapid diagnostic tests in a malaria endemic setting

Kyabayinze, Daniel J; Tibenderana, James K; Nassali, Mercy; Tumwine, Lynette K; Riches, Clare; Montague, Mark; Counihan, Helen; Hamade, Prudence; Van Geertruyden, Jean-Pierre; Meek, Sylvia

doi:10.1186/1475-2875-10-306

Cited by 42Malaria Research and ControlHemoglobinopathies and Related DisordersClinical Laboratory Practices and Quality Control

Placental Plasmodium falciparum malaria infection: Operational accuracy of HRP2 rapid diagnostic tests in a malaria endemic setting

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Kyabayinze, Daniel J, Tibenderana, James K, Nassali, Mercy, Tumwine, Lynette K, Riches, Clare, Montague, Mark, Counihan, Helen, Hamade, Prudence +2 more·2011·Malaria Journal

DOI 10.1186/1475-2875-10-306PMC PMC3206496

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Abstract

BACKGROUND: Malaria has a negative effect on the outcome of pregnancy. Pregnant women are at high risk of severe malaria and severe haemolytic anaemia, which contribute 60-70% of foetal and perinatal losses. Peripheral blood smear microscopy under-estimates sequestered placental infections, therefore malaria rapid diagnostic tests (RDTs) detecting histidine rich protein-2 antigen (HRP-2) in peripheral blood are a potential alternative. METHODS: HRP-2 RDTs accuracy in detecting malaria in pregnancy (MIP >28 weeks gestation) and placental Plasmodium falciparum malaria (after childbirth) were conducted using Giemsa microscopy and placental histopathology respectively as the reference standard. The study was conducted in Mbale Hospital, using the midwives to perform and interpret the RDT results. Discordant results samples were spot checked using PCR techniques. RESULTS: Among 433 febrile women tested, RDTs had a sensitivity of 96.8% (95% CI 92-98.8), specificity of 73.5% (95% CI 67.8-78.6), a positive predictive value (PPV) of 68.0% (95% CI 61.4-73.9), and negative predictive value (NPV) of 97.5% (95% CI 94.0-99.0) in detecting peripheral P. falciparum malaria during pregnancy. At delivery, in non-symptomatic women, RDTs had a 80.9% sensitivity (95% CI 57.4-93.7) and a 87.5% specificity (95%CI 80.9-92.1), PPV of 47.2% (95% CI 30.7-64.2) and NPV of 97.1% (95% CI 92.2-99.1) in detecting placental P. falciparum infections among 173 samples. At delivery, 41% of peripheral infections were detected by microscopy without concurrent placental infection. The combination of RDTs and microscopy improved the sensitivity to 90.5% and the specificity to 98.4% for detecting placental malaria infection (McNemar's X(2)> 3.84). RDTs were not superior to microscopy in detecting placental infection (McNemar's X(2)< 3.84). Presence of malaria in pregnancy and active placental malaria infection were 38% and 12% respectively. Placental infections were associated with poor pregnancy outcome [pre-term, still birth and low birth weight] (aOR = 37.9) and late pregnancy malaria infection (aOR = 20.9). Mosquito net use (aOR 2.1) and increasing parity (aOR 2.7) were associated with lower risk for malaria in pregnancy. CONCLUSION: Use of HRP-2 RDTs to detect malaria in pregnancy in symptomatic women was accurate when performed by midwives. A combination of RDTs and microscopy provided the best means of detecting placental malaria. RDTs were not superior to microscopy in detecting placental infection. With a high sensitivity and specificity, RDTs could be a useful tool for assessing malaria in pregnancy, with further (cost-) effectiveness studies.

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RDTs did not outperform LM to detect PCR-confirmed peripheral P. falciparum and P. vivax infections during pregnancy.
“In line with previous findings [41], RDTs did not outperform LM to detect PCR-confirmed peripheral P. falciparum and P. vivax infections during pregnancy.”
From Accuracy of an HRP-2/panLDH rapid diagnostic test to detect peripheral and placental Plasmodium falciparum infection in Papua New Guinean women with anaemia or suspected malaria (2015) · cites this paper as [41]
Previous research demonstrates near-adequate performance of RDT in febrile pregnant women in Africa.
“This observation is in keeping with previous research that demonstrates near-adequate performance in febrile pregnant women in Africa [41].”
From Accuracy of an HRP-2/panLDH rapid diagnostic test to detect peripheral and placental Plasmodium falciparum infection in Papua New Guinean women with anaemia or suspected malaria (2015) · cites this paper as [41]
In Uganda, peripheral blood HRP-2-RDT and LM detected most placental infections (histology), and performed best when combined.
“In Uganda, peripheral blood HRP-2-RDT and LM detected most placental infections (histology), and performed best when combined [41].”
From Accuracy of an HRP-2/panLDH rapid diagnostic test to detect peripheral and placental Plasmodium falciparum infection in Papua New Guinean women with anaemia or suspected malaria (2015) · cites this paper as [41]
In the Congo, HRP-2 RDT were useful for detection of placental infection (according to histology) when used in combination and in presence of fever.
“In the Congo HRP-2 RDT were useful for the detection of placental infection (according to histology) when used in combination and in presence of fever [41], however the combination of RDT and LM results did not further enhance performance during pregnancy in this study (Table 3), and the small sample size of delivery episodes precludes a meaningful sub-analysis by test criteria.”
From Accuracy of an HRP-2/panLDH rapid diagnostic test to detect peripheral and placental Plasmodium falciparum infection in Papua New Guinean women with anaemia or suspected malaria (2015) · cites this paper as [41]
In studies using both peripheral and placental blood microscopy as references, RDT sensitivity was lower when compared with placental blood microscopy.
“In studies that used both peripheral and placental blood microscopy as references, RDT sensitivity was lower when compared with placenta blood microscopy [10,13,18].”
From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [18]

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diagnostic tests in a malaria endemic setting
Kyabayinze, D. J., Tibenderana, J., Nassali, M., Tumwine, L. K., Riches, C., Montague, M., Counihan, H., Hamade, P., Geertruyden, J.-P. V., & Meek, S. (2013)
Self-citation
Accuracy of an HRP-2/panLDH rapid diagnostic test to detect peripheral and placental Plasmodium falciparum infection in Papua New Guinean women with anaemia or suspected malaria
Umbers, A. J., Unger, H. W., Rosanas-Urgell, A., Wangnapi, R. A., Kattenberg, J. H., Jally, S., Silim, S., Lufele, E., Karl, S., Ome-Kaius, M., et al. (2015) · Malaria Journal · doi:10.1186/s12936-015-0927-5 · Cited by 37 · see citing works
Comparison of placental blood microscopy and the ICT HRP2 rapid diagnostic test to detect placental malaria
Aguilar, R., Machevo, S., Menéndez, C., Bardají, A., Nhabomba, A., Alonso, P. L., & Mayor, A. (2012) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/j.trstmh.2012.05.001 · Cited by 12 · see citing works
Accuracy of an HRP-2/panLDH rapid diagnostic test to detect\n peripheral and placental Plasmodium falciparum infection in\n Papua New Guinean women with anaemia or suspected malaria
Umbers, A. J., Unger, H. W., Rosanas‐Urgell, A., Wangnapi, R. A., Kattenberg, J. H., Jally, S., Silim, S., Lufele, E., Karl, S., Ome‐Kaius, M., et al. (n.d.) · RECERCAT (Consorci de Serveis Universitaris de Catalunya)
Systematic review and meta-analysis: Rapid diagnostic tests versus placental histology, microscopy and PCR for malaria in pregnant women
Kattenberg, J. H., Ochodo, E. A., Boer, K. R., Schallig, H. D., Mens, P. F., & Leeflang, M. M. (2011) · Malaria Journal · doi:10.1186/1475-2875-10-321 · Cited by 138 · see citing works

Authors: Kyabayinze, D. J., Tibenderana, J. K., Nassali, M., Tumwine, L. K., Riches, C., Montague, M., Counihan, H., Hamade, P., Van Geertruyden, J.-P., & Meek, S.
Affiliations: Malaria Consortium (UG)
London School of Hygiene & Tropical Medicine (GB)
Mbale Hospital (UG)
Malaria Consortium (GB)
Corresponding author: Kyabayinze, Daniel J
ORCID: Kyabayinze, Daniel J
Tibenderana, James K
Nassali, Mercy
Hamade, Prudence
Venue: Malaria Journal
Publisher: Springer Science and Business Media LLC
Published: 2011-10-18
Volume: 10
Issue: 1
Pages: 306-306
ISSN: 1475-2875 (ISSN-L)
DOI: 10.1186/1475-2875-10-306
PMC: PMC3206496
OpenAlex: W2154122903
Cited by: 42
References: 49
Citations by year: 2025: 5 · 2024: 2 · 2022: 5 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 3
FWCI: 3.76
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/2.0 (tdm)
Locations: Malaria Journal (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Greater South Information System
Funders: Department for International Development
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
Keywords: placental malaria, Plasmodium falciparum, malaria in pregnancy, diagnostic accuracy, placental pathology, febrile malaria, pregnancy outcomes, malaria-endemic settings, perinatal mortality
MeSH terms: Adolescent, Adult, Antigens, Protozoan, Blood, Diagnostic Tests, Routine, Female, Humans, Microscopy, Placenta Diseases, Plasmodium falciparum, Pregnancy, Pregnancy Complications, Infectious, Sensitivity and Specificity, Protozoan Proteins, Malaria, Falciparum, Clinical Laboratory Techniques, Young Adult

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Placental Plasmodium falciparum malaria infection: Operational accuracy of HRP2 rapid diagnostic tests in a malaria endemic setting

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