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Cited by 37Malaria Research and ControlHemoglobinopathies and Related DisordersBird parasitology and diseases

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

Open access
Umbers, Alexandra J., Unger, Holger W., Rosanas-Urgell, Anna, Wangnapi, Regina A., Kattenberg, Johanna H., Jally, Shadrach, Silim, Selina, Lufele, Elvin +5 more·2015·Malaria Journal
DOI 10.1186/s12936-015-0927-5PMC PMC4617889
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Abstract

BACKGROUND: The diagnosis of malaria during pregnancy is complicated by placental sequestration, asymptomatic infection, and low-density peripheral parasitaemia. Where intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine is threatened by drug resistance, or is inappropriate due to low transmission, intermittent screening and treatment (ISTp) with rapid diagnostic tests for malaria (RDT) could be a valuable alternative. Therefore, the accuracy of RDTs to detect peripheral and placental infection was assessed in a declining transmission setting in Papua New Guinea (PNG). METHODS: The performance of a combination RDT detecting histidine-rich protein-2 (HRP-2) and Plasmodium lactate dehydrogenase (pLDH), and light microscopy (LM), to diagnose peripheral Plasmodium falciparum and Plasmodium vivax infections during pregnancy, were assessed using quantitative real-time PCR (qPCR) as the reference standard. Participants in a malaria prevention trial in PNG with a haemoglobin ≤90 g/L, or symptoms suggestive of malaria, were tested. Ability of RDT and LM to detect active placental infection on histology was evaluated in some participants. RESULTS: Among 876 women, 1162 RDTs were undertaken (anaemia: 854 [73.5 %], suspected malaria: 308 [26.5 %]). qPCR detected peripheral infection during 190 RDT episodes (165 P. falciparum, 19 P. vivax, 6 mixed infections). Overall, RDT detected peripheral P. falciparum infection with 45.6 % sensitivity (95 % CI 38.0-53.4), a specificity of 96.4 % (95.0-97.4), a positive predictive value of 68.4 % (59.1-76.8), and a negative predictive value of 91.1 % (89.2-92.8). RDT performance to detect P. falciparum was inferior to LM, more so amongst anaemic women (18.6 vs 45.3 % sensitivity, Liddell's exact test, P < 0.001) compared to symptomatic women (72.9 vs 82.4 % sensitivity, P = 0.077). RDT and LM missed 88.0 % (22/25) and 76.0 % (19/25) of P. vivax infections, respectively. In a subset of women tested at delivery and who had placental histology (n = 158) active placental infection was present in 19.6 %: all three peripheral blood infection detection methods (RDT, LM, qPCR) missed >50 % of these infections. CONCLUSIONS: In PNG, HRP-2/pLDH RDTs may be useful to diagnose peripheral P. falciparum infections in symptomatic pregnant women. However, they are not sufficiently sensitive for use in intermittent screening amongst asymptomatic (anaemic) women. These findings have implications for the management of malaria in pregnancy. The adverse impact of infections undetected by RDT or LM on pregnancy outcomes needs further evaluation.

AI snapshot

Written from the paper’s full text.

TL;DR

In Papua New Guinean pregnant women with anaemia or suspected malaria, an HRP-2/pLDH rapid diagnostic test had low sensitivity for peripheral *Plasmodium falciparum* infection compared with qPCR, especially in asymptomatic anaemic women. The RDT also missed more than half of active placental infections and most *P. vivax* infections, suggesting it is not sufficiently sensitive for intermittent screening in asymptomatic pregnancy.

Key findings

  • Among 876 women and 1162 RDT episodes, qPCR detected peripheral infection in 190 episodes (165 *P. falciparum*, 19 *P. vivax*, 6 mixed). Overall RDT sensitivity for peripheral *P. falciparum* was 45.6% (95% CI 38.0–53.4), specificity 96.4% (95.0–97.4), PPV 68.4% (59.1–76.8), and NPV 91.1% (89.2–92.8).
  • RDT sensitivity was much lower in anaemia-only episodes than in symptomatic episodes: 18.6% vs 72.9% for *P. falciparum*; LM sensitivity was 45.3% vs 82.4%, respectively. RDT and LM missed 88.0% (22/25) and 76.0% (19/25) of *P. vivax* infections.
  • In the delivery subset with placental histology (n = 158), active placental infection was present in 19.6% (31/158). Peripheral RDT, LM, and qPCR all missed more than half: sensitivities were 45.2%, 45.2%, and 41.9%, respectively; combined LM + RDT sensitivity was 54.8%.

Methods

  • Prospective diagnostic accuracy study within an IPTp trial (NCT01136850) in Madang Province, PNG, July 2010–November 2013. Participants were pregnant women tested when Hb ≤90 g/L or when malaria was clinically suspected; 876 women contributed 1162 RDT episodes.
  • Index tests were the CareStart HRP-2/pLDH combo RDT and light microscopy. qPCR was the reference standard for peripheral *P. falciparum* and *P. vivax*; placental histology was the reference for active placental infection in a subset tested at delivery. Readers were blinded to other test results.
  • Sensitivity, specificity, PPV, and NPV with 95% CIs were calculated; Liddell’s exact test compared sensitivities/specificities. The study was reported according to STARD guidelines.

Limitations

  • Stated: findings are restricted to pregnant women with moderate-to-severe anaemia and/or symptoms; RDT performance in asymptomatic non-anaemic women is unknown. Only a subset had delivery testing and placental biopsies, limiting conclusions on placental infection; histology was not evaluated against placental blood qPCR. Low malaria prevalence limits extrapolation to higher-transmission settings, and the IPTp/ITN trial context constrains interpretation.
  • Stated: qPCR species-correction of five infection episodes may have biased LM performance; the low prevalence and design did not permit evaluation of missed infections on pregnancy outcomes.
  • Evident from the text: no sample size calculation was performed for this sub-analysis, and *P. ovale* and *P. malariae* were not evaluated because of budgetary constraints.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/s12936-015-0927-5

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 35 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Among anaemic women, LM sensitivity for P. falciparum was 45.3% (95% CI 34.6-56.5).

    “LM | 10.1 (8.1, 12.3) | 45.3 (34.6, 56.5)** | 98.8 (97.8, 99.5) | 81.3 (67.4, 91.1) | 94.2 (92.3, 95.7) | 47 of 86 (54.7 %)”
    Quote in the paperSubstantial claim
  • Findingown data

    Among anaemic women, RDT sensitivity for P. falciparum was 18.6% (95% CI 11.0-28.4).

    “RDT | 10.1 (8.1, 12.3) | 18.6 (11.0, 28.4)** | 98.4 (97.3, 99.2) | 57.1 (37.2, 75.5) | 91.5 (89.4, 93.3) | 70 of 86 (81.4 %)”
    Quote in the paperSubstantial claim
  • Findingown data

    Overall, RDT negative predictive value for peripheral P. falciparum was 91.1% (95% CI 89.2-92.8).

    “a negative predictive value of 91.1 % (89.2–92.8)”
    Quote in the paperSubstantial claim
  • Findingown data

    RDT sensitivity for P. falciparum was lower than LM among symptomatic women (72.9% vs 82.4%, P=0.077).

    “compared to symptomatic women (72.9 vs 82.4 % sensitivity, P = 0.077)”
    Quote in the paperNot a substantial claim
  • Findingown data

    qPCR detected peripheral infection during 190 RDT episodes (165 P. falciparum, 19 P. vivax, 6 mixed infections).

    “qPCR detected peripheral infection during 190 RDT episodes (165 P. falciparum, 19 P. vivax, 6 mixed infections).”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 27
  • May combine two claims. 18
  • The quote only partly states this claim. 2

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Among 876 women, 1162 RDTs were undertaken (anaemia: 854 [73.5%], suspected malaria: 308 [26.5%]).

    “Among 876 women, 1162 RDTs were undertaken (anaemia: 854 [73.5 %], suspected malaria: 308 [26.5 %]).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Overall, RDT sensitivity for P. falciparum was lower than LM (45.6% vs 63.7%).

    “RDT performance to detect P. falciparum was inferior to LM”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Prevalence of peripheral P. vivax infection by qPCR was 2.2% (25/1162).

    “Prevalence of peripheral P. vivax infection by qPCR was low (n = 25)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Of 22 P. vivax infections missed by RDT, nine were detected by LM (four of them were classified as P. falciparum by LM).

    “Of 22 P. vivax infections missed by RDT nine were detected by LM (four of them were classified as P. falciparum by LM).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The geometric mean density of P. vivax infections missed by RDT was 157 parasites/μL (median 125, range 16-3341), with seven out of nine infections exhibiting a parasite density <200 parasites/μL.

    “The geometric mean density of these infections was 157 parasites/μL (median 125, range 16–3341), with seven out of nine infections exhibiting a parasite density <200 parasites/μL.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    A quarter of women (221/876) had an RDT performed at delivery.

    “A quarter of women (221/876) had an RDT performed at delivery.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    RDT failed to diagnose about half of peripheral P. falciparum infections detected by qPCR and about half of placental P. falciparum infections detected by histology.

    “In this context RDT failed to diagnose about half of peripheral and placental P. falciparum infections detected by qPCR and histology, respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Median parasite densities for P. falciparum exceeded the minimum detection threshold documented in laboratory testing of the RDT (>100/μL) and those specified by WHO (>200/μL) in all groups.

    “Poor performance observed in this study may be explained by low sensitivity to detect low density parasitaemias, although the median parasite densities for P. falciparum exceeded the minimum detection threshold documented in laboratory testing of the RDT test (>100/µL) [44] and those specified by the WHO (>200/µL) in all groups [45].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [44] Maltha J, Gillet P, Bottieau E, Cnops L, van Esbroeck M, Jacobs J. Evaluation of a rapid diagnostic test (CareStartTM Malaria HRP-2/pLDH (Pf/pan) Combo Test) for the diagnosis of malaria in a reference setting. Malar J. 2010;9:171. source

      Not checked in the free run.

    • cites [45] Bell D, Peeling RW. Evaluation of rapid diagnostic tests: malaria. Nat Rev Microbiol. 2006;4:S34–8. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Of women with an RDT at delivery, 158/221 (71.5%) had a placental biopsy taken for histological evaluation of placental malaria.

    “Of these 71.5 % (n = 158) had a placental biopsy taken for histological evaluation of placental malaria, and 31 (19.6 %) had evidence of active infection (Table 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    RDT on peripheral blood failed to detect more than half of women with active placental infection, as did LM and qPCR.

    “RDT on peripheral blood failed to detect more than half of the women with active placental infection, as did LM and qPCR (Table 3).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    A sample size calculation was performed for the original trial but not for the present sub-analysis.

    “A sample size calculation was performed for the original trial but not for the purpose of the present sub-analysis [26].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Unger HW, Ome-Kaius M, Wangnapi RA, Umbers AJ, Hanieh S, Suen CS, et al. Sulphadoxine-pyrimethamine plus azithromycin for the prevention of low birthweight in Papua New Guinea: a randomised controlled trial. BMC Med. 2015;13:9. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study was reported according to STARD guidelines.

    “The study was reported according to STARD guidelines (Standards for the reporting of diagnostic accuracy studies).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Placental malaria is principally associated with severe adverse pregnancy outcomes, including low birthweight.

    “yet it is PM that is principally associated with a number of severe adverse pregnancy outcomes, including low birthweight (LBW) [4].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Umbers AJ, Aitken EH, Rogerson SJ. Malaria in pregnancy: small babies, big problem. Trend Parasitol. 2011;27:168–75. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Readers of all index tests and reference standards were blinded to the results of the other tests.

    “Readers of all aforementioned the index tests (LM and RDT) and respective reference standards (qPCR, or placental histology) were blinded to the results of the other tests.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Diagnosis of malaria in pregnancy is complicated by low peripheral blood parasite densities and sequestration of P. falciparum-infected erythrocytes in the placental intervillous space.

    “Diagnosis is further complicated by low peripheral blood parasite densities and sequestration of Plasmodium falciparum-infected erythrocytes in the placental intervillous space, termed placental malaria (PM) [4].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Umbers AJ, Aitken EH, Rogerson SJ. Malaria in pregnancy: small babies, big problem. Trend Parasitol. 2011;27:168–75. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In PNG, gestational malarial infection is common and frequently associated with adverse pregnancy outcomes.

    “In Papua New Guinea (PNG), gestational malarial infection is common and frequently associated with adverse pregnancy outcomes [22, 23].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Stanisic DI, Moore KA, Baiwog F, Ura A, Clapham C, King CL, et al. Risk factors for malaria and adverse birth outcomes in a prospective cohort of pregnant women resident in a high malaria transmission area of Papua New Guinea. Trans R Soc Trop Med Hyg. 2015;109:313–24. source

      Not checked in the free run.

    • cites [23] Mueller I, Rogerson S, Mola GD, Reeder JC. A review of the current state of malaria among pregnant women in Papua New Guinea. PNG Med J. 2008;51:12–6.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The microscopy laboratory at the PNG Institute of Medical Research undergoes regular and external quality control.

    “The microscopy laboratory at the PNG Institute of Medical Research undergoes regular and external quality control.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    qPCR did not include P. ovale and P. malariae.

    “Plasmodium ovale and Plasmodium malariae infections in pregnant PNG women are rare [36], and budgetary constraints precluded their evaluation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Stanisic D, Moore K, Baiwog F, Ura A, Clapham C, King C, et al. Risk factors for malaria and adverse birth outcomes in a prospective cohort of pregnant Papua New Guinea women. Trans R Soc Trop Med Hyg. 2015;109:313–24. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    Two microscopists read each slide, and third reads were performed to resolve discrepant results.

    “Two microscopists read each slide, and third reads were performed to resolve discrepant results [34].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Laman M, Moore BR, Benjamin J, Padapu N, Tarongka N, Siba P, et al. Comparison of an assumed versus measured leucocyte count in parasite density calculations in Papua New Guinean children with uncomplicated malaria. Malar J. 2014;13:145. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    qPCR was performed using an established methodology with a sensitivity of 1 parasite per microliter.

    “qPCR was performed to detect P. falciparum and P. vivax infections in peripheral and placental blood samples using an established methodology with a sensitivity of 1 parasite per microliter [35].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Wampfler R, Mwingira F, Javati S, Robinson L, Betuela I, Siba P, et al. Strategies for detection of Plasmodium species gametocytes. PLoS One. 2013;8:e76316. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    RDTs perform well outside of pregnancy and WHO recommends their use for diagnosis of malaria in this context.

    “RDTs perform well outside of pregnancy and the WHO recommends their use for the diagnosis of malaria in this context [17].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] WHO. Malaria rapid diagnostic test performance. Results of WHO product testing of malaria RDTs: round 3 (2010–2011). Geneva: World Health Organization; 2011.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Combination RDTs detecting both P. falciparum-HRP-2 and genus-specific pLDH are most appropriate in PNG.

    “Given all human malaria species, bar Plasmodium knowlesi, are sympatric in PNG, combination RDTs detecting both P. falciparum-histidine-rich-protein-2 (HRP-2) and the genus-specific malaria antigen lactate dehydrogenase (pLDH) are most appropriate, and were shown to be appropriate for malaria treatment amongst febrile children in PNG [25].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Senn N, Rarau P, Manong D, Salib M, Siba P, Robinson LJ, et al. Rapid diagnostic test-based management of malaria: an effectiveness study in Papua New Guinean infants with Plasmodium falciparum and Plasmodium vivax malaria. Clin Infect Dis. 2012;54:644–51. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    PNG national guidelines recommend RDTs and LM to diagnose infection in symptomatic patients, including pregnant women.

    “PNG national guidelines recommend RDTs and light microscopy (LM) to diagnose infection in symptomatic patients, including pregnant women [24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] DOH PNGNDoH. National malaria treatment protocol. Port Moresby: Papua New Guinea National Department of Health; 2009.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    ISTp using an LDH-based RDT prevents LBW and severe anaemia to a similar extent to SP-IPTp in an area of moderately high transmission in Ghana.

    “Results of the first reported trial of ISTp, which was conducted in an area of moderately high malaria transmission in Ghana, suggest that ISTp using an lactate dehydrogenase-based RDT prevents LBW and severe anaemia to a similar extent to SP-IPTp [10]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Tagbor H, Bruce J, Agbo M, Greenwood B, Chandramohan D. Intermittent screening and treatment versus intermittent preventive treatment of malaria in pregnancy: a randomised controlled non-inferiority trial. PLoS One. 2010;5:e14425. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    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].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Kyabayinze DJ, Tibenderana JK, Nassali M, Tumwine LK, Riches C, Montague M, et al. Placental Plasmodium falciparum malaria infection: operational accuracy of HRP2 rapid diagnostic tests in a malaria endemic setting. Malar J. 2011;10:306. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Anaemia is common in pregnant and non-pregnant individuals in PNG.

    “Third, anaemia is common in pregnant and non-pregnant individuals in PNG [29], yet in the present study the proportion of anaemic women with parasitaemia was comparatively low.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Senn N, Maraga S, Sie A, Rogerson SJ, Reeder JC, Siba P, et al. Population hemoglobin mean and anemia prevalence in Papua New Guinea: new metrics for defining malaria endemicity? PLoS One. 2010;5:e9375. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    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].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Kyabayinze DJ, Tibenderana JK, Nassali M, Tumwine LK, Riches C, Montague M, et al. Placental Plasmodium falciparum malaria infection: operational accuracy of HRP2 rapid diagnostic tests in a malaria endemic setting. Malar J. 2011;10:306. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Malarial infection is a well-established risk factor for gestational anaemia, and preliminary data from the parent trial indicate the same.

    “Second, malarial infection is a well-established risk factor for gestational anaemia [1], and preliminary data from the parent trial indicates the same [46].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Desai M, ter Kuile FO, Nosten F, McGready R, Asamoa K, Brabin B, et al. Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis. 2007;7:93–104. source

      Not checked in the free run.

    • cites [46] Unger HW, Ome-Kaius M, Wangnapi R, Umbers AJ, Hanieh S, Suen CSLW. Sulphadoxine-pyrimethamine plus azithromycin for the prevention of low birthweight in Papua New Guinea: a randomised controlled trial. BMC Med. 2015;13:9. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    The differences in findings between studies may be explained by differences in parasite densities, HRP-2-RDT brand, and laboratory procedures and assays used.

    “The differences in findings may be explained by differences in parasite densities, HRP-2-RDT brand, as well as laboratory procedures and assays used.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In asymptomatic pregnant Congolese women, RDT was better at diagnosing peripheral infection detected by nested PCR compared to LM.

    “In asymptomatic pregnant Congolese women RDT was better at diagnosing peripheral infection detected by nested PCR compared to LM [43].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Matangila J, Lufuluabo J, Ibalanky A, Inocencio da Luz R, Lutumba P, Van Geertruyden J. Asymptomatic Plasmodium falciparum infection is associated with anaemia in pregnancy and can be more cost-effectively detected by rapid diagnostic test than by microscopy in Kinshasa, Democratic Republic of the Congo. Malar J. 2014;13:132. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    The low prevalence of infection reflects much of the malaria epidemiology across the Asia-Pacific region.

    “Third, the low prevalence of infection overall limits extrapolation of findings to areas of higher malaria transmission, but does reflect much of the malaria epidemiology across the Asia–Pacific region.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    qPCR species-correction of five infection episodes may have biased the diagnostic performance of LM.

    “Moreover, qPCR species-correction of five infection episodes may have biased the diagnostic performance of LM.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The small sample size increases the risk of random error and does not allow definitive conclusions regarding performance of HRP-2/pLDH-RDT to detect placental infection.

    “Second, only a subset of women were tested at delivery and had placental biopsies taken: the small sample size increases the risk of random error and does not allow definitive conclusions regarding the performance of HRP-2/pLDH-RDT to detect placental infection.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    The study was conducted within the context of an IPTp trial in women sleeping under insecticide-treated bed nets, and interpretation of the study data is limited to this context.

    “Fourth, this study was conducted within the context of an IPTp trial in women sleeping under insecticide treated bet nets. Although most RDT screening events took place at enrolment, before women received any treatment, interpretation of the study data is limited to this context.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    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.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Kyabayinze DJ, Tibenderana JK, Nassali M, Tumwine LK, Riches C, Montague M, et al. Placental Plasmodium falciparum malaria infection: operational accuracy of HRP2 rapid diagnostic tests in a malaria endemic setting. Malar J. 2011;10:306. source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductnone given

    Only a subset of women were tested at delivery and had placental biopsies taken.

    “Second, only a subset of women were tested at delivery and had placental biopsies taken: the small sample size increases the risk of random error and does not allow definitive conclusions regarding the performance of HRP-2/pLDH-RDT to detect placental infection.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Study design and conductnone given

    Microscopy and molecular diagnostic facilities at the PNG Institute of Medical Research undergo regular external quality control and operate at the highest standard.

    “Microscopy and molecular diagnostic facilities at the PNG Institute of Medical Research undergo regular external quality control and operate at the highest standard.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The few studies to evaluate RDT for P. vivax infection in non-pregnant individuals report varying performance.

    “The few studies to evaluate RDT for P. vivax infection in non-pregnant individuals report varying performance [19, 20, 44].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [19] Elahi R, Mohon A, Khan W, Haque R, Alam M. Performance of a HRP-2/pLDH based rapid diagnostic test at the Bangladesh–India–Myanmar border areas for diagnosis of clinical malaria. Malar J. 2013;12:378. source

      Not checked in the free run.

    • cites [20] Khan W, Galagan S, Prue C, Khyang J, Ahmed S, Ram M, et al. Asymptomatic Plasmodium falciparum malaria in pregnant women in the Chittagong Hill Districts of Bangladesh. PLoS One. 2014;9:e98442. source

      Not checked in the free run.

    • cites [44] Maltha J, Gillet P, Bottieau E, Cnops L, van Esbroeck M, Jacobs J. Evaluation of a rapid diagnostic test (CareStartTM Malaria HRP-2/pLDH (Pf/pan) Combo Test) for the diagnosis of malaria in a reference setting. Malar J. 2010;9:171. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Histology was not evaluated against placental blood qPCR.

    “In addition, histology was not evaluated against placental blood qPCR.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The low prevalence of malaria in this cohort and the study design did not permit an evaluation of the impact of missed infections on pregnancy outcomes.

    “Finally, the low prevalence of malaria in this cohort and the study design did not permit an evaluation of the impact of missed infections on pregnancy outcomes.”
    Quote in the paperNot a substantial claim
40 of 40

  • The authors state this as an assumption.

    All active placental infections were due to P. falciparum.

    “All active placental infections were assumed to be due to P. falciparum: P. vivax has been associated with placental changes but these differ markedly from P. falciparum and are rare [40].”

  • The paper relies on this without support.

    The performance characteristics of HRP-2/pLDH RDTs in pregnant women in PNG were unknown before this study.

    “To date, the performance characteristics of these RDTs in pregnant women in PNG remain unknown.”

  • The paper relies on this without support.

    In areas with moderate-to-high malaria transmission intensity, the majority of parasitaemic pregnant women are asymptomatic.

    “It is well established that in areas with moderate-to-high transmission intensity the majority of parasitaemic pregnant women will be asymptomatic.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Predictive-value definitions conflict with Table 2 values

    Minor

    The note defines PPV using all qPCR-positive samples and NPV using all qPCR-negative samples-definitions that instead describe sensitivity and specificity. Table 2 reports different values for each pair of measures.

  • Placental RDT negative row does not add up

    Minor

    The RDT-negative row contains 17 women with positive histology and 117 with negative histology, totaling 134 rather than the reported 137. The same entries also leave the histology-negative column three short of its stated total.

    Reported 137 · recomputed 134

  • Conflicting anaemia-only counts in the delivery subset

    Minor

    For the same 158 women with placental histology, the text gives 126 tested for asymptomatic anaemia, but later uses 122 as the anaemia-only denominator.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. WHO. WHO policy brief for the implementation of intermittent preventive treatment in malaria in pregnancy using sulfadoxine-pyrimethamine (IPTp-SP). Geneva: World Health Organization; 2014.
  2. DOH PNGNDoH. National malaria treatment protocol. Port Moresby: Papua New Guinea National Department of Health; 2009.
  3. Stanisic D, Moore K, Baiwog F, Ura A, Clapham C, King C, et al. Risk factors for malaria and adverse birth outcomes in a prospective cohort of pregnant Papua New Guinea women. Trans R Soc Trop Med Hyg. 2015;109:313–24. · DOI · Paper page
  4. Unger HW, Ome-Kaius M, Wangnapi R, Umbers AJ, Hanieh S, Suen CSLW. Sulphadoxine-pyrimethamine plus azithromycin for the prevention of low birthweight in Papua New Guinea: a randomised controlled trial. BMC Med. 2015;13:9. · DOI · Paper page
  5. National Competency Training Project. Malaria diagnosis and the new treatment protocol: a training manual for health workers in Papua New Guinea. Port Moresby: Birdwing Publishing; 2010.

Cited by

Sorted by citations

Related

Authors
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., Robinson, L. J., Rogerson, S. J., & Mueller, I.
Affiliations
  • The University of Melbourne (AU)
  • Papua New Guinea Institute of Medical Research (PG)
  • Walter and Eliza Hall Institute of Medical Research (AU)
ORCID
Venue
Malaria Journal
Publisher
Springer Science and Business Media LLC
Published
2015-10-19
Volume
14
Issue
1
Pages
412-412
ISSN
1475-2875 (ISSN-L)
DOI
10.1186/s12936-015-0927-5
PMC
PMC4617889
OpenAlex
W1846025042
Semantic Scholar
275d8c4f9db9b29e71890bd665b122dfbd26ee16
Cited by
37
References
47
Citations by year
2025: 7 · 2024: 1 · 2023: 4 · 2022: 6 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 3
FWCI
3.92
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Malaria Journal (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by)
Funders
  • National Health and Medical Research Council (AU) (1043345, 1016443, 1052960)
  • European Union Seventh Framework Programme FP7 (BE) (PREGVAX 201588)
  • Malaria in Pregnancy Consortium (46099)
  • Pfizer Australia (AU) (WS394663)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
  • Life Sciences › Immunology and Microbiology › Parasitology › Bird parasitology and diseases
Keywords
Plasmodium falciparum, malaria in pregnancy, rapid diagnostic tests, placental malaria, anemia, diagnostic accuracy, Plasmodium vivax, intermittent screening and treatment, Papua New Guinea, microscopy comparison, intermittent preventive treatment, sulfadoxine-pyrimethamine resistance
MeSH terms
Adolescent, Adult, Anemia, Antigens, Protozoan, Chromatography, Affinity, Diagnostic Tests, Routine, Female, Humans, L-Lactate Dehydrogenase, Papua New Guinea, Pregnancy, Pregnancy Complications, Infectious, Prospective Studies, Sensitivity and Specificity, Protozoan Proteins, Malaria, Falciparum, Malaria, Vivax, Young Adult, Real-Time Polymerase Chain Reaction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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