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Cited by 6Malaria Research and ControlHemoglobinopathies and Related DisordersParasitic Infections and Diagnostics

Diagnostic Accuracy of a Thick Blood Smear Compared to qPCR for Malaria Associated with Pregnancy in Colombia

Open access
Cardona-Arias, Jaiberth Antonio, Higuita Gutiérrez, Luis Felipe, Carmona-Fonseca, Jaime·2023·Tropical Medicine and Infectious Disease
DOI 10.3390/tropicalmed8020119PMC PMC9959527
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Abstract

This study aimed to evaluate the accuracy of the thick blood smear (TBS) versus quantitative polymerase chain reaction (qPCR) for the diagnosis of malaria associated with pregnancy (MAP) caused by P. falciparum or P. vivax in Colombia in its gestational malaria (GM), placental malaria (PM), and congenital malaria (CM) forms as well as to compare its accuracy in different subgroups of pregnant women according to the presence of fever, anemia and a history of malaria. This was a diagnostic evaluation of 829 pregnant women, 579 placentas, 381 umbilical cord samples, and 221 neonatal peripheral blood samples. Accuracy was evaluated based on the parameters of sensitivity, specificity, predictive values, likelihood ratios, and validity index, with their 95% confidence intervals. The frequency of GM was 36% (n = 297/829), PM 27% (n = 159/579), and CM 16.5% (n = 63/381) in umbilical cord samples and 2% (n = 5/221) in neonatal peripheral blood samples. For GM, the sensitivity was 55%, with higher rates in those infected with P. vivax (68%), with a history of malaria (69%), and with fever (96%). These three subgroups presented the best results in terms of the negative likelihood ratio and validity index. For PM, sensitivity was 8%; in subgroup analyses in terms of species, symptomatology (anemia and fever), and history of malaria, it was 1–18%, and the negative likelihood ratio was >0.80 in all subgroups. No false positives were recorded in any of the subgroups. The TBS did not detect any cases of CM. This study found the TBS yielded satisfactory results in terms of diagnosing GM for P. vivax, pregnant women with previous malaria and febrile. It also showed that the TBS is not useful for diagnosing PM and CM. It is necessary to conduct surveillance of MAP with molecular methods in in groups where TBS is deficient (asymptomatic GM, P. falciparum, and pregnant women without history of malaria) to optimize the timely treatment of PM and CM, avoid the deleterious effects of MAP and achieve the malaria elimination goals in Colombia.

AI snapshot

Written from the paper’s full text.

TL;DR

This diagnostic evaluation compared thick blood smear (TBS) against qPCR for malaria associated with pregnancy in Colombia and found TBS useful mainly for gestational malaria in P. vivax, febrile, or previously malaria-exposed pregnant women. TBS performed poorly for placental malaria and detected no congenital malaria cases.

Key findings

  • Gestational malaria: qPCR positivity was 35.8% (297/829); TBS sensitivity was 55%, specificity 100%, PPV 100%, and NPV 79.9%. Sensitivity was highest in febrile women (96%), those with malaria history (69%), and P. vivax infections (68%), but lowest in P. falciparum (30%), no fever (29%), and no malaria in the previous year (13%).
  • Placental malaria: qPCR positivity was 27.4% (159/579); TBS sensitivity was 8.2%, ranged from 1.2% to 17.6% in subgroups, with negative likelihood ratio >0.80 and Youden index <0.20 in all subgroups; no false positives were recorded.
  • Congenital malaria: qPCR detected 16.5% (63/381) in umbilical cord samples and 2% (5/221) in neonatal peripheral blood; TBS detected no cases, so accuracy parameters could not be estimated.
  • Submicroscopic cases accounted for 45% of gestational malaria, 92% of placental malaria, and 100% of congenital malaria in this study.

Methods

  • Diagnostic evaluation in Colombia’s main malaria-endemic area using samples collected 2010–2019: 829 pregnant women, 579 placentas, 381 umbilical cord blood samples, and 221 neonatal peripheral blood samples; sampling was non-probabilistic from antenatal care services.
  • TBS was the index test and qPCR the reference standard; tests used the same blood samples, were processed independently and blindly, and accuracy was assessed with sensitivity, specificity, predictive values, negative likelihood ratio, Youden index, and validity index with 95% CIs.
  • Analyses were done overall and by subgroups including P. falciparum or P. vivax, fever, anemia, malaria in the last year, and gestational malaria history; analyses used EPIDAT.

Limitations

  • Stated by the authors: low numbers of mixed malaria cases prevented diagnostic accuracy analyses for mixed infections; comprehensive analyses by parasitemia level were not conducted; qPCR cannot determine microorganism viability or transmission potential.
  • Evident from the text: most samples were not from the same mother–placenta–neonate subjects, so gestational, placental, and congenital malaria results were analyzed independently; sampling was non-probabilistic; congenital malaria accuracy was not estimable because TBS detected no cases; the febrile placental malaria subgroup had only 33 cases and could not yield accuracy estimates.

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

Integrity signals

Registry

Crossref · 10.3390/tropicalmed8020119

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 62 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Among qPCR-positive placental malaria cases, P. falciparum accounted for 45.3% (72/159).

    “The species identified with qPCR were P. falciparum, 45.3% (n = 72); P. vivax, 40.9% (n = 65); and mixed, 13.8% (n = 22)”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The qPCR reference standard correctly classifies malaria infection and species in pregnant women, placentas, umbilical cord blood, and neonatal blood.
  • Findingown data

    For gestational malaria, the thick blood smear had a positive predictive value of 100%.

    “For GM, the TBS had a sensitivity of 55%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 79.9%.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The qPCR reference standard correctly classifies malaria infection and species in pregnant women, placentas, umbilical cord blood, and neonatal blood.
  • Findingown data

    Among 579 placental blood samples, qPCR revealed that 27.4% (159/579) were positive for placental malaria.

    “The frequency of GM was 36% (n = 297/829), PM 27% (n = 159/579), and CM 16.5% (n = 63/381) in umbilical cord samples and 2% (n = 5/221) in neonatal peripheral blood samples.”
    • Also stated in: § 3. Results · plain
      “Both tests were performed on 579 placental blood samples, and the results were as follows: qPCR revealed that 27.4% (n = 159) were positive”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The qPCR reference standard correctly classifies malaria infection and species in pregnant women, placentas, umbilical cord blood, and neonatal blood.
    • Rests on an assumption: The non-probabilistic sampling and the fact that most samples were not from the same subjects do not bias the independent estimates of gestational, placental, and congenital malaria.
  • Findingown data

    Among qPCR-positive umbilical cord blood samples, P. falciparum accounted for 63.5% (40/63).

    “According to the umbilical cord blood samples, 16.5% (n = 63) were positive, P. falciparum 63.5% (n = 40), P. vivax 30.2% (n = 19), and mixed malaria 6.3% (n = 4)”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The qPCR reference standard correctly classifies malaria infection and species in pregnant women, placentas, umbilical cord blood, and neonatal blood.
  • Findingown data

    Among qPCR-positive placental malaria cases, mixed malaria accounted for 13.8% (22/159).

    “The species identified with qPCR were P. falciparum, 45.3% (n = 72); P. vivax, 40.9% (n = 65); and mixed, 13.8% (n = 22)”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The qPCR reference standard correctly classifies malaria infection and species in pregnant women, placentas, umbilical cord blood, and neonatal blood.
  • Classified as probably not a substantial claim. 29
  • May combine two claims. 32

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

    Findingown data

    Among qPCR-positive umbilical cord blood samples, mixed malaria accounted for 6.3% (4/63).

    “According to the umbilical cord blood samples, 16.5% (n = 63) were positive, P. falciparum 63.5% (n = 40), P. vivax 30.2% (n = 19), and mixed malaria 6.3% (n = 4)”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The qPCR reference standard correctly classifies malaria infection and species in pregnant women, placentas, umbilical cord blood, and neonatal blood.

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

    Findingown data

    Among qPCR-positive gestational malaria cases, mixed malaria accounted for 3.0% (8/297).

    “P. vivax, 63% (n = 187); P. falciparum, 34% (n = 102); and both species (mixed malaria), 3.0% (n = 8).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The qPCR reference standard correctly classifies malaria infection and species in pregnant women, placentas, umbilical cord blood, and neonatal blood.

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

    Findingown data

    Among qPCR-positive gestational malaria cases, P. falciparum accounted for 34% (102/297).

    “P. vivax, 63% (n = 187); P. falciparum, 34% (n = 102); and both species (mixed malaria), 3.0% (n = 8).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The qPCR reference standard correctly classifies malaria infection and species in pregnant women, placentas, umbilical cord blood, and neonatal blood.

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

    Findingown data

    Among qPCR-positive gestational malaria cases, P. vivax accounted for 63% (187/297).

    “P. vivax, 63% (n = 187); P. falciparum, 34% (n = 102); and both species (mixed malaria), 3.0% (n = 8).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The qPCR reference standard correctly classifies malaria infection and species in pregnant women, placentas, umbilical cord blood, and neonatal blood.

  • May combine two claims.

    Findingown data

    For placental malaria, the thick blood smear specificity and positive predictive value were both 100% (no false positives).

    “Specificity and positive predictive values were both 100% (no FPs).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The qPCR reference standard correctly classifies malaria infection and species in pregnant women, placentas, umbilical cord blood, and neonatal blood.

  • May combine two claims.

    Findingown data

    The frequency of GM was 36%, PM 27%, and CM 2% in neonatal peripheral blood samples and 16.5% in umbilical cord samples.

    “The frequency of GM was 36%, PM 27%, and CM 2% in neonatal peripheral blood samples and 16.5% in umbilical cord samples”
    Quote in the paperNot a substantial claim

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

    Findingown data

    In the study population, 19.1% of patients had febrile symptoms and 31.3% had anemia.

    “In the study population, 19.1% of patients had febrile symptoms and 31.3% had anemia.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    P. vivax caused 63% of cases of gestational malaria (GM), P. falciparum 34%, and mixed malaria 3%.

    “causing 63% of cases of GM (compared to 34% of P. falciparum and 3% of mixed malaria)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In this study, submicroscopic malaria accounted for 45% of all cases of GM, 92% of PM, and 100% of CM.

    “(in this study, 45% of all cases of GM, 92% of PM, and 100% of CM)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For PM, the sensitivity was 8%; in subgroup analyses according to species, symptoms, and history of malaria, it was 1-18%.

    “For PM, the sensitivity was 8%; in subgroup analyses according to species, symptoms, and history of malaria, it was 1–18%.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: qPCR is a valid reference standard for detecting malaria in pregnancy.

  • May combine two claims.

    Findingown data

    For GM, TBS presented satisfactory diagnostic accuracy parameters in pregnant women with a history of malaria (S = 69%; E = 100%, PPV = 100%, NPV = 100%, NPV = 76%; NLR = 0.3; and PPCD = 84).

    “in pregnant women with a history of malaria (S = 69%; E = 100%, PPV = 100%, NPV = 100%, NPV = 76%; NLR = 0.3; and PPCD = 84)”
    Quote in the paperSubstantial claim
    • Rests on an assumption: qPCR is a valid reference standard for detecting malaria in pregnancy.

  • May combine two claims.

    Findingown data

    In GM, classification errors occurred in 0.8% mainly in cases of mixed GM.

    “in GM, classification errors occurred in 0.8% mainly in cases of mixed GM”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    According to a recent review, thick blood smear sensitivity is low and dependent on variables such as the microscopist's experience, the quality of the slides, and the reagents.

    “According to a recent review, although TBS has been the standard for diagnosis globally, its sensitivity is low and is dependent on variables such as the microscopist’s experience, the quality of the slides, and the reagents.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Oyegoke, 2022, Malaria diagnostic methods with the elimination goal in view, Parasitol. Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Despite the thick blood smear's low sensitivity for malaria associated with pregnancy, it remains the gold standard in Colombia because of the factual impossibility of implementing molecular diagnosis in rural areas.

    “Despite the TBS’s low sensitivity for MAP, it remains as the gold standard in Colombia because of the factual impossibility of implementing molecular diagnosis in rural areas (where there are highest number of cases of malaria and MAP in Colombia) [31].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Campos, 2011, Diagnosis of gestational, congenital, and placental malaria in Colombia: Comparison of the efficacy of microscopy, nested polymerase chain reaction, and histopathology, Am. J. Trop. Med. Hyg. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The thick blood smear is not useful for the pre-elimination, elimination, and prevention of reintroduction phases.

    “but not for the following three phases: pre-elimination (rates below 5%, high coverage of a good quality control program in the clinical laboratories and medical services, and enhanced case reporting and surveillance), elimination (absence of cases), and prevention of reintroduction [32].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Oyegoke, 2022, Malaria diagnostic methods with the elimination goal in view, Parasitol. Res. source

      Not checked in the free run.

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

    Premisecitation

    Other studies found moderate sensitivity of the thick blood smear (63.7%, 95% CI 56.1-70.9).

    “in others was moderate (63.7% 95% CI, 56.1–70.9) [28]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Umbers, 2015, 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, Malar. J. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The thick blood smear is useful for the programmatic phase of malaria control.

    “Therefore, TBS is useful for the programmatic phase of malaria control”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Oyegoke, 2022, Malaria diagnostic methods with the elimination goal in view, Parasitol. Res. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The thick blood smear is deficient in asymptomatic gestational malaria, P. falciparum infections, and pregnant women without a history of malaria.

    “It is necessary to conduct surveillance of MAP with molecular methods in in groups where TBS is deficient (asymptomatic GM, P. falciparum, and pregnant women without history of malaria)”
    Quote in the paperSubstantial claim

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

    Premisecitation

    A meta-analysis reported a prevalence of 16.7% for gestational malaria, 11.0% for placental malaria, and 16.2% for congenital malaria.

    “A meta-analysis reported a prevalence of 16.7% (95% confidence interval [CI], 9.0–28.8) for GM, 11.0% (95% CI, 4.1–26.3) PM, and 16.2% (95% CI, 8.2–29.5) CM [13].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Cardona, J., and Carmona, J. (2021). Meta-analysis of the prevalence of malaria associated with pregnancy in Colombia 2000-2020. PLoS ONE, 16. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    WHO guidelines only recommend parasitological diagnosis for symptomatic individuals using light microscopy or rapid diagnostic tests.

    “Therefore, WHO guidelines only recommend parasitological diagnosis for symptomatic individuals using light microscopy or rapid diagnostic tests in order to optimize the economic use of diagnostic resources [1,11].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [1] World Health Organization (2022, December 01). World Malaria Report 2022. Available online: https://www.who.int/publications/i/item/9789240040496.

      Not checked in the free run.

    • cites [11] World Health Organization (2015). Guidelines for Treatment of Malaria.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The Colombian National Institute of Health recommends that pregnant women in endemic areas undergo thick blood smear testing during antenatal check-ups every trimester, even if asymptomatic.

    “the Colombian National Institute of Health (NIH) recommends that pregnant women in endemic areas undergo TBS testing during their antenatal check-ups every trimester, even if they are asymptomatic.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Instituto Nacional de Salud de Colombia (2022, December 01). Manual Para el Diagnóstico de Malaria no Complicada en Puestos de Diagnóstico y Tratamiento, Available online: https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/IA/INS/manual-diagnostico-malaria-no-complicada.pdf.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There is a high frequency of asymptomatic and submicroscopic cases in gestational malaria, placental malaria, and congenital malaria.

    “there is a high frequency of asymptomatic and submicroscopic cases (negative by the TBS and positive by polymerase chain reaction [PCR]) in GM, PM, and CM [13]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Cardona, J., and Carmona, J. (2021). Meta-analysis of the prevalence of malaria associated with pregnancy in Colombia 2000-2020. PLoS ONE, 16. source

      Not checked in the free run.

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

    Premisecitation

    There are reports of high sensitivity of the thick blood smear in febrile pregnant women (94.4%, 95% CI 72.7-99.9).

    “and there are reports of sensitivity high in febrile pregnant women (94.4%, 95% CI, 72.7–99.9) [29].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Kashif, 2013, Reliability of rapid diagnostic test for diagnosing peripheral and placental malaria in an area of unstable malaria transmission in Eastern Sudan, Diagn. Pathol. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The thick blood smear yielded satisfactory results for diagnosing gestational malaria in P. vivax infections, pregnant women with previous malaria, and febrile pregnant women.

    “This study found the TBS yielded satisfactory results in terms of diagnosing GM for P. vivax, pregnant women with previous malaria and febrile.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    In other contexts, satisfactory accuracy parameters have been reported for P. falciparum placental malaria even in low and moderate parasitemia, with sensitivity ranging between 76% and 78%.

    “In other contexts, satisfactory accuracy parameters have been reported for P. falciparum PM even in low (less than 1000 parasites/µL) and moderate (1000–10,000 parasites/µL) parasitemia, with sensitivity ranging between 76% and 78% [30].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Rogerson, 2003, Diagnosis of Plasmodium falciparum malaria at delivery: Comparison of blood film preparation methods and of blood films with histology, J. Clin. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The thick blood smear is not useful for diagnosing placental malaria and congenital malaria.

    “It also showed that the TBS is not useful for diagnosing PM and CM.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The higher proportion of CM cases by P. falciparum would reflect greater virulence, pathogenicity, and the ability to cross the placenta of this species.

    “the higher proportion of CM cases by P. falciparum would reflect greater virulence, pathogenicity, and the ability to cross the placenta of this species [49]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Moxon, 2020, New insights into malaria pathogenesis, Annu. Rev. Pathol. source

      Not checked in the free run.

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

    Interpretationcitation

    The study population's anemia frequency (31.3%) is consistent with the Health Situation Analysis of Colombia 2019, which reported a frequency of anemia of 28%.

    “These findings are consistent with the Health Situation Analysis of Colombia 2019, which reported a frequency of anemia of 28%”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Ministerio de Salud de Colombia (2022, December 01). Análisis de Situación de Salud (ASIS) Colombia, 2019, Available online: https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/VS/ED/PSP/asis-2019-colombia.pdf.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    qPCR was used as the reference test in all cases.

    “qPCR was used as the reference test in all cases.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The qPCR reference standard correctly classifies malaria infection and species in pregnant women, placentas, umbilical cord blood, and neonatal blood.

  • May combine two claims.

    Interpretationcitation

    The frequencies of GM (36%), PM (27%), and CM (2%) in neonatal peripheral blood and 16.5% in umbilical cord samples are higher (except for CM) than those reported in a meta-analysis in the Colombian literature (17%, 11%, and 16%, respectively).

    “which are higher (except for CM) than those reported in a meta-analysis in the Colombian literature, with frequencies of 17%, 11%, and 16%, respectively [13]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Cardona, J., and Carmona, J. (2021). Meta-analysis of the prevalence of malaria associated with pregnancy in Colombia 2000-2020. PLoS ONE, 16. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Submicroscopic cases are not detected or treated, resulting in severe outcomes for the mother and child (anemia and severe malaria) while also perpetuating parasite transmission and disease endemicity.

    “submicroscopic cases are not detected or treated, resulting in severe outcomes for the mother and child (anemia and severe malaria) while also perpetuating parasite transmission and disease endemicity [20,23,24,25,26]”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [20] Gavina, 2018, Clinical outcomes of submicroscopic infections and correlates of protection of VAR2CSA antibodies in a longitudinal study of pregnant women in Colombia, Infect. Immun. source

      Not checked in the free run.

    • cites [23] Buchwald, 2019, Clinical implications of asymptomatic Plasmodium falciparum infections in Malawi, Clin. Infect. Dis.

      Not checked in the free run.

    • cites [24] Nguyen, 2018, The persistence and oscillations of submicroscopic Plasmodium falciparum and Plasmodium vivax infections over time in Vietnam: An open cohort study, Lancet Infect. Dis. source

      Not checked in the free run.

    • cites [25] Chen, I., Clarke, S.E., Gosling, R., Hamainza, B., Killeen, G., Magill, A., O’Meara, W., Price, R.N., and Riley, E.M. (2016). “Asymptomatic” Malaria: A chronic and debilitating infection that should be treated. PLoS Med., 13. source

      Not checked in the free run.

    • cites [26] Lin, 2014, The role of submicroscopic parasitemia in malaria transmission: What is the evidence?, Trends Parasitol. source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    The thick blood smear and qPCR were applied to the same blood samples taken at the same time.

    “the TBS and qPCR were applied to the same blood samples (samples taken at the same time)”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Other authors have estimated that the thick blood smear only detects and controls 20-50% of cases.

    “Other authors have estimated that TBS only detects and controls 20–50% of cases [33,36].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [33] Zheng, 2017, Advances in molecular diagnosis of malaria, Adv. Clin. Chem. source

      Not checked in the free run.

    • cites [36] Cotter, 2013, The changing epidemiology of malaria elimination: New strategies for new challenges, Lancet source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The study evaluated a group of patients representative of those receiving the diagnostic test in routine clinical practice.

    “a group of patients representative of those receiving the diagnostic test in routine clinical practice was evaluated”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The diagnostic tests were processed independently and blindly, without knowing the results of the other test.

    “the diagnostic tests were processed independently and blindly (without knowing the results of the other test)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    PM is a difficult clinical form to diagnose, with several studies demonstrating high variability in the sensitivity and specificity of qPCR and rapid diagnostic tests.

    “PM is a difficult clinical form to diagnose (in fact, this diagnosis is restricted to the research field), with several studies demonstrating high variability in the sensitivity and specificity of qPCR and rapid diagnostic tests.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Campos, 2011, Diagnosis of gestational, congenital, and placental malaria in Colombia: Comparison of the efficacy of microscopy, nested polymerase chain reaction, and histopathology, Am. J. Trop. Med. Hyg. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    In febrile symptomatic women, this research makes no new contributions; rather, it confirms the excellent diagnostic capacity of the TBS in cases of advanced infection or parasitemia levels that cause obvious signs and symptoms.

    “In this last case, this research makes no new contributions; rather, it confirms the excellent diagnostic capacity of the TBS in cases of advanced infection or parasitemia levels that cause obvious signs and symptoms, as indicated by WHO guidelines, the Colombian CPG, and some studies on MAP [1,11,17,29].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [1] World Health Organization (2022, December 01). World Malaria Report 2022. Available online: https://www.who.int/publications/i/item/9789240040496.

      Not checked in the free run.

    • cites [11] World Health Organization (2015). Guidelines for Treatment of Malaria.

      Not checked in the free run.

    • cites [17] Ministerio de Salud y Protección Social de Colombia (2022, December 01). Guía de Práctica Clínica Diagnóstico y Tratamiento de la Malaria, Available online: https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/VS/PP/ET/Guia-atencion-clinica-malaria.pdf.

      Not checked in the free run.

    • cites [29] Kashif, 2013, Reliability of rapid diagnostic test for diagnosing peripheral and placental malaria in an area of unstable malaria transmission in Eastern Sudan, Diagn. Pathol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Histopathology can classify placental tissue into acute active infection, chronic active infection, or past infection based on the inflammatory process, which PCR cannot detect because it does not identify hemozoin.

    “Histopathology can also detect immune cell infiltrates and classify placental tissue into acute active infection (presence of parasites with little or no pigment), chronic active infection (presence of parasites and abundant pigment), or past infection (only presence of pigment) based on the inflammatory process, which PCR cannot detect because it does not identify hemozoin [31].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Campos, 2011, Diagnosis of gestational, congenital, and placental malaria in Colombia: Comparison of the efficacy of microscopy, nested polymerase chain reaction, and histopathology, Am. J. Trop. Med. Hyg. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These parameters are only affected by the disease spectrum, so patients with clearly manifested disease have better outcomes.

    “These parameters are only affected by the disease spectrum, so patients with clearly manifested disease have better outcomes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Eusebi, 2013, Diagnostic accuracy measures, Cerebrovasc. Dis. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Other studies have indicated that the diagnosis of CM is more complicated because it is an infection with low parasitic density in umbilical cord blood or peripheral blood of the newborn.

    “Other studies have indicated that the diagnosis of CM is more complicated because it is an infection with low parasitic density in umbilical cord blood or peripheral blood of the newborn.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Omer, 2020, Congenital malaria in newborns delivered to mothers with malaria-infected placenta in Blue Nile State, Sudan, J. Trop. Pediatr. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Histopathology results depend on the quality of the sample, and formalin pigment can be confused with hemozoin, leading to diagnostic errors.

    “its results depend on the quality of the sample, and the formalin pigment can be confused with hemozoin, leading to diagnostic errors [5,52,53,54]”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [5] Liu, 2016, Diagnosis of placental malaria in poorly fixed and processed placental tissue, Malar. J. source

      Not checked in the free run.

    • cites [52] Fried, 2012, Diagnosing malaria in pregnancy: An update, Expert Rev. Anti-Infect. Ther. source

      Not checked in the free run.

    • cites [53] Takem, 2013, Malaria in pregnancy, Mediterr. J. Hematol. Infect. Dis. source

      Not checked in the free run.

    • cites [54] Romagosa, 2004, Polarisation microscopy increases the sensitivity of hemozoin and Plasmodium detection in the histological assessment of placental malaria, Acta Trop. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Sensitivity and specificity demonstrate the test's ability to detect positives and negatives without being affected by disease prevalence, implying that the results could be easily applied to settings with a different prevalence.

    “sensitivity and specificity demonstrate the test’s ability to detect positives and negatives without being affected by disease prevalence, implying that the results could be easily applied to settings with a different prevalence.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Eusebi, 2013, Diagnostic accuracy measures, Cerebrovasc. Dis. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A study conducted in the same region compared TBS, nested PCR, and histopathology for the diagnosis of MM, discovering a sensitivity of 33% and a specificity of 95% for the TBS, whereas in nested PCR, these parameters were 47% and 77%, respectively, when compared to histopathology.

    “a study conducted in the same region of this research compared the TBS, nested PCR, and histopathology for the diagnosis of MM, discovering a sensitivity of 33% and a specificity of 95% for the TBS, whereas in nested PCR, these parameters were 47% and 77%, respectively, when compared to histopathology [31].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Campos, 2011, Diagnosis of gestational, congenital, and placental malaria in Colombia: Comparison of the efficacy of microscopy, nested polymerase chain reaction, and histopathology, Am. J. Trop. Med. Hyg. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Study design and conductnone given

    It is one of the few studies in the world that presents the thorough diagnostic parameters for clinical and epidemiological programs in a comprehensive manner.

    “It is one of the few studies in the world that presents the thorough diagnostic parameters for clinical and epidemiological programs in a comprehensive manner.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Comprehensive analyses based on parasitemia levels were not conducted.

    “comprehensive analyses based on parasitemia levels were not conducted.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Determination of parasitemia and classification are difficult and far from perfect; inaccurate diagnosis and classification have caused a high mortality rate, especially in children.

    “determination of parasitemia and classification are difficult and far from perfect; inaccurate diagnosis and classification have caused a high mortality rate, especially in children [51,55].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [51] Mayor, 2012, How hidden can malaria be in pregnant women? Diagnosis by microscopy, placental histology, polymerase chain reaction and detection of histidine-rich protein 2 in plasma, Clin Infect. Dis. source

      Not checked in the free run.

    • cites [55] Rehman, 2018, Microscopic malaria parasitemia diagnosis and grading on benchmark datasets, Microsc. Res. Tech. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    This study showed satisfactory results for cases of GM caused by P. vivax and in pregnant women with previous malaria, expanding the evidence in favor of the use of this test in various clinical and epidemiological situations.

    “this study showed satisfactory results for cases of GM caused by P. vivax and in pregnant women with previous malaria, expanding the evidence in favor of the use of this test in various clinical and epidemiological situations”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning

    Evidence was gathered to support the importance of active surveillance of MAP in Colombia, which requires more effort compared to passive detection because health workers must search for patients in the community.

    “Evidence was gathered to support the importance of active surveillance of MAP in Colombia, which requires more effort compared to passive detection because health workers must search for patients in the community.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

    Premisecitation

    CM is a poorly investigated event, and some authors believe that it is a disease with low occurrence, so there are many gaps in the literature.

    “In general, CM is a poorly investigated event, and some authors believe that it is a disease with low occurrence, so there are many gaps in the literature [7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] 2016, Congenital malaria: Importance of diagnosis and treatment in pregnancy, Turk. J. Pediatr. source

      Not checked in the free run.

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

    Premisecitation

    The Colombian Ministry of Health recommendations validate both venipuncture and capillary blood samples.

    “the Colombian Ministry of Health recommendations validate both types of samples [18]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Instituto Nacional de Salud de Colombia (2022, December 01). Manual Para el Diagnóstico de Malaria no Complicada en Puestos de Diagnóstico y Tratamiento, Available online: https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/IA/INS/manual-diagnostico-malaria-no-complicada.pdf.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationcitation

    Tests with better sensitivity, such as molecular techniques, are required for CM.

    “Therefore, tests with better sensitivity, such as molecular techniques, are required [6].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Omer, 2020, Congenital malaria in newborns delivered to mothers with malaria-infected placenta in Blue Nile State, Sudan, J. Trop. Pediatr. source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    It assesses diagnostic ability in key subgroups according to symptoms, malaria history, and causal species and discusses the effect of the interaction of these factors on the accuracy of the TBS.

    “It assesses diagnostic ability in key subgroups according to symptoms, malaria history, and causal species and discusses the effect of the interaction of these factors on the accuracy of the TBS.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    It is Colombia's first study with a large sample size for the mother-placenta-neonate trinomial.

    “It is Colombia’s first study with a large sample size for the mother–placenta–neonate trinomial.”
    Quote in the paperNot a substantial claim
53 of 53

  • The paper relies on this without support.

    The qPCR reference standard correctly classifies malaria infection and species in pregnant women, placentas, umbilical cord blood, and neonatal blood.

    “qPCR was used as a reference standard for diagnostic evaluation.”
    “qPCR was used as the reference test in all cases.”

  • The paper relies on this without support.

    The non-probabilistic sampling and the fact that most samples were not from the same subjects do not bias the independent estimates of gestational, placental, and congenital malaria.

    “In most cases the samples obtained were not from the same subjects (pregnant woman, placenta, umbilical cord and neonate), therefore the results of GM, PM and CM are analyzed independently.”

  • The paper relies on this without support.

    The clinical history variables (febrile state, hemoglobin, and previous diagnosis of malaria) accurately reflect the patients’ status.

    “The following variables were extracted from the clinical history: febrile state, hemoglobin, and previous diagnosis of malaria (in the last year and in the current pregnancy).”

  • The paper relies on this without support.

    TBS is commonly used in Colombia.

    “This represents the population in Colombia, where the TBS is commonly used.”

  • The paper relies on this without support.

    The study population represents the population in Colombia.

    “This represents the population in Colombia, where the TBS is commonly used.”

  • The paper relies on this without support.

    qPCR is a valid reference standard for detecting malaria in pregnancy.

    “In terms of qPCR, one of its limitations is its inability to determine the viability of the microorganism because it only detects genetic material and does not identify individuals with the ability to transmit the agent and cause new infections.”

  • The authors state this as an assumption.

    The possibility of detecting asymptomatic carriage of malaria is low in the case of the molecular diagnosis of MAP.

    “it can be assumed that the possibility of detecting asymptomatic carriage of malaria is low in the case of the molecular diagnosis of MAP.”
7 of 7

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?

  • The absence of congenital malaria in India may be due to effective control measures or underreporting associated with diagnostic limitations.

    “while the absence of congenital malaria in India may be due to effective control measures or underreporting associated with diagnostic limitations [191–193].”

    From Current update on malaria in pregnancy: a systematic review (2025) · cites this paper as [191]

    Section 4.3 (page unavailable) reports that thick blood smears detected no congenital malaria cases and explains why low parasite density can make diagnosis difficult; this supports diagnostic limitations as a possible source of missed cases. The paper studies Colombia and does not address an absence of congenital malaria in India or attribute it to effective control measures. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • High prevalence rates of malaria occur in regions such as Niger and Sudan.

    “High prevalence rates in regions such as Niger and Sudan underscore.the need for improved maternal screening and preventive measures”

    From Current update on malaria in pregnancy: a systematic review (2025) · cites this paper as [191]

    The Results report malaria test positivity among pregnant women studied in Colombia, not prevalence in Niger or Sudan. A References entry names a diagnostic study in Eastern Sudan but gives no prevalence figure; a search for Niger and Sudan found no passage establishing high prevalence in either country. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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.

  • Febrile subgroup has conflicting negative predictive values

    Minor

    The results give a negative predictive value of 91% for febrile symptomatic women, whereas the discussion gives 92% for that subgroup.

  • Two negative predictive values reported for women with a history of malaria

    Minor

    The same summary of results for pregnant women with a history of malaria reports negative predictive values of both 100% and 76%.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. 2014, Malaria and pregnancy: Complications, prevention and treatment, Prog. Obstet. Ginecol., 57, 468
  2. Malaria Policy Advisory Group World Health Organization (2017). Meeting Report of the Evidence Review Group on Malaria in Pregnancy, Geneva, Switzerland, 9–11 July 2017, World Health Organization.
  3. Guerra, 2020, Concordance analysis of three diagnostic tests for malaria in the symptomatic population of Colombian endemic municipalities, Biomedica, 40, 117
  4. Carmona, 2017, La Región “Urabá Antioqueño-Cuencas altas de los ríos Sinú y San Jorge-Bajo Cauca Antioqueño”: “guarida” del paludismo colombiano Revista de la Universidad Industrial de Santander, Salud, 49, 577

Cited by

Sorted by citations

Related

Authors
Cardona-Arias, J. A., Higuita Gutiérrez, L. F., & Carmona-Fonseca, J.
Affiliations
  • Escuela de Microbiología, Universidad de Antioquia, Medellín 050010, Colombia
  • Grupo Salud y Comunidad César Uribe Piedrahíta, Facultad de Medicina, Universidad de Antioquia, Medellín 050010, Colombia
ORCID
Venue
Tropical Medicine and Infectious Disease
Publisher
MDPI AG
Published
2023-02-14
Volume
8
Issue
2
Pages
119
ISSN
2414-6366 (ISSN-L)
DOI
10.3390/tropicalmed8020119
PMC
PMC9959527
OpenAlex
W4320919970
Semantic Scholar
7b1d215da45265b88043605c164963e46eb48ffb
Cited by
6
References
48
Citations by year
2025: 3 · 2024: 3
FWCI
1.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Tropical Medicine and Infectious Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
University of Antioquia (INV3161)
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 › Parasitic Infections and Diagnostics
Keywords
malaria in pregnancy, placental malaria, congenital malaria, Plasmodium falciparum, Plasmodium vivax, thick blood smear, qPCR, diagnostic accuracy, sensitivity and specificity, umbilical cord blood, Colombia

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.

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