What is the burden of submicroscopic malaria in pregnancy in central India?
Open accessAbstract
BACKGROUND: Conventional microscopy underestimates the burden of malarial infection when compared with molecular diagnosis using polymerase chain reaction (PCR)-based methods. Lower density parasitemias serve as a reservoir for infection. We evaluated the prevalence of submicroscopic infections in an area of unstable malarial transmission in India and determined whether these infections negatively impacted maternal or fetal outcomes. METHODS: This cross-sectional study (2007-2008) was undertaken in two districts of Chhattisgarh, recruiting women from both antenatal clinics (ANCs) and delivery units (DUs). For ANC/DU subjects, peripheral/placental blood, respectively, was obtained for conventional microscopy and collected onto filter paper for PCR analysis. RESULTS: There were 3425 pregnant women, including 2477 ANC subjects and 948 DU subjects who had both microscopic and PCR samples available. Polymerase chain reaction detected significantly more Plasmodium infections than traditional light microscopy both from peripheral (3·4 vs 1·2%; OR 2·9, 95% confidence intervals (CIs) 1·9-4·5) and placental (4·2 vs 1·7%; OR 2·5, 95% CIs 1·4-4·8) blood samples. Submicroscopic infections were not associated with anemia or severe maternal anemia among ANC or DU participants and were not associated with low birth weight (LBW) among DU participants. In contrast, microscopically detected infections were associated with severe anemia and LBW. CONCLUSIONS: In this area of unstable malarial transmission from India, submicroscopic infections did not identify a set of pregnant women at increased risk for anemia or LBW. Until PCR techniques become much less expensive and available as a point of care test for the field setting, its use will be limited for malarial detection.
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TL;DR
In this cross-sectional study in Chhattisgarh, India, PCR detected more Plasmodium infections than microscopy in pregnant women, and about two-thirds of peripheral and placental infections were submicroscopic. Submicroscopic infections were not associated with anemia or low birth weight, whereas microscopically detected infections were.
Key findings
Among 3425 pregnant women with both microscopy and PCR results (2477 antenatal clinic [ANC] and 948 delivery unit [DU] subjects), PCR detected more infections than microscopy: peripheral blood 3.4% vs 1.2% (OR 2.9, 95% CI 1.9–4.5) and placental blood 4.2% vs 1.7% (OR 2.5, 95% CI 1.4–4.8).
- Submicroscopic infections accounted for 59/89 peripheral infections (66.3%, 95% CI 55.9–75.3) and 29/45 placental infections (64.4%, 95% CI 49.8–76.8). Peripheral P. vivax infections were more often submicroscopic than P. falciparum infections (38/42, 90.5% vs 26/52, 50.0%; P<0.001); placental samples showed no significant species difference (64.7% vs 66.7%, P=0.90).
- Submicroscopic infections were not associated with anemia or severe anemia among ANC or DU participants and were not associated with low birth weight (LBW) among DU participants. In contrast, microscopically detected infections were associated with severe anemia (peripheral: 30.0% vs 3.0%; OR 13.7, 95% CI 5.3–32.5) and LBW (placental: 75.0% vs 34.0%; OR 5.8, 95% CI 1.4–33.7).
- All PCR-detected infections combined (microscopic plus submicroscopic) were associated with severe anemia (OR 3.7, 95% CI 1.6–7.8), but with a smaller effect size than microscopy alone; PCR-detected infections were not associated with LBW.
Methods
Cross-sectional study conducted June 2007–May 2008 in Rajnandgaon and Bastar districts, Chhattisgarh, central India; pregnant women aged ≥15 years were recruited from ANCs and DUs as two distinct cohorts and were not followed longitudinally.
- Peripheral blood was collected from ANC subjects; peripheral and placental blood were collected from DU subjects. Samples underwent Giemsa microscopy and filter-paper PCR using species-specific nested PCR targeting the 18s rRNA gene; hemoglobin, birth weight, and Ballard gestational age were also assessed.
- Analysis used Stata/IC 8.2 with percentages and 95% CIs, chi-square or Fisher’s exact tests, odds ratios, univariate logistic regression, and ANOVA; adjusted analyses were not performed.
Limitations
The paper states that this was a cross-sectional facility-based study rather than a prospective longitudinal study; there were no matched peripheral and placental samples; microscopy was limited to 100 fields per WHO standards; low parasitemia prevalence and rare outcomes limited power; almost one quarter of DU infections were P. vivax, which is less strongly linked with adverse pregnancy outcomes; and placental histology was not collected.
- The paper also notes that PCR was performed only on peripheral blood from ANC subjects and placental blood from DU participants, so peripheral and placental PCR could not be compared within the same women. PCR missed 10 microscopy-positive infections (5 peripheral, 5 placental), possibly because filter-paper samples had little blood and failed to amplify.
- Evident from the text: adjusted analyses were not performed, so the reported associations are unadjusted.
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Claims the paper makes
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- Findingown data§ Prevalence of microscopic and submicroscopic parasitemia
Women who did not sleep under a bednet on most nights had a higher likelihood of microscopically detected peripheral infection (P=0.014).
“Peripheral and placental infections among women who did not sleep under a bednet on most nights were more likely to have a microscopic infection, although reaching significance only for the peripheral infections ( P 5 0.014).”
Quote in the paperNot a substantial claim - Findingown data§ Prevalence of microscopic and submicroscopic parasitemia
PCR detected significantly more Plasmodium infections than traditional light microscopy from placental blood samples (4.2% vs 1.7%; OR 2.5, 95% CI 1.4-4.8).
“Similarly, the odds of detecting parasitemia by PCR were over two-fold higher than microscopy for placental samples (4.2 vs 1.7%, OR 2.5; 95% CIs 1.4-4.8).”
Quote in the paperSubstantial claim - Findingown data§ Conclusion
PCR does not appear to identify a group of women at risk for adverse maternal or infant outcome.
“do not appear to identify a group of women at risk for adverse maternal or infant outcome”
Quote in the paperSubstantial claim - Findingown data§ Birth outcomes
Having a malarial infection detected by either microscopy or PCR did not significantly increase the odds for stillbirth.
“Having a malarial infection detected by either microscopy or PCR did not significantly increase the odds for stillbirth”
Quote in the paperSubstantial claim - Findingown data§ Birth outcomes
Women with microscopically detected placental infections were more likely to deliver a low birth weight infant (OR 5.8, 95% CI 1.4-33.7) compared to women with negative smears.
“Women with microscopically detected placental infections were more likely to deliver a LBW infant (OR 5.8, 95% CIs 1.4-33.7) compared to women with negative smears.”
Quote in the paperSubstantial claim
- Findingown data§ Prevalence of microscopic and submicroscopic parasitemia
PCR did not detect 10 of the microscopically detected infections (5 peripheral, 5 placental).
“Notably, PCR did not detect 10 of the microscopically detected infections. Five of these missed infections were from peripheral samples (5.6% of peripheral infections), and the remaining five of the infections missed by PCR were from placental samples (11.1% of placental infections).”
Quote in the paperNot a substantial claim - Findingown data§ Anemia
All infections detected by PCR, including both microscopic and submicroscopic infections, were associated with an increase in the odds for severe anemia (OR 3.7; 95% CI 1.6-7.8).
“All infections detected by PCR, including both microscopic and submicroscopic infections were also associated with an increase in the odds for severe anemia (OR 3.7; 95% CIs 1.6-7.8).”
Quote in the paperSubstantial claim - Findingown data§ Discussion
Almost one quarter of the infections among DU participants in this setting was caused by P. vivax.
“almost one quarter of the infections among DU participants in this setting was caused by P. vivax”
Quote in the paperSubstantial claim - Findingown data§ Anemia
Microscopically detected placental infections were associated with an increased risk for severe maternal anemia.
“Microscopically detected placental infections were associated with an increased risk for severe maternal anemia as were PCRdetected infections (Table 3).”
Quote in the paperSubstantial claim - Findingown data§ Prevalence of microscopic and submicroscopic parasitemia
Parity did not alter the risk for submicroscopic peripheral or placental infections.
“In our cohort, neither maternal age nor parity altered the risk for submicroscopic peripheral or placental infections (Supplementary Material 1 http://dx.doi.org/10.1179/ 2047773215Y.0000000002.s1).”
Quote in the paperNot a substantial claim - Findingown data§ Birth outcomes
Mothers with positive placental microscopy delivered infants that were on average 310 g lighter than women without microscopically detected infections (P = 0.004).
“mothers with positive placental microscopy delivered infants that were 310 g lighter than women without microscopically detected infections ( P 5 0.004).”
Quote in the paperSubstantial claim - Findingown data§ Prevalence of microscopic and submicroscopic parasitemia
Among placental samples, there was no significant difference in submicroscopic infections by Plasmodium species (64.7% P. falciparum vs 66.7% P. vivax, P=0.90).
“In contrast, there was not a significant difference in submicroscopic infections by Plasmodium species among placental samples (64.7% P. falciparum vs 66.7% P. vivax , P 5 0.90).”
Quote in the paperNot a substantial claim - Findingown data§ What is the burden of submicroscopic malaria in pregnancy in central India?
Submicroscopic infections were not associated with severe maternal anemia among ANC or DU participants.
“Submicroscopic infections were not associated with anemia or severe maternal anemia among ANC or DU participants and were not associated with low birth weight (LBW) among DU participants.”
Quote in the paperSubstantial claim - Findingown data§ Anemia
Mean hemoglobin levels among women with microscopically detected infections (8.3 ± 2.4 g/dl) were significantly lower than those among women without malaria or with submicroscopic infections (P = 0.0002 by analysis of variance).
“These levels were significantly higher than the mean hemoglobin among women with microscopically detected infections (8.3 6 2.4 g/dl, P 5 0.0002 by analysis of variance).”
Quote in the paperSubstantial claim - Findingown data§ Discussion
Maternal characteristics such as age and parity did not alter the proportion of submicroscopic infections in the analysis.
“Maternal characteristics such as age and parity did not alter the proportion of submicroscopic infections in our analysis.”
Quote in the paperNot a substantial claim - Findingown data§ Birth outcomes
No association was found between PCR-detected placental infections and low birth weight.
“In contrast, no association was found between PCRdetected infections and LBW.”
Quote in the paperSubstantial claim - Findingown data§ Prevalence of microscopic and submicroscopic parasitemia
Among placental samples, 29 of 45 infections (64.4%; 95% CI 49.8-76.8) were submicroscopic.
“The proportion of submicroscopic placental infections was similar to 29 of 45 placental infections undetected by microscopy (64.4%; 95% CIs 49.8-76.8).”
Quote in the paperSubstantial claim - Findingown data§ Anemia
In pregnant women in central India, PCR detected a higher prevalence of placental malaria parasitemia than light microscopy (40/948, 4.2% vs 16/948, 1.7%; OR 2.5, 95% CI 1.4-4.8).
“PCR | 30 (3.2) | 2.6 (1.3-5.6) | 9 (1.0) | 2.5 (0.7-10.8) | 40 c (4.2) | 2.5 (1.4-4.8)”
Quote in the paperSubstantial claim - Findingown data§ Conclusion
In this South Asian setting of lower malarial transmission, PCR is a more sensitive method than microscopy for detecting malarial infections in pregnant women.
“This study confirms, in a South Asian setting of lower malarial transmission, that PCR is a more sensitive method than microscopy in detecting malarial infections in pregnant women.”
Quote in the paperSubstantial claim - Findingown data§ What is the burden of submicroscopic malaria in pregnancy in central India?
Microscopically detected infections were associated with low birth weight.
“In contrast, microscopically detected infections were associated with severe anemia and LBW.”
Quote in the paperSubstantial claim - Findingown data§ Anemia
Women with microscopically detected infections had significantly lower mean hemoglobin (8.0 ± 2.3 g/dl) than women without detectable parasites, P<0.0001.
“Women with microscopically detected infections had significantly lower hemoglobin on average (8.0 6 2.3 g/dl, P , 0.0001 by analysis of variance).”
Quote in the paperSubstantial claim - Findingown data§ Anemia
Women without any evidence of malaria by microscopy or PCR and those with submicroscopic infections had similar mean hemoglobin levels (10.1 ± 1.6 and 9.9 ± 2.1 g/dl, respectively).
“As with ANC subjects, women without any evidence of malaria by microscopy or PCR and those with submicroscopic infections had similar mean hemoglobin levels (10.1 6 1.6 and 9.9 6 2.1 g/dl, respectively).”
Quote in the paperSubstantial claim - Findingown data§ Anemia
Women with submicroscopic infections (PCR positive, slide negative) were not more likely to be severely anemic compared with women who had negative results by both PCR and microscopy (1.7% vs 3.1%).
“Women with submicroscopic infections (PCR positive, slide negative) were not more likely to be severely anemic when compared with women who had negative results by both PCR and microscopy (1.7 vs 3.1%).”
Quote in the paperSubstantial claim - Findingown data§ What is the burden of submicroscopic malaria in pregnancy in central India?
Microscopically detected infections were associated with severe anemia.
“In contrast, microscopically detected infections were associated with severe anemia and LBW.”
Quote in the paperSubstantial claim - Findingown data§ Birth outcomes
Average birth weights of infants born to women with submicroscopic infections were not significantly different from women without parasitemia by PCR or microscopy (2656.7 g vs 2576.0 g, P = 0.31).
“Furthermore, the average birth weights of infants born to women with submicroscopic infections were not significantly different than women without parasitemia by PCR or microscopy (2656.7 g vs 2576.0 g, P 5 0.31).”
Quote in the paperSubstantial claim - Findingown data§ What is the burden of submicroscopic malaria in pregnancy in central India?
Submicroscopic infections were not associated with low birth weight among DU participants.
“Submicroscopic infections were not associated with anemia or severe maternal anemia among ANC or DU participants and were not associated with low birth weight (LBW) among DU participants.”
Quote in the paperSubstantial claim - Findingown data§ Birth outcomes
Submicroscopic placental infections were not associated with an increase in the risk for low birth weight.
“Submicroscopic placental infections were also not associated with an increase in the risk for LBW.”
Quote in the paperSubstantial claim - Findingown data§ Prevalence of microscopic and submicroscopic parasitemia
Women whose homes had not been sprayed with insecticide during governmental indoor residual spraying campaigns were more likely to have a microscopically detected placental infection (P=0.004).
“Women whose homes had not been sprayed with insecticide during governmental indoor residual spraying campaigns were more likely to have a microscopically detected placental ( P 5 0.004), but not peripheral ( P 5 0.476) malarial infection.”
Quote in the paperNot a substantial claim - Findingown data§ Anemia
The odds of severe anemia were much higher among women with microscopically detected peripheral malarial infections compared to women without parasites visible on peripheral smear (30.0% vs 3.0%; OR 13.7, 95% CI 5.3-32.5).
“The odds of severe anemia were much higher among women with microscopically detected peripheral malarial infections compared to women without parasites visible on peripheral smear (30.0 vs 3.0%; OR 13.7, 95% CIs 5.3-32.5) (Table 3).”
Quote in the paperSubstantial claim - Findingown data§ Discussion
The association of malaria prevention measures with submicroscopic infections was inconsistent in the data.
“The association of malaria prevention measures with submicroscopic infections was inconsistent in our data.”
Quote in the paperNot a substantial claim - Findingown data§ What is the burden of submicroscopic malaria in pregnancy in central India?
Submicroscopic infections were not associated with anemia among ANC or DU participants.
“Submicroscopic infections were not associated with anemia or severe maternal anemia among ANC or DU participants and were not associated with low birth weight (LBW) among DU participants.”
Quote in the paperSubstantial claim - Findingown data§ Birth outcomes
Preterm birth was not more common among women infected with malaria detected either by microscopy or PCR.
“Preterm birth was also not more common among women infected with malaria detected either by microscopy or PCR.”
Quote in the paperNot a substantial claim - Findingown data§ Anemia
Submicroscopic placental infections did not confer an increased risk of severe maternal anemia.
“Again, submicroscopic placental infections did not confer an increased risk of severe anemia.”
Quote in the paperSubstantial claim - Findingown data§ Prevalence of microscopic and submicroscopic parasitemia
Among antenatal peripheral blood samples, 59 of 89 infections (66.3%; 95% CI 55.9-75.3) were submicroscopic.
“Among antenatal peripheral blood samples, 59 of 89 infections (66.3%; 95% CIs 55.9-75.3) were submicroscopic.”
Quote in the paperSubstantial claim - Findingown data§ Prevalence of microscopic and submicroscopic parasitemia
The increased detection of parasitemia by PCR compared with microscopy was evident for both P. falciparum and P. vivax in both peripheral and placental samples.
“The increased detection was evident for both P. falciparum and P. vivax in both peripheral and placental samples.”
Quote in the paperSubstantial claim - Findingown data§ Prevalence of microscopic and submicroscopic parasitemia
Maternal age did not alter the risk for submicroscopic peripheral or placental infections.
“In our cohort, neither maternal age nor parity altered the risk for submicroscopic peripheral or placental infections (Supplementary Material 1 http://dx.doi.org/10.1179/ 2047773215Y.0000000002.s1).”
Quote in the paperNot a substantial claim - Findingown data§ Prevalence of microscopic and submicroscopic parasitemia
Lack of indoor residual spraying was not associated with microscopically detected peripheral infection (P=0.476).
“Women whose homes had not been sprayed with insecticide during governmental indoor residual spraying campaigns were more likely to have a microscopically detected placental ( P 5 0.004), but not peripheral ( P 5 0.476) malarial infection.”
Quote in the paperNot a substantial claim - Findingown data§ Prevalence of microscopic and submicroscopic parasitemia
PCR detected significantly more Plasmodium infections than traditional light microscopy from peripheral blood samples (3.4% vs 1.2%; OR 2.9, 95% CI 1.9-4.5).
“The overall prevalence of parasitemia from peripheral blood samples obtained during antenatal care was 3.4% by PCRcompared with 1.2% by microscopy (OR 2.9; 95% CIs 1.9-4.5).”
Quote in the paperSubstantial claim - Findingown data§ Anemia
The effect size for severe maternal anemia was higher for microscopically detected placental infections than for PCR-identified infections.
“Similar to ANC results, the effect size was higher for microscopically detected infections compared with PCR-identified infections.”
Quote in the paperNot a substantial claim - Findingown data§ Anemia
Among ANC subjects, mean hemoglobin was similar in women without any detectable parasites by either microscopy or PCR (10.3 ± 1.5 g/dl) and in those with submicroscopic infections (10.1 ± 1.3 g/dl).
“Among ANC subjects, the mean hemoglobin was similar in women without any detectable parasites by either microscopy or PCR (10.3 6 1.5 g/dl) and in those with submicroscopic infections (10.1 6 1.3 g/ dl).”
Quote in the paperSubstantial claim - Findingown data§ Birth outcomes
PCR-detected placental infections were associated with an increased risk for severe maternal anemia.
“Positive | 32/40 (80.0%) | 1.4 (0.6-3.5) | 5/32 (15.6%) | 5.3 (1.5-15.9)”
Quote in the paperSubstantial claim - Findingown data§ Anemia
There was no association between peripheral parasitemia and a less severe anemia (Hgb <11 g/dl) whether the parasites were detected by microscopy, PCR, or both.
“There was no association between peripheral parasitemia and a less severe anemia (Hgb , 11 g/dl) whether the parasites were detected by microscopy, PCR, or both.”
Quote in the paperSubstantial claim - Premisecitation§ Introduction
Studies in Africa have consistently shown that conventional microscopy vastly underestimates infection compared to PCR in both peripheral and placental blood samples.
“These studies have consistently shown that conventional microscopy vastly underestimates infection compared to PCR in both peripheral and placental blood samples. 12-22”
Quote in the paperSubstantial claim0 of 10 sources checked- cites [12] Mockenhaupt FP, 2000, Trop Med Int Health. source
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- cites [13] Saute F, 2002, Trop Med Int Health. source
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- cites [14] Mayengue PI, 2004, Trop Med Int Health. source
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- cites [15] Walker-Abbey A, 2005, Am J Trop Med Hyg. source
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- cites [16] Adegnika AA, 2006, Am J Trop Med Hyg. source
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- cites [17] Mayor A, 2009, Malar J. source
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- cites [18] Mockenhaupt FP, 2002, J Clinical Microbiol. source
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- cites [19] Omer S, 2011, N Am J Med Sci. source
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- cites [20] Mayor A, 2012, Clin Infect Dis. source
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- cites [21] Cohee LM, 2014, Malar J. source
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- Premisecitation§ Introduction
Neither study that evaluated preterm birth found an increased risk associated with submicroscopic infection.
“Neither study that evaluated preterm birth found an increased risk associated with submicroscopic infection. 21,23”
Quote in the paperNot a substantial claim0 of 2 sources checked - Study design and conductown data§ Birth outcomes
The study was underpowered to assess stillbirth as an outcome given its rarity in the study population.
“however, the study was underpowered to assess this outcome given its rarity in our study population.”
Quote in the paperSubstantial claim - Interpretationown data§ Anemia
The effect size for severe anemia was appreciably lower when considering all PCR-detected infections than when considering microscopic infections only.
“This effect size was appreciably lower than when considering microscopic infections only.”
Quote in the paperSubstantial claim - Study design and conductown data§ Discussion
The ability to entirely exclude adverse maternal or fetal outcomes associated with submicroscopic infections was limited by both the low prevalence of parasitemia and the rarity of some outcomes.
“our ability to entirely exclude this possibility was limited by both the low prevalence of parasitemia and the rarity of some outcomes.”
Quote in the paperSubstantial claim - Interpretationown data§ What is the burden of submicroscopic malaria in pregnancy in central India?
In this area of unstable malarial transmission from India, submicroscopic infections did not identify a set of pregnant women at increased risk for anemia or LBW.
“In this area of unstable malarial transmission from India, submicroscopic infections did not identify a set of pregnant women at increased risk for anemia or LBW.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Discussion
The diminished effect size for all PCR-detected infections likely reflects the ability of PCR to detect both higher density infections, which would be identified by microscopy, and lower density infections.
“This likely reflects the ability of PCR to detect both higher density infections, which would be identified by microscopy, and lower density infections.”
Quote in the paperSubstantial claim - Study design and conductown data§ Discussion
The study lacked matched peripheral and placental samples.
“Further, we lacked matched peripheral and placental samples”
Quote in the paperNot a substantial claim - Interpretationreasoning§ Discussion
Any association between preventive measures and a reduced risk of microscopic infections may reflect underlying sociodemographics rather than protection against malaria itself.
“therefore, any association between preventive measures and a reduced risk of microscopic infections may reflect the underlying sociodemographics rather than protection against malaria itself.”
Quote in the paperNot a substantial claim
- May combine two claims. 19
- The quote only partly states this claim. 1
- Classified as probably not a substantial claim. 27
May combine two claims.
Findingown data§ DiscussionThe majority of malarial infections in pregnant women in this study were submicroscopic: 66.3% of peripheral infections and 64.4% of placental infections.
“Indeed, the majority of infections was submicroscopic (66.3% of peripheral and 64.4% of placental infections)”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ Prevalence of microscopic and submicroscopic parasitemiaWomen who did not sleep under a bednet on most nights had a higher likelihood of microscopically detected placental infection, but this was not statistically significant.
“Peripheral and placental infections among women who did not sleep under a bednet on most nights were more likely to have a microscopic infection, although reaching significance only for the peripheral infections ( P 5 0.014).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data§ Prevalence of microscopic and submicroscopic parasitemiaIn ANC samples, the proportion of submicroscopic infections was over 90% for P. vivax (38/42; 90.5%) compared to 50.0% for P. falciparum (26/52; P<0.001 comparing species).
“In ANC samples, the proportion of submicroscopic infections was over 90% for P. vivax (38/42; 90.5%) compared to only half of the P. falciparum infections (26/52; 50.0%; P , 0.001 comparing species).”
Quote in the paperSubstantial claimMay combine two claims.
Findingreasoning§ DiscussionWhen evaluating all PCR-detected infections including both microscopic and submicroscopic infections, parasitemia was associated with severe maternal anemia and low birth weight, but the effect size was diminished compared with microscopic infections considered alone.
“When evaluating all PCR-detected infections including both microscopic and submicroscopic infections, parasitemia was associated with severe maternal anemia and LBW but the effect size was diminished compared with microscopic infections considered alone.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ Birth outcomesThe prevalence of low birth weight among women with positive PCR samples (36.4%) was similar to those with negative PCR samples (34.9%) and with negative microscopy (34.0%) and much lower than women with positive microscopy (75.0%).
“Notably, the prevalence of LBW among women with positive PCR samples (36.4%) was similar to those with negative PCR samples (34.9%) and with negative microscopy (34.0%) and much lower than women with positive microscopy (75.0%).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ AnemiaNeither positive microscopy nor positive PCR from placental samples was associated with a lesser degree of anemia (Hgb < 11 g/dl).
“Neither positive microscopy nor positive PCR from placental samples was associated with a lesser degree of anemia (Hgb , 11 g/dl).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ DiscussionMicroscopically detected infections were associated with both severe anemia and low birth weight.
“This differs from the microscopically detected infections, which were associated with both severe anemia and LBW.”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown data§ AnemiaIn pregnant women in central India, PCR detected a higher prevalence of peripheral malaria parasitemia than light microscopy (84/2477, 3.4% vs 30/2477, 1.2%; OR 2.9, 95% CI 1.9-4.5).
“PCR | 45 (1.8) | 1.7 (1.0-2.8) | 40 (1.6) | 8.1 (3.2-26.3) | 84 b (3.4) | 2.9 (1.9-4.5)”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ DiscussionSubmicroscopic malarial infections in pregnant women in this study were not associated with maternal anemia of any degree or with low birth weight.
“we did not identify an association between submicroscopic infections and either maternal anemia of any degree or LBW.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Premisecitation§ IntroductionData are conflicting about the impact of submicroscopic infections on LBW; some studies suggest increased risk and others no association.
“Similarly, the data are conflicting about the impact of submicroscopic infections on LBW; some studies suggest an increased risk 16,24 in the setting of submicroscopic infections and others no association. 20-23”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [16] Adegnika AA, 2006, Am J Trop Med Hyg. source
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- cites [24] Mohammed AH, 2013, Malar J. source
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- cites [20] Mayor A, 2012, Clin Infect Dis. source
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- cites [21] Cohee LM, 2014, Malar J. source
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- cites [22] Rantala AM, 2010, Malar J. source
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- cites [23] Mockenhaupt FP, 2006, Malar J. source
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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ IntroductionSubmicroscopic infections were linked with maternal anemia in some studies but not all.
“Submicroscopic infections were linked with maternal anemia in some 17,18,20,23 but not all 12,13,15,21 studies.”
Quote in the paperNot a substantial claim0 of 8 sources checked- cites [17] Mayor A, 2009, Malar J. source
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- cites [18] Mockenhaupt FP, 2002, J Clinical Microbiol. source
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- cites [20] Mayor A, 2012, Clin Infect Dis. source
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- cites [23] Mockenhaupt FP, 2006, Malar J. source
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- cites [12] Mockenhaupt FP, 2000, Trop Med Int Health. source
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- cites [13] Saute F, 2002, Trop Med Int Health. source
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- cites [15] Walker-Abbey A, 2005, Am J Trop Med Hyg. source
Not checked in the free run.
- cites [21] Cohee LM, 2014, Malar J. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionIn one study from Northwest Colombia, 79% of all infections at delivery were submicroscopic.
“In one study from Northwest Colombia where both P. falciparum and Plasmodium vivax are present, 79% of all infections at the time of delivery were submicroscopic. 25”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [25] Arango EM, 2013, Am J Trop Med Hyg. source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
Premisecitation§ IntroductionLow-density parasitemias serve as a reservoir for continued transmission of malaria and may contribute to negative health.
“These low-density parasitemias serve as a reservoir for continued transmission of the disease and may contribute to negative health. 9-11”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionIn that Northwest Colombia study, submicroscopic infections were associated with placental villitis and intervillitis.
“Notably, these submicroscopic infections were associated with placental villitis and intervillitis, inflammatory lesions in the placenta that may contribute to poor birth outcomes.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [25] Arango EM, 2013, Am J Trop Med Hyg. source
Not checked in the free run.
May combine two claims.
Premisecitation§ IntroductionA seasoned microscopist can discern parasitemias only above approximately 100 parasites per microliter, whereas PCR can detect 1 parasite per microliter or less.
“A seasoned microscopist is only able to discern parasitemias above a density of approximately 100 parasites per microliter 6,7 compared with PCR where detection can occur at 1 parasite per microliter or less. 8”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [6] World Health Organization, 1988, Bull World Health Organ.
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- cites [7] Dowling MA, 1966, Bull World Health Organ.
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- cites [8] Kamau E, 2013, PLoS One source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionBetween low and high transmission extremes, there is an inverse relationship between the proportion of submicroscopic infections and transmission intensity (by PCR prevalence).
“Between these two extremes, there was an inverse relationship between the proportion of submicroscopic infections and the transmission intensity (by PCR prevalence).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [5] Okell LC, 2009, J Infect Dis. source
Not checked in the free run.
May combine two claims.
Premisecitation§ IntroductionThe proportion of malarial infections that are submicroscopic is higher in areas of low transmission; a meta-analysis reported 88% undetected by microscopy in low-transmission areas compared to 25.5% in high-transmission areas.
“A meta-analysis of surveys conducted in endemic areas reported that 88% of all infections went undetected by microscopy in areas of low transmission compared to only 25.5% in areas of high transmission. 5”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] Okell LC, 2009, J Infect Dis. source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductnone given§ DiscussionThe study was cross-sectional facility based rather than prospective longitudinal.
“First, this was a cross-sectional facility based study rather than a prospective longitudinal study.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone given§ DiscussionTissue sections were not collected for histology in the study.
“However, tissue sections were not collected for histology in our study.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone given§ Data management and analysisAdjusted analyses were not performed.
“Adjusted analyses were not performed.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitation§ DiscussionMicroscopic readings for initial detection of parasitemia were limited to 100 microscopic fields as per WHO standards.
“Microscopic readings for initial detection of parasitemia were limited to 100 microscopic fields as per World Health Organization standards for microscopic diagnosis of malaria. 31”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [31] World Health Organization. Parasitological confirmation of malaria diagnosis; 2009. Available from: http://whqlibdoc.who.int/publications/2010/9789241599412_eng.pdf (accessed 2013 August 16).
Not checked in the free run.
May combine two claims.
Premisecitation§ DiscussionThe DNA detected by PCR may be from a viable asexual parasite, a gametocyte, or represent nonviable DNA from past infections following treatment.
“The DNA detected by PCR may be from a viable asexual parasite, a gametocyte, or represent nonviable DNA from past infections following treatment. 35”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [35] Kain KC, 1994, J Infect Dis. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ DiscussionMicroscopy visualizes viable whole parasites in erythrocytes, while PCR detects parasite DNA.
“Microscopy visualizes viable whole parasites in erythrocytes, while PCR detects parasite DNA. 34”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [34] Singer LM, 2004, Am J Trop Med Hyg. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Interpretationreasoning§ DiscussionPCR techniques are unlikely to identify past infections that occurred remote from delivery given the clearance of nonviable DNA.
“Furthermore, PCR techniques are unlikely to identify past infections that occurred remote from delivery given the clearance of nonviable DNA.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone given§ Laboratory proceduresAn experienced microscopist blinded to PCR results and clinical history examined the blood films.
“An experienced microscopist who was blinded to the PCR results and clinical history of the subject examined the blood films.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Interpretationreasoning§ DiscussionThe detection of recent past infections may account for why the submicroscopic infections are not associated with concurrent anemia or severe anemia in the subjects.
“This detection of recent past infections may account for why the submicroscopic infections are not associated with concurrent anemia or severe anemia in our subjects”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoning§ Laboratory proceduresBecause of limited resources, PCR was performed only on peripheral blood samples from ANC subjects and placental blood samples from DU participants.
“Because of limited resources, we performed only PCR on peripheral blood samples from ANC subjects and placental blood samples from DU participants.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationreasoning§ DiscussionMore likely, submicroscopic infections reflect lower density parasitemias, which may not be as strongly linked with anemia in a population with a fairly high degree of anemia at baseline.
“More likely, submicroscopic infections reflect lower density parasitemias, which may not be as strongly linked with anemia in a population with a fairly high degree of anemia at baseline.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone given§ Data management and analysisResults of PCR and microscopy were recorded on separate forms; after double data entry, the database was rechecked for inconsistent entries and errors corrected.
“Results of the PCR and microscopy examination were recorded on separate forms. After double data entry, the database was rechecked for inconsistent entries and errors were corrected.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown data§ ResultsPeripheral dried blood spots for PCR were available for comparison with peripheral microscopy for 2477 of 2696 women recruited from ANC.
“Peripheral dried blood spots for PCR were available for comparison with peripheral microscopy for 2477 of the 2696 women recruited from the ANC.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone given§ Laboratory proceduresAll smears were rechecked by a member of the parasitology laboratory at NIMR Field Station in Jabalpur.
“All smears were rechecked by a member of the parasitology laboratory at the National Institute of Malaria Research (NIMR) Field Station in Jabalpur.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Interpretationown data§ Prevalence of microscopic and submicroscopic parasitemiaThe DNA extracted from filter paper samples that PCR missed had little blood and failed to amplify, which may have contributed to the observed results.
“The DNA extracted from these filter paper samples had little blood in them and failed to amplify; this may have contributed to the observed results.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone given§ Species-specific nested PCRAn independent research assistant unaware of participant's clinical status or microscopy results performed PCR on coded samples.
“An independent research assistant unaware of the participant's clinical status or the microscopy results performed the PCR on coded samples.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown data§ ResultsPlacental dried blood spots for PCR were available for comparison with placental blood microscopy/impression smears in 948 of 1030 women recruited from DUs.
“Placental dried blood spots for PCR were available for comparison with placental blood microscopy/impression smears in 948 of the 1030 women recruited from DUs.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Interpretationreasoning§ DiscussionThe sensitivity of microscopy for detecting parasitemia might have been slightly higher if 200 or more fields had been read in the thick blood films for initial identification of positive specimens.
“The sensitivity of microscopy for detecting parasitemia might have been slightly higher if 200 or more fields had been read in the thick blood films for initial identification of positive specimens.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone given§ Laboratory proceduresA portable Hemocue machine was used for hemoglobin estimation with the manufacturers' internal quality control before each assay.
“A portable Hemocue machine (A ¨ ngelholm, Sweden) was used for hemoglobin estimation using the manufacturers' internal quality control before each assay.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone given§ DiscussionThe use of malaria prevention measures may have been less in more impoverished women.
“The use of these measures may have been less in more impoverished women;”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown data§ Species-specific nested PCRAll negative slides that tested PCR positive and all positive slides that were PCR negative were reexamined by another expert technician blinded to microscopy, PCR, and clinical status.
“All negative slides that tested PCR positive and all positive slides that were PCR negative were reexamined by another expert technician blinded to the results of microscopy, PCR, and clinical status of the participants.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone given§ DiscussionRecruitment of an unselected population of pregnant women receiving antenatal care or at the time of delivery rather than women with symptoms of malaria was a strength of the study.
“Recruitment of an unselected population of pregnant women receiving antenatal care or at the time of delivery rather than women with symptoms of malaria was a strength of this study.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown data§ Data management and analysisPeripheral blood smear results from DU participants were not considered in this analysis because no PCR results were available for comparison.
“Peripheral blood smear results from DU participants were not considered in this analysis, as no PCR results were available for comparison.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
Limited information on the epidemiology of submicroscopic malarial infections during pregnancy is available from areas outside Africa where levels of malarial transmission are much lower.
“Limited information on the epidemiology of submicroscopic malarial infections during pregnancy is available from areas outside of Africa where levels of malarial transmission are much lower.”
The paper relies on this without support.
The clinical relevance of submicroscopic malarial infections in pregnancy has not been evaluated from the Asia-Pacific region.
“The clinical relevance of submicroscopic malarial infections in pregnancy has not been evaluated from the Asia-Pacific region where malaria prevalence is much lower than sub-Saharan Africa. 26”
The paper relies on this without support.
PCR techniques are expensive and labor intensive, require sophisticated equipment and personnel.
“since PCR techniques are expensive and labor intensive, require sophisticated equipment and personnel”
The paper relies on this without support.
P. vivax infections are less strongly linked with adverse pregnancy outcomes than P. falciparum.
“which are less strongly linked with adverse pregnancy outcomes”
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?
P. falciparum and P. vivax SMIs at delivery were associated with poor outcomes in one study from Papua New Guinea but not in studies conducted in Colombia and India.
“P. falciparum and P. vivax SMIs at delivery were associated with poor outcomes in one study from Papua New Guinea (PNG) (27) but not in studies conducted in Colombia and India (10,28).”
From Clinical outcomes of submicroscopic infections and correlates of protection of VAR2CSA antibodies in a longitudinal study of pregnant women in Colombia (2018) · cites this paper as [28]
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Flagged first, then by citations
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Burden, pathology, and costs of malaria in pregnancy: new developments for an old problem
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- Authors
- Singh, N., Bharti, P. K., Singh, M. P., Singh, R., Yeboah-Antwi, K., Desai, M., Udhayakumar, V., Muniyandi, M., Hamer, D. H., & Wylie, B. J.
- Affiliations
- National Institute for Research in Tribal Health (IN)
- National Institute of Malaria Research (IN)
- Centers for Disease Control and Prevention (US)
- Boston University (US)
- Harvard University (US)
- Corresponding author
- Singh, Neeru
- ORCID
- Venue
- Pathogens and Global Health
- Publisher
- Informa UK Limited
- Published
- 2015-01-28
- Volume
- 109
- Issue
- 1
- Pages
- 30-38
- ISSN
- 2047-7724 (ISSN-L)
- 2047-7732
- PMC
- PMC4445293
- OpenAlex
- W1994840465
- Semantic Scholar
- 18721770590924add8088eb3115821db403d5390
- Cited by
- 25
- References
- 32
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 4 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 1 · 2015: 1
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pathogens and Global Health (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Indian Council of Medical Research
- National Institutes of Health
- National Institute of Environmental Health Sciences (K23ES021471)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R03HD052167, 1 R03 HD52167-01)
- 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 › Pediatrics, Perinatology and Child Health › Global Maternal and Child Health
- Keywords
- submicroscopic malaria infection, malaria in pregnancy, Plasmodium, PCR diagnosis, conventional microscopy, placental malaria, anemia in pregnancy, low birth weight, unstable malaria transmission, Chhattisgarh, prenatal care
- MeSH terms
- Adolescent, Adult, Blood, Cross-Sectional Studies, Female, Humans, India, Infant, Newborn, Malaria, Microscopy, Pregnancy, Pregnancy Complications, Infectious, Prevalence, Polymerase Chain Reaction, Parasitemia, Young Adult
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.
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