Malaria causes long-term effects on markers of iron status in children: a critical assessment of existing clinical and epidemiological tools

Castberg, Filip C.; Sarbah, Edem W.; Koram, Kwadwo A.; Opoku, Nicholas; Ofori, Michael F.; Styrishave, Bjarne; Hviid, Lars; Kurtzhals, Jørgen A. L.

doi:10.1186/s12936-018-2609-6

Cited by 12 publications

(18 citation statements)

References 46 publications

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“…Although serum ferritin was also measured, we did not use this biomarker for defining iron status in this study because of the clear absence of correlation of this biomarker and anaemia in our study population. This finding was in accordance with findings from other teams showing that serum ferritin is less accurate in assessing ID in Malawian children even after adjustment for inflammation as malaria infection may lead to long lasting ferritin elevation [42, 100]. The second limitation is the absence of screening for malaria and any inherited disorders known to influence the markers of iron status or the biological regulation of iron homeostasis [16, 101–103].…”

Section: Discussionsupporting

confidence: 86%

Soya, maize and sorghum ready-to-use therapeutic foods are more effective in correcting anaemia and iron deficiency than the standard ready-to-use therapeutic food: randomized controlled trial

Akomo¹,

Bahwere

Murakami

et al. 2019

BMC Public Health

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Background The prevalence of anaemia and iron deficiency (ID) among children with severe acute malnutrition (SAM) and their correction during nutritional rehabilitation are not well documented. This study assessed anaemia and ID prevalence and their predictors at start of SAM treatment, and the efficacy of their treatment and effect on gut health of two novel Ready-To-Use Therapeutic foods (RUTF) prepared from soybean, maize and sorghum (SMS) with (MSMS-RUTF) or without added milk (FSMS-RUTF) compared to those of the standard formulation prepared from peanut and milk (PM-RUTF). Methods This was a 3-arms parallel groups, simple randomised, controlled non-inferiority trial in 6–59 months old Central Malawian children with SAM. Anaemia was defined using altitude- and ethnicity-adjusted haemoglobin. Iron status was defined using soluble transferrin receptor (sT f R) and body iron stores (BIS). We used Pearson’s chi-square test, t-test for paired or unpaired data, Kruskal-Wallis test for between-arm differences as appropriate and logistic regression to identify independent predictors of anaemia or iron deficiency anaemia (IDA). Results The sample size was 389. At admission, the prevalence [%(95%CI)] of anaemia was 48.9(41.4–56.5)% while that of ID and IDA were 55.7(48.6–62.5)% and 34.3(28.2–41.0)% when using sT f R criterion and 29.1(24.4–34.4)% and 28.9(23.7–34.9)% when using BIS criterion, respectively. At discharge, nutrition rehabilitation with SMS-RUTF was associated with the lowest prevalence of anaemia [12.0(6.9–20.3)% for FSMS-RUTF, 18.2(11.9–26.8)% for MSMS-RUTF and 24.5(15.8–35.9)% for PM-RUTF; p = 0.023] and IDA [7.9(3.4–17.3)% for FSMS-RUTF, 10.9(4.8–22.6)% for MSMS-RUTF and 20.5(10.7–35.5)% for PM-RUTF; p = 0.028]. SMS-RUTF was also associated with the highest increase in BIS [Change in BIS (95%CI)] among the iron deplete at admission [6.2 (3.7; 8.6), 3.2 (0.8; 5.6), 2.2 (0.2; 4.3) for the same study arms; Anova p = 0.045]. Compared to P-RUTF, FSMS-RUTF had the highest adjusted recovery rate [OR (95%CI = 0.3 (0.2–0.5) with p < 0.001 for FSMS-RUTF and 0.6 (0.3–1.0) with p = 0.068 for MSMS-RUTF]. No effect of iron content on risk of iron overload or gut inflammation was observed. Conclusions Anaemia and ID are common among children with SAM. FSMS-RUTF is more efficacious in treating anaemia and correcting BIS among this group than PM-RUTF. Trial registration This study was registered on 15 April 2015 ( PACTR201505001101224 ). Electronic supplementary material The online version of this article (10.1186/s12889-019-7170-x) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 86%

Soya, maize and sorghum ready-to-use therapeutic foods are more effective in correcting anaemia and iron deficiency than the standard ready-to-use therapeutic food: randomized controlled trial

Akomo¹,

Bahwere

Murakami

et al. 2019

BMC Public Health

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“…Samples from children (aged 1-12) were collected from Hohoe, Ghana, an area of high P . falciparum malaria transmission intensity, from May – August 2015, as described previously [ 47 , 48 ].…”

Section: Methodsmentioning

confidence: 99%

“…Study participants were enrolled on admission at Hohoe municipal hospital (Febrile children) or from within the Hohoe and Asutsauare communities after engagement with community/opinion leaders. This was followed by a durbar in the community to explain the study in the local language to the residents [ 48 ]. Subjects were recruited after informed written consent had been obtained; in the case of children, from a parent or legal guardian.…”

Section: Methodsmentioning

confidence: 99%

Acquisition and decay of IgM and IgG responses to merozoite antigens after Plasmodium falciparum malaria in Ghanaian children

et al. 2020

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Developing a vaccine against Plasmodium falciparum malaria has been challenging, primarily due to high levels of antigen polymorphism and a complex parasite lifecycle. Immunization with the P. falciparum merozoite antigens PfMSRP5, PfSERA9, PfRAMA, PfCyRPA and PfRH5 has been shown to give rise to growth inhibitory and synergistic antisera. Therefore, these five merozoite proteins are considered to be promising candidates for a second-generation multivalent malaria vaccine. Nevertheless, little is known about IgG and IgM responses to these antigens in populations that are naturally exposed to P. falciparum. In this study, serum samples from clinically immune adults and malaria exposed children from Ghana were studied to compare levels of IgG and IgM specific for PfMSRP5, PfSERA9, PfRAMA, PfCyRPA and PfRH5. All five antigens were found to be specifically recognized by both IgM and IgG in serum from clinically immune adults and from children with malaria. Longitudinal analysis of the latter group showed an early, transient IgM response that was followed by IgG, which peaked 14 days after the initial diagnosis. IgG levels and parasitemia did not correlate, whereas parasitemia was weakly positively correlated with IgM levels. These findings show that IgG and IgM specific for merozoite antigens PfMSRP5, PfSERA9, PfRAMA, PfCyRPA and PfRH5 are high in children during P. falciparum malaria, but that the IgM induction and decline occurs earlier in infection than that of IgG.

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“…Another method, the BRINDA regression correction (RC) approach, developed by the BRINDA project, does not rely on the CRP cut-off ≤5 mg/L (Namaste et al 2017). Nonetheless, Castberg et al (2018) have shown that in a malaria endemic setting the respective values of CRP and AGP came down to below the ≤5mg/L and ≤1g/L (i.e., healthy concentrations) two weeks earlier than that of ferritin which remained elevated at a substantial level. This suggests that the RC method, based on an assumption of linear regression between CRP/AGP and ferritin, may not be sufficient to fully compensate for the effect of malaria/inflammation on ferritin.…”

Section: Introductionmentioning

confidence: 95%

An alternative approach to adjust the iron status for inflammation in population: an exploratory study

Rahman

Shaheen²

2021

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Background: Iron deficiency (ID), one of the major micronutrient deficiencies globally, is challenging to measure. This is due to the dual character of ferritin which measures both the ID and concurrently affected by inflammation and infection. To address this, inflammation biomarkers—e.g., CRP (C-Reactive Protein) and AGP (Alpha-1- Acetylated Glycoprotein) are used through various standard methods to report inflammation-adjusted ID. However, there are problems with these methods and their underlying principles. An exploratory study was conducted to suggest an alternative way for inflammation adjustment with the focus on changing the inflammation-cut off point of the biomarker. Methods: Data of the Bangladesh National Micronutrient Survey 2011-12 were used in three population groups—preschool age children (6-59 month), school age children (6-14 years) and non-pregnant non-lactating women of reproductive age. Spearman Rank correlation was used between the iron status markers (ferritin, hemoglobin) vs. the inflammation biomarkers (CRP; AGP) at various cut-off levels of the inflammation markers, e.g., all-values, ≤ 5 mg/L, ≤1 mg/L, and ≤0.35 mg/L. ID was estimated over specified ranges of percentiles of the inflammation biomarker. Results: Spearman Rank correlation between CRP and ferritin showed statistically significant coefficients at various cut-offs of CRP, except at CRP≤1 mg/L in preschool children and at CRP≤0.35 mg/L in school age children. The decrease in ferritin concentration was 6.7%-11.1% across the studied populations between the inflammation-unadjusted concentration and at CRP≤1 mg/L. Generally, the prevalence of ID was higher at CRP≤1 mg/L than at CRP> 1 mg/L. These findings suggested that a single inflammation biomarker, CRP with a cut-off of >1 mg/L excluded the corresponding cases of inflammation-elevated ferritin, allowing for a simpler estimation of the inflammation-adjusted ID in this setting. Conclusion: Usage of CRP with the cut-off ≤1 mg/L is a useful, simplified and economic way to report the inflammation-adjusted ferritin-based ID in Bangladesh and similar settings with a modest infection burden. The method needs assessment in areas where the infection-burden is higher or in settings where malaria is endemic.

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Malaria causes long-term effects on markers of iron status in children: a critical assessment of existing clinical and epidemiological tools

Cited by 12 publications

References 46 publications

Soya, maize and sorghum ready-to-use therapeutic foods are more effective in correcting anaemia and iron deficiency than the standard ready-to-use therapeutic food: randomized controlled trial

Soya, maize and sorghum ready-to-use therapeutic foods are more effective in correcting anaemia and iron deficiency than the standard ready-to-use therapeutic food: randomized controlled trial

Acquisition and decay of IgM and IgG responses to merozoite antigens after Plasmodium falciparum malaria in Ghanaian children

An alternative approach to adjust the iron status for inflammation in population: an exploratory study

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