Impact of IgG response to malaria-specific antigens and immunity against malaria in pre-school children in Ghana. A cluster randomized, placebo-controlled trial (original) (raw)

Nutrient Deficiencies and Potential Alteration in Plasma Levels of Naturally Acquired Malaria-Specific Antibody Responses in Tanzanian Children

Frontiers, 2022

Immunoglobulin G (IgG) subclasses have been suggested to confer naturally acquired immunity to Plasmodium falciparum malaria. Cytophilic IgG1 and IgG3 with their potential for opsonization, phagocytosis, and antibody-dependent cellular inhibition in association with monocytes have been suggested to have a critical role in malaria. The potential for production of antibodies is influenced by micronutrient status. This study aimed at exploring the effect of micronutrients, particularly zinc status, on the profiles of IgG subclasses in 304 Tanzanian children aged ≤ 5 years. An enzyme-linked immunosorbent assay was performed using whole asexual blood stage malaria antigens to determine plasma malaria-specific antibody titers. This baseline cross-sectional study was done from 2005-2010 prior to the larger randomized control trial of the Micronutrient and Child Health (MACH) Study. Plasma concentrations of zinc and magnesium were measured by inductively coupled plasma atomic emission spectrometry and results correlated with plasma IgG subclass levels. The findings reveal zinc deficiency to possibly influence the production of IgM, total IgG, and several IgG subclasses in a malaria status-dependent manner. Among IgG subclasses, IgG3 and partly IgG2 displayed a remarkable association with zinc deficiency, particularly IgG3 which was predominant in children with malaria. Nevertheless, zinc, magnesium, and malaria status did not influence the association between IgG3 and IgG4. The study leads to the conclusion that, under conditions of micronutrient deficiency and malaria status, an imbalance in IgG subclass production may occur leading to predominantly higher levels of IgG3 and IgG2 that may not confer sufficient protection from infection. The profile of both cytophilic and non-cytophilic IgG subclasses has been shown to be variably influenced by zinc status; the effects vary with age at least in under-fives. These results provide insight for inclusion of micronutrients, particularly precise amounts of zinc, in future malaria interventional programs in endemic areas.

Effect of IgG3 Hinge Region Length Polymorphisms on Iron Fortification among Rural Pre-School Ghanaian Children and Its Associated Risk to Malaria and Anaemia

2021

Sub-Saharan African pre-school children have an interdependence among immune response, infection resistance and adaptive effect of the dietary intake. However, the long hinge region of immunoglobulin G3 makes binding easy to malaria antigens and receptors, eliciting a more protective response among subclasses of immunoglobulin G. However, it is unknown if iron-containing multimicronutrients are associated with risk of anaemia and malaria in pre-school children with hinge region G3 immunoglobulin polymorphism living in high malaria transmission areas. We aimed to determine the impact of iron fortification in pre-school children with immunoglobulin G3 hinge region length polymorphisms and their associated risk of malaria and anaemia in rural Ghana. This retrospective controlled, double blind, randomized population study was conducted over six months in rural Ghana among 6 to 35-month-old infants and young children. Participants were randomly allocated either ironfree multimicronutrien...

Effect of Iron Fortification on Anaemia and risk of Malaria among Ghanaian Pre-School Children with Haemoglobinopathies and different ABO blood groups

BackgroundHaemoglobinopathies such as sickle cell and glucose-6-phosphate dehydrogenase (G6PD) deficiency as well as differences in ABO blood group have been shown to influence the risk of malaria and/or anaemia in malaria-endemic areas. This study assessed how iron fortification in addition to weaning meals affects anaemia and the risk of malaria in Ghanaian pre-school children with haemoglobinopathies and different ABO blood groups.MethodsThis study was a double-blind, randomly clustered trial, conducted within six months among infants and young children aged 6 to 35 months in rural Ghana (775 clusters, n = 860). Participants were randomly selected into clusters to receive daily semi-liquid home-prepared meals mixed with either micronutrient powder without iron (non-iron group) or with iron (iron group; 12.5 mg of iron daily) for 5 months. Malaria infection was detected by microscopy, blood haemoglobin (Hb) level was measured with HemoCue Hb analyzer, the reversed ABO blood groupi...

Iron deficiency is associated with reduced levels of Plasmodium falciparum-specific antibodies in African children

Clinical Infectious Diseases

Background Iron deficiency (ID) and malaria are common causes of ill-health and disability among children living in sub-Saharan Africa. Although iron is critical for the acquisition of humoral immunity, little is known about the effects of ID on antibody responses to Plasmodium falciparum malaria. Methods The study included 1,794 Kenyan and Ugandan children aged 0-7 years. We measured biomarkers of iron and inflammation, and antibodies to P falciparum antigens including apical merozoite antigen 1 (anti-AMA-1) and merozoite surface antigen 1 (anti-MSP-1) in cross-sectional and longitudinal studies. Results The overall prevalence of ID was 31%. ID was associated with lower anti-AMA-1 and anti-MSP-1 antibody levels in pooled analyses adjusted for age, gender, study site, inflammation and P falciparum parasitemia (adjusted mean difference on a log-transformed scale (β) -0.46; 95 CI -0.66, -0.25 P <0.0001; β -0.33; 95 CI -0.50, -0.16 P <0.0001, respectively). Additional covariates ...

Iron Status and Associated Malaria Risk Among African Children

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2018

It remains unclear whether improving iron status increases malaria risk, and few studies have looked at the effect of host iron status on subsequent malaria infection. We therefore aimed to determine whether a child's iron status influences their subsequent risk of malaria infection in sub-Saharan Africa. We assayed iron and inflammatory biomarkers from community-based cohorts of 1309 Kenyan and 1374 Ugandan children aged 0 - 7 years and conducted prospective surveillance for episodes of malaria. Poisson regression models were fitted to determine the effect of iron status on the incidence rate ratio of malaria using longitudinal data covering a period of 6 months. Models were adjusted for age, sex, parasitemia, inflammation and study site. At baseline, the prevalence of iron deficiency (ID) was 36.9% and 34.6% in Kenyan and Ugandan children, respectively. Iron deficiency anemia (IDA) affected 23.6% of Kenyan and 17.6% of Ugandan children. Malaria risk was lower in children with ...

Decline in childhood iron deficiency after interruption of malaria transmission in highland Kenya

The American journal of clinical nutrition, 2014

Achieving optimal iron status in children in malaria-endemic areas may increase the risk of malaria. Malaria itself may contribute to iron deficiency, but the impact of an interruption in malaria transmission on the prevalence of iron deficiency is unknown. We aimed to determine whether 1) iron status improved in children living in 2 Kenyan villages with a documented cessation in malaria transmission and 2) changes in iron status correlated with changes in hemoglobin. We measured iron [hemoglobin, ferritin, soluble transferrin receptor (sTfR)] and inflammatory [C-reactive protein (CRP)] markers in paired plasma samples from 190 children aged 4-59 mo at the beginning (May 2007) and end (July 2008) of a documented 12-mo period of interruption in malaria transmission in 2 highland areas in Kenya with unstable malaria transmission and ongoing malaria surveillance. Between May 2007 and July 2008, mean (±SD) hemoglobin increased from 10.8 ± 1.6 to 11.6 ± 1.6 g/dL. Median (25th, 75th perce...