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Iron Supplements Actually Benefit Children With HIV
A new study found that iron supplements are safe for children with HIV in Uganda, as they improve hemoglobin levels without increasing malaria risk.
Uganda HIV © Adam Ján Figeľ - stock.Adobe.Com
Iron supplements are safe for kids with HIV living in Uganda, according to new research by the University of Minnesota Medical School published in the November issue of The Lancet HIV. The iron supplements also did not increase malaria infection rates, disproving previews concerns that they did.
Hemoglobin is the protein in red blood cells responsible for transporting oxygen throughout the body. Iron improves hemoglobin concentration in the blood, therefore reducing the risk of anemia. If left unchecked, anemia can lead to heart problems, a weakened immune system and organ failure. If someone is already HIV-positive, anemia adds to the burden.
Children 6 to 59 months of age are considered anemic of their values fall below 11 g/dL and children 5 to 11 years are old are considered anemic if their values fall below 11.5 g/dL.
Iron deficiency is the most common nutritional deficiency in the world, the current study reads. In addition, about 39.7% of HIV-positive children 15 and younger are iron deficient. Despite this, some pediatricians don't prescribe iron supplements, partly due to fears of increased malaria infection risk raised by the results of a study published in 2013.
However, the children who contracted malaria during that study were not sleeping under insecticide treated bed nets and only a third of total participants were on antiretroviral therapy (ART).
For the current study, which took place from May 2018 to November 2019, researchers enrolled 200 HIV-positive children who were on ART for at least six months, taking co-trimoxazole prophylaxis and sleeping under insecticide treated bed nets. The participants, between 6 months old and 12 years old, received either iron supplements or placebo for three months. Supplement dosage was dependent on age and given at home after a meal, preferably in the evening. Children 6–23 months old received tablets of 12.5 mg of ferrous sulphate and children 24 months and older were given 30 mg of ferrous sulphate.
At day 0, mean baseline of hemoglobin for both the placebo and treatment group was 11.5 g/dL. At the end of the study, the iron supplement group had hemoglobin values of 12.0 g/dL and the placebo group had values of 11.7 g/dL.
"Our findings support the WHO recommendation that iron supplements can be given to children living with HIV and moderate anemia who are taking ART, taking co-trimoxazole prophylaxis, and sleeping under insecticide-treated bed nets," co-author Anne Frosch, M.D., M.P.H., infectious disease expert at Hennepin Healthcare Research Institute in Minneapolis, Minnesota. "Future studies should assess neurodevelopmental outcomes and infectious risks, including malaria, in children living with HIV taking iron supplements."
Maternal Antibodies Interfere With Malaria Vaccine Efficacy In Infants
Maternal antibodies passed across the placenta can hinder the efficacy of malaria vaccines in infants under five months, suggesting adjustments to vaccination timing. According to research led by the Barcelona Institute for Global Health (ISGlobal) in partnership with seven African centers, maternal antibodies transferred through the placenta can hinder the effectiveness of the malaria vaccine, explaining its reduced efficacy in infants under five months. Published in Lancet Infectious Diseases, the findings suggest that children younger than the current WHO recommendations might benefit from the RTS, S and R21 malaria vaccines in regions with low malaria transmission, where maternal antibody levels against the parasite are lower (1✔ ✔Trusted SourceThe effect of Plasmodium falciparum exposure and maternal anti-circumsporozoite protein antibodies on responses to RTS,S/AS01E vaccination in infants and children: an ancillary observational immunological study to a phase 3, randomised clinical trialGo to source). 'Did You Know?Malaria is a major global public health issue; it is endemic in over 80 countries and causes around 250 million infections and 600,000 deaths annually worldwide. #medindia #malaria #publichealth'
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Milestone in Malaria Prevention The world has achieved a significant milestone with the introduction of the first two malaria vaccines—RTS, S/AS01E and the newer R21/Matrix-M—designed to protect African children from malaria caused by Plasmodium falciparum. Both vaccines target a segment of the parasite protein known as circumsporozoite (CSP) and are currently recommended for children aged 5 months and older at the time of their first dose.Advertisement
Utilizing Protein Microarrays for Antibody Measurement "We know that the RTS, S/AS01E malaria vaccine is less effective in infants under five months of age, but the reason for this difference is still debated," says Carlota Dobaño, who leads the Malaria Immunology group at ISGlobal, a center supported by "la Caixa" Foundation.To investigate this, Dobaño and her team analyzed blood samples from more than 600 children (age 5-17 months) and infants (age 6-12 weeks) who participated in the phase 3 clinical trial of RTS, S/AS01E. Using protein microarrays, they measured antibodies against 1,000 P. Falciparum antigens before vaccination to determine if and how malaria exposure and age affected IgG antibody responses to the malaria vaccine.
"This microarray approach allowed us to accurately measure malaria exposure at the individual level, including maternal exposure for infants and past infections for older children," says Didac Maciá, ISGlobal researcher and first author of the study.
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Vaccine Responses in Infants with Varying Maternal Antibody Levels The analysis of antibodies to P. Falciparum in children who had received a control vaccine instead of RTS, S/AS01E revealed a typical "exposure" signature, with high levels in the first three months of life due to the passive transfer of maternal antibodies through the placenta, a decline during the first year of life, and then a gradual increase as a result of naturally acquired infections.In children vaccinated with RTS,S/AS01E, antibodies induced by natural infections did not affect the vaccine response. However, in infants, high levels of antibodies to P. Falciparum, presumably passed from their mothers during pregnancy, correlated with reduced vaccine responses. This effect was particularly strong for maternal anti-CSP antibodies targeting the central region of the protein. Conversely, infants with very low or undetectable maternal anti-CSP IgGs exhibited similar vaccine responses as those observed in children.
The molecular mechanisms underlying this interference by maternal antibodies are not fully understood, but the same phenomenon has been observed with other vaccines such as measles.
Impact of Malaria Transmission on Vaccine Effectiveness Overall, these findings confirm something that was already suspected but not clearly demonstrated: despite their protective function, maternal anti-CSP antibodies, which decline within the first three to six months of life, may interfere with vaccine effectiveness. The higher the level of malaria transmission, the more maternal antibodies are transmitted to the baby, resulting in lower vaccine effectiveness. These findings further suggest that infants below five months of age may benefit from RTS, S or R21 vaccination in low malaria transmission settings, during outbreaks in malaria-free regions, or in populations migrating from low to high transmission settings."Our study highlights the need to consider timing and maternal malaria antibody levels to improve vaccine efficacy for the youngest and most vulnerable infants," says Gemma Moncunill, ISGlobal researcher and co-senior author of the study, together with Dobaño.
Reference:
Maternal Antibodies Disrupt Infants' Responses To Malaria Vaccines
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Maternal antibodies passed across the placenta can interfere with the response to the malaria vaccine, which would explain its lower efficacy in infants under five months of age, according to research led by the Barcelona Institute for Global Health (ISGlobal), in collaboration with seven African centers (CISM-Mozambique, IHI-Tanzania, CRUN-Burkina Faso, KHRC-Ghana, NNIMR-Ghana, CERMEL-Gabon, KEMRI-Kenya). The findings, published in Lancet Infectious Diseases, suggest that children younger than currently recommended by the WHO may benefit from the RTS,S and R21 malaria vaccines if they live in areas with low malaria transmission, where mothers have less antibodies to the parasite.
The world has reached an incredible milestone: the deployment of the first two malaria vaccines -RTS,S/AS01E and the more recent R21/Matrix-M- to protect African children against malaria caused by Plasmodium falciparum. Both vaccines target a portion of the parasite protein called circumsporozoite (CSP) and are recommended for children aged 5 months or more at the moment of the first dose.
"We know that the RTS,S/AS01E malaria vaccine is less effective in infants under five months of age, but the reason for this difference is still debated," says Carlota Dobaño, who leads the Malaria Immunology group at ISGlobal, a centre supported by "la Caixa" Foundation.
To investigate this, Dobaño and her team analysed blood samples from more than 600 children (age 5-17 months) and infants (age 6-12 weeks) who participated in the phase 3 clinical trial of RTS,S/AS01E. Using protein microarrays, they measured antibodies against 1,000 P. Falciparum antigens before vaccination to determine if and how malaria exposure and age affected IgG antibody responses to the malaria vaccine.
"This microarray approach allowed us to accurately measure malaria exposure at the individual level, including maternal exposure for infants and past infections for older children," says Didac Maciá, ISGlobal researcher and first author of the study.
The role of maternal antibodiesThe analysis of antibodies to P. Falciparum in children who had received a control vaccine instead of RTS,S/AS01E revealed a typical "exposure" signature, with high levels in the first three months of life due to the passive transfer of maternal antibodies through the placenta, a decline during the first year of life, and then a gradual increase as a result of naturally acquired infections.
In children vaccinated with RTS,S/AS01E, antibodies induced by natural infections did not affect the vaccine response. However, in infants, high levels of antibodies to P. Falciparum, presumably passed from their mothers during pregnancy, correlated with reduced vaccine responses. This effect was particularly strong for maternal anti-CSP antibodies targeting the central region of the protein. Conversely, infants with very low or undetectable maternal anti-CSP IgGs exhibited similar vaccine responses as those observed in children.
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Subscribe for FREE The molecular mechanisms underlying this interference by maternal antibodies are not fully understood, but the same phenomenon has been observed with other vaccines such as measles.Overall, these findings confirm something that was already suspected but not clearly demonstrated: despite their protective function, maternal anti-CSP antibodies, which decline within the first three to six months of life, may interfere with vaccine effectiveness. The higher the level of malaria transmission, the more maternal antibodies are transmitted to the baby, resulting in lower vaccine effectiveness. These findings further suggest that infants below five months of age may benefit from RTS,S or R21 vaccination in low malaria transmission settings, during outbreaks in malaria-free regions, or in populations migrating from low to high transmission settings.
"Our study highlights the need to consider timing and maternal malaria antibody levels to improve vaccine efficacy for the youngest and most vulnerable infants," says Gemma Moncunill, ISGlobal researcher and co-senior author of the study, together with Dobaño.
Reference: Macià D, Campo JJ, Jairoce C, et al. The effect of Plasmodium falciparum exposure and maternal anti-circumsporozoite protein antibodies on responses to RTS,S/AS01E vaccination in infants and children: an ancillary observational immunological study to a phase 3, randomised clinical trial. Lancet Infect Dis. 2024. Doi: 10.1016/S1473-3099(24)00527-9
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