Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants

Menéndez, Clara; Kahigwa, Elizeus; Hirt, R.; Vounatsou, Penelope; Aponte, John J.; Font, F.; Acosta, Camilo J.; Schellenberg, David; Galindo, Claudia; Kimario, John; Urassa, Honorathy; Brabin, Bernard; Smith, T.; Kitua, Andrew Y; Tanner, Marcel; Alonso, Pedro L.

doi:10.1016/s0140-6736(97)04229-3

Cited by 316 publications

(257 citation statements)

References 29 publications

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“…Iron supplements had no impact on the incidence of infections. This result is in agreement with several studies showing no effect of oral iron on diarrhea and respiratory illness (Heresi et al, 1995;Mitra et al, 1997) or on malaria susceptibility (Harvey et al, 1989;McGregor, 1982;Boele van Hensbroeck et al, 1995;Menedez et al, 1997). Malaria, plasmodium density, and frequency of children with high parasitemia and incidence of fever episodes decreased in the same way in both groups throughout the study.…”

Section: Discussionsupporting

confidence: 92%

Effect of daily iron supplementation on iron status, cell-mediated immunity, and incidence of infections in 6–36 month old Togolese children

Berger

Dyck²,

Galán³

et al. 2000

Eur J Clin Nutr

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Objective: To assess the impact of a daily oral iron supplementation on hematological status, cell-mediated immunity and susceptibility to infections in children living in an environment where iron de®ciency, malaria and other infections are frequent. Design: Randomized, double-blind iron supplementation including a placebo group. Setting: A village in Togo, West Africa. Subjects: Of the 229 6 ± 36-month-old children of both sexes recruited, 197 with hemoglobin concentration ! 80 gal were included and 163 completed the study. Intervention: Children received daily a placebo (n 79) or a dose of 2 ± 3 mg of elemental iron per kg of body weight (n 84) for 3 months. Hematological, nutritional and immune status were assessed at the beginning and at the end of the supplementation period, and 6 months later. Morbidity was recorded throughout the study. Results: Iron supplementation had a signi®cant and positive effect on iron status of children and no impact on the incidence of infections, especially malaria. Its probable effect on immune status was masked by interference of infections and their treatment, which contributed to improve hematological and immune status in both groups. Conclusion: According to the negative consequences of anemia and iron de®ciency on global child development, control of iron de®ciency by oral iron supplementation in young children has to be conducted, associated with prophylaxis and treatment of malaria and repeated deworming.

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Section: Discussionsupporting

confidence: 92%

Effect of daily iron supplementation on iron status, cell-mediated immunity, and incidence of infections in 6–36 month old Togolese children

Berger

Dyck²,

Galán³

et al. 2000

Eur J Clin Nutr

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“…Taken weekly, dapsone-pyrimethamine effectively reduced the risk of clinical malaria and severe anaemia when given to Tanzanian infants between 2 and 12 months of age. Once stopped, however, the group of treated children showed a significantly higher incidence rate of clinical malaria compared to the placebo group (Menendez et al, 1997). Gambian children receiving dapsone-pyrimethamine between the ages of 6 months and 5 years during the transmission season developed an increased risk of clinical malaria in the year after stopping chemoprophylaxis.…”

Section: Clinical Rebound After Chemoprophylactic Interventionsmentioning

confidence: 89%

Enhancement of naturally acquired immunity against malaria by drug use

Bijker

Sauerwein

2012

Journal of Medical Microbiology

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Combination of chemoprophylaxis with chloroquine and so-called 'controlled human malaria infections' has been shown to induce sustained and fully protective immunity against malaria in experimental settings. This opens possibilities of translating this approach into an effective and applicable strategy for the field. We review the different ways in which antimalarial drugs have been used for prevention of malaria in endemic settings and discuss the possibilities and challenges of applying a strategy of drug use and naturally acquired infection in the field. IntroductionMalaria remains one of the most important infectious diseases worldwide, causing almost 655 000 deaths per year, of which the majority are children under 5 years of age. Intense malaria control interventions during the past decade have successfully established a reduction of more than 50 % in either confirmed cases of malaria or malaria admissions and deaths in 11 countries of the WHO African region (WHO, 2011a). However, increases in the number of malaria cases in 2009 in Rwanda, Sao Tome and Principe and Zambia, which previously reported reductions, illustrate the fragility of the current successes. This underlines the need for additional and innovative strategies.Availability of an effective vaccine would greatly contribute to malaria control and elimination. It is well known that clinical immunity is acquired in endemic areas after a number of years and a sufficient number of naturally acquired infections (Snow & Marsh, 1995). The search for malaria vaccines against Plasmodium falciparum has been pursued for decades, with the main focus on the development of subunit-vaccines, but with limited success. Twenty candidate vaccines are currently under clinical investigation but only one product, RTS,S, has progressed into a phase 3 field trial having recently shown encouraging indications of protection in an interim evaluation (RTS,S Clinical Trials Partnership, 2011; WHO, 2011b).One of the shortcomings of subunit-vaccines is the inability to appropriately address the significant antigenic diversity of target epitopes and the often-observed poor immunogenicity of the soluble parasite-derived proteins used. Against that background a whole-parasite approach may perform better. Indeed, immunization with sporozoite forms has consistently been shown to induce .90 % protection in rodents and humans in experimental set-ups (Friesen & Matuschewski, 2011;Hoffman et al., 2002).Transmission intensity varies greatly in sub-Saharan Africa where individuals can be subjected to up to 10 infectious bites per night at certain periods of the year. Here, we explore the idea that using medicines together with naturally acquired infection could result in the induction of protective immunity. We will review the different ways in which antimalarial drugs have been used for prevention of malaria in endemic areas and reflect on the possibilities and challenges of applying a strategy of drug use together with naturally acquired infection in the field (see Table 1 for an ov...

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“…This has the practical consequence of supporting the use of chemoprophylaxis and of intermittent treatment in young children in areas like Ifakara town. Randomized controlled trials of maloprim prophylaxis in infants (Menendez et al, 1997) and of intermittent treatment of infants (Schellenberg et al, 2001) have already shown high efficacy and substantial benefits that will now be evaluated for their effectiveness.…”

Section: Discussionmentioning

confidence: 99%

A prospective study of Plasmodium falciparum multiplicity of infection and morbidity in Tanzanian children

Henning

Schellenberg

Smith

et al. 2004

Transactions of the Royal Society of Tropical Medicine and Hygi

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Summary Several studies suggest that in individuals with substantial previous exposure to malaria, co-infection with multiple clones of Plasmodium falciparum can protect against subsequent clinical malaria attacks. Other studies, mainly of individuals with little previous exposure, found the converse relationship. To test whether acquisition of such cross-protection tracks the acquisition of clinical immunity in general, 610 Tanzanian children aged 0-6 years were enrolled in a nine-month prospective study of the risk of morbidity in relation to parasitological status and merozoite surface protein 2 genotypes on enrolment. Prevalence of parasitaemia and multiplicity of infection increased with age. In the first year of life, the incidence of clinical malaria was almost three times higher in children with parasites at baseline than in those without. In older children, baseline P. falciparum infections appeared to protect against both parasitaemic and non-parasitaemic fever episodes. In children aged less than three years, baseline multiple infection tended to be associated with higher prospective risk of clinical malaria than single infection while in children aged more than three years the converse was found, but these effects were not statistically significant. These results provide further evidence that relationships between asymptomatic malaria infections and clinical malaria change with cumulative exposure.

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Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants

Cited by 316 publications

References 29 publications

Effect of daily iron supplementation on iron status, cell-mediated immunity, and incidence of infections in 6–36 month old Togolese children

Effect of daily iron supplementation on iron status, cell-mediated immunity, and incidence of infections in 6–36 month old Togolese children

Enhancement of naturally acquired immunity against malaria by drug use

A prospective study of Plasmodium falciparum multiplicity of infection and morbidity in Tanzanian children

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