Effect of vitamin A supplementation on morbidity due to Plasmodium falciparum in young children in Papua New Guinea

A randomised trial

Anuraj H. Shankar, Blaise Genton, Richard David Semba, Moses Baisor, Joseph Paino, Steven Tamja, Thomas Adiguma, Lee Shu Fune Wu, Lawrence Rare, James M. Tielsch, Michael P. Alpers, Keith West

Research output: Contribution to journalArticle

Abstract

Background. Many individuals at risk of malaria also have micronutrient deficiencies that may hamper protective immunity. Vitamin A is central to normal immune function, and supplementation has been shown to lower the morbidity of some infectious diseases. We investigated the effect of vitamin A supplementation on malaria morbidity. Methods. This randomised double-blind placebo-controlled trial of vitamin A supplementation took place in a P falciparum endemic area of Papua New Guinea. Of 520 potentially eligible children aged 6-60 months, 480 were randomly assigned high-dose Vitamin A (n = 239) or placebo (n = 241), every 3 months for 13 months. Malaria morbidity was assessed through weekly community-based case detection and surveillance of patients who self-reported to the health centre. Cross-sectional surveys were also done at the beginning, middle, and end of the study to assess malariometric indicators. Analyses were by intention to treat. Findings. The number of P falciparum febrile episodes (temperature ≥ 37.5°C with a parasite count of at least 8000/μL) was 30% lower in the vitamin A group than in the placebo group (178 vs 249 episodes; relative risk 0.70 [95% CI 0.57-0.87], p = 0.0013). At the end of the study P falciparum geometric mean density was lower in the vitamin A than the placebo group (1300 [907-1863] vs 2039 [1408-2951]) as was the proportion with spleen enlargement (125/196 [64%] vs 148/207 [71%]); neither difference was significant (p = 0.093 and p = 0.075). Children aged 12-36 months benefited most, having 35% fewer febrile episodes (89 vs 141; relative risk 0.65 [14-50], p = 0.0023), 26% fewer enlarged spleens (46/79 [58%] vs 67/90 [74%], p = 0.0045), and a 68% lower parasite density (1160 [95% CI 665-2022] vs 3569 [2080-6124] p = 0.0054). Vitamin A had no consistent effect on cross-sectional indices of proportion infected or with anaemia. Interpretation. Vitamin A supplementation may be an effective low-cost strategy to lower morbidity due to P falciparum in young children. The findings suggest that clinical episodes, spleen enlargement, and parasite density are influenced by different immunological mechanisms from infection and anaemia.

Original languageEnglish (US)
Pages (from-to)203-209
Number of pages7
JournalThe Lancet
Volume354
Issue number9174
DOIs
StatePublished - Jul 17 1999

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Papua New Guinea
Plasmodium falciparum
Vitamin A
Morbidity
Placebos
Malaria
Parasites
Anemia
Fever
Spleen
Intention to Treat Analysis
Micronutrients
Splenomegaly
Communicable Diseases
Immunity
Cross-Sectional Studies
Costs and Cost Analysis
Temperature
Health

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of vitamin A supplementation on morbidity due to Plasmodium falciparum in young children in Papua New Guinea : A randomised trial. / Shankar, Anuraj H.; Genton, Blaise; Semba, Richard David; Baisor, Moses; Paino, Joseph; Tamja, Steven; Adiguma, Thomas; Wu, Lee Shu Fune; Rare, Lawrence; Tielsch, James M.; Alpers, Michael P.; West, Keith.

In: The Lancet, Vol. 354, No. 9174, 17.07.1999, p. 203-209.

Research output: Contribution to journalArticle

Shankar, Anuraj H. ; Genton, Blaise ; Semba, Richard David ; Baisor, Moses ; Paino, Joseph ; Tamja, Steven ; Adiguma, Thomas ; Wu, Lee Shu Fune ; Rare, Lawrence ; Tielsch, James M. ; Alpers, Michael P. ; West, Keith. / Effect of vitamin A supplementation on morbidity due to Plasmodium falciparum in young children in Papua New Guinea : A randomised trial. In: The Lancet. 1999 ; Vol. 354, No. 9174. pp. 203-209.
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abstract = "Background. Many individuals at risk of malaria also have micronutrient deficiencies that may hamper protective immunity. Vitamin A is central to normal immune function, and supplementation has been shown to lower the morbidity of some infectious diseases. We investigated the effect of vitamin A supplementation on malaria morbidity. Methods. This randomised double-blind placebo-controlled trial of vitamin A supplementation took place in a P falciparum endemic area of Papua New Guinea. Of 520 potentially eligible children aged 6-60 months, 480 were randomly assigned high-dose Vitamin A (n = 239) or placebo (n = 241), every 3 months for 13 months. Malaria morbidity was assessed through weekly community-based case detection and surveillance of patients who self-reported to the health centre. Cross-sectional surveys were also done at the beginning, middle, and end of the study to assess malariometric indicators. Analyses were by intention to treat. Findings. The number of P falciparum febrile episodes (temperature ≥ 37.5°C with a parasite count of at least 8000/μL) was 30{\%} lower in the vitamin A group than in the placebo group (178 vs 249 episodes; relative risk 0.70 [95{\%} CI 0.57-0.87], p = 0.0013). At the end of the study P falciparum geometric mean density was lower in the vitamin A than the placebo group (1300 [907-1863] vs 2039 [1408-2951]) as was the proportion with spleen enlargement (125/196 [64{\%}] vs 148/207 [71{\%}]); neither difference was significant (p = 0.093 and p = 0.075). Children aged 12-36 months benefited most, having 35{\%} fewer febrile episodes (89 vs 141; relative risk 0.65 [14-50], p = 0.0023), 26{\%} fewer enlarged spleens (46/79 [58{\%}] vs 67/90 [74{\%}], p = 0.0045), and a 68{\%} lower parasite density (1160 [95{\%} CI 665-2022] vs 3569 [2080-6124] p = 0.0054). Vitamin A had no consistent effect on cross-sectional indices of proportion infected or with anaemia. Interpretation. Vitamin A supplementation may be an effective low-cost strategy to lower morbidity due to P falciparum in young children. The findings suggest that clinical episodes, spleen enlargement, and parasite density are influenced by different immunological mechanisms from infection and anaemia.",
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T2 - A randomised trial

AU - Shankar, Anuraj H.

AU - Genton, Blaise

AU - Semba, Richard David

AU - Baisor, Moses

AU - Paino, Joseph

AU - Tamja, Steven

AU - Adiguma, Thomas

AU - Wu, Lee Shu Fune

AU - Rare, Lawrence

AU - Tielsch, James M.

AU - Alpers, Michael P.

AU - West, Keith

PY - 1999/7/17

Y1 - 1999/7/17

N2 - Background. Many individuals at risk of malaria also have micronutrient deficiencies that may hamper protective immunity. Vitamin A is central to normal immune function, and supplementation has been shown to lower the morbidity of some infectious diseases. We investigated the effect of vitamin A supplementation on malaria morbidity. Methods. This randomised double-blind placebo-controlled trial of vitamin A supplementation took place in a P falciparum endemic area of Papua New Guinea. Of 520 potentially eligible children aged 6-60 months, 480 were randomly assigned high-dose Vitamin A (n = 239) or placebo (n = 241), every 3 months for 13 months. Malaria morbidity was assessed through weekly community-based case detection and surveillance of patients who self-reported to the health centre. Cross-sectional surveys were also done at the beginning, middle, and end of the study to assess malariometric indicators. Analyses were by intention to treat. Findings. The number of P falciparum febrile episodes (temperature ≥ 37.5°C with a parasite count of at least 8000/μL) was 30% lower in the vitamin A group than in the placebo group (178 vs 249 episodes; relative risk 0.70 [95% CI 0.57-0.87], p = 0.0013). At the end of the study P falciparum geometric mean density was lower in the vitamin A than the placebo group (1300 [907-1863] vs 2039 [1408-2951]) as was the proportion with spleen enlargement (125/196 [64%] vs 148/207 [71%]); neither difference was significant (p = 0.093 and p = 0.075). Children aged 12-36 months benefited most, having 35% fewer febrile episodes (89 vs 141; relative risk 0.65 [14-50], p = 0.0023), 26% fewer enlarged spleens (46/79 [58%] vs 67/90 [74%], p = 0.0045), and a 68% lower parasite density (1160 [95% CI 665-2022] vs 3569 [2080-6124] p = 0.0054). Vitamin A had no consistent effect on cross-sectional indices of proportion infected or with anaemia. Interpretation. Vitamin A supplementation may be an effective low-cost strategy to lower morbidity due to P falciparum in young children. The findings suggest that clinical episodes, spleen enlargement, and parasite density are influenced by different immunological mechanisms from infection and anaemia.

AB - Background. Many individuals at risk of malaria also have micronutrient deficiencies that may hamper protective immunity. Vitamin A is central to normal immune function, and supplementation has been shown to lower the morbidity of some infectious diseases. We investigated the effect of vitamin A supplementation on malaria morbidity. Methods. This randomised double-blind placebo-controlled trial of vitamin A supplementation took place in a P falciparum endemic area of Papua New Guinea. Of 520 potentially eligible children aged 6-60 months, 480 were randomly assigned high-dose Vitamin A (n = 239) or placebo (n = 241), every 3 months for 13 months. Malaria morbidity was assessed through weekly community-based case detection and surveillance of patients who self-reported to the health centre. Cross-sectional surveys were also done at the beginning, middle, and end of the study to assess malariometric indicators. Analyses were by intention to treat. Findings. The number of P falciparum febrile episodes (temperature ≥ 37.5°C with a parasite count of at least 8000/μL) was 30% lower in the vitamin A group than in the placebo group (178 vs 249 episodes; relative risk 0.70 [95% CI 0.57-0.87], p = 0.0013). At the end of the study P falciparum geometric mean density was lower in the vitamin A than the placebo group (1300 [907-1863] vs 2039 [1408-2951]) as was the proportion with spleen enlargement (125/196 [64%] vs 148/207 [71%]); neither difference was significant (p = 0.093 and p = 0.075). Children aged 12-36 months benefited most, having 35% fewer febrile episodes (89 vs 141; relative risk 0.65 [14-50], p = 0.0023), 26% fewer enlarged spleens (46/79 [58%] vs 67/90 [74%], p = 0.0045), and a 68% lower parasite density (1160 [95% CI 665-2022] vs 3569 [2080-6124] p = 0.0054). Vitamin A had no consistent effect on cross-sectional indices of proportion infected or with anaemia. Interpretation. Vitamin A supplementation may be an effective low-cost strategy to lower morbidity due to P falciparum in young children. The findings suggest that clinical episodes, spleen enlargement, and parasite density are influenced by different immunological mechanisms from infection and anaemia.

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