Insights Into Circulating Cytokine Dynamics During Pregnancy in HIV-Infected Beninese Exposed to Plasmodium falciparum Malaria

Samad A. Ibitokou Centre d'étude et de Recherche sur le Paludisme Associé à la Grossesse et à l'enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin; Institut de Recherche pour le Développement, UMR 216, Mère et enfant face aux Infections Tropicales, Paris, France; Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Paris, France

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Lise Denoeud-Ndam Centre d'étude et de Recherche sur le Paludisme Associé à la Grossesse et à l'enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin; Institut de Recherche pour le Développement, UMR 216, Mère et enfant face aux Infections Tropicales, Paris, France; Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Paris, France

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Sèm Ezinmegnon Centre d'étude et de Recherche sur le Paludisme Associé à la Grossesse et à l'enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin; Institut de Recherche pour le Développement, UMR 216, Mère et enfant face aux Infections Tropicales, Paris, France; Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Paris, France

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Rodolphe Ladékpo Centre d'étude et de Recherche sur le Paludisme Associé à la Grossesse et à l'enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin; Institut de Recherche pour le Développement, UMR 216, Mère et enfant face aux Infections Tropicales, Paris, France; Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Paris, France

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Djimon-Marcel Zannou Centre d'étude et de Recherche sur le Paludisme Associé à la Grossesse et à l'enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin; Institut de Recherche pour le Développement, UMR 216, Mère et enfant face aux Infections Tropicales, Paris, France; Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Paris, France

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Achille Massougbodji Centre d'étude et de Recherche sur le Paludisme Associé à la Grossesse et à l'enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin; Institut de Recherche pour le Développement, UMR 216, Mère et enfant face aux Infections Tropicales, Paris, France; Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Paris, France

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Pierre-Marie Girard Centre d'étude et de Recherche sur le Paludisme Associé à la Grossesse et à l'enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin; Institut de Recherche pour le Développement, UMR 216, Mère et enfant face aux Infections Tropicales, Paris, France; Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Paris, France

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Michel Cot Centre d'étude et de Recherche sur le Paludisme Associé à la Grossesse et à l'enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin; Institut de Recherche pour le Développement, UMR 216, Mère et enfant face aux Infections Tropicales, Paris, France; Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Paris, France

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Adrian J. F. Luty Centre d'étude et de Recherche sur le Paludisme Associé à la Grossesse et à l'enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin; Institut de Recherche pour le Développement, UMR 216, Mère et enfant face aux Infections Tropicales, Paris, France; Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Paris, France

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Nicaise Tuikue Ndam Centre d'étude et de Recherche sur le Paludisme Associé à la Grossesse et à l'enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin; Institut de Recherche pour le Développement, UMR 216, Mère et enfant face aux Infections Tropicales, Paris, France; Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Paris, France

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We investigated the circulating plasma levels of Th1- (Interleukin-2 [IL-2], tumor necrosis factor-α [TNF-α], interferon-gamma [IFN-γ]) and Th2-type (IL-4, IL-5, IL-10) cytokines in human immunodeficiency virus (HIV)-infected pregnant women living in a malaria-endemic area. We analyzed samples from 200 pregnant women included in the prevention of pregnancy-associated malaria in HIV-infected women: cotrimoxazole prophylaxis versus mefloquine (PACOME) clinical trial who were followed until delivery. Cytokine concentrations were measured by flow cytometry-based multiplex bead array. Significantly elevated levels of IL-10 and lower levels of TNF-α were observed at delivery compared with inclusion (P = 0.005). At inclusion, the presence of circulating IFN-γ, a higher CD4+ T cell count and having initiated intermittent preventive treatment of malaria with sulfadoxine pyrimethamine (SP-IPTp) were all associated with a lower likelihood of Plasmodium falciparum infection. At delivery, the inverse relationship between the presence of infection and circulating IFN-γ persisted, although there was a positive association between the likelihood of infection and the presence of circulating TNF-α. Initiation of antiretroviral therapy was associated with elevated IL-5 production. Consistent with our own and others' observations in HIV seronegative subjects, this study shows circulating IL-10 to be a marker of infection with P. falciparum during pregnancy even in HIV-infected women, although plasma IFN-γ may be a marker of anti-malarial protection in such women.

Author Notes

* Address correspondence to Nicaise Tuikue Ndam, UMR 216, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75006, Paris, France. E-mail: nicaise.ndam@ird.fr

Financial support: The PACOME trial received funding from SIDACTION (research grant no. AI19-3-01528).

Disclosure: The funding sources had no involvement in the design, collection, analysis, and interpretation of data, writing of the manuscript or decision to publish.

Authors' addresses: Samad A. Ibitokou, Centre d'étude et de Recherche sur le Paludisme Associé à la Grossesse et à l'enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin, E-mail: ibitokou_samad@yahoo.fr (current address: University of Texas Medical Branch, Department of Internal Medicine, Division of Infectious Disease, Galveston, TX). Lise Denoeud-Ndam, Michel Cot, Adrian J.F. Luty, and Nicaise Tuikue Ndam, Institut de Recherche pour le Développement, UMR 216, Mère et enfant face aux Infections Tropicales, Paris, France, E-mails: lisedenoeud@yahoo.fr, michel.cot@ird.fr, adrian.luty@ird.fr, and nicaise.ndam@ird.fr. Sèm Ezinmegnon, Rodolphe Ladékpo, and Achille Massougbodji, Centre d'étude et de Recherche sur le Paludisme Associé à la Grossesse et à l'enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin, E-mails: e25sem@yahoo.fr, ladekpo@yahoo.fr, and massougbodjiachille@yahoo.fr. Djimon-Marcel Zannou, Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin, E-mail: djmzannou@yahoo.fr. Pierre-Marie Girard, Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Paris, France, E-mail: pierre-marie.girard@sat.aphp.fr.

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