Anémie en milieu rural au Sud-Kivu :contribution du paludisme et de la carence en fer. Anemia in rural South Kivu: contribution of malaria and iron deficiency.

Résumé généralIntroductionL’anémie est un problème majeur de santé publique particulièrement fréquent dans les pays à faible revenu, dont la RDC, et qui affecte avec prédilection les femmes enceintes et les enfants d’âge préscolaire. Elle est associée à un risque élevé de morbidité et de mortalité. Au cours de la grossesse, l’anémie peut entraver le développement du fœtus et peut affecter négativement la santé maternelle. Chez l’enfant, l’anémie peut en plus altérer le développement physique et mental si elle n’est pas rapidement corrigée. Il est généralement admis que la carence en fer est la première cause d’anémie et les stratégies de lutte suggérées par l’Organisation mondiale de la santé en découlent. Cependant dans la région du Kivu, il n’existe que très peu d’information sur les étiologies de l’anémie et sur la contribution du paludisme et de celle de la carence en fer dans sa genèse. L’objectif global de ce travail de thèse était de contribuer à l’étude de l’anémie et de sa relation avec le paludisme et la carence en fer, en milieu rural au Sud-Kivu.Méthodes Ce travail a consisté en trois études épidémiologiques menées entre 2010 et 2014 dans la zone de santé rurale de Miti-Murhesa dans la province du Sud-Kivu à l’est de la RDC. Il s’est agit de deux études transversales et d’une étude longitudinale prospective. Cette dernière a concerné des femmes enceintes enrôlées depuis le deuxième trimestre de la grossesse à leur première consultation prénatale (CPN1) jusqu’à l’accouchement. L’une des deux études transversales a aussi recruté des femmes enceintes au deuxième trimestre de la grossesse à leur CPN1 et la deuxième a consisté en une étude en grappes à deux degrés chez des enfants d’âge préscolaire en bonne santé apparente dans la communauté. Résultats La prévalence de l’anémie chez les femmes enceintes était de 17,6% et celle de la carence en fer (ferritine ajustée) de 8%. Le paludisme était présent chez 7,5% et l’hypoalbuminémie chez 44% des sujets. La concentration plasmatique du récepteur soluble de la transferrine était plus élevée en présence du paludisme. Les facteurs significativement associés à l’anémie étaient le paludisme [ORa: 11.24 (4.98-25.37); P < 0.001], l’hypoalbuminémie [ORa: 2.14 (1.27-3.59); P = 0.004] et des valeurs élevées de la protéine C réactive [ORa: 1.94 (1.10-3.45); P = 0.022]. La carence en fer n’était pas fréquente et n’était pas significativement associée à l’anémie.La valeur médiane (EIQ) de la concentration sérique de ferritine (ajustée pour l’inflammation) était plus élevée en présence de paludisme comparée aux femmes non impaludées [82.9 μg/L (56.3-130.4) vs 39.8 μg/L (23.6-60.8); P < 0.001]. Le paludisme était plus fréquent chez les femmes sans carence en fer [ORa 6,25 (1,47-26,57); P=0,021] et chez celles n’ayant pas utilisé de moustiquaire imprégnée d’insecticide [ORa 2,24 (1,12-4,51); P=0,024].A l’admission dans l’étude prospective, 9,5% de femmes de la cohorte présentaient une infection palustre. Après régression logistique, la fréquence du paludisme était plus élevée chez les primigestes, chez les femmes avec niveau socioéconomique bas et chez celles vivant à moins de 1683 m d’altitude ;les rapports de cote ajustés (IC 95%) étaient respectivement de [2,55 (1,05-6,19) ;P=0,039] ;[4,78 (1,36-16,76) ;P=0,033] et [2,34 (1,10-5,02) ;P=0,029]. Toujours à l’admission dans la même étude, la prévalence de l’anémie était de 32%. Celle-ci était plus fréquente chez les femmes impaludées [ORa :4,20 (2,00-8,80); P<0,001] et chez celles qui n’avaient pas bénéficié d’un déparasitage dans les 3 mois avant leur admission dans l’étude [ORa :2,33 (1,25-4,35)]. A l’accouchement, le petit poids de naissance (PPN) était présent chez 6,5% des nouveau-nés. Les prédicteurs du PNN étaient l’absence d’utilisation de la MII [ORa :4,17 (1,15-14,28); P=0.030], une faible taille (<150 cm) de la mère [ORa :5,56 (2,01-15,33); P=0.001] et la présence d’anémie chez la mère à la CPN1 [ORa :4,08 (1,50-11,10); P=0.006]. Chez les enfants d’âge préscolaire, l’anémie était présente dans 46,6% des cas et la prévalence de l’anémie ferriprive chez les enfants anémiques était de 16,5%. Chez les enfants sans inflammation, la carence en fer était de 4,4% (ferritine non ajustée). Les résultats de la régression logistique ont révélé que l’anémie était significativement et indépendamment associée à la carence en fer [ORa :4,10 (2,41-6,96) ;P<0,001], à une histoire de fièvre pendant les deux semaines avant l’enquête [ORa :1,58 (1,00-2,50); P=0,049] et à un faible périmètre brachial [ORa :1,87 (1,18-2,94) ;P=0,006]. Dans un deuxième modèle ayant exclu les enfants avec carence en fer, ce sont une histoire de fièvre dans les deux semaines avant l’enquête [ORa :1,62(1,00-2,62); P=0,05] et un faible périmètre brachial [ORa :1,96(1,24-3,13); P=005] qui étaient associés significativement et indépendamment à l’anémie.Conclusion L’anémie est fréquente en milieu rural au Sud-Kivu mais la contribution de la carence en fer est faible. Néanmoins, d’autres carences nutritionnelles lui sont associées :une hypoalbuminémie chez les femmes enceintes et un faible périmètre brachial chez les enfants de moins de 5 ans. Le paludisme, d’autres infections, des états inflammatoires ainsi que le manque de déparasitage sont également d’autres facteurs qui étaient associés à l’anémie. Chez les femmes enceintes, l’absence de prévention contre le paludisme par les MII, la présence d’anémie et une faible taille de la mère étaient des prédicteurs du PPN.Une lutte intégrée contre le paludisme et d’autres maladies infectieuses ainsi que l’amélioration de l’état nutritionnel sont des facteurs vulnérables à court et moyen termes pour réduire la charge de l’anémie. Ce qui, par conséquent, contribuera à la réduction de l’incidence du PPN.Il y a une nécessité à poursuivre la recherche pour (i) identifier d’autres causes d’anémie en incluant la recherche des hémoglobinopathies et autres anomalies génétiques, (ii) améliorer les connaissances sur les meilleures stratégies de lutte contre l’anémie en intégrant la prévention contre le paludisme dans un milieu où il y a une prévalence relativement élevée d’hémoglobinopathies et autres anomalies génétiques pouvant altérer l’érythropoïèse et/ou le métabolisme du fer.Executive summary IntroductionAnemia is a worldwide public health concern, which is particularly prevalent in low and middle-income countries, including the Democratic Republic of the Congo (DRC). It affects mostly pregnant women and preschool children and is associated with a higher risk of morbidity and mortality. During pregnancy, anemia is associated with poor birth outcomes and can negatively affect maternal health. In children, anemia can also alter physical and mental development if not corrected quickly. It is generally assumed that iron deficiency is the leading cause of anemia, thus that assumption had influenced control strategies suggested by the World Health Organization. However, in the Kivu region, there is little information on the aetiologies of anemia and the contribution of malaria and that of iron deficiency in the aetiology of anemia is unknown. The overall goal of this thesis was to contribute to the study of the burden of anemia and its relationship with malaria and iron deficiency in rural South Kivu.MethodsThe data are from three epidemiological studies carried out between 2010 and 2014 in the rural health zone of Miti-Murhesa in the South Kivu province in eastern DRC. There were two cross-sectional studies and one longitudinal prospective study. In the latter, pregnant women were enrolled during the second trimester of pregnancy at their first prenatal visit (ANV1) and followed-up until delivery. One of the two cross-sectional studies also enrolled pregnant women in the second trimester of pregnancy at their ANV1 and the second consisted of a two-stage cluster study at community level in apparently healthy preschool children.ResultsThe prevalence of anemia in pregnant women was 17.6% and that of iron deficiency (adjusted ferritin) was 8%. Malaria was present in 7.5% and hypoalbuminemia in 44% of subjects. Soluble transferrin receptor concentration was higher in the presence of malaria. Factors significantly associated with anemia were malaria [ORa: 11.24 (4.98-25.37); P < 0.001], hypoalbuminemia [ORa: 2.14 (1.27-3.59); P = 0.004] and high values of the C reactive protein [ORa: 1.94 (1.10-3.45); P = 0.022]. Iron deficiency was not common and was not significantly associated with anemia.The median value (IQR) of serum ferritin concentration (adjusted for inflammation) was higher in the presence of malaria compared to non-infected women [82.9 μg/L (56.3-130.4) vs 39.8 μg/L (23.6-60.8 ); P < 0.001]. Malaria was more common in women without iron deficiency [ORa 6.25 (1.47-26.57); P = 0.021] and in those who did not use insecticide-treated mosquito nets [ORa 2.24 (1.12-4.51); P = 0.024].At admission in the prospective study, 9.5% of women in the cohort had malaria infection. After logistic regression, malaria was higher in primigravidae, among women with low socioeconomic status and those living at an altitude of less than 1683 m; the adjusted odds ratios (95% CI) were [2.55 (1.05-6.19); P = 0.039]; [4.78 (1.36-16.76); P = 0.033] and [2.34 (1.10-5.02); P = 0.029], respectively.Still at admission in the same study, the prevalence of anemia was 32%. This was more common in malaria-infected women [ORa: 4.20 (2.00-8.80); P < 0.001] and in those who were not dewormed within the last 3 months prior to admission into the study [ORa: 2.33 (1.25-4.35); P = 0.008]. At delivery, low birth weight (LBW) was present in 6.5% of new-borns. Predictors of LBW were the lack of use of ITN [ORa: 4.17 (1.15-14.28); P = 0.030], a low height (< 150 cm) of the mother [ORa: 5.56 (2.01-15.33); P = 0.001] and the presence of maternal anemia at ANV1 [ORa: 4.08 (1.50-11.10); P = 0.006].In pre-school children, anemia was present in 46.6% and the prevalence of iron deficiency among anemic children was 16.5%. In children without inflammation, iron deficiency was 4.4% (unadjusted ferritin). Logistic regression analysis revealed that anemia was significantly and independently associated with iron deficiency [ORa: 4.10 (2.41-6.96); P < 0.001], with fever during the last two weeks before the survey [ORa: 1.58 (1.00-2.50); P = 0.049] and with a low mid-upper arm circumference (MUAC) [ORa: 1.87 (1.18-2.94); P = 0.006]. In a second model that excluded children with iron deficiency, history of fever in the last two weeks before the survey [ORa: 1.62 (1.00-2.62); P = 0.05] and a low MUAC [ORa: 1.96 (1.24-3.13); P = 005] were significantly and independently associated with anemia.ConclusionAnemia is common in rural South Kivu but the contribution of iron deficiency is low. However, other nutritional deficiencies are associated: hypoalbuminemia in pregnant women and low MUAC in preschool children. Malaria, other infections, inflammatory conditions as well as lack of deworming are also other factors that were associated with anemia. In pregnant women, lack of prevention against malaria by ITNs before ANV1, presence of anemia at ANV1, and low maternal height were predictors of LBW.Integrated control of malaria and other infectious diseases as well as improving nutritional status are among vulnerable factors in the short- and middle-term to reduce the burden of anemia in South Kivu. This, in turn, will help to reduce the incidence of LBW.There is need for further research to (i) identify other causes of anemia including hemoglobinopathies and other genetic disorders, (ii) improve knowledge of the best strategies for controlling anemia by integrating prevention of malaria in an environment where there is a relatively high prevalence of hemoglobinopathies and other genetic abnormalities that may alter erythropoiesis and/or iron metabolism.Doctorat en Sciences de la santé Publiqueinfo:eu-repo/semantics/nonPublishe

How to improve women’s and partner’s participation to prenatal HIV counseling in rural and urban areas in Kivu, democratic Republic of Congo?

FLWINinfo:eu-repo/semantics/publishedAbstracts of the 6th European Congress on Tropical Medicine and International Health and 1st Mediterranean Conference on Migration and Travel Health, Verona, Italy, 6-10 September 200

Mise en place de programmes de prévention de la transmission mère-enfant du VIH dans un contexte conflictuel: exemple du Sud-Kivu, RDC

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prévalence du paludisme au deuxième trimestre de la grossesse en milieu rural au Sud-Kivu, République Démocratique du Congo

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How to improve women’s and partner’s participation to prenatal HIV counseling in rural and urban areas in Kivu, democratic republic of Congo ?

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Malaria is more prevalent than iron deficiency among anemic pregnant women at the first antenatal visit in rural South Kivu

Anemia is common during pregnancy and is associated with poor outcomes. Objectives were not only 1) to determine the prevalence of anemia and iron deficiency (ID) but also 2) to identify other factors associated with anemia in pregnant women from South Kivu province, in the eastern Democratic Republic of Congo. Between December 2013 and March 2014, 531 women attending the first antenatal visit in their second trimester of pregnancy were recruited. Sociodemographic, clinical, and biological data were collected. Hemoglobin (Hb) was determined by a portable photometer (Hemocue® Hb201+), and anemia was defined as altitude-adjusted Hb 5 mg/L and/or α-1-acid glycoprotein > 1 g/L) whereas hypoalbuminemia was defined as serum albumin < 35 g/L. A Giemsa-stained blood smear was used to diagnose malaria. The median age (interquartile range) was 25.5 (21.1–31.3) years, with anemia in 17.6% and ID in 8%. Malaria was present in 7.5% and hypoalbuminemia among 44%. Soluble transferrin receptor concentration was higher in the presence of inflammation and/or malaria. In the final logistic regression model, factors independently associated with anemia were malaria (adjusted odds ratio [aOR]: 11.24 (4.98–25.37) P < 0.001), hypoalbuminemia [aOR: 2.14 (1.27–3.59); P = 0.004] and elevated CRP [aOR: 1.94 (1.10–3.45); P = 0.022]. ID was not highly prevalent and not associated with anemia in our population. Effective control of anemia during pregnancy in this region should consider fighting malaria and other infectious diseases in combination with measures to improve women’s nutrition, both before and during pregnancy.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Facteurs démographiques, nutritionnels, cliniques et biologiques des enfants à l'admission associés à la mortalité intra-hospitalière à l'Est de la République Démocratique du Congo.

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High prevalence of anemia but low level of iron deficiency in preschool children during a low transmission period of Malaria in rural Kivu, Democratic Republic of the Congo

Anemia is a worldwide public health concern especially in preschool children in developing countries and iron deficiency (ID) is generally assumed to cause at least 50% of the cases. However, data on this contribution are scarce. To close this gap, we determined in 2013 the contribution of ID in the etiology of anemia and measured others factors associated to noniron deficiency anemia (NIDA) in 900 preschool children randomly selected during a two-stage cluster nutritional survey in the Miti-Murhesa health zone, in eastern Democratic Republic of the Congo. In these children, we collected sociodemographic, clinical, and biological parameters and determined the nutritional status according to the World Health Organization 2006 standards. Anemia was defined as altitudeadjusted hemoglobin < 110 g/L and ID was defined as serum ferritin < 12 μg/L or < 30 μg/L in the absence or presence of inflammation, respectively. Median (interquartile range) age was 29.4 (12-45) months. The prevalence of anemiawas 46.6% (391/838) among whom only 16.5% (62/377) had ID. Among children without signs of inflammation, only 4.4%(11/251) met the ferritin-based (unadjusted) definition of ID. Logistic regression analysis identified ID, history of fever during the last 2weeks andmid-upper armcircumference < 125mmas the only independent factors associated to anemia. In conclusion, anemia is a severe public health problem in the Miti-Murhesa health zone, but NIDA is mostly predominant and needs to be further studied. Control of infections and prevention of acute undernutrition (wasting) are some of appropriate interventions to reduce the burden anemia in this region.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Etude comparative de la morbidité et des pathologies responsables de la mortalité au Sud-Kivu en République Démocratique du Congo avant et après la période d'instabilité sécuritaire chronique.

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Serum soluble transferrin receptor concentrations are elevated in Congolese children with glucose-6-phosphate dehydrogenase variants, but not sickle cell variants or α-thalassemia

Background: Anemia is common in Congolese children, and inherited blood disorders may be a contributing cause. The presence of sickle cell variants, X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency and α-thalassemia, has been previously reported. G6PD A- deficiency is characterized by the co-inheritance of G6PD 376 and 202 variants and is common in sub-Saharan Africa. Objective: We aimed to measure the associations between inherited blood disorders and hemoglobin, ferritin, and soluble transferrin receptor (sTfR) concentrations in Congolese children. Methods: Venous blood was collected from 744 children aged 6-59 mo from 2 provinces. We measured biomarkers of nutritional and inflammation status and malaria. Pyrosequencing was used to detect sickle cell variants. Polymerase chain reaction was used to detect G6PD variants and a-thalassemia deletions. Results: Overall, 11% of children had a sickle cell variant, 19% of boys were G6PD A- hemizygotes, 12% and 10% of girls were G6PD A- hetero- or homozygotes, respectively, and 12% of children had a-thalassemia. Multivariable linear regression models (adjusted for age, province, altitude, malaria, and biomarkers of nutritional and inflammation status) showed that G6PD A- hemizygous boys and G6PD 376 homozygous girls had higher sTfR concentrations [geometric mean ratios (95% CIs): 1.20 (1.03, 1.39) and 1.25 (1.02, 1.53), respectively] than children with no G6PD variants. Hemoglobin and ferritin concentrations were not independently associated with any of the inherited blood disorder genotypes. Conclusions: We found that 2 G6PD variant genotypes were associated with elevated sTfR concentrations, which limits the accuracy of sTfR as a biomarker of iron status in this population.SCOPUS: ar.jinfo:eu-repo/semantics/publishe