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Incidence of malaria-related fever and morbidity due to Plasmodium falciparum among HIV1-infected pregnant women: a prospective cohort study in South Benin.

ABSTRACT: Malaria and HIV are two major causes of morbidity and mortality among pregnant women in sub-Saharan Africa. Foetal and neonatal outcomes of this co-infection have been extensively studied. However, little is known about maternal morbidity due to clinical malaria in pregnancy, especially malaria-related fever, in the era of generalized access to antiretroviral therapy and anti-malarial preventive strategies.A cohort study was conducted in order to estimate the incidence rate and to determine the factors associated with malaria-related fever, as well as the maternal morbidity attributable to malaria in a high-transmission setting of South Benin among HIV-infected pregnant women. Four-hundred and thirty-two women who participated in a randomized trial testing strategies to prevent malaria in pregnancy were included and followed until delivery, with at least three scheduled visits during pregnancy. Confirmed malaria-related fever was defined as axillary temperature >37.5°C and a concomitant, positive, thick blood smear or rapid diagnostic test for Plasmodium falciparum. Suspected malaria-related fever was defined as an axillary temperature >37.5°C and the concomitant administration of an anti-malarial treatment in the absence of parasitological investigation.Incidence rate for confirmed malaria-related fever was of 127.9 per 1,000 person-year (PY) (95% confidence interval (CI): 77.4-211.2). In multivariate analysis, CD4 lymphocytes (Relative Risk (RR) for a 50 cells/mm3 variation?=?0.82; CI: 0.71-0.96), antiretroviral treatment started before inclusion (RR?=?0.34; CI: 0.12-0.98) and history of symptomatic malaria in early pregnancy (RR?=?7.10; CI: 2.35-22.49) were associated with the incidence of confirmed or suspected malaria-related fever. More than a half of participants with parasitaemia were symptomatic, with fever being the most common symptom. The crude fraction of febrile episodes attributable to malaria was estimated at 91%.This work highlights that malaria is responsible for a substantial morbidity in HIV-infected pregnant women, with cellular immunodepression as a major determinant, and establishes the possible advantage offered by the early initiation of antiretroviral treatment.PACOME Study has been registered under the number NCT00970879.

SUBMITTER: Duvignaud A

PROVIDER: S-EPMC4089929 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Incidence of malaria-related fever and morbidity due to Plasmodium falciparum among HIV1-infected pregnant women: a prospective cohort study in South Benin.

Duvignaud Alexandre A Denoeud-Ndam Lise L Akakpo Jocelyn J Agossou Komlan V KV Afangnihoun Aldric A Komongui Didier G DG Atadokpédé Félix F Dossou-Gbété Lucien L Girard Pierre-Marie PM Zannou Djimon-Marcel DM Cot Michel M

Malaria journal 20140704

<h4>Background</h4>Malaria and HIV are two major causes of morbidity and mortality among pregnant women in sub-Saharan Africa. Foetal and neonatal outcomes of this co-infection have been extensively studied. However, little is known about maternal morbidity due to clinical malaria in pregnancy, especially malaria-related fever, in the era of generalized access to antiretroviral therapy and anti-malarial preventive strategies.<h4>Methods</h4>A cohort study was conducted in order to estimate the i ...[more]

PMID: 24996807

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Project description:BACKGROUND: Malaria transmission is complex and is believed to be associated with local climate changes. However, simple attempts to extrapolate malaria incidence rates from averaged regional meteorological conditions have proven unsuccessful. Therefore, the objective of this study was to determine if variations in specific meteorological factors are able to consistently predict P. falciparum malaria incidence at different locations in south Ethiopia. METHODS: Retrospective data from 42 locations were collected including P. falciparum malaria incidence for the period of 1998-2007 and meteorological variables such as monthly rainfall (all locations), temperature (17 locations), and relative humidity (three locations). Thirty-five data sets qualified for the analysis. Ljung-Box Q statistics was used for model diagnosis, and R squared or stationary R squared was taken as goodness of fit measure. Time series modelling was carried out using Transfer Function (TF) models and univariate auto-regressive integrated moving average (ARIMA) when there was no significant predictor meteorological variable. RESULTS: Of 35 models, five were discarded because of the significant value of Ljung-Box Q statistics. Past P. falciparum malaria incidence alone (17 locations) or when coupled with meteorological variables (four locations) was able to predict P. falciparum malaria incidence within statistical significance. All seasonal AIRMA orders were from locations at altitudes above 1742 m. Monthly rainfall, minimum and maximum temperature was able to predict incidence at four, five and two locations, respectively. In contrast, relative humidity was not able to predict P. falciparum malaria incidence. The R squared values for the models ranged from 16% to 97%, with the exception of one model which had a negative value. Models with seasonal ARIMA orders were found to perform better. However, the models for predicting P. falciparum malaria incidence varied from location to location, and among lagged effects, data transformation forms, ARIMA and TF orders. CONCLUSIONS: This study describes P. falciparum malaria incidence models linked with meteorological data. Variability in the models was principally attributed to regional differences, and a single model was not found that fits all locations. Past P. falciparum malaria incidence appeared to be a superior predictor than meteorology. Future efforts in malaria modelling may benefit from inclusion of non-meteorological factors.

Project description:BACKGROUND:Malaria in pregnancy increases the risk of maternal anemia, abortion and low birth weight. Approximately 85.3 million pregnancies occur annually in areas with Plasmodium falciparum transmission. Pregnancy has been reported to alter the pharmacokinetic properties of many anti-malarial drugs. Reduced drug exposure increases the risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of artemether and its active metabolite dihydroartemisinin in pregnant women with uncomplicated P. falciparum malaria in Uganda. METHODS:Twenty-one women with uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy received the fixed oral combination of 80 mg artemether and 480 mg lumefantrine twice daily for three days. Artemether and dihydroartemisinin plasma concentrations after the last dose administration were quantified using liquid chromatography coupled to tandem mass-spectroscopy. A simultaneous drug-metabolite population pharmacokinetic model for artemether and dihydroartemisinin was developed taking into account different disposition, absorption, error and covariate models. A separate modeling approach and a non-compartmental analysis (NCA) were also performed to enable a comparison with literature values and different modeling strategies. RESULTS:The treatment was well tolerated and there were no cases of recurrent malaria. A flexible absorption model with sequential zero-order and transit-compartment absorption followed by a simultaneous one-compartment disposition model for both artemether and dihydroartemisinin provided the best fit to the data. Artemether and dihydroartemisinin exposure was lower than that reported in non-pregnant populations. An approximately four-fold higher apparent volume of distribution for dihydroartemisinin was obtained by non-compartmental analysis and separate modeling compared to that from simultaneous modeling of the drug and metabolite. This highlights a potential pitfall when analyzing drug/metabolite data with traditional approaches. CONCLUSION:The population pharmacokinetic properties of artemether and dihydroartemisinin, in pregnant women with uncomplicated P. falciparum malaria in Uganda, were described satisfactorily by a simultaneous drug-metabolite model without covariates. Concentrations of artemether and its metabolite dihydroartemisinin were relatively low in pregnancy compared to literature data. However, this should be interpreted with caution considered the limited literature available. Further studies in larger series are urgently needed for this vulnerable group.

Dataset Information

Incidence of malaria-related fever and morbidity due to Plasmodium falciparum among HIV1-infected pregnant women: a prospective cohort study in South Benin.

Publications

Incidence of malaria-related fever and morbidity due to Plasmodium falciparum among HIV1-infected pregnant women: a prospective cohort study in South Benin.

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