ブルキナファソにおける高いB型肝炎感染率（1996-2017） : システマティックレビューとメタアナリシス

広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

In vivo/ex vivo efficacy of artemether-lumefantrine and artesunate-amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso.

BACKGROUND: Artemisinin-based combination therapy (ACT) is recommended to improve malaria treatment efficacy and limit drug-resistant parasites selection in malaria endemic areas. 5 years after they were adopted, the efficacy and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ), the first-line treatments for uncomplicated malaria were assessed in Burkina Faso. METHODS: In total, 440 children with uncomplicated Plasmodium falciparum malaria were randomized to receive either AL or ASAQ for 3 days and were followed up weekly for 42 days. Blood samples were collected to investigate the ex vivo susceptibility of P. falciparum isolates to lumefantrine, dihydroartemisinin (the active metabolite of artemisinin derivatives) and monodesethylamodiaquine (the active metabolite of amodiaquine). The modified isotopic micro test technique was used to determine the 50% inhibitory concentration (IC50) values. Primary endpoints were the risks of treatment failure at days 42. RESULTS: Out of the 440 patients enrolled, 420 (95.5%) completed the 42 days follow up. The results showed a significantly higher PCR unadjusted cure rate in ASAQ arm (71.0%) than that in the AL arm (49.8%) on day 42, and this trend was similar after correction by PCR, with ASAQ performing better (98.1%) than AL (91.1%). Overall adverse events incidence was low and not significantly different between the two treatment arms. Ex vivo results showed that 6.4% P. falciparum isolates were resistant to monodesthylamodiaquine. The coupled in vivo/ex vivo analysis showed increased IC50 values for lumefantrine and monodesethylamodiaquine at day of recurrent parasitaemia compared to baseline values while for artesunate, IC50 values remained stable at baseline and after treatment failure (p > 0.05). CONCLUSION: These findings provide substantial evidence that AL and ASAQ are highly efficacious for the treatment of uncomplicated malaria in children in Burkina Faso. However, the result of P. falciparum susceptibility to the partner drugs advocates the need to regularly replicate such surveillance studies. This would be particularly indicated when amodiaquine is associated in seasonal malaria chemoprophylaxis (SMC) mass drug administration in children under 5 years in Burkina Faso. Trial registration clinicaltrials, NCT00808951. Registered 05 December 2008,https://clinicaltrials.gov/ct2/show/NCT00808951?cond=NCT00808951&rank=1

Ex vivo anti-malarial drugs sensitivity profile of Plasmodium falciparum field isolates from Burkina Faso five years after the national policy change.

BACKGROUND: The recent reports on the decreasing susceptibility of Plasmodium falciparum to artemisinin derivatives along the Thailand and Myanmar border are worrying. Indeed it may spread to India and then Africa, repeating the same pattern observed for chloroquine resistance. Therefore, it is essential to start monitoring P. falciparum sensitivity to artemisinin derivatives and its partner drugs in Africa. Efficacy of AL and ASAQ were tested by carrying out an in vivo drug efficacy test, with an ex vivo study against six anti-malarial drugs nested into it. Results of the latter are reported here. METHODS: Plasmodium falciparum ex-vivo susceptibility to chloroquine (CQ), quinine (Q), lumefantrine (Lum), monodesethylamodiaquine (MDA), piperaquine (PPQ) and dihydroartemisinin (DHA) was investigated in children (6 months - 15 years) with a parasitaemia of at least ≥4,000/μl. The modified isotopic microtest technique was used. The results of cellular proliferation were analysed using ICEstimator software to determine the 50% inhibitory concentration (IC50) values. RESULTS: DHA was the most potent among the 6 drugs tested, with IC50 values ranging from 0.8 nM to 0.9 nM (Geometric mean IC50 = 0.8 nM; 95% CI [0.8 - 0.9]). High IC50 values ranged between 0.8 nM to 166.1 nM were reported for lumefantrine (Geometric mean IC50 = 25.1 nM; 95% CI [22.4 - 28.2]). MDA and Q IC50s were significantly higher in CQ-resistant than in CQ-sensitive isolates (P = 0.0001). However, the opposite occurred for Lum and DHA (P < 0.001). No difference was observed for PPQ. CONCLUSION: Artemisinin derivatives are still very efficacious in Burkina Faso and DHA-PPQ seems a valuable alternative ACT. The high lumefantrine IC50 found in this study is worrying as it may indicate a decreasing efficacy of one of the first-line treatments. This should be further investigated and monitored over time with large in vivo and ex vivo studies that will include also plasma drug measurements

Maternal antenatal malaria and sexually transmitted infections treatment for the prevention of low birth weight in rural areas of Burkina Faso

Abstract: Low birth weight (LBW, <2,500 g), caused by impaired fetal growth or preterm birth, is the biggest driver of neonatal mortality as it is associated with nearly 80% of all neonatal deaths in sub–Saharan Africa (SSA). In this region, maternal exposure during pregnancy to malaria and sexually transmitted infections (STIs) substantially contribute to LBW occurrence. While there is the WHO recommended sulfadoxine-pyrimethamine based intermittent preventive treatment of malaria in pregnancy (IPTp-SP) strategy to prevent malaria associated adverse birth outcomes, no chemoprevention exists for STIs. Current practices tend to associate an antibiotic efficacious on curable bacterial STIs to the routine IPTp-SP to prevent the combined effects of these infections. However, the hypothesis of whether this combination can reduce LBW is unclear.The context of this study, conducted in rural areas of Burkina Faso, is characterized by a poor socio-economic and security situation resulting in weak health indicators, difficult access to basic health services and a high prevalence of LBW and its contributing infectious factors. The overall aim of the thesis was to contribute to reducing the incidence of adverse birth outcomes in Burkina Faso by systematically adding an antibiotic efficacious on STIs to the WHO recommended IPTp-SP. Specifically, we aimed to i) determine the prevalence and factors associated with LBW; ii) determine the magnitude of pregnant women exposure to malaria and bacterial STIs (syphilis, chlamydiosis and gonorrhea); and iii) test the effects of adding two oral doses of azithromycin to the IPTp-SP strategy to reduce the risk of LBW.Our data showed that LBW prevalence remains high and represented 12% (35/291) of all live-newborns in a health facility-based study conducted in Nanoro heath district at the start of the new IPTp policy. Five years after the start of the new policy, although a reduction trend was observed, the prevalence remained high and 11% (66/600) of neonates assessed were low birth weight in a health facility-based case series study. The analyses showed that several modifiable factors can be targeted to reduce the risk of LBW. Indeed, malaria, which prevalence varied between 17 and 25% according to the diagnostic approach used, was associated with a two-time increase of the risk of LBW. Neonates born from mothers who did not uptake at least three doses of SP for malaria prophylaxis during their pregnancy were shown with a two-times increased risk of LBW. The non-use of insecticide treated nets was also significantly associated with LBW (2.5 times increase). Adolescent primigravid mothers were particularly exposed to LBW delivery, malaria, and sexually transmitted infections.The intervention study within which we included pregnant women at their early stage of pregnancy, showed that the adjunction of azithromycin to the three doses IPTp-SP could not significantly reduce the incidence of LBW across treatment arms beyond that of the three doses IPTp-SP alone (9.4% versus 8.7%). However, the reported rates were lower than that reported in our epidemiological studies, suggesting that an early and adequate initiation of the three-doses IPTp-SP still represents an effective prevention measure. We concluded that the prevalence of LBW in the context of Burkina Faso remains high and that ensuring a minimum of three doses of sulfadoxine pyrimethamine remains an effective prevention strategy. The adjunction of azithromycin to the IPTp-SP regimen did not yield any further benefits. Therefore, strengthening the three doses IPTp-SP strategy would be necessary. Additional interventions are needed to reduce the incidence of LBW so that the neonatal mortality reduction’s goal targeted by the United Nations sustainable development goals (SDGs) can be achievedRésumé: Le petit poids de naissance (PPN, <2 500 g), causé par un retard de croissance intra-utérin ou par une naissance prématurée, est le principal facteur de mortalité néonatale car il est associé à près de 80% des décès néonatals survenant en Afrique subsaharienne. Dans cette région, l'exposition maternelle pendant la grossesse au paludisme et aux infections sexuellement transmises (ISTs) est associée à la survenue de PPN. Pendant que la stratégie du traitement préventif intermittent du paludisme pendant la grossesse avec la sulfadoxine pyriméthamine (TPIg-SP) est recommandée par l’OMS pour prévenir les effets du paludisme, il n’existe aucun traitement préventif pour les ISTs. La pratique actuelle tend à associer un antibiotique efficace sur les ISTs bactériennes au TPIg-SP afin de prévenir leurs effets. Cependant, l’hypothèse que cette association réduirait le risque de PPN n'est pas encore élucidé.Le contexte de cette étude, menée en milieu rural du Burkina Faso, est caractérisé par un défi socio-économique et sécuritaire difficile résultant en de faibles indicateurs sanitaires et une prévalence élevée de PPN et de ses facteurs infectieux. Le but de cette thèse était de contribuer à la réduction de la survenue des issues défavorables de grossesse par l’adjonction systématique d’un antibiotique efficace sur les ISTs au TPIg-SP recommandé par l'OMS. Plus précisément, il s’est agi de i) déterminer la prévalence et les facteurs associés au PPN; ii) déterminer l'ampleur de l’exposition maternelle pendant la grossesse au paludisme et aux ISTs (syphilis, chlamydiose and gonorrhée); et iii) tester l’efficacité et la sécurité d’une stratégie de prévention du PPN associant deux doses d'azithromycine au TPIg-SP pour réduire le risque de PPN.Nos données montrent que la prévalence de l'insuffisance pondérale à la naissance reste élevée et qu'elle a représenté 12% (35/291) de l’ensemble des nouveau-nés vivants au cours d’une étude menée au sein des formations sanitaires du district de santé de Nanoro au début de la nouvelle politique de TPIg. Cinq ans après le début de la nouvelle politique, bien qu'une tendance à la réduction ait été observée, la prévalence est reste élevée et 11% (66/600) des nouveau-nés évalués présentaient une insuffisance pondérale à la naissance dans le cadre d'une série de cas collectés dans quatre formations sanitaires du district sanitaire de Yako.Les analyses ont montré que plusieurs facteurs modifiables peuvent être ciblés pour réduire le risque de PPN. En effet, le paludisme, dont la prévalence variait entre 17% et 25% selon l'approche diagnostique utilisée, était associé à une multiplication par deux du risque de PPN comparativement aux mères sans paludisme. Les nouveau-nés de mères n'ayant pas pris au moins trois doses de SP pour la prophylaxie du paludisme pendant la grossesse montraient également un risque de PPN multiplié par plus de deux. La non-utilisation de moustiquaires imprégnées d'insecticide était également significativement associée (2,5 fois plus) au PPN. Les adolescentes primigestes étaient particulièrement exposées à la fois au PPN, au paludisme et aux infections sexuellement transmises.L'étude d'intervention au cours de laquelle nous avons inclus des femmes enceintes à un stade précoce de leurs grossesses a montré que l'ajout d'azithromycine aux trois doses de TPIg-SP ne réduisait pas de façon significative le risque du PPN entre les bras de traitements (8.7% dans le bras intervention versus 9,4% dans le bras contrôle). Cependant, les taux rapportés étaient inférieurs à ceux de nos études épidémiologiques, suggérant ainsi qu'une initiation précoce et adéquate de la stratégie des trois doses de TPIg-SP reste une mesure de prévention efficace.Nous avons conclu que la prévalence du PPN dans le contexte du Burkina Faso reste élevée et que l'administration d'un minimum de trois doses de sulfadoxine pyriméthamine reste une stratégie de prévention efficace. L'ajout d'azithromycine au TPIg-SP n'a apporté aucun avantage supplémentaire significatif. Par conséquent, un renforcement de la stratégie du traitement préventif intermittent par la sulfadoxine-pyriméthamine (TPIg-SP) avec un minimum de trois doses est nécessaire. Des interventions supplémentaires restent néanmoins nécessaires pour réduire l’incidence du PPN afin que les objectifs de réduction de la mortalité néonatale fixés dans le cadre des objectifs du développement durables (ODD) puissent être réalisés.Doctorat en Santé Publiqueinfo:eu-repo/semantics/nonPublishe

Prevalence and determinants of anaemia among pregnant women in a high malaria transmission setting: a cross-sectional study in rural Burkina Faso.

INTRODUCTION: anemia, the commonest nutritional deficiency disorder among pregnant women in sub-Saharan Africa, is associated with severe peripartum complications. Its regular monitoring is necessary to timely inform clinical and preventive decision-making. The aim of this study was to assess the prevalence and determinants of anemia among pregnant women in rural areas of Burkina Faso. METHODS: between August 2019 and March 2020, a cross-sectional study was conducted to collect maternal sociodemographic, gynaeco-obstetric, and medical characteristics by face-to-face interview or by review of antenatal care books. In addition, maternal malaria was diagnosed by standard microscopy and the hemoglobin levels (Hb) measured by spectrophotometry. The proportion of anaemia (Hb<11.0 g/dL), moderate (7.0<Hb<9.9 g/dL) and severe (Hb<7.0 g/dL) anaemia were determined. The maternal factors associated with anaemia were identified using regression models with likelihood ratio tests. A p-value < 0.05 was considered statistically significant. RESULTS: of 594 pregnant women assessed, the mean hemoglobin level (± standard deviation) was 10.7 (±0.1) g/dL, and the prevalence of anemia was 54.4% (323/594). The proportion of moderate, and severe anemia among pregnant women was 49.2% (95% CI: 45.1%-53.2%), and 5.2% (95% CI: 3.7%-7.3%) respectively. Multivariate analysis showed that the young maternal age (<20 years old) (adjusted OR (aOR): 1.5, 95% CI: 1.1-2.3) and the presence of malaria (aOR: 2.0, 95% CI: 1.3-3.2) were independently associated with the presence of maternal anemia. CONCLUSION: anemia remains common in the study setting and interventions to strengthen malaria prevention in pregnancy, particularly among young adolescent pregnant women, are required to prevent maternal anemia

High prevalence of hepatitis B infections in Burkina Faso (1996–2017): a systematic review with meta-analysis of epidemiological studies

Abstract Background Hepatitis B virus (HBV) infection was long considered an important public health concern in Burkina Faso and still represents a major cause of liver cancer and cirrhosis in the active population. To counter the problem, a national strategic plan was developed and adopted in July 2017 to coordinate viral hepatitis elimination’s efforts. However evidence to support its implementation remains scanty and scattered. The main purpose of this study was to summarize available information from per-reviewed articles published over the last two decades to accurately estimate the prevalence of HBV infection in Burkina Faso. Methods We conducted a systematic search with meta-analysis of scientific articles using Science-Direct, Web-of-Science, PubMed/Medline, and Google Scholar. We systematically assessed all relevant publications that measured the prevalence of hepatitis B surface antigen and which were published between 1996 and 2017. We estimated the national HBV prevalence and its 95% confident interval. We subsequently adjusted the meta-analysis to possible sources of heterogeneity. Results We retrieved and analyzed a total of 22 full text papers including 99,672 participants. The overall prevalence was 11.21%. The prevalence after adjustment were 9.41%, 11.11%, 11.73% and 12.61% in the general population, pregnant women, blood donors and HIV-positive persons respectively. The prevalence was higher before implementation of HBV universal vaccination and decreased from 12.80% between 1996 and 2001 to 11.11% between 2012 and 2017. The prevalence was also higher in rural area 17.35% than urban area 11.11%. The western regions were more affected with 12.69% than the central regions 10.57%. The prevalence was 14.66% in the boucle of Mouhoun region and 14.59 in the center-west region. Aggregate data were not available for the other regions. Conclusions HBV has clearly an important burden in Burkina Faso as described by its high prevalence and this problem significantly challenges the national health care system. There is an urgent need for effective public health interventions to eliminate the problem. However, higher quality data are needed to produce reliable epidemiological estimates that will guide control efforts towards the achievement of the national strategic plan’s goals

Magnitude of low birthweight in malaria endemic settings of Nanoro, rural Burkina Faso: a secondary data analysis.

Low birthweight (LBW) is a worldwide problem that particularly affects developing countries. However, limited information is available on its magnitude in rural area of Burkina Faso. This study aimed to estimate the prevalence of low birthweight and to identify its associated factors in Nanoro health district. A secondary analysis of data collected during a cross-sectional survey was conducted to assess the prevalence of low birthweight in Nanoro health and demographic surveillance system area (HDSS). Maternal characteristics extracted from antenatal care books or by interview, completed by malaria diagnosis were examined through a multi-level logistic regression to estimate odd-ratios of association with low birthweight. Significance level was set at 5%. Of the 291 neonates examined, the prevalence of low birthweight was 12%. After adjustment for socio-demographic, obstetric and malaria prevention variables, being primigravid (OR = 8.84, [95% CI: 3.72-21.01]), or multigravid with history of stillbirth (OR = 5.03, [95% CI: 1.54-16.40]), as well as the lack of long-lasting insecticide treated bed net use by the mother the night preceding the admission for delivery (OR = 2.5, [95% CI: 1.1-5.9]) were significantly associated with neonate low birthweight. The number of antenatal visits however did not confer any direct benefit on birthweight status within this study area. The prevalence of low birthweight was high in the study area and represents an important public health problem in Burkina Faso. In light of these results, a redefinition of the content of the antenatal care package is needed

Prevalence and risk factors of malaria among first antenatal care attendees in rural Burkina Faso

Background: The WHO recommends continuous surveillance of malaria in endemic countries to identify areas and populations most in need for targeted interventions. The aim of this study was to assess the prevalence of malaria and its associated factors among first antenatal care (ANC) attendees in rural Burkina Faso. Methods: A cross-sectional survey was conducted between August 2019 and September 2020 at the Yako health district and included 1067 first ANC attendees. Sociodemographic, gyneco-obstetric, and medical characteristics were collected. Malaria was diagnosed by standard microscopy and hemoglobin level was measured by spectrophotometry. A multivariate logistic regression analysis was used to identify factors associated with malaria infection. Results: Overall malaria infection prevalence was 16.1% (167/1039). Among malaria-positive women, the geometric mean parasite density was 1204 [95% confidence interval (CI) 934–1552] parasites/µL and the proportion of very low (1–199 parasites/µL), low (200–999 parasites/µL), medium (1000–9999 parasites/µL) and high (≥ 10,000 parasites/µL) parasite densities were 15.0%, 35.3%, 38.3% and 11.4%, respectively. Age < 20 years (adjusted odds ratio (aOR): 2.2; 95% CI 1.4–3.5), anemia (hemoglobin < 11 g/deciliter) (aOR: 3.4; 95% CI 2.2–5.5), the non-use of bed net (aOR: 1.8; 95% CI 1.1–2.8), and the absence of intermittent preventive treatment with sulfadoxine–pyrimethamine (aOR: 5.8; 95% CI 2.1–24.5) were positively associated with malaria infection. Conclusions: The study showed that one out of six pregnant women had a microscopy-detected P. falciparum malaria infection at their first ANC visit. Strengthening malaria prevention strategies during the first ANC visit is needed to prevent unfavorable birth outcomes.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Association of malaria and curable sexually transmitted infections with pregnancy outcomes in rural Burkina Faso.

BACKGROUND: Malaria and curable sexually transmitted infections (STIs) are severe infections associated with poor pregnancy outcomes in sub-Saharan countries. These infections are responsible for low birth weight, preterm birth, and miscarriage. In Burkina Faso, many interventions recommended by the World Health Organization were implemented to control the impact of these infections. After decades of intervention, we assessed the impact of these infections on pregnancy outcomes in rural setting of Burkina Faso. METHODS: Antenatal care and delivery data of pregnant women attending health facilities in 2016 and 2017 were collected in two rural districts namely Nanoro and Yako, in Burkina Faso. Regression models with likelihood ratio test were used to assess the association between infections and pregnancy outcomes. RESULTS: During the two years, 31639 pregnant women received antenatal care. Malaria without STI, STI without malaria, and their coinfections were reported for 7359 (23.3%), 881 (2.8 %), and 388 (1.2%) women, respectively. Low birth weight, miscarriage, and stillbirth were observed in 2754 (10.5 %), 547 (2.0 %), and 373 (1.3 %) women, respectively. Our data did not show an association between low birth weight and malaria [Adjusted OR: 0.91 (0.78 - 1.07)], STIs [Adjusted OR: 0.74 (0.51 - 1.07)] and coinfection [Adjusted OR: 1.15 (0.75 - 1.78)]. Low birth weight was strongly associated with primigravidae [Adjusted OR: 3.53 (3.12 - 4.00)]. Both miscarriage and stillbirth were associated with malaria [Adjusted OR: 1.31 (1.07 - 1.59)], curable STI [Adjusted OR: 1.65 (1.06 - 2.59)], and coinfection [Adjusted OR: 2.00 (1.13 - 3.52)]. CONCLUSION: Poor pregnancy outcomes remained frequent in rural Burkina Faso. Malaria, curable STIs, and their coinfections were associated with both miscarriage and stillbirth in rural Burkina. More effort should be done to reduce the proportion of pregnancies lost associated with these curable infections by targeting interventions in primigravidae women