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Taylor S.M.,Duke University | Taylor S.M.,University of North Carolina at Chapel Hill | Mayor A.,Barcelona Center for International Health Research | Mombo-Ngoma G.,University of Health Sciences | And 25 more authors.
Journal of Clinical Microbiology | Year: 2014

Malaria parasite infections that are only detectable by molecular methods are highly prevalent and represent a potential transmission reservoir. The methods used to detect these infections are not standardized, and their operating characteristics are often unknown.We designed a proficiency panel of Plasmodium spp. in order to compare the accuracy of parasite detection of molecular protocols used by labs in a clinical trial consortium. Ten dried blood spots (DBSs) were assembled that contained P. falciparum, P. vivax, P. malariae, and P. ovale; DBSs contained either a single species or a species mixed with P. falciparum. DBS panels were tested in 9 participating laboratories in a masked fashion. Of 90 tests, 68 (75.6%) were correct; there were 20 false-negative results and 2 false positives. The detection rate was 77.8% (49/63) for P. falciparum, 91.7% (11/12) for P. vivax, 83.3% (10/12) for P. malariae, and 70% (7/10) for P. ovale. Most false-negative P. falciparum results were from samples with an estimd <5 parasites perl of blood. Between labs, accuracy ranged from 100% to 50%. In one lab, the inability to detect species in mixed-species infections prompted a redesign and improvement of the assay. Most PCR-based protocols were able to detect P. falciparum and P. vivax at higher densities, but these assays may not reliably detect parasites in samples with low P. falciparum densities. Accordingly, formal quality assurance for PCR should be employed whenever this method is used for diagnosis or surveillance. Such efforts will be important if PCR is to be widely employed to assist malaria elimination efforts. © 2014 American Society for Microbiology. All Rights Reserved.


Jackle M.J.,Ngounie Medical Research Center | Jackle M.J.,University of Tübingen | Blumentrath C.G.,Ngounie Medical Research Center | Blumentrath C.G.,University of Tübingen | And 9 more authors.
Malaria Journal | Year: 2013

Background: Malaria remains one of the most important infectious diseases in pregnancy in sub-Saharan Africa. Whereas seasonal malaria chemoprevention is advocated as public health intervention for children in certain areas of highly seasonal malaria transmission, the impact of seasonality on malaria in pregnancy has not yet been investigated for stable, hyper-endemic transmission settings of Equatorial Africa. The aim of this study was to investigate the influence of seasonality on the prevalence of malaria in pregnancy in Gabon. Methods. The study was conducted at a rural district hospital in Gabon between January 2008 and December 2011. At first antenatal care visits demographic data, parity, age, and gestational age of pregnant women were documented and thick blood smears were performed for the diagnosis of malaria. Seasonality and established risk factors were evaluated in univariate and multivariate analysis for their association with Plasmodium falciparum infection. Results: 1,661 pregnant women were enrolled in this study. Participants presenting during high transmission seasons were at significantly higher risk for P. falciparum infection compared to low transmission seasons (adjusted odds ratio [AOR] 1.91, 95% confidence interval [CI] 1.39-2.63, p < 0.001). Established risk factors including parity (AOR 0.45, CI 0.30-0.69, p < 0.001 for multipara versus paucipara) and age (AOR, CI and p-value for women aged 13-17, 18-22, 23-27 and ≥28 years, respectively: AOR 0.59, CI 0.40-0.88; AOR 0.57, CI 0.34-0.97; AOR 0.51, CI 0.29-0.91) were significant risk factors for P. falciparum infection. High-risk groups including nulli- and primipara and younger women aged 13-17 years showed a disproportionately increased risk for malaria in high transmission seasons from 17% to 64% prevalence in low and high transmission periods, respectively. Conclusion: Seasonal variations lead to important differences in the risk for P. falciparum infection in pregnancy in the setting of central African regions with stable and hyper-endemic malaria transmission. The seasonal increase in malaria in pregnancy is most pronounced in high-risk groups constituted by young and pauciparous women. The evaluation of tailored seasonal prevention strategies for these high-risk populations may, therefore, be warranted. © 2013 Jäckle et al.; licensee BioMed Central Ltd.


PubMed | TU Dresden, University of Tübingen, University of Barcelona and Ngounie Medical Research Center
Type: | Journal: Scientific reports | Year: 2015

Neonatal invasive disease due to Streptococcus agalactiae is life threatening and preventive strategies suitable for resource limited settings are urgently needed. Protective coverage of vaccine candidates based on capsular epitopes will relate to local epidemiology of S. agalactiae serotypes and successful management of critical infections depends on timely therapy with effective antibiotics. This is the first report on serotype distribution and antimicrobial susceptibility of S. agalactiae in pregnant women from a Central African region. Serotypes V, III, and Ib accounted for 88/109 (81%) serotypes and all isolates were susceptible to penicillin and clindamycin while 13% showed intermediate susceptibility to erythromycin.


Gonzalez R.,University of Barcelona | Gonzalez R.,Manhica Health Research Center | Mombo-Ngoma G.,Albert Schweitzer Hospital | Mombo-Ngoma G.,University of Tübingen | And 42 more authors.
PLoS Medicine | Year: 2014

Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women.A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 [13.0%]) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio [RR], 1.02 (95% CI 0.86–1.22; p = 0.80 in the ITT analysis). Women receiving MQ had reduced risks of parasitemia (63/1,372 [4.6%] in the SP group and 88/2,737 [3.2%] in the MQ group; RR, 0.70 [95% CI 0.51–0.96]; p = 0.03) and anemia at delivery (609/1,380 [44.1%] in the SP group and 1,110/2743 [40.5%] in the MQ group; RR, 0.92 [95% CI 0.85–0.99]; p = 0.03), and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year [PYAR] in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 [95% CI 0.52–0.88]; p = 0.004) and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 [0.78–0.95]; p = 0.003). There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP. The most frequently reported related adverse events were dizziness (ranging from 33.9% to 35.5% after dose 1; and 16.0% to 20.8% after dose 2) and vomiting (30.2% to 31.7%, after dose 1 and 15.3% to 17.4% after dose 2) with similar proportions in the full and split MQ arms. The open-label design is a limitation of the study that affects mainly the safety assessment.Women taking MQ IPTp (15 mg/kg) in the context of long lasting insecticide treated nets had similar prevalence rates of low birth weight as those taking SP IPTp. MQ recipients had less clinical malaria than SP recipients, and the pregnancy outcomes and safety profile were similar. MQ had poorer tolerability even when splitting the dose over two days. These results do not support a change in the current IPTp policy.ClinicalTrials.gov NCT 00811421 Pan African Clinical Trials Registry PACTR 2010020001429343Please see later in the article for the Editors' Summary. © 2014 González et al.


PubMed | University of Tübingen, University of Barcelona, ManhicaHealthResearch Center, Leiden University and 7 more.
Type: Journal Article | Journal: BMJ open | Year: 2016

One of Africas most important challenges is to improve maternal and neonatal health. The identification of groups at highest risk for adverse pregnancy outcomes is important for developing and implementing targeted prevention programmes. This study assessed whether young adolescent girls constitute a group at increased risk for adverse birth outcomes among pregnant women in sub-Saharan Africa.Data were collected prospectively as part of a large randomised controlled clinical trial evaluating intermittent preventive treatment of malaria in pregnancy (NCT00811421-Clinical Trials.gov), conducted between September 2009 and December 2013 in Benin, Gabon, Mozambique and Tanzania.Of 4749 participants, pregnancy outcomes were collected for 4388 deliveries with 4183 live births including 83 multiple gestations. Of 4100 mothers with a singleton live birth delivery, 24% (975/4100) were adolescents (19years of age) and 6% (248/4100) were aged 16years.Primary outcomes of this predefined analysis were preterm delivery and low birth weight.The overall prevalence of low birthweight infants and preterm delivery was 10% (371/3851) and 4% (159/3862), respectively. Mothers aged 16years showed higher risk for the delivery of a low birthweight infant (OR: 1.96; 95% CI 1.35 to 2.83). Similarly, preterm delivery was associated with young maternal age (16years; OR: 2.62; 95% CI 1.59 to 4.30). In a subanalysis restricted to primiparous women: preterm delivery, OR 4.28; 95% CI 2.05 to 8.93; low birth weight, OR: 1.29; 95% CI 0.82 to 2.01.Young maternal age increases the risk for adverse pregnancy outcomes and it is a stronger predictor for low birth weight and preterm delivery than other established risk factors in sub-Saharan Africa. This finding highlights the need to improve adolescent reproductive health in sub-Saharan Africa.NCT00811421; Post-results.


Schaumburg F.,University of Munster | Schaumburg F.,Albert Schweitzer Hospital | Alabi A.S.,Albert Schweitzer Hospital | Alabi A.S.,University of Tübingen | And 28 more authors.
Clinical Microbiology and Infection | Year: 2014

Staphylococcus aureus colonization is a risk factor for invasive disease. There is a need to understand S. aureus colonization in infancy as the burden of S. aureus infections in infants is high. We aimed to investigate the transmission of S. aureus between mothers and their newborns during the first year after delivery in an African setting. In a longitudinal cohort study, colonization of Gabonese mother-infant pairs was assessed at delivery and after 1, 9 and 12 months. Swabs were taken from mothers (nares, mammillae) and infants (nares and throat). Isolates were characterized and risk factors for colonization were assessed using a standardized questionnaire. We recruited 311 mothers and 318 infants including seven sets of twins. Maternal and infant colonization rates declined synchronously following a peak after 1 month at 40% (mothers) and 42% (infants). Maternal colonization was a risk factor for S. aureus carriage in infants. Based on spa typing, direct mother-to-infant transmission was evident in 5.6%. Of all methicillin-resistant isolates (n = 9), 44.4% were related to the USA300 clone; 56.7% (n = 261) of all S. aureus carried Panton-Valentine leukocidin encoding genes. Direct mother-to-infant transmission was rare and cannot explain the increase of carriage in infants within the first month. A transmission from external sources is likely and challenges the S. aureus infection control in newborns and infants in an African setting. The detection of USA300-related MRSA fuels the concern about the spread of this clone in Central Africa. © 2013 European Society of Clinical Microbiology and Infectious Diseases.


Basra A.,University of Health Sciences | Basra A.,Ngounie Medical Research Center | Basra A.,University of Tübingen | Mombo-Ngoma G.,University of Health Sciences | And 24 more authors.
Clinical Infectious Diseases | Year: 2013

Background. Urogenital schistosomiasis is a major public health problem in sub-Saharan Africa, and routine programs for screening and treatment of pregnant women are not established. Mefloquine - currently evaluated as a potential alternative to sulfadoxine-pyrimethamine as intermittent preventive treatment against malaria in pregnancy (IPTp) - is known to exhibit activity against Schistosoma haematobium. In this study we evaluated the efficacy of mefloquine IPTp against S. haematobium infection in pregnant women. Methods. Pregnant women with S. haematobium infection presenting at 2 antenatal health care centers in rural Gabon were invited to participate in this nested randomized controlled, assessor-blinded clinical trial comparing sulfadoxine-pyrimethamine with mefloquine IPTp. Study drugs were administered twice during pregnancy with a 1- month interval after completion of the first trimester. Results. Sixty-five pregnant women were included in this study. Schistosoma haematobium egg excretion rates showed a median reduction of 98% (interquartile range [IQR], 70%-100%) in the mefloquine group compared to an increase of 20% (IQR, -186% to 75%) in the comparator group. More than 80% of patients showed at least 50% reduction of egg excretion and overall cure rate was 47% (IQR, 36%-70%) 6 weeks after the second administration of mefloquine IPTp. Conclusion. When used as IPTp for the prevention of malaria, mefloquine shows promising activity against concomitant S. haematobium infection leading to an important reduction of egg excretion in pregnant women. Provided that further studies confirm these findings, the use of mefloquine may transform future IPTp programs into a 2-pronged intervention addressing 2 of the most virulent parasitic infections in pregnant women in sub-Saharan Africa. © 2012 The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.


PubMed | Leiden University, University of Tübingen, University of Barcelona, Medical University of Vienna and Ngounie Medical Research Center
Type: | Journal: International journal for parasitology | Year: 2016

An estimated 40 million women of childbearing age suffer from schistosomiasis. Animal models indicate a deleterious effect of maternal schistosomiasis on pregnancy outcomes. To date there is a lack of epidemiological evidence evaluating schistosomiasis-related morbidity in pregnancy. This study was designed to describe the impact of urogenital schistosomiasis on pregnancy outcomes in a highly endemic region of central Africa. Pregnant women attending antenatal clinics in Fougamou and Lambarn, Gabon, were consecutively screened for the presence of Schistosoma haematobium eggs in diurnal urine samples. Maternal and newborn characteristics assessed at delivery were compared between infected and uninfected mothers. The impact of maternal schistosomiasis on low birth weight and preterm delivery was assessed using logistic regression analysis. Urogenital schistosomiasis was diagnosed in 103 (9%) of 1115 pregnant women. Maternal age was inversely associated with the prevalence of urogenital schistosomiasis, with a higher burden amongst nulliparous women. Low birth weight was more common amongst infants of S. haematobium-infected mothers. This association was unaffected by controlling for demographic characteristics, gestational age and Plasmodium infection status (adjusted Odds Ratio 1.93; 95% confidence interval: 1.08-3.42). Other risk factors associated with low birth weight delivery were underweight mothers (adjusted Odds Ratio 2.34; 95% confidence interval: 1.12-4.92), peripheral or placental Plasmodium falciparum infection (adjusted Odds Ratio 2.04; 95% confidence interval: 1.18-3.53) and preterm birth (adjusted Odds Ratio 3.12; 95% confidence interval: 1.97-4.96). Preterm delivery was not associated with S. haematobium infection (adjusted Odds Ratio 1.07 95% confidence interval: 0.57-1.98). In conclusion, this study indicates that pregnant women with urogenital schistosomiasis are at an increased risk for low birth weight deliveries. Further studies evaluating targeted treatment and prevention programmes for urogenital schistosomiasis in pregnant women and their impact on delivery outcomes are warranted.


PubMed | University of Tübingen, University of Barcelona, Charité - Medical University of Berlin, University of Health Sciences and 2 more.
Type: Journal Article | Journal: The Journal of antimicrobial chemotherapy | Year: 2015

Streptococcus agalactiae constitutes an important cause of neonatal infections in sub-Saharan Africa. Sulfadoxine/pyrimethamine-the current intermittent preventive treatment of malaria in pregnancy (IPTp)-has proven in vitro activity against group B Streptococcus (GBS). Because of specific drug resistance to sulfadoxine/pyrimethamine, mefloquine-an antimalarial without in vitro activity against GBS-was evaluated as a potential alternative. This study assessed the potential of sulfadoxine/pyrimethamine-IPTp to reduce the prevalence of GBS colonization in pregnant women in Gabon when compared with the inactive control mefloquine-IPTp.Pregnant women participating in a randomized controlled clinical trial evaluating mefloquine-IPTp versus sulfadoxine/pyrimethamine-IPTp were invited to participate and recto-vaginal swabs were collected at delivery for detection of GBS colonization. Prevalence of recto-vaginal GBS colonization was compared between IPTp regimens and risk factor and birth outcome analyses were computed.Among 549 participants, 106 were positive for GBS colonization at delivery (19%; 95% CI=16%-23%). Prevalence of maternal GBS colonization showed no significant difference between the two IPTp regimens (mefloquine-IPTp: 67 of 366 women=18%; 95% CI=14%-22%; sulfadoxine/pyrimethamine-IPTp: 39 of 183 women=21%; 95% CI=15%-27%). Risk factor analysis for GBS colonization demonstrated a significant association with illiteracy (adjusted OR=2.03; 95% CI=1.25-3.30). GBS colonization had no impact on birth outcome, anaemia at delivery, gestational age and birth weight.Sulfadoxine/pyrimethamine did not reduce colonization rates when used as the IPTp drug during pregnancy. Illiteracy was associated with GBS colonization.


PubMed | University of Tübingen, University of Bonn, Max Planck Institute for Infection Biology, University of Munster and 2 more.
Type: | Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases | Year: 2016

The colonization of afro-tropical wildlife with Staphylococcus aureus and the derived clade Staphylococcus schweitzeri remains largely unknown. A reservoir in bats could be of importance since bats and humans share overlapping habitats. In addition, bats are food sources in some African regions and can be the cause of zoonotic diseases. Here, we present a cross-sectional survey employing pharyngeal swabs of captured and released bats (n=133) in a forest area of Gabon. We detected low colonization rates of S. aureus (4-6%) and S. schweitzeri (4%) in two out of four species of fruit bats, namely Rousettus aegyptiacus and Micropteropus pusillus, but not in insectivorous bats. Multilocus sequence typing showed that S. aureus from Gabonese bats (ST2984, ST3259, ST3301, ST3302) were distinct from major African human associated clones (ST15, ST121, ST152). S. schweitzeri from bats (ST1697, ST1700) clustered with S. schweitzeri from other species (bats, monkeys) from Nigeria and Cte dIvoire. In conclusion, colonization rates of bats with S. aureus and S. schweitzeri were low in our study. Phylogenetic analysis supports an intense geographical dispersal of S. schweitzeri among different mammalian wildlife hosts.

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