Arti Basra

Efficacy of Mefloquine Intermittent Preventive Treatment in Pregnancy Against Schistosoma haematobium Infection in Gabon: A Nested Randomized Controlled Assessor-Blinded Clinical Trial

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. CLINICAL TRIALS REGISTRATION NCT01132248; ATMR2010020001429343.

Transmission of Staphylococcus aureus between mothers and infants in an African setting.

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.

Prospective evaluation of artemether-lumefantrine for the treatment of non-falciparum and mixed-species malaria in Gabon

BackgroundThe recommendation of artemisinin combination therapy (ACT) as first-line treatment for uncomplicated falciparum malaria is supported by a plethora of high quality clinical trials. However, their recommendation for the treatment of mixed-species malaria and the large-scale use for the treatment of non-falciparum malaria in endemic regions is based on anecdotal rather than systematic clinical evidence.MethodsThis study prospectively observed the efficacy of artemether-lumefantrine for the treatment of uncomplicated non-falciparum or mixed-species malaria in two routine district hospitals in the Central African country of Gabon.ResultsForty patients suffering from uncomplicated Plasmodium malariae, Plasmodium ovale or mixed-species malaria (including Plasmodium falciparum) presenting at the hospital received artemether-lumefantrine treatment and were followed up. All evaluable patients (n = 38) showed an adequate clinical and parasitological response on Day 28 after oral treatment with artemether-lumefantrine (95% confidence interval: 0.91,1). All adverse events were of mild to moderate intensity and completely resolved by the end of study.ConclusionsThis first systematic assessment of artemether-lumefantrine treatment for P. malariae, P. ovale and mixed-species malaria demonstrated a high cure rate of 100% and a favourable tolerability profile, and thus lends support to the practice of treating non-falciparum or mixed-species malaria, or all cases of malaria without definite species differentiation, with artemether-lumefantrine in Gabon.Trial RegistrationClinicalTrials.gov Identifier: NCT00725777

Pyronaridine-artesunate combination therapy for the treatment of malaria.

Purpose of review Pyronaridine–artesunate is among the most promising novel artemisinin combination therapies for the treatment of malaria. A series of clinical phase II and III trials have been conducted for the indications of uncomplicated falciparum and vivax malaria in Africa and Asia. On the basis of these novel data, this review aims to provide an appraisal of current evidence and a perspective for its future role in the antimalarial portfolio. Recent findings Pyronaridine–artesunate demonstrated repeatedly high efficacy in the treatment of vivax and falciparum malaria and noninferiority was established compared to standard comparator regimens. An innovative paediatric drug formulation was developed in parallel to the tablet formulation for the treatment of young children. Pharmacokinetic analysis showed dose linearity, low interindividual variation and absence of a clinically important effect of food on the bioavailability of this drug combination. Overall tolerability and safety data are reassuring; however, further surveillance of safety in special patient populations including young children is warranted. Summary Pyronaridine–artesunate – currently under evaluation by the European Medicines Agency – may become a preferred choice as first-line therapy in malaria endemic regions based on its low cost, long shelf-life, simplified once-daily dosing regimen, proven efficacy against falciparum and vivax malaria, and the parallel clinical development of a paediatric drug formulation.

Young adolescent girls are at high risk for adverse pregnancy outcomes in sub-Saharan Africa: an observational multicountry study

Objectives 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. Setting 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. Participants 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 (≤19 years of age) and 6% (248/4100) were aged ≤16 years. Primary and secondary outcome measures Primary outcomes of this predefined analysis were preterm delivery and low birth weight. Results The overall prevalence of low birthweight infants and preterm delivery was 10% (371/3851) and 4% (159/3862), respectively. Mothers aged ≤16 years 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 (≤16 years; 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. Conclusions 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. Trial registration number NCT00811421; Post-results.

Current status of the clinical development and implementation of paediatric artemisinin combination therapies in Sub-Saharan Africa

ZusammenfassungAfrikanische Kinder unter 5 Jahren sind aufgrund der hohen Morbidität und Mortalität die global wichtigste Patientengruppe für die Therapie der Malaria. Erst seit kurzem sind Artemisininkombinationtherapien – die Erstlinientherapie der Malaria tropica – in pädiatrischen Medikamentenformulierungen entwickelt worden. Der Einsatz dieser neuen Medikamentenformulierungen verbessert die Verträglichkeit dieser Medikamente bei Kleinkindern und ist daher ein wichtiger Fortschritt im therapeutischen Management. Dennoch werden diese neuen Therapeutika derzeit großteils noch nicht von nationalen und internationalen Therapierichtlinien berücksichtigt. Daten eines kürzlich durchgeführten Surveys zeigen allerdings, dass trotz des Fehlens offizieller Empfehlungen für pädiatrische Artemisininkombinationen, diese in weiten Teilen Afrikas bereits die Erstlinientherapie darstellen. Es wird diskutiert, warum Qualitätssicherung dieser Gruppe an Malariatherapeutika besonders wichtig erscheint und welche klinische Evidenz erbracht werden sollte, um eine offizielle Empfehlung für die Verwendung von pädiatrischen Artemisininkombinationen zu erzielen.SummaryTimely treatment of infected children with artemisinin based combination therapies is an essential tool for the effective control and potential elimination of malaria. Until recently only tablet formulations have been available for the treatment of children leading to problems of swallowability, palatability and dosing. In consequence, paediatric drug formulations of artemisinin-based combination therapy (ACT) have been developed, showing a clinically significant improvement of tolerability in young children and of their implementation is an increasingly important public health issue. In this mini-review, we focus on the recent development of paediatric ACTs and their use in practice. Paediatric ACTs are formulated as syrup, powder for suspension, dispersible tablets and granules. Overall, the use of paediatric formulation results in an improved management of clinical malaria in young children. To date, only two paediatric ACTs have been certified with WHO prequalification status as an internationally accepted quality standard. Many more paediatric ACTs are available and in use in sub-Saharan Africa despite a lack of publicly available evidence from stringent clinical development programs. The conduct of effectiveness studies to support the introduction of paediatric ACTs in official treatment recommendations is crucial in the global strategy of malaria elimination and quality assurance of available products is a public health priority.

Epidemiology and management of group B streptococcal colonization during pregnancy in Africa

Group B streptococcal infections are a leading cause of neonatal morbidity and mortality. Maternal microbiological screening during pregnancy and intrapartum antimicrobial treatment of maternal group B streptococcus (GBS) colonization constitutes an effective prevention strategy to reduce early neonatal invasive disease due to GBS in the European and North American setting. Data on the prevalence of GBS colonization in pregnancy and incidence of neonatal invasive GBS disease are very limited for low-income regions. However, the first reports from sub-Saharan Africa indicate that GBS colonization rates may be comparable to industrialized countries and that related neonatal morbidity and mortality is of significance. Prior to the development of suitable prevention strategies, which are undoubtedly needed in resource poor settings, more evidence on GBS epidemiology in sub-Saharan Africa and assessment of cost effectiveness of different prevention strategies are essential.ZusammenfassungGruppe B Streptokokken stellen eine bedeutende Ursache der frühen Neugeborenen-Sepsis dar. Das in Europa und den USA eingeführte mikrobiologische Screening schwangerer Frauen auf urogenitale Gruppe B Streptokokken Kolonisation sowie die antimikrobielle Therapie bei Gruppe B Streptokokken Besiedlung reduzierte die Inzidenz der invasiven Neugeboreneninfektion durch Gruppe B Streptokokken deutlich. Für einkommensschwache Länder gibt es jedoch nur unzureichende Daten zur Prävalenz mütterlicher Gruppe B Streptokokken Kolonisation und Inzidenz invasiver Neugeboreneninfektion durch Gruppe B Streptokokken. Vereinzelte Berichte aus dem südlichen Afrika lassen jedoch annehmen, dass die Raten mütterlicher Gruppe B Streptokokken Besiedlung und assoziierter neonataler Morbidität und Mortalität ähnlich hoch sind wie in Industrieländern. Zur Entwicklung geeigneter Präventionsstrategien für das tropische Afrika sind dringend Studien zur lokalen Epidemiologie der Gruppe B Streptokokken und Kosteneffizienz potentieller Präventionsmaßnahmen notwendig.

Pyronaridine: a new 'old' drug on the verge of entering the antimalarial armamentarium.

Evaluation of: Price RN, Marfurt J, Chalfein F et al. In vitro activity of pyronaridine against mutidrug-resistant Plasmodium falciparum and Plasmodium vivax. Antimicrob. Agents Chemother. 54, 5146–5150 (2010). Pyronaridine–artesunate is a promising new artemisinin-based combination therapy for the treatment of uncomplicated falciparum malaria and the first systematically evaluated artemisinin-based combination therapy for vivax malaria. The 3-day regimen proved to be highly efficacious in clinical trials in Africa and Asia and is currently under review by the EMA. Price et al. report data of an in vitro drug-susceptibility study evaluating the activity of pyronaridine against Plasmodium vivax and Plasmodium falciparum field isolates from Papua, Indonesia. The authors demonstrate high in vitro activity of pyronaridine at low nanomolar concentrations that is only paralleled by the artemisinin class of antimalarials. Besides exciting methodological insights into the new field of in vitro drug-susceptibility testing for P. vivax, these data are encouraging evidence for the future implementation of pyronaridine in combination therapy for the fight against malaria.

Evaluation of intermittent preventive treatment of malaria against group B Streptococcus colonization in pregnant women: a nested analysis of a randomized controlled clinical trial of sulfadoxine/pyrimethamine versus mefloquine

OBJECTIVES 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. METHODS 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. RESULTS 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. CONCLUSIONS Sulfadoxine/pyrimethamine did not reduce colonization rates when used as the IPTp drug during pregnancy. Illiteracy was associated with GBS colonization.

Urogenital schistosomiasis during pregnancy is associated with low birth weight delivery: analysis of a prospective cohort of pregnant women and their offspring in Gabon

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 Lambaréné, 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.