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1.
Borrmann S Adegnika AA Matsiegui PB Issifou S Schindler A Mawili-Mboumba DP Baranek T Wiesner J Jomaa H Kremsner PG 《The Journal of infectious diseases》2004,189(5):901-908
BACKGROUND: Fosmidomycin is a new antimalarial drug with a novel mechanism of action. Studies in Africa that have evaluated fosmidomycin as monotherapeutic agent demonstrated its excellent tolerance, but 3-times-daily treatment regimens of >or=4 days were required to achieve radical cure, prompting further research to identify and validate a suitable combination partner to enhance its efficacy. METHODS: We conducted a randomized, controlled, open-label study to evaluate the efficacy and safety of fosmidomycin combined with clindamycin (n=12; 30 and 5 mg/kg body weight every 12 h for 5 days, respectively), compared with fosmidomycin alone (n=12; 30 mg/kg body weight every 12 h for 5 days) and clindamycin alone (n=12; 5 mg/kg body weight every 12 h for 5 days) for the clearance of asymptomatic Plasmodium falciparum infections in schoolchildren in Gabon aged 7-14 years. RESULTS: Asexual parasites were rapidly cleared in children treated with fosmidomycin-clindamycin (median time, 18 h) and fosmidomycin alone (25 h) but slowly in children treated with clindamycin alone (71 h; P=.004). However, only treatment with fosmidomycin-clindamycin or clindamycin alone led to the radical elimination of asexual parasites as measured by day 14 and 28 cure rates of 100%. Asexual parasites reappeared by day 28 in 7 children who received fosmidomycin (day 14 cure rate, 92% [11/12; day 28 cure rate, 42% [5/12]). All regimens were well tolerated, and no serious adverse events occurred. CONCLUSION: The combination of fosmidomycin and clindamycin is well tolerated and superior to either agent on its own with respect to the rapid and radical clearance of P. falciparum infections in African children. 相似文献
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Dietmann A Helbok R Lackner P Issifou S Lell B Matsiegui PB Reindl M Schmutzhard E Kremsner PG 《The Journal of infectious diseases》2008,197(11):1614-1620
BACKGROUND: Molecular mechanisms involved in the pathogenesis of severe malaria caused by Plasmodium falciparum are not fully understood. Matrix metalloproteinases (MMPs) are enzymes that proteolytically degrade both the extracellular matrix and nonmatrix substances with various functions in the modulation of immune response. The key inhibitors of MMPs are the tissue inhibitors of metalloproteinases (TIMPs). METHODS: We studied levels of MMP-8, MMP-9, TIMP-1, and TIMP-2 on admission and after 24 h, using an enzyme-linked immunosorbent assay, in serum specimens from 50 Gabonese children with severe malaria, 43 children with uncomplicated malaria, and 27 healthy control children. RESULTS: Serum MMP-8 and TIMP-1 levels were significantly higher in the severe malaria and uncomplicated malaria groups, compared with those in the control group (P < .001). TIMP-1 levels were significantly higher in patients with severe malaria, compared with those in patients with uncomplicated malaria (P < .001). High TIMP-1 levels were significantly correlated with malaria severity, as determined by the simplified multiorgan dysfunction score (Spearman rank-correlation coefficient, 0.55; P < .001). CONCLUSIONS: TIMP-1 is associated with signs and symptoms of severe malaria. MMP-8 levels are elevated in patients with severe or uncomplicated P. falciparum malaria. MMPs and TIMPs may be relevant in the pathogenesis of severe malaria, either as proteolytic enzymes that degrade the extracellular matrix or as effectors and regulators of the immune response. 相似文献
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Ateba Ngoa U Schaumburg F Adegnika AA Kösters K Möller T Fernandes JF Alabi A Issifou S Becker K Grobusch MP Kremsner PG Lell B 《Acta tropica》2012,124(1):42-47
Little data is available on the epidemiology of Staphylococcus aureus in Africa. In the present study we aim at characterizing the population structure of S. aureus in healthy subjects from a rural and a semi-urban area in Lambaréné, Gabon as well as in hospital staff and inpatients. In total, 500 subjects were screened for S. aureus colonization of the nares, axillae and inguinal region. Overall, 146 (29%) were positive. We found 46 different spa types. The most frequent spa types were t084 (35%) and the agr II was the most prevalent subtype of the accessory gene regulator (56%, n=82). Five isolates (3%) were methicillin resistant S. aureus (MRSA). Carriage rates of S. aureus in Gabon are comparable to developed countries. MRSA is for the first time described and could pose a significant health threat in this region with limited access to microbiological laboratory facilities and to adequate antimicrobial agents. 相似文献
4.
Lell B Missinou MA Issifou S Matsiegui PB Olola CH Taylor TE Kremsner PG 《The American journal of tropical medicine and hygiene》2005,73(3):588-592
Severe and fatal malaria is associated with the increased presence of malaria hemozoin in peripheral phagocytes. Large studies of this relationship are hampered by the fact that identifying and counting phagocytes on thick blood smears is time consuming. Distinguishing which mononuclear cells are monocytes and which granulocytes are neutrophils requires time and careful training. In this study, we evaluated a simplified method in which only the proportions of hemozoin-containing mononuclear cells and granulocytes are counted. Thick blood films from 471 Gabonese children with malaria were evaluated. We found a linear relationship and a strong correlation between the proportions of hemozoin-containing monocytes versus mononuclear cells (r = 0.85) and neutrophils versus polymorphonuclear cells (r = 0.93), respectively. The two methods had similar predictive values, as estimated by receiver operating characteristics curves. This simplified method can be used to estimate the amount of extra-erythrocytic pigment in peripheral blood, and we suggest that it may be particularly suitable for very large studies. 相似文献
5.
Dal-Bianco MP Köster KB Kombila UD Kun JF Grobusch MP Ngoma GM Matsiegui PB Supan C Salazar CL Missinou MA Issifou S Lell B Kremsner P 《The American journal of tropical medicine and hygiene》2007,77(5):939-942
Plasmodium falciparum, the most common malarial parasite in sub-Saharan Africa, accounts for a high number of deaths in children less than five years of age. In malaria-endemic countries with stable transmission, semi-immunity is usually acquired after childhood. For adults, severe malaria is rare. Infected adults have either uncomplicated malaria or asymptomatic parasitemia. During a period of one year, we screened 497 afebrile males to investigate the prevalence of asymptomatic P. falciparum parasitemia in villages near Lambaréné, Gabon by use of three different methods. A total of 52% of the individuals had parasites detected by a subtelomeric variable open reading frame polymerase chain reaction (stevor-PCR), 27% of the rapid diagnostic test results were positive, and 12% of the thick blood smears with low parasitemias had P. falciparum. Most positive cases were only detected by the stevor-PCR. Asymptomatic P. falciparum parasitemia in adults living in a malaria-endemic country is frequent. 相似文献
6.
Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon 总被引:1,自引:0,他引:1
Ramharter M Kurth F Schreier AC Nemeth J Glasenapp Iv Bélard S Schlie M Kammer J Koumba PK Cisse B Mordmüller B Lell B Issifou S Oeuvray C Fleckenstein L Kremsner PG 《The Journal of infectious diseases》2008,198(6):911-919
BACKGROUND: The development of novel artemisinin-combination therapies suitable for the treatment of pediatric patients suffering from malaria is a research priority. The aim of this study was to investigate a novel fixed-dose pyronaridine-artesunate combination for the treatment of uncomplicated falciparum malaria in Gabonese patients 2-14 years old. METHODS: The study was designed as an open-label dose-escalation study recruiting 60 pediatric patients sequentially in 4 treatment cohorts: study drugs were administered once daily for 3 days, as tablet coformulations (pyronaridine:artesunate ratios of 6:2, 9:3, and 12:4 mg/kg) and as a granule coformulation (pyronaridine:artesunate ratio of 9:3 mg/kg). The primary end points were tolerability, safety, and pharmacokinetics of pyronaridine-artesunate treatment. Efficacy was treated as a secondary outcome measure. RESULTS: The drugs had a good tolerability and safety profile, at all dose levels. Pharmacokinetic analysis revealed a dose-dependent increase in the maximum plasma/blood concentration and the area under the curve, as well as comparable relative bioavailability for the granule coformulation. Polymerase chain reaction-corrected cure rates at day 28 were 100% in per-protocol analysis, at all dose levels. CONCLUSIONS: Pyronaridine-artesunate is a promising novel artemisinin-combination therapy for pediatric patients with uncomplicated Plasmodium falciparum malaria, and the development of both the tablet and the granule coformulations is warranted. 相似文献
7.
Eubanks August Coulibaly Bakary Dembélé Keita Bintou Anoma Camille DAH Ter Tiero Elias Mensah Ephrem Maradan Gwenaëlle Bourrelly Michel Mora Marion Riegel Lucas Rojas Castro Daniela Yaya Issifou Spire Bruno Laurent Christian Sagaon-Teyssier Luis 《AIDS and behavior》2022,26(11):3524-3537
AIDS and Behavior - We investigated the rate and predictors of ineffective HIV protection in men who have sex with men (MSM) taking pre-exposure prophylaxis (PrEP) in a prospective cohort study... 相似文献
8.
Reasons for non-adherence to vaccination at mother and child care clinics (MCCs) in Lambaréné, Gabon
Norbert G. Schwarz Marjolein Gysels Christopher Pell Julian Gabor Meike Schlie Saadou Issifou Bertrand Lell Peter G. Kremsner Martin P. Grobusch Robert Pool 《Vaccine》2009
The aim of this paper is to explore attitudes of mothers towards childhood vaccinations and reasons for non-attendance and non-adherence to mother–child clinics (MCCs). Forty in-depth interviews with mothers of children under 5 years of age revealed positive attitudes towards vaccination that seem at odds with the region's observed low vaccination coverage. Important reasons for MCC non-attendance included distance to the MCC, transport costs, negative experiences at MCCs (such as interactions with unfriendly staff) and mothers’ feeling of shame provoked by different, often poverty-associated reasons such as attending the clinic with a dirty or poorly clothed child. 相似文献
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10.
Agnandji ST Lell B Soulanoudjingar SS Fernandes JF Abossolo BP Conzelmann C Methogo BG Doucka Y Flamen A Mordmüller B Issifou S Kremsner PG Sacarlal J Aide P Lanaspa M Aponte JJ Nhamuave A Quelhas D Bassat Q Mandjate S Macete E Alonso P Abdulla S Salim N Juma O Shomari M Shubis K Machera F Hamad AS Minja R Mtoro A Sykes A Ahmed S Urassa AM Ali AM Mwangoka G Tanner M Tinto H D'Alessandro U Sorgho H Valea I Tahita MC Kaboré W Ouédraogo S Sandrine Y Guiguemdé RT Ouédraogo JB Hamel MJ Kariuki S 《The New England journal of medicine》2011,365(20):1863-1875