32 research outputs found
Repeated treatment of recurrent uncomplicated Plasmodium falciparum malaria in Senegal with fixed-dose artesunate plus amodiaquine versus fixed-dose artemether plus lumefantrine: a randomized, open-label trial.
No full textBACKGROUND: The use of artemisinin-based combination therapy (ACT) is currently recommended for treating uncomplicated malaria. The objective was to assess the efficacy and safety of repeated administrations of two fixed-dose presentations of ACT--artesunate plus amodiaquine (ASAQ) and artemether-lumefantrine (AL)--in subsequent episodes of Plasmodium falciparum malaria. METHODS: A randomized comparative study was conducted in a rural community of central Senegal from August 2007 to January 2009. Children and adults with uncomplicated P. falciparum malaria were randomized to receive open-label ASAQ once daily or AL twice daily for three days. Drug doses were given according to body weight. Treatments for first episodes were supervised. For subsequent episodes, only the first intake of study drug was supervised. ECGs and audiograms were performed in patients ≥ 12 years of age. Primary outcome was adequate clinical and parasitological response rate (ACPR) after polymerase chain reaction (PCR) correction on day 28 for the first episode. RESULTS: A total of 366 patients were enrolled in the two groups (ASAQ 184, AL 182) and followed up during two malaria transmission seasons. In the intent-to-treat population, PCR-corrected ACPRs at day 28 for the first episode were 98.4% and 96.2%, respectively, in the ASAQ and AL groups. For the per-protocol population (ASAQ 183, AL 182), PCR-corrected ACPRs at day 28 for the first episode were 98.9% and 96.7%, respectively. A 100% ACPR rate was obtained at day 28 in the 60 and four patients, respectively, who experienced second and third episodes. Treatment-related adverse events were reported in 11.7% of the patients, without significant differences between the two groups. A better improvement of haemoglobin at day 28 was noted in the ASAQ versus the AL group (12.2 versus 11.8 g/dL; p = 0.03). No sign of ototoxicity was demonstrated. A prolongation of the QTc interval was observed in both groups during treatment with no clinical consequence. CONCLUSIONS: Study results confirmed the satisfactory efficacy and safety profile of ASAQ and AL. Moreover, in patients who were treated at least twice, repeated administration of ASAQ or AL did not identify any major safety issues. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00540410
Human rabies post exposure prophylaxis at the Pasteur Institute of Dakar, Senegal: trends and risk factors
No full textAbstract Background Rabies remains a major public health problem in developing countries. Most fatal rabies cases, especially in children, result from dog bites and occur in low-income countries, such as those in Sub-Saharan Africa. Rabies can be controlled through mass dog vaccination and human deaths prevented through timely and appropriate post-exposure prophylaxis (PEP). As access to appropriate PEP remains a serious challenge for bite-victims, the aim of this study was to understand the use of PEP, to evaluate the knowledge, attitudes and practices with respect to rabies and to identify risk factors related to non-compliance with PEP to define recommendations for improving PEP in Senegal. Methods This study included patients with suspicion of rabies exposure who sought PEP at the Pasteur Institute of Dakar from April 2013 to March 2014. Patients with rabies clinical symptoms, those who had already started PEP and those with exposure outside Senegal or for more than 3 months were excluded. Data on risk factors and propensity to seek and complete PEP were collected using questionnaires and phone interviews. The association between acceptability and compliance with PEP and other independent variables were evaluated using multivariate regression analysis. Results Among the 905 patients enrolled into the study, 67% were male (sex ratio M/F, 2) and 46%, children under 15 years of age. Exposures by animal bites represented 87%, whereas the remainder were due to scratches or contact; 76% were classified as WHO category III and 88% were due to dogs. Among these patients, 7% refused to start PEP and 54.5% completed the full schedule. Main factors reported by non-compliant patients were vaccine costs and affordability, and knowledge on status of biting animal. Conclusion This study shows that despite the awareness about rabies dangers and prevention, only half of the patients completed the full PEP schedule. The following recommendations, such as free of charge prophylaxis or intradermal regimens as an alternative to intramuscular regimens, should be considered to increase the adherence to PEP at the Pasteur Institute of Dakar and in Senegal
Genetic Diversity within Schistosoma haematobium: DNA Barcoding Reveals Two Distinct Groups
No full textWebster, Bonnie L. Emery, Aiden M. Webster, Joanne P. Gouvras, Anouk Garba, Amadou Diaw, Oumar Seye, Mohmoudane M. Tchuente, Louis Albert Tchuem Simoonga, Christopher Mwanga, Joseph Lange, Charles Kariuki, Curtis Mohammed, Khalfan A. Stothard, J. Russell Rollinson, DavidBackground - Schistosomiasis in one of the most prevalent parasitic diseases, affecting millions of people and animals in developing countries. Amongst the human-infective species S. haematobium is one of the most widespread causing urogenital schistosomiasis, a major human health problem across Africa, however in terms of research this human pathogen has been severely neglected.
Methodology/principal findings - To elucidate the genetic diversity of Schistosoma haematobium, a DNA 'barcoding' study was performed on parasite material collected from 41 localities representing 18 countries across Africa and the Indian Ocean Islands. Surprisingly low sequence variation was found within the mitochondrial cytochrome oxidase subunit I (cox1) and the NADH-dehydrogenase subunit 1 snad1). The 61 haplotypes found within 1978 individual samples split into two distinct groups; one (Group 1) that is predominately made up of parasites from the African mainland and the other (Group 2) that is made up of samples exclusively from the Indian Ocean Islands and the neighbouring African coastal regions. Within Group 1 there was a dominance of one particular haplotype (H1) representing 1574 (80%) of the samples analyzed. Population genetic diversity increased in samples collected from the East African coastal regions and the data suggest that there has been movement of parasites between these areas and the Indian Ocean Islands.
Conclusions/significance - The high occurrence of the haplotype (H1) suggests that at some point in the recent evolutionary history of S. haematobium in Africa the population may have passed through a genetic 'bottleneck' followed by a population expansion. This study provides novel and extremely interesting insights into the population genetics of S. haematobium on a large geographic scale, which may have consequence for control and monitoring of urogenital schistosomiasis.Copyright: © 2012 Webster et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article.NHM Repositor
Assessment of the molecular marker of Plasmodium falciparum chloroquine resistance (Pfcrt) in Senegal after several years of chloroquine withdrawal.
No full textAs a result of widespread antimalarial drug resistance, all African countries with endemic malaria have, in recent years, changed their malaria treatment policy. In Senegal, the health authorities changed from chloroquine (CQ) to a combination of sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ) in 2003. Since 2006, the artemisinin combination therapies (ACTs) artemether-lumefantrine (AL) and artesunate plus amodiaquine (AS/AQ) were adopted for uncomplicated malaria treatment. After several years of CQ withdrawal, the current study wished to determine the level of CQ resistance at the molecular level in selected sites in Senegal, because the scientific community is interested in using CQ again. Finger prick blood samples were collected from Plasmodium falciparum-positive children below the age of 10 years (N = 474) during cross-sectional surveys conducted in two study sites in Senegal with different malaria transmission levels. One site is in central Senegal, and the other site is in the southern part of the country. All samples were analyzed for single nucleotide polymorphisms (SNPs) in the P. falciparum CQ resistance transporter gene (Pfcrt; codons 72-76) using polymerase chain reaction (PCR) sequence-specific oligonucleotide probe (SSOP) enzyme-linked immunosorbent assay (ELISA) and real-time PCR methods. In total, the 72- to 76-codon region of Pfcrt was amplified in 449 blood samples (94.7%; 285 and 164 samples from the central and southern sites of Senegal, respectively). In both study areas, the prevalence of the Pfcrt wild-type single CVMNK haplotype was very high; in central Senegal, the prevalence was 70.5% in 2009 and 74.8% in 2010, and in southern Senegal, the prevalence was 65.4% in 2010 and 71.0% in 2011. Comparing data with older studies in Senegal, a sharp decline in the mutant type Pfcrt prevalence is evident: from 65%, 64%, and 59.5% in samples collected from various sites in 2000, 2001, and 2004 to approximately 30% in our study. A similar decrease in mutant type prevalence is noted in other neighboring countries. With the continued development of increased CQ susceptibility in many African countries, it may be possible to reintroduce CQ in the near future in a drug combination; it could possibly be given to non-vulnerable groups, but it demands close monitoring of possible reemergence of CQ resistance development
Age patterns of severe paediatric malaria and their relationship to Plasmodium falciparum transmission intensity.
No full textBACKGROUND: The understanding of the epidemiology of severe malaria in African children remains incomplete across the spectrum of Plasmodium falciparum transmission intensities through which communities might expect to transition, as intervention coverage expands. METHODS: Paediatric admission data were assembled from 13 hospitals serving 17 communities between 1990 and 2007. Estimates of Plasmodium falciparum transmission intensity in these communities were assembled to be spatially and temporally congruent to the clinical admission data. The analysis focused on the relationships between community derived parasite prevalence and the age and clinical presentation of paediatric malaria in children aged 0-9 years admitted to hospital. RESULTS: As transmission intensity declined a greater proportion of malaria admissions were in older children. There was a strong linear relationship between increasing transmission intensity and the proportion of paediatric malaria admissions that were infants (R2 = 0.73, p < 0.001). Cerebral malaria was reported among 4% and severe malaria anaemia among 17% of all malaria admissions. At higher transmission intensity cerebral malaria was a less common presentation compared to lower transmission sites. There was no obvious relationship between the proportions of children with severe malaria anaemia and transmission intensity. CONCLUSION: As the intensity of malaria transmission declines in Africa through the scaling up of insecticide-treated nets and other vector control measures a focus of disease prevention among very young children becomes less appropriate. The understanding of the relationship between parasite exposure and patterns of disease risk should be used to adapt malaria control strategies in different epidemiological settings
Effect of 4 years of seasonal malaria chemoprevention on the acquisition of antibodies to Plasmodium falciparum antigens in Ouelessebougou, Mali.
No full textBACKGROUND: More than 200 million people live in areas of highly seasonal malaria transmission where Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) was recommended in 2012 by WHO. This strategy is now implemented widely and protected more than 19 million children in 2018. It was previously reported that exposure to SMC reduced antibody levels to AMA1, MSP-142 and CSP, but the duration of exposure to SMC up to three 3 years, had no effect on antibody levels to MSP-142 and CSP. METHODS: In 2017, a cross-sectional survey was carried out 1 month after the last dose of SMC had been given to children aged 4-5 years randomly selected from areas where SMC had been given for 2 or 4 years during the malaria transmission season. A total of 461 children were enrolled, 242 children in areas where SMC had been implemented for 4 years and 219 children in areas where SMC had been implemented for 2 years. Antibody extracted from dry blood spots was used to measure IgG levels to the malaria antigens CSP, MSP-142 and AMA1 by ELISA. RESULTS: The prevalence of antibodies to MSP-142 was similar in children who had received SMC for 4 years compared to those who had received SMC for only 2 years (85.1 vs 86.0%, ajusted odd ratio (aOR) = 1.06, 95% confidence intervals (CI 0.62-1.80), p = 0.80). The prevalence of antibodies to AMA-1 and to CSP was not lower in children who received SMC for 4 years compared to those who had received SMC for only 2 years (95.3 vs 88.8%, aOR = 3.16, 95% CI 1.44-6.95, p = 0.004 for AMA-1; and 91.2 vs 81.9%, aOR = 3.14, 95% CI 1.70-5.76, p < 0.001 for CSP). Median antibody levels for anti-MSP-142 IgG were not significatively inferior in children who had received SMC for four rather than 2 years (0.88 (IQR: 0.64-1.15) and 0.95 ((0.68-1.15), respectively), anti-CSP (1.30 (1.00-1.56) and 1.17 (0.87-1.47)), and anti-AMA-1 (1.45 (1.24-1.68) and 1.41 (1.17-1.64)). CONCLUSION: In an area of high seasonal malaria transmission, children who had received SMC for 4 years did not had lower seropositivity or antibody levels to AMA1, MSP-142 and CSP compared to children who had received SMC for only 2 years suggesting that children who have received SMC for 4 years may not be more at risk of malaria after the cessation of SMC than children who have received SMC for a shorter period
Defying the law, negotiating change The Futanke’s opposition to the national ban on FGM in Senegal
No full textThis thesis is concerned with the politics of the preservation and ‘abandonment’ of female circumcision in Fouta Toro, Senegal. The focal point of analysis is the overt opposition to the law criminalising female genital cutting in 1999, and development projects raising awareness about excision in human rights and reproductive health education programmes. As an ethnography of the politics around bodily practices in the light of governmental and non-governmental intervention, the thesis looks at how different interest groups justify their position towards excision. This is a timely enquiry, given the Senegalese government’s ‘acceleration programme of the complete abandonment of excision by 2015’ and some Futanke leaders’ non-compliance with, and opposition to this intervention.
After providing details about ‘the ban’ on ‘female genital mutilation’ in Senegal and a critical reflection on the events that are seen to have led to the call for this ban, I carefully disentangle what ‘the opposition to the law’ is and who disagrees with ‘the abandonment’ of the practice in Fouta Toro. The central part of the thesis is guided by an analysis of how excision is embedded in constructions of personhood, sociality and ethnic identity, and how the body is imagined and located in this process. I show how conceptions of ethnic purity and pride are formulated in terms of fear about a ‘loss of culture’ and ‘foreign invasion’ which nourishes discourses of opposition to the law and non-governmental intervention. Others use ‘human rights’ associated with non-governmental organisations and the state as a vehicle to express their views against excision and those who oppose its criminalisation. I examine how idioms like ‘the state’, ‘human rights’ and ‘Futanke way of life’ feature in discourses around the ban of excision in Fouta Toro, and how respectability and honour are maintained through competing representations of the female body as a site of morality. Some claim the female body – a reproducer of cultural identities – with reference to duties through kin obligations, others with reference to ‘human rights’ and ‘the state’.
Based on 15 months’ ethnographic fieldwork in Fouta Toro and nine years working in and researching the impact of development in Senegal, this dissertation contributes to scholarship on Fouta Toro and indicates how governmental and non-governmental intervention stirs up the caste-related power structures of a society led by the Tooroɓɓe since the Islamic revolution in the 18th century. It shows how the female body is located as a site of morality, key to the reproduction of cultural identities
Molecular markers of resistance to sulphadoxine-pyrimethamine one year after implementation of intermittent preventive treatment of malaria in infants in Mali
No full textThe anti-circumsporozoite antibody response to repeated, seasonal booster doses of the malaria vaccine RTS,S/AS01E.
No full textThe recently deployed RTS,S/AS01E malaria vaccine induces a strong antibody response to the circumsporozoite protein (CSP) on the surface of the Plasmodium falciparum sporozoite which is associated with protection. The anti-CSP antibody titre falls rapidly after primary vaccination, associated with a decline in efficacy, but the antibody titre and the protective response can be partially restored by a booster dose of vaccine, but this response is also transitory. In many malaria- endemic areas of Africa, children are at risk of malaria, including severe malaria, until they are five years of age or older and to sustain protection from malaria for this period by vaccination with RTS,S/AS01E, repeated booster doses of vaccine may be required. However, there is little information about the immune response to repeated booster doses of RTS,S/AS01E. In many malaria-endemic areas of Africa, the burden of malaria is largely restricted to the rainy season and, therefore, a recent trial conducted in Burkina Faso and Mali explored the impact of repeated annual booster doses of RTS,S/AS01E given immediately prior to the malaria transmission season until children reached the age of five years. Anti-CSP antibody titres were measured in sera obtained from a randomly selected subset of children enrolled in this trial collected before and one month after three priming and four annual booster doses of vaccine using the GSK ELISA developed at the University of Ghent and, in a subset of these samples, by a multiplex assay developed at the University of Oxford. Three priming doses of RTS,S/AS01E induced a strong anti-CSP antibody response (GMT 368.9 IU/mL). Subsequent annual, seasonal booster doses induced a strong, but lower, antibody response; the GMT after the fourth booster was 128.5 IU/mL. Children whose antibody response was in the upper and middle terciles post vaccination had a lower incidence of malaria during the following year than children in the lowest tercile. Results obtained with GSK ELISA and the Oxford Multiplex assay were strongly correlated (Pearson's correlation coefficient, r = 0.94; 95% CI, 0.93-0.95). Although anti-CSP antibody titres declined after repeated booster doses of RTS,S/AS01E a high, although declining, level of efficacy was sustained suggesting that there may have been changes in the characteristics of the anti-CSP antibody following repeated booster doses.Clinical Trials Registration. NCT03143218
Artemether-lumefantrine with or without single-dose primaquine and sulfadoxine-pyrimethamine plus amodiaquine with or without single-dose tafenoquine to reduce Plasmodium falciparum transmission: a phase 2, single-blind, randomised clinical trial in Ouelessebougou, Mali.
No full textBACKGROUND: Artemether-lumefantrine is widely used for uncomplicated Plasmodium falciparum malaria; sulfadoxine-pyrimethamine plus amodiaquine is used for seasonal malaria chemoprevention. We aimed to determine the efficacy of artemether-lumefantrine with and without primaquine and sulfadoxine-pyrimethamine plus amodiaquine with and without tafenoquine for reducing gametocyte carriage and transmission to mosquitoes. METHODS: In this phase 2, single-blind, randomised clinical trial conducted in Ouelessebougou, Mali, asymptomatic individuals aged 10-50 years with P falciparum gametocytaemia were recruited from the community and randomly assigned (1:1:1:1) to receive either artemether-lumefantrine, artemether-lumefantrine with a single dose of 0·25 mg/kg primaquine, sulfadoxine-pyrimethamine plus amodiaquine, or sulfadoxine-pyrimethamine plus amodiaquine with a single dose of 1·66 mg/kg tafenoquine. All trial staff other than the pharmacist were masked to group allocation. Participants were not masked to group allocation. Randomisation was done with a computer-generated randomisation list and concealed with sealed, opaque envelopes. The primary outcome was the median within-person percent change in mosquito infection rate in infectious individuals from baseline to day 2 (artemether-lumefantrine groups) or day 7 (sulfadoxine-pyrimethamine plus amodiaquine groups) after treatment, assessed by direct membrane feeding assay. All participants who received any trial drug were included in the safety analysis. This study is registered with ClinicalTrials.gov, NCT05081089. FINDINGS: Between Oct 13 and Dec 16, 2021, 1290 individuals were screened and 80 were enrolled and randomly assigned to one of the four treatment groups (20 per group). The median age of participants was 13 (IQR 11-20); 37 (46%) of 80 participants were female and 43 (54%) were male. In individuals who were infectious before treatment, the median percentage reduction in mosquito infection rate 2 days after treatment was 100·0% (IQR 100·0-100·0; n=19; p=0·0011) with artemether-lumefantrine and 100·0% (100·0-100·0; n=19; p=0·0001) with artemether-lumefantrine with primaquine. Only two individuals who were infectious at baseline infected mosquitoes on day 2 after artemether-lumefantrine and none at day 5. By contrast, the median percentage reduction in mosquito infection rate 7 days after treatment was 63·6% (IQR 0·0-100·0; n=20; p=0·013) with sulfadoxine-pyrimethamine plus amodiaquine and 100% (100·0-100·0; n=19; p<0·0001) with sulfadoxine-pyrimethamine plus amodiaquine with tafenoquine. No grade 3-4 or serious adverse events occurred. INTERPRETATION: These data support the effectiveness of artemether-lumefantrine alone for preventing nearly all mosquito infections. By contrast, there was considerable post-treatment transmission after sulfadoxine-pyrimethamine plus amodiaquine; therefore, the addition of a transmission-blocking drug might be beneficial in maximising its community impact. FUNDING: Bill & Melinda Gates Foundation
