Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 36
Filtrar
1.
N Engl J Med ; 390(17): 1549-1559, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38669354

RESUMO

BACKGROUND: Subcutaneous administration of the monoclonal antibody L9LS protected adults against controlled Plasmodium falciparum infection in a phase 1 trial. Whether a monoclonal antibody administered subcutaneously can protect children from P. falciparum infection in a region where this organism is endemic is unclear. METHODS: We conducted a phase 2 trial in Mali to assess the safety and efficacy of subcutaneous administration of L9LS in children 6 to 10 years of age over a 6-month malaria season. In part A of the trial, safety was assessed at three dose levels in adults, followed by assessment at two dose levels in children. In part B of the trial, children were randomly assigned, in a 1:1:1 ratio, to receive 150 mg of L9LS, 300 mg of L9LS, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection, as detected on blood smear performed at least every 2 weeks for 24 weeks. A secondary efficacy end point was the first episode of clinical malaria, as assessed in a time-to-event analysis. RESULTS: No safety concerns were identified in the dose-escalation part of the trial (part A). In part B, 225 children underwent randomization, with 75 children assigned to each group. No safety concerns were identified in part B. P. falciparum infection occurred in 36 participants (48%) in the 150-mg group, in 30 (40%) in the 300-mg group, and in 61 (81%) in the placebo group. The efficacy of L9LS against P. falciparum infection, as compared with placebo, was 66% (adjusted confidence interval [95% CI], 45 to 79) with the 150-mg dose and 70% (adjusted 95% CI, 50 to 82) with the 300-mg dose (P<0.001 for both comparisons). Efficacy against clinical malaria was 67% (adjusted 95% CI, 39 to 82) with the 150-mg dose and 77% (adjusted 95% CI, 55 to 89) with the 300-mg dose (P<0.001 for both comparisons). CONCLUSIONS: Subcutaneous administration of L9LS to children was protective against P. falciparum infection and clinical malaria over a period of 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT05304611.).


Assuntos
Anticorpos Monoclonais Humanizados , Malária Falciparum , Adulto , Criança , Feminino , Humanos , Masculino , Relação Dose-Resposta a Droga , Método Duplo-Cego , Doenças Endêmicas/prevenção & controle , Injeções Subcutâneas , Estimativa de Kaplan-Meier , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Mali/epidemiologia , Plasmodium falciparum , Resultado do Tratamento , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Terapia Diretamente Observada , Combinação Arteméter e Lumefantrina/administração & dosagem , Combinação Arteméter e Lumefantrina/uso terapêutico , Adulto Jovem , Pessoa de Meia-Idade
2.
PLoS One ; 19(3): e0299082, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38446806

RESUMO

SARS-CoV-2 has claimed several million lives since its emergence in late 2019. The ongoing evolution of the virus has resulted in the periodic emergence of new viral variants with distinct fitness advantages, including enhanced transmission and immune escape. While several SARS-CoV-2 variants of concern trace their origins back to the African continent-including Beta, Eta, and Omicron-most countries in Africa remain under-sampled in global genomic surveillance efforts. In an effort to begin filling these knowledge gaps, we conducted retrospective viral genomic surveillance in Guinea from October 2020 to August 2021. We found that SARS-CoV-2 clades 20A, 20B, and 20C dominated throughout 2020 until the coincident emergence of the Alpha and Eta variants of concern in January 2021. The Alpha variant remained dominant throughout early 2021 until the arrival of the Delta variant in July. Surprisingly, despite the small sample size of our study, we also found the persistence of the early SARS-CoV-2 clade 19B as late as April 2021. Together, these data help fill in our understanding of the SARS-CoV-2 population dynamics in West Africa early in the COVID-19 pandemic.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Guiné/epidemiologia , SARS-CoV-2/genética , Pandemias , Estudos Retrospectivos , COVID-19/epidemiologia , África Ocidental/epidemiologia , Genômica
3.
BMJ Glob Health ; 9(2)2024 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-38413098

RESUMO

BACKGROUND: Seasonal malaria chemoprevention (SMC) is a main intervention to prevent and reduce childhood malaria. Since 2015, Guinea has implemented SMC targeting children aged 3-59 months (CU5) in districts with high and seasonal malaria transmission. OBJECTIVE: We assessed the programmatic impact of SMC in Guinea's context of scaled up malaria intervention programming by comparing malaria-related outcomes in 14 districts that had or had not been targeted for SMC. METHODS: Using routine health management information system data, we compared the district-level monthly test positivity rate (TPR) and monthly uncomplicated and severe malaria incidence for the whole population and disaggregated age groups (<5 years and ≥5 years of age). Changes in malaria indicators through time were analysed by calculating the district-level compound annual growth rate (CAGR) from 2014 to 2021; we used statistical analyses to describe trends in tested clinical cases, TPR, uncomplicated malaria incidence and severe malaria incidence. RESULTS: The CAGR of TPR of all age groups was statistically lower in SMC (median=-7.8%) compared with non-SMC (median=-3.0%) districts. Similarly, the CAGR in uncomplicated malaria incidence was significantly lower in SMC (median=1.8%) compared with non-SMC (median=11.5%) districts. For both TPR and uncomplicated malaria incidence, the observed difference was also significant when age disaggregated. The CAGR of severe malaria incidence showed that all age groups experienced a decline in severe malaria in both SMC and non-SMC districts. However, this decline was significantly higher in SMC (median=-22.3%) than in non-SMC (median=-5.1%) districts for the entire population, as well as both CU5 and people over 5 years of age. CONCLUSION: Even in an operational programming context, adding SMC to the malaria intervention package yields a positive epidemiological impact and results in a greater reduction in TPR, as well as the incidence of uncomplicated and severe malaria in CU5.


Assuntos
Antimaláricos , Malária , Criança , Humanos , Pré-Escolar , Antimaláricos/uso terapêutico , Estações do Ano , Guiné , Malária/epidemiologia , Malária/prevenção & controle , Quimioprevenção/métodos
5.
Oncologist ; 28(11): e1017-e1030, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37368350

RESUMO

BACKGROUND: Although non-Hodgkin lymphoma (NHL) is the 6th most common malignancy in Sub-Saharan Africa (SSA), little is known about its management and outcome. Herein, we examined treatment patterns and survival among NHL patients. METHODS: We obtained a random sample of adult patients diagnosed between 2011 and 2015 from 11 population-based cancer registries in 10 SSA countries. Descriptive statistics for lymphoma-directed therapy (LDT) and degree of concordance with National Comprehensive Cancer Network (NCCN) guidelines were calculated, and survival rates were estimated. FINDINGS: Of 516 patients included in the study, sub-classification was available for 42.1% (121 high-grade and 64 low-grade B-cell lymphoma, 15 T-cell lymphoma and 17 otherwise sub-classified NHL), whilst the remaining 57.9% were unclassified. Any LDT was identified for 195 of all patients (37.8%). NCCN guideline-recommended treatment was initiated in 21 patients. This corresponds to 4.1% of all 516 patients, and to 11.7% of 180 patients with sub-classified B-cell lymphoma and NCCN guidelines available. Deviations from guideline-recommended treatment were initiated in another 49 (9.5% of 516, 27.2% of 180). By registry, the proportion of all patients receiving guideline-concordant LDT ranged from 30.8% in Namibia to 0% in Maputo and Bamako. Concordance with treatment recommendations was not assessable in 75.1% of patients (records not traced (43.2%), traced but no sub-classification identified (27.8%), traced but no guidelines available (4.1%)). By registry, diagnostic work-up was in part importantly limited, thus impeding guideline evaluation significantly. Overall 1-year survival was 61.2% (95%CI 55.3%-67.1%). Poor ECOG performance status, advanced stage, less than 5 cycles and absence of chemo (immuno-) therapy were associated with unfavorable survival, while HIV status, age, and gender did not impact survival. In diffuse large B-cell lymphoma, initiation of guideline-concordant treatment was associated with favorable survival. INTERPRETATION: This study shows that a majority of NHL patients in SSA are untreated or undertreated, resulting in unfavorable survival. Investments in enhanced diagnostic services, provision of chemo(immuno-)therapy and supportive care will likely improve outcomes in the region.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma de Células T Periférico , Linfoma de Células T , Humanos , Adulto , Taxa de Sobrevida , Resultado do Tratamento
6.
Trop Med Int Health ; 28(7): 571-575, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37258746

RESUMO

BACKGROUND: Seasonal malaria chemoprevention (SMC) has become a critical intervention for malaria prevention and control. There is a growing interest to generate evidence that health campaigns such as SMC can be leveraged for integration or co-administration of other health efforts such as nutritional supplements, immunizations, or vitamin A. OBJECTIVE: We conducted a pilot study to assess whether nutrition assessments could be integrated into existing SMC programming in two districts in Guinea. METHODS: Of 106,480 children under 5 years of age (CU5) who received sulfadoxine-pyrimethamine plus amodiaquine as part of SMC by community drug distributors (CDDs), 2210 had their mid-upper arm circumference (MUAC) assessed by CDD supervisors. RESULTS: Of these, 177 (8.0%) had a MUAC < 125 mm and were therefore classified as acutely malnourished; 161 CU5 were referred to health facilities for follow-up. Importantly, no drop in SMC programmatic coverage was observed in districts conducting MUAC on top of SMC. Key informant interviews with district officials and focus group discussions with CDD supervisors showed a generally positive effect of integrating MUAC into SMC, although CDD supervisors had concerns about workload with added responsibilities of MUAC assessments. CONCLUSION: Integrating other health interventions with SMC is accepted-and indeed welcomed-by the population and health workers, and does not result in a drop in SMC programmatic coverage.


Assuntos
Antimaláricos , Malária , Criança , Humanos , Lactente , Pré-Escolar , Antimaláricos/uso terapêutico , Estações do Ano , Guiné , Estudos de Viabilidade , Avaliação Nutricional , Projetos Piloto , Malária/epidemiologia , Quimioprevenção/métodos
7.
Genet Res (Camb) ; 2023: 4683831, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36721432

RESUMO

Methylenetetrahydrofolate reductase (MTHFR) plays a major role in the metabolism of folates and homocysteine, which in turn can affect gene expression and ultimately promote the development of breast cancer. Thus, mutations in the MTHFR gene could influence homocysteine, methionine, and S-adenosylmethionine levels and, indirectly, nucleotide levels. Imbalance in methionine and S-adenosylmethionine synthesis affects protein synthesis and methylation. These changes, which affect gene expression, may ultimately promote the development of breast cancer. We therefore hypothesized that such mutations could also play an important role in the occurrence and pathogenesis of breast cancer in a Malian population. In this study, we used the PCR-RFLP technique to identify the different genotypic profiles of the C677T MTHFR polymorphism in 127 breast cancer women and 160 healthy controls. The genotypic distribution of the C677T polymorphism in breast cancer cases was 88.2% for CC, 11.0% for CT, and 0.8% for TT. Healthy controls showed a similar distribution with 90.6% for CC, 8.8% for CT, and 0.6% for TT. We found no statistical association between the C677T polymorphism and breast cancer risk for the codominant models CT and TT (p > 0.05). The same trend was observed when the analysis was extended to other genetic models, including dominant (p = 0.50), recessive (p = 0.87), and additive (p = 0.50) models. The C677T polymorphism of MTHFR gene did not influence the risk of breast cancer in the Malian samples.


Assuntos
Neoplasias da Mama , Metilenotetra-Hidrofolato Redutase (NADPH2) , Feminino , Humanos , Neoplasias da Mama/genética , Homocisteína , Mali , Metionina , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , S-Adenosilmetionina
8.
N Engl J Med ; 387(20): 1833-1842, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36317783

RESUMO

BACKGROUND: CIS43LS is a monoclonal antibody that was shown to protect against controlled Plasmodium falciparum infection in a phase 1 clinical trial. Whether a monoclonal antibody can prevent P. falciparum infection in a region in which the infection is endemic is unknown. METHODS: We conducted a phase 2 trial to assess the safety and efficacy of a single intravenous infusion of CIS43LS against P. falciparum infection in healthy adults in Mali over a 6-month malaria season. In Part A, safety was assessed at three escalating dose levels. In Part B, participants were randomly assigned (in a 1:1:1 ratio) to receive 10 mg of CIS43LS per kilogram of body weight, 40 mg of CIS43LS per kilogram, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection detected on blood-smear examination, which was performed at least every 2 weeks for 24 weeks. At enrollment, all the participants received artemether-lumefantrine to clear possible P. falciparum infection. RESULTS: In Part B, 330 adults underwent randomization; 110 were assigned to each trial group. The risk of moderate headache was 3.3 times as high with 40 mg of CIS43LS per kilogram as with placebo. P. falciparum infections were detected on blood-smear examination in 39 participants (35.5%) who received 10 mg of CIS43LS per kilogram, 20 (18.2%) who received 40 mg of CIS43LS per kilogram, and 86 (78.2%) who received placebo. At 6 months, the efficacy of 40 mg of CIS43LS per kilogram as compared with placebo was 88.2% (adjusted 95% confidence interval [CI], 79.3 to 93.3; P<0.001), and the efficacy of 10 mg of CIS43LS per kilogram as compared with placebo was 75.0% (adjusted 95% CI, 61.0 to 84.0; P<0.001). CONCLUSIONS: CIS43LS was protective against P. falciparum infection over a 6-month malaria season in Mali without evident safety concerns. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04329104.).


Assuntos
Anticorpos Monoclonais Humanizados , Antimaláricos , Malária Falciparum , Adulto , Humanos , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/prevenção & controle , Mali , Plasmodium falciparum , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Cefaleia/induzido quimicamente
9.
J Public Health Afr ; 13(2): 2082, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-36051529

RESUMO

Data regarding the prevalence and consequences of self-medication during the COVID-19 pandemic in Africa are very limited. The study aimed to explore the frequency and risk factors of self-medication against COVID-19 by health personnel in this study. This cross-sectional study took place in June 2021, in Conakry, in the all three national hospitals and the six community medical centers, and five primary health centers. A multivariate logistic regression model was performed to identify factors associated with self-medication. A total of 975 health workers with a median age of 31 (IQR: 27-40) years, with 504 (51.7%) women were included. The majority were clinicians: physicians (33.1%) or nurses (33.1%). Of all, 46.2% reported having had at least one COVID-19 symptom during the 12 months preceding the survey. The proportion of self-medication was 15.3% among national hospital staff, 12.20% in municipality medical centers and 22.6% in primary health centers (p=0.06). More than two-thirds (68.7%) who selfmedicated did not have a test for SARSCoV- 2 infection. They took antibiotics including azithromycin, amoxicillin, ampicillin (42.2%), acetaminophen (37.4%), vitamin C (27.9%), hydroxychloroquine (23.8%) and medicinal plants (13.6%). The median duration of self-medication was 4 days. Fatigue or asthenia, sore throat, loss of smell and sore throat of a close person were independently associated with selfmedication. Health care workers largely practiced self-medication during the Covid pandemic and without diagnostic testing. The results suggest the need for training and sensitization of medical personnel to avoid the consequences of the molecules used, including hepatotoxicity and antibiotic resistance.

10.
World J Gastroenterol ; 28(14): 1494-1498, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35582673

RESUMO

An enhanced cascade of care should include a younger population, helping to achieve the goal of the World Health Organization with a focus on elimination in the pediatric population. Furthermore, enhanced screening and awareness efforts and continued education of health care providers will improve the outcomes of chronic hepatitis C virus (HCV) infection in the pediatric population. The present work discusses and comments on the topic "cascade of care in HCV chronic pediatric patients".


Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Criança , Hepatite C/tratamento farmacológico , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/terapia , Humanos , Programas de Rastreamento , Organização Mundial da Saúde
11.
Epidemiol Infect ; 149: e223, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34579803

RESUMO

Little is known about respiratory viruses infection in Guinea. Influenza surveillance has not been implemented in Guinea mainly because of the paucity of laboratory infrastructure and capacity. This paper presents the first influenza surveillance data in Guinea.Swabs were obtained from August 2018 through December 2019 at influenza sentinel sites and transported to the Institut National de Santé Publique for testing. Ribonucleic acid was extracted and tested for the presence of influenza A and B by real-time reverse transcription-polymerase chain reaction (RT-PCR). Positive samples were further characterised to determine the subtypes and lineages of influenza viruses.A total of 862 swabs were collected and tested. Twenty-three per cent of samples tested positive for influenza A and B viruses. Characterisation of positive specimens identified influenza A/H1N1pmd09 (2.5%), influenza A/H3N2 (57.3%), influenza B/Victoria lineage (36.7%) and 7 (3.5%) influenza B with undetermined lineage. Influenza B virus activity clustered in August through November while influenza A/H3N2 displayed two clusters of activities that appeared in May through August and November through December.For the first time in Guinea, the epidemiology, diversity and period of circulation of influenza viruses were studied. The results indicate the predominance and the periods of activities of influenza B Victoria lineage and influenza A/H3N2 which are important information for preventive strategies. It is warranted to extend the influenza surveillance to other parts of Guinea to better understand the epidemiology of the viruses and monitor the emergence of influenza strains with pandemic potential.


Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/epidemiologia , Influenza Humana/virologia , Monitoramento Epidemiológico , Guiné/epidemiologia , Humanos , Estações do Ano
12.
Nature ; 597(7877): 539-543, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34526718

RESUMO

Seven years after the declaration of the first epidemic of Ebola virus disease in Guinea, the country faced a new outbreak-between 14 February and 19 June 2021-near the epicentre of the previous epidemic1,2. Here we use next-generation sequencing to generate complete or near-complete genomes of Zaire ebolavirus from samples obtained from 12 different patients. These genomes form a well-supported phylogenetic cluster with genomes from the previous outbreak, which indicates that the new outbreak was not the result of a new spillover event from an animal reservoir. The 2021 lineage shows considerably lower divergence than would be expected during sustained human-to-human transmission, which suggests a persistent infection with reduced replication or a period of latency. The resurgence of Zaire ebolavirus from humans five years after the end of the previous outbreak of Ebola virus disease reinforces the need for long-term medical and social care for patients who survive the disease, to reduce the risk of re-emergence and to prevent further stigmatization.


Assuntos
Surtos de Doenças , Ebolavirus/genética , Ebolavirus/isolamento & purificação , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/virologia , Modelos Biológicos , Animais , República Democrática do Congo/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Ebolavirus/classificação , Feminino , Guiné/epidemiologia , Doença pelo Vírus Ebola/transmissão , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Infecção Persistente/virologia , Filogenia , Sobreviventes , Fatores de Tempo , Zoonoses Virais/transmissão , Zoonoses Virais/virologia
13.
Pan Afr Med J ; 39: 2, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34178230

RESUMO

Genital schistosomiasis is mainly located in the neck of the uterus and the vagina, less frequently on the vulva, the fallopian tubes and ovaries and rarely in the body of the uterus. We here report the case of a 10-year-old girl admitted with a swelling on the vulva in whom histological examination showed cutaneous schistosomiasis due to Schistosoma haematobium. Outcome was favorable with a single 40 mg/kg mg dose of praziquantel, with tumor regression.


Assuntos
Praziquantel/administração & dosagem , Esquistossomose Urinária/diagnóstico , Doenças da Vulva/diagnóstico , Animais , Anti-Helmínticos/administração & dosagem , Criança , Feminino , Humanos , Mali , Schistosoma haematobium/isolamento & purificação , Esquistossomose Urinária/tratamento farmacológico , Doenças da Vulva/tratamento farmacológico , Doenças da Vulva/parasitologia
14.
BMC Med Genet ; 21(1): 206, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076844

RESUMO

BACKGROUND: The effect of the p.Arg72Pro variant of the P53 gene on the risk of development ofbreast cancer remains variable in populations. However, the use ofstrategies such aspoolingage-matched controls with disease may provide a consistent meta-analysis. Our goal was to perform a meta-analysis in order to assess the association of p.Arg72Pro variant of P53 gene with the risk of breast cancer. METHODS: Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Case-control studies with age-matched on breast cancer havingevaluated the genotype frequencies of the TP53 p.Arg72Pro polymorphism were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot. RESULTS: Twenty-one publications with 7841 cases and 8876 controls were evaluated in this meta-analysis. Overall, our results suggested that TP53 p.Arg72Pro was associated with the risk of breast cancer for the dominant model (OR = 1.09, 95% CI = 1.02-1.16, P = 0.01) and the additive model (OR = 1.09, 95% CI = 1.01-1.17, P = 0.03), but not for the recessive model (OR = 1.07, 95% CI = 0.97-1.18, P = 0.19). According to the ethnic group analysis, Pro allele was associated with the risk of breast cancer in Caucasians for the dominant model and additive model (P = 0.02), and Africans for the recessive model and additive model (P = 0.03). CONCLUSIONS: This meta-analysis found a significant association between TP53 p.Arg72Pro polymorphism and the risk of breast cancer. Individuals carrying at least one Pro allele were more likely to have breast cancer than individuals harboring the Arg allele.


Assuntos
Substituição de Aminoácidos , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor p53/genética , Alelos , Neoplasias da Mama/diagnóstico , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Fatores de Risco
15.
BMC Med Genet ; 21(1): 142, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620097

RESUMO

BACKGROUND: Breast cancer, the most common tumor in women in Mali and worldwide has been linked to several risk factors, including genetic factors, such as the PIN3 16-bp duplication polymorphism of TP53. The aim of our study was to evaluate the role of the PIN3 16-bp duplication polymorphism in the susceptibility to breast cancer in the Malian population and to perform a meta-analysis to better understand the correlation with data from other populations. METHODS: We analyzed the PIN3 16-bp duplication polymorphism in blood samples of 60 Malian women with breast cancer and 60 healthy Malian women using PCR. In addition, we performed a meta-analysis of case-control study data from international databases, including Pubmed, Harvard University Library, Genetics Medical Literature Database, Genesis Library and Web of Science. Overall, odds ratio (OR) with 95% CI from fixed and random effects models were determined. Inconsistency was used to assess heterogeneity between studies and publication bias was estimated using the funnel plot. RESULTS: In the studied Malian patients, a significant association of PIN3 16-bp duplication polymorphism with breast cancer risk was observed in dominant (A1A2 + A2A2 vs. A1A1: OR = 2.26, CI 95% = 1.08-4.73; P = 0.02) and additive (A2 vs. A1: OR = 1.87, CI 95% = 1.05-3.33; P = 0.03) models, but not in the recessive model (P = 0.38). In the meta-analysis, nineteen (19) articles were included with a total of 6018 disease cases and 4456 controls. Except for the dominant model (P = 0.15), an increased risk of breast cancer was detected with the recessive (OR = 1.46, 95% CI = 1.15-1.85; P = 0.002) and additive (OR = 1.11, 95% CI = 1.02-1.19; P = 0.01) models. CONCLUSION: The case-control study showed that PIN3 16-bp duplication polymorphism of TP53 is a significant risk factor for breast cancer in Malian women. These findings are supported by data from the meta-analysis carried out on different ethnic groups around the world.


Assuntos
Pareamento de Bases/genética , Neoplasias da Mama/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo Genético , Proteína Supressora de Tumor p53/genética , Adulto , Estudos de Casos e Controles , Feminino , Heterogeneidade Genética , Humanos , Mali , Modelos Genéticos , Razão de Chances , Viés de Publicação , Fatores de Risco
16.
Br J Haematol ; 190(2): 209-221, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32181503

RESUMO

Non-Hodgkin lymphoma (NHL) is the sixth most common cancer in Sub-Saharan Africa (SSA). Comprehensive diagnostics of NHL are essential for effective treatment. Our objective was to assess the frequency of NHL subtypes, disease stage and further diagnostic aspects. Eleven population-based cancer registries in 10 countries participated in our observational study. A random sample of 516 patients was included. Histological confirmation of NHL was available for 76.2% and cytological confirmation for another 17.3%. NHL subclassification was determined in 42.1%. Of these, diffuse large B cell lymphoma, chronic lymphocytic leukaemia and Burkitt lymphoma were the most common subtypes identified (48.8%, 18.4% and 6.0%, respectively). We traced 293 patients, for whom recorded data were amended using clinical records. For these, information on stage, human immunodeficiency virus (HIV) status and Eastern Cooperative Oncology Group Performance Status (ECOG PS) was available for 60.8%, 52.6% and 45.1%, respectively. Stage at diagnosis was advanced for 130 of 178 (73.0%) patients, HIV status was positive for 97 of 154 (63.0%) and ECOG PS was ≥2 for 81 of 132 (61.4%). Knowledge about NHL subclassification and baseline clinical characteristics is crucial for guideline-recommended treatment. Hence, regionally adapted investments in pathological capacity, as well as standardised clinical diagnostics, will significantly improve the therapeutic precision for NHL in SSA.


Assuntos
Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/epidemiologia , Adolescente , Adulto , África Subsaariana , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
17.
Stand Genomic Sci ; 11: 32, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27087892

RESUMO

Strain G3(T) (CSUR P207 = DSM 26203) was isolated from the fecal sample of a wild gorilla (Gorilla gorilla subsp gorilla) from Cameroon. It is a Gram-positive, facultative anaerobic short rod. This strain exhibits a 16S rRNA sequence similarity of 98.2 % with Microbacterium thalassium, the closest validly published Microbacterium species and member of the family Microbacteriaceae. Moreover, it shows a low MALDI-TOF-MS score (1.1 to 1.3) that does not allow any identification. Thus, it is likely that this strain represents a new species. Here we describe the phenotypic features of this organism, the complete genome sequence and annotation. The 3,692,770 bp long genome (one chromosome but no plasmid) contains 3,505 protein-coding and 61 RNA genes, including 4 rRNA genes. In addition, digital DNA-DNA hybridization values for the genome of the strain G3(T) against the closest Microbacterium genomes range between 19.7 to 20.5, once again confirming its new status as a new species. On the basis of these polyphasic data, consisting of phenotypic and genomic analyses, we propose the creation of Microbacterium gorillae sp. nov. that contains the strain G3(T).

18.
Microb Ecol ; 71(4): 990-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26714966

RESUMO

Strain G4(T) was isolated from the stool sample of a wild gorilla (Gorilla gorilla gorilla) from Cameroon. It is a facultative anaerobic, Gram-negative, rod-shaped bacterium. This strain exhibits a 16S rRNA nucleotide sequence similarity of 97.48% with Paenibacillus typhae, the phylogenetically closest species with standing nomenclature. Moreover, the strain G4(T) presents some phenotypic differences when compared to other Paenibacillus species and shows a low MALDI-TOF Mass Spectrometry score that does not allow any identification. Thus, it is likely that this strain represents a new species. Here, we describe the characteristics of this organism, complete genome sequence, and annotation. The 6,933,847 bp size genome (1 chromosome but no plasmid) contains 5972 protein-coding genes and 54 RNAs genes, including 44 tRNA genes. In addition, digital DNA-DNA hybridization values for the genome of the strain G4(T) against the closest Paenibacillus genomes range between 19.7 and 22.1, once again confirming its new status as a new species. On the basis of these polyphasic data, consisting of phenotypic and genomic analyses, we propose the creation of Paenibacillus camerounensis sp. nov. that contains the strain G4(T).


Assuntos
Paenibacillus/genética , Animais , Proteínas de Bactérias/genética , Sequência de Bases , Camarões , Mapeamento Cromossômico , DNA Bacteriano/genética , DNA Ribossômico/genética , Genes de RNAr , Gorilla gorilla/microbiologia , Paenibacillus/química , Paenibacillus/isolamento & purificação , Fenótipo , Filogenia , RNA Ribossômico 16S/genética , RNA de Transferência/genética , Análise de Sequência de DNA , Especificidade da Espécie
19.
Sci Rep ; 4: 7174, 2014 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-25417711

RESUMO

Wild apes are considered to be the most serious reservoir and source of zoonoses. However, little data are available about the gut microbiota and pathogenic bacteria in gorillas. For this propose, a total of 48 fecal samples obtained from 21 Gorilla gorilla gorilla individuals (as revealed via microsatellite analysis) were screened for human bacterial pathogens using culturomics and molecular techniques. By applying culturomics to one index gorilla and using specific media supplemented by plants, we tested 12,800 colonies and identified 147 different bacterial species, including 5 new species. Many opportunistic pathogens were isolated, including 8 frequently associated with human diseases; Mycobacterium bolletii, Proteus mirabilis, Acinetobacter baumannii, Klebsiella pneumoniae, Serratia marcescens, Escherichia coli, Staphylococcus aureus and Clostridium botulinum. The genus Treponema accounted for 27.4% of the total reads identified at the genus level via 454 pyrosequencing. Using specific real-time PCR on 48 gorilla fecal samples, in addition to classical human pathogens, we also observed the fastidious bacteria Bartonella spp. Borrelia spp., Coxiella burnetii and Tropheryma whipplei in the gorilla population. We estimated that the prevalence of these pathogens vary between 4.76% and 85.7%. Therefore, gorillas share many bacterial pathogens with humans suggesting that they could be a reservoir for their emergence.


Assuntos
Bactérias/isolamento & purificação , Reservatórios de Doenças , Gorilla gorilla/microbiologia , Intestinos/microbiologia , Animais , Doenças dos Símios Antropoides/epidemiologia , Doenças dos Símios Antropoides/microbiologia , Bactérias/genética , Bactérias/patogenicidade , DNA Bacteriano/análise , DNA Bacteriano/química , Fezes/microbiologia , Humanos , Repetições de Microssatélites/genética , Análise de Sequência de DNA
20.
Microb Pathog ; 77: 149-54, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25220240

RESUMO

Because of the close genetic relatedness between apes and humans, apes are susceptible to many human infectious agents and can serve as carriers of these pathogens. Consequently, they present a serious health hazard to humans. Moreover, many emerging infectious diseases originate in wildlife and continue to threaten human populations, especially vector-borne diseases described in great apes, such as malaria and rickettsiosis. These wild primates may be permanent reservoirs and important sources of human pathogens. In this special issue, we report that apes, including chimpanzees (Pan troglodytes), bonobos (Pan paniscus), gorillas (Gorilla gorilla and Gorilla beringei), orangutans (Pongo pygmaeus and Pongo abelii), gibbons (Hylobates spp., Hoolock spp. and Nomascus spp) and siamangs (Symphalangus syndactylus syndactylus and Symphalangus continentis), have many bacterial, viral, fungal and parasitic species that are capable of infecting humans. Serious measures should be adopted in tropical forests and sub-tropical areas where habitat overlaps are frequent to survey and prevent infectious diseases from spreading from apes to people.


Assuntos
Bactérias/isolamento & purificação , Transmissão de Doença Infecciosa , Fungos/isolamento & purificação , Hominidae , Parasitos/isolamento & purificação , Vírus/isolamento & purificação , Zoonoses/transmissão , Animais , Reservatórios de Doenças , Humanos , Zoonoses/microbiologia , Zoonoses/parasitologia , Zoonoses/virologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA