63 research outputs found
Evaluation of the accuracy of primary CD4 gating in Senegalese individuals coinfected with HIV and tuberculosis
Antibiotic susceptibility profile of Streptococcus pneumoniae isolated from acute respiratory infection in Dakar: a cross sectional study
Streptococcus pneumoniae is a pathogen causing pneumonia, meningitis, otitis and bacteraemia. Nowadays, S. pneumoniae is developing antibacterial resistance, particularly for those with reduced susceptibility to penicillin. The objective of this study was to assess the susceptibility profile of S. pneumoniae strains isolated from acute respiratory infections (ARIs) in children younger than 5 years of age in Dakar, Senegal. S. pneumoniae strains were isolated from broncho-alveolar lavages (BALs), nasopharyngeal swabs, and middle ear secretion from children in the Paediatric Department of Abass Ndao University Teaching Hospital and Paediatric Department of Roi Baudouin Hospital in Dakar, Senegal. The strains were cultivated on Columbia agar supplemented with 5% of horse blood and gentamicin (6 mg/L). Antibiotic susceptibility testing was performed using E-test method. A total of 34 strains of S. pneumoniae were isolated and identified in this study, among them 7 strains (20.58%) showed penicillin-resistance. Antibiotics such as amoxicillin/clavulanic acid (MIC90=0.036 μg/mL), cefuroxim (MIC90=0.38 μg/mL), cefixim (MIC90=1.5 μg/mL), as well as macrolides (azithromycin MIC90=1.5 μg/mL, clarithromycin MIC90=0.125 μg/mL) and fluoroquinolone (levofloxacin MIC90=1 μg/mL, ofloxacin MIC90=2 μg/mL) were mostly active. However, all S. pneumoniae strains were resistant to sulfamethoxazole/trimethoprim (MIC90: 32 μg/mL). Except of S. pneumoniae strains penicillin-resistance or reduced susceptibility, most strains were susceptible to β-lactams antibiotics commonly used in ARI treatment. Continuous surveillance of antimicrobial resistance patterns of pneumococcus strains is still crucial for effective control of ARIs in children
Molecular Epidemiology of HIV-1 Transmission in a Cohort of HIV-1 Concordant Heterosexual Couples from Dakar, Senegal
BACKGROUND: A large number of HIV-1 infections in Africa occur in married couples. The predominant direction of intracouple transmission and the principal external origins of infection remain important issues of debate. METHODS: We investigated HIV-1 transmission in 46 HIV-1 concordant positive couples from Dakar, Senegal. Intracouple transmission was confirmed by maximum-likelihood phylogenetic analysis and pairwise distance comparisons of HIV-1 env gp41 sequences from both partners. Standardized interview data were used to deduce the direction as well as the external sources of the intracouple transmissions. RESULTS: Conservative molecular analyses showed linked viruses in 34 (74%) couples, unlinked viruses in 6 (13%) couples, and indeterminate results for 6 (13%) couples. The interview data corresponded completely with the molecular analyses: all linked couples reported internal transmission and all unlinked couples reported external sources of infection. The majority of linked couples (93%) reported the husband as internal source of infection. These husbands most frequently (82%) reported an occasional sexual relationship as external source of infection. Pairwise comparisons of the CD4 count, antiretroviral therapy status, and the proportion of gp41 ambiguous base pairs within transmission pairs correlated with the reported order of infection events. CONCLUSIONS: In this suburban Senegalese population, a majority of HIV-1 concordant couples showed linked HIV-1 transmission with the husband as likely index partner. Our data emphasize the risk of married women for acquiring HIV-1 as a result of the occasional sexual relationships of their husbands
The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance
INTRODUCTION
Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic.
RATIONALE
We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs).
RESULTS
Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants.
CONCLUSION
Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century
Antibiotic Susceptibility of Isolated from Respiratory Tract Infections in Dakar, Senegal
Group A Streptococcus (GAS) is one of the major causes of respiratory tract infections. The objectives of this study were to identify isolates of S. pyogenes obtained from respiratory tract infections, and to assess their susceptibility to several antibiotics. A total of 40 strains were isolated and their susceptibility to 17 antibiotics was tested using a standard disk diffusion method. The minimum inhibitory concentrations (MICs) were determined using the E-test. All isolates were sensitive to β-lactam antibiotics including penicillin, amoxicillin, and cephalosporins. Macrolides remain active with the exception of spiramycin, which showed reduced susceptibility. Out of the 40 isolates, 100% of the isolates were resistant to tetracycline. Interestingly, isolates were sensitive to chloramphenicol, teicoplanin, vancomycine, and levofloxacin, providing potential alternative choices of treatment against infections with S. pyogenes
Higher Homologous and Lower Cross-Reactive Gag-Specific T-Cell Responses in Human Immunodeficiency Virus Type 2 (HIV-2) Than in HIV-1 Infection▿
Human immunodeficiency virus type 2 (HIV-2) infection results in slower CD4+ T-cell decline, lower plasma viral load levels, and hence slower progression of the disease than does HIV-1 infection. Although the reasons for this are not clear, it is possible that HIV-2 replication is more effectively controlled by host responses. We used aligned pools of overlapping HIV-1 and HIV-2 Gag peptides in an enhanced gamma interferon enzyme-linked immunospot assay to compare the levels of homologous and cross-reactive Gag-specific T-cell responses between HIV-1- and HIV-2-infected patients. HIV-2-infected patients showed broader and stronger homologous Gag-specific T-cell responses than HIV-1-infected patients. In contrast, the cross-reactive T-cell responses in HIV-2-infected patients were both narrower and weaker than those in HIV-1-infected patients, in line with overall weaker correlations between homologous and heterologous T-cell responses among HIV-2-infected patients than among HIV-1-infected patients. Cross-reactive responses in HIV-2-infected patients tended to correlate directly with HIV-1/HIV-2 Gag sequence similarities; this was not found in HIV-1-infected patients. The CD4+ T-cell counts of HIV-2-infected patients correlated directly with homologous responses and inversely with cross-reactive responses; this was not found in HIV-1-infected patients. Our data support a model whereby high-level HIV-2-specific T-cell responses control the replication of HIV-2, thus limiting viral diversification and priming of HIV-1 cross-reactive T-cell responses over time. However, we cannot exclude the possibility that HIV-2 replication is controlled by other host factors and that HIV-2-specific T-cell responses are better maintained in the context of slow viral divergence and a less damaged immune system. Understanding the nature of immune control of HIV-2 infection could be crucial for HIV vaccine design
CD4 T-cell enumeration in a field setting : evaluation of CyFlow counter using the CD4 easy count kit-dry and pima CD4 systems
BACKGROUND: Flow Cytometry (FCM) is still considered to be the method of choice for accurate CD4 enumeration. However, the use of FCM in developing countries is problematic due to their cost and complexity. Lower-cost technologies have been introduced. We evaluated CyFlow Counter together with its lyophilized reagents, and Pima CD4 in high-temperature area, using FACSCount as reference. MATERIALS AND METHODS: Whole blood samples were consecutively collected by venipuncture from 111 HIV+ patients and 17 HIV-negative donors. CD4 T-cell enumeration was performed on CyFlow Counter, Pima CD4 and FACSCount. RESULTS: CyFlow Counter and Pima CD4 systems showed good correlation with FACSCount (slope of 0.82 and 0.90, and concordance ρ(c) of 0.94 and 0.98, respectively). CyFlow Counter showed absolute or relative biases (LOA) of −63 cells/mm(3) (−245 to 120) or −9.8% (−38.1 to 18.4) respectively, and Pima CD4 showed biases (LOA) of −30 cells/mm(3) (−160 to 101) or −3.5% (−41.0 to 33.9%). CyFlow Counter and Pima CD4 showed respectively 106.7% and 105.9% of similarity with FACSCount. According to WHO-2010 ART initiation threshold of 350 cells/mm(3), CyFlow Counter and Pima CD4 showed respectively sensibility of 100% and 97%, and specificity of 91% and 93%. CyFlow Counter and Pima CD4 were strongly correlated (slope of 1.09 and ρ(c) of 0.95). These alternative systems showed good agreement with bias of 33 cells/mm(3) (−132 to 203) or 6.3% (−31.2 to 43.8), and similarity of 104.3%. CONCLUSION: CyFlow Counter using CD4 easy count kit-dry and Pima CD4 systems can accurately provide CD4 T-cell counts with acceptable agreement to those of FACSCount
Expression analysis of LEDGF/p75, APOBEC3G, TRIM5alpha, and tetherin in a Senegalese cohort of HIV-1-exposed seronegative individuals
HIV-1 replication depends on a delicate balance between cellular co-factors and antiviral restriction factors. Lens epithelium-derived growth factor (LEDGF/p75) benefits HIV, whereas apolipoprotein B mRNA-editing catalytic polypeptide-like 3G (APOBEC3G), tripartite motif 5alpha (TRIM5α), and tetherin exert anti-HIV activity. Expression levels of these proteins possibly contribute to HIV-1 resistance in HIV-1-exposed populations.We used real-time PCR and flow cytometry to study mRNA and protein levels respectively in PBMC and PBMC subsets. We observed significantly reduced LEDGF/p75 protein levels in CD4+ lymphocytes of HIV-1-exposed seronegative subjects relative to healthy controls, whereas we found no differences in APOBEC3G, TRIM5α, or tetherin expression. Untreated HIV-1-infected patients generally expressed higher mRNA and protein levels than healthy controls. Increased tetherin levels, in particular, correlated with markers of disease progression: directly with the viral load and T cell activation and inversely with the CD4 count.Our data suggest that reduced LEDGF/p75 levels may play a role in resistance to HIV-1 infection, while increased tetherin levels could be a marker of advanced HIV disease. Host factors that influence HIV-1 infection and disease could be important targets for new antiviral therapies
Inhibitory KIR/HLA incompatibility between sexual partners confers protection against HIV-1 transmission
KIR/HLA incompatibility in HIV-1 transmission and importance of the 'missing self' model : response
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