Inhibitory KIR/HLA incompatibility between sexual partners confers protection against HIV-1 transmission.

Killer immunoglobulin-like receptors (KIRs) regulate natural killer (NK) cells in a human leukocyte antigen (HLA)-dependent manner. KIR/HLA mismatched hematopoietic stem cell transplants induce alloreactive NK cells, which prevent leukemia relapse. Certain KIR/HLA combinations protect against HIV-1 infection, but the effect of KIR/HLA mismatches between sexual partners has never been investigated. In this study, we analyzed the effect of allogeneic KIR/HLA combinations on HIV-1 transmission in a West African population of HIV-1-discordant and concordant couples. HIV-1-discordant couples were characterized by recipient partners with homozygous KIR2DL2, and by a mismatched recipient partner KIR2DL1/HLA-C2 with index partner HLA-C1/C1 combination expected to allow licensed missing self NK cell killing of index partners' cells. HIV-1-concordant couples on the other hand were characterized by KIR2DL3 homozygous recipient partners with HLA-C1/C2 bearing index partners, resulting in a matched KIR/HLA combination expected to inhibit NK cell killing. In vitro cocultures of healthy donor-derived NK cells and HIV-1 patient-derived CD4(+) T cells confirmed the involvement of these allogeneic KIR/HLA combinations in NK cell-mediated CD4(+) T-cell killing. Our data suggest that KIR/HLA incompatibility between sexual partners confers protection against HIV-1 transmission and that this may be due to alloreactive NK cell killing of the HIV-1-infected partner's cells.

T-helper 17 cells are associated with pathology in human schistosomiasis.

BACKGROUND: Schistosome infections are often clinically silent, but some individuals develop severe pathological reactions. In several disease processes, T-helper 17 (Th17) cells have been linked to tissue injuries, while regulatory T cells (Tregs) are thought to downmodulate inflammatory reactions. We assessed whether bladder pathology in human Schistosoma haematobium infection is related to the balance of Th17 cells and Tregs. We used a murine model of Schistosoma mansoni infection to further investigate whether the peripheral profiles reflected ongoing events in tissues. METHODS: We characterized T-helper cell subsets in the peripheral blood of children residing in a S. haematobium-endemic area and in the peripheral blood, spleen, and hepatic granulomas of S. mansoni-infected high-pathology CBA mice and low-pathology C57BL/6 mice. RESULTS: S. haematobium-infected children with bladder pathology had a significantly higher percentage of Th17 cells than those without pathology. Moreover, the Th17/Treg ratios were significantly higher in infected children with pathology, compared with infected children without pathology. Percentages of interleukin 17-producing cells were significantly higher in spleen and granulomas of CBA mice, compared with C57BL/6 mice. This difference was also reflected in the peripheral blood. CONCLUSIONS: This is the first study to indicate that Th17 cells may be involved in the pathogenesis of human schistosomiasis.

Immunoprophylaxis failure and vaccine response in infants born to mothers with chronic hepatitis B infection in Djibouti.

BACKGROUND: In endemic areas, vertical transmission of hepatitis B virus (HBV) remains a major source of the global reservoir of infected people. Eliminating mother-to-child transmission (MTCT) of HBV is at the heart of World Health Organization's goal of reducing the incidence of HBV in children to less than 0.1% by 2030. Universal screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive measures. AIM: To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen (HBsAg)-positive mothers in Djibouti city. METHODS: We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their infants. The study ran from January 2021 to May 2022, and infants were followed up to 7 mo of age. HBV serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay (Biomérieux, Paris, France) and the automated Amplix platform (Biosynex, Strasbourg, France). All infants received hepatitis B immunoglobulin and were vaccinated against HBV at birth. These infants were closely monitored to assess their seroprotective response and for failure of immunoprophylaxis. Simple logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine response. All statistical analyses were performed with version 4.0.1 of the R software. RESULTS: Of the 50 pregnant women recruited, the median age was 31 years, ranging from 18 years to 41 years. The MTCT rate in this cohort was 4% (2/50) in HBsAg-positive women and 67% (2/3) in hepatitis B e antigen-positive women with a viral load > 200000 IU/mL. Of the 48 infants who did not fail immunoprophylaxis, 8 (16%) became poor responders (anti-HB < 100 mIU/mL) after HBV vaccination and hepatitis B immunoglobulin, while 40 (84%) infants achieved a good level of seroprotection (anti-HB > 100 mIU/mL). Factors associated with this failure of immunoprophylaxis were maternal HBV DNA levels (> 200000 IU/mL) and hepatitis B e antigen-positive status (odds ratio = 158, 95% confidence interval: 5.05-4958, P < 0.01). Birth weight < 2500 g was associated with a poor immune response to vaccination (odds ratio = 34, 95% confidence interval: 3.01-383.86, P < 0.01). CONCLUSION: Despite a failure rate of immunoprophylaxis higher than the World Health Organization target, this study showed that the combination of immunoglobulin and HBV vaccine was effective in preventing MTCT of HBV. Therefore, further studies are needed to better understand the challenges associated with immunoprophylaxis failure in infants in Djibouti city.

m-PIMA™ HIV1/2 VL: A suitable tool for HIV-1 and HIV-2 viral load quantification in West Africa.

Point-of-Care for HIV viral RNA quantification seems to be a complementary strategy to the existing conventional systems. This study evaluated the performance of the m-PIMA™ HIV1/2 Viral Load for the quantification of both HIV-1 and HIV-2 RNA viral load. A total of 555 HIV-1 and 90 HIV-2 samples previously tested by Abbott RealTime HIV-1 (Abbott, Chicago, USA) and Generic HIV-2® Charge virale (Biocentric, France) were tested using the m-PIMA™ HIV1/2 Viral Load at the HIV National Reference lab in Senegal. For HIV-1, Pearson correlation and Bland-Altman plots showed a coefficient r = 0.97 and a bias of -0.11 log10 copies/ml (95% confidence interval [CI]: -0.086 to -0.133 log10 copies/ml) for the m-PIMA™ HIV1/2 Viral Load, respectively. Sensitivity and specificity at 3 log10 copies/ml (threshold of virological failure) were 93.6% (95%[CI]: 91.5% to 95.6%) and 99.1% (95%[CI]: 98.3% to 99.9%), respectively. For HIV-2, a correlation of r = 0.95 was also noted with a bias of - 0.229 log10 copies/ml (95%[CI]: -0.161 to -0.297 log10 copies/ml). Sensitivity and specificity at 3 log10 copies/ml were 97.6% (95%[CI]: 94.3% to 100%) and 93.9% (95%[CI]: 88.9% to 98.8%), respectively. These results confirmed that m-PIMA™ HIV1/2 VL could be a good alternative for HIV-1 and HIV-2 viral load testing in decentralized settings in Senegal.

Genomic epidemiology of SARS-CoV-2 in Senegal in 2020-2021.

INTRODUCTION: In Senegal, molecular diagnosis was widely used for the detection and management of COVID-19 patients. However, genomic surveillance was very limited in the public sector. This study aimed to share the experience of a Senegalese public sector laboratory in response to the COVID-19 pandemic, and to describe the distribution of variants circulating in 2020 and 2021. METHODOLOGY: From July 2020 to December 2021, SARS-CoV-2 qRT-PCR was performed on nasopharyngeal samples from travelers and symptomatic patients at the Bacteriology and Virology Laboratory (LBV) of the Aristide le Dantec University Teaching Hospital. Samples with a cycle threshold (Ct) ≤ 30 were selected for whole-genome sequencing (WGS) using the Nanopore technology. In-house scripts were developed to study the spatial and temporal distribution of SARS-CoV-2 variants in Senegal, using our sequences and those retrieved from the GISAID database. RESULTS: Of 8,207 patients or travelers screened for SARS-CoV-2, 970 (11.8%) were positive and 386 had a Ct ≤ 30. WGS was performed on 133 samples. Concomitantly with high-quality sequences deposited in the GISAID database covering nine cities in Senegal in 2020 and 2021 (n = 1,539), we observed a high circulation of the 20A (B.1, B.1.416 and B.1.620) and 20B (B.1.1.420) lineages in 2020, while most of the samples belonged to Delta variants (AY34 and AY.34.1, 22%) in 2021. CONCLUSIONS: Despite its late involvement, COVID-19 diagnosis was routinely performed in LBV, but genomic characterization remained challenging. The genomic diversity of SARS-CoV-2 strains in Senegal reflected that observed worldwide during the first waves of the pandemic.

HIV-1 genetic diversity and drug resistance among Senegalese patients in the public health system.

In this study, we investigated the prevalence of human immunodeficiency virus type 1 (HIV-1) drug resistance mutations and genetic variability among Senegalese patients undergoing highly active antiretroviral therapy (ART) in the public health system. We conducted a cross-sectional study of 72 patients with suspected therapeutic failure. HIV-1 genotyping was performed with Viroseq HIV-1 Genotyping System v2.0 or the procedure developed by the ANRS AC11 resistance study group, and a phylogenetic analysis was performed. The median follow-up visit was at 40 (range, 12 to 123) months, and the median viral load was 4.67 (range, 3.13 to 6.94) log(10) copies/ml. The first-line therapeutic regimen was nucleoside reverse transcriptase inhibitors (NRTIs) plus efavirenz (EFV) or NRTIs plus nevirapine (NVP) (54/72 patients; 75%), and the second-line therapy was NRTIs plus a protease inhibitor (PI/r) (18/72; 25%). Fifty-five patients (55/72; 76.39%) had at least one drug resistance mutation. The drug resistance rates were 72.22 and 88.89% for the first-line and second-line ARTs, respectively. In NRTI mutations, thymidine analog mutations (TAMs) were found in 50.79% and the M184V mutation was found in 34.92% of the samples. For non-NRTI resistance, we noted a predominance of the K103N mutation (46.27%). For PI/r, several cases of mutations were found with a predominance of M46I and L76V/F at 24% each. The phylogenetic analysis revealed CRF02_AG as the predominant circulating recombinant form (43/72; 59.72%). We found a high prevalence of resistance mutations and a high rate of TAMs among Senegalese patients in the public health system. These findings emphasize the need to improve virological monitoring in resource-limited settings.

[Knowledge and practice of graduating students of pharmacy at the Cheikh Anta Diop University relating to antibiotic use and bacterial resistance in 2019 (Senegal)]. / Connaissances et pratiques des étudiants en fin d'études de pharmacie à l'Université Cheikh Anta Diop sur l'utilisation des antibiotiques et la résistance bactérienne en 2019 (Sénégal).

Introduction: pharmacy students are future providers of pharmaceutical care and should play a critical role in combating bacterial resistance (BR). The purpose of this study was to evaluate the knowledge and practice of students at the end of pharmacy course relating to BR and antibiotic use. Methods: we conducted a cross-sectional, descriptive and analytic study. The study population consisted of students enrolled in Master 2 and PhD in Pharmacy at the Cheikh Anta Diop University over the year 2019. Data were collected between July and October 2019 using an electronic questionnaire whose link was shared through the social network WhatsApp. Knowledge was assessed using a 5-point Likert scale while closed-ended questions were used to determine practice. Descriptive analyses were performed. Factors associated with practice were identified using logistic regression. Analyses were performed using the EPI InfoTM software 7.2.2.16. The significance threshold was set to 0.05. Results: out of 559 eligible students, 278 responded to the questionnaire, reflecting a participation rate of 60.6%. Of these, 72.3% reported having used antibiotics in the 12 months preceding the survey. Regarding knowledge, 85.6% of students surveyed had an adequate level. In addition, 38.2% of students had inadequate practice. These were associated with having a relative or friend as a health worker (OR = 1.69; p-value = 0.04), being a PhD student (OR = 0.55; p-value = 0.02) and having an insufficient level of knowledge (OR = 2.21; p-value = 0.02). Conclusion: this study shows that antibiotic consumption is high among pharmacy students and that their practice is inadequate despite their satisfactory level of knowledge about antibiotics and BR. It is urgent to strengthen the awareness of students and their entourage about good practices concerning antibiotic use.

Vaginal Carriage of Group B Streptococcus (GBS) in Pregnant Women, Antibiotic Sensitivity and Associated Risk Factors in Dakar, Senegal.

The eradication of neonatal Group B Streptococcus (GBS) infections, considered as a major public health priority, necessarily requires a mastery of the data on vaginal carriage in pregnant women. The aims of this study were to determine the prevalence of vaginal carriage of GBS in pregnant women, antibiotic susceptibility, and associated risk factors. This was a cross-sectional, descriptive study conducted over a period of 9 months (July 2020 to March 2021) in pregnant women between 34 and 38 weeks of gestation (WG) followed at the Nabil Choucair health center in Dakar. Identification and antibiotic susceptibility of GBS isolates were performed on the Vitek 2 from vaginal swabs cultured on Granada medium. Demographic and obstetric interview data were collected and analyzed on SPSS (version 25). The level of significance for all statistical tests was set at P < .05. The search of GBS vaginal carriage had involved 279 women aged 16 to 46 years, with a median pregnancy age of 34 (34-37) weeks' gestation. GBS was found in 43 women, for a vaginal carriage rate of 15.4%. In 27.9% (12/43) of volunteers screened, this carriage was monomicrobial, while in 72.1% (31/43) of women, GBS was associated with other pathogens such as Candida spp. (60.5%), Trichomonas vaginalis (2.3%), Gardnerella vaginalis (34.9%) and/or Mobiluncus spp. (11.6%). The level of resistance was 27.9% (12/43) for penicillin G, 53.5% (23/43) for erythromycin, 25.6% (11/43) for clindamycin and 100% for tetracycline. However, the strains had retained fully susceptible to vancomycin and teicoplanin. The main risk factor associated with maternal GBS carriage were ectocervical inflammation associated with contact bleeding (OR = 3.55; P = .005). The high rate of maternal vaginal GBS carriage and the levels of resistance to the various antibiotics tested confirm the importance of continuous GBS surveillance in our resource-limited countries.

Performance of Xpert HIV-1 viral load test in Senegal: a country of high circulation of CRF02_AG.

Introduction: the introduction of the point-of-care in HIV-1 viral load quantification appears to be a complementary strategy to the existing conventional system of the acceleration plan for the achievement of the three 90s in Senegal. The objective of this study was to evaluate the performance of the Xpert® HIV-1 viral load in the context of circulation of non-B, non-C subtypes. Methods: two hundred samples, were tested on Xpert® HIV-1 Viral Load using 1 ml of plasma in comparison to 600 µl on Abbott Real-time HIV-1 assay. The difference between viral load values was considered significant for Dlog <0.5 log copies/ml. Results: a good correlation (r=0.985) was noted and confirmed using passing-bablok regression (slope 1.048; 95% CI: 1.036 to 1.069) for 188 samples with samples. A mean difference of 0.0075 log10 copies/ml for a 95% confidence interval (CI) of 0.002 log10 copies/ml to 0.013 log10 copies/ml was obtained. Sensitivity and specificity were respectively 93.6% and 93.5% at the threshold of 1.6 log10 copies/ml and 100% and 99% at the threshold of 3.0 log10 copies/ml. Conclusion: these results show that Xpert® HIV-1 Viral Load has excellent performance. In Senegal, and can be used for HIV viral load monitoring.

Heterogeneity of the Omicron variant in Senegal.

•Omicron variant continues to progress in Senegal with the appearance of new contaminations.•IRESSEF detected the first positive case of the Omicron variant on Friday, December 3, 2021.•Since this date, the number of Omicron variant infections has increased over the weeks.•Molecular surveillance of the Omicron variant allowed us to identify a strong variation of this variant in our country.

Low-level CD4+ T cell activation in HIV-exposed seronegative subjects: influence of gender and condom use.

Immune activation has been suggested to increase susceptibility to human immunodeficiency virus type 1 (HIV-1) transmission, while at the same time it could be deemed essential for mounting an effective antiviral immune response. In this study, we compared levels of T cell activation between exposed seronegative (ESN) partners in HIV-1 discordant couples and HIV-unexposed control subjects in Dakar, Senegal. ESN subjects showed lower levels of CD38 expression on CD4(+) T cells than did control subjects. However, this was found to be associated with concurrent differences in the use of condoms: ESN subjects reported a higher degree of condom use than did control subjects, which correlated inversely with CD38 expression. In addition, we observed markedly higher levels of T cell activation in women compared with men, irrespective of sexual behavior. These findings question the relevance of low-level CD4(+) T cell activation in resistance to HIV-1 infection and underscore the need to take gender and sexual behavior characteristics of high-risk populations into account when analyzing correlates of protective immunity.

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.

Evaluation of PIMATM CD4 System for Decentralization of Immunological Monitoring of HIV-Infected Patients in Senegal.

BACKGROUND: HIV infection is a concern in the army troupes because of the risk behaviour of the military population. In order to allow regular access to CD4+ T cell enumeration of military personnel as well as their dependents and civilians living with HIV, the Senegalese Army AIDS program is implementing PIMATM Alere technology in urban and semi-urban military medical centres. Validation such device is therefore required prior their wide implementation. The purpose of this study was to compare CD4+ T cell count measurements between the PIMATM Alere to the BD FACSCountTM. METHODOLOGY: We selected a total of 200 subjects including 50 patients with CD4+ T-cells below 200/mm3, 50 between 200 and 350/mm3, 50 between 351 and 500/mm3, and 50 above 500/mm3. CD4+ T-cell count was performed on venous blood using the BD FASCountTM as reference method and the PIMATM Point of Care technology. The mean biases and limits of agreement between the PIMATM Alere and BD FACSCountTM were assessed with the Bland-Altman analysis, the linear regression performed using the Passing-Bablok regression analysis, and the percent similarity calculated using the Scott method. RESULTS: Our data have shown a mean difference of 22.3 cells/mm3 [95%CI:9.1-35.5] between the BD FACSCountTM and PIMATM Alere CD4 measurements. However, the mean differences of the two methods was not significantly different to zero when CD4+ T-cell count was below 350/mm3 (P = 0.76). The Passing-Bablok regression in categorized CD4 counts has also showed concordance correlation coefficient of 0.89 for CD4+ T cell counts below 350/mm3 whilst it was 0.5 when CD4 was above 350/mm3. CONCLUSION: Overall, our data have shown that for low CD4 counts, the results from the PIMATM Alere provided accurate CD4+ T cell counts with a good agreement compared to the FACSCountTM.

[Performance of GeneXpert MTB / RIF® in the diagnosis of extrapulmonary tuberculosis in Dakar: 2010-2015]. / Performance du GeneXpert MTB/RIF® dans le diagnostic de la tuberculose extra-pulmonaire à Dakar: 2010-2015.

INTRODUCTION: The challenge facing developing countries is the availability of methods for rapid and accurate diagnosis of tuberculosis. Some molecular techniques offer this advantage, so we used GeneXpert MTB / RIF test in the diagnosis of extra-pulmonary tuberculosis to evaluate its performance compared with conventional methods. METHODS: Between 2010 and 2015, 544 extrapulmonary clinical specimens were collected and analyzed by microscopy, culture and GeneXpert. The evaluation of antitubercular susceptibility testing was performed using the MGIT 960 system. Genotype MTBDRplus was used to confirm the cases of rifampicin resistance detected by the GX system. RESULTS: The study population included 544 patients, 55.15% men and 44.85% women. Patients age ranged from 1-92 years with the majority in the 18-45 age group. The sensitivity and the overall specificity of microscopy was 43.86% and 98.36%, 94.74% and 97.95% for GeneXpert® respectively (95% CI). There were two discrepant rifampicin-resistant results between GeneXpert test and phenotypic method. Among these cases MTBDRplus test results showed 100% agreement with those of the MGIT 960. CONCLUSION: This study shows that the GeneXpert test exhibits high sensitivity for routine diagnosis of extra-pulmonary tuberculosis and should be used instead of microscopy. The cases of rifampicin resistance detected by GeneXpert should be confirmed by other molecular testing methods before initiating treatment.

Safety, immunogenicity, and efficacy of the candidate tuberculosis vaccine MVA85A in healthy adults infected with HIV-1: a randomised, placebo-controlled, phase 2 trial.

BACKGROUND: HIV-1 infection is associated with increased risk of tuberculosis and a safe and effective vaccine would assist control measures. We assessed the safety, immunogenicity, and efficacy of a candidate tuberculosis vaccine, modified vaccinia virus Ankara expressing antigen 85A (MVA85A), in adults infected with HIV-1. METHODS: We did a randomised, double-blind, placebo-controlled, phase 2 trial of MVA85A in adults infected with HIV-1, at two clinical sites, in Cape Town, South Africa and Dakar, Senegal. Eligible participants were aged 18-50 years, had no evidence of active tuberculosis, and had baseline CD4 counts greater than 350 cells per µL if they had never received antiretroviral therapy or greater than 300 cells per µL (and with undetectable viral load before randomisation) if they were receiving antiretroviral therapy; participants with latent tuberculosis infection were eligible if they had completed at least 5 months of isoniazid preventive therapy, unless they had completed treatment for tuberculosis disease within 3 years before randomisation. Participants were randomly assigned (1:1) in blocks of four by randomly generated sequence to receive two intradermal injections of either MVA85A or placebo. Randomisation was stratified by antiretroviral therapy status and study site. Participants, nurses, investigators, and laboratory staff were masked to group allocation. The second (booster) injection of MVA85A or placebo was given 6-12 months after the first vaccination. The primary study outcome was safety in all vaccinated participants (the safety analysis population). Safety was assessed throughout the trial as defined in the protocol. Secondary outcomes were immunogenicity and vaccine efficacy against Mycobacterium tuberculosis infection and disease, assessed in the per-protocol population. Immunogenicity was assessed in a subset of participants at day 7 and day 28 after the first and second vaccination, and M tuberculosis infection and disease were assessed at the end of the study. The trial is registered with ClinicalTrials.gov, number NCT01151189. FINDINGS: Between Aug 4, 2011, and April 24, 2013, 650 participants were enrolled and randomly assigned; 649 were included in the safety analysis (324 in the MVA85A group and 325 in the placebo group) and 645 in the per-protocol analysis (320 and 325). 513 (71%) participants had CD4 counts greater than 300 cells per µL and were receiving antiretroviral therapy; 136 (21%) had CD4 counts above 350 cells per µL and had never received antiretroviral therapy. 277 (43%) had received isoniazid prophylaxis before enrolment. Solicited adverse events were more frequent in participants who received MVA85A (288 [89%]) than in those given placebo (235 [72%]). 34 serious adverse events were reported, 17 (5%) in each group. MVA85A induced a significant increase in antigen 85A-specific T-cell response, which peaked 7 days after both vaccinations and was primarily monofunctional. The number of participants with negative QuantiFERON-TB Gold In-Tube findings at baseline who converted to positive by the end of the study was 38 (20%) of 186 in the MVA85A group and 40 (23%) of 173 in the placebo group, for a vaccine efficacy of 11·7% (95% CI -41·3 to 44·9). In the per-protocol population, six (2%) cases of tuberculosis disease occurred in the MVA85A group and nine (3%) occurred in the placebo group, for a vaccine efficacy of 32·8% (95% CI -111·5 to 80·3). INTERPRETATION: MVA85A was well tolerated and immunogenic in adults infected with HIV-1. However, we detected no efficacy against M tuberculosis infection or disease, although the study was underpowered to detect an effect against disease. Potential reasons for the absence of detectable efficacy in this trial include insufficient induction of a vaccine-induced immune response or the wrong type of vaccine-induced immune response, or both. FUNDING: European & Developing Countries Clinical Trials Partnership (IP.2007.32080.002), Aeras, Bill & Melinda Gates Foundation, Wellcome Trust, and Oxford-Emergent Tuberculosis Consortium.

Chryseobacterium indologenes in a woman with acute leukemia in Senegal: a case report.

INTRODUCTION: This report documents a rare case of Chryseobacterium indologenes urinary tract infection in Senegal. Chryseobacterium indologenes is an uncommon human pathogen reported in hospital outbreaks in Taiwan and there have been some sporadic cases reported in Europe and in the USA mainly from immune-suppressed patients. CASE PRESENTATION: This case report describes a 42-year-old woman of Wolofa ethnicity who was hospitalized in our Department of Internal Medicine in a Senegalese university teaching hospital, with acute leukemia who died of severe sepsis 10 days following her hospitalization. A strain of Chryseobacterium indologenes isolated from her urine sample was resistant to several beta-lactams including ampicillin (minimum inhibitory concentrations ≥ 256 µg/mL), cefotaxime (minimum inhibitory concentrations 32 µg/mL) and imipenem (minimum inhibitory concentrations ≥ 32 µg/mL), whereas it was susceptible to piperacillin (minimum inhibitory concentrations 16 µg/mL), cefepime (minimum inhibitory concentrations 4 µg/mL), ceftazidime (minimum inhibitory concentrations 4 µg/mL), trimethoprim-sulfamethoxazole (minimum inhibitory concentrations ≤ 0.25 µg/mL) and all tested quinolones including nalidixic acid (minimum inhibitory concentrations ≤ 2 µg/mL). CONCLUSIONS: Chryseobacterium indologenes although uncommon, is an important pathogen causing infection in hospitalized patients. The management of this infection needs better identification, drug susceptibility testing and monitoring of immunosuppressed patients with long hospitalizations.

Antibiotic susceptibility of streptococcus pyogenes 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 ß-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.

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 ρc 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 ρc 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.

HIV and Tuberculosis co-infection impacts T-cell activation markers but not the numbers subset of regulatory T-cells in HIV-1 infected patients.

BACKGROUND: Tuberculosis (TB) has been shown to accelerate the clinical course of HIV infection, but the mechanisms by which this occurs are not well understood. Regulatory T-cells (Tregs) are known to dampen hyperactivation of the immune cells, but it remains unclear whether hyperactivation of T-cells in HIV infection is associated with a decrease of Tregs and what the effect Mycobacterium tuberculosis (MTB) co-infection has on T-cell activation and Tregs. OBJECTIVES: In this study, we aim to evaluate whether active TB is associated with the increased expression of T-cell activation markers and reduced number of Treg cells in HIV-1-infected patients. METHODS: This study was conducted on 69 subjects consisting of 20 HIV-infected patients, 20 HIV and MTB co-infected patients, 19 MTB-infected patients and 10 uninfected control subjects negative for both MTB and HIV. The frequencies of T-cell activation markers (CD38 and HLA-DR) and Treg cells (CD4+CD25+CD127-) were measured by flow cytometry. RESULTS: Significantly higher expression of CD38 and HLA-DR on CD4+ and CD8+ T-cells was found in MTB and HIV co-infected patients compared with HIV-infected patients. However, no significant difference in the percentage of Treg cells was reported between HIV patients with TB and those without. The study also showed a negative correlation between regulatory T-cells frequency and CD4+ T-cell counts. CONCLUSION: These results suggest that TB enhances the expression of peripheral T-cell activation markers during HIV infection, whilst having no impact on the percentages of Treg cells.