Involvement of CD95 and ligand in CD4+ T-cell and CD8+ T-cell depletion and hepatic cytolysis in patients with chronic viral hepatitis B.

BACKGROUND: Chronic viral hepatitis B (HBV) is characterised by progressive hepatocyte destruction and T-cell depletion. The mechanisms of the CD95-CD95 ligand (CD95L) signalling pathway during this chronic disease and the cirrhotic process remains unclear. OBJECTIVE: We evaluated the involvement of the CD95-CD95L receptor-ligand system in T-cell depletion and hepatic cytolysis in patients with chronic HBV. METHODS: This was a cross-sectional study conducted from September to December 2018 at the Yaoundé General Hospital, Cameroon. Four mL of whole blood was collected and analysed. The CD95 and CD95L levels, as well as the CD4+ T-cell and CD8+ T-cell counts, were performed by enzyme-linked immunosorbent assay and flow cytometry. RESULTS: Of the 130 HBV-positive patients, 36 (27.7%) were cirrhotic and 94 (72.3%) were non-cirrhotic. The cirrhotic patients had significantly elevated CD95 (p < 0.001) and CD95L (p = 0.001) plasma levels, compared with non-cirrhotic patients. The CD4/CD8 ratios were lower in cirrhotic patients, compared to non-cirrhotic patients (p < 0.001). There were statistically significant correlations between CD95 level and CD4+ T-cell counts, between CD95 level and CD8+ T-cell counts, between CD95 level and the CD4/CD8 ratio, between CD95 level and fibrosis score, and between CD95L level and fibrosis score. CONCLUSION: CD95 and CD95L could be involved in T-cell depletion and hepatic cytolysis during the pathogenesis of chronic HBV and could potentially be used as biomarkers for immunological and hepatic monitoring in patients with chronic HBV.

Preinvasive cervical lesions and high prevalence of human papilloma virus among pregnant women in Cameroon.

INTRODUCTION: With the exception of breast cancer, gynecologic neoplasms constitute the most common cancers that complicate pregnancy. Pregnancy therefore presents a window of opportunity for all pregnant women who do not take part in routine free cervical cancer screening program to undergo a free voluntary cytological test and human papillomavirus (HPV) DNA testing. This study aimed to determine prevalent HPV genotypes among pregnant women using exfoliated cells from cervical swabs and determine risk factors responsible for the upsurge of cervical precancerous lesions. METHODS: In a cross-sectional study conducted from October 2017 to March 2018, a total of 482 pregnant women were enrolled. Cervical swabs and samples for cytology were collected from each enrolled participant during their routine prenatal consultation. The Papanicolaou's (Pap) staining technique was performed and all cervical swab samples were amplified through conventional PCR. HPV genotypes were identified using the Roche Linear Array Genotyping Assay. SAS 9.2 software (SAS Institute Inc., USA) was used for statistical analysis and p values >0.05 were considered significant. RESULTS: Among the 482 participants, 354 (73.4%) had normal cytology and 128 (26.6%) had abnormal cytology. HPV DNA was identified in 62/464 (13.4%). The most prominent HPV types identified were HPV 16 (24%), HPV 18 (36.4%), HPV 45 (28%), HPV 53 (18.9%) and HPV 67 (24.3%). Early intercourse, number of sexual partners and age at first pregnancy were some of the risk factors that influenced the etiology of preinvasive cervical lesion. CONCLUSIONS: Prevalent HPV types identified in our study were HPV 16, 18, 45, 53 and 67. Organizing effective screening programs in prenatal care facilities is crucial in order to detect prevalent HR-HPV types and precursors for cervical lesions. The addition of HPV vaccination in the national immunization program with focus on the different epidemiological HPV genotypes circulating in the country is warranted.

Cytokine profile in the sputum of subjects with post-tuberculosis airflow obstruction and in those with tobacco related chronic obstructive pulmonary disease.

BACKGROUND: Previous studies have shown that tuberculosis (TB) is a risk factor for chronic airflow limitation. Chronic obstructive pulmonary disease (COPD) is recognized as the result of chronic inflammation, usually related to noxious particles. Post-TB airflow obstruction and tobacco-related COPD have the same functional pathway characterized by persistent airflow limitation. We sought to compare the profile of 29 cytokines in the sputum of subjects with post-TB airflow obstruction and those with COPD related to tobacco. RESULTS: The forced expiratory volume in the first second (FEV1) and forced expiratory volume/forced vital capacity (FEV/FVC) ratio were lower in the COPD patients with the history of smoking compared to the post-TB airflow obstruction subgroup. The stages of the disease were more advanced in COPD / tobacco patients. Among the cytokines, IL-1α, IL-1ß, MIP-1ß, sCD40L and VEGF levels were higher in COPD patients, compared to the controls with p values ​​of 0.003, 0.0001, 0.03, 0.0001 and 0.02 respectively. When the two COPD subgroups were compared, IL-1α, IL-6, TNF-α and IL-8 levels were higher in the COPD patients with the history of tobacco compared to the COPD patients with the history of TB with p-values ​​of 0.031, 0.05, 0.021 and 0.016, respectively. CONCLUSION: COPD related to tobacco is more severe than post-TB airflow obstruction. The pathogenesis of post-TB airflow obstruction appears to involve the cytokines IL-1RA, IL-1α, IL-1ß, IL-17, GRO and sCD40L, while COPD related to tobacco involves more cytokines.

Cytokine levels of interleukin-2 and 7 amongst antiretroviral therapy success and failure HIV patients attending the University Teaching Hospital, Yaoundé, Cameroon.

BACKGROUND: Immune reconstitution complications (IRC) are a major problem faced by HIV treated patients world wide. Interleukin (IL)-2 and IL-7 play vital roles in peripheral T-cell homeostasis. Our study objective was to measure and compare the blood plasma levels of IL-2 and IL-7 amongst antiretroviral therapy (ART) patients attending the Yaoundé University Teaching Hospital, Cameroon. METHODS: We performed a cross-sectional study with 296 HIV positive patients enrolled between July 2017 and May 2018 at the Yaoundé University Teaching Hospital. IL-2, IL-7, T-cell profile counts and plasma viral load were measured on whole blood specimens. Data obtained were analyzed using Graph Pad Prism 5.0 and Epi info 7.0. Software. RESULTS: IL-2 and IL-7 plasma concentration levels were higher in patients with ART failure compared to ART success, with a mean SD of 19.4±8 and 17.1±6 pg /ml, 35.26±11 and 21.5±5 pg/ml, with p < 0.001 and < 0.001. There was a direct and significant correlation between viral load, IL-2 and IL-7 with p values = 0.028, and 0.020, respectively. There was an association between IL-2, IL-7 and viral load in relation to the duration on treatment (DT), with p values = 0.003 (R2=0.041, CI= 0.069 - 0.34) ,0.017 (R2=0.027, CI=-0.30 - 0.030), and 0.001 (R2=0.048, CI=-0.047-0.76). CONCLUSION: Considering that limited surrogate markers are availiable for monitoring immune reconstitution and high associated mortality rates, IL-2 and IL-7 could be a good immunological predictor for ART failure and success in HIV infected individuals.

Rate of viral load change and adherence of HIV adult patients treated with Efavirenz or Nevirapine antiretroviral regimens at 24 and 48 weeks in Yaoundé, Cameroon: a longitudinal cohort study.

BACKGROUND: HIV-load decrease and suppression over time is associated with consistent adherence to antiretroviral therapy (ART). Our study aimed to evaluate the difference in viral load and adherence of patients treated with a combination of either Tenofovir (TDF), Lamivudine (3TC) and Efavirenz (EFV) or TDF / Zidovudine (AZT), 3TC and Nevirapine (NVP) regimens at 24 and 48 weeks. METHODS: A longitudinal study was conducted from May 2016 to June 2017 among 256 HIV infected adult patients who were enrolled at two approved treatment hospitals in Yaoundé, before the start of first-line ART. Whole blood samples were collected using standard operating procedures. HIV-loads were determined by a quantitative RealTime PCR assay. Adherence was evaluated by pharmacy refill data records. Statistical analyses were performed using the PRISM 5.0 software. RESULTS: Off the 256 HIV infected patients enrolled, 180 (70%) patients completed the study and 76 (30%) patients were lost to follow-up. The success rate in achieving viral load < 40 copies/ml was 1.8 times higher with the EFV regimen at 24 weeks and was 1.2 times higher in the NVP regimen at 48 weeks. At 48 weeks the treatment failure rate was 12.0 and 40.0% in patients on EFV and the NVP regimen, respectively. The rate of adherence varied in both ART based regimens with 84.0 to 74.0% for EFV and 65.5 to 62.5% for NVP, at 24 and 48 weeks respectively. CONCLUSION: In our study and setting, the rate of viral load decrease was higher in the NVP based regimen than with the EFV regimen. The adherence rate to ART was higher in the EFV regimen, compared to the NVP regimen. This adds to evidence that the EFV regimen is the preferred ART combination for non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Chronic obstructive pulmonary disease (COPD): neutrophils, macrophages and lymphocytes in patients with anterior tuberculosis compared to tobacco related COPD.

OBJECTIVE: The inflammatory profile of chronic obstructive pulmonary disease (COPD) related to tobacco is known in certain studies while that of the post tuberculosis form is not yet known. This study aimed to evaluate the levels of neutrophils, macrophages and lymphocytes cells in sputum of COPD patients with history of smoking or anterior tuberculosis. Enumeration of cells in samples was analyzed using standard microscopy. RESULTS: We enrolled 92 participants, 46 (50%) were COPD subjects comprising 22 (47.83%) smokers and 24 (52.17%) with anterior tuberculosis while 46 (50%) healthy persons constituted the control group. The levels of neutrophils, lymphocytes and monocytes were statistically higher in COPD patients compared to the control group with p-values of 0.0001 respectively. Neutrophils levels were higher in COPD patients with history of tobacco than in COPD patients with anterior tuberculosis with a mean rate of 4.72 × 106/ml and 2.48 × 106/ml respectively (p = 0.04). The monocytes and lymphocytes levels were not statistically different between the two sub-groups of COPD patients with p-value of 0.052 and 0.91 respectively. Neutrophils are the only inflammatory cells that were significantly higher in COPD patients with history of smoking as compared to COPD patients with anterior tuberculosis.

Observed HIV drug resistance associated mutations amongst naïve immunocompetent children in Yaoundé, Cameroon.

INTRODUCTION: The emergence of drug resistance mutations (DRMs) has been a major threat for successful lifelong combination antiretroviral therapy (cART), especially for HIV-vertically infected children within the context of the prevention of mother-to-child transmission (PMTCT). This study aimed to evaluate DRMs amongst immune competent treatment-naïve children in Cameroon. METHODS: A cross-sectional study was conducted between 2015 and 2016 amongst 55 proxy consented HIV-1 positive children, aged 9 months to 6 years. They were all immune competent, cART naïve and with unknown history of PMTCT. CD4 cell counts and genotypic drug resistance testing were performed using standard methods. RESULTS: Levels of DRMs to protease (PR) inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs were 27.6%, 3.7% and 40.7%, respectively. Only minor DRMs were observed for PR. The observed mutations for NRTI were K65R, T215I and K219E (33.0% each) and for NNRTI: V106M, Y181C and Y188H (6.0% each). Only minor accessory mutations were found in the integrase (IN) region. CONCLUSION: Despite widely available cART we still observe naïve HIV children, especially from the rural communities. We observe that a proportion of study participants had HIV-1 drug resistance associated mutations (RAMs). Data generated could help strengthen the current PMTCT programmes within the country. There is a need to upscale approaches for drug resistance testing for children in Cameroon and many other resource-limited settings.

Resistance pattern of enterobacteriaceae isolates from urinary tract infections to selected quinolones in Yaoundé.

INTRODUCTION: It is estimated that 150 million urinary tract infections (UTIs) occur yearly worldwide, resulting in more than 6 billion dollar in direct healthcare cost. The etiology of UTIs is predictable, with Escherichia coli, an Enterobacteriaceae being the principal pathogen. Quinolones are usually the drug of choice. In this study, we report the resistance pattern of Enterobacteriaceae isolates from UTIs to quinolones among in-patients and out-patients at the Yaoundé Reference Hospital in Cameroon. METHODS: A cross-sectional descriptive study was carried out for a ten-month period. Consecutive clean-catch mid-stream urine samples were collected from 207 in and out-patients. Identification was done using the Api 20E, and susceptibility testing using the Kirby Bauer's disc diffusion method and the MIC was done using the E-test. RESULTS: Out of the 207 isolates, 58(28.0%) were found to be resistant to all the quinolones used in the study. The resistances observed by species were in the order: Enterobacter 4(30.8%); Klebsiella 19(29.7%); Escherichia 25 (29.4%); Proteus 2(11.8%); Serratia 4(25.0%). Quinolone resistance for Escherichia was 42.9% for In-Patients (IP) and 16.3% for Out-Patient (OP) (P-value=0.006); Klebsiella 35.9% for IP and 20% for OP; Proteus 11.1% for IP and 12.5% for OP; Serratia 18.2% for IP and 40% for OP; Enterobacter 22.2 for IP and 50% for OP. CONCLUSION: High resistance rates to quinolones were observed not only for in-patients but also for out-patients with urinary tract enterobacterial infections. These findings demonstrate the importance of antibiotics susceptibility testing in improving quinolones prescription practices in Cameroon.

Time for Option B+? Prevalence and characteristics of HIV infection among attendees of 2 antenatal clinics in Buea, Cameroon.

As countries consider a wider use of triple antiretroviral therapy (ART) in pregnancy, which in recent World Health Organization guidelines is called Option B+, this study sought to explore the potential implications of adopting Option B+ by characterizing HIV infection in pregnant women attending 2 semiurban antenatal clinics in Cameroon. In a descriptive cross-sectional study, consenting women were screened for HIV; positive samples were confirmed using an enzyme-linked immunosorbent assay test, and CD4 levels and HIV viral loads were determined using flow cytometry and reverse transcription-polymerase chain reaction, respectively. The seroprevalence of HIV in the 407 pregnant women screened was 8.4% (95% confidence interval: 5.9%-11.5%). The majority (82.4%) of HIV-positive women had CD4 counts >350 cells/mm(3). A quarter (25%) had undetectable viral levels (<80 copies/mL). Adopting Option B+ in this setting would result in a 5-fold increase in the number of HIV-infected pregnant women being placed on lifelong triple ART.

Relationship between multiple drug resistance and biofilm formation in Staphylococcus aureus isolated from medical and non-medical personnel in Yaounde, Cameroon.

INTRODUCTION: Monitoring the prevalence of nasal carriage of multiple drug resistance (MDR) Staphylococcus aureus (SA) strains in hospital personnel is essential. These strains when transmitted from hospital personnel to patients with already weakened immune states or in-built medical devices, may limit the latter's treatment options. This study aimed at assessing the potential exposure of patients to these MDR SA in a resource-limited hospital setting by assessing the prevalence and relationship between antimicrobial susceptibility and biofilm forming capacity of SA isolates from hospital personnel. METHODS: A total of 59 bacteria isolates phenotypically identified as Staphylococcus aureus obtained from medical (39) and non-medical personnel (20) in Yaounde were used in the study. Multiple drug resistance defined as resistance to four or more of twelve locally used antibiotics were determined by Kirby Bauer disc diffusion technique whereas quantification of biofilm production was by the microtitre plate method. RESULTS: Among the 59 SA isolates, the prevalence of MDR was 50.9%. Among medical personnel 48.7% had MDR as against 55.9% for non-medical personnel (p-value=0.648). The overall percentage of weak biofilm producers was 35.6%. Although the prevalence of weak biofilm formers was higher in isolates from non-medical personnel (40%) than medical personnel (33.3%) the difference was not statistically significant (p-value= 0.246). Slightly less than half (42.9%) of the weak biofilm producers were MDR. CONCLUSION: Considering the high rates of MDR and that slightly less than half of biofilm formers were MDR, these trends need to be monitored regularly among hospital personnel in Yaounde.

Plasma concentrations of soluble Fas receptors (Fas) and Fas ligands (FasL) in relation to CD4+ cell counts in HIV-1 positive and negative patients in Yaounde, Cameroon.

BACKGROUND: Though documented that HIV infection progresses with the depletion of CD4+ cells, the exact mechanisms by which these cell depletions occur are not clearly understood. This study aimed at evaluating the plasma levels of soluble Fas receptors and ligands in HIV-infected and uninfected patients in Yaounde, Cameroon, a population with a known diversity of HIV in whom this has not been previously assessed. FINDINGS: In a cross-sectional study, 39 antiretroviral naïve HIV-1 positive and negative participants were recruited in Yaounde, Cameroon. CD4+ lymphocyte cell counts were quantified from whole blood using an automated FACScount machine (Becton-Dickinson, Belgium). Plasma samples obtained were analyzed for soluble Fas receptors and Fas ligands in both HIV-1 positive and negative samples using two different quantitative sandwich ELISA kits (Quantikine®, R&D Systems , UK).Plasma levels of Fas receptors were higher in HIV-1 positive patients (median = 1486pg/ml IQR = 1193, 1830pg/ml) compared to HIV-negative controls (median = 1244pg/ml, IQR = 1109, 1325pg/ml), p-value <0.001. Plasma levels of Fas ligands were also higher in HIV-1 positive patients (median = 154pg/ml, IQR = 111, 203pg/ml) compared to HIV-negative controls (median = 51pg/ml, IQR = 32, 88pg/ml), p-value = 0.005. Plasma concentrations of soluble fas receptors and ligands tended to be negatively correlated with the CD4+ cell counts of HIV-positive patients; the correlation coefficients were -0.34 (value = 0.78) and-0.3 (p-value = 0.51) respectively. CONCLUSIONS: In this population of patients in Cameroon, plasma concentrations of Fas receptors and Fas ligands tend to be higher in HIV-positive patients. The Fas pathway of apoptosis may have a role in the depletion of CD4+ cell counts.