CCR2 Genetic Polymorphism And Its Potential Effect On HIV Acquisition In A Population Of Children Living In The Northern Region Of Cameroon.

BACKGROUND AND OBJECTIVES: The association of chemokine receptor-2 (CCR2) polymorphism with HIV transmission or disease progression remains highly controversial. The role of CCR2-64I allele in HIV infection may differ from one population to another because of their genetic background. The objectives of this study were to characterize the CCR2 genetic polymorphism and to determine its potential effect in HIV acquisition in children living in the Northern Region of Cameroon. MATERIALS AND METHODS: A cross-sectional study was carried out in five health facilities in the Northern region of Cameroon. DNA was extracted from the Buffy coat of each participant using the QIAamp®DNA mini kit. The DNA extract was then subjected to polymorphic analyses. CCR2 genotypes were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The Chi-Squared test was used for the assessment of the Hardy-Weinberg equilibrium. RESULTS: A total of 134 children under 15 years comprised of 38 HIV-exposed infected (28.36%) and 96 HIV-exposed un-infected (71.64%) participants were recruited. Prevalences of 44.78% wild type homozygous, 48.52% heterozygous and 6.7% mutant homozygous alleles were found in the overall population. An allelic frequency of 29.69% for the mutant allele CCR2-64I was found in HIV-exposed un-infected individuals as compared to 34.21% in HIV-infected children (p=0.47). CONCLUSION: The CCR2-64I allele is relatively common in the Northern Region of Cameroon, with a similar distribution among HIV-exposed un-infected and infected children. As this allele alone does not seem to confer protection against HIV-1 infection, further studies using genotype-combination of CCR2 polymorphism and other single nucleotide polymorphisms would be of great relevance in both HIV prevention and novel therapeutic strategies.

Differential expression of Fas receptors (CD95) and Fas ligands (CD95L) in HIV infected and exposed uninfected children in Cameroon versus unexposed children.

INTRODUCTION: The number of HIV exposed uninfected (HEU) infants is increasing as vertical transmission is reducing. This subpopulation requires more investigations. This study aimed at comparing the expression level of soluble Fas receptors (FasR) and ligands (FasL) between HIV infected, HEU and unexposed children. METHODS: Eighty eight HIV-1infected, 86 HEU and 38 HIV unexposed children were recruited. Soluble FasR and FasL were measured in their plasma. Mann-Whitney U-Test was used to compare groups with 95% confidence. Spearman coefficient was used to test the correlation with CD4 and viral load (VL). RESULTS: Overall plasma levels of FasR were higher than that of FasL. The concentration of FasR and FasL were significantly higher in HIV-1 infected children in comparison to HEU and unexposed children. There was no difference in the plasma level of FasL in HIV infected compared to HEU children. A significant difference was observed between HIV infected children and HEU children (P=0.001) for the FasL. FasR were higher in both HIV infected and unexposed children compared to HEU children. There was a positive correlation (rs=+0.4; p=0.01) in ARV treated children between CD4 count and FasL concentration. Significant negative correlation (rs=-0.3; p=0.040) in ARV naïve children was observed between CD4 percentage and FasL. Significant and positive correlation (rs=+0.4; p=0.008) was observed between the VL and FasL in HIV infected, treated or not. CONCLUSION: HEU children differ from HIV infected and unexposed children as the level of FasL/R expression is concerned. HEU should be considered different from HIV unexposed although exempt from virus as some immune dysfunctions have been reported among them.

Tuberculosis diagnosis: algorithm that May discriminate latent from active tuberculosis.

Diagnosis of tuberculosis still faces a lot of challenges and is one of the priorities in the field of tuberculosis management. Deciphering the complex tuberculosis pathogenicity network could provide biomarkers for diagnosis. We discussed the distribution of HLA-B17, -DQB and -DRB together with QuantiFERON test results in tuberculosis infection. A case control study was done during which a total of 337 subjects were enrolled comprising 227 active tuberculosis (ATB), 46 latent tuberculosis infection (LTBI) and 64 healthy controls (HC). Sequence-specific primer polymerase chain reaction and immune epitope database were used to genotype samples and determine the epitope binding ability of the over-represented alleles respectively. QuantiFERON test was done according to manufacturer's instructions. The peptides HLA-B*5801 and HLA-DRB1*12 and the peptides HLA-B*5802 and HLA-DQB1*03 were found to be associated with latent tuberculosis while the haplotypes DRB1*10-DQB1*02 and DRB1*13-DQB1*06 were found to be associated with active tuberculosis (All p-values≤0.05). The association of HLA-B*5801 and HLA-B*5802 with latent tuberculosis was linked to their ability to bind or not mycobacterial antigens. DRB1*10-DQB1*02 haplotype was found to be over-represented in LTBI compared to ATB (p-value = 0.0015) while DRB1*13-DQB1*06 was found to be under-represented in LTBI compared to ATB (p-value = 0.0335). The DRB1*10-DQB1*02 haplotype was only found in the LTBI when compared with the ATB group. The present study suggests the following algorithm to discriminate LTBI from ATB: QuantiFERON+ and DRB1*10-DQB1*02 haplotype + may indicate LTBI; QuantiFERON+ and DRB1*10-DQB1*02 haplotype - may indicate ATB.

Upregulated bovine tuberculosis microRNAs Trigger oncogenic pathways: An In silico perception.

BACKGROUND/OBJECTIVE: Although microRNA (miRNA)-directed regulation of bovine tuberculosis (bTB) has already been reported, very little is known about the incited pathways and genes. We profiled bTB-upregulated miRNAs through an in silico methodology. METHODS: The data of upregulated miRNAs in bTB versus healthy controls were collected and clustered into three groups by their tissue specificity as follows: G1 (mammary gland-specific): bta-miR-146a; G2 (peripheral blood mononuclear cell-specific): bta-miR-155; and G3 (alveolar macrophage-specific): bta-miR-146a, bta-miR-155, bta-miR-142-5p, bta-miR-423-3p, bta-miR-21-5p, bta-miR-27a-3p, bta-miR-99b, bta-miR-147, bta-miR-223, and bta-let-7i. The miRNA-mRNA interaction network was defined by TargetScan. The gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways of these transcripts were examined. RESULTS: The results illustrate the induction of pathways in cancer, highly enriched, and unanimous to all three gene sets (G1, G2, and G3). Mitogen-activated protein kinase and PI3K-Akt signaling were specific to G2 and G3 with fibroblast growth factors formed the key factors. CONCLUSION: The inferred cancer cascades denote a probable modulation of innate immune response in an infectious state. These baseline pictures could lay the ground for further substantive studies.

MicroRNA hsa-miR-29a-3p is a plasma biomarker for the differential diagnosis and monitoring of tuberculosis.

The diagnosis of tuberculosis (TB) continues to pose substantial public health problems. The quest for diagnostic biomarkers for TB is therefore primordial. This study aimed to evaluate the diagnostic and anti-TB treatment monitoring potentials of some selected miRNAs. Quantitative real time polymerase chain reaction and Receiver operating characteristics were used to estimate the ability of miRNAs to discriminate between healthy controls (HEC), latent (LTB) and active TB (ATB). The study showed that: hsa-miR-29a-3p, hsa-miR-155-5p and hsa-miR-361-5p were significantly upregulated in ATB compared to HEC while hsa-miR-29a-3p, and hsa-miR-361-5p were also significantly up-regulated in ATB compared to LTB (all P ≤ 0.05). MiR-29a-3p showed a good (81.37%) distinguishing performance in discriminating ATB from HEC and a good (84.35%) diagnostic performance in discriminating ATB from LTB. The performance of miR-29a-3p present in the blood in discriminating active TB from latent TB and healthy controls indicates it may be a useful biomarker for diagnosis of TB. Because this miRNA is found in blood (plasma) which is easy to collect compared to sputum it could be used in pediatric and extra-pulmonary TB cases.

The pros and cons of the QuantiFERON test for the diagnosis of tuberculosis, prediction of disease progression, and treatment monitoring.

OBJECTIVE/BACKGROUND: Tuberculosis (TB) is a re-emerging disease with the advent of human immunodeficiency virus/AIDS infections. Discovered in 1959, diagnosed by various approaches and treated with antibiotics, the treatment of TB infection still poses public health concerns. Many cases of resistance and cross-resistance are observed. Diagnosis by culture, which is considered as the standard method, takes too long (20-30days) and is not suitable for extrapulmonary TB. QuantiFERON test, which is an indirect immunoassay based on blood, was developed. Much hope was placed in this new approach because it is based on blood, and many research teams have used it. We discuss the results of these different research groups who have used QuantiFERON for diagnosis, prediction of disease progression, or monitoring patients during the treatment of TB. METHODS: Articles published in PubMed and documents published on Google were searched with the keywords: diagnosis and TB and QuantiFERON; TB and QuantiFERON and therapeutic monitoring; interferon-γ release assay; disease progression. These articles were read and analyzed. RESULTS: The results were controversial with regards to using the QuantiFERON test for the diagnosis of TB according to the study population (ethnic group, bacillus Calmette-Guérin vaccine use) and according to the state of the immune system of the people studied (human immunodeficiency virus immunosuppression in cancer medication, hypertension). Also, research findings were controversial with regards to using QuantiFERON for monitoring TB patients on anti-TB medications. Also, the predictive positive value for the progression to TB among immigrant close contacts of both interferon-γ release assays was not better than that of the tuberculin skin test. CONCLUSION: The QuantiFERON has advantages and limitations depending on the type of population studied. Recommendations are made to improve the sensitivity and specificity and to differentiate between latent and active TB by adding other specific proteins in the Mycobacterium tuberculosis antigen cocktail.