Tuberculous Meningitis Genetic predisposition: Understanding cellular interactions, molecular mechanisms and genetic dimensions.

Tuberculous meningitis, a severe form of tuberculosis caused by Mycobacterium tuberculosis (BK), remains a major public health challenge worldwide. In addition to the complex mechanisms of the innate and adaptive immune response against Mycobacterium tuberculosis, there is a crucial genetic dimension to consider. Individuals with specific genetic variations may have altered immune responses that make them more susceptible to this form of tuberculosis. Genetic mutations in genes encoding surface receptors, adaptor proteins, kinases, transcription factors, nucleic receptors and other molecules involved in cellular interactions and molecular mechanisms have been associated with susceptibility to TB. Understanding the molecular mechanisms of immune interactions in host response to Mycobacterium tuberculosis is crucial to understanding the genetic dimension in susceptibility to tuberculosis, particularly its dreaded form of tuberculous meningitis. The aim of this update is to explore in details the key interactions between the main players in innate and adaptive immunity during infection with Mycobacterium tuberculosis, with particular emphasis on the genetic factors associated with susceptibility to tuberculosis, especially its dreaded form of tuberculous meningitis.

Impact of the first-line antiretroviral therapy on soluble markers of inflammation in cohort of human immunodeficiency virus type 1 in Moroccan patients: a prospective study.

Chronic inflammation and immune activation are a hallmark of HIV-1 infection. In this study, we assessed inflammation biomarkers in a cohort of people living with HIV-1 (PLWH) before and after long-term suppressive combined antiretroviral therapy (cART). A single-center prospective cohort study was conducted to assess inflammatory biomarkers in 86 cART-naive PLWH and after receiving suppressive cART and 50 uninfected controls. Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and soluble CD14 (sCD14) were measured using enzyme-linked immunosorbent assay (ELISA). No significant difference was found in IL-6 levels between cART-naïve PLWH and controls (p = 0.753). In contrast, TNF-α level showed a significant difference between cART naïve-PLWH and controls (p = 0.019). Interestingly, IL-6 and TNF-α levels were significantly decreased in PLWH after cART (p < 0.0001). The sCD14 showed no significant difference between cART-naïve patients and controls (p = 0.839) and similar levels were observed in pre- and post-treatment (p = 0.719). Our results highlight the critical importance of early treatment to reduce inflammation and its consequences during HIV infection.

Association between Methylene-Tetrahydrofolate Reductase C677T Polymorphism and Human Immunodeficiency Virus Type 1 Infection in Morocco.

Human immunodeficiency virus type 1 (HIV-1) infection varies substantially among individuals. One of the factors influencing viral infection is genetic variability. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is a genetic factor that has been correlated with different types of pathologies, including HIV-1. The MTHFR gene encodes the MTHFR enzyme, an essential factor in the folate metabolic pathway and in maintaining circulating folate and methionine at constant levels, thus preventing the homocysteine accumulation. Several studies have shown the role of folate on CD4+ T lymphocyte count among HIV-1 subjects. In this case-control study we aimed to determine the association between the MTHFR C677T polymorphism and HIV-1 infection susceptibility, AIDS development, and therapeutic outcome among Moroccans. The C677T polymorphism was genotyped by polymerase chain reaction followed by fragment length polymorphism digestion in 214 participants living with HIV-1 and 318 healthy controls. The results of the study revealed no statistically significant association between MTHFR C677T polymorphism and HIV-1 infection (P > .05). After dividing HIV-1 subjects according to their AIDS status, no significant difference was observed between C677T polymorphism and AIDS development (P > .05). Furthermore, regarding the treatment response outcome, as measured by HIV-1 RNA viral load and CD4+ T cell counts, no statistically significant association was found with MTHFR C677T polymorphism. We conclude that, in the genetic context of the Moroccan population, MTHFR C677T polymorphism does not affect HIV-1 infection susceptibility, AIDS development, or response to treatment. However, more studies should be done to investigate both genetic and nutritional aspects for more conclusive results.

MBL2 gene polymorphisms related to HIV-1 infection susceptibility and treatment response.

Human Mannose-binding lectin (MBL) is a protein encoded by MBL2 gene involved in the activation of the lectin-complement pathway. Several studies emphasized the role of MBL2 gene in several infectious diseases' susceptibility, including HIV-1 infection. We aim to investigate the impact of 10 MBL2 gene polymorphisms located in the promoter, 5'UTR and exon 1 regions on HIV-1 physiopathology. The polymorphisms genotyping of 400 individuals, which 200 were HIV-1 positive patients and 200 were controls, was performed by PCR-sequencing. Our results showed that rs503037 and rs1800451 polymorphisms are associated with a high risk of HIV-1 infection susceptibility while rs7096206 and rs11003123 showed a protective effect. A significant association between haplotype CGA and HIV-1 infection susceptibility was also found in the exon 1 region. Moreover, rs11003124, rs7084554, rs36014597 and rs11003123 polymorphisms revealed an association with treatment response outcome as measured by RNA viral load. This study highlights the importance of MBL2 polymorphisms in the modulation of HIV-1 infection susceptibility and the contribution to treatment response outcomes among Moroccan subjects.

[Sternocostal osteomyelitis due to Aspergillus after coronary angioplasty: a case report]. / Aspergillose sterno-costale après angioplastie coronaire: à propos d'un cas.

Sternal osteomyelitis due to aspergillosis is extremely rare. Among all cases of invasive aspergillosis reported in the literature, the incidence of osteomyelitis is less than 3%. Aspergillosis mainly affects immunosuppressed patients. Clinical and radiological manifestation is nonspecific. Contamination is primarily caused by inhaling spores, but it can also directly reach a vulnerable area after medical procedure. Diagnosis is often difficult and may take several weeks, in particular when aspergillosis is not suspected. Positive diagnosis is based on imaging tests but it is confirmed by anatomopathological and/or mycological examinations. Prognosis mainly depends on early administration of treatment. We here report the case of a 63-year-old diabetic patient with sternocostal osteomyelitis due to Aspergillus occurred after coronary angioplasty.

Programmed cell death-1 single-nucleotide polymorphism rs10204525 is associated with human immunodeficiency virus type 1 RNA viral load in HIV-1-infected Moroccan subjects.

Human Immunodeficiency Virus (HIV-1) infections are characterized by dysfunctional cellular and humoral antiviral immune responses. The progressive loss of effector functions in chronic viral infection has been associated with the up-regulation of programmed death-1 (PD-1), a negative regulator of activated T cells and Natural Killer cells. In HIV-1 infection, increased levels of PD-1 expression correlate with CD8 + T-cell exhaustion. In vitro, PD-1 blockade using PD-1 antibodies led to an increase in HIV-1 specific CD8 + T and memory B cell proliferation. We aimed to investigate the impact of PDCD1 rs10204525 polymorphism on HIV-1 susceptibility, AIDS development, and treatment response outcomes in HIV-1 infection in a Moroccan population. A total of 214 HIV-1 seropositive and 250 seronegative subjects were enrolled to investigate the association between the between the single-nucleotide polymorphism (SNP) rs10204525 of PDCD1 gene and HIV-1 pathogenesis using a predesigned TaqMan SNP genotyping assay. No significant association was found between rs10204525 and susceptibility to HIV-1 infection and AIDS development (p > 0.05). Genotype frequencies were significantly associated with the viral load before ART (p = 0.0105). HIV-1 viral load was significantly higher among subjects with the CC compared to TT genotype (p = 0.0043). In treated subjects, the median of viral load levels was significantly higher in CC and CT groups than TT subjects (p < 0.005). However, analysis of the correlation between CD4 + T-cell levels and PDCD1 polymorphism before and after ART showed no significant difference (p > 0.05). Our results demonstrated that rs10204525 polymorphism does not affect HIV-1 infection. However, this polymorphism may affect the response to treatment as measured by RNA viral load levels.

Missed opportunities for HIV testing in patients newly diagnosed with HIV in Morocco.

BACKGROUND: In Morocco, of the estimated 29,000 people living with HIV in 2011, only 20% were aware of their HIV status. More than half of diagnoses were at the AIDS stage. We assumed that people who were unaware of their infection had contacts with the healthcare system for HIV indicators that might prompt the healthcare provider to offer a test. The aim was to assess missed opportunities for HIV testing in patients newly diagnosed with HIV who accessed care in Morocco. METHODS: A cross-sectional study was conducted in 2012-2013 in six Moroccan HIV centers. Participants were aged ≥18, and had sought care within 6 months after their HIV diagnosis. A standardized questionnaire administered during a face-to-face interview collected the patient's characteristics at HIV diagnosis, HIV testing and medical history. Contacts with care and the occurrence of clinical conditions were assessed during the 3 years prior to HIV diagnosis. Over this period, we assessed whether healthcare providers had offered HIV testing to patients with HIV-related clinical or behavioral conditions. RESULTS: We enrolled 650 newly HIV-diagnosed patients (median age: 35, women: 55%, heterosexuals: 81%, diagnosed with AIDS or CD4 < 200 cells/mm3: 63%). During the 3 years prior to the HIV diagnosis, 71% (n = 463) of participants had ≥1 contact with the healthcare system. Of 323 people with HIV-related clinical conditions, 22% did not seek care for them and 9% sought care and were offered an HIV test by a healthcare provider. The remaining 69% were not offered a test and were considered as missed opportunities for HIV testing. Of men who have sex with men, 83% did not address their sexual behavior with their healthcare provider, 11% were not offered HIV testing, while 6% were offered HIV testing after reporting their sexual behavior to their provider. CONCLUSIONS: Among people who actually sought care during the period of probable infection, many opportunities for HIV testing, based on at-risk behaviors or clinical signs, were missed. This highlights the need to improve the recognition of HIV clinical indicators by physicians, further expand community-based HIV testing by lay providers, and implement self-testing to increase accessibility and privacy.

Lack of Association between IFNL3 Polymorphism and Human Papillomavirus Infection and Their Progression in HIV-Infected Women Receiving Antiretroviral Treatment.

BACKGROUND: It has been reported that interferon-λ3 (IFNL3)might influence the pathogenesis and clearance of human papillomavirus (HPV) infection. The impact of IFNL3 single-nucleotide polymorphism (SNP) on HPV infection is currently unknown. The aim of this study was to investigate the association between variants in the IFNL3 region and HPV infection in women with human immunodeficiency virus (HIV) infection. METHODS: A total of 236 HIV patients, including 65 HPV-negative and 171 HPV DNA-positive women, were enrolled into this study. The IFNL3 rs12979860 polymorphism was genotyped using a predesigned TaqMan SNP genotyping assay. RESULTS: Data showed no significant differences in genotypes or allele frequencies between the HPV DNA-positive and the HPV-negative women (p > 0.05). After dividing the HPV-positive women according to cytology results into patients with abnormal and normal lesions, the genotype and allele distribution of the SNP did not significantly differ between the 2 groups (p > 0.05). CONCLUSIONS: Our results showed that the IFNL3 rs12979860 polymorphism is not a major determinant of the susceptibility to HPV infection and their progression to abnormal cervical lesions in women living with HIV.

The Human papillomavirus among women living with Human Immunodeficiency Virus in Morocco: A prospective cross-sectional study.

INTRODUCTION: Women infected with human immunodeficiency virus (HIV) have a higher risk of contracting human papillomavirus (HPV) infections and are more prone to develop cervical cancer. The objective of this study was to determine the prevalence of HPV and its association with risk factors among Moroccan women living with HIV/AIDS. METHODOLOGY: We enrolled 251 HIV-infected non-pregnant women in Morocco from February 2013 to September 2016. Sociodemographic, lifestyles, behavioral and clinical data were collected. Polymerase chain reaction followed by sequencing were performed for molecular detection and HPV genotyping in cervical samples, respectively. RESULTS: Abnormal cervical smears were found in 34/246 patients (13.82%). The overall prevalence of HPV was 74.50%. HPV 58 was the most prevalent (39.29%) followed by HPV 18 (10.71%), HPV 70 (8.93%), HPV 33 (7.14%), HPV 6 (6.25%) and other genotypes (< 3%). Overall, high-risk HPV (HR-HPV) types were present in 75% (84/112) of patients and the prevalence of HR-HPV types in samples with abnormal Pap was higher than in normal Pap (55/83, 66.27% vs. 28/83, 33.33%, p < 0.0001). Univariate analyses showed that none of the socio-demographic and behaviors factors was associated with HPV infection. Moreover, Pap results were not affected by HPV status (p = 0.532). Whereas, CD4 T-cell counts above 200/mm3 at enrolment were apparently not protective to HPV infection. We found a high prevalence of HPV infection and HR-HPV types among HIV-positive women that significantly associated with abnormal Pap. CONCLUSION: Our findings suggest a high prevalence of HPV infection with high-risk types was observed among HIV-positive women warrant to implement a regular screening by Pap smear.

TP53 R72P Polymorphism and Susceptibility to Human Papillomavirus Infection Among Women With Human Immunodeficiency Virus in Morocco: A Case-control Study.

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide. HPV is the main causative agent for cervical cancer. The HPV oncoprotein E6 binds to the tumor suppressor gene product p53, promoting its degradation; the Arg allele of TP53 R72P polymorphism binds more ardently with HPV E6 than the Pro variant. Here, we investigated whether TP53 R72P gene variant, rs104252, was associated with susceptibility to HPV infection in women with human immunodeficiency virus (HIV). METHODS: We analyzed 200 HPV-positive and 68 uninfected women with HIV. Genomic DNA was isolated from cervical swab. The TP53 R72P polymorphism was genotyped by PCR-RFLP. Unconditional logistic regression was used to assess the association between polymorphism and the clinical, lifestyle, and behavioral data. RESULTS: The genotype and allele frequencies of rs104252 variant did not differ between women without or with HPV infection (P > 0.05). Moreover, the p53 polymorphism was not associated with cervical cytology. In contrast, when we analyzed according to behavior factors, the P72P genotype was more frequent among HPV-positive smoker women. However, no significant relationship was found between alcohol, contraceptive use, and number of partners with TP53 R72P genotype distributions among HPV-positive cases (P > 0.05). CONCLUSIONS: The R72 variant of p53 R72P is not associated with HPV infection and progression of lesions. There was no association between this variant and behavior factors in HPV-positive cases. The P72P genotype may be more frequent among HPV-positive smoker women.

Diabetes and human immunodeficiency virus infection: Epidemiological, therapeutic aspects and patient experience.

INTRODUCTION: Nationally, no data on the association between human immunodeficiency virus infection and diabetes have been published. OBJECTIVES: To review the epidemiological, clinical and therapeutic data and evaluate the experience of people living with HIV and suffering from diabetes. METHODS: Our study population was composed of 190 outpatients (87 males and 103 females) attending the Infectious Diseases department of the University Hospital Center of Casablanca (Ibn Rochd). Using the computerized medical records, we identified patients with HIV-Diabetes and collected their epidemiological, clinical and therapeutic data. At the enrollment date of each patient, we measured anthropometric parameters (weight, height, waist circumference, hip circumference, and arm circumference). We also asked each patient, about the impression on their bodies' appearance and the degree of concern with regard to the diabetes. RESULTS: The population of patients with HIV, the prevalence of diabetes was 10.5%, among the patients taking an antiretroviral therapy, the prevalence was 13.5%. Diabetes has been diagnosed in 113 patients before the discovery of their HIV infection. At time of recruitment, 111 of them were under antiretroviral therapy for a mean period of 3.1years. Zidovudine was the most prescribed drug followed by lamivudine. Type 2 diabetes was diagnosed in 144 patients. Eighty-seven patients feel conscious about their body appearance which makes them feel bad about the way they look. Metformin was prescribed in 46 cases. The majority of patients (73.1%) considered diabetes as a second health problem. Only 46 patients were well balanced. CONCLUSION: The multidisciplinary consultation and patient education should enable an appropriate management of diabetes in HIV infected patients.

Risk factors for liver fibrosis among human immunodeficiency virus monoinfected patients using the FIB4 index in Morocco.

AIM: To study the prevalence and risk factors of significant hepatic fibrosis in Moroccan human immunodeficiency virus (HIV) monoinfected patients. METHODS: We conducted a cross-sectional study among HIV monoinfected patients (negative for hepatitis B surface antigen and hepatitis C antibody). Clinical and laboratory data were collected from the data base of the Infectious Diseases Unit in Ibn Rochd Hospital Center [age, gender, duration of HIV infection, CD4 T lymphocyte count, HIV viral load, glycemia and current or prior use of antiretroviral and antiretroviral therapy (ART) duration]. The primary outcome was a FIB4 score > 1.45. Multivariable logistic regression identified independent risk factors for FIB4 > 1.45. RESULTS: A FIB4 score > 1.45 was identified in 96 among 619 (15.5%). HIV monoinfected patients followed up between September 1990 and September 2012. Multivariate analysis showed that only a viral load > 75 (OR = 2.23, 95%CI: 1.36-3.67), CD4 > 200 cells/mm(3) (OR = 0.39, 95%CI: 0.21-0.72) and age at FIB4 index calculation (OR = 1.10, 95%CI: 1.07-1.13) were independently associated with the occurrence of FIB4 index (> 1.45). Gender, duration of HIV infection, glycemia, use of antiretroviral therapy and ART duration were not associated with significant fibrosis by FIB4. CONCLUSION: FIB4 score > 1.45 was found in 15.5% of Moroccan HIV monoinfected patients. Age, HIV viremia > 75 copies/mL and CD4 count > 200 cells/mm(3) are associated with liver fibrosis. Further studies are needed to explore mechanisms for fibrosis in HIV monoinfected patients.

[Causes of death among 91 HIV-infected adults in the era of potent antiretroviral therapy]. / Causes de décès de 91 patients ayant une infection à VIH traités par des antirétroviraux.

OBJECTIVE: To describe the causes of death occurring during the antiretroviral therapy in Casablanca. METHODS: Retrospective study of a cohort of HIV positive patients attending the infectious diseases unit of Casablanca receiving antiretroviral therapy. Files of 91 patients who died were analyzed. RESULTS: Since June 1999, 1243 patients were treated and 91 deaths occurred (7, 3%). The mean age at time of death was 36 years. Forty-six patients were male (50, 5%) and 86 were stage C (94, 5%). At the initiation of treatment, mean CD4 count was 96 cells/mL (1-626) and mean plasma HIV- RNA was 5, 65 log10. They have received antiretroviral therapy for a mean of 9 months (1-48 months). At time of death, 37 patients (52, 8%) had a CD4 count greater than 200 cells/mL and 16 patients (23%) had undetectable plasma viral load. In 57 cases (63%), the death occurred within the first year after start of antiretroviral therapy. The main causes of death were: tuberculosis (35%), cryptosporidiosis (19%), cryptococcosis (13%), cerebral toxoplasmosis (9%), Kaposi sarcoma (6%), non Hodgkin's lymphoma (2%), atypical mycobacteriosis (2%), cerebral lymphoma (1%), aspergillosis (1%), HIV wasting syndrome (1%) and cancer of cervix (1%). Non AIDS related deaths were noticed in three cases (3%) and the immune reconstitution inflammatory syndrome in six cases (7%). CONCLUSION: In Casablanca, the main cause of death among HIV-infected patients is tuberculosis. Collaboration between the national tuberculosis and AIDS programs has been established to improve the prevention, detection, diagnosis and management of HIV/tuberculosis co infection.