ABSTRACT
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.
Subject(s)
Genetic Predisposition to Disease , Mycobacterium tuberculosis , Tuberculosis, Meningeal , Humans , Tuberculosis, Meningeal/genetics , Tuberculosis, Meningeal/immunology , Mycobacterium tuberculosis/immunology , Immunity, Innate/genetics , Adaptive Immunity/geneticsABSTRACT
Interleukin-6 (IL-6), a pro-inflammatory cytokine, is an important regulator of the inflammatory immune response. We aimed to assess the association of common single nucleotide polymorphisms (SNPs) in IL-6 (rs1800795 G > C, rs1800797 A > G) and interleukin-6 receptor (IL-6R) (rs2228145 A > C) genes with HIV-1 infection, AIDS progression, and response to treatment. In this case-control study involving 199 individuals living with HIV-1 and 200 HIV-uninfected controls, we conducted genotyping of IL-6/IL-6R SNPs using TaqMan real-time PCR assays. Soluble IL-6 levels were measured using ELISA. No associations were found between the investigated SNPs and HIV infection. However, a significant association was noted between the C-G and G-A haplotypes and susceptibility to HIV-1 infection. Additionally, a significant association was revealed between HIV-1 RNA viral loads and IL-6 SNP G > C in the post-treatment HIV group. Interestingly, we observed a significant association between the investigated SNPs and protection against progression to AIDS, namely the IL-6 G > A SNP in its recessive model and the IL-6R A > C SNP in its codominant and dominant models. Nevertheless, we found no significant differences between IL-6 levels and the different genotypes and alleles of the IL-6 gene either before or after combination antiretroviral therapy. IL-6 promoter haplotypes are associated with susceptibility to HIV-1 infection. Furthermore, IL-6 A > G and IL-6R A > C polymorphisms have been associated with protection against AIDS progression. Interestingly, the IL-6 G > C SNP may affect the response to treatment in people living with HIV-1.
ABSTRACT
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.
Subject(s)
HIV Infections , HIV Seropositivity , HIV-1 , Mannose-Binding Lectin , Humans , Genotype , Polymorphism, Genetic , Haplotypes , Mannose-Binding Lectin/genetics , HIV Infections/genetics , Genetic Predisposition to DiseaseABSTRACT
Vaccine preventable diseases (VPDs) are a prevailing concern among the adult population, despite availability of vaccines. Unlike pediatric vaccination programs, adult vaccination programs lack the required reach, initiative, and awareness. Clinical studies and real-world data have proven that vaccines effectively reduce the disease burden of VPDs and increase life expectancy. In Tunisia and Morocco, the national immunization program (NIP) focuses more on pediatric vaccination and have limited vaccination programs for adults. However, some vaccination campaigns targeting adults are organized. For example, influenza vaccination campaigns prioritizing at risk adults which includes healthcare professionals, elderly, and patients with comorbidities. Women of childbearing age who have never been vaccinated or whose information is uncertain are recommended to receive tetanus vaccination. Tunisia NIP recommends rubella vaccine mainly for women of childbearing age, while in Morocco, national vaccination campaigns were organized for girls and women (up to 24 years of age) to eliminate rubella. Further, travelers from both countries are recommended to follow all requirements and recommendations in the travel destination. The objective of this manuscript is to provide an overview of the global disease burden of common VPDs including (but not limited to) meningococcal diseases, pneumococcal diseases, hepatitis, and influenza. The review also provides an overview of clinical data and guidelines/recommendations on adult vaccination practices, with special focus on Tunisia and Morocco. Some European and North American countries have concrete recommendations and strategies for adult vaccination to keep the VPDs in check. In Morocco and Tunisia, although, there are sporadic adult vaccination initiatives, the efforts still need upscaling and endorsements to boost vaccination awareness and uptake. There is a need to strengthen strategies in both countries to understand the disease burden and spread awareness. Additional studies are needed to generate economic evidence to support cost-effectiveness of vaccines. Integration of private and public healthcare systems may further improve vaccination uptake in adults.
Subject(s)
Influenza Vaccines , Influenza, Human , Adult , Aged , Child , Female , Humans , Morocco , Tunisia , VaccinationABSTRACT
INTRODUCTION: The Ibn Rochd CHU is a tertiary care structure that provides care for the most severe cases of COVID-19 requiring hospitalisation in intensive care. The objective of study is to describe the complementary medical and psychological care of patients with COVID-19 in the endocrinology department after a stay in intensive care. PATIENTS AND METHODS: This is a descriptive observational study of patients transferred from the intensive care unit to the endocrinology service following a COVID-19 infection during the period from 17 April 2020 to May 26, 2020. Clinical characteristics of the patients and complications related to COVID-19 infection were studied; a nutritional assessment using the MNA nutritional status assessment questionnaire; psychological assessment using quality-of-life questionnaires (Hamilton depression and anxiety, HAD, SF36, PCLS); a treatment satisfaction questionnaire (TQCMII) and an assessment of patient autonomy by the ADL score. RESULT: Our study included 41 patients with an average age of 55 years (19-85 years), a sex ratio M/F of 1.05, 43.9% were diabetic, 34.1% hypertensive, 4.9% asthmatic and 5% obese, and 51.2% were severe and critical cases. The average ICU stay is 8.42 days, requiring intubation in 12.2% of cases. All patients were treated with the Hydroxychloroquine, Azithromycin, vitamin C, zinc and corticosteroid protocol, 14.6% had undernutrition and 65.9% had a risk of undernutrition. The average BMI was 25.34 kg/m2 (17-42), 61% had experienced weight loss, which was greater than 8 kg in 26.1% of cases, 12.2% of patients were not autonomous, 12.2% had moderate depression, 2.4% severe depression, 14.6% mild to moderate anxiety, 12.2% severe anxiety and 29.3% suffered acute post-traumatic stress disorder. CONCLUSION: Patients with COVID-19 are, in addition to the complications from coronavirus infection, vulnerable to undernutrition, psychological and motor complications. Additional care before discharge is essential for better integration of patients into their families.
Subject(s)
COVID-19 , Critical Care , Humans , Hydroxychloroquine , Intensive Care Units , Middle Aged , Patient Discharge , SARS-CoV-2ABSTRACT
BACKGROUND: In the era of "test and treat strategy", CD4 testing remains an important tool for monitoring HIV-infected individuals. Since conventional methods of CD4 count measurement are costly and cumbersome, POC CD4 counting technique are more affordable and practical for countries with limited resources. Before introducing such methods in Morocco, we decided to assess their reliability. METHODS: In this study 92 blood samples from HIV-infected patients, were tested by PIMA and FACSPresto to derive CD4 count. Flow cytometry using FacsCalibur, was used as reference method for CD4 count comparison. Linear regression, Bland-Altman analysis were performed to assess correlation and agreement between these POC methods and the reference method. In addition, sensitivity and specificity, positive predictive value (PPV), negative predictive value (NPV) and misclassification percentage at 350 and 200 CD4 count thresholds; were also determined. Finally, because FACSPresto can also measure hemoglobin (Hb) concentration, 52 samples were used to compare FACSPresto against an automated hematology analyzer. RESULTS: The coefficient of determination R2 was 0.93 for both methods. Bland-Altman analysis displayed a mean bias of - 32.3 and - 8.1 cells/µl for PIMA and FACSPresto, respectively. Moreover, with a threshold of 350 CD4 count, PIMA displayed a sensitivity, specificity, PPV, NPV, were 88.57%, 94.12%, 91.18%, 92.31%; respectively. FACSPresto showed 88.23%, 96.23%, 93.75% and 92.73%; respectively. Furthermore, the upward misclassification percentage was 8.57 and 5.88%, for PIMA and FACSPresto, respectively; whereas the downward misclassification percentage was 7.84% and 7.54%; respectively. With 200 cells/µl threshold, PIMA had a sensitivity, specificity, PPV and NPV of 83.33%, 98.53%, 93.75% and 95.71%, respectively. Regarding FACSPresto, sensitivity, specificity, PPV and NPV was 82.35%, 98.57%, 88.57% and 95.83%; respectively. Upward misclassification percentage was 5.56% and 5.88%, for PIMA and FACSPresto, respectively; whereas downward misclassification percentage was 4.41% and 4.29%; respectively. Finally, the hemoglobin measurement evaluation displayed an R2 of 0.80 and a mean bias of - 0.12 with a LOA between - 1.75 and 1.51. CONCLUSION: When compared to the reference method, PIMA and FACSPresto have shown good performance, for CD4 counting. The introduction of such POC technology will speed up the uptake of patients in the continuum of HIV care, in our country.
Subject(s)
CD4 Lymphocyte Count/methods , Flow Cytometry , HIV Infections/diagnosis , Point-of-Care Testing , Automation, Laboratory , CD4-Positive T-Lymphocytes/cytology , Humans , Morocco , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
BACKGROUND: Leptospirosis is an anthropozoonotic reemerging neglected infectious disease underreported in most developing countries. A cross-sectional study was performed between 17 and 23 February 2014 to estimate the seroprevalence of leptospirosis among high-risk populations in Casablanca (Morocco). METHODS: A total of 490 human serum samples (97.6% males) were collected in 3 high-risk occupational sites including the biggest meat slaughterhouse (n = 208), a poultry market (n = 121), and the fish market (n = 161). A total of 125 human blood samples were also collected from the general population and used in this study as a control group. To detect the presence of anti-Leptospira, sera were screened with in-house IgG and IgM enzyme-linked immunosorbent assay (ELISA). Positive samples were tested by Microscopic Agglutination Technique (MAT) using a panel of 24 serovar cultures and cut point of 1 : 25. RESULTS: Seroprevalence of leptospirosis among the control group was 10.4% (13/125). A high seropositivity among the overall seroprevalence of 24.1% (118/490) was observed in the high-risk groups of which 7.3% (36/490), 13.7% (67/490), and 3.1% (15/490) were for anti-Leptospira IgM, IgG, and both IgG and IgM antibodies, respectively. Most of the positive individuals were occupationally involved in poultry (37.2%), followed by the market fish (26.1%) and the meat slaughterhouse (14.9%) workers. Among all ELISA-positive serum samples, 20.3% (n = 24) had positive MAT responses, of which the Icterohaemorrhagiae (n = 7) is the most common infecting serogroup followed by Javanica (4), Australis (2), and Sejroe, Mini, and Panama (one in each). In the remaining 8 MAT-positive sera, MAT showed equal titers against more than one serogroup. CONCLUSION: Individuals engaged in risk activities are often exposed to leptospiral infection. Therefore, control and prevention policies toward these populations are necessary.
ABSTRACT
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.
Subject(s)
Antiviral Agents/therapeutic use , Disease Progression , HIV Infections/virology , Interferons/genetics , Papillomavirus Infections/genetics , Papillomavirus Infections/immunology , Adult , Aged , Cross-Sectional Studies , Female , Genetic Predisposition to Disease , Genotype , HIV Infections/drug therapy , Humans , Middle Aged , Polymorphism, Single Nucleotide , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/virology , Young AdultABSTRACT
Human Immunodeficiency Virus type 1 (HIV-1) infection and progression varies widely among individuals. Interferon-λ3 exerts anti-HIV function by activating JAK/STAT pathway-mediated innate immunity. Therefore, we aimed to investigate the association between single nucleotide polymorphisms of the interleukin 28B (IL28B) gene, and the risk of acquisition, AIDS development and therapeutic outcome of HIV-1 in a Moroccan population. A total of 266 HIV-1 seropositive and 158 HIV-1 seronegative subjects were enrolled. Genotyping of rs12979860 of the IL28B was performed using a predesigned TaqMan SNP genotyping assay. No significant association was found between IL28B rs12979860 polymorphism and susceptibility to HIV-1 infection and AIDS development (pâ¯>â¯.05). However, in HIV-1 treated patients carrying CC genotype had a more pronounced high levels of CD4+ T-cell compared to subjects with TT genotype (pâ¯=â¯.0004). Interestingly, regarding HIV-1 viral load no significant differences between IL28B genotypes in treated and untreated patients were observed (pâ¯<â¯.05). IL28B rs12979860 polymorphism not influences the susceptibility to HIV-1 and the AIDS development. However, this polymorphism may affect the response to treatment as measured by CD4+ T cell counts.
Subject(s)
Acquired Immunodeficiency Syndrome/immunology , CD4-Positive T-Lymphocytes/immunology , Genotype , HIV-1/physiology , Interleukins/genetics , Acquired Immunodeficiency Syndrome/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antiretroviral Therapy, Highly Active , Female , Gene Frequency , Genetic Predisposition to Disease , HIV Seropositivity , Humans , Interferons , Male , Middle Aged , Morocco , Polymorphism, Single Nucleotide , Treatment Outcome , Viral Load/genetics , Young AdultABSTRACT
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.