SFRP1 variations influence susceptibility and immune response to Mycobacterium tuberculosis in a Chinese Han population

ObjectivesSFRP1 acts as a well-established inhibitory regulator of the Wnt signaling pathway, whose polymorphisms have been demonstrated to be associated with the risk of inflammation, infection as well as cancer. We verified the hypothesis that single nucleotide polymorphisms (SNPs) within SFRP1 gene are associated with susceptibility and clinical characteristics of tuberculosis disease in a Chinese Han population.MethodsSix candidate SNPs were genotyped using MassARRAY method in a case–control design (260 tuberculosis patients and 252 healthy controls). A comprehensive analysis of single locus including the genotypic, allelic frequencies and the genetic models, haplotypic construction as well as gene–gene interaction was conducted to investigate the relationships between SNPs and TB. Significant SNPs were further interrogated in relation to TB clinical features and host inflammatory status.ResultsGenotype frequencies of rs4736958 and rs7832767 within SFRP1 gene were significantly different (p = 0.011, p = 0.008, respectively) between tuberculosis group and control group. Subjects carrying C allele for rs4736958 showed a decreased tuberculosis risk (OR = 0.66, 95% CI = 0.51–0.87, p = 0.003), whereas individuals carrying rs7832767 T allele had a significant increased risk in tuberculosis susceptibility (OR = 1.32, 95% CI = 1.01–1.74, p = 0.046). Genetic model analysis revealed that dominant, co-dominant and recessive models of rs4736958 were associated with decreased susceptibility to tuberculosis (p all < 0.05), while the recessive and co-dominant models of rs7832767 were related to significantly increased risk for tuberculosis (p all < 0.05). There was a reduced tuberculosis risk in association with the haplotype CC (representing rs3242 and rs4736958) of SFRP1 (OR = 0.73, 95% CI = 0.56–0.96, p = 0.026). Further stratification analysis indicated that TB patients with genotype CT for rs4736958 were associated with higher CRP concentrations, and heterozygous patients (CT genotype) of rs7832767 trended towards greater ESR levels.ConclusionSNPs rs4736958 and rs7832767 of SFRP1 gene were significantly associated with tuberculosis susceptibility and might influence the expression levels of inflammatory markers of tuberculosis patients in a Chinese Han population.     

MBL2 gene polymorphisms and susceptibility to tuberculosis in a northeastern Brazilian population

The innate immune system represents the first line of host defense against pathogens. Genetics factors regulating the immune responses play a role in the susceptibility to infectious diseases, such as tuberculosis (TB). We analyzed MBL2 promoter and exon 1 functional single nucleotide polymorphisms (SNPs) in a group of 155 TB patients and 148 healthy controls in order to evaluate their influence on the onset of infection and TB development. There was no association between MBL2 −550 HL promoter polymorphisms and susceptibility to develop TB, but heterozygous −221 Y/X genotype was significantly more frequent in pulmonary TB patients than controls. Moreover, MBL2 exon 1 O allele, was significantly associated with susceptibility to TB development in general (p = 0.023, OR = 1.61, 95% CI 1.05–2.49) and pulmonary TB (p = 0.0008, OR = 2.16, 95% CI 1.35–3.46); C allele at codon 57, as well as A/C genotype, were significantly more frequent in TB patients than in controls. Our results indicate that MBL2 polymorphisms, especially at codon 57, could be considered as risk factors for TB development.     

The association between CYP2E1 polymorphisms and hepatotoxicity due to anti-tuberculosis drugs: A meta-analysis

BackgroundAlthough there have been previous studies on the potential association between cytochrome P450 2E1 (CYP2E1) polymorphisms and the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH), the results have generally been controversial.MethodsWe searched Medline/PubMed, EMBASE, Web of Science, and the Cochrane Library using the following key words: cytochrome P450 2E1, CYP2E1, polymorphism, tuberculosis and TB. The strength of the association between the CYP2E1 PstI/RsaI and DraI polymorphism and ATDH risk as measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied.ResultsCompared with the wild genotype (c1/c1), the OR of ATDH was 1.41 (95% CI: 1.1–1.82, P = 0.007) for the PstI/RsaI polymorphism, and 0.78 (95% CI: 0.51–1.18, P = 0.23) for the DraI polymorphism. Compared with individuals with N-acetyltransferase 2 (NAT2) fast or intermediate acetylator genotype and c1/c1 genotype patients who were NAT2 slow acetylators and carried the high activity CYP2E1 c1/c1 genotype had higher risk for ATDH (OR = 3.10, P < 0.0001).ConclusionThe present meta-analysis indicates that the CYP2E1 c1/c1 genotype may be a risk factor for ATDH, and the concomitant presence of the slow acetylator NAT2 genotype may further increase this risk.     

Polymorphisms in the prostaglandin receptor EP2 gene confers susceptibility to tuberculosis

ObjectivesProstaglandin E2 (PGE2) is an important lipid mediator of the inflammatory immune response during acute and chronic infections. PGE2 modulates a variety of immune functions via four receptors (EP1–EP4), which mediate distinct PGE2 effects. Mice lacking EP2 are more susceptible to infection by Mycobacterium tuberculosis (M.tb), have a higher bacterial load, and increase size and number of granulomatous lesions. Our aim was to assess whether single nucleotide polymorphisms (SNPs) in EP2 increase the risk of tuberculosis.MethodsDNA re-sequencing revealed five common EP2 variants in the Chinese Han population. We sequenced the EP2 gene from 600 patients and 572 healthy controls to measure SNP frequencies in association with tuberculosis infections (TB) within the population.ResultsThe rs937337 polymorphism is associated with increased risk to tuberculosis (p = 0.0044, odds ratio [OR], 1.67; 95% confidential interval,1.22–2.27). The rs937337 AA genotype and the rs1042618 CC genotype were significantly associated with TB. An estimation of the frequencies of haplotypes revealed a single protective haplotype GACGC for tuberculosis (p = 0.00096, odds ratio [OR], 0.56; 95% confidential interval, 0.41–0.77). Furthermore, we determined that the remaining SNPs of EP2 were nominally associated with clinical patterns of disease.ConclusionsWe identified genetic polymorphisms in EP2 associated with susceptibility to tuberculosis within a Chinese population. Our data support that EP2 SNPs are genetic predispositions of increased susceptibility to TB and to different clinical patterns of disease.     

Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials

BackgroundNovel vaccine strategies are required to provide protective immunity in tuberculosis (TB) and prevent development of active disease. We investigated the safety and immunogenicity of a novel TB vaccine candidate, H4:IC31 (AERAS-404) that is composed of a fusion protein of M. tuberculosis antigens Ag85B and TB10.4 combined with an IC31® adjuvant.MethodsBCG-vaccinated healthy subjects were immunized with various antigen (5, 15, 50, 150 μg) and adjuvant (0, 100, 500 nmol) doses of the H4:IC31 vaccine (n = 106) or placebo (n = 18) in two randomized, double-blind, placebo-controlled phase I studies conducted in a low TB endemic setting in Sweden and Finland. The subjects were followed for adverse events and CD4⁺ T cell responses.ResultsH4:IC31 vaccination was well tolerated with a safety profile consisting of mostly mild to moderate self-limited injection site pain, myalgia, arthralgia, fever and post-vaccination inflammatory reaction at the screening tuberculin skin test injection site. The H4:IC31 vaccine elicited antigen-specific CD4⁺ T cell proliferation and cytokine production that persisted 18 weeks after the last vaccination. CD4⁺ T cell expansion, IFN-γ production and multifunctional CD4⁺ Th1 responses were most prominent after two doses of H4:IC31 containing 5, 15, or 50 μg of H4 in combination with the 500 nmol IC31 adjuvant dose.ConclusionsThe novel TB vaccine candidate, H4:IC31, demonstrated an acceptable safety profile and was immunogenic, capable of triggering multifunctional CD4⁺ T cell responses in previously BCG-vaccinated healthy individuals. These dose-escalation trials provided evidence that the optimal antigen-adjuvant dose combinations are 5, 15, or 50 μg of H4 and 500 nmol of IC31.Trial registration: ClinicalTrials.gov, NCT02066428 and NCT02074956.     

Factors of loss to follow-up during tuberculosis treatment in a low-incidence region

ObjectiveThe proportion of successfully treated tuberculosis (TB) patients remains below the WHO target in France, because of a high proportion of loss to follow-up. We aimed to identify factors associated with loss to follow-up in northern France, a low-incidence area.MethodsBetween 1997 and 2017, all consecutive patients diagnosed with TB at the Tourcoing Hospital, except those infected with multidrug-resistant or extensively drug-resistant strains, were included in a retrospective cohort study. A logistic regression analysis was performed to determine factors associated with loss to follow-up.ResultsOne hundred and ninety patients were included. Previous TB treatment was reported in 32 patients (17%), extrapulmonary TB in 107 (56%), and HIV infection in 44 (23%). The proportion of loss to follow-up was 15%. In multivariate analysis, the risk of loss to follow-up decreased in case of first TB treatment (OR 0.36; 95% CI: 0.14–0.92, P = 0.03) and increased in non-HIV-infected patients (OR 7.67; 95% CI: 1.00–59.0, p = 0.05). Support for compliance was more frequent in HIV-infected patients (23% vs. 7%, p = 0.005).ConclusionThe proportion of loss to follow-up was high. HIV infection was associated with a lower risk of loss to follow-up, likely to be due to more frequent support for compliance.     

Genetic variants at 18q11.2 and 8q24 identified by genome-wide association studies were not associated with pulmonary tuberculosis risk in Chinese population

ObjectiveGenome-wide association study (GWAS) recently identified several susceptibility loci in ASAP1 gene on chromosome 8q24 for tuberculosis (TB) in a Russian population, but no relevant studies have been performed to validate these findings. In addition, previous GWAS in Ghana and Gambia found that the variant rs4331426 at 18q11.2 was a susceptibility locus for TB. However, the follow-up studies reported conflicting results. Herein, we investigated the contribution of genetic variants at 8q24 and 18q11.2 to TB in Chinese population.MethodsWe genotyped four genetic variants at 8q24 (rs10956514 and rs11774633) and 18q11.2 (rs4331426 and rs6507226) in a case–control study with 355 newly bacteriologically confirmed pulmonary TB cases and 395 healthy controls using TaqMan allelic discrimination assay. Subsequently, we conducted a meta-analysis including 4 reported studies in Chinese populations and our case–control study with a total of 3118 cases and 3226 controls to further evaluate the relationship between rs4331426 at 18q11.2 and TB risk.ResultsWe did not find significant association between genetic variants at 8q24 and risk of TB (rs10956514: OR = 0.89, 95%CI: 0.72–1.09, P = 0.253; rs11774633: OR = 0.86, 95%CI: 0.69–1.08, P = 0.206). We did not observe significant association for genetic variants at 18q11.2 (rs4331426: OR = 0.62, 95%CI: 0.34–1.14, P = 0.122; and rs6507226: OR = 0.98, 95%CI: 0.80–1.20, P = 0.853). Moreover, the pooled results from the Meta-analysis further supported that rs4331426 at 18q11.2 was not associated with TB risk in Chinese population (OR = 0.90, 95% CI: 0.63–1.29).ConclusionsOur findings indicate that TB risk-associated loci at 8q24 and 18q11.2 identified by GWAS from the other populations may not contribute to TB susceptibility in Chinese population.     

Humoral,T-cell and B-cell immune responses to seasonal influenza vaccine in solid organ transplant recipients receiving anti-T cell therapies

BackgroundWe analyzed the impact of the anti-T-cell agents basiliximab and antithymocyte globulins (ATG) on antibody and cell-mediated immune responses after influenza vaccination in solid-organ transplant recipients.Methods71 kidney and heart transplant recipients (basiliximab [n = 43] and ATG [n = 28]) received the trivalent influenza vaccine. Antibody responses were measured at baseline and 6 weeks post-vaccination by hemagglutination inhibition assay; T-cell responses were measured by IFN-γ ELISpot assays and intracellular cytokine staining (ICS); and influenza-specific memory B-cell (MBC) responses were evaluated using ELISpot.ResultsMedian time of vaccination from transplantation was 29 months (IQR 8–73). Post-vaccination seroconversion rates were 26.8% for H1N1, 34.1% for H3N2 and 4.9% for influenza B in the basiliximab group and 35.7% for H1N1, 42.9% for H3N2 and 14.3% for influenza B in the ATG group (p = 0.44, p = 0.61, and p = 0.21, respectively). The number of influenza-specific IFN-γ-producing cells increased significantly after vaccination (from 35 to 67.5 SFC/10⁶ PBMC, p = 0.0007), but no differences between treatment groups were observed (p = 0.88). Median number of IgG-MBC did not increase after vaccination (H1N1, p = 0.94; H3N2 p = 0.34; B, p = 0.79), irrespective of the type of anti-T-cell therapy.ConclusionsAfter influenza vaccination, a significant increase in antibody and T-cell immune responses but not in MBC responses was observed in transplant recipients. Immune responses were not significantly different between groups that received basiliximab or ATG.     

rs2243268 and rs2243274 of Interleukin-4 (IL-4) gene are associated with reduced risk for extrapulmonary and severe tuberculosis in Chinese Han children

Interleukin-4 (IL-4) and IL-10, which are produced by Th2 cells, serve as anti-inflammatory cytokines in the immune responses to tuberculosis (TB). In order to investigate the association between susceptibility to TB and single-nucleotide polymorphisms (SNPs) of the IL-4 and IL-10 genes, a case–control study including 346 TB patients and 374 healthy controls was performed in Chinese Han children in North China. Though no significant differences in the allelic and genotypic distributions of SNPs of these two genes were observed between control group and TB group, rs2243268-A and rs2243274-G of the IL-4 gene were associated with reduced risk of developing extrapulmonary tuberculosis (EPTB) (P_rs2243268 = 0.005 and P_rs2243274 = 0.004) and severe TB (P_rs2243268 = 0.003 and P_rs2243274 = 0.003). The haplotype comprising rs2243268-A and rs2243274-G was found to be a resistance factor against EPTB and severe TB. In addition, after stimulation with inactivated H37Rv, blood samples of the rs2243268 AA + AC carriers showed significantly reduced IL-10 production (P = 0.045) compared to the CC carriers. In conclusion, rs2243268-A and rs2243274-G of the IL-4 gene were found to confer resistance to EPTB and severe TB in Chinese Han children.     

Association of HLA-DP variants with the responsiveness to Hepatitis B virus vaccination in Korean Infants

Recently, HLA-DP single nucleotide polymorphisms (SNPs) have been reported to be related to responsiveness to hepatitis B virus (HBV) vaccination. The aim of this study was to investigate associations between HLA-DP SNPs and responsiveness to HBV vaccine in Korean infants. A total of 290 healthy Korean infants who were registered to Seoul Metropolitan Public Cord Blood Bank during the period of February 2007 to December 2011 were enrolled. Anti-HBs antibody level was analyzed after three doses of HBV vaccination. Genotyping of HLA-DPA1 SNPs (rs3077 and rs3830066) and HLA-DPB1 SNPs (rs7770370, rs7770501, rs3128961, and rs9277535) were performed by PCR-sequencing. HLA-A, -B, and –DRB1 genotyping was also performed by PCR-sequence-specific oligonucleotide probe kits. HLA-DPB1 SNPs (rs7770370, rs7770501, rs3128961, and rs9277535) were associated with HBV vaccine response. Allele frequencies of rs7770370 A, rs7770501 C, rs3128961 G, and rs9277535 A were significantly higher in responders than in non-responders (all p < 0.01). Anti-HBs antibody levels were different according to genotypes of DPB1 rs7770370, rs7770501, rs3128961, and rs9277535 (all p < 0.01). In multivariate analysis, HLA-DPB1 rs7770370 AA genotype was significantly associated with HBV vaccine response (relative risk, RR = 2.5, p = 0.033) and high-titer vaccine response (RR = 2.7, p < 0.001). In conclusion, HLA-DPB1 SNPs were significantly associated with responses to HBV vaccination in Korean infants.     

Rubella specific cell-mediated and humoral immunity following vaccination in college students with low antibody titers

ObjectiveThis study measured cell-mediated immunity (CMI) and antibodies to clarify the basis of rubella reinfection after vaccination.MethodsIn a pool of 65 college students, 39 who exhibited hemagglutination–inhibition (HI) antibody titers against rubella of ≤1:16 were vaccinated with a rubella vaccine. The CMI was assessed with interferon-gamma release assay.ResultsThere was low correlation (r = 0.24) between the antibody titers and interferon-gamma levels at pre-vaccination status. Preexisting interferon-gamma levels were low in some subjects with low HI antibody titers of 1:8 and 1:16. Fifty-seven percent (4/7) of the subjects who were antibody-negative with past history of rubella vaccination at entry onto the study exhibited CMI. And 57% (4/7) of the subjects remained antibody-negative following a second vaccination, despite exhibiting CMI. HI antibody titers increased significantly after vaccination, whereas post-vaccination interferon-gamma levels did not exhibit significant increases. When subjects were divided (based on their past history of vaccination and antibody values) into natural infection and vaccination groups, HI antibody titers (mean ± SD) increased to 1:2^4.4 ± 1.4 from 1: 2^3.2 ± 0.4 (p = 0.065) in the natural infection group and to 1:2^4.4 ± 1.0 from 1:2^3.0 ± 0.8 (p < 0.00001) in the vaccination group following vaccination. The same classification revealed that interferon-gamma values did not increase significantly in either group following vaccination, but the interferon-gamma values at pre- and post-vaccination in the natural infection group were significantly higher than those at pre- and post-vaccination in the vaccination group (p < 0.05 and p < 0.05, respectively).ConclusionPre-vaccination interferon-gamma levels in each HI antibody titer group were similar. And there were some subjects with antibody-positive exhibited CMI-negative. These data may explain why rubella reinfection can occur in vaccinated seropositive individuals.     

Risk factors for tuberculosis among health care workers in South India: a nested case–control study

ObjectiveThe epidemiology of tuberculosis (TB) among health care workers (HCWs) in India remains under-researched. This study is a nested case–control design assessing the risk factors for acquiring TB among HCWs in India.Study Design and SettingsIt is a nested case–control study conducted at a tertiary teaching hospital in India. Cases (n = 101) were HCWs with active TB. Controls (n = 101) were HCWs who did not have TB, randomly selected from the 6,003 subjects employed at the facility. Cases and controls were compared with respect to clinical and demographic variables.ResultsThe cases and controls were of similar age. Logistic regression analysis showed that body mass index (BMI) <19 kg/m² (odds ratio [OR]: 2.96, 95% confidence interval [CI]: 1.49–5.87), having frequent contact with patients (OR: 2.83, 95% CI: 1.47–5.45) and being employed in medical wards (OR: 12.37, 95% CI: 1.38–110.17) or microbiology laboratories (OR: 5.65, 95% CI: 1.74–18.36) were independently associated with increased risk of acquiring TB.ConclusionHCWs with frequent patient contact and those with BMI <19 kg/m² were at high risk of acquiring active TB. Nosocomial transmission of TB was pronounced in locations, such as medical wards and microbiology laboratories. Surveillance of high-risk HCWs and appropriate infrastructure modifications may be important to prevent interpersonal TB transmission in health care facilities.     

Therapeutic immunisation plus cytokine and hormone therapy improves CD4 T-cell counts,restores anti-HIV-1 responses and reduces immune activation in treated chronic HIV-1 infection

BackgroundThis randomised, open label, phase I, immunotherapeutic study investigated the effects of interleukin (IL)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), recombinant human growth hormone (rhGH), and therapeutic immunisation (a Clade B DNA vaccine) on combination antiretroviral therapy (cART)-treated HIV-1-infected individuals, with the objective to reverse residual T-cell dysfunction.MethodsTwelve HIV-1⁺ patients on suppressive cART with baseline CD4 T-cell counts >400 cells/mm³ blood were randomised into one of three groups: (1) vaccine, IL-2, GM-CSF and rhGH (n = 3); (2) vaccine alone (n = 4); or (3) IL-2, GM-CSF and rhGH (n = 5). Samples were collected at weeks 0, 1, 2, 4, 6, 8, 12, 16, 24 and 48. Interferon (IFN)-γ, IL-2, IL-4 and perforin ELISpot assays performed at each time point quantified functional responses to Gag p17/p24, Nef, Rev, and Tat peptides; and detailed T-cell immunophenotyping was undertaken by flow cytometry. Proviral DNA was also measured.ResultsMedian baseline CD4 T-cell count was 757 cells/mm³ (interquartile range [IQR] 567–886 cells/mm³), median age 48 years (IQR 42–51 years), and plasma HIV-1-RNA <50 copies/ml for all subjects. Patients who received vaccine plus IL-2, GM-CSF and rhGH (group 1) showed the most marked changes. Assessing mean changes from baseline to week 48 revealed significantly elevated numbers of CD4 T cells (p = 0.0083) and improved CD4/CD8 T-cell ratios (p = 0.0033). This was accompanied by a significant reduction in expression of CD38 on CD4 T cells (p = 0.0194), significantly increased IFN-γ and IL-2 production in response to Gag (p = 0.0122) and elevated IFN-γ production in response to Tat (p = 0.041) at week 48 compared to baseline. Subjects in all treatment groups showed significantly reduced PD-1 expression at week 48 compared to baseline, with some reductions in proviral DNA.ConclusionsMultifarious immunotherapeutic approaches in the context of fully suppressive cART further reduce immune activation, and improve both CD4 T-lymphocyte counts and HIV-1-specific T-cell responses (NCT01130376).     

Association between the PTPN22 1858C/T gene polymorphism and tuberculosis resistance

Previous studies identified the functional polymorphism 1858C/T in the gene PTPN22 in association with several autoimmune diseases and with resistance to tuberculosis (TB). This study is the first to investigate the association between pulmonary TB and the PTPN22 1858C/T polymorphism in the Brazilian Amazon. We conducted a case-control study involving a group of 413 individuals, comprised of 208 TB carriers and 205 controls. No significant association between the PTPN22 1858T allele frequency in controls (2.4%) and TB carriers (2.7%, p = 0.982, odds ratio (OR) = 0.89, 95% confidence interval = 0.37–2.13) was identified in the Brazilian Amazon population. An additional evaluation by meta-analysis, however, suggested a protective role of the T allele in relation to TB (pooled OR = 0.44, p = 0.011). These results suggest that the PTPN22 1858T allele serves as a protective genetic factor for TB in those individuals who carry this minor allele.     

Vitamin D,bone mineral density and body mass index in eating disorder patients

AimTo investigate associations of vitamin D with BMD and BMI in ED patients.MethodsVitamin D, BMD and BMI for 50 patients admitted to a specialised ED inpatient unit were measured. Patients were aged 15–54 years with BMI 8–25 kg/m².ResultsOf the patients, 18% were vitamin D deficient. There was a significant linear relationship between vitamin D and BMD T-score at the lumbar spine (p = 0.029), femoral neck (p < 0.001) and total hip (p = 0.001). There was no relationship between vitamin D and BMI. There was a significant linear relationship between BMI and BMD T-score at the lumbar spine (p < 0.001), femoral neck (p = 0.008) and total hip (p = 0.001).ConclusionsLow vitamin D and low BMI are associated with low BMD in ED patients. Despite widespread belief that it is not necessary, our findings suggest it is appropriate to measure vitamin D in ED patients. It should not be assumed ED patients take supplements.     

La tuberculose du sujet âgé : épidémiologie et devenir des patients suivis en ambulatoire à Abidjan

BackgroundVery few works approach elderly's tuberculosis (TB) in developing countries. The aim of this study is to present elderly's TB epidemiology and the outcomes of the ambulatory follow-up of the tuberculous patients aged more than 65 years old (TBE) compared to the TB among patients less than 65 years old (TBY).MethodsOur study is retrospective covering period of January 1999 to June 2006 activities of Adjamé’s antituberculous center. It is a comparative study between patients of at least 65 years and patients of less than 65 years when the diagnosis of TB was made.ResultsAmong 36,923 cases of TB, the proportion of TBE is 2.33%. In case of TBE, the sex-ratio is 2.16 versus 1.50 among TBY (P < 0.001). Localization of TB is pulmonary in 61.70% among TBE versus 67.26% among TBY (P = 0.058). Among elderly's TB, the osteoarticular localization is more frequent. TB-VIH co-infection prevalence is estimated to 9.05% among elderly's TB versus 44.38% among patients of less than 65 years (P < 0.001). The therapeutic success rate within elderly patients is 52.16% years versus 61.42% when it was patients of less than 65 years. The proportion of lost at follow-up and the rate of patient transfers within the elderly's TB are the most raised.ConclusionThe elderly's TB is rare with a more masculine predominance. TB-VIH co-infection is not important among elderly's TB. The aged patient follow-up must be improved.     

Impact of polymorphisms in the HCP5 and HLA-C,and ZNRD1 genes on HIV viral load

AIMSSingle nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determine the influence of HCP5 rs2395029, HLA-C rs9264942, and ZNRD1 rs3869068 on VL in antiretroviral-naïve individuals and on time to the first VL < 51 copies/ml and on CD4⁺ T-cell recovery after initiation of combination antiretroviral therapy (cART).Material and methodsWe genotyped the rs2395029 (A > C), rs9264942 (T > C), and rs3869068 (C > T) SNPs in 1897 Caucasians from The Danish HIV Cohort Study — a prospective, nationwide, population-based study of HIV-infected individuals in Denmark. General linear models evaluated the effect of SNPs on VL in antiretroviral-naïve individuals 0–18 months after diagnosis and on CD4⁺ T-cell recovery during cART. Cox proportional hazard regression analysis assessed the association with time to first VL < 51 copies/ml. All models were assuming additive genetic effects.ResultsThe rs2395029, rs9264942, and rs3869068 minor alleles were associated with lower VL in antiretroviral-naïve individuals (rs2395029: [mean VL (copies/ml)], A/A: 70,795 [61,660–79,433], A/C: 33,884 [19,498–58,884], P = 0.002; rs9264942: TT: 81,283 [67,608–97,724], T/C: 63,096 [54,954–75,858], CC: 38,905 [25,119–58,884], P < 0.0001; rs3869068, CC: 72,444 [63,096–83,176], C/T: 45,709 [33,113–64,565], TT: 58,884 [20,417–169,824], P = 0.01). Moreover, the C-alleles of rs2395029 and rs9264942 were associated with shorter time to VL < 51 copies/ml: (HR [95% confidence interval], 1.67 [1.09–1.72], P = 0.008; 1.16 [1.06–1.28], P = 0.002; 1.30 [1.08–1.53], P = 0.005, respectively, adjusted for last VL before cART). None of the SNPs predicted CD4⁺ T-cell recovery during cART.ConclusionsThe minor alleles of rs2395029, rs9264942, and rs3689068 associate with lower VL among antiretroviral-naïve individuals and with shorter time to first VL < 51 copies/ml during cART even after adjustment for VL before cART.     

Efficacy of 23-valent pneumococcal polysaccharide vaccine in preventing community-acquired pneumonia among immunocompetent adults: A systematic review and meta-analysis of randomized trials

BackgroundData on the efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPV-23) in preventing adult community-acquired pneumonia (CAP) among the target population of individuals aged over 65 years and high-risk individuals aged 19–64 years are conflicting. As the Advisory Committee on Immunization Practices (ACIP) has recently demonstrated PPV-23 is likely beneficial to immunocompromised adults by the Grading, Assessment, Development, and Evaluation (GRADE) framework, we conducted meta-analysis to examine its efficacy in an immunocompetent population.MethodsWe searched the PUBMED, EMBASE, and Cochrane Library databases for randomized trials. Overall relative risks (RRs) with 95% confidential intervals (CIs) were calculated, and the Cochrane Q test (p, I²) was performed. Outcomes were assessed by the GRADE framework.ResultsSeven randomized trials involving 156,010 participants were included in this meta-analysis. High-quality evidence revealed that PPV-23 was weakly associated with the prevention of all-cause pneumonia ([RR] 0.87, [95%CI] 0.76–0.98, p = 0.11, I² = 43%), especially among the target population ([RR] 0.72, [95%CI] 0.69–0.94, p = 0.58 I² = 0%), the elderly group aged over 40 years ([RR] 0.80, [95%CI] 0.69–0.94) and the Japanese population ([RR] 0.72, [95%CI] 0.59–0.88, p = 0.24, I² = 30%). The target population included adults aged over 65 years and patients at high risk of pneumonia due to chronic lung disease, chronic obstructive pulmonary disease or living in a nursing home. Protective trends of PPV-23 in the outcomes of pneumococcal pneumonia ([RR] 0.54, [95%CI] 0.18–1.65, p = 0.01, I² = 77%) and mortality due to pneumonia ([RR] 0.67, [95%CI] 0.43–1.04, p = 0.67, I² = 0%) were observed, although the results were statistically insignificant, possibly due to the small number of trials included. PPV-23 did not prevent all-cause mortality ([RR] 1.04, [95%CI] 0.87–1.24, p = 0.95, I² = 0%).ConclusionsPPV-23 provided weak protection against all-cause pneumonia in an immunocompetent population, especially among the target population. The additional benefit of PPV-23 in preventing CAP further supports its application in the target population.     

Association between SNPs in miRNA-machinery genes and chronic hepatitis B in the Chinese Han population

Single nucleotide polymorphisms (SNPs) in miRNA-machinery genes can influence their generation and maturation, then expression and structure. To explore the relationship between three SNPs (rs3757 in DGCR8, rs636832 in AGO1, rs7813 in GEMIN4) in miRNA-machinery genes and chronic hepatitis B, we genotyped the SNPs by high resolution melting method (HRM) in a case-control study of 332 unrelated chronic hepatitis B patients and 352 unrelated healthy controls in Western China. Interestingly, the rs636832 was significantly associated with the susceptibility of CHB (genotype: AA/GA/GG: p = 0.010; allele: A/G: OR = 0.727, 95% CI = 0.575–0.920, p = 0.008). The minor allele A of rs636832 was significantly associated with a decreased risk of CHB. Additionally, the dominant model AG + GG vs. AA showed a risk of 1.442-fold (p = 0.018) with CHB. Further exploration for the association between rs636832 and HBV-DNA load in 329 cases showed no significant difference (genotype: p = 0.321; allele: p = 0.148). Neither did the association between rs636832 and the status of HBsAg and HbeAg (HBsAg: genotype p = 0.337, allele p = 0.436; HBeAg: genotype p = 0.861, allele p = 0.822). Our study first provided the evidence that rs636832 in AGO1 was associated with chronic HBV infection susceptibility in Chinese Han population. Further epidemiological and functional studies in larger populations are warranted to verify our results.