Detection of splenic microabscesses with ultrasound as a marker for extrapulmonary tuberculosis in patients with HIV: A systematic review.

BACKGROUND: In 2015, 1.2 million new cases of tuberculosis (TB) were diagnosed in patients with HIV. Diagnostic limitations and resource shortages in endemic areas can delay diagnosis and treatment, particularly with extrapulmonary TB (EPTB). Research suggests that ultrasound can identify splenic microabscesses caused by EPTB, but data are limited on the frequency of this finding in patients with culture-proven EPTB. OBJECTIVES: To estimate the frequency of splenic EPTB microabscesses detected with ultrasound in patients with HIV and TB co-infection. METHODS: Studies published in six major databases as of November 2017 were systematically reviewed based on the PRISMA guidelines. Cohen's kappa test was used to determine inter-rater agreement. Articles included for data abstraction passed the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) evaluation. Freeman-Tukey transformation was used to calculate weighted proportions. Heterogeneity was evaluated by Forest plot and I2 calculation. RESULTS: After abstract screening, article review and QUADAS-2 evaluation, five studies were selected for data extraction. A total of 774 patients in these studies were infected with HIV. Splenic lesions were seen with ultrasound in 21.0% of patients with HIV (95% confidence interval (CI) 10.6 - 33.8). TB diagnosed by culture, biopsy, smear, or molecular methods was found to be the cause of 88.3% (95% CI 72.3 - 97.9) of splenic microabscesses seen on ultrasound in patients with HIV. CONCLUSIONS: Ultrasound evaluation of the spleen in patients with HIV and symptoms suggestive of TB in endemic regions is a viable diagnostic adjunct. Ultrasound detection of splenic microabscesses in HIV patients is probably sufficient indication to initiate TB treatment prior to obtaining culture data. Strong conclusions cannot be drawn owing to the high heterogeneity of this small number of studies.

CD226 gene polymorphism (rs763361 C>T) is associated with susceptibility to type 1 diabetes mellitus among Egyptian children.

OBJECTIVE: Genetic factors contribute significantly to type 1 diabetes (T1D) etiology. A single nucleotide polymorphism in the CD226 gene (rs763361 C>T) has been associated with T1D susceptibility in European patients, but data from other populations is limited. Our aim was to study the contribution of this polymorphism to T1D susceptibility among Egyptian children. METHODS: A case-control study including 74 children with T1D and 82 healthy children as a control group. Genotyping of CD226 gene polymorphism was performed for all participants by DNA extraction followed by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The frequency of T allele was 78.4% in patients and 68.3% in controls (OR, 1.68; 95% CI, 1.01-2.8; P=0.046). TT, TC, and CC genotypes were found in 62.2%, 32.4%, and 5.4% of the patients, respectively, and in 41.5%, 53.7%, and 4.9% of controls, respectively. Under the recessive model, TT genotype was significantly associated with T1D risk (OR, 2.32; 95% CI, 1.21-4.41; P=0.010). The mean age at diabetes onset was significantly lower in patients carrying T allele compared with C allele (8.03±3.8 year vs. 10.5±2.54 year; P<0.001) and among those with TT genotype compared with the pooled TC+CC genotypes (7.5±2.6 year vs. 10.6±2.6 year; P<0.001). No significant difference was found between genotypes or alleles regarding the HbA1c level. CONCLUSION: T allele and TT genotype of the CD226 rs763361 polymorphism is associated with susceptibility to T1D and with a lower age of disease onset among Egyptian children.

Analysis of HCV co-infection with occult hepatitis B virus in patients undergoing IFN therapy.

BACKGROUND/AIM: Occult hepatitis B virus (HBV) infection is characterized by the presence of HBV DNA in the absence of hepatitis B surface antigen (HBsAg) in the patient serum. Although such infections have been identified in patients with chronic hepatitis C, the clinical significance of those co-infections is still not understood. Our aim was, therefore, to assess the prevalence and clinical consequences of occult HBV infection in chronic hepatitis C patients undergoing antiviral therapy. METHODS: The study population consisted of 53 HBsAg-negative patients with chronic hepatitis C treated with IFN/ribavirin or IFN/ribavirin/amantadine. Nine patients experienced a viral breakthrough (BT), 30 were non-responders (NR) and 14 were responders (R). HBV-DNA detection by PCR was performed using primers specific for the S region of the HBV genome and HCV-RNA detection by PCR with primers localised in both the 5'NC and core region of HCV genome, before, during and after treatment. Viral genome sequences were also studied. RESULTS: Occult HBV genomes were found in the serum of four of 53 (7.5%) patients, unrelated to anti-HBc status. No significant differences in biochemical, virological, or histological markers, age, duration of infection, were observed in patients with or without HBV DNA. There was an inverse correlation in the evolution of HBV DNA and HCV RNA levels. Direct sequencing showed that S gene of occult HBV presented mutations in the "a" determinant while no specific mutation in the core region of HCV was observed. None of the four patients co-infected with HBV and HCV were responders to anti-HCV therapy. CONCLUSION: In our clinical setting, the prevalence of occult HBV co-infection among patients with chronic hepatitis C was low and independent of the presence of markers of previous HBV infection. Further studies in larger cohort of patients are warranted to determine if occult HBV co-infection may be involved in HCV resistance to combination therapy.

Genetic variability of hepatitis C virus in chronically infected patients with viral breakthrough during interferon-ribavirin therapy.

Little is known about hepatitis C virus (HCV) breakthrough during antiviral therapy, although it would help in understanding HCV resistance to current antiviral treatments. To analyse the implication of virological factors and the vigour of humoral immune responses in this phenomenon, we studied nine chronic hepatitis C patients with a viral breakthrough during IFN/ribavirin combination therapy, as well as five responders and five non-responders. The IRES and regions coding for the capsid protein, the PePHD domain of envelope glycoprotein E2 and the NS5A and 5B proteins were amplified by RT-PCR before treatment, before and during breakthrough, and after treatment. The major variant sequence was obtained by direct sequencing. The heterogeneity of quasispecies was studied by SSCP in all patients and sequencing after cloning in seven genotype 1b-infected patients. Humoral responses against HCV epitopes were also analysed. The major sequences of IRES, PePHD, and NS5B remained stable during treatment, regardless of the treatment response. However, the capsid protein and the regions flanking PePHD showed sequence variations in breakthrough patients, although no specific mutation was identified. The variable V3 region of NS5A, but not the PKR-binding domain and the ISDR, seemed to be associated with differences in response to treatment. The analysis of HCV quasispecies revealed no characteristic pattern during treatment in breakthrough patients, whose HCV genome profiles looked most similar to that of non-responders. The humoral response was similar between groups. In conclusion, viral breakthrough does not seem to be due to selection of resistant strains with signature mutations.