Mycobacterium tuberculosis strains with phenotypically susceptible rpoB mutations (rifampicin discordant) have emerged following implementation of rapid molecular drug resistance testing for tuberculosis. Whilst rifampicin resistance is known to be associated with resistance to other rifamycins (rifapentine and rifabutin) as well as isoniazid and pyrazinamide, rifampicin discordant strains have shown high rates of susceptibility to isoniazid and rifabutin. However, pyrazinamide susceptibly testing results have not been reported. We evaluated pyrazinamide resistance in 80 rifampicin discordant and 25 rifampicin and isoniazid susceptible isolates from KwaZulu-Natal in South Africa using Mycobacteria Growth Indicator Tube method and sequencing of the pncA. We also compared susceptibility of pyrazinamide with that of isoniazid. Pyrazinamide resistance was found in 6/80 (7.5%) rifampicin discordant isolates. All pyrazinamide resistant isolates were also resistant to isoniazid and pyrazinamide resistance was found to be associated with isoniazid resistance. No pyrazinamide resistance was found among the isoniazid susceptible isolates. Given the low prevalence of pyrazinamide resistance in rifampicin discordant TB, this anti-TB drug still has a significant role in the treatment of these patients. Performing pyrazinamide susceptibility testing remains a challenge, our findings show that isoniazid susceptible isolates are unlikely to be resistant to pyrazinamide among the discordant TB isolates.
Objectives Genital herpes simplex virus (HSV) infections are common in South Africa and worldwide. While HSV-2 is known to cause genital lesions, HSV-1 is better known to cause oral infections. Due to the global rise in genital HSV-1 infections, we aimed to compare the genital cytokine environment associated with HSV-1 and HSV-2 infections and their relation to the proinflammatory genital immune environment associated with HIV risk in African women. Methods HSV-1 and HSV-2 DNA were detected by quantitative real-time PCR in menstrual cup specimens collected from 251 HIV-negative women participating in the CAPRISA 083 study in Durban, South Africa. HSV shedding was defined as detection at >150 copies/mL. Forty-eight cytokines were measured in genital fluid by multiplexed ELISA, and multivariable regression models determined associations between genital cytokines and HSV DNA detection. Results HSV-1 DNA detection (24/251 (9.6%)) and shedding (13/24 (54.2%)) was more common than HSV-2 (detection in 14/251 (5.6%), shedding in 0/14). None of the women with detectable HSV had evidence of genital lesions. HSV-2 DNA detection was associated with increased interleukin (IL)−18 and decreased cutaneous T-cell attracting chemokine concentrations, but only in univariable analysis. By contrast, in both univariable and multivariable analyses, the detection of HSV-1 DNA was associated with reduced concentrations of granulocyte-colony stimulating factor, IL-7, IL-4, platelet-derived growth factor-ββ and five proinflammatory cytokines associated with HIV risk: IL-6, IL-1β, macrophage inflammatory protein (MIP)−1α, MIP-1β and tumour necrosis factor-α. Conclusions That HSV-1 DNA was more commonly detected and shed than HSV-2 emphasises the need for clinical screening of both viruses, not just HSV-2 in young women. Efforts to reduce genital inflammation may need to consider implementing additional strategies to mitigate a rise in HSV replication.
Azithromycin regimens have been considered first-line treatment for Mycoplasma genitalium (M. genitalium), a sexually transmitted infection (STI) associated with adverse pregnancy outcomes. However, recent years have seen rapid emergence of macrolide resistance in M. genitalium as a result of widespread administration of azithromycin. Currently, there are limited data on macrolide resistance in pregnant women from KwaZulu-Natal (KZN), South Africa. This study investigated the prevalence of M. genitalium and emerging patterns of macrolide resistance in pregnant women from KZN.This was a sub-study of a larger study which involved laboratory-based detection of STIs in pregnant women. In the main study, pregnant women provided urine samples for detection of STIs. For this study, deoxyribose nucleic acid (DNA) extracted from stored urine was used to determine emerging macrolide resistance by amplification of the 23S ribosomal ribonucleic acid (rRNA) gene of M. genitalium by polymerase chain reaction (PCR) and sequencing of amplicons to identify mutations associated with resistance. The Allplex™ MG & AziR assay was used as a confirmatory assay.The prevalence of M. genitalium in pregnant women was 5.9% (13 out of 221). Sequencing of PCR amplicons did not reveal the presence of the A2059G and A2058G mutations associated with macrolide resistance. These findings were confirmed by the Allplex™ MG & AziR assay.Despite the lack of resistance to macrolides in this study population, continued antimicrobial resistance surveillance for M. genitalium in pregnant women is important because azithromycin is now part of the South African national STI syndromic management guidelines for vaginal discharge syndrome.
Background: Human cyclophilin A (CypA) encoded by peptidyl prolyl isomerase A gene ( PPIA ), enhances HIV-1 replication by aiding capsid uncoating. The association of genetic variation in the PPIA regulatory region with susceptibility to HIV-1 infection, disease progression, and gene expression among black South Africans at risk for infection or infected with HIV-1 is unknown. Methods: We genotyped 539 participants from 2 longitudinal study cohorts of black South Africans at high risk for infection or infected with HIV-1 for PPIA regulatory single nucleotide polymorphisms by polymerase chain reaction–restriction fragment length polymorphism. Results: Minor allele (G) of SNP rs6850 (rs6850 G) significantly associated with higher viral loads (mean 4.85 versus 4.46 log copies/mL, P = 0.0006) and lower CD4 + T-cell counts (mean 506 versus 557 cells/μL, P = 0.0256) during the acute phase of infection in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 002 cohort. Consistently, rs6850 G significantly associated with higher viral loads (mean 4.49 versus 4.01 log copies/mL, P < 0.0001) and lower CD4 + T-cell counts (mean 442 versus 494 cells/μL, P = 0.0002) during the early chronic phase of infection in the CAPRISA 002 cohort; rs6850 G further associated significantly with rapid CD4 + T-cell decline in the CAPRISA 002 cohort ( P = 0.0481) and Sinikithemba chronic infection cohort ( P = 0.0156). Interestingly, rs6850 G significantly associated with elevated CypA mRNA levels in HIV-1–positive individuals ( P = 0.0061). Conclusions: These data suggest that rs6850 G enhances HIV-1 replication through upregulation of CypA expression following HIV-1 infection. The data support ongoing efforts to develop anti–HIV-1 drugs that block interaction of HIV-1 and cellular proteins.
Background/Objective The diagnosis of tuberculous meningitis (TBM) in resource poor TB endemic environments is challenging. The accuracy of current tools for the rapid diagnosis of TBM is suboptimal. We sought to develop a clinical-prediction rule for the diagnosis of TBM in a high HIV prevalence setting, and to compare performance outcomes to conventional diagnostic modalities and a novel lipoarabinomannan (LAM) antigen detection test (Clearview-TB®) using cerebrospinal fluid (CSF). Methods Patients with suspected TBM were classified as definite-TBM (CSF culture or PCR positive), probable-TBM and non-TBM. Results Of the 150 patients, 84% were HIV-infected (median [IQR] CD4 count = 132 [54; 241] cells/µl). There were 39, 55 and 54 patients in the definite, probable and non-TBM groups, respectively. The LAM sensitivity and specificity (95%CI) was 31% (17;48) and 94% (85;99), respectively (cut-point ≥0.18). By contrast, smear-microscopy was 100% specific but detected none of the definite-TBM cases. LAM positivity was associated with HIV co-infection and low CD4 T cell count (CD4<200 vs. >200 cells/µl; p = 0.03). The sensitivity and specificity in those with a CD4<100 cells/µl was 50% (27;73) and 95% (74;99), respectively. A clinical-prediction rule ≥6 derived from multivariate analysis had a sensitivity and specificity (95%CI) of 47% (31;64) and 98% (90;100), respectively. When LAM was combined with the clinical-prediction-rule, the sensitivity increased significantly (p<0.001) to 63% (47;68) and specificity remained high at 93% (82;98). Conclusions Despite its modest sensitivity the LAM ELISA is an accurate rapid rule-in test for TBM that has incremental value over smear-microscopy. The rule-in value of LAM can be further increased by combination with a clinical-prediction rule, thus enhancing the rapid diagnosis of TBM in HIV-infected persons with advanced immunosuppression.
Type 1 interferons (IFNs) induce the expression of the tripartite interaction motif (TRIM) family of E3 ligases, but the contribution of these antiviral factors to HIV pathogenesis is not completely understood. We hypothesized that the increased expression of select type 1 IFN and TRIM isoforms is associated with a significantly lower likelihood of HIV-1 acquisition and viral control during primary HIV-1 infection. We measured IFN-α, IFN-β, myxovirus resistance protein A (MxA), human TRIM5α (huTRIM5α), and TRIM22 mRNA levels in peripheral blood mononuclear cells (PBMCs) of high-risk, HIV-1-uninfected participants and HIV-1-positive study participants. Samples were available for 32 uninfected subjects and 28 infected persons, all within 1 year of infection. HIV-1-positive participants had higher levels of IFN-β (P = 0.0005), MxA (P = 0.007), and TRIM22 (P = 0.01) and lower levels of huTRIM5α (P < 0.001) than did HIV-1-negative participants. TRIM22 but not huTRIM5α correlated positively with type 1 IFN (IFN-α, IFN-β, and MxA) (all P < 0.0001). In a multivariate model, increased MxA expression showed a significant positive association with viral load (P = 0.0418). Furthermore, TRIM22 but not huTRIM5α, IFN-α, IFN-β, or MxA showed a negative correlation with plasma viral load (P = 0.0307) and a positive correlation with CD4(+) T-cell counts (P = 0.0281). In vitro studies revealed that HIV infection induced TRIM22 expression in PBMCs obtained from HIV-negative donors. Stable TRIM22 knockdown resulted in increased HIV-1 particle release and replication in Jurkat reporter cells. Collectively, these data suggest concordance between type 1 IFN and TRIM22 but not huTRIM5α expression in PBMCs and that TRIM22 likely acts as an antiviral effector in vivo.
Knowledge, perceptions and attitudes about physiotherapy has affected its status. In a developing profession whose patient base is still significantly dependent on referral from medical practitioners, certain stereo-typic attitudes about it require attention. This study investigated the knowledge, perceptions and attitudes of the 2009 final year medical, occupational therapy and sport science students at one university in KwaZulu natal, regarding physio therapy. A saturation sample of 292 students from the selected groups was invited to participate in the study. The cross sectional survey used a questionnaire with open and closed ended questions. The data was reduced to percentages and analysed using chi square tests at p< 0, 05. The overall response rate was 51% with 95% occupational therapy, 71% sport science and only 31% medical students responding. About 74% of the respondents had adequate knowledge about physiotherapy. Seventy five percent of medical and 50% of oT students knew that physiotherapists were first contact practitioners. over 50% of the respondents who had experienced physiotherapy displayed positive attitudes and felt that physio-therapy was a good career choice. Massage was the best known (95%) and electrotherapy the least known (44%) modality. orthopedics (88%), sports physio therapy (84%) and rehabilitation (78%) were better known. we conclude that the response rate to the study especially by medical students is of concern despite the overall positive attitudes displayed by the participants.
Introduction: Mycoplasma hominis and Ureaplasma parvum have been recently linked to sexually transmitted diseases and other conditions. There are a limited number of studies conducted on South African pregnant women that have assessed the prevalence and risk factors for genital mycoplasmas. Methodology: This study included 264 HIV infected pregnant women attending the King Edward VIII antenatal clinic in eThekwini, South Africa. DNA was extracted using the PureLink Microbiome kit and pathogens were detected using the TaqMan Real-time PCR assays. The statistical data analysis was conducted in a freely available Statistical Computing Environment, R software, version 3.6.3 using the RStudio platform. Results: The prevalence of M. hominis and U. parvum, was 215/264 (81.4%), and 203/264 (76.9%), respectively. In the M. hominis positive group, a significantly (p = 0.004) higher proportion, 80.5% tested positive for U. parvum infection when compared to 61.2% among the M. hominis negative. Of the U. parvum positive women, a significantly (p = 0.004) higher proportion of women (85.2%) tested positive for M. hominis when compared to 68.9% among the U. parvum negative. In the unadjusted and adjusted analysis, being M. hominis positive increased the risk for U. parvum by approximately 3 times more (p = 0.014) and 4-fold (p = 0.008), respectively. Conclusions: This study showed a significant link between M. hominis and U. parvum infection. To date, there are a limited number of studies that have investigated M. hominisbeing a risk factor for U. parvum infection. Therefore, the data presented in the current study now fills in this gap in the literature.
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