Vulvar cancer is not a disease of the elderly: Treatment and outcome at a tertiary referral centre in South Africa.

BACKGROUND: An increase in vulvar cancer in young women is attributed to infection with oncogenic human papillomavirus (HPV). South Africa (SA) has a high prevalence of HPV, and it was therefore hypothesised that women with vulvar cancer here would be younger than in high-income countries (HICs). OBJECTIVE: To describe age, cancer stage, treatment and outcome of patients with vulvar cancer at a tertiary referral centre in SA. METHODS: In a retrospective observational study, patient records of women diagnosed with vulvar cancer between 2001 and 2014 were reviewed and demographic and surgical details captured. Histology results of vulvar biopsies and resected specimens were checked for HPV changes, koilocytes and usual-type vulval intraepithelial neoplasia. Patients were restaged using the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system to allow for comparison of outcomes. Five-year disease-specific survival probability curves were generated using Kaplan-Meier analysis. RESULTS: The mean age of the 180 patients in the study was 52.5 years. Those who had documented HPV changes on histological specimens had a mean age of 50.4 years. More than 50% of the patients had advanced-stage disease, and 62.7% were treated with primary surgery. Five-year disease-specific survival probabilities were similar to those reported in the literature. CONCLUSIONS: Vulvar cancer should not be regarded as a disease of the elderly in SA, as women with vulvar cancer are 10 - 15 years younger than in HICs. A large proportion of patients present with advanced-stage disease. Health professionals should be alert to vulvar lesions, especially in women with abnormal Pap smears, to reduce the morbidity and mortality of this disease.

Genome and MIC stability in Mycobacterium tuberculosis and indications for continuation of use of isoniazid in multidrug-resistant tuberculosis.

Mycobacterium tuberculosis strains resistant to two or more of the first line antituberculosis drugs (MDR) are a serious threat to successful tuberculosis control programmes. For this retrospective study, 85 follow-up drug resistant isolates from 23 patients residing in a community with a high incidence of tuberculosis were collected and the level of in-vitro resistance to antibiotics determined quantitatively. PCR-SSCP and sequencing techniques were used to screen for gene mutations associated with resistance in 31 follow-up samples from a smaller group of eight patients. DNA fingerprint analysis was done on sequential isolates to confirm identity. Although treatment had a profound effect on changes in drug resistance patterns, the MIC for a particular agent remained constant in follow-up isolates. DNA fingerprinting and mutational analysis (14 different loci) showed that the genome of MDR strains of M. tuberculosis is relatively stable during the course of therapy. The rpoB gene was the most frequently mutated structural gene involved in drug resistance and a novel C to T mutation upstream of open reading frame (ORF)1 of the inhA operon was detected. No evidence was found of the presence of strain W (New York) in this group of MDR strains. The results stress the importance of confirming individuality of strains for the accurate calculation of frequencies of particular mutations associated with drug resistance, particularly in a high incidence area. Approximately one-half (47.8%) of the patients had isolates resistant to concentrations just above the critical concentration for isoniazid (MICs of 0.2-5 mg/L). Therefore, these patients and their contacts who develop primary drug-resistant tuberculosis may respond to higher dosages of treatment which could have a considerable impact on the cost and the ease of management of resistant tuberculosis.

Mycobacterium tuberculosis efpA encodes an efflux protein of the QacA transporter family.

The Mycobacterium tuberculosis H37Rv efpA gene encodes a putative efflux protein, EfpA, of 55,670 Da. The deduced EfpA protein was similar in secondary structure to Pur8, MmrA, TcmA, LfrA, EmrB, and other members of the QacA transporter family (QacA TF) which mediate antibiotic and chemical resistance in bacteria and yeast. The predicted EfpA sequence possessed all transporter motifs characteristic of the QacA TF, including those associated with proton-antiport function and the motif considered to be specific to exporters. The 1,590-bp efpA open reading frame was G+C rich (65%), whereas the 40-bp region immediately upstream had an A+T bias (35% G+C). Reverse transcriptase-PCR assays indicated that efpA was expressed in vitro and in situ. Putative promoter sequences were partially overlapped by the A+T-rich region and by a region capable of forming alternative secondary structures indicative of transcriptional regulation in analogous systems. PCR single-stranded conformational polymorphism analysis demonstrated that these upstream flanking sequences and the 231-bp, 5' coding region are highly conserved among both drug-sensitive and multiply-drug-resistant isolates of M. tuberculosis. The efpA gene was present in the slow-growing human pathogens M. tuberculosis, Mycobacterium leprae, and Mycobacterium bovis and in the opportunistic human pathogens Mycobacterium avium and Mycobacterium intracellular. However, efpA was not present in 17 other opportunistically pathogenic or nonpathogenic mycobacterial species.