Ranmini Kularatne

Dual Pulmonary Infection with Mycobacterium tuberculosis and Pneumocystis carinii in Patients Infected with Human Immunodeficiency Virus

During a 22-month period, we identified 39 patients with human immunodeficiency virus (HIV) infection (mean CD4(+) count, 90 cells/mm(3)) who were hospitalized with pneumonia and who had sputum and/or other specimens that tested concurrently positive for both Mycobacterium tuberculosis and Pneumocystis carinii. The most common chest x-ray abnormality was a reticulonodular pattern or bilateral infiltrates (n=26). Serum lactate dehydrogenase levels were elevated in 17 (85%) of 20 of patients tested (mean value, 2208 U/L). Mean O(2) saturation and PO(2) were 89% and 64 mm Hg, respectively. A majority (24 patients [62%]) received both antituberculous and anti-PCP therapy (17 with steroids), and 22 improved. All ten patients who received no treatment for PCP improved and were discharged from the hospital, whereas 4 (80%) of the 5 persons who received no antituberculous treatment had a poor outcome (P<.001; OR=43). Patients with HIV or acquired immune deficiency syndrome may present with both TB and PCP; of the 2, TB seems to account for the most severe features of disease.

Multidrug-resistant gonorrhea: A research and development roadmap to discover new medicines

Emilie Alirol and colleagues discuss the development of new treatments for gonorrhea.

Staphylococcus aureus bacteraemia in Gauteng academic hospitals, South Africa

INTRODUCTION Methicillin-resistant Staphylococcus aureus (MRSA) infections are responsible for longer hospital stays, increased hospital costs, and poorer outcomes compared to methicillin-sensitive S. aureus (MSSA) infections. We aimed to describe the epidemiology of S. aureus bacteraemia (SAB) and to determine factors associated with MRSA infection in South Africa. METHODS Cases of SAB were reported from September 2012 to September 2013 from three sentinel sites. A case was defined as the isolation of S. aureus from a blood culture during a 21-day period. Detailed clinical information was collected. Multivariable logistic regression was done to determine factors associated with MRSA infection and mortality. RESULTS There were 442 cases of SAB reported; antimicrobial susceptibility testing was performed on 240 isolates (54%). Thirty-six percent (86/240) of cases had an MRSA infection. A longer hospital stay before positive specimen collection (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.02-1.13, p=0.004), hospitalization in the last year (OR 15.7, 95% CI 2.5-99.5, p=0.003), HIV infection (OR 4.9, 95% CI 1.05-22.90, p=0.044), and antibiotic use in the previous 2 months (OR 0.1, 95% CI 0.01-0.68, p=0.022) were independent predictors of MRSA. Older age, and in particular age 25-44 years (OR 22.2, 95% CI 2.7-185.5, p=0.004, compared to those aged<5 years), was the only independent predictor of mortality amongst cases with SAB. MRSA isolates were non-susceptible to more antimicrobial agents compared to MSSA isolates. CONCLUSIONS HIV infection was an independent risk factor for MRSA infection. The selection of appropriate empirical antimicrobial treatment is essential in patients with MRSA infections because of non-susceptibility to many other antimicrobial classes.

Emergence of azole-resistant Candida parapsilosis causing bloodstream infection: results from laboratory-based sentinel surveillance in South Africa

OBJECTIVES To compare Candida species distribution and antifungal susceptibility at South African public- and private-sector hospitals. METHODS From February 2009 through to August 2010, laboratory-based surveillance for candidaemia was undertaken at 11 public-sector hospitals and >85 private-sector hospitals across South Africa. A case was defined as a patient of any age admitted to a sentinel hospital with isolation of Candida species from blood culture. Viable isolates were identified and tested for antifungal susceptibility at a reference laboratory. Demographic and limited clinical data were abstracted from laboratory records. RESULTS In total, 2172 cases of candidaemia were detected. Among patients with available data, almost two-thirds were critically ill (719/1138, 63%). On multivariable analysis, neonates [adjusted OR (aOR), 2.2; 95% CI, 1.5-3.1; P < 0.001] and patients diagnosed in Gauteng province (aOR, 1.9; 95% CI, 1.3-2.7; P < 0.001) or in the private sector (aOR, 1.9; 95% CI, 1.2-3.2; P = 0.008) were significantly more likely to be infected with Candida parapsilosis than any other Candida species. Of 531 C. parapsilosis isolates, only 199 (37%) were susceptible to fluconazole and voriconazole; 44% (123/282) of fluconazole-resistant isolates were voriconazole cross-resistant. Factors associated with fluconazole non-susceptible C. parapsilosis infection on multivariable analysis included diagnosis in Gauteng province (aOR, 4.2; 95% CI, 2.7-6.7; P < 0.001), an ICU (aOR, 2.3; 95% CI, 1.5-3.6; P < 0.001) or the private sector (aOR, 2.2; 95% CI, 1.4-3.5; P < 0.001). CONCLUSIONS The dominance of triazole non-susceptible C. parapsilosis limits the choice of antifungal agents for management of candidaemia among critically ill neonates, children and adults in resource-limited South African hospitals.

Prevalence and trends of Staphylococcus aureus bacteraemia in hospitalized patients in South Africa, 2010 to 2012 : laboratory-based surveillance mapping of antimicrobial resistance and molecular epidemiology

Introduction We aimed to obtain an in-depth understanding on recent antimicrobial resistance trends and molecular epidemiology trends of S. aureus bacteraemia (SAB). Methods Thirteen academic centres in South Africa were included from June 2010 until July 2012. S. aureus susceptibility testing was performed on the MicroScan Walkaway. Real-time PCR using the LightCycler 480 II was done for mecA and nuc. SCCmec and spa-typing were finalized with conventional PCR. We selected one isolate per common spa type per province for multilocus sequence typing (MLST). Results S. aureus from 2709 patients were included, and 1231 (46%) were resistant to methicillin, with a significant decline over the three-year period (p-value = 0.003). Geographical distribution of MRSA was significantly higher in Gauteng compared to the other provinces (P<0.001). Children <5 years were significantly associated with MRSA with higher rates compared to all other age groups (P = 0.01). The most prevalent SCCmec type was SCCmec type III (531 [41%]) followed by type IV (402 [31%]). Spa-typing discovered 47 different spa-types. The five (87%) most common spa-types were t037, t1257, t045, t064 and t012. Based on MLST, the commonest was ST612 clonal complex (CC8) (n = 7) followed by ST5 (CC5) (n = 4), ST36 (CC30) (n = 4) and ST239 (CC8) (n = 3). Conclusions MRSA rate is high in South Africa. Majority of the isolates were classified as SCCmec type III (41%) and type IV (31%), which are typically associated with hospital and community- acquired infections, respectively. Overall, this study reveals the presence of a variety of hospital-acquired MRSA clones in South Africa dominance of few clones, spa 037 and 1257. Monitoring trends in resistance and molecular typing is recommended to detect changing epidemiological trends in AMR patterns of SAB.

Prevalence and Hospital Management of Amphotericin B Deoxycholate-Related Toxicities during Treatment of HIV-Associated Cryptococcal Meningitis in South Africa

Background We aimed to establish the prevalence of amphotericin B deoxycholate (AmBd)-related toxicities among South African patients with cryptococcosis and determine adherence to international recommendations to prevent, monitor and manage AmBd-related toxicities. Methods Clinical data were collected from cases of laboratory-confirmed cryptococcosis at 25 hospitals, October 2012 –February 2013. Anemia was defined as hemoglobin (Hb) concentration <10 g/dl, hypokalemia as serum potassium (K) <3.4 mEq/L and nephrotoxicity as an increase in serum creatinine (Cr) to >1.1 times the upper limit of normal. To determine adherence to toxicity prevention recommendations, we documented whether baseline Hb, K and Cr tests were performed, whether pre-emptive hydration and IV potassium chloride (KCl) was administered prior to 80% and 60% of AmBd doses and whether daily oral KCl supplementation was given ≥60% of the time. To determine adherence to monitoring recommendations, we ascertained whether a daily fluid chart was completed, Hb was monitored weekly and K or Cr were monitored bi-weekly. Results Of 846 patients, clinical data were available for 76% (642/846), 82% (524/642) of whom received AmBd. Sixty-four per cent (n = 333) had documented baseline laboratory tests, 40% (n = 211) were given pre-emptive hydration and 14% (n = 72) and 19% (n = 101) received intravenous and oral KCl. While on AmBd, 88% (n = 452) had fluid monitoring; 27% (n = 142), 45% (n = 235) and 44% (n = 232) had Hb, K and Cr levels monitored. Toxicities developed frequently during treatment: anemia, 16% (86/524); hypokalemia, 43% (226/524) and nephrotoxicity, 32% (169/524). Conclusion AmBd-related toxicities occurred frequently but were potentially preventable with adequate monitoring, supplemental fluid and electrolyte therapies.

Trends in Neisseria gonorrhoeae Antimicrobial Resistance over a Ten-Year Surveillance Period, Johannesburg, South Africa, 2008–2017

Background: In South Africa, sexually transmitted infections (STIs) are managed through a syndromic approach at primary healthcare centres (PHCs). Neisseria gonorrhoeae is the predominant cause of male urethritis syndrome. We describe antimicrobial resistance patterns and trends in Neisseria gonorrhoeae during a ten-year surveillance period at a large PHC in Johannesburg. Methods: Neisseria gonorrhoeae was cultured from genital discharge swab specimens obtained from consenting adult patients presenting at the Alexandra Health Centre in Johannesburg between 2008 and 2017. Isolates were tested for antimicrobial susceptibility by Etest™ (cefixime, ceftriaxone, ciprofloxacin) or agar dilution (penicillin, tetracycline, azithromycin). Results: During the period of surveillance, high-level resistance prevalence increased from 30% to 51% for penicillin (p-value for trend < 0.001), 75% to 83% for tetracycline (p-value for trend = 0.008), and 25% to 69% for ciprofloxacin (p-value for trend < 0.001). Analysis did not reveal high-level resistance to spectinomycin or a minimum inhibitory concentration (MIC) creep for extended-spectrum cephalosporins, and the prevalence of intermediate-resistance to azithromycin was less than 5%. Conclusions: High prevalence resistance to penicillin, tetracycline, and ciprofloxacin in N. gonorrhoeae obviates their use in future national treatment algorithms for genital discharge. It is essential to continue monitoring for emerging resistance to currently recommended antimicrobial therapy in this rapidly evolving pathogen.

Use of rapid point-of-care diagnostic tests for the elimination of congenital syphilis: what is the evidence?

Congenital syphilis constitutes a major preventable public health problem, that has been targeted for elimination by the World Health Organisation. Adverse pregnancy outcomes occur in upto 80% of u...

Adult gonorrhea, chlamydia and syphilis prevalence, incidence, treatment and syndromic case reporting in South Africa: Estimates using the Spectrum-STI model, 1990-2017

Objectives To estimate trends in prevalence and incidence of syphilis, gonorrhea and chlamydia in adult men and women in South Africa. Methods The Spectrum-STI tool estimated trends in prevalence and incidence of active syphilis, gonorrhea and chlamydia, fitting South African prevalence data. Results were used, alongside programmatic surveillance data, to estimate trends in incident gonorrhea cases resistant to first-line treatment, and the reporting gap of symptomatic male gonorrhea and chlamydia cases treated but not reported as cases of urethritis syndrome. Results In 2017 adult (15–49 years) the estimated female and male prevalences for syphilis were 0.50% (95% CI: 0.32–0.80%) and 0.97% (0.19–2.28%), for gonorrhea 6.6% (3.8–10.8%) and 3.5% (1.7–6.1%), and for chlamydia 14.7% (9.9–21%) and 6.0% (3.8–10.4%), respectively. Between 1990 and 2017 the estimated prevalence of syphilis declined steadily in women and men, probably in part reflecting improved treatment coverage. For gonorrhea and chlamydia, estimated prevalence and incidence showed no consistent time trend in either women or men. Despite growing annual numbers of gonorrhea cases − reflecting population growth − the estimated number of first line treatment-resistant gonorrhea cases did not increase between 2008 and 2017, owing to changes in first-line antimicrobial treatment regimens for gonorrhea in 2008 and 2014/5. Case reporting completeness among treated male urethritis syndrome episodes was estimated at 10–28% in 2017. Conclusion South Africa continues to suffer a high STI burden. Improvements in access and quality of maternal, STI and HIV health care services likely contributed to the decline in syphilis prevalence. The lack of any decline in gonorrhea and chlamydia prevalence highlights the need to enhance STI services beyond clinic-based syndromic case management, to reinvigorate primary STI and HIV prevention and, especially for women, to screen for asymptomatic infections.

Trends in the relative prevalence of genital ulcer disease pathogens and association with HIV infection in Johannesburg, South Africa, 2007–2015

Background In South Africa, treatment of genital ulcer disease (GUD) occurs in the context of syndromic management. GUD aetiological studies have been conducted in Johannesburg since 2007. We report on GUD pathogen prevalence, sero-prevalence of STI co-infections and aetiological trends among GUD patients presenting to a community-based primary healthcare facility in Johannesburg over a 9-year period. Methods and findings GUD surveys were conducted from January to April each year. Consecutive genital ulcers were sampled from consenting adults. Swab-extracted DNA was tested by multiplex real-time PCR assays for herpes simplex virus (HSV), Treponema pallidum (TP), Haemophilus ducreyi (HD) and Chlamydia trachomatis (CT). HSV-positive DNA extracts were further subtyped into HSV-1 and HSV-2 using a commercial PCR assay; CT-positive extracts were tested with an in-house PCR assay specific for serovars L1-L3 (lymphogranuloma venereum). Sera were tested for HIV, HSV-2, and syphilis co-infections. Giemsa-stained ulcer smears were screened for Klebsiella granulomatis by microscopy. Data were analysed with STATATM version 14. Of 771 GUD specimens, 503 (65.2%) had a detectable pathogen: HSV 468 (60.7%); TP 30 (3.9%); CT L1-3 7 (0.9%); HD 4 (0.5%). No aetiological agents were detected in 270 (34.8%) ulcer specimens. Seroprevalence rates were as follows: HIV 61.7%; HSV-2 80.2% and syphilis 5.8%. There was a strong association between GUD pathogen detection and HIV seropositivity (p < 0.001); 68% of cases caused by HSV were co-infected with HIV. There was a significant decline in the relative prevalence of ulcer-derived HSV over time, predominantly from 2013–2015 (p-value for trend = 0.023); and a trend towards a decrease in the HIV seropositivity rate (p-value for trend = 0.209). Conclusions HSV remains the leading cause of pathogen-detectable GUD in South Africa. The prevalence of HIV co-infection among GUD patients is high, underlining the importance of linkage to universal HIV testing and treatment in primary healthcare settings.