51 research outputs found
Antifungal susceptibility profile of yeast isolates from sterile sites at a tertiary hospital in South Africa
Invasive infections caused by yeasts are associated with high mortality and morbidity, and resistance to antifungal agents is increasing. Candida
spp. has emerged as the leading cause of systemic nosocomial fungal infections. The aim of this study was to identify yeast isolates from sterile site
specimens to species level, and to determine their susceptibility to fluconazole and voriconazole, at the National Health Laboratory, Service Dr George
Mukhari Tertiary Laboratory from March to August 2007. Candida isolates were identified to species level using a germ tube test and/or Api® ID 32C
kits. Antifungal susceptibility testing to fluconazole and voriconazole was performed using the disc diffusion method in accordance with the Clinical
and Laboratory Standards Institute guidelines. All of the Candida isolates were from the neonatal intensive care unit (NICU), with the exception of two.
The distribution of yeast isolates was as follows: C. krusei (41.9%), C. albicans (32.3%), C. inconspicua (5.5%), C. parapsilosis (2%), C. tropicalis (1.5%),
C. sake (1.5%), C. lambica (1.5%), and C. valida (0.5%). Cryptococcus neoformans (11%), C. albidus (0.5%), Rhodotorula glutinis (1%), and C. humicola
(0.5%) were also isolated. Of the isolated C. albicans, 61% were susceptible to fluconazole. A possible C. krusei outbreak could have occurred in the
NICU during the study period. Voriconazole was the most susceptible antifungal agent to various yeast pathogens. The results of this study on azoles
susceptibility testing of yeasts show that voriconazole may prove to be a valuable alternative antifungal agent in this tertiary hospital for the treatment
of infections caused by yeasts, including Candida spp.http://www.sajei.co.za/index.php/SAJEI 2312-0053hb201
Pregnancy incidence and correlates during the HVTN 503 Phambili HIV vaccine trial conducted among South African women
BACKGROUND: HIV prevention trials are increasingly being conducted in sub-Saharan Africa. Women at risk for HIV are also at risk of pregnancy. To maximize safety, women agree to avoid pregnancy during trials, yet pregnancies occur. Using data from the HVTN 503/"Phambili" vaccine trial, we report pregnancy incidence during and after the vaccination period and identify factors, measured at screening, associated with incident pregnancy. METHODS: To enrol in the trial, women agreed and were supported to avoid pregnancy until 1 month after their third and final vaccination ("vaccination period"), corresponding to the first 7 months of follow-up. Unsterilized women, pooled across study arms, were analyzed. Poisson regression compared pregnancy rates during and after the vaccination period. Cox proportional hazards regression identified associations with first pregnancy. RESULTS: Among 352 women (median age 23 yrs; median follow-up 1.5 yrs), pregnancy incidence was 9.6/100 women-years overall and 6.8/100 w-yrs and 11.3/100 w-yrs during and after the vaccination period, respectively [Rate Ratio = 0.60 (0.32-1.14), p = 0.10]. In multivariable analysis, pregnancy was reduced among women who: enrolled at sites providing contraception on-site [HR = 0.43, 95% CI (0.22-0.86)]; entered the trial as injectable contraceptive users [HR = 0.37 (0.21-0.67)] or as consistent condom users (trend) [HR = 0.54 (0.28-1.04)]. Compared with women with a single partner of HIV-unknown status, pregnancy rates were increased among women with: a single partner whose status was HIV-negative [HR = 2.34(1.16-4.73)] and; 2 partners both of HIV-unknown status [HR = 4.42(1.59-12.29)]. Women with 2 more of these risk factors: marijuana use, heavy drinking, or use of either during sex, had increased pregnancy incidence [HR = 2.66 (1.24-5.72)]. CONCLUSIONS: It is possible to screen South African women for pregnancy risk at trial entry. Providing injectable contraception for free on-site and supporting consistent condom use may reduce incident pregnancy. Screening should determine the substance use, partnering, and HIV status of both members of the couple for both pregnancy and HIV prevention. Trial Registration SA National Health Research Database DOH-27-0207-1539; Clinicaltrials.gov NCT0041372
Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine Induced immune responses
BACKGROUND: Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses. METHODS: Vaccine-induced immunogenicity was ascertained by interferon-γ ELISpot assays on the first 186 enrolled participants receiving two vaccinations. Analyses, stratified by study arm/sex, were performed on baseline demographics [sex, age, Body Mass Index (BMI), site, Adenovirus Type-5 (Ad5) titer, Herpes Simplex Virus Type-2 (HSV2) status, heavy drinking]. Multivariate logistic regression determined predictors. RESULTS: Of the 186 participants, 53.7% (n = 100) were female, median BMI was 22.5 [IQR: 20.4-27.0], 85.5% (n = 159) were Ad5 seropositive, and 18.8% (n = 35) drank heavily. All vaccine recipients responded to both clade B (n = 87; 47%) and/or C (n = 74; 40%), p = 0.17. In multivariate analysis, female sex [Adjusted Odds Ratio (AOR): 6.478; p = 0.0159], overweight/obese BMI (AOR: 0.186; p = 0.0452), and heavy drinking (AOR: 0.270; p = 0.048) significantly predicted immune response to clade C for any antigens. A marginally significant predictor of clade C-pol antigen was female sex (AOR: 3.182; p = 0.0500). CONCLUSIONS: Sex, BMI, and heavy drinking affected vaccine-induced HIV-1 specific immune responses to clade C antigens. The role of female sex and overweight/obese BMI boosting and suppressing vaccine-induced HIV-1 specific immune responses, respectively, requires elucidation, including any effect on HIV vaccine efficacy, especially in the era of colliding epidemics (HIV and obesity)
IS6110 Restriction Fragment Length Polymorphism Typing of Drug-resistant Mycobacterium tuberculosis Strains from Northeast South Africa
Tuberculosis (TB) remains a deadly infectious disease affecting
millions of people worldwide; 95% of TB cases, with 98% of death occur
in developing countries. The situation in South Africa merits special
attention. A total of 21,913 sputum specimens of suspected TB patients
from three provinces of South Africa routinely submitted to the TB
laboratory of Dr. George Mukhari (DGM) Hospital were assayed for
Mycobacterium tuberculosis (MTB) growth and antibiotic
susceptibility. The genetic diversity of 338 resistant strains were
also studied. DNA isolated from the strains were restricted with Pvu
II, transferred on to a nylon membrane and hybridized with a
PCR-amplified horseradish peroxidase 245 bp IS6110 probe. Of the 338
resistant strains, 2.09% had less than 5 bands of IS6110, and 98% had 5
or more bands. Unique restriction fragment length polymorphism (RFLP)
patterns were observed in 84.3% of the strains, showing their
epidemiological independence, and 15.7% were grouped into 22 clusters.
Thirty-two strains (61.5%) from the 52 that clustered were from
Mpumalanga, 16/52 (30.8%) from Gauteng, and 4/52 (9.6%) from Limpopo
province. Clustering was not associated with age. However, strains from
male patients in Mpumalanga were more likely to be clustered than
strains from male patients in Limpopo and/or Gauteng province. The
minimum estimate for the proportion of resistant TB that was due to
transmission is 9.06% (52-22=30/331). Our results indicate that
transmission of drug-resistant strains may contribute substantially to
the emergence of drug-resistant tuberculosis in South Africa
IS6110 restriction fragment length polymorphism typing of drug-resistant Mycobacterium tuberculosis strains from northeast South Africa
Tuberculosis (TB) remains a deadly infectious disease affecting millions of people worldwide; 95% of TB cases,
with 98% of death occur in developing countries. The situation in South Africa merits special attention.
A total of 21,913 sputum specimens of suspected TB patients from three provinces of South Africa routinely
submitted to the TB laboratory of Dr. George Mukhari (DGM) Hospital were assayed for Mycobacterium tuberculosis
(MTB) growth and antibiotic susceptibility. The genetic diversity of 338 resistant strains were also
studied. DNA isolated from the strains were restricted with Pvu II, transferred on to a nylon membrane and
hybridized with a PCR-amplified horseradish peroxidase 245 bp IS6110 probe. Of the 338 resistant strains,
2.09% had less than 5 bands of IS6110, and 98% had 5 or more bands. Unique restriction fragment length
polymorphism (RFLP) patterns were observed in 84.3% of the strains, showing their epidemiological independence,
and 15.7% were grouped into 22 clusters. Thirty-two strains (61.5%) from the 52 that clustered
were from Mpumalanga, 16/52 (30.8%) from Gauteng, and 4/52 (9.6%) from Limpopo province. Clustering
was not associated with age. However, strains from male patients in Mpumalanga were more likely to be
clustered than strains from male patients in Limpopo and/or Gauteng province. The minimum estimate for
the proportion of resistant TB that was due to transmission is 9.06% (52-22=30/331). Our results indicate
that transmission of drug-resistant strains may contribute substantially to the emergence of drug-resistant
tuberculosis in South Africa.The National Research
Foundation of South Africahttp://www.jhpn.net/index.php/jhpnam2016Medical Microbiolog
Correlation between CT features of active tuberculosis and residual metabolic activity on end-of-treatment FDG PET/CT in patients treated for pulmonary tuberculosis
Patients who complete a standard course of anti-tuberculous treatment (ATT) for
pulmonary tuberculosis and are declared cured according to the current standard
of care commonly have residual metabolic activity (RMA) in their lungs on
fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography
(FDG PER/CT) imaging. RMA seen in this setting has been shown to be associated with
relapse of tuberculosis. The routine clinical use of FDG PET/CT imaging for treatment
response assessment in tuberculosis is hindered by cost and availability. CT is a more
readily available imaging modality. We sought to determine the association between CT
features suggestive of active tuberculosis and RMA on FDG PET/CT obtained in patients
who completed a standard course of ATT for pulmonary tuberculosis. We prospectively
recruited patients who completed a standard course of ATT and declared cured based
on negative sputum culture. All patients had FDG PET/CT within 2 weeks of completing
ATT. We determined the presence of RMA on FDG PET images. Among the various
lung changes seen on CT, we considered the presence of lung nodule, consolidation,
micronodules in tree-in-bud pattern, FDG-avid chest nodes, and pleural effusion as
suggestive of active tuberculosis. We determine the association between the presence
of RMA on FDG PET and the CT features of active tuberculosis. We include 75 patients
with a mean age of 36.09 ± 10.49 years. Forty-one patients (54.67%) had RMA on
their FDG PET/CT while 34 patients (45.33%) achieved complete metabolic response to
ATT. There was a significant association between four of the five CT features of active
disease, p < 0.05 in all cases. Pleural effusion (seen in two patients) was the only CT feature of active disease without a significant association with the presence of RMA. This
suggests that CT may be used in lieu of FDG PET/CT for treatment response assessment
of pulmonary tuberculosis.CRDF Global for the project titled: The Clinical Research Unit (CRU) for the Advancement of Tuberculosis (TB) Biomarker-Targeted Interventions.http://frontiersin.org/Medicinedm2022Medical MicrobiologyNuclear Medicin
Antimicrobial Susceptibility Patterns of Selected Bacteraemic Isolates from South African Public Sector Hospitals, 2010
We report on antimicrobial susceptibility surveillance data for six key bloodstream pathogens (Escherichia coli, Klebsiella
pneumoniae, Enterobacter spp., Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus) identified in
public sector hospitals in South Africa during 2010. Major findings include the accelerated emergence of carbapenem resistance
among K. pneumoniae and Enterobacter species, with overall susceptibility rates of 98% and 96% for ertapenem, and above 99%
for meropenem and imipenem. Levels of resistance among P. aeruginosa and A. baumannii remain high in all centres, with few
changes since 2009. Large decreases in piperacillin-tazobactam susceptibility rates were noted at three institutions, probably
related to methodological issues. S. aureus remains a major pathogen countrywide, with between 30-60% of isolates resistant
to cloxacillin [methicillin-resistant S. aureus (MRSA)]. Ongoing surveillance for antimicrobial resistance is vital, and the use of a
centralised data extraction system may aid in this.http://www.sajei.co.za/index.php/SAJE
Pregnancy incidence and correlates during the HVTN 503 Phambili HIV vaccine trial conducted among South African women.
Background: HIV prevention trials are increasingly being conducted in sub-Saharan Africa. Women at risk for HIV are also at risk of pregnancy. To maximize safety, women agree to avoid pregnancy during trials, yet pregnancies occur. Using data from the HVTN 503/‘‘Phambili’’ vaccine trial, we report pregnancy incidence during and after the vaccination period and identify factors, measured at screening, associated with incident pregnancy. Methods: To enrol in the trial, women agreed and were supported to avoid pregnancy until 1 month after their third and final vaccination (‘‘vaccination period’’), corresponding to the first 7 months of follow-up. Unsterilized women, pooled
across study arms, were analyzed. Poisson regression compared pregnancy rates during and after the vaccination period. Cox proportional hazards regression identified associations with first pregnancy. Results: Among 352 women (median age 23 yrs; median follow-up 1.5 yrs), pregnancy incidence was 9.6/100 women-years overall and 6.8/100 w-yrs and 11.3/100 w-yrs during and after the vaccination period, respectively [Rate Ratio = 0.60 (0.32– 1.14), p = 0.10]. In multivariable analysis, pregnancy was reduced among women who: enrolled at sites providing contraception on-site [HR = 0.43, 95% CI (0.22–0.86)]; entered the trial as injectable contraceptive users [HR = 0.37 (0.21–0.67)] or as consistent condom users (trend) [HR = 0.54 (0.28–1.04)]. Compared with women with a single partner of HIV-unknown status, pregnancy rates were increased among women with: a single partner whose status was HIV-negative [HR = 2.34(1.16–4.73)] and; 2 partners both of HIV-unknown status [HR = 4.42(1.59–12.29)]. Women with 2 more of these risk factors: marijuana use, heavy drinking, or use of either during sex, had increased pregnancy incidence [HR = 2.66 (1.24–5.72)]. Conclusions: It is possible to screen South African women for pregnancy risk at trial entry. Providing injectable contraception for free on-site and supporting consistent condom use may reduce incident pregnancy. Screening should determine the substance use, partnering, and HIV status of both members of the couple for both pregnancy and HIV
prevention
Case-fatality and sequelae following acute bacterial meningitis in South Africa, 2016 through 2020
OBJECTIVES : Providing country-specific estimates of case fatality and sequelae from bacterial meningitis (BM) is important to evaluate and monitor progress toward the World Health Organization's roadmap to “defeating meningitis by 2030”.
METHODS : From 2016-2020, GERMS-SA conducted enhanced surveillance at 26 hospitals across South Africa. Episodes of laboratory-confirmed BM due to Streptococcus pneumoniae, Haemophilus influenzae , and Neisseria meningitidis were included. Risk factors for in-hospital death and sequelae at hospital discharge among survivors were analyzed.
RESULTS : Of 12,717 invasive bacterial infections reported nationally, 39% (4980) were from enhanced surveillance sites, including 4159 pneumococcal, 640 H. influenzae , and 181 meningococcal infections. BM accounted for 32% (1319/4159) of pneumococcal, 21% (136/640) of H. influenzae , and 83% (151/181) of meningococcal invasive diseases. Clinical data were available for 91% (1455/1606) of BM: 26% (376/1455) were aged <5 years, 50% (726/1455) were female, and 62% (723/1171) with known HIV results, were HIV-infected. In-hospital case fatality was 37% (534/1455), and 24% (222/921) of survivors had adverse sequelae. Risk factors for death included altered mental status, HIV infection, and comorbidities. Risk factors for adverse sequelae included altered mental status and antimicrobial nonsusceptibility.
CONCLUSION : BM in South Africa has a high case fatality, and adverse sequelae frequently occur among survivors. Those with comorbidities (including HIV) are at the highest risk.The NICD of the National Health
Laboratory Service.http://www.elsevier.com/locate/ijidhj2023Medical Microbiolog
Continued Follow-Up of Phambili Phase 2b Randomized HIV-1 Vaccine Trial Participants Supports Increased HIV-1 Acquisition among Vaccinated Men.
CAPRISA, 2015.Abstract available in pdf
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