39 research outputs found
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
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
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
Original Article
The pancreas taken from the frog (Rana nigromaculata) was fixed in 1% OsO_4 and sliced into ultrathin sections for electron microscopic studies. The following observations were made: 1. A great \u27number of minute granules found in the cytoplasm of a pancreatic cell were called the microsomes, which were divided into two types, the C-microsome and S-microsome. 2. Electron microsopic studies of the ergastoplasm showed that it is composed of the microsome granules and A-substance. The microsomes were seen embedded in the A-substance which was either filamentous or membranous. The membranous structure, which was called the Am-membrane, was seen to form a sac, with a cavity of varying sizes, or to form a lamella. 3. The Am-membrane has close similarity to α-cytomembrane of Sjostrand, except that the latter is rough-surfaced. It was deduced that the Am-membrane, which is smooth-surfaced, might turn into the rough-surfaced α-cytomembrane. 4. There was the Golgi apparatus in the supranuclear region of a pancreatic cell. It consisted of the Golgi membrane, Golgi vacuole and. Golgi vesicle. 5. The mitochondria of a pancreatic cell appeared like long filaments, and some of them were seen to ramify. 6. The membrane of mitochondria, i. e. the limiting membrane, consisted of the Ammembrane. The mitochondria contained a lot of A-substances, as well as the C-microsomes and S-microsomes. When the mitochondria came into being, there appeared inside them chains of granules, which appeared like strips of beads, as the outgrowths of the A-substance and the microsome granules attached to the Am-membrane. They are the so-called cristae mitochondriales. 7. The secretory granules originate in the microsomes. They came into being when the microsomes gradually thickened and grew in size as various substances became adhered to them. Some of the secretory granules were covered with a membrane and appeared like what they have called the intracisternal granule of Palade.It seemed that this was a phenomenon attendant upon the dissolution and liqutefaction of the secretory granule. 8. Comparative studies were made of the ergastoplasm of the pancreatic cells from the frogs in hibernation, the frogs artificially hungered, the frogs which were given food after a certain period of fasting, the frogs to which pilocarpine was given subcutaneously, and the very young, immature frogs. The studies revealed that the ergastoplasm of the pancreatic cells greatly varied in form with the difference in nutritive condition and with different developmental stages of the cell. The change in form and structure occured as a result of transformation of the microsomes and A-substance. The ergastoplasm, even after it has come into being, might easily be inactivated if nutrition is defective. The ergastoplasm is concerned in the secretory mechanism, which is different from the secretory phenomenon of the secretory granules. It would seem that structurally the mitochondria have no direct relation to this mechanism
Vaccine efficacy of ALVAC-HIV and bivalent subtype C gp120–MF59 in adults
BACKGROUND : A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox–protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1–2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. METHODS : In this phase 2b–3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections of ALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gp120–MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. RESULTS : In January 2020, prespecified criteria for non-efficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month followup, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P = 0.84). CONCLUSIONS : The ALVAC–gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity.Supported by grants (HHSN272201300033C and HHSN272201600012C)
to Novartis Vaccines and Diagnostics (now part of the
GlaxoSmithKline [GSK] Biologicals) by the National Institute of
Allergy and Infectious Diseases (NIAID) of the National Institutes
of Health (NIH) for the selection and process development of the
two gp120 envelope proteins TV1.C and 1086.C; by the Bill and
Melinda Gates Foundation Global Health Grant (OPP1017604)
and NIAID for the manufacture and release of the gp120 clinical
grade material; and by U.S. Public Health Service Grants — UM1
AI068614 to the HIV Vaccine Trials Network (HVTN), UM1
AI068635 to the HVTN Statistical and Data Management Center,
and UM1 AI068618 to the HVTN Laboratory Center — from the
NIAID. GSK Biologicals contributed financially to the provision of
preexposure prophylaxis to trial participants. The South African
Medical Research Council supported its affiliated research sites.http://www.nejm.orgam2022School of Health Systems and Public Health (SHSPH