Non-fermenter Gram-negative bacilli at a tertiary hospital, South Africa.

Background: Non-fermenting Gram-negative bacilli (NFGNB) are a significant cause of healthcare-associated infections and are often implicated in nosocomial outbreaks. Non- fermenting Gram-negative bacilli tend to have variable susceptibility patterns that make the choice of empiric therapy difficult and thus treatment must be based on in vitro susceptibility testing of each antimicrobial agent. Objectives: To describe the epidemiology of the NFGNB isolated from adult patients at Chris Hani Baragwanath Hospital (CHBAH) and to assess their antimicrobial susceptibility patterns in order to guide empiric therapy and inform infection prevention and control practices. Method: Organisms isolated from sterile sites of adult in-patients between 01 January 2016 to 31 December 2018 were retrospectively analysed. Results: A total of 2005 NFGNB isolated. Blood cultures were the most common specimen type (91.4%). Acinetobacter species were the most commonly isolated organisms (65.1%), followed by Pseudomonas species (26.5%). The majority of NFGNB were isolated from patients in surgical wards (38.9%) followed by medical wards (35.2%). Most (60%) of the Acinetobacter species were extremely drug resistant. Pseudomonas species were more susceptible than the Acinetobacter species with an overall susceptibility rate of 86% for Pseudomonas species. Conclusion: The rates of antimicrobial resistance demonstrated among Acinetobacter and Pseudomonas species were high, which illustrates the threat of antimicrobial resistance also seen worldwide. An emergence of NFGNB with intrinsic multidrug resistance (Stenotrophomonas maltophilia and Burkholderia cepacia) was noted. We suggest empiric therapy with a carbapenem sparing regimen of piperacillin-tazobactam in combination with amikacin and that empiric therapy be reviewed annually when cumulative antibiograms are done. Contribution: Understanding of the distribution and antimicrobial susceptibility patterns of NFGNB at CHBAH.

Evaluating systematic targeted universal testing for tuberculosis in primary care clinics of South Africa: A cluster-randomized trial (The TUTT Trial).

BACKGROUND: The World Health Organization (WHO) recommends systematic symptom screening for tuberculosis (TB). However, TB prevalence surveys suggest that this strategy does not identify millions of TB patients, globally. Undiagnosed or delayed diagnosis of TB contribute to TB transmission and exacerbate morbidity and mortality. We conducted a cluster-randomized trial of large urban and rural primary healthcare clinics in 3 provinces of South Africa to evaluate whether a novel intervention of targeted universal testing for TB (TUTT) in high-risk groups diagnosed more patients with TB per month compared to current standard of care (SoC) symptom-directed TB testing. METHODS AND FINDINGS: Sixty-two clinics were randomized; with initiation of the intervention clinics over 6 months from March 2019. The study was prematurely stopped in March 2020 due to clinics restricting access to patients, and then a week later due to the Coronavirus Disease 2019 (COVID-19) national lockdown; by then, we had accrued a similar number of TB diagnoses to that of the power estimates and permanently stopped the trial. In intervention clinics, attendees living with HIV, those self-reporting a recent close contact with TB, or a prior episode of TB were all offered a sputum test for TB, irrespective of whether they reported symptoms of TB. We analyzed data abstracted from the national public sector laboratory database using Poisson regression models and compared the mean number of TB patients diagnosed per clinic per month between the study arms. Intervention clinics diagnosed 6,777 patients with TB, 20.7 patients with TB per clinic month (95% CI 16.7, 24.8) versus 6,750, 18.8 patients with TB per clinic month (95% CI 15.3, 22.2) in control clinics during study months. A direct comparison, adjusting for province and clinic TB case volume strata, did not show a significant difference in the number of TB cases between the 2 arms, incidence rate ratio (IRR) 1.14 (95% CI 0.94, 1.38, p = 0.46). However, prespecified difference-in-differences analyses showed that while the rate of TB diagnoses in control clinics decreased over time, intervention clinics had a 17% relative increase in TB patients diagnosed per month compared to the prior year, interaction IRR 1.17 (95% CI 1.14, 1.19, p < 0.001). Trial limitations were the premature stop due to COVID-19 lockdowns and the absence of between-arm comparisons of initiation and outcomes of TB treatment in those diagnosed with TB. CONCLUSIONS: Our trial suggests that the implementation of TUTT in these 3 groups at extreme risk of TB identified more TB patients than SoC and could assist in reducing undiagnosed TB patients in settings of high TB prevalence. TRIAL REGISTRATION: South African National Clinical Trials Registry DOH-27-092021-4901.

Retrospective analysis of Vitek®2 performance compared to manual broth micro-dilution for colistin susceptibility testing of Acinetobacter baumanniicomplex isolates in South Africa.

The manual broth micro-dilution (mBMD) is the recommended reference method for colistin minimum inhibitory concentration determination; however, it is not as readily available in South Africa as the Vitek®2. This retrospective study compared the performance of Vitek®2 against mBMD in determining the colistin minimum inhibitory concentration of 337 extensively drug-resistant Acinetobacter baumannii complex isolates. Vitek®2 yielded a categorical agreement of 89%, an essential agreement of 56%, a major error rate of 8% and a very major error rate of 55%. The Vitek®2 is not an alternative to mBMD for colistin susceptibility testing.

Using surrogate vaccines to assess feasibility and acceptability of future HIV vaccine trials in men: a randomised trial in inner-city Johannesburg, South Africa.

BACKGROUND: Developing an effective HIV vaccine is the overriding priority for HIV prevention research. Enrolling and maintaining cohorts of men into HIV vaccine efficacy trials is a necessary prerequisite for the development and licensure of a safe and efficacious vaccine. METHODS: One hundred-fifty consenting HIV-negative men were enrolled into a pilot 1:1 randomised controlled trial of immediate vaccination with a three-dose hepatitis B vaccine compared to deferred vaccination (at 12 months) to investigate feasibility and acceptability of a future HIV vaccine trial in this population. Adverse events, changes in risk behaviour, acceptability of trial procedures and motivations for participation in future trials were assessed. RESULTS: Men were a median 25 years old (inter-quartile range = 23-29), 53% were employed, 90% secondary school educated and 67% uncircumcised. Of the 900 scheduled study visits, 90% were completed in the immediate vaccination arm (405/450) and 88% (396/450) in the delayed arm (P = 0.338). Acceptability of trial procedures and services was very high overall. However, only 65% of the deferred group strongly liked being randomised compared to 90% in the immediate group (P = 0.001). Informed consent processes were viewed favourably by 92% of the delayed and 82% of the immediate group (P = 0.080). Good quality health services, especially if provided by a male nurse, were rated highly. Even though almost all participants had some concern about the safety of a future HIV vaccine (98%), the majority were willing to participate in a future trial. Future trial participation would be motivated mainly by the potential for accessing an effective vaccine (81%) and altruism (75%), rather than by reimbursement incentives (2%). CONCLUSIONS: Recruitment and retention of men into vaccine trials is feasible and acceptable in our setting. Findings from this surrogate vaccine trial show a high willingness to participate in future HIV vaccine trials. While access to potentially effective vaccines is important, quality health services are an equally compelling incentive for enrolment.

Quality control and performance of HIV rapid tests in a microbicide clinical trial in rural KwaZulu-Natal.

BACKGROUND: Quality control (QC) and evaluation of HIV rapid test procedures are an important aspect of HIV prevention trials. We describe QC and performance of two rapid tests, Determine™ and Uni-Gold™ used in a microbicide clinical trial in rural KwaZulu-Natal, South Africa. METHODS/RESULTS: Internal QC of both HIV rapid tests was conducted at the trial site using a Uni-Gold control kit (Uni-Gold™Recombigen® HIV). Both assays produced the expected results for a total of 4637 QC tests. Study participants were tested for HIV at screening and, if enrolled, at regular time points throughout the study. Positive or discordant results were confirmed by a double HIV immunoassay testing strategy at a local laboratory. Overall, 15292 HIV rapid test were performed. Sensitivity and specificity of Determine was 98.95% (95% CI: 97.72-99.61) and 99.83% (95% CI: 99.70-99.91) respectively [positive predictive value (PPV) 97.91% (95% CI: 96.38-98.92)], for Uni-Gold it was 99.30% (95% CI: 98.21-99.81) and 99.96% (95% CI: 99.88-99.99) respectively [PPV 99.47% (95% CI: 98.46-99.89)]. CONCLUSIONS: The results suggest that a Uni-Gold control kit can be used for internal QC of both Uni-Gold and the HIV-1 component of the Determine rapid tests. Both rapid tests performed proficiently in the trial population.