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Background Interim results from the CHER trial showed that early antiretroviral therapy (ART) was life-saving for HIV-infected infants. Given limited options and potential for toxicity with life-long ART, CHER compared early limited ART with deferred ART. Methods CHER was an open 3-arm trial in HIV-infected asymptomatic infants aged <12 weeks with CD4% ≥25%. Infants were randomized to deferred (ART-Def) or immediate ART for 40weeks (ART-40W) or 96weeks (ART-96W), followed by interruption. Criteria for ART initiation in ART-Def and re-initiation after interruption were CD4% <25% in infancy; otherwise <20% or CDC severe stage B or stage C disease. Lopinavir-ritonavir, zidovudine, lamivudine was the first-line regimen at ART initiation and re-initiation. The primary endpoint was time-to-failure of first-line ART (immunological/clinical/virological) or death. Comparisons were by intent-to-treat, using time-to-event methods. Findings 377 infants were enrolled: median age 7.4weeks; CD4% 35% and HIV RNA log 5.7copies/ml. Median follow-up was 4.8 years; 34 (9%) were lost-to-follow-up. Median time to ART initiation in ART-Def was 20 (IQR 16–25) weeks. Time to restarting ART after interruption was 33 (26–45) weeks in ART-40W and 70 (35–109) weeks in ART-96W; at trial end 19% and 32% respectively, remained off ART. Proportions of follow-up time spent on ART were 81%, 70% and 69% in ART-Def, ART-40W and ART-96W arms. 48/125(38%), 32/126(25%) and 26/126(21%) children reached the primary endpoint; hazard ratio (95%CI), relative to ART-Def, was 0.59(0.38-0.93, p=0.02) for ART-40W and 0.47(0.27-0.76, p=0.002) for ART-96W. Seven children (3 ART-Def, 3 ART-40W, 1 ART-96W) switched to second-line ART. Interpretation Early limited ART had superior clinical/immunological outcome with no evidence of excess disease progression during subsequent interruption and less overall ART exposure than deferred ART. Longer time on primary ART permits longer subsequent interruption with marginally better outcomes.

Shewanella (Pseudomonas) putrefaciens is a rare pathogen in humans, and to our knowledge only 13 cases of S. putrefaciens bacteremia have ever been reported in the literature. In this retrospective study we describe 28 cases of S. putrefaciens bacteremia: 16 in premature and 1-day-old neonates, 9 in adults, and 3 in children younger than 1 year of age. All the babies presented with respiratory distress and/or pneumonia. Six of the adults had associated traumatic lesions of the lower extremity, and of the eight patients who died of sepsis, six were neutropenic. Polymicrobial bacteremia was seen in 18 cases. Three syndromes of bacteremic infection with S. putrefaciens appear to exist: the first is associated with prematurity and congenital pneumonia; the second with ulceration of the lower extremities; and the third (which is more fulminant), with an underlying debility. The findings in these 28 cases confirm the fact that S. putrefaciens can invade the bloodstream; however, the presence of concurrent bacteremia makes it difficult to determine the pathogenic role of this organism in septicemia.

BackgroundDespite the availability of TB infection control guidelines, and good levels of healthcare worker knowledge about infection control, often these measures are not well implemented. This study sought to determine the factors associated with healthcare workers’ good TB infection control practices in primary health care facilities in the Free State Province, South Africa.MethodsA cross-sectional self-administered survey among nurses (n = 202) and facility-based community healthcare workers (n = 34) as well as facility observations were undertaken at all 41 primary health care facilities in a selected district of the Free State Province.ResultsThe majority of respondents were female (n = 200; 87.7 %) and the average age was 44.19 years (standard deviation ±10.82). Good levels of knowledge were recorded, with 42.8 % (n = 101) having an average score (i.e. 65–79 %) and 31.8 % (n = 75) a good score (i.e. ≥ 80 %). Most respondents (n = 189; 80.4 %) had positive attitudes towards TB infection control practices (i.e. ≥ 80 %). While good TB infection control practices were reported by 72.9 % (n = 161) of the respondents (i.e. ≥75 %), observations revealed this to not necessarily be the case. For every unit increase in attitudes, good practices increased 1.090 times (CI:1.016–1.169). Respondents with high levels of knowledge (≥80 %) were 4.029 (CI: 1.550–10.469) times more likely to have good practices when compared to respondents with poor levels of knowledge (<65 %). The study did not find TB/HIV-related training to be a predictor of good practices.ConclusionsPositive attitudes and good levels of knowledge regarding TB infection control were the main factors associated with good infection control practices. Although many respondents reported good infection control practices - which was somewhat countered by the observations - there are areas that require attention, particularly those related to administrative controls and the use of personal protective equipment.

BackgroundHealth education is important to empower patients and encourage their contribution towards tuberculosis (TB) control. In South Africa, health education activities are integrated into services provided at the primary health care (PHC) level. This study was conducted in a high TB burden metropolitan area in South Africa. The objective was to assess TB-related knowledge, attitudes and infection control practices of patients attending PHC facilities.MethodsIn September and October 2015, a cross-sectional survey using fieldworker-administered questionnaires was conducted among patients older than 17 years attending 40 PHC facilities in the Mangaung Metropolitan. Convenience sampling was used to select patients. Participation in the study was voluntary. Descriptive, inferential and multivariate logistic regression analyses were performed. Statistical significance was considered at alpha <0.05 and 95% confidence interval.ResultsA total of 507 patients’ data were included in the analysis. Most of the patients knew that TB transmission is facilitated by crowded conditions (84.6%) and that pulmonary TB is contagious (73.0%). Surprisingly, the majority of patients also believed that one can get TB from sharing toothbrushes (85.0%) or kissing (65.0%). An overwhelming majority of patients perceived TB to be serious (89.7%), and concurred that taking treatment (97.2%) and opening windows to prevent transmission in PHC facilities (97.0%) are important. Being employed (AOR: 11.5; CI: 4.8–27.6), having received TB infection control information from a PHC facility (AOR: 2.2; CI: 1.5–3.4), and being a TB patient (AOR: 1.6; CI: 1.02–2.46) increased the likelihood of adopting good infection control practices.ConclusionThese findings highlight the need for health education efforts to strengthen accurate information dissemination to promote sound TB knowledge and attitudes among patients attending PHC facilities. Health education efforts should also capitalise on the positive finding of this study that information dissemination at PHC facilities increases good infection control practices.

BackgroundTuberculosis (TB) infection control at primary healthcare (PHC) level remains problematic, especially in South Africa. Improvements are significantly dependent on healthcare workers’ (HCWs) behaviours, underwriting an urgent need for behaviour change. This study sought to 1) identify factors influencing TB infection control behaviour at PHC level within a high TB burden district and 2) in a participatory manner elicit recommendations from HCWs for improved TB infection control.MethodA qualitative case study was employed. TB nurses and facility managers in the Mangaung Metropolitan District, South Africa, participated in five focus group and nominal group discussions. Data was thematically analysed.ResultsUtilising the Information Motivation and Behaviour (IMB) Model, major barriers to TB infection control information included poor training and conflicting policy guidelines. Low levels of motivation were observed among participants, linked to feelings of powerlessness, negative attitudes of HCWs, poor district health support, and general health system challenges. With a few exceptions, most behaviours necessary to achieve TB risk-reduction, were generally regarded as easy to accomplish.ConclusionsStrategies for improved TB infection control included: training for comprehensive TB infection control for all HCWs; clarity on TB infection control policy guidelines; improved patient education and awareness of TB infection control measures; emphasis on the active role HCWs can play in infection control as change agents; improved social support; practical, hands-on training or role playing to improve behavioural skills; and the destigmatisation of TB/HIV among HCWs and patients.

Childhood tuberculous meningitis is associated with serious long-term sequelae, including mental retardation, behavior disturbances, and motor handicap. Brain damage in tuberculous meningitis results from a cytokine-mediated inflammatory response, which causes vasculitis and obstructive hydrocephalus. Thalidomide, a potent tumor necrosis factor alpha inhibitor, was well tolerated and possibly showed some clinical benefit in children with tuberculous meningitis during a pilot study. The purpose of the present study was to assess the effect of adjunctive thalidomide in addition to standard antituberculosis and corticosteroid therapy on the outcome of tuberculous meningitis. Thalidomide (24 mg/kg/day orally) or placebo was administered in a double-blind randomized fashion for 1 month to patients with stage 2 or 3 tuberculous meningitis. The study was terminated early because all adverse events and deaths occurred in one arm of the study (thalidomide group). Thirty of the 47 children enrolled received adjunctive thalidomide, of whom 6 (20%) developed a skin rash, 8 (26%) hepatitis, and 2 (6%) neutropenia or thrombocytopenia. Four deaths (13%) occurred in patients with very severe neurologic compromise at baseline; two deaths were associated with a rash. Motor outcome after 6 months of antituberculosis therapy was similar in the two groups, even though the thalidomide group showed greater neurologic compromise on admission. In addition, the mean IQ of the two treatment groups did not differ significantly (mean IQ thalidomide group 57.8 versus mean IQ control group 67.5; P = .16). These results do not support the use of adjunctive high-dose thalidomide therapy in the treatment of tuberculous meningitis.

Arterial stroke is the main cause of poor outcome in childhood tuberculous meningitis. Aspirin has an antithrombotic action at low dose and anti-ischemic and anti-inflammatory properties, which are dose-related. The aim of the study was to explore the possible benefits of aspirin in children with tuberculous meningitis. A total of 146 consecutive children with a diagnosis of probable tuberculous meningitis were studied. Patients were randomized into 3 groups: (1) placebo group, (2) low-dose aspirin group, and (3) high-dose aspirin group. Twenty-nine additional patients who received aspirin before admission were excluded from the randomized study, but continued on low-dose aspirin. Aspirin, irrespective of dose, did not show any significant benefit regarding morbidity (hemiparesis and developmental outcome) and mortality. Aspirin was well tolerated, but 1 death was probably related to aspirin. The fact that the outcome of the high-dose aspirin group compared favorably with the other treatment groups despite younger age and more severe neurological involvement at baseline needs further investigation.