Proportion of tuberculosis transmission that takes place in households in a high-incidence area

The prevalence of infection among household contacts of people with tuberculosis is high. This information frequently guides active case finding. We analysed DNA fingerprints of Mycobacterium tuberculosis from 765 tuberculosis patients in Ravensmead and Uitsig, adjacent suburbs of Cape Town, South Africa. In 129 households in which DNA fingerprints were available for more than one patient, we identified 313 patients, of whom 145 (46%) had a fingerprint pattern matching that of another member of the household. The proportion of transmission in the community that took place in the household was 19%, and therefore, in this high-incidence area, tuberculosis transmission occurs mainly outside the household.     

Effects of instruction by practice assistants on inhaler technique and respiratory symptoms of patients. A controlled randomized videotaped intervention study

BACKGROUND: Many patients with asthma or chronic obstructive pulmonary diseaseuse their medication inhalers incorrectly. General practitioners,pharmacists and other health care providers do not always havethe opportunity to instruct patients in correct inhaler technique. OBJECTIVE: To find out whether the inhaler technique and respiratory symptomsof patients can be improved after instruction by practice assistants. METHODS: Single blind, randomized intervention study in which 48 patientswho had been using a dry powder inhaler for at least one monthtook part. Their inhaler technique was videotaped on two visitswith a two-week interval between visits. The inhaler techniqueon the videos was subsequently scored by two experts on ninecriteria. At both visits the patients completed a questionnaireabout their respiratory symptoms. After the first video, 25patients were randomly chosen to receive instruction from oneof six practice assistants who had followed a one evening courseabout inhaler instruction, and who had been issued an instruction-set. RESULTS: The patients who received instruction had a significantly greaterreduction in number of mistakes at the second visit than thepatients who did not (P = 0.01). The instructed patients alsoreported less dyspnoea at the second visit (P = 0.03). No effectof instruction was found on wheezing, cough and sputum production. CONCLUSION: The inhaler technique of patients can be improved significantlyby the instruction of patients by trained practice assistants,possibly resulting in less dyspnoea. Keywords. Administration-inhalation, obstructive lung diseases, airways symptoms, patient-education, general practice.     

Influence of sulphasalazine and mesalazine on cellular and biochemical oxygen metabolite production. Effect of in vivo administration and an in vitro analysis.

Oxidative damage has been implicated in the pathogenesis of inflammatory bowel disease. In the present study sulphasalazine and mesalazine (5-aminosalicylic acid) in vitro were shown to possess scavenging activity and to attenuate the production of oxygen metabolites by neutrophils. In a double-blind randomized crossover study, with five patients with inflammatory bowel disease in remission and four healthy controls, we evaluated the influence of in vivo administration of sulphasalazine and mesalazine on the neutrophil oxygen metabolite production in vitro. Apart from a small but significant increase in the neutrophil H2O2 and O2 production by sulphasalazine, in particular in controls, in vivo administration of both drugs hardly affected the oxygen metabolite-producing capacity of the cells. This observation was confirmed by in vitro preincubation of neutrophils with the drugs and subsequent oxygen metabolite production analysis. It is concluded that sulphasalazine and mesalazine do not influence the oxidative capacity of neutrophils, but scavenge and attenuate the production of oxygen metabolites when present in the immediate surroundings of the cells. Thus, protection against oxidative damage is definitely one of the modes of action of these drugs.     

Lung volumes measured by the forced rebreathing technique in children with airways obstruction.

Forced rebreathings may recruit trapped gas into the mixing process. Therefore, we assessed the validity and reproducibility of measurements of residual volume (RVN2) by forced rebreathing in a closed circuit using N2 as indicator gas (N2FR) in children with airways obstruction. Validity was studied from measurements of RV obtained by N2FR, by helium dilution during resting ventilation, and by body plethysmograph at low panting frequency in young patients (8-18 yrs, 13 with asthma, forced expiratory volume in one second (FEV1) 93.0 +/- 22.8% pred; 12 with cystic fibrosis (CF), FEV1 80.4 +/- 16.4% pred). Reproducibility of RVN2 was assessed from duplicate measurements in 73 patients with asthma before and after bronchodilation (FEV1 81.4 +/- 13.7 and 99.6 +/- 11.5% pred, respectively), and in nine patients with CF; the total lung capacity (TLC) was unaffected by bronchodilation; 3,797 +/- 830 ml and 3,807 +/- 843 ml, respectively. Gas dilution methods gave comparable results in all subjects but gave lower values than plethysmography in patients with cystic fibrosis. Reproducibility was satisfactory, median differences between duplicate measurements of RVN2 and TLCN2 varying between 13 and 46 ml, respectively. We conclude that N2FR is quickly performed and well-tolerated. Lung volumes are highly reproducible and agree well with those obtained with the helium dilution method. Deep inspirations do not seem to overcome gas trapping in patients with CF.     

Phenotypic variability in childhood TB: implications for diagnostic endpoints in tuberculosis vaccine trials

The endpoint definition for infant tuberculosis (TB) vaccine trials should match the TB disease phenotype expected in the control arm of the study population. Our aim was to analyse selected combinations of the clinical, radiological, and microbiological features of pulmonary TB among children investigated under vaccine trial conditions, in order to estimate case frequency for a range of expected TB phenotypes. Two thousand one hundred and eighty five South African children were investigated over a nine-year period (2001-2009). Evidence of TB exposure and classical symptoms were several times more common than chest radiography (CXR) compatible with TB, or positive Mycobacterium tuberculosis culture. Discordance between clinical, radiological, and microbiological features was common in individual children. Up to one third of children with compatible CXR, and up to half the children who were M. tuberculosis culture positive, were asymptomatic. The culture positive rate fell over time, although rates of TB exposure and compatible chest radiography increased. Consequently, the annual incidence of diagnostic combinations that included M. tuberculosis culture fell to <0.2%. However, in this study population (children <2 years of age), annual incidence of the TB disease phenotype that included the triad of TB exposure, symptoms, and compatible CXR, approached 1% (n = 848 per 100,000). These findings allow modelling of expected TB case frequency in multi-centre infant TB vaccine trials, based upon benchmarking of diagnostic data against the key indicator variables that constitute the building blocks of a trial endpoint.     

The impact of a change in bacille Calmette-Guérin vaccine policy on tuberculosis incidence in children in Cape Town, South Africa

BACKGROUND: A decision by the South African National Department of Health to change the route of administration and strain of bacille Calmette-Guérin (BCG) vaccine was implemented in Cape Town, South Africa, between July and December 2000. This provided an opportunity to compare the incidence of tuberculosis and proportion with disseminated disease in children less than 2 years old before and after the changeover from percutaneous (PC) Tokyo 172 BCG to intradermal (ID) 1331 Danish BCG immunization. METHODS: Clinical records of all tuberculosis patients aged less than 2 years at diagnosis and born between January 1, 1999, and June 30, 2000 (PC cohort) and between January 1, 2001, and June 30, 2002 (ID cohort) were collected. All cases were reviewed for likelihood of TB, its severity and disease dissemination. RESULTS: The number of reported patients with tuberculosis in the PC cohort was 1369 and in the ID cohort 1397, giving incidence rates of 866 (95% confidence interval [CI], 821-913) and 858 (95% CI, 814-904) per 100,000 person-years, respectively. The proportion who had disseminated disease (meningitis and/or miliary spread) was significantly lower in the ID cohort (4.7%) than in the PC cohort (8.6%) (relative risk, 0.54; 95% CI, 0.40-0.72). Those not vaccinated had a significantly higher proportion of disseminated disease cases (29.2%) than the PC and ID groups combined (6.6%) (relative risk, 4.4; 95% CI, 2.7-6.7). CONCLUSION: A program using Danish 1331 BCG given intradermally did not prevent more tuberculosis cases in children overall as compared with a program using Tokyo 172 BCG given percutaneously but reduced the proportion with disseminated disease.     

Development and evaluation of a new chest radiograph reading and recording system for epidemiological surveys of tuberculosis and lung disease.

OBJECTIVE: The development and evaluation of a new chest radiograph reading and recording system (CRRS) for community surveys of tuberculosis (TB) and lung disease. DESIGN: An experienced pulmonologist read 2608 chest X-rays (CXRs) performed as part of a TB prevalence survey using the newly developed CRRS. The kappa (kappa) for inter-reader agreement was calculated after a second reader reported on a stratified random sample of 810 (31%) of the 2608 CXRs. The kappa for intra-reader agreement was calculated from the repeated reporting of a stratified random sample of 104 CXRs. RESULTS: The kappa agreement between the two readers was 0.69 (95%CI 0.64-0.74) for abnormalities consistent with TB and 0.47 (95%CI 0.42-0.53) for any abnormalities. The kappa for intra-reader agreement was 0.90 (95%CI 0.81-0.99) for abnormalities consistent with TB and 0.85 (95%CI 0.74-0.95) for any abnormalities. CONCLUSION: This standardised method for CXR reading and recording provides satisfactory inter- and intra-reader agreement, making it suitable for surveys of TB and other forms of lung disease in the community. Its use will permit comparisons of results obtained in different surveys.     

Recurrent tuberculosis in the Netherlands – a 24-year follow-up study, 1993 to 2016

BackgroundNot all treated tuberculosis (TB) patients achieve long-term recovery and reactivation rates reflect effectiveness of TB treatment.AimWe aimed to estimate rates and risk factors of TB reactivation and reinfection in patients treated in the Netherlands, after completed or interrupted treatment.MethodsRetrospective cohort study of TB patients with available DNA fingerprint data, registered in the Netherlands Tuberculosis register (NTR) between 1993 and 2016. Reactivation was defined as an identical, and reinfection as a non-identical Mycobacterium tuberculosis strain in sequential episodes.ResultsReactivation rate was 55/100,000 person-years (py) for patients who completed, and 318/100,000 py for patients who interrupted treatment. The risk of reactivation was highest in the first 5 years after treatment in both groups. The incidence rate of reactivation was 228/100,000 py in the first 2 years and 57/100,000 py 2–5 years after completed treatment. The overall rate of reinfection was 16/100,000 py. Among those who completed treatment, patients with male sex, mono or poly rifampicin-resistant TB and a previous TB episode had significantly higher risk of reactivation. Extrapulmonary TB was associated with a lower risk. Among patients who interrupted treatment, directly observed treatment (DOT) and being an undocumented migrant or people experiencing homelessness were associated with a higher risk of reactivation.ConclusionsBoth patients who completed or interrupted TB treatment should be considered as risk groups for reactivation for at least 2–5 years after treatment. They patients should be monitored and guidelines should be in place to enhance early detection of recurrent TB.     

Willingness to participate in trials and to be vaccinated with new tuberculosis vaccines in HIV-infected adults

Background:

New tuberculosis (TB) vaccines are required to meet global targets for TB control.

Objectives:

To determine willingness to participate (WTP) in new TB vaccine trials, willingness to be vaccinated with a newly licensed TB vaccine and associated factors among human immunodeficiency virus (HIV) infected persons.

Setting:

Two primary care clinics in South Africa.

Design:

Cross-sectional study design. Participants were asked about WTP and willingness to be vaccinated. Demographic, clinical, knowledge of TB and perception of risk information were collected. Log binomial regression was used to determine associated factors.

Results:

A total of 827 participants were included in the analysis: 80.4% female, 72.2% on antiretroviral therapy, median age 35 years (interquartile range [IQR] 29–42 years), CD4 count 523 cells/µl (IQR 427–659 cells/µl). WTP and willingness to be vaccinated were high, at 84.5% and 92.6%, respectively. WTP was associated with knowledge about TB (prevalence ratio [PR] 1.10, 95% confidence interval [CI] 1.03–1.17) and perception of risk (PR 1.07, 95%CI 1.01–1.13). Willingness to be vaccinated was associated with employment (PR 1.04, 95%CI 1.01–1.08) and perception of risk (PR 1.05, 95%CI 1.01–1.09).

Conclusions:

There was high WTP in TB vaccine trials and willingness to be vaccinated among HIV-infected patients with good TB knowledge and high perceived risk of contracting TB.