High rate of transmission among contacts in large London outbreak of isoniazid mono-resistant tuberculosis.

BACKGROUND: For a continuing London outbreak of isoniazid mono-resistant tuberculosis (TB), we aimed to determine transmission rates and risk factors for contacts of early cases, in order to inform future guidance on contact tracing. METHODS: Paper-based proformas were completed by TB nurses, and then analysed using EpiInfo/SAS statistical software. RESULTS: Forty community contacts (11%) became cases, 45 (13%) were recommended chemoprophylaxis and 270 (76%) were discharged clear of infection. The highest transmission rate was among contacts exposed to two or more cases (29% became cases) and close contacts of sputum smear-positive cases (22%). Other risk factors were being male and exposure to drug-using cases or cases with prison links. The number needed to be screened (NNS) to detect one case was lowest [5 (95% CI: 4-8)] for contacts of sputum smear-positive pulmonary cases, although the NNS was still only 20 (95% CI:8-72) for casual contacts of smear-positive cases. CONCLUSIONS: Transmission of disease to contacts was high (11%) compared with other documented outbreaks (0.7-2%). The results support recommended guidelines for contact tracing but also provide grounds to recommend, for outbreak cases, screening of casual contacts of smear-positive cases and contacts exposed to more than one case, drug users or prisoners.

Molecular epidemiology of tuberculosis in England, 1998.

SETTING: England. OBJECTIVE: To investigate the proportion of tuberculosis (TB) cases attributable to recent transmission and factors associated with clustering. DESIGN: Demographic, clinical and microbiological surveillance data were collated from all new culture-confirmed cases in 1998. Using insertion sequence (IS) 6110 restriction fragment length polymorphism (RFLP) typing, strains were classified as clustered (identical patterns) or unique and risk factors were determined using multivariable logistic regression. RESULTS: RFLP patterns were available for 2265 of 3713 (61%) cases: 1808 had >or=5 IS6110 copies, while 372 cases were in 152 clusters, giving an estimated proportion due to recent transmission of 12.2%.Pulmonary disease (aOR 1.6; 95%CI 1.1-2.2), previous treatment (aOR 3.7; 2.2-6.5) and homelessness (aOR 5.5; 1.2-24.1) were independent risk factors for clustering. Fourteen per cent of patients of Indian subcontinent origin were clustered compared with 27% of white patients. Many clusters spanned ethnic groups (45%) and geographical regions (47%). CONCLUSION: The calculated proportion of TB cases due to recent transmission is low.Adjusting for missed cases and study duration, it increases to 27.6%. Many cases may arise from reactivation or acquisition outside England. Transmission within England accounted for approximately one in four cases and occurred over wide geographic areas, between ethnic groups and among the homeless. Molecular epidemiology can inform local and national public health action.

Therapeutic trial of diazepam versus placebo in acute chloroquine intoxications of moderate gravity.

OBJECTIVE: Acute chloroquine intoxication is responsible for a membrane-stabilising effect which results in electrocardiographic (ECG) and hemodynamic disturbances. Diazepam is used in acute chloroquine intoxication on the basis of clinical and experimental observations, but its utility alone, in man, remains unproven. The goal of this study was to verify whether diazepam alone has an effect on the membrane-stabilising effect observed in moderately severe chloroquine intoxications. DESIGN: Prospective, multi-center, double-blind, placebo-controlled study. SETTING: Prehospital mobile intensive care units (Paris) and hospital intensive care units (paris and Dakar). PATIENTS AND PARTICIPANTS: Adults with moderately severe intoxication defined as: a suspected ingested dose of 2 or more but less than 4 g, systolic blood pressure (SBP) higher than 80 mmHg, QRS duration less than 0.12 s and the absence of dysrhythmia at inclusion. INTERVENTIONS: Patients received either a loading dose of 0.5 mg/kg diazepam followed by an infusion of 1 mg/kg over 24 h or an equivalent volume of placebo. MEASUREMENTS AND RESULTS: Outcome was measured by serial assessments of SBP, ECG (QRS and QT segments) and clinical deterioration. There were no significant differences observed in the initial or serial ECG or SBP measurements. There were no deaths and no patient had to be removed from the study due to clinical deterioration. CONCLUSIONS: Diazepam, at the dose studied, does not appear to reverse the chloroquine-induced membrane-stabilising effect in acute moderately severe chloroquine intoxication. Supportive intensive care of these intoxications appears to be all that is necessary.