Alistair Story

Tuberculosis in London - the importance of homelessness, problem drug use and prison

Background: The control of tuberculosis (TB) is founded on early case detection and complete treatment of disease. In the UK, TB is concentrated in subgroups of the population in large urban centres. The impact of homelessness, imprisonment and problem drug use on TB control in London is reviewed. Methods: A cohort study was undertaken of all patients with TB in Greater London to determine the point prevalence of disease in different groups and to examine risk factors for smear positivity, drug resistance, treatment adherence, loss to follow-up and use of directly observed therapy (DOT). Results: Data were collected on 97% (1941/1995) of eligible patients. The overall prevalence of TB was 27 per 100 000. An extremely high prevalence of TB was seen in homeless people (788/100 000), problem drug users (354/100 000) and prisoners (208/100 000). Multivariate analysis showed that problem drug use was associated with smear positive disease (OR 2.2, p<0.001), being part of a known outbreak of drug resistant TB (OR 3.5, p = 0.001) and loss to follow-up (OR 2.7, p<0.001). Imprisonment was associated with being part of the outbreak (OR 10.3, p<0.001) and poor adherence (OR 3.9, p<0.001). Homelessness was associated with infectious TB (OR 1.6, p = 0.05), multidrug resistance (OR 2.1, p = 0.03), poor adherence (OR 2.5, p<0.001) and loss to follow-up (OR 3.8, p<0.001). In London, homeless people, prisoners and problem drug users collectively comprise 17% of TB cases, 44% of smear positive drug resistant cases, 38% of poorly compliant cases and 44% of cases lost to follow-up. 15% of these patients start treatment on DOT but 46% end up on DOT. Conclusions: High levels of infectious and drug resistant disease, poor adherence and loss to follow-up care indicate that TB is not effectively controlled among homeless people, prisoners and problem drug users in London.

Molecular Epidemiology of Disease Due to Mycobacterium bovis in Humans in the United Kingdom

ABSTRACT Mycobacterium bovis is the causative agent of bovine tuberculosis, with a wide host range. Fifty human M. bovis isolates were typed using spoligotyping and variable number tandem repeats (VNTR). Fifteen of these spoligotypes have not yet been recorded in cattle. The predominant spoligotype in humans and cattle was subdivided by VNTR.

Crack Cocaine and Infectious Tuberculosis

We hypothesize that crack cocaine is independently associated with smear-positive tuberculosis (TB). In a case–control study of TB in London, 19 (86%) of 22 crack cocaine users with pulmonary TB were smear positive compared with 302 (36%) of 833 non–drug users. Respiratory damage caused by crack cocaine may predispose drug users to infectivity.

Tuberculosis in disadvantaged groups.

Tuberculosis remains predominantly a disease of the disadvantaged and marginalized. The incidence of the disease is increasing in many industrially developed countries, particularly among the poor, ethnic minorities, prisoners and other institutionalized persons, and the socially isolated and hard to reach groups. Strengthening of the tuberculosis services is required to care for these groups. Millions of people in the developing nations are disadvantaged by poverty and inequity, and recent health sector reforms have not always been entirely in their interest. A further serious problem is the HIV/AIDS pandemic, which not only facilitates the spread of tuberculosis but, by its associated stigma, leads to delayed treatment seeking and poor adherence to therapy. In recent times, emphasis has moved away from didactic principles of tuberculosis “control” to community-and patient-centered health services, based on analysis of local factors affecting case finding and adherence to therapy.

Estimating infectious diseases incidence: validity of capture–recapture analysis and truncated models for incomplete count data

Capture-recapture analysis has been used to evaluate infectious disease surveillance. Violation of the underlying assumptions can jeopardize the validity of the capture-recapture estimates and a tool is needed for cross-validation. We re-examined 19 datasets of log-linear model capture-recapture studies on infectious disease incidence using three truncated models for incomplete count data as alternative population estimators. The truncated models yield comparable estimates to independent log-linear capture-recapture models and to parsimonious log-linear models when the number of patients is limited, or the ratio between patients registered once and twice is between 0.5 and 1.5. Compared to saturated log-linear models the truncated models produce considerably lower and often more plausible estimates. We conclude that for estimating infectious disease incidence independent and parsimonious three-source log-linear capture-recapture models are preferable but truncated models can be used as a heuristic tool to identify possible failure in log-linear models, especially when saturated log-linear models are selected.

Increasing antituberculosis drug resistance in the United Kingdom: analysis of National Surveillance Data.

Objective To identify recent trends in, and factors associated with, resistance to antituberculosis drugs in England, Wales, and Northern Ireland. Design Cohort of tuberculosis cases reported to the enhanced tuberculosis surveillance system matched to data on drug susceptibility and national strain typing data. Setting England, Wales, and Northern Ireland 1998-2005. Main outcome measures Unadjusted and adjusted odds ratios for drug resistance and associated factors. Proportion of multidrug resistant tuberculosis cases clustered. Results 28 620 culture confirmed cases were available for analysis. The proportion of cases resistant to isoniazid increased from 5% to 7%. Rifampicin resistance increased from 1.0% to 1.2% and multidrug resistance from 0.8% to 0.9%. Ethambutol and pyrazinamide resistance remained stable at around 0.4% and 0.6%, respectively. Regression analyses showed a significant increase in isoniazid resistance outside London (odds ratio 1.04, 95% confidence interval 1.01 to 1.07, a year, associated with changes in age (0.98, 0.98 to 0.99, a year), place of birth (1.49, 1.16 to 1.92), and ethnicity (P<0.05). In London, the rise (1.05, 1.02 to 1.08, a year) was related mainly to an ongoing outbreak. Increases in rifampicin resistance (1.06, 1.01 to 1.11, a year) and multidrug resistance (1.06, 1.00 to 1.12, a year) were small. A fifth of patients with multidrug resistant tuberculosis in 2004-5 had indistinguishable strain types, and one case was identified as extensively drug resistant. Conclusions The rise in isoniazid resistance reflects increasing numbers of patients from sub-Saharan Africa and the Indian subcontinent, who might have acquired resistance abroad, and inadequate control of transmission in London. The observed increases highlight the need for early case detection, rapid testing of susceptibility to drugs, and improved treatment completion.

Tuberculosis and social exclusion.

Developed countries need new strategies for controlling tuberculosis

Record-linkage and capture-recapture analysis to estimate the incidence and completeness of reporting of tuberculosis in England 1999-2002.

In 1999 the Enhanced Tuberculosis Surveillance (ETS) system was introduced in the United Kingdom to strengthen surveillance of tuberculosis (TB). The aim of this study was to assess the use of record-linkage and capture-recapture methodology for estimating the completeness of TB reporting in England between 1999 and 2002. Due to the size of the TB data sources sophisticated record-linkage software was required and the proportion of false-positive cases among unlinked hospital-derived TB records was estimated through a population mixture model. This study showed that record-linkage of TB data sources and cross-validation with additional TB-related datasets improved data quality as well as case ascertainment. Since the introduction of ETS observed completeness of notification in England has increased and the results were consistent with expected levels of under-notification. Completeness of notification estimated by a log-linear capture-recapture model was highly inconsistent with prior estimates and the validity of this methodology was further examined.

No increase in human cases of Mycobacterium bovis disease despite resurgence of infections in cattle in the United Kingdom

A resurgence of Mycobacterium bovis infections in cattle in the United Kingdom since the 1980s has raised concern about risks to human health. Enhanced surveillance data for England, Wales and Northern Ireland between 1993 and 2003 of culture-positive human M. bovis cases identified 315 M. bovis infections; the mean annual number of cases was 28 (range 12-41). The most frequently reported exposures were consumption of unpasteurized dairy products 41/83 (49%) and exposure to cattle 45/123 (37%). Of all cases, 249 (83%) were born before 1960. Of 50 cases born after 1960, only 14 were born in the United Kingdom. Over the same time period the annual number of new herd infections increased from 332 to 1749 as derived from the UK State Veterinary Service database. In conclusion, despite a more than fivefold increase in cattle herd infections during the 1990s, there was no increase in reported human cases.

HIV prevalence and testing practices among tuberculosis cases in London - A missed opportunity for HIV diagnosis?

Background: Universal testing for HIV in patients with tuberculosis (TB) has been advocated for over a decade. The aim of this study was to describe the prevalence and testing practices of HIV in TB centres in London. Methods: A cohort study was undertaken of all patients with TB in Greater London in 2003–4 (n = 1941). Logistic regression was used to assess factors affecting being offered and accepting testing and having a positive HIV result. Results: The overall known prevalence of HIV was 9.9% (193/1941). In those with a test result (including those diagnosed previously) it was 25.6%. Overall, 50.8% of patients aged ⩾20 years without previous testing were offered HIV testing and, of these, 73% accepted. In multivariable analysis, factors associated with being HIV positive were age 20–49 years, black ethnicity and being born overseas. Those with smear-negative disease and with a poor understanding of English were significantly less likely to be offered HIV testing. Factors associated with refusal of an offered test were female gender or age >49 years. HIV status was not associated with smear status, drug resistance or death, but was associated with CNS disease (OR 1.8, 95% CI 1.0 to 3.0, p = 0.003). Conclusions: Nearly half the patients with TB in London in 2003–4 were not offered HIV testing. In those offered testing, uptake was high. Patients in higher risk groups were more likely to be offered testing but, even within the highest risk groups, testing was not universally offered. This represents a missed opportunity for diagnosing HIV in patients with TB in London.