Judith R. Glynn

Worldwide Occurrence of Beijing/W Strains of Mycobacterium tuberculosis: A Systematic Review

Strains of the Beijing/W genotype family of Mycobacterium tuberculosis have caused large outbreaks of tuberculosis, sometimes involving multidrug resistance. This genetically highly conserved family of M. tuberculosis strains predominates in some geographic areas. We have conducted a systematic review of the published reports on these strains to determine their worldwide distribution, spread, and association with drug resistance. Sixteen studies reported prevalence of Beijing strains defined by spoligotyping; another 10 used other definitions. Beijing strains were most prevalent in Asia but were found worldwide. Associations with drug resistance varied: in New York, Cuba, Estonia, and Vietnam, Beijing strains were strongly associated with drug resistance, but elsewhere the association was weak or absent. Although few reports have measured trends in prevalence, the ubiquity of the Beijing strains and their frequent association with outbreaks and drug resistance underline their importance.

Why do young women have a much higher prevalence of HIV than young men? A study in Kisumu, Kenya and Ndola, Zambia

Objective: To examine the factors responsible for the disparity in HIV prevalence between young men and women in two urban populations in Africa with high HIV prevalence. Design: Cross-sectional survey, aiming to include 1000 men and 1000 women aged 15-49 years in Kisumu, Kenya and Ndola, Zambia. Methods: Participants were interviewed and tested for HIV and other sexually transmitted infections. Analyses compared the marital and non-marital partnership patterns in young men and women, and estimated the likelihood of having an HIV-infected partner. Results: Overall, 26% of individuals in Kisumu and 28% in Ndola were HIV-positive. In both sites, HIV prevalence in women was six times that in men among sexually active 15-19 year olds, three times that in men among 20-24 year olds, and equal to that in men among 25-49 year olds. Age at sexual debut was similar in men and women, and men had more partners than women. Women married younger than men and marriage was a risk factor for HIV, but the disparity in HIV prevalence was present in both married and unmarried individuals. Women often had older partners, and men rarely had partners much older than themselves. Nevertheless, the estimated prevalence of HIV in the partners of unmarried men aged under 20 was as high as that for unmarried women. HIV prevalence was very high even among women reporting one lifetime partner and few episodes of sexual intercourse. Conclusions: Behavioural factors could not fully explain the discrepancy in HIV prevalence between men and women. Despite the tendency for women to have older partners, young men were at least as likely to encounter an HIV-infected partner as young women. It is likely that the greater susceptibility of women to HIV infection is an important factor both in explaining the male-female discrepancy in HIV prevalence and in driving the epidemic. Herpes simplex virus type 2 infection, which is more prevalent in young women than in young men, is probably one of the factors that increases womens susceptibility to HIV infection.

HIV-1 and recurrence, relapse, and reinfection of tuberculosis after cure: a cohort study in South African mineworkers

BACKGROUND The proportion of recurrent tuberculosis cases attributable to relapse or reinfection and the risk factors associated with these different mechanisms are poorly understood. We followed up a cohort of 326 South African mineworkers, who had successfully completed treatment for pulmonary tuberculosis in 1995, to determine the rate and mechanisms of recurrence. METHODS Patients were examined 3 and 6 months after cure, and then were monitored by the routine tuberculosis surveillance system until December, 1998. IS6110 DNA fingerprints from initial and subsequent episodes of tuberculosis were compared to determine whether recurrence was due to relapse or reinfection All patients gave consent for HIV-1 testing. FINDINGS During follow-up (median 25.1 months, IQR 13.2-33.4), 65 patients (20%) had a recurrent episode of tuberculosis, a recurrence rate of 10.3 episodes per 100 person-years at risk (PYAR)-16.0 per 100 pyar in HIV-1-positive patients and 6.4 per 100 pyar in HIV-1-negative patients. Paired DNA fingerprints were available in 39 of 65 recurrences: 25 pairs were identical (relapse) and 14 were different (reinfection). 93% (13/14) of recurrences within the first 6 months were attributable to relapse compared with 48% (12/25) of later recurrences. HIV-1 infection was a risk factor for recurrence (hazard ratio 2.4, 95% CI 1.5-4.0), due to its strong association with disease caused by reinfection (18.7 2.4-143), but not relapse (0.58; 0.24-1.4). Residual cavitation and increasing years of employment at the mine were risk factors for relapse. INTERPRETATION In a setting with a high risk of tuberculous infection, HIV-1 increases the risk of recurrent tuberculosis because of an increased risk of reinfection. Interventions to prevent recurrent disease, such as lifelong chemoprophylaxis in HIV-1-positive tuberculosis patients, should be further assessed.

How Soon after Infection with HIV Does the Risk of Tuberculosis Start to Increase? A Retrospective Cohort Study in South African Gold Miners

BACKGROUND Infection with human immunodeficiency virus (HIV) increases the risk of tuberculosis (TB), but no study has assessed how this risk changes with time since HIV seroconversion. METHODS The incidence of pulmonary TB was estimated in miners with and those without HIV infection in a retrospective cohort study. HIV test results were linked to routinely collected TB, demographic, and occupational data. The rate ratio (RR) for the association between HIV status and TB was estimated by time since HIV seroconversion, calendar period, and age. RESULTS Of the 23,874 miners in the cohort, 17,766 were HIV negative on entry, 3371 were HIV positive on entry, and 2737 seroconverted during follow-up (1962 had a seroconversion interval of < or =2 years). A total of 740 cases of TB were analyzed. The incidence of TB increased with time since seroconversion, calendar period, and age. TB incidence was 2.90 cases/100 person-years at risk (pyar) in HIV-positive miners and was 0.80 cases/100 pyar in HIV-negative miners (adjusted RR, 2.9 [95% confidence interval {CI}, 2.5-3.4]). TB incidence doubled within the first year of HIV infection (adjusted RR, 2.1 [95% CI, 1.4-3.1]), with a further slight increase in HIV-positive miners for longer periods, up to 7 years. CONCLUSION The increase in the risk of TB so soon after infection with HIV was unexpected. Current predictive models of TB incidence underestimate the effect of HIV infection in areas where TB is endemic.

Population-level effect of HIV on adult mortality and early evidence of reversal after introduction of antiretroviral therapy in Malawi

Summary Background Malawi, which has about 80 000 deaths from AIDS every year, made free antiretroviral therapy available to more than 80 000 patients between 2004 and 2006. We aimed to investigate mortality in a population before and after the introduction of free antiretroviral therapy, and therefore to assess the effects of such programmes on survival at the population level. Methods We used a demographic surveillance system to measure mortality in a population of 32 000 in northern Malawi, from August, 2002, when free antiretroviral therapy was not available in the study district, until February, 2006, 8 months after a clinic opened. Causes of death were established through verbal autopsies (retrospective interviews). Patients who registered for antiretroviral therapy at the clinic were identified and linked to the population under surveillance. Trends in mortality were analysed by age, sex, cause of death, and zone of residence. Findings Before antiretroviral therapy became available in June, 2005, mortality in adults (aged 15–59 years) was 9·8 deaths for 1000 person-years of observation (95% CI 8·9–10·9). The probability of dying between the ages of 15 and 60 years was 43% (39–49) for men and 43% (38–47) for women; 229 of 352 deaths (65·1%) were attributed to AIDS. 8 months after the clinic that provided antiretroviral therapy opened, 107 adults from the study population had accessed treatment, out of an estimated 334 in need of treatment. Overall mortality in adults had decreased by 10% from 10·2 to 8·7 deaths for 1000 person-years of observation (adjusted rate ratio 0·90, 95% CI 0·70–1·14). Mortality was reduced by 35% (adjusted rate ratio 0·65, 0·46–0·92) in adults near the main road, where mortality before antiretroviral therapy was highest (from 13·2 to 8·5 deaths per 1000 person-years of observation before and after antiretroviral therapy). Mortality in adults aged 60 years or older did not change. Interpretation Our findings of a reduction in mortality in adults aged between 15 and 59 years, with no change in those older than 60 years, suggests that deaths from AIDS were averted by the rapid scale-up of free antiretroviral therapy in rural Malawi, which led to a decline in adult mortality that was detectable at the population level. Funding Wellcome Trust and British Leprosy Relief Association.

Educational attainment and HIV‐1 infection in developing countries: a systematic review

OBJECTIVES  To assess whether educational status is associated with HIV‐1 infection in developing countries by conducting a systematic review of published literature.

Systematic review exploring time trends in the association between educational attainment and risk of HIV infection in sub-Saharan Africa.

Objective:To assess the evidence that the association between educational attainment and risk of HIV infection is changing over time in sub-Saharan Africa. Design and methods:Systematic review of published peer-reviewed articles. Articles were identified that reported original data comparing individually measured educational attainment and HIV status among at least 300 individuals representative of the general population of countries or regions of sub-Saharan Africa. Statistical analyses were required to adjust for potential confounders but not over-adjust for variables on the causal pathway. Results:Approximately 4000 abstracts and 1200 full papers were reviewed. Thirty-six articles were included in the study, containing data on 72 discrete populations from 11 countries between 1987 and 2003, representing over 200 000 individuals. Studies on data collected prior to 1996 generally found either no association or the highest risk of HIV infection among the most educated. Studies conducted from 1996 onwards were more likely to find a lower risk of HIV infection among the most educated. Where data over time were available, HIV prevalence fell more consistently among highly educated groups than among less educated groups, in whom HIV prevalence sometimes rose while overall population prevalence was falling. In several populations, associations suggesting greater HIV risk in the more educated at earlier time points were replaced by weaker associations later. Discussion:HIV infections appear to be shifting towards higher prevalence among the least educated in sub-Saharan Africa, reversing previous patterns. Policy responses that ensure HIV-prevention measures reach all strata of society and increase education levels are urgently needed.

Definition of the Beijing/W Lineage of Mycobacterium tuberculosis on the Basis of Genetic Markers

ABSTRACT Mycobacterium tuberculosis Beijing genotype strains are highly prevalent in Asian countries and in the territory of the former Soviet Union. They are increasingly reported in other areas of the world and are frequently associated with tuberculosis outbreaks and drug resistance. Beijing genotype strains, including W strains, have been characterized by their highly similar multicopy IS6110 restriction fragment length polymorphism (RFLP) patterns, deletion of spacers 1 to 34 in the direct repeat region (Beijing spoligotype), and insertion of IS6110 in the genomic dnaA-dnaN locus. In this study the suitability and comparability of these three genetic markers to identify members of the Beijing lineage were evaluated. In a well-characterized collection of 1,020 M. tuberculosis isolates representative of the IS6110 RFLP genotypes found in The Netherlands, strains of two clades had spoligotypes characteristic of the Beijing lineage. A set of 19 Beijing reference RFLP patterns was selected to retrieve all Beijing strains from the Dutch database. These reference patterns gave a sensitivity of 98.1% and a specificity of 99.7% for identifying Beijing strains (defined by spoligotyping) in an international database of 1,084 strains. The usefulness of the reference patterns was also assessed with large DNA fingerprint databases in two other European countries and for identification strains from the W lineage found in the United States. A standardized definition for the identification of M. tuberculosis strains belonging to the Beijing/W lineage, as described in this work, will facilitate further studies on the spread and characterization of this widespread genotype family of M. tuberculosis strains.

Profile: The Karonga health and demographic surveillance system

The Karonga Health and Demographic Surveillance System (Karonga HDSS) in northern Malawi currently has a population of more than 35 000 individuals under continuous demographic surveillance since completion of a baseline census (2002–2004). The surveillance system collects data on vital events and migration for individuals and for households. It also provides data on cause-specific mortality obtained by verbal autopsy for all age groups, and estimates rates of disease for specific presentations via linkage to clinical facility data. The Karonga HDSS provides a structure for surveys of socio-economic status, HIV sero-prevalence and incidence, sexual behaviour, fertility intentions and a sampling frame for other studies, as well as evaluating the impact of interventions, such as antiretroviral therapy and vaccination programmes. Uniquely, it relies on a network of village informants to report vital events and household moves, and furthermore is linked to an archive of biological samples and data from population surveys and other studies dating back three decades.

Vaccine Effectiveness Estimates, 2004–2005 Mumps Outbreak, England

As vaccinated children approach adolescence, immunity wanes, which may contribute to outbreaks.