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Biomedical subjects

Judith R Glynn

Publications and source records attributed to Judith R Glynn.

At least 19 recordsLinked to original sources
PubMed2006

Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies.

OBJECTIVE: To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection. BACKGROUND: The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women. DESIGN: Systematic review and meta-analysis of longitudinal studies. METHODS: PubMed, Embase and relevant conference abstracts were systematically searched to identify longitudinal studies in which the relative timing of HSV-2 infection and HIV infection could be established. Where necessary, authors were contacted for separate estimates in men and women, adjusted for age and a measure of sexual behaviour. Summary adjusted RR were calculated using random-effects meta-analyses where appropriate. Studies on recent HSV-2 incidence as a risk factor for HIV acquisition were also collated. RESULTS: Of 19 eligible studies identified, 18 adjusted for age and at least one measure of sexual behaviour after author contact. Among these, HSV-2 seropositivity was a statistically significant risk factor for HIV acquisition in general population studies of men [summary adjusted RR, 2.7; 95% confidence interval (CI), 1.9-3.9] and women (RR, 3.1; 95% CI, 1.7-5.6), and among men who have sex with men (RR, 1.7; 95% CI, 1.2-2.4). The effect in high-risk women showed significant heterogeneity, with no overall evidence of an association. CONCLUSIONS: Prevalent HSV-2 infection is associated with a three-fold increased risk of HIV acquisition among both men and women in the general population, suggesting that, in areas of high HSV-2 prevalence, a high proportion of HIV is attributable to HSV-2.

Female↗
PubMed2006

Emergence of a three codon deletion in gag p17 in HIV type 1 subtype C long-term survivors, and general population spread.

In a population-based study in northern Malawi we investigated HIV-1 subtype C gag and env gene sequences associated with long-term survival. DNA samples were available from 31 individuals surviving between population surveys carried out in the 1980s and 1990s. Most survivors with paired sequences dating from the 1980s and the 1990s had a three codon deletion in the gag p17 region of the sequence retrieved from the sample collected in the 1990s that was not present in the sequence from the same individual dating from the 1980s. This deletion was also not present in any other 1980s sequences from Malawi, but was common in samples collected in Malawi in the 1990s. The deletion is equivalent to the loss of three amino acids in the D helix region of the gag protein, and may be associated with longer survival and onward transmission.

Amino Acid Sequence↗
PubMed2006

Tuberculosis transmission attributable to close contacts and HIV status, Malawi.

We conducted the first molecular study of tuberculosis (TB) to estimate the role of household contact and transmission from HIV-positive putative source contacts (PSCs) in a high HIV-prevalence area. TB patients in a long-term population-based study in Malawi were asked about past contact with TB. DNA fingerprinting was used to define clusters of cases with identical strains. Among 143 epidemiologically defined PSC-case pairs, fingerprinting confirmed transmission for 44% of household and family contacts and 18% of other contacts. Transmission was less likely to be confirmed if the PSC were HIV positive than if he or she was HIV negative (odds ratio 0.32, 95% confidence interval [CI] 0.14-0.74). Overall, epidemiologic links were found for 11% of 754 fingerprint-clustered cases. We estimate that 9%-13% of TB cases were attributable to recent transmission from identifiable close contacts and that nearly half of the TB cases arising from recent infection had acquired the infection from HIV-positive patients.

AIDS-Related Opportunistic Infections↗
PubMed2006

BCG vaccine effectiveness against Buruli ulcer: a case-control study in Benin.

BCG remains the only possible prophylactic intervention against Buruli ulcer (BU). Estimating its public health impact on BU control is an important issue. We conducted a case-control study to investigate the vaccine effectiveness of routine BCG vaccine against BU in southern Benin. From August 2002 to August 2003, BCG vaccination status was obtained for 279 clinically diagnosed BU cases and 988 age- and sex-matched neighborhood controls. BCG coverage, which was estimated by the presence of a scar or a vaccination record, was 64.5% in cases and 67.2% in controls. There was no evidence of a protective effect of routine BCG vaccination against BU in southern Benin (vaccine effectiveness adjusted for socioeconomic status = 12%, 95% confidence interval = -24% to 37%).

Adolescent↗
PubMed2005

Effect of HIV on work-related injury rates in South African gold miners.

OBJECTIVE: Work-related injuries have severe, well-documented economic and social impacts, and injury is a leading cause of death in working adults. As adults of working age are one of the groups most affected by the HIV epidemic, the interaction between work-related injuries and HIV is important. The objective was to calculate the effect of HIV on the rate and severity of work-related injuries by duration of infection. DESIGN AND METHODS: A large, retrospective seroincident cohort of South African gold miners was studied. Data routinely collected by the mines, and assurance company injury data were analysed. HIV-positive and negative miners were compared, allowing the calculation of injury rates and rate ratios. Severity of injuries was measured by the number of days away from work, percentage of permanent disability, and fatalities. RESULTS: Results were available for 1661 HIV-positive and 6166 HIV-negative miners over 10 years. HIV infection increased the rate of work-related injuries overall (adjusted rate ratio, 1.3; 95% confidence interval, 1.1-1.4), but had less effect on severe injuries. Injury rates in HIV-positive men prior to the first positive test were similar to those in HIV-negative men. The injury rate rose soon after the first HIV positive test. After seroconversion there was only weak evidence of an increase in injury rates by duration of infection. CONCLUSION: This is the first study to demonstrate an increase in injury rates in HIV-positive individuals. The increase may reflect direct effects of HIV infection as well as behaviour change once HIV is diagnosed.

Adult↗
PubMed2005

The importance of recent infection with Mycobacterium tuberculosis in an area with high HIV prevalence: a long-term molecular epidemiological study in Northern Malawi.

BACKGROUND: The proportion of cases of tuberculosis due to recent infection can be estimated in long-term population-based studies using molecular techniques. Here, we present what is, to our knowledge, the first such study in an area with high human immunodeficiency virus (HIV) prevalence. METHODS: All patients with tuberculosis in Karonga District, Malawi, were interviewed. Isolates were genotyped using restriction-fragment-length polymorphism (RFLP) patterns. Strains were considered to be "clustered" if at least 1 other patient had an isolate with an identical pattern. RESULTS: RFLP results were available from 83% of culture-positive patients from late 1995 to early 2003. When strains with <5 bands were excluded, 72% (682/948) were clustered. Maximum clustering was reached using a 4-year window, with an estimated two-thirds of cases due to recent transmission. The proportion clustered decreased with age and varied by area of residence. In older adults, clustering was less common in men and more common in patients who were HIV positive (adjusted odds ratio, 5.1 [95% confidence interval, 2.1-12.6]). CONCLUSIONS: The proportion clustered found in the present study was among the highest in the world, suggesting high rates of recent transmission. The association with HIV infection in older adults may suggest that HIV has a greater impact on disease caused by recent transmission than on that caused by reactivation.

AIDS-Related Opportunistic Infections↗
PubMed2005

Mycobacterium tuberculosis Beijing genotype, northern Malawi.

In a 7-year population-based study in Malawi, we showed that Beijing genotype tuberculosis (TB) increased as a proportion of TB cases. All the Beijing genotype strains were fully drug sensitive. Contact histories, TB type, and case-fatality rates were similar for Beijing and non-Beijing genotype TB.

Adolescent↗
PubMed2004

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.

AIDS-Related Opportunistic Infections↗
PubMed2004

Factors affecting HIV concordancy in married couples in four African cities.

OBJECTIVE: To determine risk factors for HIV transmission within married couples in four urban populations in sub-Saharan Africa. METHODS: Data from a cross-sectional population-based study were used. Representative random samples approximating 1000 men and 1000 women in each of four cities of Kisumu (Kenya), Ndola (Zambia), Cotonou (Benin), and Yaoundé (Cameroon), were interviewed and tested for sexually transmitted infections (STI). Married couples were identified as concordant negative, discordant, or concordant positive for each STI. After excluding concordant HIV negative couples, analysis of behavioural and STI risk factors for HIV positive concordancy was undertaken across the four cities and in each city separately where sample size allowed. RESULTS: Among 221 couples in which at least one member was HIV positive, we found that the only significant risk factor for positive HIV concordancy was herpes simplex type 2 (HSV-2) status. After adjusting for age and city of residence the odds ratio for HIV concordancy compared to couples with neither spouse HSV-2 positive was 3.4 (95% confidence interval, 0.62-18.4) for couples with one partner HSV-2 positive and 8.6 (95% confidence interval, 1.6-45.0) for couples with both partners HSV-2 positive. The same trends were seen in Kisumu and Ndola when they were analysed separately (numbers were small in the other cities). CONCLUSIONS: Although cross-sectional studies are not ideal for delineating the sequence of transmission events, this study adds to the evidence that HSV-2 is a key risk factor in promoting HIV transmission.

Adolescent↗
PubMed2004

DNA fingerprint changes in tuberculosis: reinfection, evolution, or laboratory error?

BACKGROUND: DNA fingerprint patterns of Mycobacterium tuberculosis strains vary within individuals and between epidemiologically linked individuals because of pattern evolution, new infections, and laboratory error. We explored the importance of these factors. METHODS: Cultures from individuals in northern Malawi who had been diagnosed with tuberculosis (TB) during 1996-2001 were fingerprinted with restriction fragment-length polymorphism (RFLP). Probable laboratory error was inferred by use of dates or isolated positive cultures. Pattern evolution was explored within and between individuals, and the relative importance of relapse and reinfection was estimated in individuals with recurrent TB. RESULTS: RFLP results were available for 930 isolates from 806 individuals. The maximum laboratory-error rate was 3.9%. Pattern evolution was more common in linked individuals (17%) than on relapse (11%) or during treatment (3%). Twenty individuals had recurrent TB after completing treatment: in human immunodeficiency virus (HIV)-positive individuals, 7 of 12 recurrences were due to reinfection, compared with 0 of 8 in HIV-negative individuals (P=.01). CONCLUSIONS: The rate of DNA fingerprint-pattern evolution is not linear, and rates of change calculated from repeat cultures within individuals may not be applicable to transmission between individuals. The high proportion of recurrence due to reinfection found in HIV-positive individuals suggests that secondary prophylaxis and/or antiretroviral treatments are needed for such individuals.

Adolescent↗
PubMed2004

Trends in tuberculosis and the influence of HIV infection in northern Malawi, 1988-2001.

OBJECTIVE: To document the changing incidence and patterns of tuberculosis (TB) in rural Africa and the extent to which they are influenced by HIV. METHODS: As part of longstanding epidemiological studies in Karonga District, Malawi, a series of case control studies of TB and HIV were conducted from 1988 onwards. Data from these studies, from a total population survey, and from the Malawi national census have been used to reconstruct the changes in the TB epidemic in the area from 1988 to 2001, examining the role of HIV. RESULTS: The incidence of all confirmed TB, and of new smear-positive TB, in adults increased to peak in the late 1990s but appears to have decreased since. Two-thirds of cases are now HIV positive. The rise in incidence was greatest in the 30-44-year-old age group and was particularly marked for women, leading to a decrease in the male : female ratio for TB incidence from 1.3 to 0.8. The proportion of new smear-positive TB cases attributable to HIV increased from 17% in 1988-1990 to 57% in 2000-2001, but the estimated rate of smear-positive TB in the absence of HIV decreased from 0.78/1000 to 0.45/1000. CONCLUSIONS: Without HIV the incidence of smear-positive TB would have fallen in this population. Instead it has risen and is predominantly affecting young adults and women. There is some evidence that the HIV-associated TB epidemic may have passed its peak.

AIDS-Related Opportunistic Infections↗
PubMed2004

HIV and pulmonary tuberculosis: the impact goes beyond those infected with HIV.

BACKGROUND: HIV infection increases the risk of tuberculosis. The HIV epidemic is also likely to have an indirect effect on the incidence of tuberculosis because of the increased number of infectious individuals in the population. This should be apparent as an increase in tuberculosis among HIV-negative individuals, but this has not previously been demonstrated directly. METHODS: A retrospective cohort study was conducted in four gold mines in South Africa, including all miners who had HIV tests in 1991-1997. Tuberculosis was detected by annual screening, contact tracing and self-presentation of symptomatic patients. RESULTS: The annual incidence of new pulmonary tuberculosis in the mines rose from 0.53% in 1991 to 1.0% in 1997. The HIV status was known for 23 874 miners, of whom 3371 were HIV positive on entry and 2737 seroconverted during follow-up. The incidence of tuberculosis was higher among HIV-positive miners than HIV-negative miners from 1992 onwards, and the proportion of tuberculosis attributable to HIV increased from 0% in 1991 to over 40%. The incidence of tuberculosis increased in HIV-negative miners from 1995 onwards; incidence in the late 1990s was double that in the early 1990s. CONCLUSION: HIV infection has dramatically increased the incidence of tuberculosis. There was a direct increase in those who were HIV infected, but also a doubling in tuberculosis incidence in those remaining HIV negative, implying considerable ongoing Mycobacterium tuberculosis transmission. This has occurred despite active case finding and directly observed therapy, which exceeds WHO targets for cure rates. Further interventions targeted at both HIV and tuberculosis are needed.

AIDS-Related Opportunistic Infections↗
PubMed2004

Does increased general schooling protect against HIV infection? A study in four African cities.

BACKGROUND: The association between educational attainment and risk of HIV infection varies between populations and over time. Earlier studies in sub-Saharan Africa have found that those with more education are at increased risk of HIV infection. METHODS: We investigated the associations between general schooling and both HIV and herpes simplex-2 (HSV-2) infection using data from the multicentre study on factors determining the differential spread of HIV in four African cities. Cross-sectional general population studies were conducted in 1997-1998 in Cotonou (Benin), Yaoundé (Cameroon), Kisumu (Kenya), and Ndola (Zambia), including about 2000 adults in each city. RESULTS: There was no association between schooling and HIV infection in men or women in Kisumu or Ndola. Women in Yaoundé and men in Cotonou, with more schooling, were less likely to be HIV positive. These associations persisted after adjusting for sociodemographic factors. Similar trends in men in Yaoundé and women in Cotonou were not statistically significant. Increased schooling was associated with significantly decreased risk of HSV-2 infection in women in Kisumu and Ndola and men in Cotonou. In all the cities those with more education tended to report less risky sexual behaviour. CONCLUSIONS: There was no evidence of an increased risk of HIV infection associated with education as seen in earlier studies. In each city there was some evidence of lower HIV or HSV-2 infection rates and less risky sexual behaviour associated with increased education levels. The most educated may be responding more readily to health education programmes. The challenge is to extend this to the rest of the population.

Adolescent↗
PubMed2004

Performance of commercially available enzyme immunoassays for detection of antibodies against herpes simplex virus type 2 in African populations.

Data are accumulating on the performance of enzyme immunoassays (EIAs) for the detection of herpes simplex virus type 2 (HSV-2) infection in North America and Europe, but little is known about their performance in other populations. Nine test kits were evaluated with 330 serum samples from sub-Saharan Africa. The tests were first compared to the monoclonal antibody (MAb) EIA (Central Public Health Laboratory, London, United Kingdom). Samples that gave discordant results in the MAb EIA and in the three tests that performed best compared to the MAb EIA were tested by Western blotting (University of Washington, Seattle). A random sample of concordant samples was also tested, and the sensitivities and specificities of the different tests were calculated, taking into account this sampling strategy. The sensitivities of the tests ranged from 86 to 100%; the specificities ranged from 47 to 99%. The tests that performed best were the Gull Premier EIA (sensitivity, 86.3%; specificity, 97.6%) and the Kalon Biological (sensitivity, 92.3%; specificity, 97.7%) and Biokit (sensitivity, 86.7%; specificity, 92.6%) tests. It cannot be assumed that enzyme immunoassays for the detection of HSV-2 infection that perform well in industrialized countries will perform equally well in other populations.

Adolescent↗
PubMed2004

Definition of the Beijing/W lineage of Mycobacterium tuberculosis on the basis of genetic markers.

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.

China↗
PubMed2004

Timing and reconstruction of the most recent common ancestor of the subtype C clade of human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) subtype C is responsible for more than 55% of HIV-1 infections worldwide. When this subtype first emerged is unknown. We have analyzed all available gag (p17 and p24) and env (C2-V3) subtype C sequences with known sampling dates, which ranged from 1983 to 2000. The majority of these sequences come from the Karonga District in Malawi and include some of the earliest known subtype C sequences. Linear regression analyses of sequence divergence estimates (with four different approaches) were plotted against sample year to estimate the year in which there was zero divergence from the reconstructed ancestral sequence. Here we suggest that the most recent common ancestor of subtype C appeared in the mid- to late 1960s. Sensitivity analyses, by which possible biases due to oversampling from one district were explored, gave very similar estimates.

Evolution, Molecular↗
PubMed2004

Cotrimoxazole prophylaxis reduces mortality in human immunodeficiency virus-positive tuberculosis patients in Karonga District, Malawi.

OBJECTIVE: To estimate the impact of cotrimoxazole prophylaxis on the survival of human immunodeficiency virus (HIV)-positive tuberculosis (TB) patients. METHODS: A cohort study with a historical comparison group was conducted. End-of-treatment outcomes and 18-month survival were compared between TB patients registered in 1999 and patients registered in 2000 in Karonga District, Malawi. Case ascertainment, treatment and outpatient follow-up were identical in the two years except that in 2000 cotrimoxazole prophylaxis was offered to HIV-positive patients in addition to routine care. The prophylaxis was provided from the time a patient was identified as HIV-positive until 12 months after registration. Analyses were carried out on an intention-to-treat basis for all TB patients, and also separately by HIV status, TB type and certainty of diagnosis. FINDINGS: 355 and 362 TB patients were registered in 1999 and 2000, respectively; 70% were HIV-positive. The overall case fatality rate fell from 37% to 29%, i.e. for every 12.5 TB patients treated, one death was averted. Case fatality rates were unchanged between the two years in HIV-negative patients, but fell in HIV-positive patients from 43% to 24%. The improved survival became apparent after the first 2 months and was maintained beyond the end of treatment. The improvement was most marked in patients with smear-positive TB and others with confirmed TB diagnoses. CONCLUSION: Survival of HIV-positive TB patients improved dramatically with the addition of cotrimoxazole prophylaxis to the treatment regimen. The improvement can be attributed to cotrimoxazole because other factors were unchanged and the survival of HIV-negative patients was not improved. Cotrimoxazole prophylaxis should therefore be added to the routine care of HIV-positive TB patients.

AIDS-Related Opportunistic Infections↗