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Biomedical subjects

P E Fine

Publications and source records attributed to P E Fine.

At least 19 recordsLinked to original sources
PubMed2001

The development of the HIV epidemic in Karonga District, Malawi.

OBJECTIVE: To investigate the prevalence and sociodemographic risk factors for HIV infection, during the early stages of the epidemic, in a rural area of northern Malawi. METHODS: As part of a community-based study of mycobacteria, socioeconomic data and HIV results are available on approximately 30,000 individuals from random population samples in 1981-1984 and 1987-1989 from a rural area of Malawi. These have been analysed to characterize the early stages of the HIV epidemic. RESULTS: The earliest HIV-positive specimens were collected in 1982. HIV prevalence in individuals aged 15-49 years was 0.1% in the early 1980s and 2.0% in the late 1980s. In the early 1980s, eight out of 11 HIV-positive individuals were new immigrants to the district or had recently returned there. In the late 1980s, immigration and having spent time outside the district continued to be major risk factors for HIV. HIV infection was more common in those with occupations other than subsistence farming, in those with more schooling, and in those in the best housing. The association with schooling was seen at all ages for both men and women. CONCLUSION: Immigration and travel were important in the repeated introduction and establishment of the HIV epidemic. The association with schooling is similar to that found elsewhere in Africa.

Adolescent↗
PubMed2001

Patterns and implications of naturally acquired immune responses to environmental and tuberculous mycobacterial antigens in northern Malawi.

Interferon (IFN)-gamma responsiveness to 12 purified protein derivative (PPD) and new tuberculin antigens from 9 species of mycobacteria was assessed, using a whole blood assay, in 616 young adults living in northern Malawi, where Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination provides no protection against pulmonary tuberculosis. The prevalence of IFN-gamma responsiveness was highest for PPDs of M. avium, M. intracellulare, and M. scrofulaceum (the MAIS complex). Correlations between responsiveness paralleled genetic relatedness of the mycobacterial species. A randomized, controlled trial was carried out, to assess the increase in IFN-gamma responsiveness to M. tuberculosis PPD that can be attributed to M. bovis BCG vaccination. The BCG-attributable increase in IFN-gamma response to M. tuberculosis PPD was greater for individuals with low initial responsiveness to MAIS antigens than for those with high initial responsiveness. Although not statistically significant, the trend is consistent with the hypothesis that prior exposure to environmental mycobacteria interferes with immune responses to BCG vaccination.

Antigens, Bacterial↗
PubMed2001

Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy.

More than 36000 individuals living in rural Malawi were skin tested with antigens derived from 12 different species of environmental mycobacteria. Most were simultaneously tested with RT23 tuberculin, and all were followed up for both tuberculosis and leprosy incidence. Skin test results indicated widespread sensitivity to the environmental antigens, in particular to Mycobacterium scrofulaceum, M. intracellulare and one strain of M. fortuitum. Individuals with evidence of exposure to 'fast growers' (i.e. with induration to antigens from fast growers which exceeded their sensitivity to tuberculin), but not those exposed to 'slow growers', were at reduced risk of contracting both tuberculosis and leprosy, compared to individuals whose indurations to the environmental antigen were less than that to tuberculin. This evidence for cross protection from natural exposure to certain environmental mycobacteria may explain geographic distributions of mycobacterial disease and has important implications for the mechanisms and measurement of protection by mycobacterial vaccines.

Adolescent↗
PubMed2001

BCG: the challenge continues.

It is widely recognized that BCG provides inconsistent and often inadequate protection against tuberculosis; however, simple estimates of efficacy fail to reflect the complexity of protection within, let alone between, populations. A decline in protection with an increase in age at vaccination has been seen in many studies. This may reflect 2 things: (i) that as people age they are exposed to a variety of mycobacterial challenges which may interfere with, or mask, the protection of BCG; and/or (ii) that the vaccine is better at protecting against primary disease than against either reactivation- or reinfection-type disease. These factors need to be taken into consideration when interpreting the results obtained with screening vaccines in animal models, as most of these models mimic acute primary-type disease. In addition, we have no evidence that the protection induced by BCG lasts for > 15 y, in any population. Recent data from South India indicate a complex interaction of age and time effects: BCG imparted consistent protection in children, but no protection for subjects > 15 y old, and may even have imparted negative protection among these older individuals. If true, these findings have important implications for efforts to develop a vaccine against adult pulmonary tuberculosis.

Adult↗
PubMed2001

The effect of age and study duration on the relationship between 'clustering' of DNA fingerprint patterns and the proportion of tuberculosis disease attributable to recent transmission.

Though it is recognized that the extent of 'clustering' of isolates from tuberculosis cases in a given population is related to the amount of disease attributable to recent transmission, the relationship between the two statistics is poorly understood. Given age-dependent risks of disease and the fact that a long study (e.g. spanning several years) is more likely to identify transmission-linked cases than a shorter study, both measures, and thus the relationship between them, probably depend strongly on the ages of the cases ascertained and study duration. The contribution of these factors is explored in this paper using an age-structured model which describes the introduction and transmission of M. tuberculosis strains with different DNA fingerprint patterns in The Netherlands during this century, assuming that the number of individuals contacted by each case varies between cases and that DNA fingerprint patterns change over time through random mutations, as observed in several studies. Model predictions of clustering in different age groups and over different time periods between 1993 and 1997 compare well against those observed. According to the model, the proportion of young cases with onset in a given time period who were 'clustered' underestimated the proportion of disease attributable to recent transmission in this age group (by up to 25% in males); for older individuals, clustering overestimated this proportion. These under- and overestimates decreased and increased respectively as the time period over which the cases were ascertained increased. These results have important implications for the interpretation of estimates of the proportion of disease attributable to recent transmission, based on 'clustering' statistics, as are being derived from studies of the molecular epidemiology of tuberculosis in many populations.

Adolescent↗
PubMed2001

Comparison of two versus three smears in identifying culture-positive tuberculosis patients in a rural African setting with high HIV prevalence.

SETTING: Karonga district, northern Malawi. OBJECTIVE: To compare the sensitivity and specificity of two versus three smears for the diagnosis of pulmonary tuberculosis in a setting with high HIV prevalence. DESIGN: A total of 1992 pulmonary tuberculosis suspects with three sputum smears taken over a 2-7 day period and at least one culture result were studied. Smears were auramine stained and examined using fluorescence microscopy, and positives were confirmed with Ziehl-Neelsen staining and light microscopy. Cultures were set up on Löwenstein-Jensen media. True negative and positive status was defined on the basis of culture. The sensitivity, specificity, and positive and negative predictive values of two and three smears were compared. RESULTS: Compared to culture, the sensitivity, specificity, and positive and negative predictive values of three smears were 70%, 98%, 92%, and 92%, respectively. Restriction to the first two smears gave similar results. Of those detected as smear-positive using three smears, at least 97% would have been detected by two. Among those with HIV serology results available, the sensitivity of two smears for detecting culture-positive tuberculosis was identical to that using three. CONCLUSION: In this setting, using fluorescence and light microscopy, collecting two smears rather than three would only marginally reduce sensitivity and would slightly improve the specificity of diagnosis of tuberculosis; this is unaffected by HIV status. The potential for improving specificity is important because of the costs of misdiagnosis. In practice, both sensitivity and specificity may be increased due to the time saved by examining two rather than three smears.

AIDS-Related Opportunistic Infections↗
PubMed2000

Lifetime risks, incubation period, and serial interval of tuberculosis.

The lifetime risk of developing disease, the incubation period, and the time period between infection and transmission (the serial interval) are three important measures for interpreting trends in tuberculous infection and disease but are complicated by strong age dependencies regarding disease risk and by the potential for reinfection to occur. By using a model of the epidemiology of tuberculosis in England and Wales, the authors demonstrated that all three measures changed dramatically during the 20th century largely as a result of declines in the risk of infection. The estimated lifetime risk was highest following infection in early adulthood and declined with year of infection; the age-weighted average was approximately 12% during the last 50 years. Incubation period distributions depend on whether they are viewed prospectively (from infection to disease onset) or retrospectively (since infection for cases with disease onset at a particular time). As children rarely develop infectious forms of tuberculosis, infections acquired in childhood are associated with considerably longer serial intervals than those acquired in adulthood. These unusual properties are probably shared by other infections with long intervals between infection and disease. The results are important for interpreting data on transmission patterns, as are now being derived from molecular epidemiologic studies.

Adult↗
PubMed2000

Whole blood assays for interferon-gamma: practicalities and potential for use as diagnostic tests in the field.

Recent years have seen the introduction of a number of whole-blood assays, in which unseparated heparinized blood is stimulated with antigen either overnight or for as long as 6 days, and cytokine production is measured in the plasma or supernatant. These assays have potential for use in the field as immunodiagnostic assays, as they require only a small blood sample and basic laboratory facilities. Use of these assays in a large study of the immunological effects of BCG vaccination in Malawi has shown that the diluted blood, 6-day whole-blood assays is robust, and can be used to assess T-cell responses to both crude and recombinant antigens. If used with antigens specific to Mycobacterium leprae, these assays could be used to measure exposure of M. leprae within communities or populations, or to aid the early diagnosis of leprosy.

Antigens, Bacterial↗
PubMed2000

Trends in antituberculosis drug resistance in Karonga District, Malawi, 1986-1998.

SETTING: Karonga District, Malawi. OBJECTIVES: To examine long term trends in initial and acquired resistance to antituberculosis drugs in a rural area of Africa. DESIGN: Monitoring of all patients with culture-confirmed tuberculosis 1986-1998. RESULTS: Initial drug resistance results were available for 1121 patients. The proportion resistant to any of the first line drugs (streptomycin, isoniazid, rifampicin or ethambutol) was 9.6%, and to isoniazid 7.2%. Initial resistance to at least isoniazid and rifampicin (multidrug resistance) was seen in only six patients. No initial resistance to ethambutol was found. There was no significant change in initial drug resistance over time. Overall, 22/120 (18%) patients with previous treatment were resistant to at least one drug; only one had multidrug resistance. Acquired resistance decreased over the period of the study. There were no associations between age, sex or human immunodeficiency virus (HIV) status and initial or acquired drug resistance. CONCLUSIONS: Changes in acquired resistance may reflect the recent performance of a control programme more quickly than those in initial resistance. It is encouraging that acquired resistance decreased and levels of multidrug resistance were low despite more than a decade of use of rifampicin. The lack of association between HIV and drug resistance confirms findings elsewhere in Africa.

Adult↗
PubMed2000

BCG scars in northern Malawi: sensitivity and repeatability of scar reading, and factors affecting scar size.

SETTING: Karonga district, northern Malawi. OBJECTIVE: To assess the sensitivity and repeatability of BCG scar reading, and factors affecting scar size. DESIGN: Follow-up of individuals aged > 3 months who were recruited into a BCG vaccine trial (1986-1989), and of infants vaccinated in health centres (1989-1991), who were examined for presence and size of BCG scars in subsequent years. All examinations were carried out blind of information on true vaccination status or the results of previous examinations. RESULTS: For trial individuals who were considered scar negative at recruitment and received BCG, the sensitivity of scar reading was > or = 93%, repeatability was > or = 94% for those < 60 years old at vaccination, and only around 1% were assessed as having > 1 BCG scar post-vaccination. For infants vaccinated when < 1 month old in health centres, the proportion who still had recognisable scars 4 years later was < 80%. Scars were larger in individuals with a prior BCG vaccination, and for those aged 15-59 at vaccination the scars were approximately 1 mm larger for males than for females. CONCLUSIONS: A BCG scar is a highly sensitive and repeatable indicator of vaccination status when the vaccine is properly handled, delivered appropriately, and given at over 3 months of age, but not for vaccinations given within 1 month of birth. Given that most vaccinations in the world are given soon after birth, this low sensitivity will lead to both vaccine coverage and vaccine efficacy being underestimated in studies in which vaccination status is inferred from the presence/absence of a distinctive BCG scar. Age-sex patterns identified for scar size show important similarities to those found with skin test responses to tuberculin.

Adolescent↗
PubMed1999

Transmissibility and persistence of oral polio vaccine viruses: implications for the global poliomyelitis eradication initiative.

The global poliomyelitis eradication initiative has been a tremendous success, with current evidence suggesting that wild poliovirus will cease to circulate anywhere in the world soon after the year 2000. As the goal of wild poliovirus eradication is approached, concern has been raised about the potential for persistent transmission of oral polio vaccine (OPV) viruses, as these viruses are known to revert toward wild-type neurovirulence. This paper has been extracted from a document prepared for the World Health Organization on the implications of OPV transmissibility for the strategy of stopping OPV vaccination after global eradication of wild polioviruses. The authors review the empirical evidence on OPV transmissibility available from household and community transmission studies and from mass-vaccination experiences. They then consider theoretical measures of transmissibility and persistence for wild and OPV viruses (secondary attack rate, basic reproduction number, and critical populations' size), to assess whether transmissibility of OPV viruses is sufficient to allow persistence of these viruses after cessation of vaccination. The findings indicate that OPV viruses could persist under various plausible circumstances, and that this potential should be a major consideration when planning the cessation of OPV vaccination.

Disease Reservoirs↗
PubMed1999

Influence of sampling on estimates of clustering and recent transmission of Mycobacterium tuberculosis derived from DNA fingerprinting techniques.

The availability of DNA fingerprinting techniques for Mycobacterium tuberculosis has led to attempts to estimate the extent of recent transmission in populations, using the assumption that groups of tuberculosis patients with identical isolates ("clusters") are likely to reflect recently acquired infections. It is never possible to include all cases of tuberculosis in a given population in a study, and the proportion of isolates found to be clustered will depend on the completeness of the sampling. Using stochastic simulation models based on real and hypothetical populations, the authors demonstrate the influence of incomplete sampling on the estimates of clustering obtained. The results show that as the sampling fraction increases, the proportion of isolates identified as clustered also increases and the variance of the estimated proportion clustered decreases. Cluster size is also important: the underestimation of clustering for any given sampling fraction is greater, and the variability in the results obtained is larger, for populations with small clusters than for those with the same number of individuals arranged in large clusters. A considerable amount of caution should be used in interpreting the results of studies on clustering of M. tuberculosis isolates, particularly when sampling fractions are small.

Bias↗
PubMed1999

Interpreting the decline in tuberculosis: the role of secular trends in effective contact.

BACKGROUND: The dramatic decline in tuberculosis (TB) in developed countries during the past century has been attributed to many factors, including improvements in living and social conditions and, more recently, effective treatment. Each of these changes should have reduced the average number of individuals 'effectively contacted' (i.e. sufficiently to transmit infection) by each infectious TB case. METHOD: Estimates of the average number of individuals effectively contacted by each infectious TB case, for each year since 1900 in England and Wales, are derived as the ratio between published estimates of the annual risk of infection and estimates of the prevalence of infectious cases, as derived using a published model of the epidemiology of TB. RESULTS: The results suggest that each infectious case contacted, on average, about 22 individuals in 1900 sufficiently to transmit Mycobacterium tuberculosis infection, and that this number declined to about 10 by 1950 and to approximately one by 1990. CONCLUSIONS: Although several factors contributed to the decline in TB in developed countries during this century, a major contributor has been the decline in the number of effective contacts by each case over time. Similar declines have doubtless occurred over the past century for many infections in developed countries.

Adolescent↗
PubMed1999

Tuberculin sensitivity: conversions and reversions in a rural African population.

SETTING: Karonga District, northern Malawi, 1980-1989. OBJECTIVE: To measure and interpret incidence and prevalence of tuberculin sensitivity. DESIGN: Tuberculin testing carried out within two total population surveys. Tuberculin 'positivity' and 'conversion' were defined using criteria recommended by the Tuberculosis Surveillance Research Unit and the American Thoracic Society, respectively. RESULTS: Data on 64,225 tests were available for analysis, including paired results on 6991 individuals tested in both surveys. Frequency distributions of induration varied by age, sex, BCG scar status and zone within the district. The prevalence of 'positivity' was similar in males and females until age 15, then higher among males, and was consistently higher among individuals with than among those without a BCG scar. Tuberculin 'conversion' rates estimated from cross-sectional data ranged from 0.34 to 1.15 per cent per annum. Conversion rates derived from longitudinal data were found to increase linearly with age, and the reversion rates declined rapidly with age among younger individuals. Such trends, which have been reported in other populations, are shown here to arise as an artefact of test instability. Prospective follow-up of observed converters showed greatly increased risks of tuberculosis, in particular during the two years following the second ('converted') test (relative risk > 10). CONCLUSION: Estimation of a convincing 'true' annual risk of infection from tuberculin survey data is not possible from either cross-sectional or longitudinal data, due to misclassifications and the instability of delayed type hypersensitivity over time. An apparent increase in infection risk with age can arise as an artefact of test instability. BCG-induced tuberculin sensitivity declines rapidly in this population in most individuals. It is necessary to consider tuberculin reversions, whether real or apparent, when interpreting tuberculin data on individuals or populations.

Adolescent↗