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Biomedical subjects

R J Hayes

Publications and source records attributed to R J Hayes.

At least 37 records · Page 2Linked to original sources
PubMed2001

HIV-1 subtypes and the HIV epidemics in four cities in sub-Saharan Africa.

OBJECTIVE: To describe the distribution of HIV-1 subtypes in two cities with high HIV prevalence (Kisumu, Kenya and Ndola, Zambia) and two with relatively low prevalence (Cotonou, Benin and Yaoundé, Cameroon), and to examine whether the differences in prevalence of HIV infection could be due to the predominance within the infected populations of subtypes with differing efficiency of heterosexual transmission. METHODS: For around 100 randomly selected HIV-positive sera from the general population and 60 from sex workers in each city, the HIV-1 subtype was determined in the envfragment. For between 19 and 52 of the sera from the general population and 20-32 sera from sex workers, the subtype was also determined in the gag fragment. RESULTS: Over 70% of infections in Cotonou, Yaoundé and Kisumu were with subtype A (by env). However, around one-half of subtype A infections in Cotonou and Yaoundé were found to be the circulating recombinant form CRF02_AG when the gag fragment was also examined. A large number of different HIV strains were found in Yaoundé, including some belonging to group O. Over 20% of infections in Kisumu and around 10% in Yaoundé were with isolated intersubtype recombinant forms. All but a few infections in Ndola were with subtype C and no recombinants were found. CONCLUSIONS: The pattern of distribution of subtypes that we found does not suggest that differences in circulating subtypes play a major role in explaining the differences in prevalence of HIV-1 infection between the four cities. The emergence and spread of recombinants requires close surveillance to adapt testing strategies if needed, to inform vaccine development and to ascertain their role in the future spread of HIV.

Adolescent↗
PubMed2001

The interrelation of HIV, cervical human papillomavirus, and neoplasia among antenatal clinic attenders in Tanzania.

OBJECTIVES: To determine the prevalence and interrelation of cervical human papillomavirus (HPV) genotypes, squamous intraepithelial lesions (SIL), HIV, and other reproductive tract infections (RTIs) among urban antenatal clinic attenders in Mwanza, Tanzania. METHODS: Genital swabs were collected from 660 pregnant women and tested for a range of RTIs and for cervical cytology. Cervical HPV-DNA was detected by PCR and genotyped. HIV and syphilis serologies were performed. RESULTS: HPV prevalence was 34% (209/612 women). Of the 144 typeable samples, 83% were high risk (HR-HPV) oncogenic strains (56% HPV 16 related types). SIL was detected in 43 women (7%), with high grade SIL in 3%. There was a high prevalence of HIV (15%), and of any RTI (83%). Genital warts were detected in 20 women (3%). HPV infection was associated with some behavioural factors (short duration of relationship, single status, not using condoms) and gonorrhoea. There was no overall association between HPV and HIV (OR=1.02, 95% CI 0.6-1.6), but a non-significant trend towards a stronger association with HR-HPV in women aged 15-19 (OR=2.79, 95% CI 0.8-9.5) and women aged > or =30 (OR=3.20, 95% CI 0.7-15). SIL was associated with HPV (OR=3.66, 95% CI 1.9-7.0), but not significantly with HIV (OR=1.54, 95% CI 0.7-3.4). Prevalence of SIL was higher among women dually positive for HPV/HIV compared to HPV infection only (21% v 12%), although this difference was not statistically significant (p=0.17). CONCLUSIONS: HPV infection was highly prevalent in this young antenatal population. The association of HIV with HR-HPV types in older women may suggest that the principal HIV/HPV interaction in this population is for HIV to upregulate HPV persistence, leading to subsequent development of SIL.

Adolescent↗
PubMed2000

HIV infection and silicosis: the impact of two potent risk factors on the incidence of mycobacterial disease in South African miners.

OBJECTIVE: To investigate the combined effects of HIV infection and silicosis on mycobacterial disease. DESIGN AND SETTING: A retrospective cohort of 1374 HIV-positive and 2648 HIV-negative miners who attended a South African gold mining hospital and primary health clinics. PARTICIPANTS: Miners who had been tested for HIV, with consent, at primary health clinics during 1991-1996, predominantly because of a symptomatic sexually transmitted disease. RESULTS: Tuberculosis (TB) incidence was 4.9 and 1.1 per 100 person-years in HIV-positive and HIV-negative miners respectively. The incidence of Mycobacterium kansasii disease was also high (0.32 and 0.10 per 100 person-years, respectively). Silicosis was highly prevalent, implying inadequate dust control, and was a significant TB risk factor among both HIV-positive and HIV-negative men (adjusted incidence rate ratios 1.4-2.5 according to radiological severity). The data were consistent with the risks of silicosis and HIV combining multiplicatively, but did not fit an additive model. The incidence of HIV-associated TB increased significantly during the study, with no corresponding change in HIV-negative rates, to reach 16.1 per 100 person-years among HIV-positive silicotics. CONCLUSIONS: The risks of silicosis and HIV infection combine multiplicatively, so that TB remains as much a silica-related occupational disease in HIV-positive as in HIV-negative miners, and HIV-positive silicotics have considerably higher TB incidence rates than those reported from other HIV-positive Africans. The increasing impact of HIV over time may indicate epidemic TB transmission with rapid disease development in HIV-infected miners. Similar but currently unrecognized interactions may be contributing to TB control problems in other industrializing countries affected by the HIV epidemic.

AIDS-Related Opportunistic Infections↗
PubMed2000

Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis.

OBJECTIVE: To systematically review studies of male circumcision and the risk of HIV-1 infection in men in sub-Saharan Africa, and to summarize the findings in a meta-analysis. DESIGN: A meta-analysis of observational studies. METHODS: A systematic literature review was carried out of studies published up to April 1999 that included circumcision as a risk factor for HIV-1 infection among men in sub-Saharan Africa. A random effects meta-analysis was used to calculate a pooled relative risk (RR) and 95% confidence interval (CI) for all studies combined, and stratified by type of study population. Further analyses were conducted among those studies that adjusted for potential confounding factors. RESULTS: Twenty-seven studies were included. Of these, 21 showed a reduced risk of HIV among circumcised men, being approximately half that in uncircumcised men (crude RR = 0.52, CI 0.40-0.68). In 15 studies that adjusted for potential confounding factors, the association was even stronger (adjusted RR = 0.42, CI 0.34-0.54). The association was stronger among men at high risk of HIV (crude RR = 0.27; adjusted RR = 0.29, CI 0.20-0.41) than among men in general populations (crude RR = 0.93; adjusted RR = 0.56, CI 0.44-0.70). CONCLUSION: Male circumcision is associated with a significantly reduced risk of HIV infection among men in sub-Saharan Africa, particularly those at high risk of HIV. These results suggest that consideration should be given to the acceptability and feasibility of providing safe services for male circumcision as an additional HIV prevention strategy in areas of Africa where men are not traditionally circumcised.

Africa South of the Sahara↗
PubMed2000

Interactions between herpes simplex virus type 2 and human immunodeficiency virus type 1 infection in African women: opportunities for intervention.

Sexually transmitted diseases (STDs) are cofactors for human immunodeficiency virus (HIV) transmission, but the specific role of herpes simplex virus type 2 (HSV-2) is unclear. This study aimed to examine the in vivo relationships between HSV-2 and HIV-1 in 300 women in Bangui, Central African Republic. Sera were tested for syphilis, HIV-1, HSV-2 antibody, and levels of vitamins A and E. Genital specimens were tested for other STDs. HSV-2 DNA and HIV-1 RNA were quantified in cervicovaginal lavage. The prevalences of HSV-2 antibody (91% vs. 78%, P=.02), HSV-2 shedding (43% vs. 22%, P=. 003), and levels of HSV-2 DNA (P=.01) were all significantly higher among HIV-1-seropositive than among HIV-1-seronegative women. There was a significant correlation between genital HIV-1 RNA and HSV-2 DNA levels (P=.02) among the 23 women who were shedding HSV-2 DNA. If confirmed, such associations highlight the urgent need for HSV-2 control measures in populations at high risk of both infections.

Black People↗
PubMed2000

Syndromic treatment of sexually transmitted diseases reduces the proportion of incident HIV infections attributable to these diseases in rural Tanzania.

OBJECTIVES: To compare the proportion of HIV seroconversions attributable to other sexually transmitted diseases in the intervention and comparison arms of the Mwanza sexually transmitted diseases (STD) intervention trial. DESIGN: Case-control study of 96 cases of HIV seroconversion and 974 HIV-negative controls, nested within the Mwanza trial cohort. METHODS: Data on reported STD symptoms during 2 years of follow-up, and serological evidence of recent syphilis, were used to obtain odds ratios (ORs) for HIV seroconversion, adjusted for community, age, marital status, sex partners and travel. Population-attributable fractions (PAF) of HIV seroconversions associated with these STD exposures were calculated separately for the intervention and comparison arms, and for men and women. RESULTS: In men in the comparison arm, adjusted ORs for ulcers (14.8), discharge (3.3), any symptom (4.1) and any STD (4.0) were highly significant. There were no significant associations between HIV incidence and STD exposures in the intervention arm. The PAF were consistently higher in the comparison arm than the intervention arm. In men, the PAF for any STD was 39.6% [95% confidence interval (CI), 12.4-58.3)] in the comparison arm but only 12.0% (CI, 0.0-35.9) in the intervention arm. The PAF for women were lower than for men. CONCLUSIONS: These are minimal PAF estimates and they do not account for STD effects on HIV infectiousness. Nevertheless, a substantial proportion of new HIV infections in men in the comparison arm were attributable to STD. Lower PAF in the intervention arm than in the comparison arm for men provide further evidence of the role of STD cofactors in HIV transmission, supporting the hypothesis that the Mwanza intervention reduced the duration of symptomatic STD, thus reducing the HIV risk associated with such STD.

Adolescent↗
PubMed2000

Model-based evaluation of single-round mass treatment of sexually transmitted diseases for HIV control in a rural African population.

OBJECTIVES: To compare the impact of single-round mass treatment of sexually transmitted diseases (STD), sustained syndromic treatment and their combination on the incidence of HIV in rural Africa. METHODS: We studied the effects of STD interventions by stochastic simulation using the model STDSIM. Parameters were fitted using data from a trial of improved STD treatment services in Mwanza, Tanzania. Effectiveness was assessed by comparing the prevalences of gonorrhoea, chlamydia, syphilis and chancroid, and the incidence of HIV, in the general adult population in simulations with and without intervention. RESULTS: Single-round mass treatment was projected to achieve an immediate, substantial reduction in STD prevalences, which would return to baseline levels over 5-10 years. The effect on syphilis was somewhat larger if participants cured of latent syphilis were not immediately susceptible to re-infection. At 80% coverage, the model projected a reduction in cumulative HIV incidence over 2 years of 36%. A similar impact was achieved if treatment of syphilis was excluded from the intervention or confined to those in the infectious stages. In comparison with sustained syndromic treatment, single-round mass treatment had a greater short-term impact on HIV (36 versus 30% over 2 years), but a smaller long-term impact (24 versus 62% over 10 years). Mass treatment combined with improved treatment services led to a rapid and sustained fall in HIV incidence (57% over 2 years; 70% over 10 years). CONCLUSIONS: In populations in which STD control can reduce HIV incidence, mass treatment may, in the short run, have an impact comparable to sustained syndromic treatment. Mass treatment combined with sustained syndromic treatment may be particularly effective.

Adolescent↗
PubMed2000

Design and analysis issues in cluster-randomized trials of interventions against infectious diseases.

This paper discusses the application of the cluster-randomized trial (CRT) design to evaluate the effectiveness of interventions against infectious diseases. In addition to the usual rationale for this design, there are a number of other advantages that are peculiar to the study of infectious diseases. In particular, CRTs are able to measure the overall effect of an intervention at the population level, capturing both the direct effect of an intervention on an individual's susceptibility to infection, and also the indirect effects due to changes in risks of transmission to other individuals, or to the mass effect or 'herd immunity' resulting from intervening in a large proportion of the population. We briefly review published CRTs of interventions against infectious diseases, most of which have been conducted in the developing countries where such diseases predominate. The focus is on trials in which communities or other large groupings are randomized, and in which impacts on infectious disease incidence or mortality are assessed. We then discuss three issues that are of special relevance to CRTs of infectious diseases. First, issues relating to the definition and size of clusters; secondly, the role of matching or stratification, and the choice of matching factors; and thirdly, the definition of direct and indirect effects of intervention, and methods of assessing these components in a CRT. We conclude by outlining some areas for future research.

Biometry↗
PubMed1999

Simple sample size calculation for cluster-randomized trials.

BACKGROUND: Cluster-randomized trials, in which health interventions are allocated randomly to intact clusters or communities rather than to individual subjects, are increasingly being used to evaluate disease control strategies both in industrialized and in developing countries. Sample size computations for such trials need to take into account between-cluster variation, but field epidemiologists find it difficult to obtain simple guidance on such procedures. METHODS: In this paper, we provide simple formulae for sample size determination for both unmatched and pair-matched trials. Outcomes considered include rates per person-year, proportions and means. For simplicity, formulae are expressed in terms of the coefficient of variation (SD/mean) of cluster rates, proportions or means. Guidance is also given on the estimation of this value, with or without the use of prior data on between-cluster variation. CASE STUDIES: The methods are illustrated using two case studies: an unmatched trial of the impact of impregnated bednets on child mortality in Kenya, and a pair-matched trial of improved sexually-transmitted disease (STD) treatment services for HIV prevention in Tanzania.

Child, Preschool↗
PubMed1999

Nontuberculous mycobacteria: defining disease in a prospective cohort of South African miners.

A gold mining work force was followed prospectively over 1 yr for sputum nontuberculous mycobacterial (NTM) isolates. NTM were isolated from 118 men, of whom 32 (27%) met the American Thoracic Society (ATS) case-definitions for pulmonary NTM disease (23 M. kansasii, seven M. scrofulaceum, one M. avium, and one M. abscessus). Determining isolate significance was difficult because most men had been started on presumptive TB treatment before isolate identification (70%). Histologic criteria were considered inappropriate for this high M. tuberculosis incidence population, particularly for patients who had stabilized on presumptive TB treatment. Among men not meeting case-definitions, indicators of disease were significantly more prevalent for M. kansasii than for M. fortuitum, the local laboratory contaminant (ORs: 6.5 for cough, 7. 2 for smear-positivity, 36.0 for radiologic changes, and 14.3 for presumptive TB treatment), suggesting underdiagnosis of M. kansasii disease. Of 53 men with definite or possible M. kansasii disease, 18 (34%) were HIV-positive. HIV-associated M. kansasii disease occurred at an early stage of immunosuppression (median CD4 count, 381 x 10(6)/L) with a good outcome (83% cured after 12 mo of treatment). ATS case-definitions for NTM disease are difficult to apply in this population, and treatment decisions should be guided by the pathogenic potential of the isolate.

Adult↗
PubMed1999

Use of miniradiographs to detect silicosis. Comparison of radiological with autopsy findings.

Radiological and routine autopsy findings from 241 South African gold miners were compared, using pathology as the "gold standard." Previous annual screening miniradiographs were read independently by two readers, using the International Labor Office (ILO) grading system, without reference to personal identifiers. Individual and consensus silicosis grades were recorded for each subject. When pathological and radiological silicosis were defined as any abnormal grade, the sensitivity and specificity of the radiological diagnosis was 67.5% and 80%, with positive and negative predictive values of 63% and 83%. Most undetected autopsy silicosis was early-grade. Using higher pathological and radiological grades to define silicosis (5 nodules or more and ILO grades 1/1 and above), sensitivity and specificity increased to 71% and 96%, and positive and negative predictive values increased to 76% and 95%, respectively. Use of a consensus grade made little difference to results from individual readers. For each radiological definition, sensitivity was considerably higher than, but specificity was similar to, that found in a previous study of South African gold miners which used the same pathology source and standard sized films. The difference between these two study findings, and unexpected demonstration of higher sensitivity from miniradiographs, suggests that further research is required into factors affecting radiological interpretation before silicosis grading can be considered to be adequately standardized.

Adult↗
PubMed1999

The immune response to Mycobacterium tuberculosis in HIV-infected and uninfected adults in Uganda: application of a whole blood cytokine assay in an epidemiological study.

SETTING: Out-patient clinic, Entebbe, Uganda. BACKGROUND: It has been proposed that 'type 1' cytokines are essential in protective immunity to Mycobacterium tuberculosis and that suppression of 'type 1' or a switch to a 'type 2' profile is deleterious. We employed a simple assay to examine whether the dependence of the immunological responses to mycobacterial antigens on a range of explanatory factors could be determined in a population where tuberculosis is endemic. OBJECTIVE: To determine the relationship between the tuberculin skin test response and cytokine profile, and the effect of human immunodeficiency virus (HIV) infection. DESIGN: A cross-sectional study of 97 Ugandan adults (22 HIV-positive, 75 HIV-negative). Whole blood was stimulated in vitro using mycobacterial antigens (purified protein derivative [PPD] and culture filtrate proteins [CFP]). 'Type 1' cytokines (gamma interferon [IFN-gamma] and interleukin-2 [IL-2]), 'type 2' cytokines (IL-5 and IL-10) and tumour necrosis factor alpha (TNF-alpha) were measured in culture supernatants. RESULTS: Among HIV-negative subjects, a positive tuberculin skin test was associated with type 1 or mixed (type 1 + type 2) cytokine production, but a positive IFN-gamma response also occurred in a proportion of tuberculin skin test negative subjects (36% for PPD, 17% for CFP). In association with HIV infection, IFN-gamma responses to mycobacterial antigens were profoundly impaired (odds ratio [OR] 0.10 for PPD, 0.06 for CFP, P< or =0.001), but production of IL-2, IL-5 and TNF-alpha was relatively sustained, and IL-10 increased or sustained (OR 3.97 for PPD, P = 0.01, 1.14 for CFP, P = 0.99). CONCLUSION: The type 1/type 2 cytokine balance was not defined by the tuberculin skin test response, and may have a closer relation to protective immunity. IFN-gamma production was strikingly impaired in association with HIV infection, while production of type 2 cytokines was sustained or increased. Use of a simple assay allowed a large sample of subjects to be examined, producing epidemiologically meaningful results.

Adolescent↗
PubMed1998

Verbal autopsies for adult deaths: their development and validation in a multicentre study.

BACKGROUND: Verbal autopsy (VA) has been widely used to ascertain causes of child deaths, but little is known about the usefulness of VA for adult deaths. This paper describes the process used to develop a VA tool for adult deaths and the results of a multicentre validation of this tool. METHODS: A mortality classification was developed by including causes of death that might be arrived at by VAs and causes that are responsive to public health interventions. An algorithm was designed for each cause in the classification, based on classifying symptoms into essential, supportive and differential. A structured questionnaire designed to elicit information on these symptoms was developed in English translated into the local languages. The tool was validated on deaths occurring at hospitals in Tanzania (315 deaths), Ethiopia (249) and Ghana (232). Hospital records of all adult deaths occurring at the study hospitals from June 1993 to April 1995 were collected prospectively. Non-medical interviewers with at least 12 years of formal education conducted VA interviews. Causes of death were diagnosed by a panel of physicians and by a computerized algorithm. The validity of the VA was assessed by comparing the VA diagnoses with hospital diagnoses. RESULTS: Specificity of VAs by physicians fell below 95% only for acute febrile illness (AFI) and TB/AIDS. Sensitivity and positive predictive value (PPV), however, varied widely both across the sites and between causes. Sensitivity was > 75% for tetanus, rabies, direct maternal causes, injuries and TB/AIDS and ranged between 60% and 74% for diarrhoea, acute abdominal conditions and AFI. The PPV was > 75% for tetanus, rabies, hepatitis and injuries and ranged between 60 and 74% for meningitis, AFI, TB/AIDS and direct maternal causes. When the communicable diseases were combined in a single group, the sensitivity was 82%, specificity 78% and PPV 85%. For the group of noncommunicable diseases the corresponding sensitivity, specificity and PPV were 71%, 87% and 67%, respectively. Use of an algorithm resulted in lower sensitivity, specificity and PPV than the VAs by physician. CONCLUSION: VAs by a panel of physicians performed better than an opinion-based algorithm. The validity of VA diagnosis was highest for AFI, direct maternal causes, TB/AIDS, tetanus, rabies and injuries.

Adult↗
PubMed1998

An analysis of the geographical distribution of severe malaria in children in Kilifi District, Kenya.

BACKGROUND: Although malaria is known to be a major cause of child mortality and morbidity throughout sub-Saharan Africa there are few detailed studies of malaria mortality rates and incidence of severe malarial disease in defined communities. We have studied the geographical pattern of admissions to hospital with severe malaria and the stability of this pattern over time in Kilifi District on the Kenyan Coast. METHODS: Over a 2-year period all children under 5 years of age with severe malaria admitted to the district hospital and living in a rural study population of about 50,000 people were identified. Annual censuses were carried out in the study area, and all households were mapped using a hand-held satellite navigation system. The resulting databases were linked using a geographical information system (GIS). RESULTS: Using methods originally developed for the study of the geographical distribution of childhood leukaemia we assessed the spatial pattern of hospital admission rates for severe malaria. As expected, admission rates were significantly higher in children with easier access to the hospital. For example, those living more than 25 km from the hospital had admission rates which were about one-fifth of those for children living within 5 km of the hospital. Those living more than 2.5 km from the nearest road had admission rates that were about half of those for children living within 0.5 km of a road. We also investigated short-term local fluctuations in severe malaria and found evidence of space-time clustering of severe malaria. CONCLUSIONS: Hospital admission rates for severe malaria are higher in households with better access to hospital than in those further away. The finding of space-time clusters of severe malaria suggests that it would be of value to conduct case-control studies of environmental, genetic and human behavioural factors involved in the aetiology of the disease.

Animals↗
PubMed1998

Spectrum of disease among HIV-infected adults hospitalised in a respiratory medicine unit in Abidjan, Côte d'Ivoire.

SETTING: Respiratory medicine wards of the University Teaching Hospital, Abidjan, Côte d'Ivoire. OBJECTIVES: To describe the spectrum of opportunistic infection among human immunodeficiency virus (HIV) infected adults hospitalised in the respiratory medicine unit in Abidjan, and the level of immunosuppression at which these diseases occur. DESIGN: Cross-sectional study. RESULTS: Overall, 75% of patients were HIV-positive: among these patients, the most frequent diagnosis was tuberculosis, in 61%, followed by bacterial pneumonia (15%), Gram-negative septicaemia (particularly non-typhoid Salmonella) (9%) and empyema (5%). Atypical pneumonias appeared to be rare. Most HIV-positive patients had CD4 counts indicative of advanced immunosuppression: 36% had CD4 counts below 100 x 10(6)/l, 19% between 100 and 199 x 10(6)/l, 29% between 200 and 499 x 10(6)/l, and 16% above 500 x 10(6)/l. Overall in-hospital mortality was 27% for HIV-positive patients and 22% for HIV-negative patients (P = 0.5). In a multivariate analysis, the strongest independent risk factors for death were cachexia (odds ratio [OR] 7.4, 95% confidence interval [CI] 2.1-26.3), male sex (OR 4.5, 95% CI 1.2-17.4) and age over 40 (OR 4.1, 95% CI 1.0-17.2). CONCLUSIONS: Tuberculosis and bacterial infections are the major causes of respiratory morbidity in immunosuppressed HIV-infected adults in this population. Efforts to improve the management of HIV-related disease need to focus on prevention and treatment of these infections.

AIDS-Related Opportunistic Infections↗
PubMed1998

The validity of verbal autopsies for assessing the causes of institutional maternal death.

This report presents data from a study carried out in three African countries to assess the validity of verbal autopsies--based on information about symptoms and signs observed antemortem by relatives or associates of deceased individuals--for determining the causes of institutional maternal death. The validity of the verbal autopsy was assessed for each cause of death; and for groups of "direct" and "indirect" maternal causes, by comparing the verbal autopsy diagnoses with the reference diagnoses and calculating their sensitivity, specificity, and positive predictive value. Verbal autopsies were found to be highly specific (98 percent specificity for all causes of maternal death) but not very sensitive (< or = 60 percent sensitivity for all causes except ante/postpartum hemorrhage). Verbal autopsy estimates of cause-specific mortality were comparable to expected values for most of the causes. The study shows that certain direct causes of hospital-based maternal mortality can be determined by means of verbal autopsies with a reasonable level of confidence.

Adolescent↗