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Biomedical subjects

J Whitworth

Publications and source records attributed to J Whitworth.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study.

BACKGROUND: An association between HIV-1 and malaria is expected in theory, but has not been convincingly shown in practice. We studied the effects of HIV-1 infection and advancing immunosuppression on falciparum parasitaemia and clinical malaria. METHODS: HIV-1-positive and HIV-1-negative adults selected from a population-based cohort in rural Uganda were invited to attend a clinic every 3 months (routine visits) and whenever they were sick (interim visits). At each visit, information was collected on recent fever, body temperature, and malaria parasites. Participants were assigned a clinical stage at each routine visit and had regular CD4-cell measurements. FINDINGS: 484 participants made 7220 routine clinic visits between 1990 and 1998. Parasitaemia was more common at visits by HIV-1-positive individuals (328 of 2788 [11.8%] vs 231 of 3688 [6.3%], p<0.0001). At HIV-1-positive visits, lower CD4-cell counts were associated with higher parasite densities, compared with HIV-1-negative visits (p=0.0076). Clinical malaria was significantly more common at HIV-1-positive visits (55 of 2788 [2.0%] vs 26 of 3688 [0.7%], p=0.0003) and the odds of having clinical malaria increased with falling CD4-cell count (p=0.0002) and advancing clinical stage (p=0.0024). Participants made 3377 interim visits. The risk of clinical malaria was significantly higher at visits by HIV-1-positive individuals than HIV-1-negative individuals (4.0% vs 1.9%, p=0.009). The risk of clinical malaria tended to increase with falling CD4-cell counts (p=0.052). INTERPRETATION: HIV-1 infection is associated with an increased frequency of clinical malaria and parasitaemia. This association tends to become more pronounced with advancing immunosuppression, and could have important public-health implications for sub-Saharan Africa.

Adolescent↗
PubMed2000

23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomised and placebo controlled trial.

BACKGROUND: Infection with Streptococcus pneumoniae is a frequent and serious problem for HIV-immunosuppressed adults. Vaccination is recommended in the USA and Europe, but there are no prospective data that show vaccine efficacy. METHODS: 1392 (937 female) HIV-1-infected adults in Entebbe, Uganda, were enrolled. 697 received 23-valent pneumococcal polysaccharide vaccine and 695 received placebo. The primary endpoint was first event invasive pneumococcal disease. Secondary endpoints included vaccine serogroup-specific invasive disease, all (probable and definite) pneumococcal events, all-cause pneumonia, and death. FINDINGS: First invasive events occurred in 25 individuals (24 bacteraemias, one pyomyositis), 15 in the vaccine arm and ten in the placebo arm (hazard ratio [HR] 1.47; 95% CI 0.7-3.3). 22 isolates (88%) were of vaccine-specific serogroups with 15 events in the vaccine arm compared with seven in the placebo arm (HR 2.10; 0.9-5.2). All pneumococcal events had a similar distribution (20 vs 14; HR 1.41; 0.7-2.8) though all-cause pneumonia was significantly more frequent in the vaccine arm (40 vs 21; HR 1.89; 1.1-3.2). Mortality was unaffected by vaccination. INTERPRETATION: 23-valent pneumococcal polysaccharide vaccination is ineffective in HIV-1-infected Ugandan adults and probably has little, or no, public health value elsewhere in sub-Saharan Africa. Increased rates of pneumococcal disease in vaccine recipients may necessitate a reappraisal of this intervention in other settings.

AIDS-Related Opportunistic Infections↗
PubMed2000

An improved algorithm for determining HIV type 1 subtypes in a primary laboratory in Uganda.

A pilot study was undertaken with the objective of developing a simple, economical, and efficient algorithm through which to subtype HIV-1 in a large epidemiological cohort study in Uganda. A peptide enzyme immunoassay (PEIA) employing both V3 and gp41 regions and a heteroduplex mobility assay (HMA) were evaluated in comparison with DNA sequencing. Of 146 samples selected, 115 (79%) were successfully sequenced. Taking sequence data as the "gold standard," other assays were compared with these data. The HMA correctly identified 95 (83%) of the samples, and only 1 sample was wrongly identified. The V3 PEIA alone and in combination with gp41 peptides correctly identified 76 and 78% of the samples, respectively; however, the number of wrongly identified samples was four times less with the combination compared with V3 peptides alone (4 versus 16%). The sensitivity, specificity, and positive and negative predictive values for serotype A and D samples were greater for the combination than V3 peptides alone. We have described a new algorithm to segregate subtypes A and D. This algorithm uses the two peptide assays followed by HMA and then DNA sequencing for untypable samples, giving an accuracy of 95% at a cost of 37 and 21% for consumables compared with subtyping all the samples by HMA or DNA sequencing, respectively. This proposed approach is suitable for epidemiological studies in Uganda and other regions with a predominance of A and D subtypes.

Algorithms↗
PubMed2000

Molecular epidemiology of HIV type 1 in a rural community in southwest Uganda.

The molecular epidemiology of a population-based cohort in a cluster of 15 villages in southwestern Uganda was investigated by sequencing part of the p24 gag gene and performing heteroduplex mobility assays (HMAs) of the V3 region of the env gene. Sequence and HMA data, obtained for 69 and 88 proviruses, respectively, showed that the clade A and D viruses were present at a ratio of about 0.67:1. No other clades were detected. Thirteen (22%) of 59 proviruses for which both gag and env data were obtained appeared to be recombinants. Although both clade A and D viruses were present in 13 of the villages, their distribution was unequal: for example, from env data 59% of clade A viruses were found in the eastern villages, compared with only 27% of clade D viruses. Phylogenetic (maximum likelihood) analysis of the p24 gag sequences showed a total of five clusters supported by bootstrap resampling values above or close to 75%. Four clusters were sexual partners, but there was no known sexual contact between the persons in the other cluster. The DNA sequences showed between 0.5 and 8.3% divergence from the cohort clade A or D consensus sequences. The sequences were not closely related to those published for other clade A or D proviruses.

Acquired Immunodeficiency Syndrome↗
PubMed2000

A monoclonal blocking EIA for herpes simplex virus type 2 antibody: validation for seroepidemiological studies in Africa.

A competitive type-specific enzyme-linked immunosorbent assay (ELISA) for herpes simplex virus type 2 (HSV-2) antibody was developed using an infected cell antigen and a monoclonal antibody to glycoprotein G-2. This assay has been validated for use for epidemiological studies using a large panel of sera collected in rural Uganda and a panel of 143 sera characterised previously by Western blotting, the 'gold standard' for HSV type-specific serology. This evaluation was found to have a sensitivity of 96% and a specificity of 91% in comparison with Western blot on 143 sera from clinic patients. The ELISA had a sensitivity of 93% and a specificity of 91% in comparison with Western blot on 495 sera collected in Uganda. The assay showed good reproducibility and a low percentage of sera gave equivocal results, indicating its suitability for epidemiological studies.

Antibodies, Monoclonal↗
PubMed2000

Vaccines for the control of HIV/AIDS.

This review discusses the feasibility of an HIV vaccine and describes the history, efficacy and potential to succeed of old and new vaccine concepts.

AIDS Vaccines↗
PubMed2000

Use of alternative medicine by patients undergoing cardiac surgery.

OBJECTIVE: Complementary and alternative medicine may influence cardiac surgical care by inducing coagulopathies and interacting with perioperative medications. We evaluated the significance of complementary and alternative medicine use in an acutely ill cardiac surgical population and assessed the willingness of patients to reveal these activities to their physicians and surgeons. METHODS: A total of 376 consecutive patients undergoing preoperative or postoperative cardiothoracic surgical evaluations at an urban academic medical center were approached to complete a survey regarding use and attitudes toward complementary and alternative medicine. All surveys were administered and collected between March and May 1998. RESULTS: Completion rate was 70% (n = 263). Respondents were predominantly male (72%), white (76%), and well educated (59%). The overall rate of complementary and alternative medicine use was 75%, but excluding prayer and vitamins, which are often not considered complementary and alternative medicine therapies, the rate was 44%. There was no correlation between the use of complementary and alternative medicine and the parameters of gender, age, race, or education level. Only 17% responded that they had discussed complementary and alternative medicine with their physicians, and 48% responded that they did not want to discuss the topic at all. CONCLUSIONS: Complementary and alternative medicine is used as frequently in patients undergoing cardiac surgery, as in the general population. Physicians and surgeons should be aware that patients have no inherent predisposition toward or against using complementary and alternative medicine, but that they are unlikely to volunteer their experience with it. The unwillingness of patients to discuss complementary and alternative medicine with physicians has serious implications for their safety, especially in acute care situations.

Adult↗
PubMed2000

Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum.

Multilocus genotyping of microbial pathogens has revealed a range of population structures, with some bacteria showing extensive recombination and others showing almost complete clonality. The population structure of the protozoan parasite Plasmodium falciparum has been harder to evaluate, since most studies have used a limited number of antigen-encoding loci that are known to be under strong selection. We describe length variation at 12 microsatellite loci in 465 infections collected from 9 locations worldwide. These data reveal dramatic differences in parasite population structure in different locations. Strong linkage disequilibrium (LD) was observed in six of nine populations. Significant LD occurred in all locations with prevalence <1% and in only two of five of the populations from regions with higher transmission intensities. Where present, LD results largely from the presence of identical multilocus genotypes within populations, suggesting high levels of self-fertilization in populations with low levels of transmission. We also observed dramatic variation in diversity and geographical differentiation in different regions. Mean heterozygosities in South American countries (0.3-0.4) were less than half those observed in African locations (0. 76-0.8), with intermediate heterozygosities in the Southeast Asia/Pacific samples (0.51-0.65). Furthermore, variation was distributed among locations in South America (F:(ST) = 0.364) and within locations in Africa (F:(ST) = 0.007). The intraspecific patterns of diversity and genetic differentiation observed in P. falciparum are strikingly similar to those seen in interspecific comparisons of plants and animals with differing levels of outcrossing, suggesting that similar processes may be involved. The differences observed may also reflect the recent colonization of non-African populations from an African source, and the relative influences of epidemiology and population history are difficult to disentangle. These data reveal a range of population structures within a single pathogen species and suggest intimate links between patterns of epidemiology and genetic structure in this organism.

Africa↗
PubMed1999

The prognostic value of the World Health Organisation staging system for HIV infection and disease in rural Uganda.

OBJECTIVE: To assess whether the WHO staging classification for HIV provides prognostically valuable and applicable information in rural Uganda. PATIENTS AND STUDY DESIGN: Data were obtained from a population-based cohort of 232 HIV-infected individuals. METHODS: Clinical information was obtained using a detailed questionnaire and ascertained by physical examination. Participants were seen routinely every 3 months and when they were sick. A computer algorithm based on clinical history, examination and laboratory findings was used to stage HIV-positive participants at each routine visit. Kaplan-Meier survival estimates and the Cox proportional hazard model were used to assess the prognostic strength of the clinical and laboratory categories of the system. RESULTS: An attendance rate of 81% and 799 person-years of follow-up were achieved. Survival probability estimates at 6 years from being seen in clinical stages 1, 2, 3 and 4 were 63, 46, 24 and 6% respectively. When staging was revised to incorporate lymphocyte categories, the survival probabilities were 73, 62, 39 and 6% respectively. Unexplained prolonged fever and severe bacterial infection had survival probabilities closer to stage 2 conditions, mucocutaneous herpes simplex virus infection for more than 1 month and crytosporidiosis with diarrhoea for more than 1 month closer to stage 3 and oral candidiasis closer to stage 4 conditions. CONCLUSIONS: Even without the laboratory markers, the clinical category of the WHO staging system is useful for predicting survival in individuals with HIV disease. This is important for areas with limited access to laboratory markers. A simple rearrangement of a few clinical conditions could improve the prognostic significance of the WHO system.

AIDS-Related Opportunistic Infections↗
PubMed1999

HIV-1 RNA levels in an African population-based cohort and their relation to CD4 lymphocyte counts and World Health Organization clinical staging.

Apart from a small number of reports from people who are based in hospitals, data on viral load in HIV-infected people in sub-Saharan Africa, where most infections occur, are lacking. We report serum HIV-1 RNA levels in a population-based cohort in rural Uganda using the nucleic acid sequence-based amplification procedure (NASBA) test kit and describe their relation to CD4 counts and World Health Organization (WHO) clinical staging. The median (interquartile range [IQR]) viral loads were 87,000 copies/ml (37,500-295,000 copies/ml) in 40 prevalent cases infected for >6 years, and 31,000 copies/ml (7800-174,000 copies/ml) in 65 incident cases with seroconversion dates within the previous 6 years. Although we found a correlation between viral load and absolute CD4 count (p < .0001), there was no evidence for an association with CD4 decline (p = .1). Overall, there was a significant trend of increasing viral load with worsening clinical stage from a median viral load of 15,000 for those in WHO stage 1 (asymptomatic) to 150,600 copies/ml for those in stage 4 (AIDS; p < .001). However, the association was seen only in incident cases. Thus, we found that the NASBA test on serum was a useful indicator of disease stage especially in persons known to be infected for <6 years. Such baseline data are important for vaccine research, and if antiretroviral drugs become available to more than a few people in Africa, it will be important that accurate viral load estimations are available at least in a proportion of people to monitor the effectiveness of treatment, and measure the compliance and emerging resistance to these drugs.

Adult↗
PubMed1999

Barriers to improving endodontic care: the views of NHS practitioners.

AIMS: Concerns have been expressed about the technical quality of NHS endodontic treatment. Bringing performance into line with guidelines for good practice needs to be underpinned by an understanding of barriers to compliance. To this end, our research involved an exploratory investigation of the factors influencing the behaviour of general dental practitioners in their practice of endodontics. MATERIALS AND METHODS: Subjects 12 dental practitioners, representative of varying levels of professional experience and status, and of compliance with good practice guidelines. Data collection In-depth interviews, following a topic guide. Analysis Identification, abstraction and charting of major themes. FINDINGS: Informants' responses suggested that general dental practitioners' endodontic practice is influenced by a complex web of factors. A key barrier to high quality treatment is the NHS remuneration scheme. Undergraduate and postgraduate education and training are also highly influential on practice. Dentists reported employing a range of strategies to manage the time-cost tensions imposed by the remuneration system. Perceived deficiencies in the content and delivery of postgraduate training were highlighted by our informants. CONCLUSIONS: There was a perception among our informants that the NHS fee structure needs to be revised. Their views suggest that a system which rewards quality rather than volume may be more appropriate, but, we believe, such a system would need to take into account efficiency as well as effectiveness. Modification of the current system of postgraduate training in endodontics is also indicated by the views expressed in the interviews. From the diversity of views and from a critical review of the literature, we conclude that flexibility is the key note in changing practice, with no single strategy likely to be universally appropriate.

Attitude of Health Personnel↗
PubMed1999

The burden of mucocutaneous conditions and the association with HIV-1 infection in a rural community in Uganda.

OBJECTIVE: To determine the prevalence of mucocutaneous conditions and their association with HIV-1 infection in a rural community in Uganda. METHODS: In a prospective cohort study, participants were recruited from a large population study and invited to attend a clinic every 3 months for a detailed medical interview and a thorough physical examination. All findings including mucocutaneous findings were coded onto a standard questionnaire. RESULTS: By the end of 1996, 436 participants had provided 1450 person years of observation (pyo); 646 pyo in HIV-positives and 804 pyo in HIV-negatives. Overall, 70% of participants had a skin condition during follow-up, and although skin conditions were significantly more common in HIV-positive subjects, the background level in HIV-negative subjects was high (77.3% and 63.6%, respectively). Herpes zoster, thin/sparse hair, maculo-papular rash and prurigo were significantly more common in the HIV-positives. Kaposi sarcoma, palmar/plantar rash and herpes zoster had positive predictive values for HIV infection of over 80%. Oral conditions were found in over 40% of participants and were significantly more common in HIV-positive subjects. Oral candidiasis and Kaposi sarcoma were significantly more frequent among HIV-positives. CONCLUSION: HIV infection increases the already high burden of mucocutaneous diseases in this rural population. We identified some conditions that are more common in HIV and others that can be used as indicators of HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1999

Implementation of a comprehensive AIDS education programme for schools in Masaka District, Uganda.

As part of a large IEC (Information, Education and Communication)/STD intervention trial, a 19-lesson, comprehensive school-based AIDS education programme was implemented and evaluated in 50 primary and 16 secondary schools in 12 parishes of Masaka District, Uganda. A series of three teacher-training and evaluation workshops spread over a year was held in each parish, between which teachers implemented the programme in the classroom. One hundred and forty-eight teachers were trained and about 3,500 students were subsequently exposed to the programme. Both teachers and students responded positively, which suggests that this type of programme has much to offer young people who attend school. However, some problems were encountered: language, programme content, community resistance to teaching about condoms, and several practical issues. Proposed solutions include flexibility with the English language policy, alternative approaches to role play activities, targeting influential individuals with information about the need for young people to learn about safer sex, and a parallel community-based IEC programme to facilitate community acceptance of the need for the programme. In addition, implementation may be incomplete unless comprehensive AIDS education is fully incorporated into the curriculum, and properly examined. These findings are placed in the context of other life skills/AIDS education programmes being introduced both in Uganda and elsewhere in Africa.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Determinants of attendance and patient satisfaction at eye clinics in south-western Uganda.

PURPOSE: To identify the reasons for subjects deciding to attend or not attend local and referral ophthalmology clinics in south-west Uganda, and to establish the levels of satisfaction of clinic attenders with the services they received. METHODS: A population survey identified subjects with ocular conditions who were referred to the local clinic or the district hospital. All non-attenders and a group of attenders were interviewed at home. RESULTS: 31% of those referred did not attend the local clinic. The most common reasons were 'too busy' (29%) or 'unwilling to buy spectacles' (17%). Less than half of attenders were satisfied, mainly because of no perceived clinical improvement or having to buy spectacles. Only 13% of those referred to the district hospital clinic attended. The main reasons for non-attendance were high transport cost and fear of the clinic. CONCLUSION: Attendance and satisfaction with the community ophthalmology service could be improved by more intensive motivation and explanation for patients, and assistance with spectacle and transport costs. The use of aphakic motivators should be tested in this context.

Community Health Centers↗
PubMed1999

HLA-A, -B, -C, -DRB1, DRB3, DRB4, DRB5 and DQB1 polymorphism detected by PCR-SSP in a semi-urban HIV-positive Ugandan population.

PCR-SSP was used to HLA-type a cohort of Ugandan HIV-positive individuals. The results represent a more comprehensive description of HLA in an African population than previously described and are in concordance with data from a general Black population. Substantial differences exist between this population and Caucasoid populations in which immunological responses to HIV have been investigated; this emphasises that the main HLA-restrictive elements for HIV-specific cytotoxic T lymphocytes will most likely be different for each population.

Base Sequence↗
PubMed1999

Type of partnership and heterosexual spread of HIV infection in rural Uganda: results from simulation modelling.

The objective was to estimate the likely percentage of HIV infections that may be attributable to one-off partnerships (such as those between female sex workers and their clients) and longer-term partnerships in rural Uganda. This was addressed by the application of a microsimulation model (SimulAIDS) of the transmission dynamics of HIV infection, drawing on data from a population cohort of 10,000 in rural Uganda. For a scenario reproducing documented characteristics of the study population in 1990, when adult HIV prevalence was 9%, and during subsequent follow up (1990-1994), when adult HIV incidence was 8 per 1000 person-years, the percentage of HIV infections in men (women) attributed to one-off partnerships decreased from 96% (26%) during 1980 to 67% (8%) in 1989 and 22% (5%) in 1994. Reducing HIV transmission between one-off partners early in an HIV epidemic may substantially limit the potential for the spread of HIV infection. At a later phase, prevention must also focus on control of transmission between longer-term HIV-discordant partners.

Adult↗