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Biomedical subjects

D W Mulder

Publications and source records attributed to D W Mulder.

At least 19 recordsLinked to original sources

Seroprevalence and incidence of genital ulcer infections in a rural Ugandan population.

OBJECTIVES: To determine age-sex specific seroprevalence and incidence rates of Treponema pallidum, Haemophilus ducreyi, and HSV-2; to assess the association between HIV-1 status and incidence of these STIs; and HSV-2 serostatus with number of lifetime sexual partners. METHODS: Antibodies against HIV-1, T pallidum, H ducreyi, and HSV-2 infections were tested using approximately 1000 paired (2 year interval) sera collected from a rural adult (15-54 years) population cohort in south west Uganda. RESULTS: Overall HIV-1 prevalence was 4.9%. Prevalence for T pallidum was 12.9% among males and 12.6% among females. The corresponding rates for H ducreyi were 9.8% and 7.3% respectively. HSV-2 prevalence rates were considerably lower in males (36.0%) than in females (71.5%), p < 0.001. Incidence rates for T pallidum per 1000 person years of observation were 8.4 for males and 12.3 for females. The corresponding rates for H ducreyi were 24.6 and 20.0 and for HSV-2 were 73.2 and 122.9 per 1000 person years of observation, respectively. The RR of HSV-2 incidence was 3.69 in HIV seropositive cases versus HIV seronegative after adjusting for age and sex. The corresponding RR for H ducreyi was 3.50 among female HIV positive cases versus negatives with no effect seen in males. Association between HIV-1 prevalence and prevalence of other STIs was significant (Mantel-Haenszel test) for H ducreyi (p = 0.01) and for HSV-2 (p = 0.004) but not for T pallidum (p > 0.4). HSV-2 prevalence was associated with number of lifetime sexual partners (females, p = 0.003; males, p = 0.08). CONCLUSIONS: The results have provided a reliable estimate of the magnitude of the STI problem and demonstrated an association between HIV-1 status and serology of other STIs in a general rural population in sub-Saharan Africa. The study has also highlighted a correlation between HSV-2 seropositivity and number of reported lifetime sexual partners.

AIDS-Related Opportunistic Infections↗

Mortality associated with HIV-1 infection over five years in a rural Ugandan population: cohort study.

OBJECTIVE: To assess the impact of HIV-1 infection on mortality over five years in a rural Ugandan population. DESIGN: Longitudinal cohort study followed up annually by a house to house census and medical survey. SETTING: Rural population in south west Uganda. SUBJECTS: About 10,000 people from 15 villages who were enrolled in 1989-90 or later. MAIN OUTCOME MEASURES: Number of deaths from all causes, death rates, mortality fraction attributable to HIV-1 infection. RESULTS: Of 9777 people resident in the study area in 1989-90, 8833 (90%) had an unambiguous result on testing for HIV-1 antibody; throughout the period of follow up adult seroprevalence was about 8%. During 35,083 person years of follow up, 459 deaths occurred, 273 in seronegative subjects and 186 in seropositive subjects, corresponding to standardised death rates of 8.1 and 129.3 per 1000 person years. Standardised death rates for adults were 10.4 (95% confidence interval 9.0 to 11.8) and 114.0 (93.2 to 134.8) per 1000 person years respectively. The mortality fraction attributable to HIV-1 infection was 41% for adults and was in excess of 70% for men aged 25-44 and women aged 20-44 years. Median survival from time of enrollment was less than three years in subjects aged 55 years or more who were infected with HIV-1. Life expectancy from birth in the total population resident at any time was estimated to be 42.5 years (41.4 years in men; 43.5 years in women), which compares with 58.3 years (56.5 years in men; 60.5 years in women) in people known to be seronegative. CONCLUSIONS: These data confirm that in a rural African population HIV-1 infection is associated with high death rates and a substantial reduction in life expectancy.

Adolescent↗

HIV-1 disease progression and AIDS-defining disorders in rural Uganda.

BACKGROUND: The majority of people infected with HIV-1 live in Africa, yet little is known about the natural history of the disease in that continent. We studied survival times, disease progression, and AIDS-defining disorders, according to the proposed WHO staging system, in a population-based, rural cohort in Uganda. METHODS: In 1990 we recruited a random sample of people already infected with HIV-1 (as prevalent cases) detected during the initial survey round of a general-population study to form a natural-history cohort. Individuals from the general-population cohort who seroconverted between 1990 and 1995 (incident cases) were also invited to enroll. Participants were seen routinely every 3 months and when they were III. FINDINGS: By the end of 1995, 93 prevalent cases and 86 incident cases had been enrolled. Four patients in the prevalent group were in stage 4 (AIDS) at the initial visit. During the next 5 years, 37 prevalent cases progressed to AIDS. Seven incident cases progressed to AIDS and the cumulative progression to AIDS at 1, 3, and 5 years after seroconversion was 2%, 6%, and 22%, respectively. The cumulative probability of AIDS at 4 years from entering stages 1, 2, and 3 was 11%, 33%, and 58%, respectively. There were 47 deaths among prevalent cases and seven among incident cases during follow-up. The cumulative mortality 4 years after patients entered stages 1, 2, 3, and 4 was 9%, 33%, 56%, and 86%, respectively. The median survival after the onset of AIDS was 9.3 months. INTERPRETATION: Our results are important for the setting of priorities and rationalisation of treatment availability in countries with poor resources. We found that progression rates to AIDS are similar to those in developed countries for homosexual cohorts and greater than for cohorts infected by other modes of transmission. However, we have found that the rates of all-cause mortality are much higher and the progression times to death are shorter than in developed countries.

Acquired Immunodeficiency Syndrome↗

Proportion of HIV infections attributable to other sexually transmitted diseases in a rural Ugandan population: simulation model estimates.

BACKGROUND: Unprotected heterosexual contact in the presence of other sexually transmitted diseases (STD) enhances the probability of HIV transmission. The objective of this study was to estimate the proportion of HIV infections attributable to STD in rural Uganda. METHODS: Simulation modelling scenarios of the transmission dynamics of HIV infection and of ulcerative and non-ulcerative STD were employed to address this objective, drawing on data from a specific rural population cohort of 10,000 in south-west Uganda. RESULTS: In simulations of the initial 10-year period of the HIV epidemic (1980-1990), over 90% of HIV infections were attributed to STD. Even given conservative assumptions about the prevalence of STD and about their enhancing effects on HIV transmission, STD played a critical role in the rapid and extensive spread of HIV infection. The role of STD decreased with progression of the HIV epidemic. CONCLUSIONS: In developing countries, control of the spread of HIV infection may benefit substantially from successful STD intervention programmes, and particularly in areas where HIV infection is not already well established.

Adolescent↗

An HIV-1 natural history cohort and survival times in rural Uganda.

OBJECTIVE: To describe a population-based rural cohort of HIV-1-seropositive and seronegative individuals established in 1990 in south-west Uganda, and determine survival times in the cohort. DESIGN: Prospective cohort study. METHODS: Participants were recruited from a large population study, and invited to attend a clinic every 3 months. They were seen by clinicians who administered detailed medical questionnaires and undertook a physical examination. RESULTS: By the end of 1995, 390 (79%) of the 491 people asked to enrol in the natural history cohort (NHC) had done so. Ninety-three were prevalent cases of HIV infection detected during the initial survey round of the general population cohort in 1989/1990, 66 were subsequent incident cases, 177 were age-matched HIV-negative controls and 54 were HIV-negative spouses of HIV-positive individuals. Twenty participants seroconverted in the NHC. The age-standardized mortality rates per 1000 person-years for the prevalent, incident, and negative cases were 156.5 [95% confidence interval (CI), 115.8-211.4], 35.0 (95% CI, 16.4 75.0) and 13.5 (95% CI, 7.3-25.1), respectively. The median survival time from enrolment to death for the prevalent cases was 4.5 years (95% CI, 3.5- > 5.2); > 5.4 years from seroconversion for the incident cases; and > 5.2 years from enrolment for the HIV-negative cases. The 5-year cumulative survival for prevalents, incidents and HIV-negative participants was 46%, 83% and 94%, respectively. CONCLUSIONS: We have described an NHC of HIV-positive and HIV-negative participants which is representative of the general population. The NHC was established over 5 years ago; it is continuing and we are maintaining good compliance rates. Survival probabilities in the cohort were lower than most other reported studies.

Adolescent↗

Post-natal incidence of HIV-I infection among children in a rural Ugandan population: no evidence for transmission other than mother to child.

We conducted a prospective cohort study to determine the post-natal incidence of and possible transmission routes for HIV-I infection in rural Ugandan children. The cohort consisted of the population of a cluster of 15 villages in Masaka District, south-west Uganda, and was enrolled in 1989-1990 through a demographic and serological survey. During the period 1991-1993 the population was resurveyed annually. A total of 5492 children aged 0-12 years were enrolled; of these, 41 (0.7%) were seropositive infants. A total of 3941 (72%) children were HIV-negative on enrolment and had at least one follow-up specimen. During 8596 person-years of observation only I seroconversion was observed, an incidence rate of 0.12 (95% CI 0.00-0.35) per 1000 years of observation. The transmission of HIV was most probably through breast milk. The case corresponds to a rate of 1.1 per 1000 in households with one or more HIV-positive adults (874 years of observation); no incident case was observed in households with only seronegative adults (6423 years of observation). Thus, HIV infection among children aged 0-12 years in this population is virtually exclusively the result of mother-to-child transmission. No infections were observed attributable to parenteral exposure, non-sexual casual or household contact, or insects.

Adolescent↗

The orphan problem: experience of a sub-Saharan Africa rural population in the AIDS epidemic.

An assessment of the prevalence of orphans and the magnitude of their problems and the extent to which HIV-1 is contributing to this was done in a rural population in South-West Uganda with an HIV-1 seroprevalence of 8% among adults. Slightly over 10% of children aged less than 15 years were reported to have lost one or both parents. Loss of the father alone (6.3%) was more common than loss of the mother alone (2.8%). Generally orphans were living with their surviving parent or other relatives but it was also noted in this study that some children with both parents alive lived with relatives as part of the extended family system. HIV-1 seroprevalence rates were higher among orphans than among non-orphans and were up to 6 times higher in the 0-4 year age group. Seropositivity rates were also higher among surviving parents of orphans than among parents of non-orphans. No significant difference in mortality between orphans and non-orphans was observed. During a 3-year follow-up period a total of 169 children became orphans and 43% of these cases resulted from the death of an HIV-1 positive parent. There was a limited effect on school attendance by orphanhood. The HIV-1 epidemic has substantially increased the number of orphans in this community, a finding which is probably typical of many other sub-Saharan African countries. It appears that these orphans were generally well looked after within the community. This coping capacity may, however become overstretched if the epidemic evolves further.

Acquired Immunodeficiency Syndrome↗

Verbal autopsy as a tool for diagnosing HIV-related adult deaths in rural Uganda.

BACKGROUND: In general, information on the causes of adult deaths in developing countries is scarce. More specifically, relatively little is known about the effect of HIV-1 associated disease on adult mortality in general populations. In this study we have used a verbal autopsy technique to ascertain whether adult deaths were associated with HIV-1 in a rural population with a prevalence of HIV-1 infection of 8%, and used HIV-1 antibody status to validate the verbal autopsy findings. METHODS: All adult deaths in the population cohort that occurred between December 1990 and November 1993 were identified through a monthly death registration system. Approximately 2 months after death, a relative of the deceased was interviewed by a trained nurse, and questionnaires were assessed by at least two independent clinicians; all were unaware of the HIV serostatus of the deceased. RESULTS: A total of 155 adult deaths was assessed, i.e. 53% of all recorded adult deaths. Of those assessed half were HIV-1 positive. In all 47% of deaths were classified as HIV-related. The overall specificity and positive predictive value of the verbal autopsy tool were both 92%; in those aged 13-44 years (83 adults) the corresponding values were 85% and 95% respectively. The verbal autopsy estimated HIV-1 attributable mortality fraction was similar to the calculated fraction based on prospective data. CONCLUSIONS: The results of this study suggest that verbal autopsy studies may assist in providing data on HIV-associated mortality in general populations and may be useful as surveillance tools.

Adolescent↗

Incidence of HIV-1 infection in adults and socio-demographic characteristics of seroconverters in a rural population in Uganda: 1990-1994.

BACKGROUND: To evaluate HIV-1 incidence among adults and socio-demographic risk factors in a rural population in Uganda, a prospective cohort study was carried out. METHODS: All consenting adult residents in a cluster of 15 neighbouring villages of the Masaka District of south-west Uganda have been participating in annual socio-demographic and serological surveys since November 1989. Those who had a negative serostatus when they were first tested and had at least one serostatus assessment during the 4 years of follow-up (1990-1994) have been evaluated for HIV-1 seroconversion. Incidence rates have been calculated per 1000 person-years of observation and socio-demographic characteristics assessed for association with recent seroconversion. RESULTS: At the baseline survey, of 4175 adults with assessable serostatus (79% of all censused adults), 342 (8.2%) were seropositive. During 12588.2 person-years of follow-up 89 seroconversions were identified corresponding to an incidence rate of 7.1 (95% CI: 5.6-8.5). Overall rates were highest in females aged 20-24 years (15.2) and in males aged 20-44 years (11.6). There was a significant interaction between age and sex; the ratio of the rate in females to that in males decreased from 3.3:1 to 0.5:1 with increasing age. Rates for males aged > or = 20 years were four times higher than those for younger males. Other significant socio-demographic correlates with risk included not belonging to the majority tribe, non-Muslim religion and length of stay on compound of less than 10 years. Incidence rates did not show any clear trends with time. CONCLUSION: These findings further emphasize the need for targeted interventions.

Adolescent↗

Clinical observations on acute poliomyelitis.

During the years of the polio epidemics, most patients with the poliovirus had little or no paralysis. In those with paralytic polio, the extent of involvement of the anterior horn cells was often underestimated. Thus, patients with post-polio syndrome now often report that a limb was uninvolved; however, the original record will show clear evidence of initial paralysis that improved so that the patient no longer recognized the weakness. The epidemics were associated with great anxiety involving the patients, their families and all of society. Treatment was for the most part ineffective and was sometimes confused or inappropriate. Patients developed coping techniques that have been singularly useful and effective. These coping techniques often include strategies that require maximal athletic development of little-used muscles. The coping techniques developed by post-polio patients would be of great benefit to patients with other forms of disability. Review of the medical histories, biographies, and autobiographies of patients who had severe disability because of poliomyelitis reveals that they adopted firm convictions about their disease and their recovery. We must be aware of these convictions if we are to treat their later disabilities. These convictions include the belief that their condition can only improve, that their improvement is related primarily to the willingness of the patient to engage in exercise, and that improvement is more a thing of the spirit than of medication. Associated with this conviction is denial--often concurred with by the family--of the extent of the disability. Furthermore, the confusion of physicians that patients witnessed during the great epidemics suggests to patients that physicians can be of little help to them now. Convictions that were invaluable to patients who were young and vigorous become a liability when aging and progressive weakness supervene. Patients who had adapted to muscle weakness through great physical and emotional effort are unable to continue functions they had regained. However, such patients cannot accept that they do not continue to improve. Some become depressed, but this is unusual.

Acute Disease↗

Human immunodeficiency virus (HIV-1) seropositivity among children in a rural population of south-west Uganda: probable routes of exposure.

Serological studies on 7796 rural Ugandans showed 377 (4.8%) were HIV-1 antibody-positive, of whom 343 (8.2%) were adults, ten (0.4%) 5-12-year-olds and 24 (1.7%) under 5 years of age. Serological tests done on 18 mothers of the under-5s showed 17 to be HIV-1-positive. One mother was persistently negative. Her child had a history of multiple injections. Structured interviews with parents or guardians of the ten HIV-1-seropositive children aged 5-12 years to determine possible sources of exposure revealed that six were vertically infected and that blood transfusion, injections and sexual exposure each accounted for one case. It was not possible to identify a source of exposure in one instance. There was no evidence that casual household contact or scarifications played a role in the transmission of HIV-1 in children in this population. Our data show that in this rural population HIV-1 seropositivity in children is mainly associated with seropositivity in the mothers and that HIV-1 infection in children aged between 5 and 12 years is rare.

Adult↗

Methods used to study household coping strategies in rural South West Uganda.

This paper describes the data collection methods used in a longitudinal study of the coping strategies of 27 households in three villages in the study area of the MRC/ODA Research Programme on AIDS in Uganda. After pre-testing and piloting, 9 local interviewers made regular visits to the 27 study households over a period of just over one year. The households were purposively selected to represent different household types and socioeconomic status categories. Data were obtained through participant observation using a checklist to ensure systematic collection of data on household activities. Debriefing sessions with the interviewers after the visits provided opportunities for the discussion of the findings and exploration of themes for further study. On the basis of the study findings, and data from the Programme's general study population survey rounds, broad indicators of household 'vulnerability' were identified. A participatory appraisal technique, 'well-being ranking', was used at the end of the study in order to test the viability of the chosen indicators. It is proposed that the example of the research method, which relied on local people not only as interviewers but also as co-investigators in the research, be used to guide future research approaches. The participation of the study community at every stage of research and design, as well as monitoring and evaluation of supportive interventions, is strongly encouraged.

Acquired Immunodeficiency Syndrome↗

Modelling the impact of alternative HIV intervention strategies in rural Uganda.

OBJECTIVE: To assess the likely impact on HIV incidence of increased condom use, a reduction in casual sexual partners, treatment programmes for other sexually transmitted diseases (STD) and combinations of these in rural Uganda. METHODS: A simulation model for the transmission dynamics of HIV infection and STD was employed, drawing on data from a rural population cohort in South-West Uganda with an HIV prevalence of 9% among adults in 1990. RESULTS: For the scenario most consistent with data from the study population, 39% of all adult HIV infections were averted, in the 10 years from 1990, when condoms were used consistently and effectively by 50% of men in their contacts with one-off sexual partners (such as bar girls and commercial sex workers). Reducing by 50% the frequency of men's sexual contacts with one-off partners averted 68% of infections. Reducing by 50% the duration of all STD episodes averted 43% of infections. Combining these three interventions averted 82% of all adult infections in the 10 years from 1990. CONCLUSION: A substantial proportion of HIV infections may be averted in general populations through interventions targeted only on less regular sexual partnerships.

Adult↗

Migration and HIV-1 seroprevalence in a rural Ugandan population.

OBJECTIVE: To study the association between change of residence and HIV-1 serostatus in a rural Ugandan population. DESIGN: A longitudinal cohort study. METHODS: As part of the annual surveillance of a population cohort of approximately 10,000 individuals in a rural subcounty of southwest Uganda, information has been collected for all adults on change of residence over a 3-year period and its association with HIV-1 serostatus. Sera were collected by a medical team during home visits. Antibody testing was performed at the Uganda Virus Research Institute using two independent enzyme immunoassay systems and Western blot when appropriate. RESULTS: At the fourth survey-round, age and sex-standardized seroprevalence rates were 7.9% overall; the rate was 5.5% for 2,129 adults who had not changed address since the first survey, 8.2% for 336 who moved within the village, 12.4% for 128 who moved to a neighbouring village, 11.5% for 1,130 who had left the area and 16.3% for 541 who had joined the study area during the previous 3 years (P << 0.001, 4 degrees of freedom). We also observed an inverse relationship between years lived at the present house at the time of the first survey and both seroprevalence and subsequent seroincidence rates. The reported numbers of lifetime sexual partners were higher in those who changed residence. CONCLUSION: Change of residence is strongly associated with an increased risk of HIV-1 infection in this rural population and is likely to be the result of more risky sexual behaviour among those who move. These findings have important implications for the design of AIDS control programmes and intervention studies.

Adult↗

Two-year HIV-1-associated mortality in a Ugandan rural population.

The mortality in 15 villages in South-West Uganda was studied in relation to HIV infection. After a population census, serum samples were tested for antibodies to HIV-1. Deaths were ascertained over 2 years. Unequivocal HIV-1 serology results were available for 9389 individuals. The prevalence of infection was 4.8% for all ages and 8.2% for adults (aged 13 or more). 198 deaths were recorded during 15,725 person years of observation. Mortality among seronegative adults was 7.7 per 1000 and among seropositive adults 115.9 per 1000. The excess annual death rate associated with HIV-1 infection was 5.3 per 1000 and in adults 7.9 per 1000. Highest excess mortality was 16.9 per 1000 in the age group 25-34. Among adults, half of all deaths and among those aged 13-44 over 80% of deaths were attributable to HIV-1 infection. These results show the strong impact that HIV-1 infection is having on mortality in a rural area of Uganda where the overall HIV-1 adult prevalence rate is below 10%--a rate lower than in many other parts of East Africa.

Adolescent↗

Recognition, treatment seeking behaviour and perception of cause of malaria among rural women in Uganda.

This study was conducted in order to understand how women in rural Uganda recognise malaria, their treatment-seeking behaviour when malaria is suspected and how the perception of cause may influence this behaviour. Focus group discussions and semi-structured interviews were held with women selected from the general population and from women attending health clinics for both preventive and curative services. The main finding of this study was that the word used for malaria in the local language, omusujja, covered a broad symptom complex which did not consistently correspond to the clinical case definition of malaria. Since there was no specific word for 'malaria', the study was broadened to encompass omusujja. The women reported that omusujja was an important health problem which had various causes, including poor diet, environmental conditions, and the bites of mosquitoes. The symptoms associated with omusujja were quite varied and ranged from generally 'feeling unwell' to a specific fever diagnosis (usually in children) of 'a rise in body temperature'. Women recognised that omusujja posed a particular threat to pregnant women. Preventive actions recommended by the women were in line with their perceptions of cause. The respondents usually mentioned the use of herbs as the first treatment action, followed by the purchase of tablets from shops, with the final recourse being the formal health sector if the previous actions had not effected a cure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗