Evaluation of multiplex real-time PCR for detection of Haemophilus ducreyi, Treponema pallidum, herpes simplex virus type 1 and 2 in the diagnosis of genital ulcer disease in the Rakai District, Uganda.

OBJECTIVE: To develop a real-time PCR assay that reliably and accurately detects the predominant sexually transmitted aetiological agents of genital ulcer disease (GUD) (Haemophilus ducreyi, Treponema pallidum and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)) and to assess the use of real-time PCR diagnostic testing in a rural African field site. METHODS: Two multiplex real-time PCR reactions were used to detect H ducreyi/and HSV-1/HSV-2 in ulcer swabs from 100 people with symptomatic genital ulcers in rural Rakai, Uganda. Results were compared with syphilis, HSV-1 and HSV-2 serology. RESULTS: Of 100 GUD samples analysed from 43 HIV positive and 57 HIV negative individuals, 71% were positive for one or more sexually transmitted infection (STI) pathogens by real-time PCR (61% for HSV-2, 5% for T pallidum, 3% for HSV-1, 1% for H ducreyi and 1% for dual H ducreyi/HSV-2). The frequency of HSV in genital ulcers was 56% (32/57) in HIV negative individuals and 77% (33/43) in HIV positive individuals (p = 0.037). Assay reproducibility was evaluated by repeat PCR testing in the USA with 96% agreement (kappa = 0.85). CONCLUSIONS: STI pathogens were detected in the majority of GUD swab samples from symptomatic patients in Rakai, Uganda, by real-time PCR. HSV-2 was the predominant cause of genital ulcers. Real-time PCR technology can provide sensitive, rapid and reproducible evaluation of GUD aetiology in a resource-limited setting.

Aetiology of genital ulcer disease in female partners of male participants in a circumcision trial in Uganda.

HIV acquisition is associated with herpes simplex virus type 2 (HSV-2) infection and genital ulcer disease (GUD). Three randomized control trials demonstrated that male circumcision significantly decreases HIV, HSV-2, human papillomavirus and self-reported GUD among men. GUD is also decreased among female partners of circumcised men, but it is unknown whether male circumcision status affects GUD pathogens in female partners. For the evaluation of GUD aetiology, two separate multiplex assays were performed to detect Haemophilus ducreyi, Treponema pallidum, HSV-1 and HSV-2. Of all the female GUD swabs evaluated, 67.5% had an aetiology identified, and HSV-2 was the primary pathogen detected (96.3%). However, there was no difference in the proportion of ulcers due to HSV-2 or other pathogens between female partners of circumcised men (11/15, 73.3%) compared with uncircumcised men (15/25, 60.0%, P = 0.39). The seroprevalence of HSV-2 is high in this population and therefore most of the detected HSV-2 infections represent reactivation. Since GUD is associated with HIV acquisition and one-third of GUD in this study did not have an aetiological agent identified, further research is needed to better understand the aetiology of GUD in Africa, and its relationship to circumcision and HIV infection.

Ocular injuries in patients with major trauma.

AIM: To study the epidemiology of ocular injuries in patients with major trauma in the UK, determining the incidence and causes of ocular injuries, and their association with facial fractures. METHODS: A retrospective analysis of the Trauma Audit Research Network database from 1989 to 2004, looking at data from 39,073 patients with major trauma. RESULTS: Of the 39,073 patients with major trauma, 905 (2.3%) patients had associated ocular injuries and 4082 (10.4%) patients had a facial fracture (zygoma, orbit or maxilla). The risk of an eye injury for a patient with a facial fracture is 6.7 times as that for a patient with no facial fracture (95%, confidence interval 5.9 to 7.6). Of the patients with major trauma and an eye injury, 75.1% were men, and the median age was 31 years. 57.3% of ocular injuries were due to road traffic accidents (RTAs). CONCLUSION: The incidence of ocular injuries in patients with major trauma is low, but considerable association was found between eye injuries and facial fractures. Young adults have the highest incidence of ocular injury. RTAs are the leading cause of ocular injuries in patients with major trauma. It is vital that all patients with major trauma are examined specifically for an ocular injury.

Identification of plasma cells in lung alveoli and interstitial tissues after localized lung immunization.

Large numbers of antibody-forming cells (AFC) can be identified with the Jerne plaque assay in immunized lung lobes of the beagle dog after localized instillation of particulate antigen. Published data suggest that these AFC are secreting antibody and are responsible for increased levels of specific antibody in immunized lung lobes. If AFC in the lung are actively secreting antibody, there should be an increase in the number of mature plasma cells in lung lobes exposed to antigen. The purposes of this study were to evaluate the number of lymphoid cells present in immunized and control lung lobes and to determine if lung immunization produces a localized increase in the number of plasma cells. Sheep red blood cells (SRBC), autologous dog red blood cells, and saline were instilled into specific lung lobes of beagle dogs with the aid of a fiberoptic bronchoscope. Light and transmission electron microscopy studies of tissues from lung lobes instilled with SRBC showed perivascular infiltrates and intra-alveolar accumulations of lymphoid cells which were not present in control lung lobes. The morphology of these lymphoid cells ranged from small lymphocytes through mature plasma cells. From 5% to 15% of the cells present in the interstitial tissues and alveoli of immunized lung lobes were plasma cells. These observations suggest that lymphoid cells which entered the SRBC immunized lung can mature to plasma cells which are probably responsible for the local production of antigen-specific antibody.

Demographic impact of HIV infection in rural Rakai district, Uganda: results of a population-based cohort study.

OBJECTIVES: To examine HIV-1-related mortality and demographic impact in a high HIV prevalence rural district of Uganda. DESIGN: One-year follow-up (1990-1991) in a population-based rural cohort. SETTING AND PARTICIPANTS: Annual enumeration of all consenting residents of 1945 households in 31 randomly selected community clusters in Rakai District. Subjects provided yearly HIV serological samples, behavioral and health information. MAIN OUTCOME MEASURE: Mortality in HIV-infected and uninfected persons. RESULTS: Mortality among HIV-seropositive adults aged > or = 15 years of 118.4 per 1000 person-years (PY) was substantially higher than in HIV-seronegative adults [12.4 per 1000 PY; relative risk (RR), 9.5; 95% confidence interval (CI), 6.0-14.9]. Infant mortality among offspring of HIV-infected mothers was almost double that for uninfected women (210 compared with 111 per 1000 live births; RR, 1.9; 95% CI, 1.0-3.5). Adult HIV-related mortality was associated with HIV prevalence and, in this cohort, with higher education, non-agricultural occupation and residence in roadside trading centers. We estimate that adult HIV prevalence in the district is 13% and adult HIV attributable mortality 52%. For all ages combined, district HIV attributable mortality is 28%. CONCLUSION: HIV is the leading cause of adult death in Rakai. Its effects on mortality are particularly marked in the most economically active sectors. However, the overall crude birth rate in the district (45.7 per 1000 population) remains higher than the crude death rate (28.1 per 1000 population), resulting in continued rapid population growth.

HIV risk factors in three geographic strata of rural Rakai District, Uganda.

OBJECTIVES: To examine risk factors for HIV-1 infection in three geographic strata (main road trading centers that service local and international traffic, small trading villages on secondary dirt roads that serve as foci for local communications, and agricultural villages off main and secondary roads) in Rakai District, Uganda. DESIGN AND METHODS: Serological, sociodemographic, knowledge/behaviors and health survey conducted in 21 randomly selected community clusters; complete data were collected for 1292 consenting adults. RESULTS: Fifteen per cent of the men and 24% of the women were HIV-1-positive. On univariate analysis, several sociodemographic and behavioral factors were significantly associated with risk of HIV infection, including age, place of residence, travel, occupation, marital status, number of sex partners, sex for money or gifts, history of sexually transmitted disease (STD), and history of injections. On multivariate analysis, age, residence and number of sex partners remained significantly associated with HIV infection in both sexes; a history of STD and not having been circumcised were significant in men. There was a significant interaction between place of residence and reported number of sex partners: for any given level of sexual activity, the risk of HIV infection was markedly increased if the background community prevalence was high. CONCLUSION: Sexual transmission appears to be the primary behavioral risk factor for infection, but the risks associated with this factor vary substantially between the three geographic strata. These data can be used to design targeted interventions.

Trends in HIV-1 prevalence may not reflect trends in incidence in mature epidemics: data from the Rakai population-based cohort, Uganda.

OBJECTIVES: To assess whether trends in serial HIV-1 prevalence reflect trend in HIV incidence, and to decompose the effects of HIV-1 incidence, mortality, mobility and compliance on HIV-1 prevalence in a population-based cohort. DESIGN: Two-year follow up (1990-1992) of an open cohort of all adults aged 15-59 years, resident in a sample of 31 representative community clusters in rural Rakai District, Uganda. METHODS: A detailed household enumeration was concluded at baseline and in each subsequent year. All household residents were listed, and all deaths and in- and out-migrations that occurred in the intersurvey year wee recorded. In each year, all consenting adults were interviewed and provided a serological sample; 2591 adults aged 15-59 years were enrolled at baseline. RESULTS: HIV prevalence among adults declined significantly 1990 and 1992 (23.4% at baseline, 21.8% in 1991, 20.9% in 1992; P < 0.05). Declining prevalence was also observed in subgroups, including young adults aged 15-24 years (from 20.6 to 16.2% over 3 years; P < 0.02), women of reproductive age (from 27.1 to 23.5%; P < 0.05), and pregnant women (from 25.4 to 20.0%; not significant), However, HIV incidence did not change significantly among all adults aged 15-59 years (2.1 +/- 0.4 per 100 person-years of observation (PYO) in 1990-1991 and 2.0 +/- 0.3 per 100 PYO in 1991-1992], nor in population subgroups. HIV-related mortality was high (13.5 per 100 PYO among the HIV-positive), removing more infected persons that were added by seroconversion. Net out-migration also removed substantial numbers of HIV-positive individuals. CONCLUSIONS: In this mature HIV epidemic, HIV prevalence declined in the presence of stable and incidence. HIV-related mortality contributed most to the prevalence decline. Prevalence was not an adequate surrogate measure of incidence, limiting the utility or serial prevalence measures in assessing the dynamics of the HIV epidemic and in evaluating the impact of current preventive strategies.

PIP: Findings are reported from a 2-year follow-up study of an open cohort of people aged 15-59 years living in a sample of 31 representative community clusters in rural Rakai district, Uganda, to measure whether trends in serial HIV-1 prevalence reflect trends in HIV incidence, and to gain insight into the effects of HIV-1 incidence, mortality, mobility, and compliance upon HIV-1 prevalence. In each year of study, all consenting adults provided a serological sample and were interviewed; 2591 adults were enrolled at baseline. HIV prevalence among adults declined significantly between 1990 and 1992; from 23.4% in 1990, to 21.8% in 1991, and 20.9% in 1992. Declining prevalence was also observed in subgroups, including young adults aged 15-24 years from 20.6% to 16.2%, reproductive-age women from 27.1% to 23.5%, and pregnant women from 25.4% to 20.0%. The decline in HIV prevalence among pregnant women, however, is not significant. HIV incidence did not change significantly among all adults aged 15-59 years, nor in population subgroups. HIV-related mortality was 13.5/person-year of observation among those who were HIV-positive. Substantial numbers of HIV-infected individuals were also loss to emigration.

Adolescents, sexual behaviour and HIV-1 in rural Rakai district, Uganda.

OBJECTIVES: To describe the epidemiology of HIV-1 infection among adolescents aged 13-19 years, in rural Rakai district, Uganda. STUDY DESIGN: Baseline survey and 2-year follow-up (1990-1992) of adolescents in a population-based, open rural cohort. METHODS: Annual enumeration and behavioral/serological survey of all consenting adolescents aged 13-19 years at recruitment, residing in 31 randomly selected community clusters. RESULTS: At baseline, of 909 adolescents present in study clusters, 824 (90.6%) provided interview data and serological samples. No adolescents aged 13-14 years were HIV-infected. Among those aged 15-19 years, 1.8% of men and 19.0% of women were HIV-positive. Among young women aged 15-19 years in marital/consensual union, 21.3% were HIV-positive; this rate did not differ significantly from the 29.1% prevalence in those reporting non-permanent relationships; prevalence was significantly lower in women reporting no current relationship (4.3%). After multivariate adjustment, female sex, age 17-19 years, residence in trading centers/trading villages and a history of sexually transmitted disease symptoms remained significantly associated with HIV infection. Seventy-nine per cent of adolescents provided a follow-up serological sample. No young men aged 13-14 years seroconverted during the study; in young women aged 13-14 years, HIV seroincidence was 0.6 per 100 person-years (PY) of observation. Among young men aged 15-19 years, there were 1.1 +/- 0.6 seroconversions per 100 PY of observation prior to age 21 years; among women 15-19 years, the incidence rate was 3.9 +/- 1.0 per 100 PY of observation prior to age 21 years. The mortality rate among HIV-positive adolescents aged 15-19 years, at 3.9 per 100 PY of observation, was 13-fold higher than that among the HIV-uninfected. By 1992, knowledge of sexual transmission was almost universal, the proportions reporting multiple partners had decreased and condom use had increased over baseline. CONCLUSIONS: Adolescents, and young women in particular, are vulnerable to HIV infection. Despite reported behavioral changes, HIV incidence rates remain substantial, and there is a need for innovative HIV preventive measures.

The social dynamics of HIV transmission as reflected through discordant couples in rural Uganda.

OBJECTIVE: To describe the role of men and women as sources of HIV transmission and to estimate HIV incidence among discordant couples resident in diverse rural communities in Uganda. SETTING: Rakai, a rural district in Uganda, East Africa. METHODS: A population-based cohort study, which has been conducted as annual serological and behavioral surveys since 1989. Community clusters were stratified into trading centers on main roads, intermediate trading villages on secondary roads and agricultural villages off roads. In the 1990 survey round, serological data were available for 79 discordant and 411 concordant HIV-negative couples aged 13-49 years. The present analysis examines sex-specific seropositivity associated with place of residence and the incidence of seroconversion among discordant couples between 1990 and 1991. RESULTS: Seventy-nine discordant couples were followed; the HIV-positive partner was male in 44 couples (57%) and female in 35 couples (43%). There was marked variation in the sex of the seropositive partner by place of residence: women were the HIV-positive partner in 57% of couples from trading centers, 52% from intermediate villages, and 20% from agricultural communities (P < 0.008). Condom use was higher in discordant couples in which the man was the uninfected partner (17.1%) rather than the woman (9.5%). HIV-positive women, but not HIV-positive men, reported significantly more sexual partners and more genital ulcers than seronegative individuals of the same sex. Seroincidence rates among men and women in discordant relationship were 8.7 and 9.2 per 100 person-years (PY), respectively, which was much higher than in concordant seronegative couples (men, 0.82; women, 0.87 per 100 PY). CONCLUSIONS: In this Ugandan population, men are the predominant source of new infections in rural villages. Risk factors and preventive behaviors vary with the sex of the infected partner, and seroconversion rates are similar in both sexes.

PIP: The analysis of marital relationships in rural Uganda in which one partner is infected with human immunodeficiency virus (HIV) revealed important information about the social dynamics of HIV transmission. As part of an ongoing cohort study of over 3000 adults in southwestern Uganda's Rakai district, data were collected on 79 discordant couples. The HIV-infected partner was male in 44 couples (57%) and female in 35 couples (43%). In the trading centers and intermediate trading villages, women were more likely to be the HIV-infected partner (57% and 52%, respectively); in rural areas, however, the male partner was the HIV carrier in 80% of discordant couples. 14.3% of women in female HIV-positive compared to only 2.1% of those in male HIV-positive discordant relationships reported two or more sexual partners in the year preceding the interview; there was no significant difference on this factor among HIV-positive and HIV-negative men (48.8% and 45,7%, respectively). 17.1% of seronegative men with HIV-infected wives compared to only 9.5% of seropositive men with seronegative wives used condoms with their partner. During the one-year study period, the rate of seroconversion was 8.7/100 years of observation for men and 9.2 for women. Extrapolation of the data from this study to the district as a whole suggests that 18.7% of couples have at least one HIV-infected member. Needed are campaigns to promote monogamy and condom use, particularly among men from rural areas who travel to high prevalence trading areas.

Male circumcision and HIV acquisition and transmission: cohort studies in Rakai, Uganda. Rakai Project Team.

BACKGROUND: Male circumcision is associated with reduced HIV acquisition. METHODS: HIV acquisition was determined in a cohort of 5507 HIV-negative Ugandan men, and in 187 HIV-negative men in discordant relationships. Transmission was determined in 223 HIV-positive men with HIV-negative partners. HIV incidence per 100 person years (py) and adjusted rate ratios (RR) and 95% confidence intervals (CI) were estimated by Poisson regression. HIV-1 serum viral load was determined for the seropositive partners in HIV-discordant couples. RESULTS: The prevalence of circumcision was 16.5% for all men; 99.1% in Muslims and 3.7% in non-Muslims. Circumcision was significantly associated with reduced HIV acquisition in the cohort as a whole (RR 0.53, CI 0.33-0.87), but not among non-Muslim men. Prepubertal circumcision significantly reduced HIV acquisition (RR 0.49, CI 0.26-0.82), but postpubertal circumcision did not. In discordant couples with HIV-negative men, no serconversions occurred in 50 circumcised men, whereas HIV acquisition was 16.7 per 100 py in uncircumcised men (P = 0.004). In couples with HIV-positive men, HIV transmission was significantly reduced in circumcised men with HIV viral loads less than 50000 copies/ml (P = 0.02). INTERPRETATION: Prepubertal circumcision may reduce male HIV acquisition in a general population, but the protective effects are confounded by cultural and behavioral factors in Muslims. In discordant couples, circumcision reduces HIV acquisition and transmission. The assessment of circumcision for HIV prevention is complex and requires randomized trials.

Mortality associated with HIV infection in rural Rakai District, Uganda.

OBJECTIVE: To assess mortality impact of HIV in rural Uganda. METHODS: An open cohort of 19983 adults aged 15-59 years, in Rakai district was followed at 10 month intervals for four surveys. Sociodemographic characteristics and symptomatology/disease conditions were assessed by interview. Deaths among residents and out-migrants were identified household census. Mortality rates were computed per 1000 person years (py) and the rate ratio (RR) of death in HIV-positive/HIV-negative subjects, and the population attributable fraction (PAF) of death were estimated according to sociodemographic characteristics. Mortality associated with potential AIDS defining symptoms and signs was assessed. RESULTS: HIV prevalence was 16.1%. Mortality was 132.6 per 1000 py in HIV-infected versus 6.7 per 1000 py in uninfected subjects, and 73.5% of adult deaths were attributable to HIV infection. Mortality increased with age, but the highest attributable risk of HIV associated deaths were observed in persons aged 20-39 years (PAF > 80%) and in women. HIV associated mortality was highest in the better educated (PAF > or = 75%) and among government employees (PAF > or = 82%). Of the HIV-positive subjects 40.5% reported no illness < 10 months preceding death, symptoms were poor predictors of death (sensitivity 1.6-38.8%), and only 9.1% met the World Health Organization clinical definition of AIDS. Infant mortality rates in babies of HIV-infected and uninfected mothers were 209.4 and 97.7 per 1000, respectively. CONCLUSION: HIV is taking substantial toll in this population, particularly among the younger better educated adults, and infants. Symptomatology or the World Health Organization definition of AIDS are poor predictors of death.

Age of male circumcision and risk of prevalent HIV infection in rural Uganda.

OBJECTIVE: To assess whether circumcision performed on postpubertal men affords the same level of protection from HIV-1 acquisition as circumcisions earlier in childhood. DESIGN: Cross-sectional study of a population-based cohort. SETTING: Rakai district, rural Uganda. METHODS: A total of 6821 men aged 15-59 years were surveyed and venous blood samples were tested for HIV-1 and syphilis. Age at circumcision was dichotomized into men who were circumcised before or at age 12 years (prepubertal) and men circumcised after age 12 years (postpubertal). Postpubertal circumcised men were also subdivided into those reporting circumcision at ages 13-20 years and > or = 21 years. RESULTS: HIV-1 prevalence was 14.1% in uncircumcised men, compared with 16.2% for men circumcised at age > or = 21 years, 10.0% for men circumcised at age 13-20 years, and 6.9% in men circumcised at age < or = 12 years. On bivariate analysis, lower prevalence of HIV-1 associated with prepubertal circumcision was observed in all age, education, ethnic and religious groups. Multivariate adjusted odds ratio of prevalent HIV-1 infection associated with prepubertal circumcision was 0.39 [95% confidence interval (CI), 0.29-0.53]. In the postpubertal group, the adjusted odds ratio for men circumcised at ages 13-20 years was 0.46 (95% CI, 0.28-0.77), and 0.78 (95% CI, 0.43-1.43) for men circumcised after age 20 years. CONCLUSIONS: Prepubertal circumcision is associated with reduced HIV risk, whereas circumcision after age 20 years is not significantly protective against HIV-1 infection. Age at circumcision and reasons for circumcision need to be considered in future studies of circumcision and HIV risk.

Relative risks and population attributable fraction of incident HIV associated with symptoms of sexually transmitted diseases and treatable symptomatic sexually transmitted diseases in Rakai District, Uganda. Rakai Project Team.

OBJECTIVES: To assess the linkage of sexually transmitted disease (STD) symptoms and treatable STD to HIV incidence. DESIGN: Analysis of a randomized trial of STD control for HIV prevention, Rakai, Uganda. METHODS: Consenting adults 15-59 years of age were seen at 10-monthly home visits, interviewed regarding STD symptoms, and asked to provide samples for HIV and STD diagnoses. HIV incidence was determined in 8089 HIV-negative subjects over 10 457 person years. Adjusted rate ratios (RR) and 95% confidence intervals (CI) of HIV acquisition associated with genital ulcer disease (GUD) and discharge/dysuria were used to estimate the population attributable fraction (PAF) of HIV acquisition. HIV transmission risks associated with STD symptoms in HIV-positive partners of 167 HIV discordant couples and the numbers of sexual partners reported by HIV-positive subjects were used to estimate the PAF of HIV transmission attributable to STD. RESULTS: HIV prevalence was 16%. The risk of HIV acquisition was increased with GUD (RR 3.14; CI 1.98-4.98) and in males with discharge/dysuria (RR 2.44; CI 1.17-5.12), but not in females with discharge/dysuria. The PAF of HIV acquisition was 9.5% (CI 2.8-15.8%) with any of the three STD symptoms. The PAF for GUD was 8.8% (CI 3.7-13.8), but only 8.2% of reported GUD was caused by treatable syphilis or chancroid . The PAF for discharge/dysuria in males was 6.7% (CI 1.1-13.8), but only 25% of symptomatic males had concurrent gonorrhea or chlamydial infection. No significant differences were seen in PAF between study treatment arms. The PAF of HIV transmission associated with STD symptoms in HIV-positive persons was indirectly estimated to be 10.4%. CONCLUSION: In this mature, generalized HIV epidemic setting, most HIV seroconversion occurs without recognized STD symptoms or curable STD detected by screening. Therefore, syndromic management or other strategies of STD treatment are unlikely to substantially reduce HIV incidence in this population. However, STD is associated with significant HIV risk at the individual level, and STD management is needed to protect individuals.

A randomized, community trial of intensive sexually transmitted disease control for AIDS prevention, Rakai, Uganda.

OBJECTIVE: To describe the design and first-round survey results of a trial of intensive sexually transmitted disease (STD) control to reduce HIV-1 incidence. STUDY DESIGN: Randomized, controlled, community-based trial in Rakai District, Uganda. METHODS: In this ongoing study, 56 communities were grouped into 10 clusters designed to encompass social/sexual networks; clusters within blocks were randomly assigned to the intervention or control arm. Every 10 months, all consenting resident adults aged 15-59 years are visited in the home for interview and sample collection (serological sample, urine, and, in the case of women, self-administered vaginal swabs). Sera are tested for HIV-1, syphilis, gonorrhea, chlamydia, trichomonas and bacterial vaginosis. Following interview, all consenting adults are offered directly observed, single oral dose treatment (STD treatment in the intervention arm, anthelminthic and iron-folate in the control arm). Treatment is administered irrespective of symptoms or laboratory testing (mass treatment strategy). Both arms receive identical health education, condom and serological counseling services. RESULTS: In the first home visit round, the study enrolled 5834 intervention and 5784 control arm subjects. Compliance with interview, sample collection and treatment was high in both arms (over 90%). Study arm populations were comparable with respect to sociodemographic and behavioral characteristics, and baseline HIV and STD rates. The latter were high: 16.9% of all subjects were HIV-positive, 10.0% had syphilis, and 23.8% of women had trichomonas and 50.9% had bacterial vaginosis. CONCLUSIONS: Testing the effects of STD control on AIDS prevention is feasible in this Ugandan setting.

PIP: An ongoing (1994-98) randomized, community-based trial in Uganda's Rakai District is assessing the assumption that intensive sexually transmitted disease (STD) control efforts result in marked declines in HIV/AIDS prevalence. Described, in this article, are the project design and findings of the first-round baseline survey. 56 communities were grouped into 10 clusters designed to encompass social/sexual networks and clusters within blocks were randomly assigned to the intervention or control arm. All consenting permanent residents of the district are visited in their homes at 10-month intervals where they are administered extensive questionnaires, provide urine and vaginal swab samples, and are offered mass treatment regardless of symptoms or laboratory testing (single oral dose STD treatment in the intervention arm and anthelmintics and iron folate in the control arm). Both groups receive identical health education, condom promotion, and serologic counseling services. In the first round of home visits, 5834 intervention and 5784 control arm subjects were enrolled, representing about 90% of eligible adults. The groups were comparable in terms of sociodemographic and behavioral characteristics and baseline rates of HIV and STDs. 16.9% of subjects were HIV-positive, 10.0% had syphilis, 23.8% of women had trichomonas, and 50.9% had bacterial vaginosis. Detailed STD assessment is expected not only to document the relationship between STD control and HIV, but also to identify which STDs confer the greatest population attributable risk for HIV transmission, facilitating targeted control efforts in the future.

Translation of polysomal messenger RNA during epidermal differentiation.

Translation in vitro of messenger RNA obtained from preparations of active polysomes isolated from the epidermal basal, spinous, and granular cells of the newborn rat has provided evidence that in the context of differentiation in this tissue, control of protein synthesis is exerted at the level of transcription. The data supporting this hypothesis are reviewed.

Postpartum return of ovarian activity in nonbreastfeeding women monitored by urinary assays.

Assays of first morning urine samples for pregnanediol-3 alpha-glucuronide (PdG), estradiol-17 beta-glucuronide (E2G), and LH were used to monitor endocrine function in 16 regularly cycling women and 22 postpartum nonbreastfeeding women. Twice weekly blood samples were also obtained from the postpartum group. Ovulation was inferred by a significant rise in LH and PdG, and reversal of the E2G to PdG ratio. Luteal phase PdG excretion was measured by the peak of smoothed PdG levels and the area under the smoothed luteal phase PdG curve. The lower limits of normal established in 16 cycling women were a peak luteal phase PdG of 4 micrograms/ml and an area under the PdG curve of 20 micrograms/ml. In the postpartum women, 32% of first cycles were anovulatory, and among ovulatory cycles, 73% had abnormally low luteal phase PdG excretion or short luteal phases. In second and subsequent cycles, 15% were anovulatory and 26% had luteal phase abnormalities. There was a progressive increase in luteal PdG excretion from the first to third cycles. The mean delay before first ovulation was 45.2 days, and no woman ovulated before 25 days after delivery. The correlations between blood and urinary hormone levels were 0.78 for PdG, 0.65 for E2G, and 0.55 for LH. We conclude that assays of daily early morning urine samples provide reliable information on ovulation and luteal phase adequacy, and that there is gradual recovery of pituitary ovarian function after parturition.

Determinants of preterm delivery and intrauterine growth retardation in north-east Brazil.

A case-control study was conducted in Natal, north-east Brazil to determine the risk factors for low birthweight (LBW). Cases were 429 preterm and 422 intrauterine growth retarded (IUGR) singleton infants. Controls were 2555 infants of normal birthweight and gestational age. The prevalence of LBW was 10% (5.1% preterm and 4.9% IUGR). Logistic regression was used to estimate the adjusted odds ratios of LBW, and attributable risk per cent (AR%) was used to estimate the proportion of LBW that might be prevented. The preventable determinants of preterm delivery were births to women less than 20, (AR = 7.1%), low maternal weight less than 50 kg (AR = 20.5%), smoking during pregnancy (AR = 14.6%) and infrequent antenatal visits (AR = 28.1%). Other important determinants of preterm delivery were prior LBW births, gestational illness and vaginal bleeding. The main preventable causes of IUGR were low maternal weight (AR = 17.8%), low maternal education (AR = 11.6%), smoking (AR = 14.8%), and inadequate antenatal care (AR = 11.6%). Other risk factors for IUGR include primiparity, prior LBW births, and illness during gestation. In this population, the focus of short-term preventive programme should be improvement in maternal nutrition, cessation of smoking, reduction of births to women under 20, and improved antenatal care.

Risk factors for preterm and term low birthweight in Ahmedabad, India.

To identify and quantify risk factors for preterm and term low birthweight (LBW) we conducted a hospital-based case-control study, linked with a population survey in Ahmedabad, India. The case-control study of 673 term LBW, 644 preterm LBW cases and 1465 controls showed that low maternal weight, poor obstetric history, lack of antenatal care, clinical anaemia and hypertension were significant independent risk factors for both term and preterm LBW. Short interpregnancy interval was associated with an increased risk of preterm LBW birth while primiparous women had increased risk of term LBW. Muslim women were at a reduced risk of term LBW, but other socioeconomic factors did not remain significant after adjusting for these more proximate factors. Estimates of the prevalence of risk factors from the population survey was used to calculate attributable risk. This analysis suggested that a substantial proportion of term and preterm LBW births may be averted by improving maternal nutritional status, anaemia and antenatal care.

PIP: In 1987-1988, researchers compared data on 1317 low birth weight (LBW) infants and 1465 control infants born in 3 teaching hospitals in Ahmedabad, India to calculate attributable risk (AR) for factors contributing to low birth weight. 673 of the infants were full term yet LBW due to intrauterine growth retardation. 644 of LBW infants were preterm births. They also conducted a population survey in Ahmedabad to estimate the prevalence of risk factors. LBW prevalence stood at 30%. Low maternal weight, poor pregnancy history, lack of prenatal care, clinical anemia, and hypertension were all significant independent risk factors for term and preterm LBW infants (p.05). Primiparous women were more likely to have a term LBW infant than other women (p.05). Interpregnancy intervals =or 6 months was more likely to result in delivery of a preterm LBW infant than longer interpregnancy intervals (p.05). Muslim women were at a much lower risk of delivering a term LBW infant than were Hindu women (p.05). Other than primiparity for term LBW infants (AR=21.9%), maternal weight between 41-45 kg was the single greatest risk factor for LBW (AR=21.5% for term and 19.8% for preterm). Yet low maternal weight had greater adjusted odds ratios (OR) than did maternal weight between 41-45 kg (OR=6.9 and 6.2 vs. OR=3.1 and 2.9). Maternal weight was used to measure nutritional status. Clinical anemia also carried a high Ar, especially for term LBW infants (3.7-8.2% vs. 2.8-7.3% for preterm infants). Another risk factor with considerable AR was no prenatal care (5.8% for term and 14.4% for preterm). These results emphasized the need for health and nutrition interventions to reduce the incidence of both preterm and term LBW infants in urban India.

Validation of the diagnosis of childhood morbidity using maternal health interviews.

The diagnosis of childhood illness by maternal health interview surveys is widely used to estimate the prevalence of childhood morbidity in developing countries. To determine the validity of interview-based diagnoses, and to define simple, sensitive and specific diagnostic algorithms, we compared symptoms and signs reported by mothers during structured interviews with physicians' diagnoses for 271 children on the Philippine island of Cebu. The 271 children had 318 physician diagnosed illnesses: 105 acute lower respiratory infections (ALRI), 121 diarrhoeas, 36 measles, 50 upper respiratory infections (URTI), 5 roseola infantums and one milaria rubria. An algorithm for measles (age greater than or equal to 120 days, rash and fever greater than or equal to 3 days and fading of rash) had a sensitivity and specificity of 94%. For ALRI an algorithm of cough, dysponea and fever had a sensitivity of 82%, but specificity was lower in comparison with URTI (58%) than with children who had no respiratory illness (79%). Inclusion of signs of respiratory distress (flaring of nostrils, intercostal retraction) raised the specificity to 83-84%, but reduced sensitivity to 68%. Diagnosis of diarrhoea based on frequent loose or liquid stools had a sensitivity of 95-97% and specificity of 80% in children with or without concomitant non-diarrhoeal illnesses. Addition of questions on numbers of stools (greater than or equal to 6 per day), and no signs of dehydration increased specificity to 95% but reduced the sensitivity to 84-86%. However, specific signs of dehydration were not well reported by the mothers.(ABSTRACT TRUNCATED AT 250 WORDS)