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H Grosskurth

Publications and source records attributed to H Grosskurth.

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Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial.

A randomised trial was done to evaluate the impact of improved sexually transmitted disease (STD) case management at primary health care level on the incidence of HIV infection in the rural Mwanza region of Tanzania. HIV incidence was compared in six intervention communities and six pair-matched comparison communities. A random cohort of about 1000 adults aged 15-54 years from each community was surveyed at baseline and at follow-up 2 years later. Intervention consisted of establishment of an STD reference clinic, staff training, regular supply of drugs, regular supervisory visits to health facilities, and health education about STDs. 12,537 individuals were recruited. Baseline HIV prevalences were 3.8% and 4.4% in the intervention and comparison communities, respectively. At follow-up, 8845 (71%) of the cohort were seen. Of those initially seronegative, the proportions seroconverting over 2 years were 48 of 4149 (1.2%) in the intervention communities and 82 of 4400 (1.9%) in the comparison communities. HIV incidence was consistently lower in the intervention communities in all six matched pairs. Allowing for the community-randomised design and the effects of confounding factors, the estimated risk ratio was 0.58 (95% CI 0.42-0.79, p = 0.007). No change in reported sexual behaviour was observed in either group. We conclude that improved STD treatment reduced HIV incidence by about 40% in this rural population. This is the first randomised trial to demonstrate an impact of a preventive intervention on HIV incidence in a general population.

Adolescent↗

Structure and epitope characterisation of the O-specific polysaccharide of Proteus mirabilis O28 containing amides of D-galacturonic acid with L-serine and L-lysine.

The O-specific polysaccharide of Proteus mirabilis O28 was found to contain D-galactose, D-galacturonic acid (GalA), 2-acetamido-2-deoxy-D-glucose, L-serine, L-lysine, and O-acetyl groups in molar ratios 1:2:1:1:1:1, the amino acids being linked via their alpha-amino group to the carboxyl group of GalA. The polysaccharide was studied using 1H- and 13C-NMR spectroscopy, including selective spin-decoupling, one-dimensional total correlation spectroscopy, two-dimensional homonuclear correlation spectroscopy (COSY), heteronuclear 13C,1H COSY, one-dimensional NOE, and two-dimensional rotating-frame NOE spectroscopy and partial acid hydrolysis followed by borohydride reduction, methylation, and GLC/MS analysis of the derived glycosyl alditols. The following structure of the repeating unit was established: [formula: see text] Epitope specificity of the P. mirabilis O28 polysaccharide was analysed using a homologous rabbit polyclonal antiserum in quantitative precipitation, passive immunohemolysis, and inhibition of passive immunohemolysis. Study with related synthetic glycopolymers (2-acrylamidoethyl glycosides of amides of alpha-D-GalA with amino acids copolymerised with acrylamide) showed the importance of D-GalA(L-Lys) for manifesting serological specificity of the O-antigen. Serological cross-reactions between P. mirabilis O28, S1959, and R14/S1959 (a transient-like form) are discussed.

Amides↗

A community trial of the impact of improved sexually transmitted disease treatment on the HIV epidemic in rural Tanzania: 1. Design.

OBJECTIVE: To describe the rationale and design of a randomized trial of the impact of improved services for the treatment of sexually transmitted diseases (STD) on the incidence of HIV infection in Mwanza Region, Tanzania. METHODS: The likely impact of improved STD treatment services on HIV incidence, and the need for empirical information on the effectiveness of this intervention strategy, are discussed. The rationale and design of such an intervention programme in Mwanza Region, and of a community-randomized trial to measure the impact of the programme on HIV and other STD, are presented. Problems in the design and interpretation of the trial are reviewed. RESULTS: Results of the baseline survey of the cohort of over 12,000 adults in 12 communities are presented in a companion paper. CONCLUSION: There is an urgent need for effective preventive measures against the HIV epidemic in sub-Saharan Africa and other developing regions. Improved STD treatment has been promoted as a potentially effective strategy, but there is little empirical information on its impact. The trial in Mwanza Region is the first randomized study of this intervention and should provide valuable data for health policy makers.

Adult↗

A community trial of the impact of improved sexually transmitted disease treatment on the HIV epidemic in rural Tanzania: 2. Baseline survey results.

OBJECTIVES: To determine baseline HIV prevalence in a trial of improved sexually transmitted disease (STD) treatment, and to investigate risk factors for HIV. To assess comparability of intervention and comparison communities with respect to HIV/STD prevalence and risk factors. To assess adequacy of sample size. SETTING: Twelve communities in Mwanza Region, Tanzania: one matched pair of roadside communities, four pairs of rural communities, and one pair of island communities. One community from each pair was randomly allocated to receive the STD intervention following the baseline survey. METHODS: Approximately 1000 adults aged 15-54 years were randomly sampled from each community. Subjects were interviewed, and HIV and syphilis serology performed. Men with a positive leucocyte esterase dipstick test on urine, or reporting a current STD, were tested for urethral infections. RESULTS: A total of 12,534 adults were enrolled. Baseline HIV prevalences were 7.7% (roadside), 3.8% (rural) and 1.8% (islands). Associations were observed with marital status, injections, education, travel, history of STD and syphilis serology. Prevalence was higher in circumcised men, but not significantly after adjusting for confounders. Intervention and comparison communities were similar in the prevalence of HIV (3.8 versus 4.4%), active syphilis (8.7 versus 8.2%), and most recorded risk factors. Within-pair variability in HIV prevalence was close to the value assumed for sample size calculations. CONCLUSIONS: The trial cohort was successfully established. Comparability of intervention and comparison communities at baseline was confirmed for most factors. Matching appears to have achieved a trial of adequate sample size. The apparent lack of a protective effect of male circumcision contrasts with other studies in Africa.

Adolescent↗

Antimicrobial susceptibility, auxotype and plasmid content of Neisseria gonorrhoeae in northern Tanzania: emergence of high level plasmid mediated tetracycline resistance.

OBJECTIVE: To study the antimicrobial susceptibility, plasmid content, auxotype and serogroup of strains of Neisseria gonorrhoeae isolated from an urban population of STD clinic attenders in Northern Tanzania. METHODS: The minimum inhibitory concentrations of nine common antimicrobial agents were measured by the agar dilution method against 130 strains of Neisseria gonorrhoeae isolated in a free government STD clinic in Mwanza town. The auxotype, plasmid content and serogroup of these strains were also determined by conventional techniques. RESULTS: 65 strains (50%) were penicillinase producers (PPNG), and 34 (26%) exhibited chromosomally mediated resistance to penicillin. Seven (5%) were sensitive to tetracycline; 78 (60%) showed intermediate levels of resistance, and 45 (35%) had high level plasmid mediated resistance (TRNG), all of which carried a 25.2 MDa plasmid. 79 strains (61%) showed decreased sensitivity to trimethoprim-sulphamethoxazole, and five (4%) were resistant to this agent. All isolates were fully sensitive to spectinomycin, azithromycin, cefotaxime, cefuroxime, norfloxacin and ciprofloxacin. One hundred and one strains (78%) were of type W11/111, 22 type W1, and seven cross reacting strains. The W1 strains were significantly more likely to be carrying plasmid mediated resistance to both penicillin and tetracycline. Six different auxotypes were present, the major type requiring proline. Plasmid profiles showed the presence of both the 3.2 MDa and the 4.4 MDa beta-lactamase encoding plasmids. CONCLUSION: a high proportion of gonococcal isolates remain resistant to penicillin in this region, and most isolates are now also resistant to tetracycline, with the emergence of plasmic mediated tetracycline resistance. Trimethoprim-sulphonamide sensitivity is also decreasing. The population of strains is heterogeneous, and both African and Asian beta-lactamase encoding plasmids are present.

Animals↗

Risk assessment and other screening options for gonorrhoea and chlamydial infections in women attending rural Tanzanian antenatal clinics.

Sexually transmitted diseases (STDs) are a major cause of morbidity and mortality in developing countries and may play a key role in enhancing the heterosexual transmission of human immunodeficiency virus (HIV). Treatment of STDs is one of the most cost-effective of all health interventions in developing countries; however, STDs among women in rural populations have received little attention. In this study, we report that prevalences of STDs among 964 women attending antenatal clinics in a rural area of the United Republic of Tanzania. A total of 378 (39%) of these women were infected with at least one STD pathogen, 97 (10%) had syphilis, and 81 (8%) has Neisseria gonorrhoeae (NG) and/or Chlamydia trachomatis (CT) infection. The recommended syndromic approach to screening for NG/CT infection, based on reported genital symptoms, had a low sensitivity (43%) and failed to discriminate between infected and uninfected women. A risk score approach that we developed, based on sociodemographic and other factors associated with NG/CT infection, had a higher sensitivity and lower cost per true case treated than other approaches, although its positive predictive value was only about 20%.

Adult↗

Solution conformation of the tetrasaccharide glycoside Xyl beta 1-(Man alpha 1-3)2Man beta 1-4Glc beta 1R from the mollu-series glycosphingolipids.

The conformation of Xyl beta 1-(Man alpha 1-3)2Man beta 1-4Glc beta 1-OCH2CH(N3)CH(OH) CH = CHC13H27 tetrasaccharide glycoside in Me2SO-d6 was investigated with use of a distance mapping procedure based on rotating-frame NOE and hydrogen bond constraints, and Molecular Mechanics calculations. The Man alpha 1-3Man beta linkage was found to be well defined in a single conformation, whereas some flexibility could be assumed for the remaining two glycosidic linkages. Similar conclusions, though based on a smaller number of constraints, were drawn for the title compound anchored in mixed D2O/dodecylphosphocholine-d38 micelles.

Carbohydrate Conformation↗

Lay health beliefs concerning HIV and AIDS--a barrier for control programmes.

Work in AIDS control in East Africa revealed widespread lay health beliefs concerning HIV infection and AIDS amongst health workers and members of the general population at both lower and higher risk of infection. The beliefs were often factually incorrect and undermining to AIDS control in the field of information, education and communication (IEC). The beliefs were conveyed informally but their origins could often be traced. Local media were important sources. The beliefs were powerful, persistent and resistant to conventional educational methods. Their prevalence and type changed with time in different groups. A model of how the beliefs came to be generated is proposed and reasons suggested for their persistence and strength. A current programme for countering the beliefs is described. An additional important group of policy and scientific beliefs were also identified amongst policy makers and scientists. It is noted that these phenomenon are international and not confined to Africa.

Acquired Immunodeficiency Syndrome↗

Sentinel surveillance for HIV-1 among pregnant women in a developing country: 3 years' experience and comparison with a population serosurvey.

OBJECTIVES: To establish unlinked, anonymous sentinel surveillance for HIV-1 among pregnant women attending an antenatal clinic, to determine age-specific seroprevalences, to monitor trends and to compare seroprevalence with that detected by a population serosurvey. To establish the sustainability and costs of surveillance. DESIGN: Sentinel surveillance for HIV through serial collection of unlinked, anonymous seroprevalence data from antenatal care; comparison of sentinel data with those from a population serosurvey; financial and general audit of the sentinel surveillance. SETTING: A community antenatal clinic in a large urban centre, Mwanza Municipality, Tanzania, eastern Africa, between October 1988 and September 1991. PATIENTS: Pregnant women attending for antenatal care. MAIN OUTCOME MEASURE: Age-specific HIV-1 seroprevalences, trends over time, difference from age-specific population seroprevalences, sustainability and costs. RESULTS: Overall HIV-1 seroprevalence was 11.5% (95% confidence interval, 10.5-12.4); differences in age-specific prevalences were not significant. There was no clear evidence of change in seroprevalence over the study period in any age group, although there was some indication of a rise in some age groups in 1988-1989. Sentinel surveillance among pregnant women may have significantly underestimated population HIV-1 seroprevalence for women under the age of 35 years. HIV-1 surveillance proved feasible and sustainable. Additional recurrent costs were US$1.7 per specimen for unlinked anonymous testing and US$0.57 per woman for syphilis screening. CONCLUSIONS: HIV-1 seroprevalence did not change significantly over 3 years, probably implying a substantial incidence of HIV-1 infection. In this setting seroprevalence in pregnant women may have underestimated population seroprevalence in women aged under 35 years. With modest inputs and good organization unlinked anonymous HIV-1 sentinel surveillance of pregnant women can be introduced and sustained in an African setting. This may usefully be carried out in conjunction with syphilis screening.

AIDS Serodiagnosis↗

A population-based study of syphilis and sexually transmitted disease syndromes in north-western Tanzania. 1. Prevalence and incidence.

OBJECTIVE: To determine the prevalence of syphilis and the prevalence and incidence of self-reported STD syndromes in the population of Mwanza Region, North-Western Tanzania. METHODS: A population-based random cluster sample survey, stratified by rural, roadside or urban residence, of 4173 individuals aged 15-54 years was performed in 1990-91. The seroprevalence of syphilis (using TPHA and RPR) and the prevalence and incidence of self-reported genital ulcer syndrome (GUS) and genital discharge syndrome (GDS) were determined. RESULTS: Active syphilis was detected in 9% of the adult population, while 15% had serological evidence of past or current infection. Seroprevalence was significantly lower in the rural than in the roadside and urban populations, but there was little difference between men and women. Amongst men, a history of GDS was reported by 28%, and a history of GUS by 14%, with point prevalences of 2.3% and 1.3% respectively. Annual incidence among men were 6.8% for GDS and 3.6% for GUS. Women reported these conditions less frequently. There was little difference between the strata in the prevalence or incidence of reported STD syndromes. CONCLUSION: Sexually transmitted diseases represent a major public health problem in both the rural and urban populations of Mwanza Region.

Adolescent↗

A population-based study of syphilis and sexually transmitted disease syndromes in north-western Tanzania. 2. Risk factors and health seeking behaviour.

OBJECTIVE: To determine risk factors for syphilis and sexually transmitted disease (STD) syndromes, and to study health seeking behaviour among those with STD syndromes, in the population of Mwanza Region, North-Western Tanzania. METHODS: A population-based random cluster sample survey, stratified by rural, roadside or urban residence, of 4173 individuals aged 15-54 years was performed in 1990-91. The seroprevalence of syphilis and the prevalence and incidence of self-reported genital ulcer syndrome (GUS) and genital discharge syndrome (GDS) are reported in the accompanying paper. This paper reports on risk factors for these conditions and on health seeking behaviour among those reporting them. RESULTS: In both sexes, the risk of STDs increased with the reported number of sexual partners in the previous five years. Men who were separated, divorced or widowed were at increased risk of STDs, but this was not the case among women. Higher educational status was associated with an increased risk of urethral discharge in males but with a decreased prevalence of syphilis in females. Male circumcision was associated with an increased risk of urethral discharge but a reduced prevalence of syphilis. Nearly all men, and 90% of women, reporting symptoms of genital discharge or ulceration had sought treatment. Of these, approximately 70% of males and 60% of females had sought treatment in the official health sector. CONCLUSIONS: Targetted health education concerning risk reduction for HIV infection and other STDs should be a high priority in this population. Improved case management of STDs in health centres and dispensaries may have a substantial impact on the incidence of these infections.

Adolescent↗

Sentinel surveillance for HIV-1 infection: how representative are blood donors, outpatients with fever, anaemia, or sexually transmitted diseases, and antenatal clinic attenders in Mwanza Region, Tanzania?

OBJECTIVE: To assess the validity of extrapolation from sentinel data by comparing the HIV-1 prevalence of various sentinel groups with that of the general population in Mwanza Region, Tanzania. METHODS: In a population survey, 4161 individuals were selected in a stratified random cluster sample. Sentinel groups (all in the age group 15-54 years) included blood donors (n = 1090); patients examined at district hospitals for the presence of malaria parasites (n = 1488), anaemia (n = 1339), or syphilis (n = 33); and antenatal clinic attenders (n = 1193). The HIV-1 serostatus of individuals selected from the population survey was tested using enzyme-linked immunosorbent assay (ELISA) and Western blot; 51% of the blood donors were tested using HIVCHEK, and all others using ELISA. HIV-1 prevalence was standardized for age, sex, and urban/non-urban location. RESULTS: HIV-1 prevalence (standardized by age, sex, and residence) in Mwanza Region was 4.0% (3.0% in non-urban areas and 11.3% in town). The standardized HIV-1 prevalences in the sentinel groups were: blood donors, 4.5%; patients with fever, 11.6%; patients with anaemia, 8.9%; urban sexually transmitted disease patients, 27.1%; urban antenatal clinic attenders, 11.8%. The crude prevalence in blood donors was 6.0%. CONCLUSION: Blood donors who are related to blood recipients appear to be a representative sentinel group in this region, provided that data are standardized for age, sex, and urban/non-urban location. Patients with fever and antenatal clinic attenders may reflect trends, but data from patients with fever markedly overestimate, and data from antenatal clinic attenders underestimate, population HIV-1 prevalence. Because self-selection of blood donors may become more pronounced, this comparison should be repeated later or elsewhere, should the opportunity arise.

Adolescent↗

The structure of the O-specific polysaccharide chain of the lipopolysaccharide of Salmonella arizonae O61.

The O-specific polysaccharide was obtained by mild degradation of the Salmonella arizonae O61 lipopolysaccharide with acid. It contained 2-acetamido-2-deoxy-D-glucose, 2-acetamidino-2,6-dideoxy-L-galactose (FucAm), and 7-acetamido-3,5,7,9-tetradeoxy-5-[(R)-3-hydroxybutyramido]-D- glycero-L-galacto-nonulosonic acid (Sug). On the basis of partial acid hydrolysis with 0.1 M HCl, solvolysis with anhydrous HF in methanol, and 1H- and 13C-NMR analysis (including 1H/13C inversely correlated spectroscopy for localisation of N-acyl substituents), it was concluded that the O-specific polysaccharide had the following structure. ----3)-alpha-L-FucAm-(1----3)-alpha-D-GlcNAc-(1----8)-beta-Sug+ ++-(2---- The O-antigen of S. arizonae O61 is structurally related to that of Pseudomonas aeruginosa O12, thus explaining the known serological cross-reactivity between these micro-organisms.

Carbohydrate Conformation↗

The epidemiology of HIV-1 infection in urban areas, roadside settlements and rural villages in Mwanza Region, Tanzania.

OBJECTIVE: To determine the prevalence of HIV-1 infection and to identify the most important risk factors for infection. DESIGN: A cross-sectional population survey carried out in 1990 and 1991 in Mwanza Region, Tanzania. METHODS: Adults aged 15-54 years were selected from the region (population, 2 million) by stratified random cluster sampling: 2434 from 20 rural villages, 1157 from 20 roadside settlements and 1554 from 20 urban wards. Risk factor information was obtained from interviews. All sera were tested for HIV-1 antibodies using enzyme-linked immunosorbent assay (ELISA); sera non-negative on ELISA were also tested by Western blot. RESULTS: The response rate was 81%. HIV-1 infection was 1.5 times more common in women than in men; 2.5% of the adult population in rural villages, 7.3% in roadside settlements and 11.8% in town were infected. HIV-1 infection occurred mostly in women aged 15-34 years and men aged 25-44 years. It was associated with being separated or widowed, multiple sex partners, presence of syphilis antibodies, history of genital discharge or genital ulcer, travel to Mwanza town, and receiving injections during the previous 12 months, but not with male circumcision. CONCLUSION: This study confirms that HIV-1 infection in this region in East Africa is more common in women than in men. The results are consistent with the spread of HIV-1 infection along the main roads. There is no evidence that lack of circumcision is a risk factor in this population.

Adolescent↗

The value of urine specimens in screening for male urethritis and its microbial aetiologies in Tanzania.

OBJECTIVE: To evaluate the first void urine (FVU) specimen in screening for urethritis and its microbial aetiologies in a male African population in which urinary schistosomiasis is also prevalent. PATIENTS AND METHODS: Two hundred and forty eight males aged 15-54 years provided FVU specimens: 55 patients from a clinic for sexually transmitted diseases (STD), 151 patients from a medical outpatient clinic and 42 villagers from an area of high endemicity for S haematobium. Specimens were tested for leucocyte esterase (LE) using a dipstick (Nephur-Test+Leuco, Boehringer-Mannheim France SA). Ova of S haematobium were sought in terminal urine samples from all subjects. For all STD patients, and all medical outpatients with a positive LE test, urine and urethral swabs were tested for Chlamydia trachomatis antigen, and urethral swabs were tested for Neisseria gonorrhoeae by gram stain and isolation. RESULTS: The prevalence of LE positivity was 38/41 in STD patients with urethral signs or symptoms (93%), 5/14 among other STD patients (36%), 21/151 among medical outpatients (15%) and 13/42 among villagers (31%). As a screening test for urethral infection (detection of gonorrhoea or chlamydia and/or > or = 5 polymorphs per high power field on gram stain) the LE test had a sensitivity of 94% and a specificity of 53% among STD patients. Of 24 STD patients with gonococcal or chlamydial infection, 23 had a positive LE test (96%). Among general medical outpatients, 12 of 22 with a positive LE test had either conventionally defined urethritis or gonococcal or chlamydial infection, giving a positive predictive value of 55% for the LE test in this group. Of 18 subjects in all groups with urinary schistosomiasis nine had a positive LE test (50%), although three of these also had gonorrhoea. Chlamydial antigen was detected in the FVU specimen of all six subjects in whom it was detected in a urethral swab, and in an additional three subjects in the outpatient group. CONCLUSIONS: The FVU, which is an easily collected and non-invasive specimen, can provide valuable information on the prevalence of urethritis and on its microbial aetiology among the general male population in African countries.

Adolescent↗

Cost-effectiveness of improved treatment services for sexually transmitted diseases in preventing HIV-1 infection in Mwanza Region, Tanzania.

BACKGROUND: A community-randomised trial was undertaken to assess the impact, cost, and cost-effectiveness of averting HIV-1 infection through improved management of sexually transmitted diseases (STDs) by primary-health-care workers in Mwanza Region, Tanzania. METHODS: The impact of improved treatment services for STDs on HIV-1 incidence was assessed by comparison of six intervention communities with six matched communities. We followed up a random cohort of 12,537 adults aged 15-54 years for 2 years to record incidence of HIV-1 infection. The total and incremental costs of the intervention were estimated (ingredients approach) and used to calculate the total cost per case treated, the incremental cost per HIV-1 infection averted, and the incremental cost per disability-adjusted life-year (DALY) saved. FINDINGS: During 2 years of follow-up, 11,632 cases of STDs were treated in the intervention health units. The baseline prevalence of HIV-1 infection was 4%. The incidence of HIV-1 infection during the 2 years was 1.16% in the intervention communities and 1.86% in the comparison communities. An estimated 252 HIV-1 infections were averted each year. The total annual cost of the intervention was US$59,060 (1993 prices), equivalent to $0.39 per head of population served. The cost for STD case treated was $10.15, of which the drug cost was $2.11. The incremental annual cost of the intervention was $54,839, equivalent to $217.62 per HIV-1 infection averted and $10.33 per DALY saved (based on Tanzanian life expectancy) or $9.45 per DALY saved (based on the assumptions of the World Development Report). In a sensitivity analysis of factors influencing cost-effectiveness, cost per DALY saved ranged from $2.51 to $47.86. INTERPRETATION: Improved management of STDs in rural health units reduced the incidence of HIV-1 infection in the general population by about 40%. The estimated cost-effectiveness of this intervention ($10 per DALY) compares favourably with that of, for example, childhood immunisation programmes ($12-17 per DALY). Cost-effectiveness should be further improved when the intervention is applied on a larger scale. Resources should be made available for this highly cost-effective HIV control strategy.

Adolescent↗