Treatment of acquired hemophilia by the Bonn-Malmo Protocol: documentation of an in vivo immunomodulating concept

Acquired hemophilia (AH) is an extremely rare condition in which autoantibodies (inhibitors) against clotting factor VIII induce acute and life-threatening hemorrhagic diathesis because of abnormal blood clotting. The mortality rate of AH is as high as 16%, and current treatment options are associated with adverse side effects. We investigated a therapeutic approach for AH called the modified Bonn-Malmo Protocol (MBMP). The aims of MBMP include suppression of bleeding, permanent elimination of inhibitors, and development of immune tolerance, thereby avoiding long-term reliance on coagulation products. The protocol included immunoadsorption for inhibitor elimination, factor VIII substitution, intravenous immunoglobulin, and immunosuppression. Thirty-five high-titer patients with critical bleeding who underwent MBMP were evaluated. Bleeding was rapidly controlled during 1 or 2 apheresis sessions, and no subsequent bleeding episodes occurred. Inhibitor levels decreased to undetectable levels within a median of 3 days (95% confidence interval [95% CI], 2-4 days), factor substitution was stopped within a median of 12 days (95% CI, 11-17 days), and treatment was completed within a median of 14 days (95% CI, 12-17 days). Long-term follow-up (7 months-7 years) showed an overall response rate of 88% for complete remission (CR). When cancer patients were excluded, the CR rate was 97%.     

Laboratory studies on Yersinia pestis during the 1991 outbreak of plague in Lushoto, Tanzania.

Thirty-one specimens from patients involved in an outbreak of plague were cultured. Suspicious isolates were presumptively identified by colonial characteristics, simple strains and by API 20E, and confirmed by inoculation into white mice. Antimicrobial susceptibility testing was also done. The isolation rate of Y. pestis was 22.6%. All isolates were uniformly sensitive to tetracycline, streptomycin, sulphadimidine and chloramphenicol; moderately sensitive to erythromycin, and resistant to trimethoprim. Y. pestis was confirmed as a cause of the epidemic and sensitivity of Y. pestis to the four antimicrobial agents used was demonstrated. It is recommended that laboratories in zonal hospitals serving areas with plague foci should be provided with facilities for isolation and preliminary identification of Y. pestis in order to speed up diagnosis of plague outbreaks. Confirmation of the identity, biotyping and antibiotic susceptibility testing should be undertaken in a well established national reference laboratory. This appears to be the first publication on bacteriological investigations of human plague in Tanzania.     

Molecular characterization of Haemophilus ducreyi isolates from different geographical locations

The technique of random amplified polymorphic DNA (RAPD) was adapted and optimized to study Haemophilus ducreyi isolates. A panel of 43 strains isolated from chancroid patients from different countries in Africa, Europe, North America, and Asia were characterized. The strains were also studied with respect to lipooligosaccharide (LOS) migration and immunoblotting patterns and the presence of cytolethal distending toxin genes. The RAPD method with the OPJ20 primer generated nine banding patterns (1 to 9). The majority of the isolates were clustered into two major profiles, 14 and 13 strains into profiles 1 and 2, respectively, and just a few strains revealed patterns 3 and 4. The isolates from Thailand were exceptional in that they showed greater diversity and were represented by six different RAPD patterns, i.e., patterns 3 and 5 to 9. The LOS migration and immunoblotting analyses revealed two different patterns, which indicated long and short forms of LOS; the former was found in 20/23 tested strains. Two strains that expressed the short form of LOS were grouped into RAPD pattern 4. The absence of cdtABC genes was observed in only 4/23 strains, and three of these isolates were assigned to RAPD pattern 4. Our results showed limited genotypic and phenotypic variations among H. ducreyi strains, as supported by the conserved RAPD and LOS profiles shared by the majority of the studied strains. However, the RAPD method identified differences between strains, including those from different geographic areas, which indicate the potential of RAPD as an epidemiological tool for the typing of H. ducreyi isolates in countries where chancroid is endemic.     

Evaluation of a prototype Amplicor PCR assay for detection of human immunodeficiency virus type 1 DNA in blood samples from Tanzanian adults infected with HIV-1 subtypes A, C and D.

BACKGROUND: In previous evaluations, the standard Amplicor HIV-1 DNA PCR test (Roche Diagnostic Systems) has been reported to have low sensitivity for the detection of some non-B HIV-1 subtypes. It has therefore become necessary to determine the performance of commercially available as well as prototype HIV-1 PCR assays for HIV-1 DNA detection in samples from various geographical settings, in order to assess their ability to detect the different HIV-1 genotypes. OBJECTIVES: To determine the performance of the prototype Roche Amplicor version 1.5 PCR test in comparison to that of the standard Roche Amplicor PCR test for the detection of HIV-1 DNA in blood samples from HIV-1 seropositive pregnant Tanzanian women infected with various HIV-1 subtypes. STUDY DESIGN: This was a cross-sectional study done on 161 blood samples collected from 106 HIV-1 seropositive and 55 seronegative asymptomatic pregnant women attending antenatal clinic in Dar es Salaam, Tanzania. METHODS: Cell pellets for PCR were prepared from EDTA blood by the Amplicor whole blood PCR sample preparation method. Plasma was used for HIV serology by enzyme linked immunosorbent assays. Subtyping was done by the heteroduplex mobility assay (HMA) using cell pellets and/or plasma. RESULTS: The sensitivities of the prototype PCR and the standard assays were 99.1% (105/106) and 97% (99/102), respectively. All samples from 55 HIV-1 seronegative women were negative by both PCR assays. Among the 101 samples subtyped by HMA, 48 (47%) were subtype A, 30 (30%) subtype C, 20 (20%) subtype D and 3 (3%) were indeterminate. In the standard DNA PCR assay, a statistically significantly higher proportion of subtype A samples had a low level of reactivity as measured as optical density compared with the subtypes C and D samples while in the prototype assay all three subtypes showed a high level of reactivity. CONCLUSIONS: The Amplicor version 1.5 DNA PCR test has a high sensitivity for the detection of HIV-1 DNA in blood samples from Tanzanian adults. Since performance of this assay does not appear to be influenced by differences in HIV-1 subtypes A, C and D, it has the potential for use in the detection of HIV-1 DNA in samples from geographic areas where these subtypes are prevalent.     

Health care seeking behaviour for sexually transmitted diseases among commercial sex workers in Morogoro,Tanzania

A qualitative study was conducted in a community of 100 female, self-employed commercial sex workers (CSWs), in Morogoro township, Tanzania. Data was gathered through key informant interviews and open-ended questionnaires. Respondents had extensive experiential knowledge of STDs and HIV/AIDS. They pursued several different avenues in attempting to prevent STDs including eating nutritiously to enhance immunologic status, using condoms, and vaginal washing after each act of intercourse. When they acquired a symptomatic STD, they pursued different avenues of treatment including self-treatment with known herbs, traditional healers (herbalists), injectionists, pharmacies, government hospitals, and private clinics. Almost all CSWs explored all options. Many of the key elements for an effective STD prevention and control program are in place and will be made more effective by training medical personnel, traditional healers, and sex workers themselves. Nous avons effectuéune étude qualitative auprès d'une communautéde 100 femmes travaillant comme prostituées indépendantes dans le township de Morogoro, en Tanzanie. Nous avons rassembléces données au cours d'entretiens avec des informatrices cl es et à l'aide de questionnaires ouverts. Les personnes interrogées ont de vastes connaissances, dérivées de l'expérience, sur les maladies sexuellement transmissibles (MST) et le Sida. Elles utilisent différents types de stratégie pour essayer d'éviter les MST, y compris une alimentation destinée à augmenter la résistance immunologique, l'utilisation de préservatifs et le lavage du vagin après chaque acte sexuel. Lorsque ces femmes attrapent une MST symptomatique, elles essaient différents types de traitement, y compris l'automédication par les plantes médicinales connues, les guérisseurs traditionnels (herboristes), les injections, les pharmacies, les hôpitaux publics et les cliniques privées. Presque toutes les prostituées explorent la totalitédes options disponibles. La plupart des éléments indispensables à la création d'un programme de prévention et de contrôle des MST efficace est déjà en place, et l'effcacitéde ce programme sera encore accrue par la formation du personnel médical, des guérisseurs traditionnels et des prostituées elles-mêmes. En un estudio cualitativo llevado a cabo en una comunidad de 100 trabajadoras sexuales independientes en la ciudad de Morogoro, Tanzania, se obtuvieron datos a través de entrevistas informantes claves, y cuestionarios abiertos. Las entrevistadas mostraron tener amplios conocimientos prácticos sobre enfermedades de transmisión sexual, HIV y sida. Seguían varios métodos diferentes para intentar impedir las enfermedades de transmisión sexual, por ejemplo, comer alimentos nutritivos para aumentar su sistema inmunológico, y utilizar condones y lavados vaginales después de cada relación sexual. Si notaban síntomas de alguna enfermedad de transmisión sexual, seguían tratamientos variados como automedicarse con infusiones conocidas, pedir ayuda a curanderos tradicionales (herbolarios), con inyecciones, en farmacias, hospitales estatales y clínicas privadas. Casi todas las entrevistadas exploraban todas las opciones posibles. Muchos de los elementos clave para lograr una prevención adecuada ya están funcionando, además de un programa de control contra las enfermedades de transmisión sexual que seráz más efica si se educa adecuadamente al personal médico, a los curanderos tradicionales y a las mismas trabajadoras sexuales.     

The prevalence and incidence of HIV-1 infection and syphilis in a cohort of police officers in Dar es Salaam, Tanzania: a potential population for HIV vaccine trials

OBJECTIVES: To assess the suitability of a cohort of police officers in Dar es Salaam for HIV vaccine trials by determining the prevalence and incidence of HIV-1 infection, active syphilis and their associated factors. Design and setting: An open cohort study of police officers in Dar es Salaam, Tanzania. METHODS: Recruitment of police officers began in 1994. A standardized questionnaire was completed at enrolment and subsequent visits. HIV antibodies were determined using two consecutive enzyme-linked immunosorbent assays. Samples repeatedly discordant on the two tests were tested by a Western blot assay. Treponema pallidum antibodies were first determined by Venereal Disease Research Laboratory (VDRL) test and reactive sera were confirmed by Treponema pallidum hemagglutination test. RESULTS: At the end of 1996 a total of 2850 police officers had been recruited of whom 2733 (96%) consented to be tested for HIV. The overall HIV-1 seroprevalence at recruitment was 13.8% (378 of 2733). Females had a significantly higher HIV-1 seroprevalence, 18.0% (55 of 306), as compared to males, 13.3% (323 of 2427), P< 0.05. From a total of 2215 married police officers, 585 (26.4%) responded to a question on extramarital sex within the previous 3 months of whom 36.2% (212 of 585) admitted to have had at least one extramarital sexual intercourse. Condoms were not used during these encounters by 178 of 212 (84.0%). As of 31st December 1998, among the 1524 males observed for 2553 person-years (PYAR), 50 had seroconverted and among 200 females observed for 357 PYAR, eight had seroconverted. The overall crude HIV-1 incidence was thus 19.9/1000 PYAR; 19.6 and 22.4/1000 PYAR for males and females, respectively. The overall prevalence and incidence of active syphilis were 3.1% (88 of 2850) and 8.6/1000 PYAR (26 of 3149), respectively. Males had a higher prevalence of active syphilis, 84 of 2525 (3.3%) than females, five of 325 (1.5%), P = 0.09. CONCLUSIONS: There was high risk sexual practice including low condom use in this cohort of police officers. The incidence and prevalence of HIV infection were high. Police officers in Dar es Salaam are therefore a potential population group for HIV vaccine evaluation.     

Comparing Couples’ and Individual Voluntary Counseling and Testing for HIV at Antenatal Clinics in Tanzania: A Randomized Trial

Voluntary counseling and testing (VCT) for couples (CVCT) is an important HIV-prevention effort in sub-Saharan Africa where a substantial proportion of HIV transmission occurs within stable partnerships. This study aimed to determine the acceptance and effectiveness of CVCT as compared to individual VCT (IVCT). 1,521 women attending three antenatal clinics in Dar es Salaam were randomized to receive IVCT during that visit or CVCT with their husbands at a subsequent visit. The proportion of women receiving test results in the CVCT arm was significantly lower than in the IVCT arm (39 vs. 71%). HIV prevalence overall was 10%. In a subgroup analysis of HIV-positive women, those who received CVCT were more likely to use preventive measures against transmission (90 vs. 60%) and to receive nevirapine for themselves (55 vs. 24%) and their infants (55 vs. 22%) as compared to women randomized to IVCT. Uptake of CVCT is low in the antenatal clinic setting. Community mobilization and couple-friendly clinics are needed to promote CVCT.