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Background: We investigated gender differences in treatment outcome during first line antiretroviral treatment (ART) in a hospital setting in Tanzania, assessing clinical, social demographic, virological and immunological factors., Methods: We conducted a cohort study involving HIV infected patients scheduled to start ART and followed up to 1 year on ART. Structured questionnaires and patients file review were used to collect information and blood was collected for CD4 and viral load testing. Gender differences were assessed using Kruskal-Wallis test and chi-square test for continuous and categorical data respectively. Survival distributions for male and female patients were estimated using the Kaplan-Meier method and compared using Cox proportional hazards models., Results: Of 234 patients recruited in this study, 70% were females. At baseline, women had significantly lower education level; lower monthly income, lower knowledge on ARV, less advanced HIV disease (33% women; 47% men started ART at WHO stage IV, p = 0.04), higher CD4 cell count (median 149 for women, 102 for men, p = 0.02) and higher BMI (p = 0.002). After 1 year of standard ART, a higher proportion of females survived although this was not significant, a significantly higher proportion of females had undetectable plasma viral load (69% women, 45% men, p = 0.003), however females ended at a comparable CD4 cell count (median CD4, 312 women; 321 men) signifying a worse CD4 cell increase (p = 0.05), even though they still had a higher BMI (p = 0.02). The unadjusted relative hazard for death for men compared to women was 1.94. After correcting for confounding factors, the Cox proportional hazards showed no significant difference in the survival rate (relative hazard 1.02)., Conclusion: We observed women were starting treatment at a less advanced disease stage, but they had a lower socioeconomical status. After one year, both men and women had similar clinical and immunological conditions. It is not clear why women lose their immunological advantage over men despite a better virological treatment response. We recommend continuous follow up of this and more cohorts of patients to better understand the underlying causes for these differences and whether this will translate also in longer term differences.

Objectives: To compare the presence and quantity of cervicovaginal HIV among HIV seropositive women with clinical herpes, subclinical HSV-2 infection and without HSV-2 infection respectively; to evaluate the association between cervicovaginal HIV and HSV shedding; and identify factors associated with quantity of cervicovaginal HIV., Design: Four groups of HIV seropositive adult female barworkers were identified and examined at three-monthly intervals between October 2000 and March 2003 in Mbeya, Tanzania: (1) 57 women at 70 clinic visits with clinical genital herpes; (2) 39 of the same women at 46 clinic visits when asymptomatic; (3) 55 HSV-2 seropositive women at 60 clinic visits who were never observed with herpetic lesions; (4) 18 HSV-2 seronegative women at 45 clinic visits. Associations of genital HIV shedding with HIV plasma viral load (PVL), herpetic lesions, HSV shedding and other factors were examined., Results: Prevalence of detectable genital HIV RNA varied from 73% in HSV-2 seronegative women to 94% in women with herpetic lesions (geometric means 1634 vs 3339 copies/ml, p = 0.03). In paired specimens from HSV-2 positive women, genital HIV viral shedding was similar during symptomatic and asymptomatic visits. On multivariate regression, genital HIV RNA (log10 copies/mL) was closely associated with HIV PVL (β = 0.51 per log10 copies/ml increase, 95%CI:0.41-0.60, p<0.001) and HSV shedding (β = 0.24 per log10 copies/ml increase, 95% CI:0.16-0.32, p<0.001) but not the presence of herpetic lesions (β = -0.10, 95%CI:-0.28-0.08, p = 0.27)., Conclusions: HIV PVL and HSV shedding were more important determinants of genital HIV than the presence of herpetic lesions. These data support a role of HSV-2 infection in enhancing HIV transmissibility.

One-health approaches have started being applied to health systems in some countries in controlling infectious diseases in order to reduce the burden of disease in humans, livestock and wild animals collaboratively. However, one wonders whether the problem of lingering and emerging zoonoses is more affected by health policies, low application of one-health approaches, or other factors. As part of efforts to answer this question, the Southern African Centre for Infectious Disease Surveillance (SACIDS) smart partnership of human health, animal health and socio-economic experts published, in April 2011, a conceptual framework to support One Health research for policy on emerging zoonoses. The main objective of this paper was to identify which factors really affect the burden of disease and how the burden could affect socio-economic well-being. Amongst other issues, the review of literature shows that the occurrence of infectious diseases in humans and animals is driven by many factors, the most important ones being the causative agents (viruses, bacteria, parasites, etc.) and the mediator conditions (social, cultural, economic or climatic) which facilitate the infection to occur and hold. Literature also shows that in many countries there is little collaboration between medical and veterinary services despite the shared underlying science and the increasing infectious disease threat. In view of these findings, a research to inform health policy must walk on two legs: a natural sciences leg and a social sciences one.

In 2005, Muhimbili University of Health and Allied Sciences (MUHAS) in Tanzania and the University of California San Francisco (UCSF) in the United States joined to form a partnership across all the schools in our institutions. Although our goal is to address the health workforce crisis in Tanzania, we have gained much as institutions. We review the work undertaken and point out how this education partnership differs from many research collaborations. Important characteristics include: (i) activities grew out of MUHAS's institutional needs, but also benefit UCSF; (ii) working across professions changed the discourse from 'medical education' to 'health professions education'; (iii) challenged by gaps in our respective health-care systems, both institutions chose a new focus, interprofessional team work; (iv) despite being so differently resourced, MUHAS and UCSF seek strategies to address growing class sizes; and (v) we involved a wider range of people - faculty, administrators, students, and residents - at both institutions than is usually the case with research. This partnership has convinced us to exhort other academic leaders in the health arena to seek opportunities together to enlighten and enliven our educational enterprises.

Enterobacter hormaechei and Cronobacter sakazakii are amongst the most important causes of outbreaks of neonatal sepsis associated with powdered milk. In this study, we report for the first time an outbreak of a novel Enterobacter sp. harbouring bla(CTX-M-15) in a neonatal unit in Tanzania. Seventeen Gram-negative enteric isolates from neonatal blood cultures were studied. Antibiotic susceptibility was assessed by disc diffusion testing, and the presence of the bla(CTX-M-15) gene was established by polymerase chain reaction (PCR) and sequencing. Isolates were typed by pulsed-field gel electrophoresis (PFGE). Identification by biochemical profiling was followed by nucleotide sequencing of 16S ribosomal DNA (rDNA), rpoB and hsp60 alleles. Environmental sampling was done and control measures were established. Isolates were initially misidentified based on their fermentation characteristics and agglutination as Salmonella enterica serotype Paratyphi. All isolates were resistant to multiple antibiotics, except for ciprofloxacin and carbapenems, and were found to harbour bla(CTX-M-15) on a 291-kb narrow-range plasmid. PFGE analysis indicated the clonal outbreak of a single strain, infecting 17 neonates with a case fatality rate of 35%. The same strain was isolated from a milk bucket. Phylogenetic analysis using 16S rDNA, rpoB and hsp60 sequences permitted no definitive identification, clustering the strains in the Enterobacter cloacae complex with similarities of 92-98.8%. The data describe an outbreak of a novel bla(CTX-M-15)-positive, multiresistant Enterobacter strain in an African neonatal unit that can easily be misidentified taxonomically. These data highlight the need for constant surveillance of bacteria harbouring extended-spectrum β-lactamases as well as improvements in hygiene measures in developing countries., (Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Human immunodeficiency virus (HIV) DNA polymerase chain reaction (PCR) test using venous blood sample has been used for many years in low resource settings for early infant diagnosis of HIV infection in children less than 18 months. The aim of this study was to evaluate and compare the performance characteristics of Amplicor HIV-1 DNA assay version 1.5 following processing of venous blood and dried blood spot (DBS) samples by Roche manual DNA extraction and automated Roche MagNA Pure LC instrument (MP) for HIV-1 DNA PCR testing in Dar es Salaam, Tanzania, in order to scale up early infant diagnosis of HIV infection in routine practice. Venous blood samples from children under 18 months born to HIV-infected mothers between January and April 2008 were collected. Venous blood was used to prepare cell pellet and DBS samples. DNA extractions by manual procedure and MP were performed each on cell pellet, venous blood and DBS samples and tested by Amplicor HIV-1 DNA assay. Of 325 samples included, 60 (18.5%) were confirmed HIV-infected by manual extraction performed on cell pellets. Sensitivity of the assay following MP processing of venous blood was 95% (95% CI; 86.1-99.0%) and 98.3% (95% CI; 91.1 to 99.9%) for the manual extraction and processing by MP performed on DBS samples. Specificity of the assay with all DNA extraction methods was 99.6% (95% CI; 97.9 to 100%). Performance of the assay with Roche manual extraction and processing by MP on DBS samples compared well with Roche manual extraction performed on cell pellet samples. The choice of DNA extraction method needs to be individualized based on the level of laboratory facility, volume of testing and cost benefit analysis before it is adopted for use.

Objective: The main aim of this study was to reduce breast-milk transmission of HIV-1 by treating HIV-1-infected women with highly active antiretroviral therapy (HAART) during breastfeeding., Methods: Mitra Plus was an open-label, nonrandomized, prospective cohort study. HIV-1-infected pregnant women in Dar es Salaam were treated with zidovudine (ZDV) + lamivudine (3TC) + nevirapine (NVP). NVP was later replaced by nelfinavir for mothers with CD4 cell counts >200 cells per microliter or with adverse reaction to NVP. HAART was initiated at 34 weeks of gestation. For women with symptomatic HIV infection or CD4 cell counts below 200 cells per microliter, HAART was started earlier if possible. Treatment of the mothers was stopped at 6 months except for those mothers who needed HAART for their own health. The infants received ZDV + 3TC for 1 week after birth. Mothers were advised to exclusively breastfeed and to wean abruptly between 5 and 6 months. Transmission of HIV-1 was analyzed using the Kaplan-Meier survival technique. Cox regression was used for comparison with the breastfeeding population of the Petra trial arm A., Results: There were 441 infants included in the analysis of HIV-1 transmission. The cumulative transmission of HIV-1 was 4.1 % [95% confidence interval (CI): 2.2 to 6.0] at 6 weeks, 5.0% (95% CI: 2.9 to 7.1) at 6 months, and 6.0% (95% CI: 3.7 to 8.3) at 18 months after delivery. The cumulative risk of HIV transmission between 6 weeks and 6 months was 1.0% and between 6 months and 18 months 1.1%. The cumulative HIV infection or death rate was 8.6% (95% CI: 6.0 to 11.2) at 6 months and 13.6% (95% CI: 10.3 to 16.9) at 18 months after delivery. Viral load at enrollment and duration of HAART before delivery were significantly associated with transmission but CD4 cell count at enrollment was not. The median time of breastfeeding was 24 weeks. The transmission in the Mitra Plus study was about half of the transmission in the breastfeeding population in the Petra trial arm A at 6 months after delivery (adjusted relative hazard = 0.49, P < 0.001). The combined outcome HIV infection or death was significantly lower in the Mitra Plus study than in the breastfeeding population in the Petra trial arm A at 18 months (adjusted relative hazard = 0.61, P = 0.007). NVP-related mucocutaneous rash was demonstrated in 6.5% of 429 NVP-exposed women. The incidence of NVP-related grade 3 or 4 hepatotoxicity was low (0.5%)., Conclusions: HAART given to HIV-infected mothers in late pregnancy and during breastfeeding resulted in a low postnatal HIV transmission similar to that previously demonstrated in the Mitra study in Dar es Salaam using infant prophylaxis with 3TC during breastfeeding. The extended maternal prophylaxis with HAART for prevention of mother-to-child transmission of HIV-1 for breastfeeding mothers who do not need HAART for their own health should be further evaluated and compared with the use of infant postnatal antiretroviral prophylaxis regarding safety and cost-effectiveness.

Objective: To investigate the possibility of reducing mother-to-child transmission (MTCT) of HIV-1 through breast-feeding by prophylactic antiretroviral (ARV) treatment of the infant during the breast-feeding period., Design: An open-label, nonrandomized, prospective cohort study in Tanzania (Mitra)., Methods: HIV-1-infected pregnant women were treated according to regimen A of the Petra trial with zidovudine (ZDV) and lamivudine (3TC) from week 36 to 1 week postpartum. Infants were treated with ZDV and 3TC from birth to 1 week of age (Petra arm A) and then with 3TC alone during breast-feeding (maximum of 6 months). Counseling emphasized exclusive breast-feeding. HIV transmission was analyzed using the Kaplan-Meier survival technique. Cox regression was used for comparison with the breast-feeding population in arm A of the Petra trial, taking CD4 cell count and other possible confounders into consideration., Results: There were 398 infants included in the transmission analysis in the Mitra study. The estimated cumulative proportion of HIV-1-infected infants was 3.8% (95% confidence interval [CI]: 2.0 to 5.6) at week 6 after delivery and 4.9% (95% CI: 2.7 to 7.1) at month 6. The median time of breast-feeding was 18 weeks. High viral load and a low CD4 T-cell count at enrollment were associated with transmission. The Kaplan-Meier estimated risk of HIV-1 infection at 6 months in infants who were HIV-negative at 6 weeks was 1.2% (95% CI: 0.0 to 2.4). The cumulative HIV-1 infection or death rate at 6 months was 8.5% (95% CI: 5.7 to 11.4). No serious adverse events related to the ARV treatment of infants occurred. The HIV-1 transmission rate during breast-feeding in the Mitra study up to 6 months after delivery was more than 50% lower than in the breast-feeding population of Petra arm A (relative hazard=2.61; P=0.001; adjusted values). The difference in transmission up to 6 months was significant also in the subpopulation of mothers with CD4 counts>or=200 cells/microL., Conclusions: The rates of MTCT of HIV-1 in the Mitra study at 6 weeks and 6 months after delivery are among the lowest reported in a breast-feeding population in sub-Saharan Africa. Prophylactic 3TC treatment of infants to prevent MTCT of HIV during breast-feeding was well tolerated by the infants and could be a useful strategy to prevent breast milk transmission of HIV when mothers do not need ARV treatment for their own health.

Objectives: To determine trends in the prevalence and aetiological distribution of genital ulcer syndrome (GUS) in a cohort of female bar workers and to assess factors associated with these trends., Methods: An open cohort of 600 women at high risk of HIV and sexually transmitted infection (STI) was offered screening and treatment for STI at 3-month intervals. The prevalence of GUS and associated aetiological agents (Herpes simplex virus (HSV), Treponema pallidum and Haemophilus ducreyi) were monitored over 27 months through clinical examination, dry lesion swabbing and multiplex polymerase chain reaction. The effects of HIV status and other factors on the prevalence trends of STI were assessed., Results: A total of 753 women were recruited into the cohort over 10 examination rounds. At recruitment, the seroprevalence was 67% for HIV and 89% for HSV type 2 (HSV-2). During follow-up, 57% of ulcers had unknown aetiology, 37% were due to genital herpes and 6% to bacterial aetiologies, which disappeared completely in later rounds. The absolute prevalence of genital herpes remained stable at around 2%. The proportion of GUS caused by HSV increased from 22% to 58%, whereas bacterial causes declined. These trends were observed in both HIV-negative and HIV-positive women., Conclusions: The changes observed in the frequency and proportional distribution of GUS aetiologies suggest that regular STI screening and treatment over an extended period can effectively reduce bacterial STI and should therefore be sustained. However, in populations with a high prevalence of HSV-2, there remains a considerable burden of genital herpes, which soon becomes the predominant cause of GUS. Given the observed associations between genital herpes and HIV transmission, high priority should be given to the evaluation of potential interventions to control HSV-2 either through a vaccine or through episodic or suppressive antiviral therapy and primary prevention.

In the United Republic of Tanzania, 457 voluntary blood donors were enrolled in hepatitis B virus (HBV) serological screening; 4.8% (22/457) carried HBsAg, 13.6% (3/22) of whom were HBeAg-positive. The mean age among HBeAg-negative carriers was 31 years. HBV DNA was detectable in 81.8% (18/22), the mean level was 3.67 (+/-1.77) log copies/ml. Genotype A was determined in 90.9% (20/22) and 18/20 were classified into subgenotype Aa (Asia/Africa). The basal core promoter, precore and partial core nucleotide sequences were analyzed in the 18 strains; T1809/T1812 ("Kozak" sequence) and A/T1888 (encapsidation signal) variants were identified in 100% and 78%, respectively. The complete genome sequencing for one of the Tanzanian strains revealed no recombination. In conclusion, HBV seroprevalence is high among general population in Tanzania, and the HBV/Aa-infection is predominant. The indicated tendency to early HBeAg seroconversion and declining of the viral load should be confirmed further in case-control studies., (2006 Wiley-Liss, Inc.)

The aim of this study was to evaluate the performance of two antibody enzyme-linked immunosorbent assays (ELISAs) [Vironostika Uni-Form II plus O and Enzygnost anti-HIV-1/2 Plus], and two antigen/antibody combination ELISAs [Murex and Vironostika HIV Uni-Form II] for use in an alternative confirmatory HIV diagnostic testing strategy in Dar es Salaam, Tanzania. Altogether, 1380 serum samples were included. All ELISA reactive samples were tested using the Inno-Lia antibody assay and discrepant samples were tested on the Innotest p24 antigen assay. Three hundred and one (21.8%) samples were confirmed HIV-1 antibody positive by Inno-Lia including 27/508 (5.3%) from blood donors, 65/511 (12.7%) from pregnant women and 209/361 (57.9%) from hospital patients. The sensitivity at initial testing was 100% (95% CI; 98.8-100%) for all assays except Vironostika Uni-Form II plus O (99.7%; 95% CI; 98.2-99.9%) which showed one false negative sample at initial testing but 100% sensitivity after repeat testing. The final specificity at repeat testing was 100% (95% CI; 99.7-100%) for Enzygnost anti-HIV-1/2 Plus, 99.4% (95% CI; 98.8-99.8%) for each of the antigen/antibody combination ELISAs and 97.9% (95% CI; 96.8-98.6%) for Vironostika plus O ELISA. An alternative confirmatory HIV testing strategy based on initial testing on any of the two antigen/antibody assays followed by testing of reactive samples on the Enzygnost anti-HIV-1/2 Plus assay gave 100% specificity (95% CI; 99.7-100%).

Herpes simplex virus type 2 (HSV-2) is a common sexually transmitted infection in sub-Saharan Africa. Glycoprotein G (gG) of HSV-2 elicits a type-specific antibody response and is widely used for serodiagnosis. gG is cleaved into a secreted portion (sgG-2) and a highly O-glycosylated mature portion (mgG-2). The performances of these two native immunosorbent purified antigens were compared in an enzyme-linked immunosorbent assay (ELISA) format with a commercially available assay (FOCUS2) using sera from blood donors (n = 194) and individuals (n = 198) with genital ulcer disease (GUD) from Tanzania. Discordant results were resolved by Western blotting. The HSV-2 seroprevalence for blood donors was estimated as 42%, and that for the GUD cohort was estimated as 78%. The prevalence increased significantly with age for both cohorts and was higher among human immunodeficiency virus (HIV)-positive individuals than among HIV-negative subjects. In the GUD cohort with a high HSV-2 prevalence, all three assays showed statistically similar performances, with sensitivities between 97% and 99% and specificities in the range of 86% to 91%. In contrast, among blood donors with a lower seroprevalence, the mgG-2-based ELISA presented significantly higher specificity (97%) than the sgG-2 ELISA (89%) and FOCUS2 (74%). Overall, the mgG-2 ELISA gave a high performance, with negative and positive predictive values of 96% for blood donors and a negative predictive value of 95% and a positive predictive value of 97% for the GUD cohort. We conclude that native purified mgG-2 showed the highest accuracy for detection of HSV-2 in patient sera from Tanzania and is therefore suitable for seroprevalence studies as well as in clinical settings.

The objective of this study was to analyze the mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load at enrollment (36 weeks of gestation) in a cohort of HIV-1-seropositive breast-feeding women at the Dar es Salaam site of the multicenter Petra trial (a mother-to-child HIV-1 transmission intervention trial using antiretroviral therapy). Antiretroviral treatment was not available in this setting apart from the short treatment given within the trial around delivery to prevent mother-to-child transmission of HIV. T-lymphocyte subsets were determined by flow cytometry. Plasma HIV-1 RNA was quantified by the Amplicor HIV-1 RNA Monitor v 1.5 assay. Mortality after delivery was analyzed using the life-table technique and Cox regression. The analysis included 266 mothers. The CD4 cell counts at enrollment were <200 cells/mm in 14.5% of the mothers. The viral load at enrollment was >100,000 RNA copies/mL in 33.6% of the mothers. The mortality 24 months after delivery was 6.7% (95% CI = 3.1-10.1%). The mortality 24 months after delivery was 29.9% (95% CI = 13.1-46.9%) for mothers with <200 CD4 cells/mm at enrollment, 3.3% (95% CI = 0-6.6%) for mothers with 200-499 CD4 cells/mm, 2.9% (95% CI = 0-7.1%) for mothers with >500 CD4 cells/mm (P = 0.0000), 15.0% (95% CI = 6.6-23.4%) for mothers with viral load >100,000 copies/mL at enrollment, and 2.8% (95% CI = 0-5.6%) for mothers with viral load <100,000 copies/mL (P = 0.0000). In the multivariate analysis CD4 cell counts and viral load were both independent risk factors for mortality (P < 0.001 and P = 0.004, respectively). In conclusion, the mortality was high among women with severe immunosuppression or high viral load at enrollment, but not in the rest of the women. CD4 lymphocyte count in late pregnancy was a better predictor of death within 2 years than was viral load. The results support the World Health Organization recommendation to initiate antiretroviral treatment in resource-limited settings in HIV-1-infected adults with CD4 cell counts <200/mm and show that this is appropriate also among perinatal women.

Background: In Tanzania information is lacking on the prevalence of HIV infection in surgical patients in tertiary care facilities, in whom there are many points of special interest., Objective: To determine the prevalence of HIV infection and associated clinical and demographic features among hospitalised surgical patients at Muhimbili National Hospital (MNH)., Setting: Muhimbili National Hospital., Materials and Methods: Consecutive newly admitted patients were tested for HIV antibodies after pre-test counselling. Sera were tested using a dual ELISA algorithm. The data were analysed to determine the prevalence of HIV infection and relationships of serostatus with clinical and socio-demographic characteristics., Results: Of 1,534 patients admitted during the study, 1,031(67.2%) consented to HIV testing following pre-test counselling. The prevalence of AIDS-related clinical features in patients who declined to be HIV tested was similar to that of seronegative patients, but significantly lower than that of seropositive patients. The overall age-adjusted HIV prevalence was 10.5% (95% CI = 9.9-14.0). The highest age-specific HIV prevalence was in the age group 35-44 years at 27.9%. No one was infected in the age group 0-4 years (n = 111). Differences in prevalence between age groups were statistically significant (p < 0.0001). Patients with granulomatous and suppurative infections had HIV prevalence of 28.3%. Twenty of 124 seropositive patients (16.1%) died in hospital compared to 58 of 907(6.4%) of seronegative patients (p = 0.0001)., Conclusion: At Muhumbili National Hospital overall HIV prevalence in hospitalised surgical patients were 10.5%, compared to an overall national prevalence of 6.7%. Patients in the age groups 25 to 34 and 35 to 44 years had HIV seroprevalence of 26.8% and 27.9% respectively. Patients with infective conditions had the highest HIV prevalence. HIV seropositive patients were associated with higher hospital mortality than seronegative patients.

Antibodies specific for the cytolethal-distending toxin of Haemophilus ducreyi (HdCDT) complex and for the CdtA, CdtB, and CdtC components were measured by ELISA in the sera of 50 patients with culture and/or PCR proven chancroid, 42 patients with periodontitis, 50 blood donors from Tanzania, 50 blood donors from Sweden. In addition, the biological activity e.g. neutralization capacity of the sera were tested. Our results demonstrate that majority of chancroid patients and healthy individuals had detectable levels of serum antibodies to HdCDT complex and to separate toxin components. However, high levels (> or =100 units) of antibodies to HdCDT complex were significantly more prevalent in the sera of patients with both chancroid and periodontitis than in the sera of the corresponding controls (P=0.001 and P=0.04, respectively). In the sera of the 50 patients with chancroid, antibodies to CdtA, CdtB, and CdtC were detected in 50, 35, and 34 individuals, respectively. Antibodies to CdtC, being less frequently detected than the antibodies to other components, show a good correlation with the neutralizing capacity of sera. High levels of neutralizing antibodies (> or =160) were detected in only 22 and 2% of the patients with chancroid and periodontitis, respectively. The data suggest that the low levels of anti-HdCDT antibodies, which include neutralizing antibodies, may contribute to limited protection in chancroid and since anti-HdCDT antibodies, may be detected in healthy individuals and in patients with certain disease conditions (e.g. periodontitis), they may not be specific markers for chancroid infection.

The aim of this study was to determine the acceptability of HIV counseling and testing and participation in a mother-to-child HIV-1 transmission intervention study using antiretroviral therapy in Dar es Salaam, Tanzania, one of the sites for the Joint United Nations Program on AIDS (UNAIDS) multicenter Petra trial. HIV testing was offered to all pregnant women who visited three prenatal clinics in Dar es Salaam before 34 weeks' gestation. Group or individual pretest counseling was performed by trained midwives. Laboratory diagnosis of HIV infection was based on two sequential anti-HIV enzyme-linked immunosorbent assays. Posttest counseling was given 2 weeks later to women who wished to know their HIV status. HIV testing was offered to a total of 10,010 pregnant women from June 1996 to May 1998, of whom 76.4% (7647 of 10,010) agreed to be tested. The prevalence of HIV-1 infection was 13.7% (1050 of 7647). Overall, 68.1% (5205 of 7647) returned for their results. Of the HIV-1-seropositive respondents, 27.4% (288 of 1050) agreed to participate in the Petra trial after fulfilling the eligibility criteria. Only 16.7% (48 of 288) of the enrolled women disclosed their positive HIV serostatus to their sexual partners. The main reasons for not disclosing the HIV serostatus were fear of stigma and divorce. Sixty percent (29 of 48) of the informed sex partners agreed to be tested for HIV and 69% (20 of 29) tested HIV seropositive. Pregnancy recurrence rate was 4.4 per 100 women years (18 pregnancies during 408 women years of follow-up) with 10 of 18 (55.6%) women not wanting to carry the pregnancy to term. In conclusion, this information is useful in planning intervention programs for prevention of mother-to-child HIV-1 transmission and it shows that improvements are required in counseling.

Between March and September of 1995, women receiving family planning (FP) services in three large clinics in Dar es Salaam, Tanzania were invited to participate in a cross-sectional study. Consenting women were interviewed to obtain information about HIV risk factors, and blood for HIV testing was collected. The prevalence of HIV was 16.9% (95% CI: 14.4%-19.3%). The risk of HIV increased significantly with age. Compared with married women, the risk of HIV was significantly higher among cohabiting women (age-adjusted OR = 2.3; 95% CI = 1.5-3.5) and among women who were single, divorced or widowed (age-adjusted OR = 2.3; 95% CI = 1.2-4.4). The risk of HIV was also significantly higher among hotel workers (age-adjusted OR = 4.3; 95% CI = 1.4-12.9). Women with laboratory evidence of sexually transmitted diseases were at increased risk of HIV. This study shows that HIV is a major public health problem among FP clients in Tanzania. Innovative HIV interventions are needed to reduce further spread of HIV infection.

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.

The aim of this study was to determine the prevalence of HIV-1 infection, the clinical spectrum of HIV-1-associated conditions and HIV-1-associated mortality among children hospitalized in the medical paediatric wards at Muhimbili Medical Centre (MMC), Dar es Salaam, Tanzania. All children admitted to the medical paediatric wards of MMC between August 1995 and January 1996 were eligible for the study. Testing for HIV antibodies was done using 2 consecutive enzyme linked immunosorbent assays (ELISAs). ELISA-reactive samples from children aged 18 months and below were further tested by a recently developed heat-denatured p24 antigen assay. The prevalence of HIV-1 infection among the 2015 children studied was 19.2%. When present for 14 days or more, fever, cough, diarrhoea, ear discharge, oral ulcers and skin rash were all significantly more common in HIV-1-infected than in HIV-uninfected children (p < 0.001). In the multivariate analysis cough, ear discharge, oropharyngeal ulcers and skin rash were found to be the most important symptoms. Clinical signs found to be significantly associated with HIV-1 infection in the univariate analysis were wasting, stunting, hair changes, oral thrush, oropharyngeal ulcers, lymphadenopathy, lung consolidation and lung crepitations (p < 0.001). In the multivariate analysis, oral thrush, lung crepitations, cervical lymphadenopathy, wasting and inguinal lymphadenopathy were found to be the most important signs. The 3 most common diagnoses in HIV-1-infected children were acute respiratory infection (ARI) (39.4%), malnutrition (38.1%) and tuberculosis (19.3%), while in HIV-uninfected children they were malaria (47.0%), ARI (25.0%) and malnutrition (16.1%). The mortality rate was 21.4% in HIV-1-infected children and 8.4% in HIV-uninfected children (p < 0.001). In conclusion, the prevalence of HIV-1 infection among hospitalized children at the main hospital in Dar es Salaam was high and associated with high mortality. Many symptoms and signs are indicative of HIV-1 infection, but appropriate laboratory testing is required for diagnosis.

Objective: To determine immunoglobulin levels in HIV-1 seronegative and HIV-1 seropositive children at different clinical stages of HIV infection., Design: Cross-sectional study., Setting: Lugalo and Mwanayamala mother and child clinics in Dar es Salaam., Subjects: Two hundred and ninety-nine children aged 18 months to five years., Main Outcome Measures: Estimation of immunoglobulin classes (IgG, IgA, IgM, IgD and IgE)., Results: Mean serum levels of all immunoglobulin classes were significantly higher (p < 0.0001) among the HIV-1 seropositive children (IgG = 22.9 g/l, IgA = 2.2 g/l, IgM 2.7 g/l, IgD 101.5 IU/ml and IgE 887.7 IU/ml) than among the HIV-1 seronegative children (IgG = 11.3 g/l, IgA = 1.0 g/l, IgM = 1.5 g/l, IgD = 27.8 UI/ml and IgE 341.3 UI/ml). The percentages of HIV-infected children with immunoglobulin concentrations above mean level were 83% for IgG, 77% for IgA, 78% for IgM, 73% for IgD and 78% for IgE., Conclusion: HIV seropositive children have higher levels of immunoglobulin than seronegative children. There was no correlation between the levels of immunoglobulin classes and CDC clinical staging.

Objective: To determine the seroprevalence of the main transfusion-associated viral infections and syphilis among blood donors in Muhimbili Medical Centre, Dar es salaam, Tanzania., Design: Cross sectional study., Setting: The blood bank unit of Muhimbili Medical Centre in Dar es salaam, Tanzania., Subjects: A consecutive sample of 300 blood donors., Investigations: Search for the presence of antibodies to: human immunodeficiency virus (anti-HIV), hepatitis C virus (anti-HCV), hepatitis B surface antigen (anti-HBs), human T-lymphotropic virus type 1 (anti-HTLV-1), syphilis and for hepatitis B surface antigen (HbsAg)., Results: The overall frequency of anti-HIV, anti-HCV, anti-HBs, HbsAg, anti-HTLV-1, and syphilis antibodies were 8.7%, 8%, 20%, 11%, 0%, and 12.7%, respectively. Among the HIV seronegative donors, the frequency of anti-HCV, anti-HBs, HBsAg, anti-HTLV-1, and syphilis antibodies were 8.8%, 22%, 11%, 0%, and 10.9%, respectively. HIV-seropositive donors had an increased risk for being positive for syphilis antibodies (OR = 3.6, 95% CI 1.4-9.0) and HBsAg (OR = 4.0, 95% CI 1.0-18.8), but not anti-HCV (OR = 0.9, 95% CI 0.86-0.97), anti-HBs (OR = 1.0, 95% CI 0.2-5.3) or anti-HTLV-1 (OR = 0.0)., Conclusion: Donor blood including that from HIV-seronegative donors, has high frequency of HCV, HBV, and syphilis antibodies but not anti-HTLV-1. A significant association exists in the occurrence of HIV, HBV and syphilis; and due to the association of syphilis and HIV, clients with history of sexually transmitted disease should be excluded during donor selection. From these observations were recommend: (i) routine screening of donor blood for HIV, HCV, HBV, and syphilis antibodies but not HTLV-1 and; (ii) a larger study to generate more accurate estimates of the magnitude the transfusion-transmissible infectious diseases.

One hundred and eighty one liquid and 183 powder preparations were purchased from different herbalists practising in open air markets in Hala District Dar es Salaam Region and analysed for total viable aerobic plate counts. Isolated microorganisms were identified by conventional microbiological and biochemical methods. The study revealed that the level of bacterial contamination in both liquid and powder drug samples was significantly higher (P <0.01) compared to the acceptable levels of 105/cfc/g. For fungi, the level of contamination in powders was highly significant (P <0.02) while in liquids the levels were not significant (P <0.2) when compared to the acceptable levels of 104/cfc/g. In both preparations, two potentially pathogenic organisms, Klebsiella spp. and Pseudomonas spp., were isolated. The level of contamination with these bacteria was significantly high (P <0.01) in both preparations. Other pathogenic micro notorganisms recovered were Candida spp. and Escherichia coll The level of contamination with these agents was significantly high (P < 0.01) in the powders. These results indicate that liquid and powder herbal preparations commonly sold by traditional herbalists in open air markets in Dar es Salaam are frequently contaminated by bacteria and fungi. Some of these microbial contaminants are potential pathogens of man, and may thus predispose the patients taking these preparations to the risk of acquiring infections. These contaminated medicinal preparations may also facilitate transfer of strains of microorganisms which harbour antibiotic resistance genes. In view of these findings, it is recommended to conduct further studies to find out how these herbalists collect, prepare, store and dispense the drugs. Attempts should also be made to train traditional herbalists the fundamental aspects of Good Manufacturing Practices, with a view to improving their skills in proper handling of drugs in order to minimise chances of contamination.

Objectives: To determine the risk factors for HIV seroconversion and assess the association between contraceptive use and HIV infection among women attending three large family planning clinics in Dar es Salaam, Tanzania., Design: Prospective cohort study., Methods: Between 1992 and 1995, 2471 HIV-negative women were followed prospectively. Information about sociodemographic characteristics, sexual behavior, contraceptive use and other risk factors was collected at recruitment and updated at follow-up visits. At the end of the study, specimens were collected for HIV testing and laboratory diagnosis of sexually transmitted diseases., Results: The overall HIV incidence was 3.4 per 100 person-years [95% confidence interval (Cl), 2.6-4.1]. The risk of HIV seroconversion decreased with increasing age (P=0.04, test for trend). Women reporting three or more sex partners during the follow-up period had the highest risk of HIV [age-adjusted relative risk (RR), 4.89; 95% Cl, 2.61-9.17]. Having an uncircumcised husband was associated with a significantly increased risk of HIV (age-adjusted RR, 3.60; 95% Cl, 1.12-11.59). The risk of HIV was also significantly increased among women with gonorrhoea (age-adjusted RR, 3.51; 95% Cl, 1.60-7.71) and candidiasis at baseline (age-adjusted RR, 1.98; 95% Cl, 1.17-3.33) and among women reporting alcohol consumption during the follow-up period. After controlling for other risk factors, the risk of HIV infection amongst users of oral contraceptive, intrauterine device and injectable contraceptive was not significantly increased. Similarly, there was no significant trend associated with increasing duration of use of any of these contraceptive methods., Conclusion: These findings confirm that a large number of new HIV infections continue to occur in this population. Reassuringly, no significant association was observed between HIV and use of specific contraceptive methods. Interventions to reduce further spread of HIV are still urgently needed.

Objective: To study late postnatal transmission of human immunodeficiency virus type 1 in a cohort of children born to HIV-1-seropositive mothers who delivered at Muhimbili Medical Centre in Dar es Salaam, Tanzania., Materials and Methods: Since 1991 a prospective cohort study of mother-to-child transmission of HIV-1 has been conducted at Muhimbili Medical Centre in Dar es Salaam. HIV-1-seropositive mothers and age-matched seronegative controls were recruited into the cohort at delivery together with their newborns. Diagnosis of HIV-1 infection in children was based on polymerase chain reaction, HIV-1 p24 antigen tests and HIV antibody tests. Late postnatal transmission was defined as HIV-1 infection occurring after 6 months of age in a child who was uninfected at 6 months of age and who had an HIV-1-seropositive mother. Children born to HIV-seronegative mothers were used as controls. Breast-feeding was universal in this cohort. CD4 and CD8 T lymphocytes were assayed by flow cytometry in the mothers., Results: Among 139 children born to HIV-1-seropositive mothers and known to be HIV-uninfected at 6 months of age, 8 children became HIV-1-infected at the end of their first year of life or later. No conversions were observed in children younger than 11 months. The 8 conversions were observed during a follow-up covering 1555 child months between 6 and 27 months of age corresponding to a conversion rate of 6.2 per 100 child years. Among 260 children with HIV-seronegative mothers no child became HIV-infected during the follow-up. The percentage of CD4 T lymphocytes was similar in mothers with early and late transmission but was significantly lower in transmitting than in nontransmitting mothers., Conclusion: Because no HIV-1 infection occurred in children with HIV-seronegative mothers, we conclude that the observed infections at the end of the first year of life or later among children born to HIV-seropositive women were caused by late transmission from mother to child, most likely through breast-feeding.

The objective was to determine whether there is an association between carriage of oral yeasts, malnutrition and HIV-1 infection among Tanzanian children. A case-control study design within a cross-sectional study was used, and the outcome was carriage of oral yeasts. The exposure variables were malnutrition and HIV-1 antibody, and confounders to be adjusted for were age, sex, and breastfeeding. The study was carried out in Dar-es-Salaam, Tanzania, in two maternal and child health (MCH) clinics that offer routine medical checkups to all expectant mothers and children aged between 0 and 5 years in the catchment area. A total of 882 children aged between 18 months and 5 years participated. Smears from the tongue and buccal mucosa were examined for oral yeasts. Malnutrition was categorized according to standards on the MCH chart and World Health Organization/Centers for Disease Control (WHO/CDC) standards as weight-for-height (wasted), weight-for-age (underweight), and height-for-age (stunted). HIV-1 infection was determined by an enzyme-linked immunosorbent assay. Reactive sera were confirmed by Western Blot. About 27% of the children were slightly or severely malnourished according to standards on the MCH chart. According to WHO/CDC standards, 2.6% were wasted, 16.3% were underweight, and 29.6% were stunted. Fourteen (1.6%) were seropositive for HIV-1 antibody. Hyphal forms and blastospores were much more frequent among children infected with HIV-1 with odds ratios ranging from 3.8 (95% CI: 1.3;11.2) to 6.2 (95% CI: 2.1;18.4) depending on categorization of malnutrition. Malnutrition was a risk factor, too, albeit to a much lesser and insignificant degree. The study supports our previous findings that malnutrition may predispose to carriage of oral yeasts and subsequent infection. However, in this study population HIV infection was clearly the predominant risk factor.

We designed a study to assess the nutritional status of children under five years of age attending MCH clinics in Dar es Salaam. This was a cross-sectional anthropometric study involving children 6-24 months who from July to August 1993 were attending Magomeni MCH clinic and those aged 18 months to five years who were attending Lugalo and Mwananyamala MCH clinics for routine growth monitoring and for vaccination between May to August 1994. The data collected included age, birthweight, sex, weight, height, breastfeeding status and HIV-1 serostatus. Of the 1854 children enrolled (961 boys and 893 girls) 31.6% were stunted, 14.6% were underweight and 2.9% were wasted. The highest percentage of stunting and wasting was observed between 11 and 25 months and 36 to 40 months. Of the 849 children tested for HIV-1, 14 (1.7%) were seropositive and two out of 770 (0.3%) were born with low weight. HIV seropositivity and low birthweight were both associated with stunting and wasting. We conclude that malnutrition is still a sizeable problem among children attending urban MCH clinics in Dar es Salaam especially among those aged less than three years, to whom special malnutrition control strategies should be targeted. There is also a need to identify factors responsible for the observed decline in MCH attendance with age and correct the situation.

Antimicrobial resistance has become a major medical and public health problem. The main factor responsible for development and spread of bacterial resistance is injudicious use of antimicrobial agents which has resulted in most gram positive and gram negative bacteria continuously developing resistance to the antimicrobials in regular use at different time periods. In East Africa, among E. coli in urinary tract infections, more than 80% are currently resistant to ampicillin, cotrimoxazole and tetracycline while more than 80% of the isolates are still susceptible to nitrofurantoin, gentamicin and third generation cephalosporins. Penicillin G resistant strains of pneumococci were first reported in 1967 but had gradually increased to about 20% in 1991. Among group A streptococci, all natural strains are still sensitive to penicillin G while resistance to tetracycline has reached alarming proportions. In Tanzania, more than 65% of N. gonorrhoeae isolates are beta-lactamase producers, however, spectinomycin, second and third generation cephalosporins and ciprofloxacin are effective against most strains. Vibrio cholerae 01 strains resistant to multiple antibiotics are widely spread globally, however, there are recent reports indicating that withdrawal of the drugs can lead to loss of the antibiotic resistance factors. Despite varied susceptibility of N. meningitidis strains world wide, isolates in Tanzania are still susceptible to commonly available drugs including penicillin G and chloramphenicol. Available methods for control of spread of bacterial resistance include rational use of antimicrobial agents including control in animal husbandry, change to newer antimicrobials, rotational use of drugs and constant surveillance for emerging bacterial resistance.

In order to assess the prognostic value of lymphocyte subsets and immune activation markers in HIV-1 infected Tanzanian patients, peripheral white blood cell(WBC) count, total lymphocytes, CD4+ and CD8+ T-lymphocytes and Beta-2 microglobulin (B-2M) concentrations were determined among healthy HIV-1 seronegative Tanzanian blood donors and in infected Tanzania individuals in different clinical stages of HIV-1 infection. CD4+ T-lymphocytes, CD8+ T-lymphocyte percentages, CD4:CD8 lymphocyte ratios and the concentrations of B-2M were strongly correlated with the clinical stages of HIV-1 infection. These results suggest that B-2M could be a useful prognostic marker in HIV-1 infection in settings where T-lymphocyte subset determinations cannot be done.

The present study, based on 158 HIV seropositives and 167 HIV seronegatives, demonstrates that saliva collected with the Omni-SAL device and tested with GACELISA (an IgG antibody capture ELISA) is an effective non-invasive alternative to serum for anti-HIV IgG antibody screening. The study also shows that a conventional serum Western blot kit can be used, with slight modifications, for confirmatory testing of saliva specimens. Collecting saliva with the Omni-SAL device had a very good acceptance rate among Tanzanian subjects, and although this diagnostic method is not yet known by the general public, 65% of the study participants preferred to give saliva instead of blood for HIV testing.

Human immunodeficiency infection and AIDS are a major recent microbial infection in east Africa with serious health and socioeconomic impacts in the region. At present HIV infection and AIDS account for more than 50% of adult medical admissions into some of the national and provincial hospitals as well as for 10-15% of paediatric admissions. AIDS is also at present the commonest cause of death among those aged 15-45 years. Tuberculosis, a closely associated disease to HIV infection, has increased more than three fold in some countries in the region. The prevalence of HIV infection currently ranges from 10-30% among adults in urban areas and from less than 1% to 25% in adults in rural areas; since this prevalence is still rising, the full impact of the AIDS problem in east Africa is yet to be realised. This is different from the situation in many developed countries where AIDS is no longer a priority health issue and where peak prevalences of the infection have been reached. The differences in HIV prevalences between east Africa and developed countries are due to poverty, ignorance, high prevalence of other STDs and associated cultural and traditional practices which prevail and facilitate HIV transmission in the region. While more than 80% of HIV infection in east Africa is transmitted through heterosexual intercourse, 5-15% of cases are perinatally transmitted and the remaining cases are transmitted through blood and blood products. While a lot of scientific advances have been made in immunopathology of AIDS, diagnostics and in social behavioural studies, we are still a long way towards getting curative therapy and or effective preventive vaccines. Recent discovery that use of zidovudine can significantly reduce perinatal HIV transmission is an additional breakthrough. While knowledge and tools for preventing HIV transmission are available in the world, prospects for AIDS control in east Africa appear gloomy unless major efforts are made in the reduction of poverty, ignorance and in the control of other common sexually transmitted diseases.

Seroprevalence of HIV-1 infection was determined in children aged between eighteen months and five years, attending maternal and child health (MCH) clinics in Dar es Salaam, Tanzania. A total of 889 children were eligible for the study, however seven children could not be enrolled because their mothers/guardians absconded and blood could not be drawn from 21 children due to refusal of mothers/guardians and from another 12 children due to technical reasons. Therefore, the participation rate was 95.5%. Of the 849 children screened, 14 (1.65%) were found to have IgG anti HIV-1 antibodies in their sera. The main clinical features found in children with symptomatic HIV-1 disease were weight loss, generalized lymphadenopathy, recurrent fevers, and prolonged diarrhoea. The utility of clinical features suggestive of HIV-1 infection (according to CDC classification) in identifying HIV-1 infection in children was evaluated and found to have high sensitivity (100%), specificity (96.9%) and negative predictive value (100%), but a low positive predictive value (35%). Marked variations in progression to symptomatic phase were noted, whereby some relatively young children had progressed to symptomatic phase (CDC class P-2A), while some older children were still in the asymptomatic stage (CDC class P-1 C). None of the symptomatic HIV-1 infected children presented with neurological disease, severe opportunistic infections, or malignancies. Although reduced mid-upper arm circumference and weight-for-age were associated with HIV seropositivity, these clinical parameters had low positive predictive values compared to the CDC classification.

Serum levels of immunoglobulin classes and IgG subclasses were determined in healthy seronegative (n = 50) and in HIV-1 seropositive adults (n = 50) from Tanzania, a region with heterosexual HIV-1 transmission pattern. The mean levels of total IgG, IgG1, IgG3, IgA, IgM, and IgD obtained were found to be significantly higher in HIV-1 seropositive sera than in control sera. The mean IgA, IgM, IgD and IgG3 levels showed an increasing trend with progression from asymptomatic phase to AIDS phase. The mean levels for total IgG, IgG1 and IgG2 remained constant while that for IgG4 decreased with progression to AIDS phase. From the findings, it is concluded that polyisotypic hypergammaglobulinaemia and serum IgG subclass changes occur in HIV-1 seropositive individuals in Tanzania. The characteristic changes observed for IgD, IgG3 and IgG4 levels with evolution from asymptomatic to AIDS phases could be of value in monitoring disease progression.

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.