Tuberculosis among the elderly in Tanzania: disease presentation and initial response to treatment.

BACKGROUND: Reports on tuberculosis (TB) presentation among the elderly in sub-Sahara Africa are scarce at a time when the elderly population is increasing. This dearth of information is likely to lead to an increase in the number of undetected TB cases in the region. OBJECTIVE: To describe TB presentation and response to anti-tuberculosis treatment at 2 months among elderly patients. METHODS: Consecutive patients referred to TB centres in Dar es Salaam, Tanzania, underwent clinical, microbiological and chest X-ray (CXR) evaluations at baseline and after 2 months of anti-tuberculosis treatment. Patients aged 60 years were considered elderly and those aged 18-59 years formed the comparison group. RESULTS: Elderly patients with TB were more likely to have smear-negative TB (76.7% vs. 49.3%, P < 0.0001) and lower-zone lesions on CXR (41% vs. 17%, P < 0.001), but less likely to have cavities on CXR (77.6% vs. 50.4%, P < 0.0001) than the comparison group. Hypertension and diabetes mellitus were more common among the elderly than among controls. Mortality at 2 months was respectively 18.6% and 8.1% among the elderly and among controls. Human immunodeficiency virus infection and smoking increased mortality, while hypertension was associated with reduced mortality. CONCLUSION: TB in the elderly was associated with atypical clinical and radiological presentations. A high index of suspicion could minimise delays in diagnosis and treatment.

Nutritional status of HIV-infected women with tuberculosis in Dar es Salaam, Tanzania.

SETTING: Tuberculosis (TB) treatment clinics in Dar es Salaam, Tanzania. OBJECTIVE: To quantify anthropometrics and intake of en-ergy and protein among human immunodeficiency virus (HIV) positive women with TB. DESIGN: HIV-positive women with newly diagnosed TB were assessed on their anthropometric characteristics and dietary intake. Energy and protein intake were determined using Tanzania food composition tables and compared with standard recommendations. Patients were re-evaluated after 4-6 months of anti-tuberculosis treatment. RESULTS: Among 43 women, the baseline median CD4 count was 209 cells/µl (range 8-721); 19 (44%) had a CD4 count of <200; 20 (47%) were on antiretroviral therapy. Body mass index was <18.5 kg/m(2) in 25 (58%); the median food insecurity score was 6. The median level of kcal/day was 1693 (range 1290-2633) compared to an estimated need of 2658; the median deficit was 875 kcal (range -65-1278). The median level of protein/day was 42 g (range 27-67) compared to 77 g estimated need; the median protein deficit was 35 g (range 10-50). The median weight gain among 29 patients after 4-6 months was 6 kg. CONCLUSION: HIV-positive women with TB have substantial 24-h deficits in energy and protein intake, report significant food insecurity and gain minimal weight on anti-tuberculosis treatment. Enhanced dietary education together with daily supplementation of 1000 kcal with 40 g protein may be required.

Pneumocyctis pneumonia and pulmonary tuberculosis among HIV-infected patients at Muhimbili National Hospital, Tanzania.

BACKGROUND: Respiratory infections such as pulmonary tuberculosis (PTB) and pneumonia are significant causes of morbidity and mortality in HIV infection. Recent studies have shown an increase in Pneumocystis jerovecii pneumonia (PCP) in Sub-Saharan Africa. This study determines the prevalence of PCP and other pulmonary infections among HIV patients at HIV clinics in Tanzania. METHODS: HIV infected patients with cough were enrolled between May and November 2006. Sputum induction was done and examined for PCP using Toluidine blue stain and Polymerase chain reaction. Ziehl-Neelsen stain was also done for PTB. RESULTS: Nine of the 125 (7.2%) had smear positive PTB. PCP was diagnosed in 10.4% (13/125) by Toluidine blue, while PCR was positive in 3.6% (3/88). Low CD4+ cell counts were associated with increased risk to both PCP and PTB. CONCLUSION: PCP is still low in Tanzania. PTB remains the major respiratory problem in HIV patients with cough. Toluidine blue staining is not reliable for PCP diagnosis

Completion of isoniazid preventive therapy and survival in HIV-infected, TST-positive adults in Tanzania.

SETTING: The World Health Organization recommends the use of isoniazid preventive therapy (IPT) for human immunodeficiency virus (HIV) infected patients with a positive tuberculin skin test (TST). However, due to concerns about the effectiveness of IPT in community health care settings and the development of drug resistance, these recommendations have not been widely implemented in countries where tuberculosis (TB) and HIV co-infection is common. OBJECTIVE: To evaluate the effectiveness of IPT on survival and TB incidence among HIV-infected patients in Tanzania. DESIGN: A cohort study nested within a randomized trial of HIV-infected adults with baseline CD4 counts of ≥ 200 cells/µ l was conducted to compare survival and incidence of active TB between TST-positive subjects who did or did not complete 6 months of IPT in the period 2001-2008. RESULTS: Of 558 TST-positive subjects in the analytic cohort, 488 completed 6 months of IPT and 70 did not. Completers had a decrease in mortality compared to non-completers (HR 0.4, 95%CI 0.2-0.8). However, the protective effect of IPT on the incidence of active TB was non-significant (HR 0.6, 95%CI 0.3-1.3). CONCLUSION: Completion of IPT is associated with increased survival in HIV-infected adults with CD4 counts ≥ 200 cells/µ l and a positive TST.

Disseminated tuberculosis in human immunodeficiency virus infection: ineffective immunity, polyclonal disease and high mortality.

BACKGROUND: Disseminated tuberculosis (TB) is a major cause of death in patients with the acquired immune-deficiency syndrome (AIDS), but its pathogenesis and clinical features have not been defined prospectively. METHODS: Human immunodeficiency virus (HIV) infected adults with a CD4 count ≥ 200 cells/µl and bacille Calmette-Guérin scar underwent immunologic evaluation and subsequent follow-up. RESULTS: Among 20 subjects who developed disseminated TB, baseline tuberculin skin tests were ≥15 mm in 14 (70%) and lymphocyte proliferative responses to Mycobacterium tuberculosis were positive in 14 (70%). At the time of diagnosis, fever ≥2 weeks plus ≥5 kg weight loss was reported in 16 (80%) patients, abnormal chest X-rays in 7/17 (41%), and positive sputum cultures in 10 (50%); median CD4 count was 30 cells/µl (range 1-122). By insertion sequence (IS) 6110 analysis, 14 (70%) blood isolates were clustered and 3/8 (37%) concurrent sputum isolates represented a different strain (polyclonal disease). Empiric TB treatment was given to eight (40%) patients; 11 (55%) died within a month. CONCLUSIONS: Disseminated TB in HIV occurs with cellular immune responses indicating prior mycobacterial infection, and IS6110 analysis suggests an often lethal combination of reactivation and newly acquired infection. Control will require effective prevention of both remotely and recently acquired infection, and wider use of empiric therapy in patients with advanced AIDS and prolonged fever.

Low BMI and falling BMI predict HIV-associated tuberculosis: a prospective study in Tanzania.

BACKGROUND: Low body mass index (BMI) is a known risk factor for tuberculosis (TB) in people without human immunodeficiency virus (HIV), but there are no prospective studies linking BMI to the risk of HIV-associated TB. DESIGN: In HIV-infected adults with CD4 counts ≥ 200 cells/µl receiving placebo in a TB booster vaccine trial in Dar es Salaam, Tanzania, we measured BMI at baseline and Year 1, and related baseline BMI and change in BMI to the risk of developing TB. RESULTS: We documented 92 cases of TB among 979 subjects followed for a mean of 3.2 years. Compared to subjects who did not develop TB, subjects who developed TB had a lower baseline BMI (23.2 vs. 24.6 kg/m(2), P = 0.006), and a greater BMI decline from baseline to Year 1 (-0.4 vs. 0.6 kg/m(2), P < 0.001). In multivariate analyses, baseline BMI was associated with the risk of developing TB (hazard ratio [HR] per kg/m(2) 0.94, 95%CI 0.90-0.99, P = 0.028), as was the change in BMI from baseline to Year 1 (HR per kg/m(2) 0.79, 95%CI 0.71-0.87, P < 0.001). Subjects with a baseline BMI < 17 kg/m(2) were more likely to develop TB (HR 3.72, 95%CI 1.16-12.0, P = 0.028). CONCLUSION: Low and falling BMI predict HIV-associated TB.

Enhancing adherence to antiretroviral therapy at the HIV clinic in resource constrained countries; the Tanzanian experience.

OBJECTIVE: To evaluate various strategies aimed at improving adherence to antiretroviral therapy (ART). METHODS: Patients initiated on ART at Muhimbili National Hospital HIV clinic were randomly assigned to either regular adherence counseling, regular counseling plus a calendar, or regular counseling and a treatment assistant. Patients were seen monthly; during these meetings self-reported adherence to treatment was recorded. Disease progression was monitored clinically and immunologically. RESULTS: Of the 621 patients randomized, 312 received regular counseling only, 242 regular counseling and calendars, while 67 had treatment assistants in addition to regular counseling. The mean (SD) follow-up time was 14.5 (4.6) months. During follow-up 20 (3.2%) patients died, and 102 (16.4%) were lost to follow-up; this was similar in all groups. In 94.8% of all visits, patients reported to have adhered to treatment. In only 39 (0.7%) visits did patients report a < or = 95% adherence. There were no differences in adherence (P = 0.573) or differences in CD4 count and weight changes over time in the interventions. CONCLUSIONS: Good adherence to ART is possible in resource constrained countries. Persistent adherence counseling in clinic settings by itself may be effective in improving adherence to ART.

University partnership to address the shortage of healthcare professionals in Africa.

The shortage of qualified health professionals is a major obstacle to achieving better health outcomes in many parts of the world, particularly in Africa. The role of health science universities in addressing this shortage is to provide quality education and continuing professional development opportunities for the healthcare workforce. Academic institutions in Africa, however, are also short of faculty and especially under-resourced. We describe the initial phase of an institutional partnership between the Muhimbili University of Health and Allied Sciences (MUHAS) and the University of California San Francisco (UCSF) centred on promoting medical education at MUHAS. The challenges facing the development of the partnership include the need: (1) for new funding mechanisms to provide long-term support for institutional partnerships, and (2) for institutional change at UCSF and MUHAS to recognize and support faculty activities that are important to the partnership. The growing interest in global health worldwide offers opportunities to explore new academic partnerships. It is important that their development and implementation be documented and evaluated as well as for lessons to be shared.

Introduction of regular formative assessment to enhance learning for clinical students at Muhimbili University College, Tanzania.

OBJECTIVE: To determine if undertaking regular Formative Assessment (FA) in the setting of our medical school enhanced the students' learning experience. METHODS: An FA intervention was designed and implemented with clinical students during their clerkship in the academic year 2003/04. FA was administered as structured verbal comments on daily clinical case presentations. Evaluation of the intervention included pre- and post-surveys exploring the perceptions of students and teachers on the quality of the learning experience. Focus group discussions with students and with teachers were held at the start and conclusion of the intervention to identify strengths and weaknesses of FA. FINDINGS: All participating teachers perceived that students were interested in learning before the intervention. Teachers who perceived that students achieved the set learning objectives increased from 0% before to 28% after the intervention. Most teachers (71%) and students (86%) perceived FA to enrich students' learning experience. Students appreciated the positive change in teachers' attitudes during the FA intervention. Both students and teachers recommended that FA become a regular and routine activity. CONCLUSIONS: Students and teachers viewed FA as a positive, feasible intervention. They thought it enriched the learning process and recommended it be a routine learning activity.

Diversity of lepidopteran stem borers on monocotyledonous plants in eastern Africa and the islands of Madagascar and Zanzibar revisited.

Surveys were completed in Eritrea, Ethiopia, Kenya, Madagascar, Mozambique, Tanzania, Uganda and Zanzibar to assess the lepidopteran stem borer species diversity on wild host plants. A total of 24,674 larvae belonging to 135 species were collected from 75 species of wild host plants belonging to the Poaceae, Cyperaceae and Typhaceae. Amongst them were 44 noctuid species belonging to at least nine genera, 33 crambids, 15 pyralids, 16 Pyraloidea species not yet identified, 25 tortricids and three cossids. The noctuid larvae represented 73.6% of the total number of larvae collected, with 66.3, 3.5 and 3.8% found on Poaceae, Cyperaceae and Typhaceae, respectively. The Crambidae, Pyralidae, Tortricidae and Cossidae represented 19.8, 1.9, 2.5 and 0.1% of the total larvae collected, respectively, with 90.4% of the Crambidae and Pyralidae collected from Poaceae, and 99.7% of the Tortricidae collected from Cyperaceae. The lepidopteran stem borer species diversity in the wild host plants was far more diverse than previously reported.

Estimation of CD4 T-lymphocyte counts from percent CD4 T-lymphocyte determinations in HIV-1-infected subjects in sub-Saharan Africa.

The relationship between CD4 percent and CD4 count has been reported to be different in industrialized countries compared to sub-Saharan Africa, where often only the former is reliable. CD4 determinations from an open cohort of hotel workers in Dar es Salaam followed between 1990 and 1998 were evaluated. T-lymphocyte determinations were offered once a year to 190 HIV-1 seropositive, 80 seroconverters and 495 sex and age matched HIV-seronegative subjects. After log transformation of the CD4 percent and CD4 counts a good fit to a linear regression curve was found, R(2) 0.697. The CD4 percent corresponding to a CD4 count of 200 cells/mm(3) was found to be 9.8%. CD4 percent determination can be useful to estimate CD4 counts, but needs to be locally standardized. The CD4 percent in Africa corresponding to AIDS defining CD4 counts seems to be lower than in the industrialized world.

Dropouts in a long-term follow-up study involving voluntary counseling and HIV testing: experience from a cohort of police officers in Dar Es Salaam, Tanzania.

BACKGROUND: Results of most population-based studies primarily are derived from people who responded positively and thereby continued to participate in such studies. It is, however, equally important to know the characteristics of study subjects who drop out to learn the reasons that kept them from continuing to participate in the study, especially because they had initially agreed to participate in such a study. In studies with long-term follow-up, reasons for nonresponse may provide invaluable information that may be gathered through continued contact with study subjects who have withdrawn from the study. OBJECTIVES: To determine characteristics of study participants who withdrew from an ongoing study of police officers, which involved counseling and HIV testing, and to determine reasons for their discontinued participation. METHODS: Demographic characteristics of a cohort of police officers who had been participating in a study to determine their suitability for HIV vaccine trials were analyzed. Characteristics of those who did not return for the second survey of appointments for HIV testing were compared with those who continued their participation. A randomly selected sample of 132 police officers who did not participate in the second survey of HIV testing were asked why they did not return. Answers were obtained from 84 people who had discontinued their participation. RESULTS: Of eligible police officers, 2087 (72.1%) responded to the call for follow-up appointments, whereas 807 (27.9%) did not return. Those who did not return to participate in the second survey had significantly higher rates of HIV seropositivity (17.2%) than those who did return (13.5%) (p <.05). The rate of return in unmarried participants was worse (p <.05) than the rate among married participants. Rates of sexual contacts with partners other than their spouses and levels of alcohol consumption did not differ between the two groups. Reasons for dropping out of the study included fear of knowing results of HIV testing in 54.6%, lack of time to continue in 34.5%, and fears about job security in 3.6%. CONCLUSION: Fears of finding out that one might be seropositive need to be answered at recruitment, and practical arrangements must be made to facilitate further follow-up. A bias for lower incidence might be introduced in vaccine trials if participants thought to be at highest risk for HIV infection discontinue participation.

Clinical features of tuberculosis among adults in sub-Saharan Africa in the 21st century.

Although tuberculosis was unknown in sub-Saharan Africa before the 19th century, rapid spread of infections due to Mycobacterium tuberculosis occurred during the 20th century and could be found in up to 50% of the adult population by the 1950s. Owing to changes in age structure, rapid urbanization associated with overcrowding living conditions, increasing poverty and the HIV epidemic a 300-400% increase in tuberculosis cases and deaths has been reported from sub-Saharan Africa. Persons dually infected with HIV and tuberculosis may have active tuberculosis with typical or atypical clinical features and/or involving multiple organ systems. In addition, mycobacteraemia associated with non-specific clinical features is common among HIV-infected persons, especially if they are severely immunocompromised. Because of the atypical clinical features these patients are easily misdiagnosed and are therefore likely to die from what is otherwise a curable illness. Consequently there is a need to better characterize the clinical features of all forms of tuberculosis, especially in the presence of HIV infection.

HIV infection in elderly medical patients.

OBJECTIVE: To determine the prevalence and presentation of HIV-infection among medical admissions aged 55 years and above. DESIGN: Prospective cross-sectional study. SETTING: Dar es Salaam, Tanzania. SUBJECTS: Consecutive patients aged 55 years and above hospitalised in the medical wards of the Muhimbili Medical Centre in Dar es Salaam from February to May 1998. RESULTS: The overall HIV-1 seroprevalence was 15.0% (38/253); and by sex it was 18.5 % (28/ 151) among males compared to 9.8% (10/102) amongfemales (p=0.06). The HIV-1 prevalence among those aged 55 to 59 years was 29.7%. There was no association between HIV- 1 serostatus and whether one lived in a rural or urban area, marital status, level of education nor socio-economic status. The main presenting features in patients who were found to be HIV-1 seropositive were wasting 44.7%, fever 39.5%, pallor 34.2% and weight loss 31.6%. Only six (15.8%) of the 38 patients were initially suspected to have been HIV-infected before laboratory results were obtained. CONCLUSIONS: HIV-infection is a notable problem in the population of elderly medical admissions in Dar es Salaam. The possibility of HIV-infection should be considered among elderly patients with clinical features of immunodeficiency. HIV/AIDS prevention programmes directed towards the elderly should be established.

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.

Isoniazid prophylaxis for tuberculosis prevention among HIV infected police officers in Dar es Salaam.

OBJECTIVE: To determine the acceptability, compliance and side effects of isoniazid (INH) prophylaxis against tuberculosis among HIV infected police officers (PO) in Dar es Salaam. DESIGN: A nested study from a prospective follow up of a cohort of police officers. SETTING: Dar es Salaam, Tanzania. SUBJECTS: One hundred and forty three HIV-1 infected police officers. MAIN OUTCOME MEASURES: Acceptance and compliance to INH prophylaxis. RESULTS: Of the 400 HIV-1 infected officers, 143 (35.7%) came forward for post-test counselling and HIV test results. Sixty per cent (87/143) of them accepted to be on INH prophylaxis. However only 42.5% (37/87) came forward for evaluation regarding their suitability for INH prophylaxis. During the evaluation, eight (21.6%) of 37 otherwise asymptomatic PO were found to have active pulmonary tuberculosis (TB). Eventually only 29 PO were actually started on INH, and only 16 (55.2%) of them completed the six months course. No serious side effects were observed. One PO developed TB two months after loss to follow up before completing the six months. CONCLUSIONS: There was low acceptability of and poor compliance with INH prophylaxis among the HIV-1 infected PO despite being educated on the benefits of prophylaxis. The prevalence of PTB among asymptomatic HIV-1 infected PO was high, and therefore persons with HIV infection should be examined for TB even in the absence of symptoms.

Fatal Mycobacterium tuberculosis bloodstream infections in febrile hospitalized adults in Dar es Salaam, Tanzania.

Causes of community-acquired bloodstream infections (BSIs) in sub-Saharan Africa are unknown with regard to mycobacteria and fungi. We prospectively studied 517 consecutive febrile (axillary temperature, > or =37.5 degrees C) adults (> or =15 years of age) admitted to one hospital in Tanzania. After hospital admission and informed consent, blood was drawn for culture (of bacteria, mycobacteria, and fungi), determination of human immunodeficiency virus type 1 (HIV-1) status, and malaria smears. Malaria smears were prepared for a control group of 150 afebrile patients. One hundred and forty-five patients (28%) had BSI. Of these 145 patients, 118 (81%) were HIV-1-infected. HIV-positive patients were more likely than HIV-negative ones to have BSI (118 of 282 vs. 27 of 235; P < .0001). The three most frequently isolated pathogens were Mycobacterium tuberculosis (60 [39%]), non-typhi Salmonella species (29 [19%]), and Staphylococcus aureus (13 [8.3%]). The incidence of malaria parasitemia was similar in study and control patients (9.5% vs. 8%). In this patient population with high prevalence of HIV-1 infection, M. tuberculosis has become the foremost cause of documented BSI.