Preventive chemotherapy for HIV-associated tuberculosis in Uganda: an operational assessment at a voluntary counselling and testing centre.

OBJECTIVE: To assess the operational aspects of isoniazid preventive chemotherapy (IPT) for tuberculosis in persons dually infected with HIV and Mycobacterium tuberculosis identified at an independent HIV voluntary counselling and testing centre in Kampala, Uganda. DESIGN: HIV-infected persons were counselled, had active tuberculosis excluded by medical examination, and were offered purified protein derivative (PPD) skin testing. PPD-positive persons were offered isoniazid 300 mg daily for 6 months. Drugs were supplied, and toxicity and compliance were assessed monthly. Utilization of service, cost, and sustainability were also assessed. RESULTS: Between 14 June 1991 and 30 September 1992, 9862 persons tested HIV-positive. Of 5594 HIV-infected clients who returned to collect test results, only 1524 (27%) were enrolled. Of those, 1344 were tuberculin-tested (88%); 180 were not tested because of active tuberculosis, serious illnesses, refusal, and other reasons. Of the 1344, 250 (19%) did not return for test reading and 515 were negative (47% of tests read). Of 579 tuberculin-positive persons, 59 (10%) were excluded from preventive chemotherapy because of tuberculosis and other respiratory illnesses. Of 520 persons given isoniazid, 62% collected at least 80% of their drug supplies. No major toxicity was observed. One case of tuberculosis occurred in the first month of treatment. Cost of HIV counselling and testing was US $18.54 per person and cost of follow-up counselling and social support was US $7.89. CONCLUSIONS: Important factors were identified which caused attrition, such as limited motivation by counsellors to discuss tuberculosis issues during HIV pre- and post-test counselling, insufficient availability of medical screening, shifting of sites to collect pills, and frequent tuberculin-negative tests. Active tuberculosis among 6% of persons screened suggests that voluntary counselling and testing sites may be important for tuberculosis case finding and underscores the need to exclude tuberculosis carefully before starting IPT. In developing countries, further studies assessing the feasibility of IPT within tuberculosis and HIV/AIDS programme conditions are needed. Cost-effectiveness of IPT, compared with passive case finding, and its sustainability should be assessed before national policies are established.

PIP: Those infected with human immunodeficiency virus (HIV) have a 5-10% risk per year of developing active tuberculosis, and this disease may accelerate the clinical course of HIV infection. Thus, a study was conducted in Uganda to assess the cost-effectiveness and acceptability of isoniazid preventive chemotherapy (IPT) for patients dually diagnosed with HIV and Mycobacterium tuberculosis. Of the 1344 HIV-infected patients at an independent HIV testing and counseling center in Kampala who were initially screened for participation in this study, 6% had signs of active tuberculosis. Selected for participation in the study were 520 subjects with no signs of active tuberculosis. Of these, 322 (62%) were considered compliant with the treatment regimen on the basis of their appearance for all scheduled appointments for pill distribution. One case of active tuberculosis occurred during the first month of IPT and most likely represented a case that went undetected in the screening process. No treatment-associated toxicity was reported. The cost of the HIV testing and counseling was US$18.54 per patient; that of follow-up counseling and support was $7.89. When administrative costs for the study were included in the calculation, the cost of IPT increased to $60.19 per person. Although reactivation of tuberculosis may have been prevented in up to 62% of subjects who received IPT, numerous factors mitigate against the routine implementation of such a treatment program, most notably its high cost and a shortage of voluntary HIV centers in developing countries. Needed are studies that evaluate the long-term community health, social, and economic benefits of such a program as well as further investigations of the impact of tuberculosis on the pace of progression from HIV to acquired immunodeficiency syndrome (AIDS).

Absence of Mycobacterium avium complex disease in patients with AIDS in Uganda.

The absence of disease due to Mycobacterium avium in Ugandan patients with AIDS, which we previously observed in a blood culture study, has been confirmed and our observations have been extended to 165 additional clinical isolates. Fourteen soil and water samples from the Ugandan environment have been cultured and revealed a high frequency of isolation of M. avium. The absence of M. avium complex disease in Uganda remains unexplained.

Community-acquired pneumonia in Ugandan adults: short-term parenteral ampicillin therapy for bacterial pneumonia.

A hospital-based prospective study of 99 patients with community-acquired pneumonia (CAP) was carried out in Kampala, Uganda. We evaluated microbiological etiologies, clinical features and effectiveness of short-term parenteral ampicillin followed by oral amoxicillin for these patients in relation to HIV-status. We demonstrated a very high prevalence (75%) of HIV-1 infection. No significant difference was observed with respect to age, gender, prior antibiotic usage, symptoms, laboratory data or bacterial etiology between HIV-1-infected and HIV-uninfected CAP patients. Most strains of Streptococcus pneumoniae (n = 19) and Haemophilus influenzae (n = 8) isolated from HIV-1-infected patients were penicillin-resistant (95%) and beta-lactamase producing (75%) strains, respectively. A high percentage of good clinical response was found in both HIV-1-infected (81%) and HIV-uninfected (86%) among 39 patients with CAP due to a defined bacterial pathogen. These data support the use of short-term parenteral ampicillin for patients with bacterial CAP irrespective of HIV-status.

Causes of lower respiratory infection in HIV-infected Ugandan adults who are sputum AFB smear-negative.

SETTING: Mulago national referral and teaching hospital. OBJECTIVE: To assess the etiology of lower respiratory infections in HIV-infected Ugandan adults who are sputum acid-fast bacilli (AFB) smear-negative. DESIGN: A descriptive cross-sectional study. Participants included consecutive adult patients admitted to medical wards with respiratory symptoms of at least 3 weeks and infiltrates on chest radiograph. Those who were sputum AFB smear-negative and HIV-positive underwent bronchoscopy and bronchoalveolar lavage (BAL). BAL fluid was obtained and stained for AFB and Pneumocystis carinii, and cultured for bacteria and fungi. RESULTS: Of 198 patients screened, 48 were sputum smear-positive for AFB. Sixty-seven were excluded for various reasons, leaving 83 patients who met the inclusion criteria and underwent bronchoscopy: 32 (38.6%) patients had P. carinii infection, 20 (24%) had pulmonary tuberculosis, nine (11%) had pulmonary Kaposi's sarcoma and pyogenic bacteria were identified in seven (8%). No aetiological diagnosis was found in 24 (30%) patients. CONCLUSION: P. carinii and Mycobacterium tuberculosis were the commonest causes of disease among sputum AFB smear-negative, HIV-positive adults presenting to Mulago Hospital. Pulmonary Kaposi's sarcoma and pyogenic bacteria occurred with less frequency.

Tuberculosis care in community care organizations in sub-Saharan Africa: practice and potential.

SETTING: Community care organizations in sub-Saharan Africa. OBJECTIVES: To evaluate current tuberculosis (TB) care in community health care organizations in sub-Saharan Africa, to assess their potential contribution to tuberculosis care, and to develop a model for expanded community participation in effective TB control. DESIGN: Quantitative assessment of tuberculosis care and cross-sectional assessment of qualitative measures in 14 community care organizations in Uganda, Zambia, South Africa and Malawi. RESULTS: The community care organizations assessed mainly provided care for human immunodeficiency virus (HIV) and aquired immune deficiency syndrome (AIDS) patients, and received funding from non-governmental organizations. Shortcomings in tuberculosis care included delays in diagnosis (which was often not based on sputum examination), drug shortages, low completion rates, high default rates, inadequate recording, little interaction with government tuberculosis programmes, and inadequate training of staff. However, one organization that provided primarily tuberculosis care and collaborated closely with the district tuberculosis programme and hospital attained a high treatment completion rate. The strong points of the community care organizations that favour a potential role of community participation in tuberculosis care were accessibility and staff motivation. CONCLUSION: Despite most community care organizations' shortcomings in tuberculosis care, they do have the potential to improve the care of tuberculosis patients, thus reducing the load on overstretched health facilities. Their potential impact on tuberculosis control depends on their population coverage and sustainability. HIV/AIDS community care organizations with strengthened management of tuberculosis care could serve as a model for expanded community participation in tuberculosis control. Operational research is needed to assess the feasibility and cost-effectiveness of community-based TB care.

Anti-tuberculosis drug resistance surveillance in Uganda 1996-1997.

SETTING: Drug resistance surveillance conducted by the National Tuberculosis and Leprosy Control Programme (NTLP) Uganda from 1996-1997 in collaboration with the Armauer Hansen Institute/German Leprosy Relief Association (GLRA), Germany, for the WHO/IUATLD Global Project on Anti-Tuberculosis Drug Resistance Surveillance. OBJECTIVE: To determine the prevalence of primary and acquired anti-tuberculosis drug resistance in Uganda. DESIGN: The survey area covered three GLRA-supported operational NTLP zones, corresponding to 50% of the Ugandan population. A representative random sampling of individual patients was chosen as sampling procedure. Altogether 586 smear-positive TB patients (537 new cases and 49 previously treated cases) were included in the survey. RESULTS: For primary resistance the results were as follows: isoniazid (H) 6.7%, rifampicin (R) 0.8%, ethambutol (E) 6.1%, streptomycin (S) 13.4%, thioacetazone (T) 3.2%, pyrazinamide (Z) 0%, multidrug resistance (MDR) 0.5%; for acquired resistance they were: H 37.8%, R 4.4%, S 22.2%, E 11.1%, T 20.0%, Z 0%, and MDR 4.4%. CONCLUSION: According to these data the NTLP Uganda has been effective in preventing high levels of primary drug resistance. If it is assumed that the sampling process reflects the distribution of new patients and previously treated patients in the study areas, the amount of acquired resistance (any resistance) in the community of smear-positive patients is approximately 5%. To further monitor programme performance the NTLP will embark on a nationwide survey in 1998/1999.

Risk factors for relapse in human immunodeficiency virus type 1 infected adults with pulmonary tuberculosis.

SETTING: A study conducted by the Uganda-Case Western Reserve University Research Collaboration in Kampala, Uganda, a country with high incidence rates of tuberculosis (TB) and human immunodeficiency virus type 1 (HIV-1) infection. OBJECTIVE: To assess clinical, microbiologic and radiographic factors associated with risk for relapse in HIV-infected adults treated for initial episodes of pulmonary TB. DESIGN: Nested case-control study within a randomized prospective clinical trial comparing the safety and efficacy of thiacetazone- and rifampicin-containing regimens for TB treatment in HIV-infected adults. RESULTS: The analysis was based on 119 patients who completed therapy. Median follow-up for all subjects was 22.3 months. Ten patients relapsed a median of 12.7 months after the end of therapy; seven of these were initially treated with the thiacetazone (T)-containing regimen. Each relapse case was matched to four controls by length of follow-up after initial TB treatment. In a univariate analysis risk for relapse was associated with treatment with the T-containing regimen (OR = 4.2, P = 0.08), age > or = 30 yrs (OR = 2.9, P = 0.16), and irregular compliance (OR = 3.6, P = 0.1). Baseline anergy on Mantoux tuberculin skin testing, cavitary disease, radiographic extent of disease and sputum bacillary burden, two month culture negativity, and residual cavitary disease at the end of treatment did not differ between relapses and controls. CONCLUSION: Older HIV-1 infected patients, those with poor treatment compliance, and those being treated with T-containing regimens, may be at increased risk for relapse after TB treatment and require closer post-treatment surveillance. Risk for relapse in HIV-infected adults with pulmonary TB after treatment with a nine month rifampicin-containing regimen was low (3.1 per 100 person-years observation) compared with those treated with a thiacetazone-containing regimen (10.1 per 100 person-years observation).

Impact of human immunodeficiency virus type-1 infection on the initial bacteriologic and radiographic manifestations of pulmonary tuberculosis in Uganda. Makerere University-Case Western Reserve University Research Collaboration.

SETTING: TB Treatment Centre, Kampala, Uganda. OBJECTIVE: To evaluate the impact of human immunodeficiency virus (HIV) co-infection on the bacteriologic and radiographic presentation of pulmonary tuberculosis (TB) in Uganda, a nation with high rates of Mycobacterium tuberculosis and HIV infection. DESIGN: To compare baseline characteristics among HIV-infected and non-HIV-infected adults with initial newly-diagnosed episodes of culture-confirmed pulmonary TB screened for participation in a randomized prospective TB treatment trial. RESULTS: Negative and paucibacillary (very scanty or scanty) sputum acid fast bacilli (AFB) smears were more frequent in HIV-infected patients presenting with pulmonary TB (P = 0.007). More HIV-infected individuals also had sputum cultures that required 7-8 weeks incubation until positivity than non-HIV-infected patients (P < 0.01). Lower lung field and diffuse pulmonary infiltrates were more frequent among HIV-infected patients. Rates of atypical X-ray presentations and cavitary disease were comparable between HIV-seropositive and -seronegative patients; however, atypical disease was more frequent in HIV-infected patients with small tuberculin reactions or tuberculin anergy (PPD = 0 mm). CONCLUSION: HIV co-infection was associated with a higher frequency of negative and paucibacillary sputum AFB smears. The differences in the diagnostic yields of microscopy and culture between HIV-infected and non-HIV-infected individuals were small and do not, in our opinion, significantly affect the utility of these important diagnostic tests in developing countries. Examining more than one sputum specimen and monitoring cultured specimens for a full 8 weeks may assist in optimizing the diagnostic yield. Upper lobe infiltrates and cavitary disease are still the most frequent radiographic presentations of pulmonary TB in HIV-infected and non-HIV-infected adults in countries with a high prevalence of TB.

Occurrence of Shiga toxin-producing Escherichia coli in fecal samples from children with diarrhea and from healthy zebu cattle in Uganda.

Fecal samples collected from 237 diarrheic infants in Kampala, Uganda and from 159 healthy cattle from a ranch in the Central Region of Uganda were investigated for the presence of Escherichia coli O157 and other types of Shiga toxin-producing E. coli (STEC). E. coli O157 were not detected in 150 stool samples from children which were cultivated on sorbitol MacConkey agar. A search for all types of STEC performed on 87 additional human stool samples with an enzyme-immunoassay for Shiga toxins (Premier EHEC) was also negative. Forty-two stool samples from infants were additionally investigated for enteropathogenic E. coli (EPEC) by DNA-hybridization with an eae-specific gene probe. Compared to STEC, EPEC were frequent and found in six (14.3%) of these 42 randomly selected stool specimens. We were further interested in the role of cattle as a reservoir for STEC in Uganda. STEC were isolated from 45 of 159 cattle from a herd in the Central Region of Uganda. STEC strains from cattle belonged to 16 different O- and nine different H-types and nine O:H types were identical to those found in bovine STEC from other continents. Only one bovine STEC strain was positive for the eae-gene, and O-groups associated with enterohemorrhagic E. coli (EHEC) types (O26, O103, O111, O145 and O157) were not found. Our report demonstrates that STEC are not frequent in urban children in Uganda, but domestic cattle were identified as an important natural reservoir for these organisms in this country.

Disseminated aspergillus fumigatus infection: case report.

A case of disseminated aspergillus fumigatus infection is reported in a 43 year old Ugandan female with no known immune system disorder(not neutropenic and HIV-1 sero negative). She presented with multiple cutaneous ulcers, recurrent empyema thoracis, a past history of intra-abdominal abscess and bowel infarction. Empirical treatment for tuberculosis was previously given without improvement. A diagnosis of aspergillus fumigatus based on a combination of tissue wet potassium hydroxide preparation, fungal culture and tissue histologic typing was made. Despite antifungal therapy with intravenous amphotericin B infusion in 5% dextrose, after a normal baseline renal function test, the patient died in the second week of admission. Autopsy showed disseminated aspergillosis involving the pleural space, pericardium, spleen, and meningitis in addition to the cutaneous sites. Disseminated aspergillus fumigatus infection in a non-immunocompromised is rare antemortem diagnosis. This case highlights the difficulty in making a diagnosis in the face of many endemic conditions with similar presentation.

Isolation and characteristics of Mycobacterium avium complex from water and soil samples in Uganda.

SETTING: Mycobacterium avium complex organisms have not been isolated from late stage AIDS patients in Uganda. This could possibly be due to the absence of M. avium complex in the Uganda environment. OBJECTIVE AND DESIGN: Determine whether M. avium complex organisms could be isolated from water and soils collected in the living environment of Ugandan AIDS patients. RESULTS: Representatives of the M avium complex were isolated from 3 of 7 (43%) water and 3 of 7 (43%) soil samples collected in Kampala, Uganda. The average number of colony-forming units per ml water was 3.3 and average colony-forming units per gram of soil was 7825. In terms of growth characteristics, antimicrobial susceptibility patterns, and the presence or absence of plasmids and IS901, Ugandan M. avium complex isolates were similar to those isolated from the US and European AIDS patients and their environment. CONCLUSIONS: M. avium complex organisms sharing genetic and physiological characteristics of M. avium complex isolates recovered from patients with AIDS can be isolated from water and soil samples in Uganda.

Absence of bacteremia with Mycobacterium avium-intracellulare in Ugandan patients with AIDS.

Disseminated infection with Mycobacterium avium-intracellulare is the most common systemic bacterial infection in American patients with the acquired immunodeficiency syndrome. Blood cultures for mycobacteria were obtained from 50 severely ill Ugandan patients fulfilling the World Health Organization criteria for AIDS and considered late in the course of their illness; 98% had antibody to HIV by ELISA. All blood cultures were negative. These data suggest that disseminated infection with M. avium-intracellulare is infrequent in Ugandan patients with AIDS, if it occurs at all.

The influence of human immunodeficiency virus infection on tuberculosis in Kampala, Uganda.

The clinical, radiographic, and microbiologic features of 59 patients with pulmonary tuberculosis in Kampala, Uganda were studied and correlated with the serologic reactivity to the human immunodeficiency virus (HIV) of these patients. Two-thirds of the patients with tuberculosis were HIV-seropositive. Histories of fever and weight loss were more prominent in HIV-seropositive patients, and perihilar and basilar infiltrative diseases were more frequently seen in HIV-seropositive patients. Although all patients responded similarly to drug therapy, cutaneous drug reactions were seen in nearly one-third of HIV-seropositive patients receiving thiacetazone.

Reduced sensitivity of tuberculosis serodiagnosis in patients with AIDS in Uganda.

SETTING: The diagnostic utility of serodiagnosis of tuberculosis in HIV-infected persons was studied in Kampala, Uganda. OBJECTIVE: This study was undertaken to evaluate the utility of a recently described serologic assay for the diagnosis of tuberculosis in HIV-infected patients. DESIGN: The study was undertaken as a cross-sectional survey of 349 subjects, including human immunodeficiency virus-infected and uninfected patients with tuberculosis and control subjects. Serum from each subject was assayed by enzyme-linked immunosorbent assay (ELISA) for IgG antibody to the 30,000 dalton antigen of Mycobacterium tuberculosis. RESULTS: Test sensitivity dropped from 0.62 in non HIV-infected tuberculous patients to 0.28 in HIV-infected patients. CONCLUSIONS: ELISA serodiagnosis of tuberculosis may have a markedly decreased utility in populations where HIV infection is prevalent.

Mycobacterium africanum subtype II is associated with two distinct genotypes and is a major cause of human tuberculosis in Kampala, Uganda.

The population structure of 234 Mycobacterium tuberculosis complex strains obtained during 1995 and 1997 from tuberculosis patients living in Kampala, Uganda (East Africa), was analyzed by routine laboratory procedures, spoligotyping, and IS6110 restriction fragment length polymorphism (RFLP) typing. According to biochemical test results, 157 isolates (67%) were classified as M. africanum subtype II (resistant to thiophen-2-carboxylic acid hydrazide), 76 isolates (32%) were classified as M. tuberculosis, and 1 isolate was classified as classical M. bovis. Spoligotyping did not lead to clear differentiation of M. tuberculosis and M. africanum, but all M. africanum subtype II isolates lacked spacers 33 to 36, differentiating them from M. africanum subtype I. Moreover, spoligotyping was not sufficient for differentiation of isolates on the strain level, since 193 (82%) were grouped into clusters. In contrast, in the IS6110-based dendrogram, M. africanum strains were clustered into two closely related strain families (Uganda I and II) and clearly separated from the M. tuberculosis isolates. A further characteristic of both M. africanum subtype II families was the absence of spoligotype spacer 40. All strains of family I also lacked spacer 43. The clustering rate obtained by the combination of spoligotyping and RFLP IS6110 analysis was similar for M. africanum and M. tuberculosis, as 46% and 49% of the respective isolates were grouped into clusters. The results presented demonstrate that M. africanum subtype II isolates from Kampala, Uganda, belong to two closely related genotypes, which may represent unique phylogenetic branches within the M. tuberculosis complex. We conclude that M. africanum subtype II is the main cause of human tuberculosis in Kampala, Uganda.