Clinical presentation, natural history, and cumulative death rates of 230 adults with primary cryptococcal meningitis in Zambian AIDS patients treated under local conditions.

SETTING: Inpatient medical wards, Department of Medicine, University Teaching Hospital, Lusaka, Zambia. OBJECTIVE: To define the natural history, clinical presentation, and management outcome of microbiologically confirmed cryptococcal meningitis in adult AIDS patients treated under local conditions where antifungal and antiretroviral therapies are not routinely available. DESIGN: A descriptive, longitudinal, observational study. METHODS: All adult patients admitted to the medical wards of the University Teaching Hospital, Lusaka, Zambia with cerebrospinal fluid culture proved, primary cryptococcal meningitis, during a 12 month period were enrolled into the study. The following details were acquired: clinical features, HIV status, laboratory data, treatment accorded, and survival. RESULTS: A total of 230 patients with primary cryptococcal meningitis were studied (median age 32 years; range 15-65 years; 112 males, 118 females). Cryptococcal meningitis was the first AIDS defining illness in 210 (91%) patients. One hundred and thirty of the 230 (56%) patients had received treatment with fluconazole monotherapy and 100 (43%) patients received palliative care only without any antifungal therapy. A 100% case fatality rate was observed in both groups at follow up: by seven weeks in the untreated group and at six months in the fluconazole treated group. The cumulative median survival from time of diagnosis was 19 days (range 1-164 days) for the fluconazole treated group and 10 days (range 0-42 days) for the untreated group. CONCLUSION: Cryptococcal meningitis, under current treatment accorded at the University Teaching Hospital, Lusaka, has a 100% mortality in young Zambian adults with AIDS. The current treatment accorded to Zambian adults with cryptococcal meningitis is inappropriate. An urgent need exists to improve strategies for the clinical management of AIDS patients in poor African countries. The wider ethical and operational issues of making available antifungals to African AIDS patients are discussed.

Spondyloarthropathy and human immunodeficiency virus infection in Zambia.

OBJECTIVE: To explore the relationship between spondyloarthropathy (SpA) and infection with the human immunodeficiency virus (HIV) in black Zambians. METHODS: Consecutive patients attending an arthritis clinic in a 30 month period were assessed clinically and tested for the presence of antibodies to HIV. HLA-B27 gene was investigated by polymerase chain reaction and T cell subsets were tested in selected subgroups. RESULTS: Of 595 new attendees, 272 were diagnosed with SpA [130 reactive arthritis (ReA), 128 undifferentiated SpA (uSpA), 13 psoriatic arthritis (PsA), 1 ankylosing spondylitis] and 146 with a reactive type arthritis alone (AA) without preceding clinical trigger infection or SpA features. HIV seroprevalence was 98% in uSpA, 94% PsA, 87% ReA, 64% AA; vs approximately 50% among hospital outpatients and 30% of the adult urban population. Prevalence of SpA is calculated at approximately 180/100,000 in HIV positive and approximately 15/100,000 in HIV negative in the general population. Dysentery was the most common identified trigger. Positive HIV status correlated strongly with SpA features and aggressive sustained disease. At onset 80% of patients were in WHO clinical stage 1 (no disease or lymphadenopathy alone), with a mean CD4+ count of 279/microl. Stage 4 patients had a mean CD4+ count of 60/microl and inactive arthritis. The B27 gene was absent in 30 patients tested. CONCLUSION: ReA is the most common inflammatory joint disorder in black Zambians and is closely linked to HIV infection and not B27, even though our subjects had clinical and radiological characteristics similar to those reported in HLA-B27 positive Caucasians. The changing epidemiology of SpA in this region has important practical and educational implications.

Twice weekly tuberculosis preventive therapy in HIV infection in Zambia.

BACKGROUND: A randomized double-blind placebo-controlled trial was conducted to estimate the efficacy of preventive therapy for tuberculosis (TB) in HIV-infected adults in Lusaka, Zambia. The main outcome measures were the incidence of TB, mortality and adverse drug reactions. METHODS: During a 2 year period, 1053 HIV-positive individuals without evidence of clinical TB were randomly assigned to receive 6 months of isoniazid twice a week (H), or 3 months of rifampicin twice a week (R) plus pyrazinamide (Z), or a placebo. Therapy was taken twice a week and was self administered. Subjects presenting with symptoms during the follow-up period were investigated for TB. RESULTS: The 1053 subjects in the study were followed up for a total of 1631 person-years (median = 1.8 years). Twenty-nine subjects were taken off treatment as a result of adverse drug reactions. A total of 96 cases of TB/probable TB (59 TB and 37 probable TB) were diagnosed during the study period and 185 deaths were reported. One hundred and fifteen subjects (11%) did not return to the study clinic at any time after enrolment. The incidence of TB was lower in those subjects on preventive therapy (H and RZ groups combined) compared with those on placebo (rate ratio = 0.60, 95% CI: 0.36-1.01, P = 0.057), as was the incidence of TB/probable TB (rate ratio = 0.60, 95% CI: 0.40-0.89, P = 0.013). The effect of preventive therapy was greater in those with a tuberculin skin test (TST) of 5 mm or greater, in those with a lymphocyte count of 2x10(9)/l or higher, and in those with haemoglobin of 10 g/dl or higher. There was no difference in mortality rates between the preventive therapy and placebo groups. The effect of preventive therapy declined after the first year of the study so that by 18 months the rates of TB in the treated groups were similar to that in the placebo group. CONCLUSION: This study has demonstrated that preventive therapy with either twice weekly isoniazid for 6 months or a combination of rifampicin and pyrazinamide for 3 months reduced the incidence of TB in HIV-infected persons in Zambia. No effect was observed on mortality. The effect was greatest in persons who had a positive TST or a lymphocyte count of 2x10(9)/l or greater, indicating that preventive therapy may be more effective in people with less advanced immunosuppression. The limited duration of the protective effect reported in this study raises the question of the need for lifelong preventive therapy or re-prophylaxis.

Radiological features of pulmonary tuberculosis in 963 HIV-infected adults at three Central African Hospitals.

Tuberculosis is one of the most important infectious complications in human immunodeficiency virus (HIV)-infected individuals in sub-Saharan Africa. In this radiological study, we detail the chest radiographic findings of Zairean and Zambian adults with a diagnosis of AIDS and tuberculosis as seen at three Central African Hospitals. Between 1992 and 1995, consecutive chest radiographs of 963 HIV-infected adults aged between 16 years and 56 years with microbiologically confirmed tuberculosis (TB) were reviewed: (1) 362 adults from Sendwe General Hospital, Lubumbashi, Zaire, (2) 175 from Mama Yemo Hospital, Kinshasa, Zaire, and (3) 426 adults from The University Teaching Hospital (UTH), Lusaka, Zambia. During the same period consecutive chest radiographs from 1000 age-matched HIV-negative adults with tuberculosis were collected for comparative purposes. Comparison of the two groups showed that the HIV-infected group of patients with tuberculosis had a significantly higher proportion of lymphadenopathy (26% vs 13%; P = 0.001), pleural effusions (16% vs 6.8%; P = 0.001), miliary shadowing (9.8% vs 5%; P = 0.001), an interstitial pattern (12% vs 7%; P = 0.01) and consolidation (10% vs 3%; P = 0.001). There was significantly less cavitation (33% vs 78%; P = 0.001) and atelectasis (12% vs 24%; P = 0.001) seen in the HIV-positive group compared to the HIV-negative group of patients. These patterns of radiographic changes were consistently seen across all three hospital sites. The radiographic appearances in HIV-infected individuals with TB is discussed.

Neopterin, beta 2-microglobulin, and acute phase proteins in HIV-1-seropositive and -seronegative Zambian patients with tuberculosis.

Neopterin is a biochemical marker for the activation of the cell-mediated immune system. We measured neopterin, beta 2-microglobulin, and acute phase proteins in 31 HIV-seropositive and -seronegative Zambian patients with tuberculosis, using stored sera that had been obtained at the beginning and at end of antituberculosis treatment. In both HIV-seropositive and -seronegative patients neopterin and acute phase proteins were elevated when tuberculosis was initially diagnosed and fell during treatment. In contrast, the mean beta 2-microglobulin level increased during antituberculous therapy in the HIV-seropositive group. Serum neopterin levels at diagnosis were correlated with other parameters of disease activity (fever, anemia, and weight loss). In both groups, patients with persistently elevated neopterin levels at the end of treatment were more likely to suffer relapse of tuberculosis or other adverse health events in the subsequent follow-up period. Neopterin can be used to monitor the response to antituberculous therapy in both HIV-seropositive and -seronegative patients and may have a prognostic value for the patients' wellbeing in the follow-up period.

Enteropathy in Zambians with HIV related diarrhoea: regression modelling of potential determinants of mucosal damage.

BACKGROUND: AIDS is characterised by small intestinal mucosal damage, but its aetiopathogenesis is poorly understood. Enteric infections in Africa differ from those in northern countries, where protozoan infections have been associated with severe enteropathy in AIDS patients. AIMS: To characterise enteropathy in Zambian AIDS patients compared with local controls, and to assess relative contributions of enteric infection, nutritional impairment, and immune dysfunction. METHODS: Computer aided mucosal morphometry of small intestinal biopsy specimens from 56 HIV infected Zambians with persistent diarrhoea and 26 diarrhoea free controls, followed by regression modelling. RESULTS: Patients with HIV related diarrhoea had reduced villous height and increased crypt depth compared with controls. There was no difference between HIV positive and negative controls. In regression models applied to AIDS mucosal measurements, villous height and crypt depth were related to nutritional parameters and to serum soluble tumour necrosis factor receptor p55 concentration. Crypt depth was also related to lamina propria plasma cell count. Intestinal infection was found in 79%, which consisted predominantly of microsporidia in 34%, Isospora belli in 24%, and Cryptosporidium parvum in 21%, but detection of these enteropathogens was not related to severity of enteropathy. CONCLUSIONS: Nutritional and immune disturbances were associated with enteropathy, accounting for over one third of the variation in mucosal morphometric parameters.

PIP: The relative contributions of enteric infection, nutritional impairment, and immune dysfunction to AIDS-related enteropathy were investigated in a comparative study of small intestinal biopsy specimens from 56 HIV-positive patients from Lusaka, Zambia, with persistent diarrhea and 26 diarrhea-free controls. Compared with both HIV-positive and HIV-negative controls, patients with HIV-related diarrhea had a 40% reduction in mean villous height and a 19% increase in mean crypt depth. In regression models applied to AIDS mucosal measurements, villous height and crypt depth were related to nutritional parameters and to the serum soluble tumor necrosis factor receptor p55 concentration. Crypt depth also was related to lamina propria plasma cell count. Intestinal infection, primarily microsporidia, was detected in 79% of cases; however, the presence of enteropathogens was not related to the severity of enteropathy. These findings suggest that nutritional and immune disturbances account for more than 33% of the variation in mucosal morphometric parameters in AIDS-related enteropathy.

Systemic immune activation as a potential determinant of wasting in Zambians with HIV-related diarrhoea.

Wasting in African AIDS patients is severe, and its aetiology is probably multifactorial: persistent diarrhoea, poverty and tuberculosis may all contribute. We report a cross-sectional study of body composition measured anthropometrically in 75 adult patients with HIV-related persistent diarrhoea in Lusaka, and its relationship to gastrointestinal infection and systemic immune activation assessed using serum neopterin and soluble tumour necrosis factor receptor (sTNF-R55) concentrations. Patients as a group were generally severely wasted (mean body mass index (BMI) 15.8 kg/m2, range 11-22), but the severity of wasting was related neither to oesophageal candidiasis nor to intestinal infection. In men but not women, all measures of nutritional status were negatively related to serum sTNF-R55 concentration (fat-free mass in men, r = -0.64; 95% CI: -0.80, -0.41; p < 0.0001). Some wasted patients had cutaneous features of malnutrition, again associated with higher sTNF55 concentrations, and two had peripheral oedema. The diarrhoea-wasting syndrome in this part of Africa seems to be associated with evidence of high cytokine activity in men, rather than oesophageal candidiasis or any particular intestinal opportunistic infection. This immune activation requires further investigation in the context of the sex difference we have observed.

Albendazole chemotherapy for treatment of diarrhoea in patients with AIDS in Zambia: a randomised double blind controlled trial.

OBJECTIVE: To determine the value of short course, high dose albendazole chemotherapy in the treatment of persistent diarrhoea related to HIV in unselected patients in urban Zambia. DESIGN: A randomised double blind placebo controlled trial of albendazole 800 mg twice daily for two weeks. Patients were monitored intensively for one month and followed for up to six months. SETTING: Home care. AIDS services in Lusaka and Ndola. PATIENTS: 174 HIV seropositive patients with persistent diarrhoea (defined as loose but not bloody stools three or more times a day for three weeks or longer). No investigations were undertaken except HIV testing after counselling. MAIN OUTCOME MEASURES: Proportion of time periods during which diarrhoea was experienced after completion of treatment; proportion of patients with full remission after completion of treatment; mortality. RESULTS: The patients taking albendazole had diarrhoea on 29% fewer days than those taking placebo (P < 0.0001) in the two weeks after treatment. The benefit of albendazole was maintained over six months. In patients with a Karnofsky score of 50 to 70 (needing help with activities of daily living and unable to work, but not needing admission to hospital) diarrhoea was reduced by 50%. Remission was obtained in 26% of all patients who received albendazole (P = 0.004 against 9% receiving placebo), and this difference was maintained over six months (log rank test, P = 0.003). Albendazole had no effect on mortality. Minimal adverse effects were noted. CONCLUSIONS: For HIV infected Zambians with diarrhoea of more than three weeks' duration albendazole offers substantial relief from symptoms and may be used empirically, without prior investigation.

PIP: A randomized double blind placebo controlled trial was conducted in Zambia at the home care service of the University Teaching Hospital in Lusaka, the Ndola Central Hospital in the north, and the Kara HIV Counselling and Testing Project in central Lusaka to determine the extent albendazole can treat or suppress diarrhea in AIDS patients. The trial also aimed to identify a chemotherapeutic agent that could achieve diarrhea treatment or suppression and be administered in the community without prior investigation. Clinical researchers randomly allocated 174 HIV-positive patients with persistent diarrhea (i.e., loose but not bloody stools at least 3 times/day) to the group that received 800 mg albendazole twice daily for 2 weeks or the placebo group. They followed the patients for 6 months. The albendazole group had diarrhea less often than the placebo group for the entire 6 month period. The difference was significant at all time points (p 0.025) except at 5-8 weeks. At 3-4 weeks post-treatment, the reduction in diarrhea was significant among patients at the Kara Trust (31% reduction; p = 0.004) and in Ndola (41% reduction; p 0.0001) but not at the University Teaching Hospital (10% reduction). Two weeks after treatment, the albendazole group had diarrhea on 29% fewer days than the placebo group (p 0.0001). During the post-treatment weeks of 9-16, the albendazole group experienced diarrhea on 42% fewer days than the placebo group (p = 0.002). Throughout the entire 6-month period, patients in the albendazole group were more likely to achieve remission of diarrhea than the placebo group (e.g., 26% vs. 9%, p = 0.003). The proportion of patients who were in remission increased to 35% when the researchers excluded deaths and withdrawals from treatment. Patients who had a Karnofsky score (a measure of overall severity of illness at the time of entry into the study) of 50-70 benefitted the most from albendazole treatment for diarrhea. Albendazole had no significant effect on mortality. The researchers surmised that much of albendazole's effectiveness was due to its effect on microsporidia infections.

The impact of human immunodeficiency virus on response to treatment and recurrence rate in patients treated for tuberculosis: two-year follow-up of a cohort in Lusaka, Zambia.

To examine the effect of HIV on response to treatment and recurrence rate in patients with tuberculosis (TB), we have followed 239 previously untreated, adult, TB patients in a prospective cohort study in Lusaka, Zambia. One hundred and seventy-four (73%) were HIV-1 antibody positive. Patients with sputum smear positive, miliary, or meningeal TB were prescribed 2 months daily streptomycin, thiacetazone, isoniazid, rifampicin, pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid. Thirty-five per cent of HIV-positive (HIV+ve) and 9% of HIV-negative (HIV-ve) patients were known to have died before the scheduled end of treatment. Surviving HIV+ve patients showed weight gain and improvement in symptoms and laboratory and radiological findings similar to HIV-ve patients. The risk of cutaneous drug reaction was 17% (95% CI: 12-25%) in HIV+ve, and 4% (1-13%) in HIV-ve patients. Severe rashes were attributed to thiacetazone. Recurrence of active TB was examined among 64 HIV+ve and 37 HIV-ve patients who successfully completed treatment, with mean follow-up after the end of treatment of 13.5 and 16.8 months, respectively. The rate of recurrence was 22/100 person years (pyr) for HIV+ve patients and 6/100 pyr for HIV-ve patients, giving a recurrence rate ratio of 4.0 (95% CI 1.2-13.8, P = 0.03).

PIP: In 1989, researchers followed 239 newly diagnosed adult patients with tuberculosis (TB), never previously treated for TB, for two years to examine the response to TB treatment among patients with and without HIV infection and the TB recurrence rate. They were patients in the medical wards and the chest clinic outpatients' department of the University Teaching Hospital in Lusaka, Zambia. 174 (73%) tested positive for HIV. HIV-positive patients were more likely than HIV-negative patients to have extrapulmonary and both pulmonary and extrapulmonary TB (35% and 26% for both, respectively vs. 17% and 12%, respectively; p 0.001). They were less likely to have positive sputum tests than HIV-negative patients (36% vs. 57% for smear; p = 0.005 and 39% vs. 55% for culture; p = 0.03). HIV-positive patients were more likely to receive standard TB therapy (62% vs. 37%), while HIV-negative patients were more likely to receive short course therapy (62% vs. 37%; p = 0.001). HIV-positive patients were more likely than HIV-negative patients to die before completion of treatment (35% vs. 9%). Surviving HIV-positive patients gained weight and experienced improvement in symptoms at the same rate as did surviving HIV-negative patients. They also had similar laboratory and radiological findings. HIV-positive patients had a higher risk of cutaneous drug reaction than HIV-negative patients (17% vs. 4%; hazard ratio = 5.1; p = 0.03). One HIV-positive patient with a rash died. Thiacetazone was responsible for the rashes. Among the HIV-positive and HIV-negative patients who successfully completed treatment, the active TB recurrence rate was greatest for HIV-positive patients (22 vs. 6/100 person years; rate ratio = 4; p = 0.03). Yet, all but one of the HIV-positive cases with recurrent TB responded well to TB treatment. High recurrence rates pose renewed potential sources of infection and a high cost of renewed treatment.

Tuberculin sensitivity and HIV-1 status of patients attending a sexually transmitted diseases clinic in Lusaka, Zambia: a cross-sectional study.

A cross-sectional study to estimate the prevalence of latent tuberculosis (TB) in a group of Zambians at high risk of human immunodeficiency virus type 1 (HIV-1) infection and to examine the effect of HIV-1 infection on the tuberculin response was conducted in the University Teaching Hospital in Lusaka, Zambia during July to September 1990. Patients were selected from those presenting to the out-patient clinic for first referral with either sexually transmitted or skin disease. 268 adults were included in the study; 158 (59%; 95% confidence interval [CI] = 53-65%) were HIV-1 antibody positive. Of 82 HIV-1 negative participants who returned for Mantoux skin test reading, 51 (62%; 95% CI = 57-67%) had a positive test reaction (diameter > or = 10 mm) after receiving 2 units of RT-23 tuberculin. Of 106 HIV-1 positive participants who returned, only 32 (30%; 95% CI = 26-34%) had a diameter > or = 10 mm. Nine (28%) of the HIV-1 positive and Mantoux positive participants had large reactions > or = 30 mm, compared to 4 (8%) of the HIV-1 negative, Mantoux positive participants (P = 0.03). Results in the HIV-1 negative group indicated a prevalence of latent TB of 62% in this population. HIV-1 infection was associated with a much higher frequency of negative response to tuberculin and with a few large skin test responses. Thus, in populations where HIV seropositivity is high, Mantoux skin tests cannot be used to assess those with latent TB who might benefit from chemoprophylaxis.

PIP: A cross-sectional study of the Mantoux response and HIV-1 status of a sample of patients with sexually transmitted diseases and skin diseases in Lusaka, Zambia, sought to estimate the prevalence of latent tuberculous infection. The sample was selected from patients attending the sexually transmitted diseases/dermatology section at the University Teaching Hospital, Lusaka, Zambia, between July and September 1990. A questionnaire regarding socioeconomic factors, history of TB, contact with TB, location and documentation of bacillus Calmette-Guerin (BCG) scar(s) and history of BCG vaccination was completed, and a physical examination for acquired immune deficiency syndrome (AIDS) was carried out. The Mantoux result was recorded as the average diameter of induration, measured in 2 perpendicular directions by the pen and palpation method. A total of 158 patients (59%) were HIV-1 positive. Of the 66 women who took part, 46 (70%) were HIV-1 positive; of the 201 men, 112 (56%) were HIV-1 positive (p = 0.06). 232 patients had sexually transmitted diseases, the commonest being genital ulceration; 123/231 (53%) were HIV-1 positive. The remaining 36 patients had skin diseases, the commonest being herpes zoster; 32/36 (89%) were HIV-1 positive. Of the 267 patients remaining in the study, 193 (72%) returned to have their Mantoux test read, 188 within 48-72 h. 106 (67%) HIV-1 positive patients and 82 (75%) HIV-1 negative patients returned. Of the 82 HIV-1 negative patients, 51 (62%) had a Mantoux reaction or= 10 mm; 55 (67%) had a reaction or= 5 mm. Of the 106 HIV-1 positive patients, only 32 (30%) had a Mantoux reaction or= 10 mm; 35 (33%) had a response or= 5 mm. Comparing HIV-1 negative and HIV-1 positive participants gave a significant odds ratio of 3.85 for a Mantoux response or= 10 mm. Among the individuals with a Mantoux reaction or= 10 mm, 9/32 (28%) of HIV-1 positive participants had a megareaction or= 30 mm, while megareactions occurred in 4/51 (8%) of HIV-1 negative participants (odds ratio 4.6).

The impact of human immunodeficiency virus on mortality of patients treated for tuberculosis in a cohort study in Zambia.

We have examined the impact of human immunodeficiency virus (HIV) on mortality of patients treated for tuberculosis in a prospective study in Lusaka, Zambia. Patients with sputum smear-positive, miliary, or meningeal tuberculosis were prescribed 2 months' daily streptomycin, thiacetazone, isoniazid, rifampicin, and pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid. 239 patients (65 HIV-negative and 174 HIV-positive) were followed to 2 years from start of treatment. The crude mortality rate ratio for HIV-positive compared with HIV-negative patients over 2 years was 5.00 (95% confidence interval 2.30-10.86). Median survival for HIV-positive patients from the start of treatment was 22 months. At least 34% of HIV-positive patients for whom cause of death was known died from tuberculosis, three-quarters of these during the first month of treatment. Risk factors for death in HIV-positive patients included multi-site tuberculosis, history of prolonged diarrhoea or fever, oral thrush, splenomegaly, anergy to tuberculin, low weight, anaemia or lymphopenia, and poor compliance with regimens containing rifampicin and pyrazinamide. Tuberculosis, even treated, was a major cause of death in patients with HIV infection.

PIP: The impact of HIV on mortality is described in a prospective study of tuberculosis patients in Lusaka, Zambia, where more than 70% of newly diagnosed tuberculosis patients have concurrent HIV infection. Patients attending the University Teaching Hospital in Lusaka, Zambia, were recruited to a prospective cohort study from April to December 1989. Of the 239 patients included in the follow-up study, 174 (73%) were HIV-1 positive by ELISA. A higher proportion of HIV-positive patients were 25-34 years old, and they more often had a negative tuberculin response, anemia, or lymphopenia at recruitment. The probability of survival for HIV-negative and HIV-positive patients was, respectively: at 2 months 95% and 89%; at 6 months 95% and 76%; at 12 months 91% and 66%; at 18 months 87% and 55%; and at 24 months 87% and 48%. The median survival of HIV-positive patients was 22 months. The crude, 2-year mortality rate ratio for HIV-positive compared with HIV-negative patients was 5 (p 0.001). Mortality was higher for patients with both pulmonary and extrapulmonary disease than for those with either pulmonary or extrapulmonary disease alone; for individual sites, only lymph node disease was associated with a significantly higher mortality than other sites (p = 0.01). At presentation prolonged fever, prolonged diarrhea, oral Candida or splenomegaly, negative tuberculin response, anemia or lymphopenia and low weight were associated with higher mortality. Among the 39 patients seen at 2 months who had been prescribed short-course chemotherapy, subsequent mortality was lower in the group who reported receiving all 60 doses of either rifampicin or pyrazinamide or both (20 patients) than among those who had not (19 patients¿ (rate ratio 0.24, p = 0.02). 47 of the 81 patients died within 24 months of the start of treatment, 5 HIV-negative and 42 HIV-positive. 3 of 5 HIV-negative patients for whom information was available died of active tuberculosis. Among HIV-positive patients, 14 of 42 died of active tuberculosis and 2 more of complications of tuberculosis.

Serum lipids and lipoprotein in adult Ghanaians.

OBJECTIVES: To date, no measurement of serum lipid levels in healthy adult Ghanaians have been carried out. This study was undertaken with the objective of providing reference values for serum lipid levels in the Ghanaian population. DESIGN/SETTING: Fasting serum lipid levels were measured in 79 adult Ghanaians living in an urban setting. Volunteers were randomly selected from the work force of the University of Ghana in Accra. There were 54 males and 25 females in the study population. RESULTS: The mean serum cholesterol (SC) for Ghanaian males was 4.27 +/- 1.00 mmol L-1. A value of 4.34 +/- 1.12 mmol L-1 was obtained for the females in this study. High-density lipoprotein cholesterol (HDL-C) in Ghanaian males averaged 1.37 +/- 0.44 mmol L-1 and 1.47 +/- 0.50 mmol L-1 in females. There was no statistically significant difference in low-density-lipoprotein cholesterol (LDL-C) and very-low-density-lipoprotein cholesterol (VLDL-C) levels between the females and males in this study. CONCLUSIONS: Compared to other studies, our results show that populations in Europe and North America have higher levels of total cholesterol and LDL cholesterol than Ghanaians. The levels of HDL cholesterol as well as VLDL cholesterol are higher in Ghanaians than in Europeans and Americans. Further work needs to be done to compare lipid levels in urban and rural Ghanaians as well as in those with cardiovascular disorders.

The impact of HIV on infectiousness of pulmonary tuberculosis: a community study in Zambia.

OBJECTIVE: To examine the impact of HIV on infectiousness of pulmonary tuberculosis (TB). DESIGN: A cross-sectional tuberculin survey carried out among household contacts of HIV-1-positive and negative patients with bacteriologically confirmed pulmonary TB. Contacts were also examined for active TB. SETTING: Index cases were recruited from patients attending the University Teaching Hospital in Lusaka, Zambia and household contacts were examined during visits to their homes within Lusaka. PATIENTS, PARTICIPANTS: A total of 207 contacts of 43 HIV-positive patients, and 141 contacts of 28 HIV-negative patients with pulmonary TB were examined. MAIN OUTCOME MEASURES: Proportion of contacts of HIV-positive and negative index cases with a positive tuberculin response (diameter of induration > or = 5 mm to a dose of 2 tuberculin units). RESULTS: Fifty-two per cent of contacts of HIV-positive pulmonary TB patients had a positive tuberculin response compared with 71% of contacts of HIV-negative patients (odds ratio, 0.43; 95% CI, 0.26-0.72; P < 0.001). This difference persisted after allowing for between-household variations in the tuberculin response. Tuberculin response in the contact was related to age of contact, intimacy with the index case and crowding in the household. However, the effect of HIV status of the index case was not confounded by these variables. Tuberculin response in the contact was also related to the number of bacilli seen in the sputum smear of the index case which partially explained the effect of HIV status of the index case. Active TB was diagnosed in 4% of contacts of HIV-positive and 3% of contacts of HIV-negative cases, respectively (P = 0.8). CONCLUSIONS: HIV-positive patients with pulmonary TB may be less infectious than their HIV-negative counterparts and this may partly be explained by lower bacillary load in the sputum.

PIP: Between April and December 1989, the chest clinic of the University Teaching Hospital in Lusaka, Zambia, confirmed pulmonary tuberculosis (TB) in 141 adults, 95 (67%) of whom were HIV-1 seropositive. Health workers made home visits to 71 of the index cases (43 HIV-1 positive and 28 HIV-1 negative) to learn whether the 348 household members would also develop TB, thus allowing researchers to determine the effect of HIV on infectiousness of TB. Contacts of HIV-1 positive patients developed TB at a lower rate than did those of HIV-1 negative patients (52% vs. 71%; odds ratio [OR] = 0.43; p .001). This difference continued even after controlling for between-household variations, indicating that confounding variables did not account for the difference. Age of contact, intimacy with the index case, and crowding in the household were associated with the tuberculin response in the contact, but they did not confound the effect of HIV status. Tuberculin response in the contact was associated with the number of bacilli in the sputum smear (crude OR = 3.13; p = .013, and adjusted OR =1.84; p = .28), suggesting that the number of bacilli somewhat explained the difference in infectiousness between HIV-1 positive and HIV-1 negative patients. 12 contacts (8 of HIV-positive cases and 4 of HIV-negative cases) developed active TB after the TB diagnosis in the index case. These findings clearly demonstrated that infection with Mycobacterium tuberculosis was less likely in household members of HIV-1 positive cases than in those of HIV-1 negative cases. The lower bacillary load in the sputum in HIV- 1 cases may have accounted somewhat for the lower infectiousness of pulmonary TB.

Negative sputum smear results in HIV-positive patients with pulmonary tuberculosis in Lusaka, Zambia.

During recruitment to a prospective study of tuberculosis patients in Lusaka, Zambia, 109 had pulmonary disease proven by sputum culture for Mycobacterium tuberculosis, of whom 72 were HIV-1 antibody-positive and 37 were HIV-negative. Among these culture-proven cases, 43% of the HIV-positive patients had a negative sputum smear, compared with 24% of the HIV-negative cases. There was a strong trend towards lower grade or negative sputum smear in the HIV-positive group (P = 0.003). HIV-positive cases also had lower colony counts on culture and colonies took longer to appear. The findings imply that cases of HIV-associated pulmonary tuberculosis may frequently be missed and emphasise the need for new diagnostic methods.

The impact of human immunodeficiency virus on presentation and diagnosis of tuberculosis in a cohort study in Zambia.

Two hundred and forty-nine patients with tuberculosis were recruited to a cohort study to investigate the interaction between tuberculosis and HIV in Lusaka, Zambia; findings at presentation are presented here. One hundred and eighty-two (73%; 95% confidence interval 67-79%) of the cases were HIV-1 antibody positive. The diagnosis of tuberculosis was confirmed by microscopy for acid-alcohol fast bacilli, culture of Mycobacterium tuberculosis, or histology in 74% of all cases. HIV negative and positive cases differed in site of disease: among HIV negative patients 72% had pulmonary disease alone, 16% extrapulmonary disease alone and 12% had both, whereas among HIV positive patients 40% had pulmonary disease alone, 34% extrapulmonary disease alone and 26% both (P < 0.001). HIV negative and positive cases were compared with regard to outcome of diagnostic procedures: 55% of HIV negative cases could be diagnosed at enrollment by sputum smear, but only 35% of HIV positive cases (P < 0.01). Among pulmonary cases confirmed by sputum culture, 76% of HIV negative patients had a positive sputum smear, compared with 57% of HIV positive patients (P = 0.09). Pleural and pericardial disease were difficult to confirm, but culture of pleural fluid was positive in 12/46 HIV positive patients, compared with 0/11 HIV negative patients. Lymph node disease was readily confirmed by biopsy. The tuberculin test was positive in only 30/110 (27%) of HIV positive cases, but in 21/38 (55%) of HIV negative cases (P < 0.01). Mycobacterium tuberculosis was cultured in 57% of HIV negative cases and 54% of HIV positive cases; no atypical mycobacteria were isolated. Initial resistance to isoniazid was present in isolates from 5% of cases with a positive culture.

Community-based high blood pressure programs in sub-Saharan Africa.

We studied residents of urban and rural areas of Ghana from 1972 through 1987 to evaluate the health burden of cardiovascular diseases, especially high blood pressure, in these African communities. Among urban adults, the prevalence of hypertension was 8% to 13%, compared to only 4.5% among rural adults. Overall, rates were higher among men than among women. However, the rate of hypertension was the same for men and women over 40 years old. The prevalence of hypertension was 29% for persons aged 35 and older, compared to 3.9% for persons under 35 years of age. Of the 24% of the study participants who were aware of their hypertension status, only a third were undergoing treatment, and only half of those were receiving adequate treatment. The determinants of hypertension include age, family history, body mass index, parity, and alcohol use. On a continent where over 80% of the health budget is spent on communicable diseases such as malaria, this study represents one of the few early attempts to understand the magnitude of the health burden of noncommunicable diseases in Africa.

Use of prednisolone in the treatment of HIV-positive tuberculosis patients.

Corticosteroids are beneficial in the treatment of some forms of tuberculosis, but their role in TB affecting HIV-positive patients is not clear. During a cohort study of tuberculosis patients in Lusaka, Zambia, prednisolone was prescribed for specific indications. Six of 47 (13 per cent) of patients who received prednisolone early in treatment developed herpes zoster, compared with 2 of 118 (2 per cent) of those who did not. Three patients who received prednisolone developed Kaposi's sarcoma, compared with none who did not. At 2 months patients who had received prednisolone showed a greater improvement in generalized lymphadenopathy and cough. Controlled studies of the risks and benefits of administration of corticosteroids to HIV-positive TB patients are urgently needed.