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Biomedical subjects

P Nunn

Publications and source records attributed to P Nunn.

At least 55 records · Page 3Linked to original sources
PubMed1992

Cohort study of human immunodeficiency virus infection in patients with tuberculosis in Nairobi, Kenya. Analysis of early (6-month) mortality.

Retrospective studies suggest that the mortality rate from HIV-1-associated tuberculosis is greater than that from tuberculosis alone, but it is not clear if this is due to failure of antituberculosis treatment or to the complications of HIV-1 infection. We have carried out a prospective cohort study of patients with tuberculosis in Nairobi, Kenya, to compare mortality rates, risk factors, and causes of death in HIV-1 positive and HIV-1 negative patients. One hundred seven HIV-1 positive and 174 HIV-1 negative patients with tuberculosis attending two tuberculosis treatment centers in Nairobi were enrolled and followed monthly. Mortality was significantly higher in HIV-1 positive than in HIV-1 negative patients within 6 months of the start of antituberculosis treatment after adjustment for age, sex, and education (rate ratio = 3.8; 95% confidence interval, 1.7 to 8.1; p less than 0.001). Most of the excess mortality occurred after the first month of treatment and was due to nontuberculous infections. Predictors for mortality differed greatly between HIV-1 positive and HIV-1 negative patients. Mortality was greater in HIV-1 positive patients treated with a "standard" regimen for tuberculosis than in HIV-1 positive patients receiving a "short-course" regimen (p = 0.08 when adjusted for all independent risk factors). Tuberculosis control programs in developing countries need to implement "short-course" regimens and train health workers to recognize and treat nontuberculous infections to maintain their effectiveness in the face of the HIV epidemic.

AIDS-Related Opportunistic Infections↗
PubMed1991

Cutaneous hypersensitivity reactions due to thiacetazone in HIV-1 seropositive patients treated for tuberculosis.

The effects of the human immunodeficiency virus (HIV) on tuberculosis management was investigated in 227 patients initially treated with a regimen containing streptomycin, isoniazid, and thiacetazone (STH). 93 of these 227 were HIV-seropositive. 60 patients, of whom 18 were HIV-seropositive, received a regimen consisting of streptomycin, isoniazid, rifampicin, and pyrazinamide (SHRZ) in the initial phase, and thiacetazone and isoniazid (TH) in the continuation phase. Cutaneous hypersensitivity reactions occurred in 22 of 111 (20%) HIV-seropositive patients, and in 2 of 176 (1%) HIV-seronegative patients (RR = 18, 95% CI 4.4-76, p less than 10(-7]. During the first 8 weeks of treatment 18 reactions occurred among the 93 HIV-seropositive patients on STH, whereas no reaction occurred in 17 HIV-seropositive patients during the initial phase of SHRZ/TH (p = 0.04). None of the 18 HIV-seropositive patients with cutaneous reactions who were subsequently challenged with isoniazid reacted, nor did any of the 10 tested with streptomycin, but 6 of the 7 challenged with thiacetazone reacted. 3 patients (all HIV-positive and with toxic epidermal necrolysis) died as a result of the cutaneous reaction. These results have major implications for tuberculosis control programmes in Africa.

Adult↗
PubMed1990

Impact of HIV on tuberculosis in Zambia: a cross sectional study.

OBJECTIVE: To examine the contribution of HIV infection to the apparently increasing incidence of tuberculosis in central Africa. DESIGN: Cross sectional study. SETTING: Outpatient clinic in teaching hospital, Lusaka, Zambia. PATIENTS: 346 Adult patients with tuberculosis. RESULTS: Overall, 206 patients (60%; 95% confidence interval 54% to 65%) were positive for HIV: in one or both assays used. The peaks for both tuberculosis and HIV infection were among men aged 25-34 years and women aged 14-24 years. Of patients with confirmed pulmonary tuberculosis, 73/149 (49%; 41% to 57%) were positive for HIV; 67/83 (81%; 70% to 89%) patients with pleural disease and 16/19 (84%; 60% to 97%) patients with pericardial disease were positive. HIV positive patients with positive sputum culture were less likely to have had a positive sputum smear, and their chest x ray films less often showed classic upper zone disease or cavitation. Of 72 patients who fulfilled clinical criteria for AIDS, 17 were negative for HIV. CONCLUSIONS: The high prevalence of HIV in patients with tuberculosis suggests that an epidemic of reactivating tuberculosis is arising in those who are infected with HIV. The redirection of public health priorities towards tuberculosis would focus on a major treatable and preventable complication of the AIDS epidemic.

Adolescent↗
PubMed1990

Impact of human immunodeficiency virus on transmission and severity of tuberculosis.

It is now clear that tuberculosis is one of the major diseases associated with human immunodeficiency virus (HIV) infection and the acquired immune deficiency syndrome both in developing countries and in disadvantaged groups in the northern hemisphere. In the USA, and probably several other countries, the annual incidence of tuberculosis is rising as a result of the HIV epidemic. This is probably a result of an increase in both pulmonary and, especially, extrapulmonary tuberculosis, due to reactivation of latent infections, but a secondary increase in the infection rate is also possible. The hard-won gains in tuberculosis control of the last 30 years are thus in jeopardy. This article focuses on the effect HIV is likely to have on the known risk factors for infection with Mycobacterium tuberculosis and for reactivation. Whilst HIV-associated tuberculosis may be indistinguishable from HIV-negative disease, it is likely in other cases to present diagnostic difficulties, to respond poorly to treatment with more adverse effects, and to result in high early mortality, although this may not be due directly to tuberculosis. HIV-associated tuberculosis thus represents a major challenge to physicians, especially in developing countries, but like other forms of tuberculosis it is (i) treatable and (ii) preventable.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Pulmonary function after bone marrow transplantation for chronic myeloid leukaemia.

Pulmonary function was measured before and at intervals after treatment in 44 patients who received a bone marrow transplant for chronic myeloid leukaemia in the chronic phase. All patients were treated with cytotoxic drugs, total body irradiation, and post-graft immunosuppression. Thirty four patients surviving for 12 months were followed at three monthly intervals and 16 patients for 24 months. Fifteen patients received unmanipulated donor marrow cells and 29 patients received donor marrow cells depleted of lymphocytes ex vivo with the monoclonal antibody Campath-1. The 21 patients treated early in this study received 10 Gy of total body irradiation whereas the 23 patients treated more recently, who were all T lymphocyte depleted, received 12 Gy. Pretransplant lung function for the group was normal and was similar in survivors (n = 34) and nonsurvivors (n = 10), and in smokers (n = 8) and non-smokers (n = 36). (Carbon monoxide transfer factor--TLCO) was under 75% of predicted normal in nine patients before transplantation. TLCO, carbon monoxide transfer coefficient (KCO), FEV1, and vital capacity (VC) values were lower 6 and 12 months after bone marrow transplant than initially. The greatest decline was in TLCO, from an initial value of 89% to 66% at 6 and 70% at 12 months. The 16 longer term survivors showed significant recovery of function between 6 and 24 months after bone marrow transplant for TLCO, KCO, and VC, the increase ranging from 6.3% to 7.3% predicted. Airflow obstruction (FEV1/VC ratio less than 70%) developed in one patient. The major factors associated with deterioration in pulmonary function at 6 and 12 months after transplantation in the 34 survivors (stepwise multiple regression analysis) were (a) transplantation with T cell depleted donor marrow (p less than 0.005) and higher total body irradiation dose (p less than 0.02) with a fall in KCO and an increase in the FEV1/VC ratio; (b) chronic graft versus host disease with a fall in VC (p less than 0.01); and less fall in KCO (p less than 0.01); and (c) acute graft versus host disease with a fall in FEV1 (p less than 0.01). It is considered that most patients who survive the short term risks of bone marrow transplant have only minor long term impairment of pulmonary function.

Adolescent↗
PubMed1987

AIDS and Africa.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Pulmonary sarcoidosis: alterations in bronchoalveolar lymphocytes and T cell subsets.

Peripheral blood and bronchoalveolar lavage lymphocyte subpopulations have been evaluated in 14 patients with pulmonary sarcoidosis and eight normal subjects, monoclonal antibodies of the leu series being used. No significant alterations of T lymphocyte subpopulations were found in the peripheral blood of sarcoidosis patients. There was, however, a significantly greater proportion of T suppressor-cytotoxic cells (36.0 (SD 17.6%] in the bronchoalveolar lavage fluid of patients than of normal subjects (15% (5.6%); p less than 0.01), but a decrease in the proportion of T helper-inducer cells (51.1% (18%) v 79.3% (9%). These changes correlated with the duration of the disease but not with other clinical, radiological, physiological, or biochemical criteria. Patients were followed up for six to 20 months and five patients had a repeat bronchoalveolar lavage and lymphocyte subpopulation evaluation after three to 14 months. The initial pulmonary T lymphocyte subset proportions were not predictive of clinical, physiological, or radiological alterations during follow up. There was also no consistent pattern in the relationship between change in T subset proportions and change in clinical physiological, and radiological features in the five patients having a repeat lavage. Lymphocyte surface marker studies may indicate immunopathogenetic mechanisms in sarcoidosis but do not appear to be good predictors of clinical outcome.

Adult↗
PubMed1984

Airways obstruction associated with graft versus host disease after bone marrow transplantation.

Eight patients, five with chronic granulocytic leukaemia and three with severe aplastic anaemia, developed moderately severe airflow obstruction after allogeneic bone marrow transplantation. All eight had clinically and radiologically normal lungs before undergoing transplantation. Treatment in the patients with chronic granulocytic leukaemia before transplantation included high dose total body irradiation. All eight patients developed acute and chronic graft versus host disease after transplantation. The pulmonary syndrome consisted of cough, dyspnoea, and wheezing beginning six to 20 weeks after transplantation, with ratios of forced expiratory volume in one second (FEV1) to vital capacity (VC) falling to 60% or less of predicted values. The three patients with severe aplastic anaemia had relatively mild graft versus host disease and acute chest infection may have initiated or contributed to their airways obstruction, which subsequently resolved. The five patients with chronic granulocytic leukaemia had more severe graft versus host disease and more progressive respiratory problems; two died and three continued to have persistent airflow obstruction 11, 15, and 20 months after transplantation. None of those with chronic granulocytic leukaemia improved. Transfer factor (TLCO) was reduced in all patients after bone marrow transfer and did not improve; in the patients with chronic granulocytic leukaemia the reduction in TLCO preceded the fall in FEV1/VC ratio. Open lung biopsy in one of the patients with chronic granulocytic leukaemia showed obliterative bronchiolitis with lymphocytic infiltration consistent with graft versus host disease. Bronchodilators were of no benefit in the management of these patients, but prompt treatment of infection and early use of corticosteroids may have contributed to the improvement seen in the patients with severe aplastic anaemia.

Adolescent↗
PubMedDate not supplied

Thiacetazone--avoid like poison or use with care?

Recent 5 reports of severe cutaneous hypersensitivity reactions in patients infected with human immunodeficiency virus (HIV) and with tuberculosis treated with thiacetazone have prompted the World Health Organization to advise against the use of thiacetazone in patients known, or suspected, to be infected with HIV. Because the poorest countries will have great difficulty in replacing thiacetazone, the history, metabolism and possible mechanisms underlying the toxicity of this inexpensive, but problematic, drug are reviewed. Guidelines for National Tuberculosis Control Programme policies in response to thiacetazone toxicity are discussed, taking into account the differing levels of resources available to developing countries.

Adult↗
PubMedDate not supplied

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.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

High mortality rates in tuberculosis patients in Zomba Hospital, Malawi, during 32 months of follow-up.

There is little information about long-term follow-up in patients with smear-negative pulmonary tuberculosis (PTB) or extrapulmonary tuberculosis (EPTB) who have been treated under routine programme conditions in sub-Saharan Africa. A prospective study was carried out to determine outcome 32 months from start of treatment in an unselected cohort of 827 adults TB inpatients registered at Zomba Hospital, Malawi, in 1 July-31 December 1995. By 32 months, 351 (42%) patients had died. Death rates were 30% (95% confidence interval [95% CI] 25-35%) in 386 patients with smear-positive PTB, 60% (95% CI 53-67%) in 211 patients with smear-negative PTB and 47% (95% CI 40-54%) in 230 patients with EPTB. Of the 793 patients with concordant HIV test results 612 (77%) were HIV seropositive: 47% HIV-positive patients were dead by 32 months compared with 27% HIV-negative patients (adjusted hazard ratio [HR] 2.3; 95% CI 1.7-3.1, P < 0.001). Smear-negative PTB patients had the highest death rates during the 32-month follow-up (HR 2.7; 95% CI 2.1-3.5, P < 0.001 compared to smear-positive patients), followed by EPTB patients (HR 1.9; 95% CI 1.5-2.5, P < 0.001 compared to smear-positive patients). When analysis was restricted to after the treatment period had finished (i.e., months 12-32), the differences in mortality were maintained for HIV-serostatus and for types of TB. Low-cost, easy to implement strategies for reducing mortality in HIV-positive TB patients in sub-Saharan Africa (such as the use of trimethoprim-sulphamethoxazole prophylaxis) need to be tested urgently in programme settings.

Adolescent↗
PubMedDate not supplied

Screening pulmonary tuberculosis suspects in Malawi: testing different strategies.

Alternative strategies for screening tuberculosis (TB) suspects are needed in sub-saharan Africa. Ambulatory adult TB suspects who were seen in the chronic cough room of Queen Elizabeth Central Hospital, Blantyre, Malawi, were assessed with respect to appropriateness of referral. Appropriate referrals (patients with cough 3 weeks or longer, weight loss and no antibiotic response) were screened by 3 sputum specimens for microscopy and culture of Mycobacterium tuberculosis and chest radiography (CXR). Hypothetical strategy A (screening by sputum smear examination followed by CXR in patients with negative sputum smears) was compared with strategy B (screening by CXR followed by sputum smear examination in patients with a CXR consistent with TB) in terms of diagnostic efficacy and cost. Of 1127 patients referred to the cough room, 402 (38%) were appropriate TB suspect referrals. Of these, 111 (28%) were sputum smear-positive, 213 (53%) were culture-positive, and 221 (55%) had smear and/or culture-positive evidence of TB. Routine CXR was consistent with pulmonary (P) TB in 230 patients (57%). With strategy A, 243 (60%) patients were diagnosed as PTB, but 40 (25%) of those not diagnosed as PTB had positive mycobacterial cultures. With strategy B, 230 patients (57%) were diagnosed as PTB, but 53 (31%) of those not diagnosed as PTB had positive mycobacterial cultures, including 13 with smear-positive sputum. The cost per diagnosed case of PTB was US$ 4.63 with strategy A and US$ 5.44 with strategy B. Screening patients with good criteria of TB has high diagnostic sensitivity, but screening by CXR is less effective and more costly than screening by sputum smear microscopy.

Adolescent↗
PubMedDate not supplied

Delays in diagnosis and treatment of smear-positive tuberculosis and the incidence of tuberculosis in hospital nurses in Blantyre, Malawi.

There is little information about nosocomial transmission of tuberculosis (TB) in sub-Saharan Africa. A study was carried out to examine the process of diagnosis and treatment of smear-positive pulmonary TB patients in Queen Elizabeth Central Hospital, Blantyre, Malawi, and the incidence of TB in nurses working in specific departments of the hospital. Case notes of 1365 patients with smear-positive pulmonary TB, diagnosed and treated at the hospital in 1993 and 1994, were analysed. The number of qualified nurses who worked in specific departments of the hospital between 1993 and 1994 and the number who were diagnosed and treated for TB during this period were obtained from nursing records. 787 patients (58%) were diagnosed as out-patients and 578 (42%) were diagnosed in hospital wards, 544 from medical wards. In medical wards, there were long delays from the time of admission to diagnosis and start of anti-TB treatment in new and previously treated TB patients. Of 310 qualified nurses, 12 (4%) were treated for TB in 1993-1994; 4 (14%) of 29 nurses working in the medical wards developed TB. The results indicate the importance of finding simple measures in resource-poor countries to improve the diagnosis and treatment of TB in hospital patients in order to decrease the risk of nosocomial TB transmission.

Adult↗