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Biomedical subjects

A Zumla

Publications and source records attributed to A Zumla.

At least 37 records · Page 2Linked to original sources

Local regulation of glucocorticoid activity in sites of inflammation. Insights from the study of tuberculosis.

In sites of inflammation there is a change in the equilibrium between the enzymes that inactivate cortisol by conversion to cortisone and those that reactivate cortisone by conversion to cortisol. Current evidence suggests that during an immune response with a Type 1 cytokine profile such as tuberculosis, there is locally enhanced reductase activity with locally increased cortisol concentrations due to recruitment of cortisone. This results in enhanced cortisol mediated feedback on the inflammatory process, and deviation of the response towards Type 2. Preliminary data suggest that eventually, in the presence of Type 2 cytokine polarization, the enzyme equilibrium may reverse again and cortisol is then locally inactivated to cortisone. Together with changes in glucocorticoid receptor expression and function this may result in local cortisol resistance and susceptibility to tissue damage mediated by proinflammatory cytokines. These observations help to explain the sequence of events in several infectious, inflammatory and autoimmune diseases.

Animals↗

Impact of HIV infection on tuberculosis.

Tuberculosis is increasing in prevalence in many countries and is now the leading infectious cause of death world wide, being responsible for three million deaths annually. Infection with HIV, likewise increasing in prevalence, has emerged as the most important predisposing factor for developing overt tuberculosis in people co-infected with Mycobacterium tuberculosis. Owing to the widespread geographical overlap of these two infections, it is estimated that in 1999, HIV related tuberculosis will reach one million cases and will cause 30% of the expected 2.5 million AIDS related deaths. Tuberculosis in HIV infected individuals may have unusual clinical features and can cause diagnostic difficulties. Despite the effectiveness of modern short course treatment, the mortality of HIV related tuberculosis during and after treatment remains high, and this may be due to other HIV related infections. The "cursed duet" of infection with both HIV and M tuberculosis is generating a threat to human health of unparalleled proportions which, if not taken seriously by health workers and decision makers, could become totally unmanageable.

AIDS-Related Opportunistic Infections↗

Increased cortisol: cortisone ratio in acute pulmonary tuberculosis.

To evaluate a possible role for altered cortisol metabolism in mediating the immunoparesis associated with progressive tuberculosis (TB), we have studied the hypothalamic-pituitary-adrenal axis, and the activities of the 11beta-hydroxysteroid dehydrogenases (11-HSDs) that interconvert active cortisol and inactive cortisone. In active pulmonary tuberculosis (PTB), the ratio of cortisol/cortisone metabolites in 24-h urine showed a shift towards active cortisol (ratio, 1.19 +/- 0.1, n = 16 versus 0. 89 +/- 0.05 in cured pulmonary tuberculosis (CTB), n = 13, p < 0. 01; and 0.78 +/- 0.04 healthy volunteers (HV), n = 11, p < 0.005). Conversion of cortisone (administered as 25 mg orally) to cortisol in peripheral plasma was higher in PTB (peak 1,157 +/- 55 nM, n = 14 versus 862 +/- 50 nM in CTB, n = 10, p < 0.005, and 882 +/- 73 nM in HV, n = 10; p < 0.005). Cortisol/cortisone ratio was increased in bronchoalveolar lavage fluid in PTB (7.73 +/- 1.48, mean +/- SE, n = 13) compared with HV (4.05 +/- 0.38, n = 11, p < 0.05) but was not different in plasma (PTB, 3.25 +/- 0.68; HV, 4.01 +/- 0.92). Responses of plasma cortisol to dexamethasone, CRH stimulation, and multidose ACTH stimulation were not different. These data suggest that in pulmonary tuberculosis, central control of glucocorticoid production is normal but that peripheral metabolism, in particular in the lung, is deviated in favor of the active metabolite cortisol. This offers a possible mechanism to explain the immunoparesis observed in progressive pulmonary tuberculosis.

Adolescent↗

Referral times of Vietnamese refugees with tuberculosis in camps in Hong Kong.

SETTING: Two closed camps in Hong Kong for Vietnamese refugees. OBJECTIVE: To determine the referral times by clinicians (doctor's delay) of cases of tuberculosis (TB) from refugee camp clinics to the hospital/chest clinic. DESIGN: Retrospective case-note study of 97 Vietnamese patients receiving treatment for tuberculosis. RESULTS: The sites of TB were pulmonary (n = 61), glandular (n = 15), pleural effusion (n = 15), and other (n = 6). The median referral time was 18 days (range 0-417). Median consultations numbered three (range 1-16). Fifty-three (54.6%) patients were prescribed antibiotics. Thirty-nine (40%) patients were referred within 10 days; of these, 18 were referred the same day. These 39 patients were less likely to have received antibiotics (9/39 [23.1%] vs 44/58 [75.9%], relative risk [RR] 0.3 95% confidence interval [CI] 0.17-0.55), but were equally likely to have been physically examined (RR 0.66, 95%CI 0.39-1.1). Sixteen (16.5%) patients were referred after 90 days. They attended the clinic more often (median attendances 6.5 vs 3, P = 0.0002), and were prescribed more antibiotic courses (mean antibiotic prescriptions 1.6 vs 0.7, P = 0.03). CONCLUSION: Referral times by these clinicians varied widely, with long delays for approximately 60% of patients. Guidelines pertinent to primary care clinicians are needed to heighten their awareness of tuberculosis to prevent referral delays and subsequent TB treatment.

Adolescent↗

HIV-1 seroprevalence in Zambian patients with acute diarrhea: a community-based study.

The seroprevalence of HIV-1 in sub-Saharan African patients with diarrhea in the community remains largely unknown. We present the findings of a 2-month study that we undertook to ascertain the seroprevalence of HIV-1 in Zambian patients presenting with acute diarrhea in a community-based health center. A total of 256 patients with diarrhea and 140 apparently healthy controls was seen. Of the patients with diarrhea, 161 were < 16 years old and 95 were adults. Most children with diarrhea were < 6 years old (147 of 161; 91%). Overall, 81 of 256 (32%) patients with diarrhea were HIV-1-seropositive. When results from children < 18 months old and possibly having maternal anti-HIV-1 antibodies were excluded, 64 of 172 (37%) patients with diarrhea were HIV-seropositive. Rates of HIV-1 seropositivity for patients with diarrhea were significantly higher than were rates for diarrhea-free controls (p < .001 for both the total population; odds ratio [OR], 95% confidence interval [CI], 1.42 < 2.48 < 4.35) and population > 18 months old (OR, 95% CI, 1.54 < 2.90 < 5.49). Among children between 18 months and 5 years old, 14 of 63 (22%) were HIV-1-seropositive compared with 8 of 62 (13%) without diarrhea (p > .05, not significant). Moreover, 49 of 95 (52%) adults with acute diarrhea were HIV-1-seropositive compared with 10 of 44 (23%) healthy adult controls (p < .003; OR, 95% CI, 1.51 < 3.62 < 8.87). No significant differences were found in HIV-1 seroprevalence rates between males and females in all age groups. These data show a close association between acute diarrhea and HIV seropositivity in Zambian adults in the community.

Acute Disease↗

The effects of BCG immunization and human immunodeficiency virus infection on dual skin test reactions to purified protein derivative and Mycobacterium avium sensitin among adults in Zambia.

SETTING: University hospital in Lusaka, Zambia. OBJECTIVE: To determine the effects of childhood bacille Calmette-Guerin (BCG) immunization and human immunodeficiency virus (HIV) infection on dual skin test reactions to purified protein derivative (PPD) and Mycobacterium avium sensitin (MAS) in a developing country. DESIGN: Descriptive cross-sectional study. RESULTS: Dual skin testing was performed on 112 adults, 58 HIV-positive and 54 HIV-negative. Forty-seven (42%) of 112 had PPD reactions > or =10 mm and 52 (46%) had MAS reactions > or =10 mm. PPD reactions > or =10 mm were present in 30 (63%) of 48 BCG-positive subjects compared to 17 (27%) of 64 BCG-negative subjects (P<0.001). Nineteen (33%) of 58 PPD or MAS skin test positive subjects were PPD dominant, 15 (26%) were MAS dominant, and 24 (41%) were non-dominant. MAS dominant and non-dominant reactions were significantly reduced in HIV-positive subjects, and non-dominant reactions were increased in BCG-positive subjects. CONCLUSIONS: Childhood BCG immunization is associated with PPD reactions > or =10 mm among adults. Reduced PPD reaction rates in HIV-positive adults appear to be due to a loss of BCG-induced PPD reactivity. Prior infection with M. avium complex is detectable in a significant proportion of adults in a developing country.

Adult↗

A study of maternal mortality at the University Teaching Hospital, Lusaka, Zambia: the emergence of tuberculosis as a major non-obstetric cause of maternal death.

SETTING: The Department of Obstetrics and Gynaecology, University Teaching Hospital, Lusaka, Zambia. OBJECTIVES: To ascertain 1) the non-obstetric causes of maternal mortality, 2) the importance of tuberculosis as a cause of maternal deaths, and 3) the trends in the aetiology of non-obstetric causes of maternal deaths during the past decade in the light of the human immunodeficiency virus epidemic. DESIGN: A 2-year retrospective study of the aetiology of all maternal deaths occurring at the University Teaching Hospital (UTH), Lusaka, Zambia between 1 January 1996 and 31 December 1997. Comparison of these data with available data published between 1974 and 1989. RESULTS: There were 251 maternal deaths recorded during the study period. Of these, 106 (42%) were due to direct (obstetric) causes and 145 (58%) were due to indirect (non-obstetric) causes. Malaria (30%), tuberculosis (25%) and unspecified chronic respiratory tract infections (22%) accounted for 77% of non-obstetric causes of maternal deaths and 44% of all causes of maternal deaths. The diagnosis of AIDS was closely linked with that of tuberculosis (92% of cases), and unspecified chronic respiratory illnesses (97%), but not with malaria (37%). The maternal mortality ratio for UTH was calculated at 921 per 100,000 live births, a significant increase from the 118 noted in 1982 and 667 in 1989. CONCLUSIONS: Despite improved obstetric services, the maternal mortality ratios at UTH, Lusaka, have increased eight-fold over the past two decades. This dramatic increase is mainly due to non-obstetric causes of death. Malaria and AIDS-associated tuberculosis and unspecified 'chronic respiratory illnesses' are now major causes of maternal death in Zambia. Greater emphasis is urgently required on early detection, accurate diagnosis, treatment and prevention of malaria and tuberculosis in pregnancy. Further definition of chronic 'unspecified' respiratory illnesses is also required.

Acquired Immunodeficiency Syndrome↗

Tuberculosis.

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Antitubercular Agents↗

Spread of Neisseria meningitidis group A clone III-I meningitis epidemic into Zambia.

The epidemic of Neisseria meningitidis group A clone III-I strain began with the 1987 outbreak in Mecca, Saudi Arabia. Intense epidemics in African countries occurred the following year. Clone III-I was first isolated from Africa in 1988 in Chad, followed by epidemics in Ethiopia (1989), Kenya and Tanzania (1989), and The Central African Republic (1992). We report an epidemic of Neisseria meningitidis group A clone III-I afflicting Zambia during a 2-year period (April 1992-May 1994). This extension of the 'meningitis belt' southwards into Central Africa is cause for concern. Active surveillance for this disease should be carried out by all African countries, even those outside the well described sub-Saharan 'meningitis belt'.

Bacterial Typing Techniques↗

Human immunodeficiency virus-associated diarrhea and wasting in Zambia: selected risk factors and clinical associations.

A significant association was observed among human immunodeficiency virus (HIV)-positive adult cases in Lusaka, Zambia compared with HIV-negative controls for chronic diarrhea (68% versus 22%; P < 0.05), weight loss (54% versus 30%; P < 0.05), lymphadenopathy (44% versus 15%; P < 0.05), and skin eruption (33% versus 7%; P < 0.05). Among the HIV-positive children, a higher proportion had clinical evidence of tuberculosis when compared with HIV-negative children (8% versus 1%; P < 0.05). The study demonstrated an association between weight loss in HIV-positive adults and children and chronic diarrhea (odds ratio [OR] = 12.7, 95% confidence interval [CI] = 6.4-25.5; P < 0.001), persistent cough (OR = 7.2, 95% CI = 2.9-14.5; P < 0.001), and an age of 31-45 years (OR = 3.8, 95% CI = 1.8-8.3; P < 0.01). The factors associated with mortality in HIV positive patients included chronic diarrhea (OR = 7.4, 95% CI = 1.6-34; P < 0.01), and lymphadenopathy (OR = 3.89, 95% CI = 1.2-12.2; P < 0.04).

Adolescent↗