Tuberculosis and immunodeficiency in HIV-1-infected patients in Africa.
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HIV Infections↗
Biomedical subjects
N Luo
Publications and source records attributed to N Luo.
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.
AIDS-Related Opportunistic Infections↗
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.
Adolescent↗
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.
Adolescent↗
Protein structure prediction based on statistical potential.
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Biometry↗
Ab initio study of the electrostatic multipole nature of torsional potentials in CH3SSCH3, CH3SSH, and HOOH.
The origin of torsional potentials in H3CSSCH3, H3CSSH, and HOOH and the anisotropy of the local charge distribution has been analyzed in terms of atomic multipoles calculated from the ab initio LCAO-MO-SCF wave function in the 6-31G* basis set. The results indicate that for longer -S-S-bonds the major contribution to these torsional barriers are electrostatic interactions of the atomic multipoles located on two atoms forming the rotated bond. This finding demonstrates the important role of electrostatic 1-2 interatomic interactions, usually neglected in conformational studies. It also opens the possibility to derive directly from accurate ab initio wave functions a simple nonempirical torsional potential involving atomic multipoles of two bonded atoms defining the torsional angle. For shorter -O-O- bonds, use of more precise models and inclusion of 1-3 interactions seems to be necessary.
Chemistry, Organic↗
An algorithm for converting a virtual-bond chain into a complete polypeptide backbone chain.
A systematic analysis is presented of the algorithm for converting a virtual-bond chain, defined by the coordinates of the alpha-carbons of a given protein, into a complete polypeptide backbone. An alternative algorithm, based upon the same set of geometric parameters used in the Purisima-Scheraga algorithm but with a different "linkage map" of the algorithmic procedures, is proposed. The global virtual-bond chain geometric constraints are more easily separable from the loal peptide geometric and energetic constraints derived from, for example, the Ramachandran criterion, within the framework of this approach.
Algorithms↗
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↗
Oral ciprofloxacin versus ceftriaxone for the treatment of urethritis from resistant Neisseria gonorrhoeae in Zambia.
Neisseria gonorrhoeae strains resistant to treatment with penicillin, tetracycline, and/or spectinomycin are increasing in prevalence in many parts of the world. In Zambia, 52% of N. gonorrhoeae isolates produced beta-lactamase in 1986. Few oral regimens have proven effective for treatment of resistant N. gonorrhoeae. We conducted a prospective, double-blind, randomized clinical trial of 250 mg of ciprofloxacin given orally versus 250 mg of ceftriaxone given intramuscularly for treatment of uncomplicated gonococcal urethritis in adult males. Two hundred men were enrolled and treated. The two groups were comparable in age (27.5 years), prevalence of latent syphilis (14 and 10%), and human immunodeficiency virus infection (32 and 38%). Of 165 patients with cultures positive for N. gonorrhoeae who returned for follow-up, ciprofloxacin cured 83 of 83 (100%), including 26 with penicillinase-producing N. gonorrhoeae (PPNG) and 21 with N. gonorrhoeae with chromosomally mediated resistance to multiple antibiotics (CMRNG), and ceftriaxone cured 81 of 82 (98.7%), including 30 with PPNG and 19 with CMRNG. Both treatment regimens were well tolerated. Chlamydia trachomatis in urethral exudate was found by direct fluorescent-antibody microscopic examination or by culture in 10 (5%) participants. All N. gonorrhoeae isolates were inhibited by ceftriaxone at 0.06 micrograms/ml, except one which was inhibited at 0.125 micrograms/ml, while ciprofloxacin inhibited all isolates at 0.03 micrograms/ml. Ciprofloxacin is a safe and effective therapy for uncomplicated gonococcal urethritis, including that caused by PPNG and CMRNG in human immunodeficiency virus-infected men.
Adult↗
Perinatal transmission of HIV-I in Zambia.
OBJECTIVE--To determine the occurrence of vertical transmission of HIV-I from women positive for the virus and the prognosis for their babies. DESIGN--Women presenting in labour were tested for HIV-I. Their newborn babies were also tested. Women positive for the virus were followed up with their babies for two years. SETTING--Teaching hospital in Lusaka, Zambia. SUBJECTS--1954 Women, of whom 227 were seropositive. Of 205 babies, 192 were positive for HIV-I. After birth 109 seropositive mothers and their babies and 40 seronegative mothers and their babies were available for follow up. MAIN OUTCOME MEASURES--Serological examination of mothers and their babies by western blotting. Birth weight and subsequent survival of babies. Women and babies were tested over two years for signs of seroconversion and symptoms of infection with HIV, AIDS related complex, and AIDS. RESULTS--Of the 109 babies born to seropositive mothers and available for follow up, 18 died before 8 months, 14 with clinical AIDS. Of the 91 remaining, 23 were seropositive at 8 months. By 24 months 23 of 86 surviving babies were seropositive, and a further five infected babies had died, four were terminally ill, 17 had AIDS related complex, and two had no symptoms. The overall rate of perinatal transmission was 42 out of 109 (39%). The overall mortality of infected children at 2 years was 19 out of 42 (44%). Before the age of 1 year infected children had pneumonia and recurrent coughs, thereafter symptoms included failure to thrive, recurrent diarrhoea and fever, pneumonia, candidiasis, and lymphodenopathy. All babies had received live attenuated vaccines before 8 months with no adverse affects. CONCLUSIONS--Vertical transmission from infected mothers to their babies is high in Zambia and prognosis is poor for the babies. Perinatal transmission and paediatric AIDS must be reduced, possibly by screening young women and counselling those positive for HIV-I against future pregnancy.
Acquired Immunodeficiency Syndrome↗
HIV seroprevalence in critically ill patients in Zambia.
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Adult↗
Immunology of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. An update.
Recent advances in the understanding of the pathogenesis of infection with human immunodeficiency virus (HIV) stems from the demonstration that the membrane glycoprotein, CD4, is the cellular receptor for HIV. This glycoprotein is found mainly on the surface of a major subpopulation of T lymphocytes and also on macrophages, natural killer cells, some B lymphocytes, and neuronal cells. Cells infected with HIV may be destroyed or have their normal function impaired. Host immune responses to HIV are poor and are not sustained. Neutralizing antibody often is not produced, or HIV may escape from normal immunosuppressive mechanisms through the process of rapid antigenic variation. Factors and markers that may be important in the outcome or that may predict progression of HIV infection are genetic (Gc type), environmental (nutritional status or intercurrent sexually transmitted diseases sustained by the host), and immunologic (rate of decline in number and impairment of function of CD4 lymphocytes and of decline in antibody titers to HIV core protein, p24). A recombinant vaccine will probably be developed for testing in future clinical trials.
Acquired Immunodeficiency Syndrome↗
Recruitment to a trial of tuberculosis preventive therapy from a voluntary HIV testing centre in Lusaka: relevance to implementation.
To determine the number of clients attending for voluntary human immunodeficiency virus (HIV) testing who are able to enter a trial of preventive therapy for tuberculosis, and the factors that determine who receives therapy, we studied 475 consecutive people attending for an HIV test at Lusaka's first voluntary HIV testing centre and the preventive therapy study clinic at the University Teaching Hospital, Lusaka, Zambia. Semi-structured interviews were conducted by counsellors and collated with recruitment data from the trial. Two hundred and twenty-five people were seropositive, of whom 201 returned to collect their results; 77 (38%) of these (16% of the total number screened) entered the trial. Reasons for not entering the trial included exclusion by trial protocol (30), including 18 who had active tuberculosis; psychological adjustment to a positive result (27); death (6); worries about confidentiality (3); the experimental nature of the trial (12); attitudes of staff in the hospital (5); and cost of transport (7). Targeting preventive therapy at those who are already choosing to be tested for HIV seems appropriate and may be cost-effective. Although visiting a hospital may deter some people, the prevalence of active tuberculosis among this group emphasized the importance of arranging adequate screening facilities.
AIDS Serodiagnosis↗
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↗
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.
AIDS-Related Opportunistic Infections↗