Quantitative bacillary response to treatment in HIV-associated pulmonary tuberculosis

A group of 122 patients with culture-proven pulmonary tuberculosis were recruited to examine the concentrations of Mycobacterium tuberculosis in sputum and the relationship to HIV-1 antibody status. They were followed for up to 28 days from the start of antituberculous chemotherapy to assess the early bacillary response to two chemotherapeutic regimens. Of 67 treated with streptomycin, thiacetazone, and isoniazid 17 were HIV positive, and subsequently 55, of whom 20 were HIV positive, were treated with streptomycin, rifampin, isoniazid, and pyrazinamide. The mean initial concentration of M. tuberculosis in the sputum of the HIV-negative patients was significantly higher than in HIV-positive patients (6.95 and 6.34 log colony-forming units respectively; p = 0.019). The HIV-positive patients had less radiologic evidence of disease and significantly fewer zones of lung affected with cavities. The response to treatment was similar, but with HIV-positive patients more likely to become culture negative by 28 days. The differences that exist between HIV-positive and HIV-negative patients are minor, and standard regimens are at least as effective in HIV-positive patients in the first month of treatment.     

The prevalence of herpes family virus DNA in the conjunctiva of patients positive and negative for human immunodeficiency virus using the polymerase chain reaction

OBJECTIVE: To help understand the pathogenesis of herpes family virus ocular infection among patients positive for HIV, the authors compared the rates of detection of herpes family virus DNA from the conjunctiva of patients who are positive and negative for human immunodeficiency virus (HIV) using the polymerase chain reaction (PCR). DESIGN: Cross-sectional study. PARTICIPANTS: The conjunctival scrapings of 30 patients positive for HIV and 30 patients negative for HIV were examined. INTERVENTION: PCR was used to assay for the presence of herpes simplex virus type 1 (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) DNA (n = 240 samples). MAIN OUTCOME MEASURE: The rate of detection of virus DNA in the two groups, controlling for age, gender, and race, was measured. RESULTS: HSV and VZV DNA were not detected in any of the HIV-positive or HIV-negative samples. CMV DNA was detected in 20% (6 of 30) of patients positive for HIV and was undetected in control subjects negative for HIV (P = 0.01). EBV DNA was detected in 40% (12 of 30) of patients positive for HIV and in 47% (14 of 30) of control subjects negative for HIV (P = 0.58). CONCLUSIONS: There was no difference in the frequency of detection of HSV, VZV, or EBV DNA from the conjunctiva of patients positive or negative for HIV. Only CMV DNA was detected at a significantly higher rate in the conjunctiva of patients positive for HIV compared with control subjects negative for HIV. These different rates of peripheral virus shedding may be one possible explanation for the different rates of clinical infection among the herpes family viruses among patients positive for HIV.     

Extrapulmonary tuberculosis. Experience at a general hospital (1980-1993)

In order to know extrapulmonary tuberculosis in our environment the results of all samples submitted for culture of mycobacteria to the Microbiology Department, Fundación Jiménez Díaz, from 1980 to 1993 were analyzed. During this period 290 cases of extrapulmonary cases were diagnosed, 101 from 1980 to 1985 and 189 from 1986 to 1993. The most common site of infection before 1985 was in genitourinary tract (42.6%); in contrast, from 1986 onwards the more common sites of infection were pleural (22.8%), genitourinary tract and lymphatic glands (22.2% in both sites). When EPT was compared in the two periods of time the observations made were a relative decrease of genitourinary infections (p = 0.00004) and increase in disseminated (p = 0.015) and pleural tuberculosis (p = 0.011) from 1986 compared with previous years. From 1986 a greater proportion of disseminated form was observed (p < 0.0001) in positive-HIV patients and of genitourinary (p = 0.011) and pleural (p = 0.076) forms in negative HIV-patients. In conclusion, extrapulmonary tuberculosis has increased in our environment during the period 1980-1993, and this increase is not attributable only to positive-HIV patients. The distribution of clinical forms of this disease was different in the two studied periods and among positive and negative HIV patients.     

The scourge of HIV-related tuberculosis: a cohort study in a district general hospital in Malawi

Malawi is similar to a number of other African countries in having an escalating, HIV-related, tuberculosis (TB) epidemic. A prospective study was carried out to determine the pattern of disease and HIV serostatus in unselected, adult, TB patients consecutively admitted to a large, district general hospital in Zomba (in the Southern region of Malawi). Clinical details were obtained, from the district TB register, for the 714, adult TB patients, aged > or = 15 years, who were registered with the district TB officer between 1 July and 31 December in 1995. Patients were counselled, and offered HIV testing using an ELISA and particle agglutination test. Concordant HIV-test results were available for 686 (96%) of the subjects: 547 (80%) of these were HIV-seropositive and 139 seronegative. The HIV-positive patients were significantly younger than the HIV-negative patients and significantly more HIV-positive patients were males (P < 0.05 for each). The proportions of HIV-positive subjects who were new patients, had been previously treated for TB, had pulmonary TB (PTB), had smear-positive PTB or had different types of extrapulmonary TB were similar to those of the HIV-negative. A high percentage of an unselected cohort of adult TB patients admitted to a district, general hospital in Malawi, particularly of the younger age groups was therefore HIV-positive. The pattern of disease was uninfluenced by the HIV serostatus. The large number of cases registered emphasises the severity of the current epidemic of TB in Malawi and its impact upon young adults.     

Clinical utility of the polymerase chain reaction in the diagnosis of extrapulmonary tuberculosis

This study examines the diagnostic utility of the polymerase chain reaction (PCR) in 156 patients (five human immunodeficiency virus (HIV) seropositive) suspected of extrapulmonary tuberculosis. The results of PCR in 226 samples from 11 different sites were compared with the results of microscopy and culture. Positive culture results were predicted in 86% of samples by PCR but in only 31% by microscopy. Specificity of PCR was 92%. In cases with culture-proven tuberculosis, PCR identified all 11 microscopy positive cases and 19 of 24 (79%) of the microscopy-negative cases. In four patients, PCR excluded the diagnosis of tuberculosis in microscopy-positive samples, which were later shown to contain mycobacteria other than Mycobacterium tuberculosis or laboratory contaminants. In 20 patients (microscopy, PCR and culture negative) a trial of antituberculous drugs was given, but patients showed no improvement and treatment was stopped. In 17 patients, all culture negative (in nine PCR was positive, three of whom also had positive microscopy) the diagnosis was probable tuberculosis based on clinical findings and response to treatment. This polymerase chain reaction has a much higher sensitivity than microscopy and can facilitate therapeutic decisions for those with suspected extrapulmonary tuberculosis.     

PCR-based rapid detection of Mycobacterium tuberculosis in blood from immunocompetent patients with pulmonary tuberculosis

A PCR test based on insertion sequence IS1081 was developed to detect Mycobacterium tuberculosis complex organisms in the peripheral blood. The method was applied to blood samples from immunocompetent individuals with localized pulmonary tuberculosis. Seven of 16 (43.75%) blood samples were found to be positive for the circulating DNA copies of M. tuberculosis complex.     

Evaluation of a commercial immunodiagnostic kit incorporating lipoarabinomannan in the serodiagnosis of pulmonary tuberculosis in Ghana

We evaluated 'Mycodot', a commercially marketed immunodiagnostic test for tuberculosis which detects antibodies to lipoarabinomannan antigen. Serum was tested from 52 patients with newly diagnosed smear-positive pulmonary tuberculosis, of whom 20 were HIV-positive and 32 HIV-negative. Control sera were taken from 40 patients of whom 20 had acute non-tuberculous lobar pneumonia and 20 patients had no respiratory disease. The test was found to have a very high specificity of 97.5% (95% CI:92.5-100%). However, the sensitivity in HIV-negative patients was 56% (95% CI:39-73%), and was substantially lower at 25% (95% CI:6-44%) in HIV-positive patients. In conclusion: 'Mycodot' was found to be a highly specific and easily performed assay. However, the poor sensitivity, especially in HIV-infected patients, renders it unlikely to be useful either as a primary or adjunctive diagnostic test for tuberculosis, particularly in countries with a high prevalence of HIV. A larger trial of this assay in Ghana was not deemed necessary.     

Determination of 7alpha-hydroxycholesterol in dog plasma by high-performance liquid chromatography with fluorescence detection

One of the groups at highest risk of anal cancer is homosexual and bisexual men. Like cervical cancer, anal cancer is associated with human papillomavirus (HPV) infection. Anal HPV infection was characterized in a study of 346 human immunodeficiency virus (HIV)-positive and 262 HIV-negative homosexual and bisexual men. Anal HPV DNA was detected in 93% of HIV-positive and 61% of HIV-negative men by polymerase chain reaction. The spectrum of HPV types was similar in HIV-positive and HIV-negative men, with HPV-16 the most common type. Infection with multiple HPV types was found in 73% of HIV-positive and 23% of HIV-negative men. Among HIV-positive men who were positive by hybrid capture for group B HPV types (16/18/31/33/35/39/45/51/52/56/58) or group A types (6/11/42/43/44), lower CD4 cell levels were associated with higher levels of group B DNA (P = .004) but not group A DNA. These data suggest increased replication of the more oncogenic HPV types with more advanced immunosuppression.     

Diagnosis of extrapulmonary tuberculosis by a commercial polymerase chain reaction kit

The Roche Amplicor Mycobacterium tuberculosis PCR test was compared with mycobacterial culture for direct detection of M. tuberculosis in extrapulmonary specimens. From January 1995 to October 1996, 124 clinical specimens from 112 patients were assessed, including 47 body fluids, 61 tissue specimens and 16 abscesses. The sensitivity and specificity of Amplicor PCR compared to culture were 63.6% and 93.1% respectively. Analysis of 7 PCR-positive, culture-negative specimens confirmed that all were from patients with recently diagnosed tuberculosis under treatment. Eight specimens were PCR negative-culture positive, including a pleural fluid containing inhibitory substances. On acid-fast bacilli (AFB) smear-negative specimens, sensitivity and specificity were 53 and 100% respectively. The best results for Amplicor PCR were obtained with abscesses and biopsies. It is concluded that this test, highly specific for the diagnosis of tuberculosis, is at least as sensitive on extrapulmonary specimens as on smear-negative respiratory specimens.     

Membrane and soluble forms of Fas (CD95) and Fas ligand in peripheral blood mononuclear cells and in plasma from human immunodeficiency virus-infected persons

The expression of membrane-bound Fas ligand (FasL) and Fas in lymphocytes and monocytes and levels of soluble forms of FasL (sFasL) and Fas (sFas) in plasma from human immunodeficiency virus (HIV)-positive and -negative subjects was evaluated. Surface FasL was detectable on monocytes, but poorly so on lymphocytes, even in the presence of KB8301, a metalloproteinase inhibitor. Unexpectedly, monocytes of HIV-positive subjects expressed less FasL than those of HIV-negative volunteers. sFasL levels in plasma of HIV-positive persons were elevated and correlated with levels in plasma and with HIV RNA burden. sFas levels in plasma of HIV-positive subjects were also elevated and correlated with Fas expression in apoptotic lymphocytes. Finally, culture-induced lymphocyte apoptosis of HIV-positive subjects was enhanced by anti-Fas agonistic antibody but was not inhibited by anti-FasL blocking antibodies. These results suggest that significant dysregulation of both Fas and FasL occurs in HIV infection and contributes to increased sensitivity of lymphocytes to apoptosis.     

Efficacy of a short 6 month therapeutic coursefor HIV infected tuberculosis patients in Abidjan, C?te d''Ivoire

From December 1992 to February 1993, 104 newly diagnosed pulmonary tuberculosis patients were enrolled in a prospective cohort study to assess the response to the 6 month-short-course regimen implemented in Cote d'Ivoire. This treatment encompassed the daily intake of Rifampicin and Pyrazinamide for 2 months followed by Rifampicin and Isoniazid for the remaining 4 months. All the patients were enrolled at the Treichville Tuberculosis Treatment Centre in Abidjan, and a follow-up of 6 months was observed for each patient. All in all, 41 patients were HIV-positive whereas 63 where HIV-negative. No statistical difference was noted between HIV-positive and HIV-negative patients with regard to the completion of therapy (85% versus 87%). The cure rate after an effective 6 month-therapy was similar among HIV-positive and HIV-negative patients (83% versus 84%) as well as the treatment failure rate which was 2.4% and 3% respectively. The results clearly indicate that the 6 month-short-course regimen policy implemented in C?te d'Ivoire is as effective for the treatment of HIV-associated tuberculosis as for the treatment of tuberculosis.     

Congenital bronchoesophageal fistula in an adult

The seroprevalence of human herpesvirus 8 (HHV-8) in the Swiss population was investigated. By enzyme-linked immunosorbent assay, sera reactive to the recombinant HHV-8 antigen orf 65.2 were found in 24% of human immunodeficiency virus (HIV)-positive patients without and in 92% of HIV-positive patients with Kaposi's sarcoma. Surprisingly, 20% of homosexual HIV-negative men, versus only 7% of heterosexual HIV-negative individuals and 5% of blood donors, had antibodies to HHV-8.     

Kidney morphological changes in relation to long-term renal function and metabolic control in adolescents with IDDM

OBJECTIVE: To investigate the impact of HIV infection on the prevalence, incidence and short-term prognosis of squamous intraepithelial lesions (SIL), in a prospective study with 1-year follow-up. METHODS: Between 1993 and 1995, 271 HIV-positive and 171 HIV-negative women at high risk of HIV infection were recruited, 365 (82.6%) of whom completed the 1-year follow-up. The women underwent a Papanicolaou smear test at inclusion and at 6 and 12 months. Human papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. RESULTS: The SIL prevalence ranged from 7.5% for HIV-negative to 31.3% for HIV-positive women with CD4 cell counts < 500 x 10(6)/l (P < 0.001). Other factors associated independently and significantly with SIL prevalence were HPV-16, 18, 33 and related types, HPV-31, -35, -39 and related types, lifetime number of partners, younger age, past history of SIL and lack of past cervical screening. The SIL incidence ranged from 4.9% in HIV-negative women to 27% in HIV-positive women with CD4 cells < 500 x 10(6)/l (P < 0.001). Progression from low- to high-grade SIL during follow-up was detected in 38.1% of HIV-positive women with CD4 cells < or = 500 x 10(6)/l but in no HIV-negative nor HIV-positive women with CD4 cells > 500 x 10(6)/l. HPV-16, 18, 33 and related types were also associated with higher incidence of SIL and progression from low- to high-grade SIL. CONCLUSION: HIV-induced immunodeficiency is associated with high prevalence, incidence and persistence/progression of SIL. A pejorative influence of HIV infection without marked immunodeficiency is less clear. HIV-positive women with SIL may thus benefit from early treatment when a useful immune response is still present.     

Effect of pharmacist interventions on medication use and cost in hospitalized patients with or without HIV infection

Pharmacotherapeutic interventions and drug acquisition costs in HIV-positive and HIV-negative patients on a hospital medical service were studied. In November and December 1995, HIV-positive and HIV-negative patients were randomly selected and matched on the basis of admission date. Pharmacotherapeutic interventions were recorded by a pharmacist until the time of discharge. Drug acquisition costs were obtained through records of medications ordered. The two patient groups were compared with respect to length of stay (LOS), number and cost of medications, and number of interventions. HIV-positive patients had significantly more medication orders and required more interventions than HIV-negative patients. Mean LOS was not significantly different. HIV status and number of medications were significantly associated with requiring five or more interventions. Drug acquisition costs were significantly higher in the HIV-positive group. The mean pharmacist-attributed cost saving per patient was $134 for HIV-positive patients and $27 for HIV-negative patients. HIV-positive patients required more interventions and consumed more medication resources than HIV-negative patients. Pharmacist interventions produced drug acquisition cost savings for both groups, with more savings being realized for positive patients.     

Pleural effusion in patients infected with the human immunodeficiency virus

In order to analyze the etiology, cytological and biochemical characteristics, and outcome of pleural disease in patients infected with HIV, the medical records of 86 HIV-positive patients with pleural effusion were reviewed. Controls were 106 HIV-negative patients with parapneumonic or tuberculous effusion. Most HIV-positive patients were intravenous drug abusers (95.3%). Pleural effusions in HIV-positive patients were caused by infections in 76 (89.4%) cases. Parapneumonic effusion was diagnosed in 59 patients and tuberculous pleuritis in 15 patients. Staphylococcus aureus was the most frequently isolated bacteria. Parameters for differentiating complicated cases of parapneumonic exudate from uncomplicated cases, such as pleural fluid pH < 7.20 (sensitivity 80% vs. 84.3%), pleural fluid glucose < 35 mg/dl (sensitivity 45% vs. 56.25%) pleural fluid LDH > 1600 UI/l (sensitivity 85% vs. 62.50%), showed similar sensitivity in HIV-positive and HIV-negative patients. Monocytes in pleural fluid were significantly decreased in tuberculous pleuritis in HIV-positive patients (506 +/- 425 vs. 1014 +/- 1196 monocytes/ml, p < 0.05). No significant differences were detected in the outcome of HIV-positive and HIV-negative patients with pleural disease. It can be concluded that the pleural effusion was of predominantly infectious etiology in HIV-positive patients from populations with a high prevalence of intravenous drug abuse. Neither the biochemical parameters in pleural fluid nor the outcome differed significantly between HIV-positive and HIV-negative patients.     

Host immune suppression after small bowel/liver transplantation in rats

Biopsy samples from seven patients with acquired immunodeficiency syndrome were screened for Mycoplasma fermentans, M. pneumoniae and M. genitalium infection by the polymerase chain reaction. M. fermentans DNA was detected in four patients. Various tissues were evaluated and the mycoplasma were mainly detected from lymph nodes. Moreover, mycoplasma genus-specific DNA was isolated from peripheral blood mononuclear cells of asymptomatic human immunodeficiency virus(HIV)-infected individuals (two of 31 HIV-infected individuals). These data suggest that mycoplasma infection in AIDS patients is not uncommon.     

Predictive value of cytomegalovirus (CMV) antigenemia and digene hybrid capture DNA assays for CMV disease in human immunodeficiency virus-infected patients

Oral ganciclovir prophylaxis decreases the incidence of cytomegalovirus (CMV) disease among persons infected with the human immunodeficiency virus (HIV), but universal prophylaxis is not cost-effective. We evaluated urine and peripheral blood mononuclear cell cultures, a qualitative and quantitative antigenemia assay, and a commercially available CMV DNA hybridization assay for their ability to predict CMV disease in 138 HIV-infected patients. During a median follow-up of 10 months, 23 patients (17%) developed CMV disease. The sensitivity, specificity, positive predictive value, negative predictive value, and mean lead times for the antigenemia assay (with use of a threshold of 8 positive cells per 10(5) peripheral blood mononuclear cells as a positive) were 74%, 91%, 63%, 95%, and 95 days, respectively. Corresponding figures for the DNA hybridization assay were 91%, 64%, 34%, 97%, and 152 days. These assays can identify patients at increased risk of CMV disease and should allow a strategy of preemptive therapy to be tested.     

Seropositive rheumatoid arthritis with interstitial lung disease in giant cell arteritis

Unusually high mortality rates have been recorded among HIV-infected tuberculosis patients in urban Africa 6 and 12 months after initiation of tuberculosis treatment--a trend that impedes efforts to achieve the 85% cure rate target set by the World Health Organization. This study investigated tuberculosis treatment outcomes in relation to HIV serostatus in a rural district of Malawi (Ntcheu). All 205 smear-positive pulmonary tuberculosis patients newly diagnosed in the district in 1995 received 2 months of daily supervised streptomycin, rifampicin, isoniazid, and pyrazinamide in the hospital followed by 6 months of isoniazid and thiacetazone at home. HIV testing, offered to all tuberculosis patients, was accepted by 110 (54%), 73 (66%) of whom were HIV-positive. By the end of treatment, 126 patients (61%) had been cured and 56 (27%) had died. Significantly fewer HIV-positive patients or patients who declined HIV testing were cured (59% and 55%, respectively) than those who agreed to testing and were HIV-negative (84%). The mortality rate was 29% among patients who tested HIV-positive, 8% among those with a negative test result, and 34% among patients who declined HIV testing. Acceptance of HIV testing improved over the course of the study period in response to changes in counseling techniques, especially clarification that blood taken for HIV testing would not be used for transfusions. Overall, these findings suggest that, in areas where HIV infection is prevalent, an 85% tuberculosis cure rate may be unrealistic.     

Utility of major leukocyte subpopulations for monitoring secondary cytomegalovirus infections in renal-allograft recipients by PCR

The feasibility of the major peripheral blood leukocyte (PBL) subsets for use in qualitative and quantitative PCR to monitor secondary cytomegalovirus (CMV) infection and ganciclovir therapy was assessed with 188 blood samples derived from 40 CMV immunoglobulin G-positive renal-allograft recipients. In pp65 antigen-positive patients all leukocyte fractions, but only 79.5% of plasma preparations, were PCR positive. In pp65 antigen-negative samples from patients after antiviral treatment only 7.3% of polymorphonuclear cell (PMNL) samples, but 81.8% of peripheral blood mononuclear cells (PBMC), and 10.9% of plasma samples remained PCR positive. Similarly, in patients with latent infections only 5.0% of PMNL, but 51.7% of PBMC preparations, and 8.0% of plasma samples were PCR positive. Regarding patients with active CMV infection, CMV DNA copy numbers in PMNL correlated significantly with pp65 antigen-positive cell counts before and after onset of ganciclovir therapy. Significant differences in CMV DNA copy numbers in PMNL and plasma were observed (i) between patients with symptomatic infection and those with asymptomatic infection and (ii) between patients with active infection and those with latent infection. In contrast, PBMC harbored equally low CMV DNA levels both in patients with active infection and those with latent infections, and no decline of CMV DNA load in PBMC was observed during antiviral treatment. We conclude that detection of CMV DNA in PMNL, not in PBMC, is associated with active infections and is more sensitive than detection of CMV DNA in plasma. Negative PCR results for PMNL after antiviral therapy indicate recovery, and fewer unwanted positive results occur compared to PBMC and plasma. Therefore, purified PMNL should be preferred for analysis by qualitative CMV PCR to avoid unwanted positive results. The CMV DNA load in PBMC compared with that in PMNL is negligible during active infection, so mixed PBL are sufficient for use in quantitative PCR.     

The renal medullary thick ascending limb as a model for understanding lipid mediators in sepsis

OBJECTIVE: To evaluate the impact of HIV illness on psychiatric and psychosocial functioning over 3 years in a sample of male and female HIV-positive injecting drug users (IDU), with a comparison group of HIV-negative male and female IDU. DESIGN: As part of a multidisciplinary study, 121 men (69 HIV-positive, 52 HIV-negative) and 66 women (36 HIV-positive, 30 HIV-negative) were evaluated semiannually for seven visits. Attrition, unrelated to sex or serostatus, was 33%. RESULTS: At baseline, rates of major depression and dysthymia ranged from 15% (HIV-negative men) to 33% (HIV-positive men and HIV-negative women). Global impairment was in the range found in psychiatric patients (mean Global Assessment of Functioning scores, 46-51). Higher levels of social support and less social conflict were independently associated with decreased distress and improved global functioning among both men and women. For both HIV-positive groups, degree of improvement over time was related to degree to HIV progression: those who remained healthier in terms of CD4 count and illness stage showed more improvement. HIV-seronegative status was associated with less distress for men but not for women. Overall, women reported higher levels of psychiatric distress than men. CONCLUSIONS: High rates of psychopathology were found in this IDU cohort, independent of HIV status and sex. Although rates of psychopathology, injecting drug use and distress declined slightly during the study, they remained elevated; accordingly, psychiatric services are indicated for this population.