Tuberculous hepatosplenic abscess, human immunodeficiency virus infection and multiresistant tuberculosis

BACKGROUND: Tuberculosis (TB) with liver and/or spleen abscess (HSA) formation in HIV-positive patients is uncommon. PATIENTS AND METHODS: One hundred and thirty-seven HIV positive patients with TB were studied from January 93 to June 95. Patients with tuberculous HSA were enrolled in the study. Diagnosis was obtained by recovery of Mycobacterium tuberculosis in clinical specimens and the presence of hypoechogenic lesions in liver and/or spleen. RESULTS: M. tuberculosis isolates were resistant to some of the usual drugs in 51 patients. Twenty of these patients had HSA (39%) and in 18 patients the antibiotic sensitivity testing showed resistance to isoniazid, rifampin, ethambutol, and streptomycin. The remaining 86 patients had episodes of TB with drug-susceptible microorganism and only three patients had HSA (3%) (p < 0.001). The 23 patients with tuberculous HSA had a mean CD4+ lymphocyte count of 33 x 10(6) cells/L (2-111) and 7 had a previous episode of TB. The abdominal echography showed hepatosplenomegaly in all cases. Abscesses were located at the liver in 12 patients (52%), spleen in 18 (78%) and both organs in 7 (30%). In 16 cases a corticosteroid therapy was indicated. In the 3 patients with susceptible TB and HSA the clinical course was good. The 20 patients with resistant TB died. CONCLUSION: Abdominal TB in HIV-positive patients and HSA formation appears to be more common in severely immunosuppressed patients, with resistant TB and its mortality rate is high. The response to therapy with antituberculous drugs is slow and sometimes the administration of corticosteroids is necessary for the resolution of symptoms.     

Serum vitamin A levels during tuberculosis and human immunodeficiency virus infection

Vitamin A deficiency during tuberculosis and human immunodeficiency virus (HIV) infection has not been characterized. A cross-sectional study was conducted among HIV-infected adults with tuberculosis in Butare, Rwanda, in which 29% of the subjects had serum vitamin A levels consistent with deficiency (<1.05 micromol/L). Women had mean serum vitamin A levels of 1.22+/-0.45, compared with 1.47+/-0.68 in men (P < 0.07). A total of 37% of subjects with recent weight loss had vitamin A levels consistent with deficiency, compared with 14% of subjects without weight loss (P < 0.02). This study suggests that vitamin A deficiency is common among adults with tuberculosis and HIV infection in Rwanda.     

Culture-positive tuberculosis in human immunodeficiency virus type 1-infected children

BACKGROUND: Adults infected by HIV have increased susceptibility to Mycobacterium tuberculosis and progress more rapidly to disease. HIV and tuberculosis (TB) coinfection in children has been reported but often lacks bacterial confirmation. We report on the clinical picture, special investigations, clinical course and outcome of 14 children with HIV infection and culture-confirmed TB from a developing country. METHODS: The clinical records of all children, from 1992 to 1997, with HIV infection and culture-proved TB were reviewed. RESULTS: Fourteen (10.4%) of 135 children with vertically transmitted HIV infection, 93% <2 years of age, fit the criteria. Nonresolving pneumonia (4) and otorrhoea (6) were common complaints. A Mantoux test was positive (> or =15 mm) in 6 of 11 children. Extrapulmonary TB was present in 5 cases. Ear swabs were the source of M. tuberculosis culture in 3. Chest radiographs were abnormal in all with hilar and paratracheal lymphadenopathy present in 7. A source case with pulmonary TB was identified for 10. Susceptibility tests were done on 9 strains of which 1 was drug-resistant. Four children were culture-positive 4 to 10 months after initiation of TB treatment. Mortality was 21% and 3 were lost to follow-up. CONCLUSIONS: In HIV-infected children the Mantoux skin test remains useful and culture specimens should be obtained from all sources. Response to treatment is unpredictable, and for this reason repeated cultures should be taken during treatment and a 9-month course of treatment considered.     

T cell cytokine responses in persons with tuberculosis and human immunodeficiency virus infection

Tuberculosis causes more extensive and life-threatening disease in patients with HIV infection than in immunocompetent persons. To investigate the hypothesis that these severe manifestations of tuberculosis may be due to alterations in cytokine production, we evaluated cytokine patterns in HIV-infected tuberculosis patients. Upon stimulation with Mycobacterium tuberculosis in vitro, PBMC from HIV-infected tuberculosis patients had reduced proliferative and type 1 responses, compared with HIV-seronegative tuberculosis patients. The reduction in proliferative responses was independent of the CD4 cell count, but the reduced type 1 response was a direct result of CD4 cell depletion. There was no enhancement of type 2 cytokine production in HIV-infected patients, although production of IL-10 was prominent in all tuberculosis patients. In HIV-infected tuberculosis patients, M. tuberculosis-induced proliferative responses were significantly enhanced by neutralizing antibodies to IL-10 but not by antibodies to IL-4 or by recombinant IL-12. The M. tuberculosis-induced type 1 response was augmented both by antibodies to IL-10 and by recombinant IL-12. Tuberculosis in the context of HIV infection is characterized by diminished type 1 responses, probably induced by immunosuppressive cytokines produced by macrophages/monocytes, rather than by type 2 cells.     

Mycobacterium avium complex and Mycobacterium tuberculosis in patients infected with the human immunodeficiency virus

Primary care physicians play an important role in identifying and treating bacterial infections in adults infected with the human immunodeficiency virus (HIV). Mycobacterium avium complex and Mycobacterium tuberculosis are pathogens that can cause systemic or local infection in these patients. We review the epidemiology, pathogenesis, clinical presentation, and principles of treatment for these two mycobacterial pathogens. Because M tuberculosis disease is preventable and curable and yet communicable, physicians should maintain a high degree of suspicion for tuberculosis in HIV-infected adults. In comparison, the goal of treating M avium complex in patients with advanced HIV disease is to reduce constitutional symptoms and improve survival.     

Euthanasia: reconciling culture and human rights

Effects of the farnesylcysteine mimetic, farnesylthiosalicylate on the activation of myeloid cells were studied. In dimethyl-sulfoxide-differentiated HL60 cells and in human neutrophils farnesylthiosalicylate (< or = 20 microM) dose-dependently elevated cytosolic Ca2+ concentrations, suggesting phospholipase-C-mediated release of the ion from intracellular stores. In human neutrophils, in addition to the production of inositol trisphosphate, farnesylthiosalicylate induced activation of the NADPH oxidase and translocation of the cytosolic oxidase components p47-phox and p67-phox to the membrane. The calcium signal, inositol-trisphosphate production and superoxide generation elicited by farnesylthiosalicylate were partially blocked by treatment of the cells with pertussis toxin, consistent with participation of pertussis-toxin-sensitive and pertussis-toxin-resistant elements. In HL60 cells, farnesylthiosalicylate (< or = 20 microM) did not activate NADPH oxidase but dose-dependently augmented PMA-elicited activity of the enzyme. This effect was resistant to pertussis-toxin treatment. In vitro augmentation of PKC-mediated phosphorylation of histone and cytosolic p47-phox by farnesylthiosalicylate and the finding that downregulation of PKC abrogated potentiation of NADPH oxidase activity by farnesylthiosalicylate were compatible with the involvement of PKC in the response of HL60 cells to farnesylthiosalicylate. It is suggested that the effects of farnesylthiosalicylate on myeloid cells reflect interaction of the analog with prenylcysteine-docking sites on cellular signaling elements.     

Multidrug-resistant tuberculosis. 5. Human immunodeficiency virus infection and multidrug-resistant tuberculosis

Outbreaks of multidrug-resistant tuberculosis (MDR-TB) among human immunodeficiency virus (HIV)-infected persons reported in the United States were very serious and the risks were increased by the delay of diagnosis, rapid progression from infection to active disease, inadequate therapy and poor tuberculosis (TB) control. Prevalence of drug-resistant TB among HIV-infected patients in Japan was studied. The results of drug susceptibility were collected through the nationwide working group for a survey of HIV-infected TB. Data of susceptibility for 39 cases were obtained. The isolates of two cases were resistant to isoniazid and rifampicin (including clinical failure of response), although no outbreak of MDR-TB was found in Japan. Case study of a patient who developed MDR-TB revealed that drug resistance might be selected by insufficient anti-TB therapy. The rate of resistance to any of the anti-TB drugs in HIV-infected patients seemed to be high, although strictly evaluation was difficult due to no standardization for drug susceptibility testing. Of 9 cases with resistance to any of the anti-TB drugs, 8 had extrapulmonary TB including 5 cases of disseminated TB. In contrast thirteen of 30 cases without drug resistance had extrapulmonary TB. Since it has been reported that HIV infection is related to increased rates of drug resistance of TB bacilli, treatment with four-drug regimen should be started and sufficient courses of therapy are needed in HIV-infected TB patients.     

Resistant Mycobacterium tuberculosis: its relation with coinfection with human immunodeficiency virus. 5-year study

BACKGROUND: To analyze the situation of resistance to antituberculous drugs among strains of Mycobacterium tuberculosis recovered in our environment during a five-year period and its relationship with HIV co-infection. PATIENTS AND METHODS: Review of the Mycobacterium tuberculosis strains recovered from patients aged older than 14 years in Hospital Joan March from 1992 to 1996 of which a susceptibility testing study by means of the multiple proportions method was available. The initial or secondary resistance was considered according to the previous antituberculosis treatment antecedent. RESULTS: The susceptibility testing was available from 179 cases (136 males and 43 females) out of a total of 214. The overall resistance rate to any of the tested drugs was 10.1% (18 cases) with a 4% (6 cases) of initial and 38.7% (12 cases) secondary resistances. Co-infection with HIV showed not to be a risk factor for the development of resistance. No significant increase was observed analyzing the temporal trend through the five years studied. CONCLUSIONS: At present, the situation of resistance to Mycobacterium tuberculosis seems not to be alarming in our environment. Co-infection with HIV has not been shown to be associated with an increase in resistance rates.     

Neopterin and human immunodeficiency virus infection

We report a 53-year-old female autopsy case of multiple sclerosis with bilateral continuous cystic lesions along the lateral ventricles and caudate-callosal angles (Wetterwinkel). The pathophysiological mechanisms underlying these peculiar huge cystic lesions can be explained by the appearance of necrotic tissue during the recurrent relapsing stages of the disease, and then, by the absorption and scavenging of activated microglias. Poor astrocytic gliosis, which might be an effect of frequent use of corticosteroids during the clinical course makes the cavities bigger.     

The clinical characteristics of pleural tuberculosis in patients with and without human immunodeficiency virus infection

OBJECTIVE: To determine whether or not there are differences in the characteristics of pleural tuberculosis (PT) related to whether patients are or are not infected by human immunodeficiency virus (HIV). METHODS: We conducted a retrospective study of the medical histories of patients diagnosed of PT in our hospital between 1986 and 1993. RESULTS: We found no significant differences in the proportions of tuberculosis patients with or without HIV infection (8% versus 11%) who were diagnosed of PT. Of the 119 patients diagnosed of PT, 10% were also HIV positive. The HIV patients had more serious forms of PT, and among them there was a higher incidence of pleural discharge, more isolations of Mycobacterium tuberculosis in sputum and pleural fluid (42% and 45% versus 13% and 15%, p < 0.05), and more deaths before end of treatment (17% versus 1%, p < 0.05). The HIV patients had a lower rate of positive results in Mantoux's intradermal reaction test (17% versus 67%, p < 0.01), however, and fewer positive results for pleural biopsy (36% versus 84% positivity for granulomas, p < 0.01). CONCLUSIONS: The frequency of PT was similar for subjects with and without HIV infection in our study. In patients with both HIV and PT pleural fluid and sputum cultures are more useful diagnostic tools than pleural biopsy, and the former tests should therefore be stressed.     

Immunopathogenesis of human immunodeficiency virus

Human immunodeficiency virus (HIV) types 1 and 2 infect cells of the immune system and initiate a robust immune response which counteracts the viral spread but also accelerates the destruction of the immune system. Many pathogenic mechanisms have been proposed which include viral gene products, syncytium formation, direct virus killing of cells, apoptosis, autoimmunity, cytokine and chemokine expression, superantigens, virus directed cell-mediated cytolysis, and disruption of the lymphoid architecture. At present, there is no unifying theory or experimental proof of a single or a predominant mechanism for the pathogenesis of the HIV disease. This review is intended to highlight areas of HIV research relevant to the understanding of HIV immunopathogenesis.     

Virulence of human immunodeficiency virus

Virulence is relative capacity of a virus, compared to other closely related viruses, to produce disease in a host. Viral strains considered as virulent have been described in HIV-1 infected patients. They are characterized in vitro by enhanced cellular host range, rapid kinetic of replication and increased capacity of syncytium induction. Some genetic modification of the V3 loop in the envelope gene have been associated with the emergence of these strains. But at AIDS diagnosis, and even at the terminal stage of AIDS, only about half of the patients harbour syncytium inducing variants. There are much evidence for continuous viral replication throughout all stages of HIV-1 infection. There is no viral latency state in the natural HIV infection. This increasing viral burden might have a pivotal role in the pathogenesis of HIV disease. HIV-2 is less pathogenic than HIV-1. The nature of the viral determinants responsible for this reduced virulence remains unknown. In the simian immunodeficiency virus model, virulent and avirulent strains have been described and the nef gene seems to have a critical role in pathogenicity.     

Surrogate marker of preclinical tuberculosis in human immunodeficiency virus infection: antibodies to an 88-kDa secreted antigen of Mycobacterium tuberculosis

Antibodies to purified, size-fractionated secreted proteins of Mycobacterium tuberculosis in sera from patients with human immunodeficiency virus (HIV) infection and active tuberculosis (HIV/TB patients), and in stored sera obtained from the same patients prior to clinical manifestation of TB, were evaluated by ELISA, and the repertoire of antigens recognized was analyzed by immunoblotting. Compared with non-HIV/TB patients, HIV/TB patients had lower levels of anti-mycobacterial antibodies, and these were directed toward a restricted set of antigens. Antibodies to an 88-kDa secreted antigen were present in the sera of 74% of HIV/TB patients during the years (1.5-6) prior to manifestation of active, clinical tuberculosis, although only 66% were positive by the time tuberculosis was diagnosed. The presence of antibodies to the 88-kDa antigen can serve as a surrogate marker for identifying HIV-infected persons with active, subclinical disease who are at a high risk of developing clinical tuberculosis.     

Ultrastructure and morphogenesis of human immunodeficiency virus

The ultrastructure and morphogenesis of human immunodeficiency virus (HIV) were elucidated by observation with several techniques including immunoelectron microscopy and cryo-microscopy. The virus particle consists of an envelope, a core and matrix. The virus particles were observed extracellularly as having one of three profiles: (1) a centric or an eccentric electron-dense core, (2) rod-shaped electron-dense core, and (3) doughnut-shaped. HIV-1 particles in the hydrated state were observed by high resolution electron cryo-microscopy to be globular, and the lipid membrane was clearly resolved as a bilayer. Many projections around the circumference were seen to be knob-like. The shapes and sizes of the projections, especially head parts, were found to vary in each projection. By isolation with Nonidet P40 and glutaraldehyde, HIV-1 cores were confirmed to consist of p24 protein by immunogold labeling. When the virus enters the cell, two entry modes were found: membrane fusion and endocytosis. No structures resembling virus particles could be seen in the cytoplasm after viral entry. In HIV-1-infected cells, positive reactions by immuno-labeling suggest that HIV-1 Gag may be produced in membrane-bound structures and transported to the cell surface by cytoskeletons. Then a crescent electron-dense layer was first formed underneath the cell membrane. Finally, the virus particle was released from the cell surface. Several cell clones producing defective particles were isolated from MT-4/HIV-1 cells. Among them, doughnut-shaped or teardrop-shaped particles were seen to be produced in the extracellular space. In the doughnut-shaped particles, Gag p17 and p24 proteins faced each other against the inner electron dense ring, suggesting that the inner ring consists of a precursor Gag protein.