Clinical forms and outcome of tuberculosis in HIV-infected patients in a tertiary hospital in São Paulo - Brazil

Klautau, Giselle Burlamaqui; Kuschnaroff, Tuba M

doi:10.1590/s1413-86702005000600004

Cited by 20 publications

(14 citation statements)

References 37 publications

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“…Consistent with the findings of earlier studies, male gender was associated with lower concentrations [20,21] as was low haemoglobin, which has previously been linked to poorer TB outcomes [22]. HIV coinfection may also be a factor; in a group of 34 coinfected patients receiving 600mg of rifampicin daily, where reported C max concentrations of < 8µg/ml occurred in 77% of cases and 35% of these concentrations were < 4µg/ml.…”

Section: Discussionsupporting

confidence: 84%

Low rifampicin concentrations in tuberculosis patients with HIV infection

Gengiah

Botha

Soowamber

et al. 2014

J Infect Dev Ctries

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Introduction: The efficacy of tuberculosis (TB) treatment in Human Immunodeficiency Syndrome (HIV) co-infected patients may be compromised by genetic and pharmacokinetic variation in drug disposition. Rifampicin is a critical component of TB treatment. We investigated the influence of drug transporter gene polymorphisms on rifampicin concentrations in TB-HIV co-infected patients in Durban, South Africa. Methodology: Rifampicin concentrations were measured 2.5 hours post-dose (approximated peak, C 2.5hr ) in patients receiving either 450mg or 600mg rifampicin, randomized to either integrated or sequential antiretroviral treatment. Patients were genotyped for SLCO1B1 (rs4149032) polymorphisms. A mixed effects regression model was fitted to assess the influence of various factors on rifampicin concentrations. TB recurrence rates were also estimated. Results: In 57 patients, median (IQR) C 2.5hr was 3.6 (2.8-5.0) µg/mL. Polymorphism frequency in the SLCO1B1 (rs4149032) drug transporter gene was high (0.76) and was associated with low median rifampicin C 2.5hr , 3.7 (2.8-5.0) µg/mL in the heterozygous and 3.4 (2.7-4.7) µg/mL in the homozygous variant carriers. Concentrations were also low in males (p < 0.0001) and those with low haemoglobin (p = 0.02). Although reinfection could not be distinguished from reactivation for the 43 patients followed post trial, the incidence of TB recurrence was 7.1 per 100 person-years. Of the eight patients in whom TB recurred, seven had the polymorphism. Conclusion: Approximated peak rifampicin concentrations were well below the recommended target range of 8 to 24 μg/mL in this patient population with its high frequency of the SLCO1B1 (rs4149032) polymorphism. Increased rifampicin dosage may be warranted in African, HIV-TB co-infected patients.

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Section: Discussionsupporting

confidence: 84%

Low rifampicin concentrations in tuberculosis patients with HIV infection

Gengiah

Botha

Soowamber

et al. 2014

J Infect Dev Ctries

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“…In a study from Brazil, the mean CD4 cell count of patients with extrapulmonary TB was 184/μL [21], but in our series the median was 49/μL. This could be a genuine biological difference or could be attributable to our patients having more advanced disease at presentation.…”

Section: Discussioncontrasting

confidence: 58%

“…Current HIV seroprevalence in Lusaka is probably close to the 2002 estimate of 22% such that a huge pool of at-risk persons is fuelling the epidemic of dual infection [19]. It has been known for many years that increasing immunodeficiency changes the clinical presentation so that extrapulmonary TB comes to dominate the clinical picture; abdominal TB is an important manifestation of extrapulmonary TB [20,21]. …”

Section: Discussionmentioning

confidence: 99%

Clinical and ultrasonographic features of abdominal tuberculosis in HIV positive adults in Zambia

et al. 2009

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BackgroundThe diagnosis of abdominal tuberculosis (TB) is difficult, especially so in health care facilities in developing countries where laparoscopy and colonoscopy are rarely available. There is little information on abdominal TB in HIV infection. We estimated the prevalence and clinical features of abdominal (excluding genitourinary) TB in HIV infected adults attending the University Teaching Hospital, Zambia.MethodsWe screened 5,609 medical inpatients, and those with fever, weight loss, and clinical features suggestive of abdominal pathology were evaluated further. A clinical algorithm was used to specify definitive investigations including laparoscopy or colonoscopy, with culture of biopsies and other samples.ResultsOf 140 HIV seropositive patients with these features, 31 patients underwent full evaluation and 22 (71%) had definite or probable abdominal TB. The commonest presenting abdominal features were ascites and persistent tenderness. The commonest ultrasound findings were ascites, para-aortic lymphadenopathy (over 1 cm in size), and hepatomegaly. Abdominal TB was associated with CD4 cell counts over a wide range though 76% had CD4 counts <100 cells/μL.ConclusionThe clinical manifestations of abdominal TB in our HIV-infected patients resembled the well-established pattern in HIV-uninfected adults. Patients with fever, weight loss, abdominal tenderness, abdominal lymphadenopathy, ascites and/or hepatomegaly in Zambia have a high probability of abdominal TB, irrespective of CD4 cell count.

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“…41 In addition, BM suppression is a known complication of mycobacterial diseases such as tuberculosis, in which IFN␥ signaling is high. 42 Given our findings in Irgm1 Ϫ/Ϫ mice, we speculate that the tight control of IFN signaling is as important for human HSCs as it is in the murine system. Whether the human homolog of Irgm1, IRGM, fulfills this function remains controversial.…”

Section: Irgm1 Negatively Regulates Ifn Signaling In Hscs 1531mentioning

confidence: 65%

Irgm1 protects hematopoietic stem cells by negative regulation of IFN signaling

King

Baldridge

Weksberg

et al. 2011

Blood

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The IFN-inducible immunity-related p47 GTPase Irgm1 has been linked to Crohn disease as well as susceptibility to tuberculosis. Previously we demonstrated that HSC quiescence and function are aberrant in mice lacking Irgm1. To investigate the molecular basis for these defects, we conducted microarray expression profiling of Irgm1-deficient HSCs. Cell-cycle and IFN-response genes are up-regulated in Irgm1(-/-) HSCs, consistent with dysregulated IFN signaling. To test the hypothesis that Irgm1 normally down-regulates IFN signaling in HSCs, we generated Irgm1(-/-)Ifngr1(-/-) and Irgm1(-/-)Stat1(-/-) double-knockout animals. Strikingly, hyperproliferation, self-renewal, and autophagy defects in Irgm1(-/-) HSCs were normalized in double-knockout animals. These defects were also abolished in Irgm1(-/-)Irgm3(-/-) double-knockout animals, indicating that Irgm1 may regulate Irgm3 activity. Furthermore, the number of HSCs was reduced in aged Irgm1(-/-) animals, suggesting that negative feedback inhibition of IFN signaling by Irgm1 is necessary to prevent hyperproliferation and depletion of the stem cell compartment. Collectively, our results indicate that Irgm1 is a powerful negative regulator of IFN-dependent stimulation in HSCs, with an essential role in preserving HSC number and function. The deleterious effects of excessive IFN signaling may explain how hematologic abnormalities arise in patients with inflammatory conditions.

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Clinical forms and outcome of tuberculosis in HIV-infected patients in a tertiary hospital in São Paulo - Brazil

Cited by 20 publications

References 37 publications

Low rifampicin concentrations in tuberculosis patients with HIV infection

Low rifampicin concentrations in tuberculosis patients with HIV infection

Clinical and ultrasonographic features of abdominal tuberculosis in HIV positive adults in Zambia

Irgm1 protects hematopoietic stem cells by negative regulation of IFN signaling

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