Management of tuberculosis and latent tuberculosis infection in human immunodeficiency virus‐infected persons

The syndemic of human immunodeficiency virus (HIV)/tuberculosis (TB) co‐infection has grown as a result of the considerable sociogeographic overlaps between the two epidemics. The situation is particularly worrisome in countries with high or intermediate TB burden against the background of a variable HIV epidemic state. Early diagnosis of TB disease in an HIV‐infected person is paramount but suffers from lack of sensitive and specific diagnostic tools. Enhanced symptom screening is currently advocated, and the wide application of affordable molecular diagnostics is urgently needed. Treatment of TB/HIV co‐infection involves the concurrent use of standard antiretrovirals and antimycobacterials during which harmful drug interaction may occur. The pharmacokinetic interaction between rifamycin and antiretrovirals is a case in point, requiring dosage adjustment and preferential use of rifabutin, if available. Early initiation of antiretroviral therapy is indicated, preferably at 2 weeks after starting TB treatment for patients with a CD4 of <50 cells/μL. Development of TB‐immune reconstitution inflammatory syndrome (TB‐IRIS) is however more frequent with early antiretroviral therapy. The diagnosis of TB‐IRIS is another clinical challenge, and cautious use of corticosteroids is suggested to improve clinical outcome. As a preventive measure against active TB disease, the screening for latent TB infection should be widely practiced, followed by at least 6–9 months of isoniazid treatment. To date tuberculin skin test remains the only diagnostic tool in high TB burden countries. The role of alternative tests, for example, interferon‐γ release assay, would need to be better defined for clinical application.     

Measures of site resourcing predict virologic suppression,immunologic response and HIV disease progression following highly active antiretroviral therapy (HAART) in the TREAT Asia HIV Observational Database (TAHOD)

Objectives

Surrogate markers of HIV disease progression are HIV RNA in plasma viral load (VL) and CD4 cell count (immune function). Despite improved international access to antiretrovirals, surrogate marker diagnostics are not routinely available in resource‐limited settings. Therefore, the objective was to assess effects of economic and diagnostic resourcing on patient treatment outcomes.

Methods

Analyses were based on 2333 patients initiating highly active antiretroviral therapy (HAART) from 2000 onwards. Sites were categorized by World Bank country income criteria (high/low) and annual frequency of VL (≥3, 1–2 or <1) or CD4 (≥3 or <3) testing. Endpoints were time to AIDS/death and change in CD4 cell count and VL suppression (<400 HIV‐1 RNA copies/mL) at 12 months. Demographics, Centers for Disease Control and Prevention (CDC) classification, baseline VL/CD4 cell counts, hepatitis B/C coinfections and HAART regimen were covariates. Time to AIDS/death was analysed by proportional hazards models. CD4 and VL endpoints were analysed using linear and logistic regression, respectively.

Results

Increased disease progression was associated with site‐reported VL testing less than once per year [hazard ratio (HR)=1.4; P=0.032], severely symptomatic HIV infection (HR=1.4; P=0.003) and hepatitis C virus coinfection (HR=1.8; P=0.011). A total of 1120 patients (48.2%) had change in CD4 cell count data. Smaller increases were associated with older age (P<0.001) and ‘Other’ HIV source exposures, including injecting drug use and blood products (P=0.043). A total of 785 patients (33.7%) contributed to the VL suppression analyses. Patients from sites with VL testing less than once per year [odds ratio (OR)=0.30; P<0.001] and reporting ‘Other’ HIV exposures experienced reduced suppression (OR=0.28; P<0.001).

Conclusion

Low measures of site resourcing were associated with less favourable patient outcomes, including a 35% increase in disease progression in patients from sites with VL testing less than once per year.     

Clinical,hematological, and biochemical features of Hb SC disease

Twenty-seven patients were seen and followed at our Sickle Cell Center over a period of seven years. Their clinical, hematological, and biochemical features were determined and compared to those of patients with sickle cell anemia who were concurrently investigated. The data indicate that the mild anemia of hemoglobin (Hb) SC disease is slightly microcytic and hyperchromatic. Parameters of hemolysis and the complications of chronic hemolytic anemia (cholelithiasis, leg ulcers, hepatomegaly, and cardiomegaly) are milder in Hb SC disease than in sickle cell anemia. Asplenia and its sequelae (increased platelet count and reduced serum IgM levels) are less frequent in Hb SC disease. Cerebrovascular accidents and the decreased leukocyte alkaline phosphatase scores are similar in both diseases. Thromboembolic complications, retinopathy, and renal papillary necrosis are more frequent in Hb SC disease.     

Kostmann's syndrome

Kostmann's syndrome is a rare congenital disorder of neutrophil production due to impairment of myeloid differentiation in the bone marrow, with the neutrophil count being characteristically less than 500 x 10(3) cells/l (normal: 2-7 x 10(9)/l). Severe persistent neutropenia results in an increased susceptibility to frequent bacterial infections. The condition can be treated with recombinant human granulocyte colony-stimulating factor (G-CSF). Although several articles have addressed the clinicopathological and haematological aspects of this disorder, little or no information has been available concerning the radiological findings in this disorder. This report summarizes the clinical features, radiological findings and management of a patient with Kostmann's syndrome.     

Non-sporulating Chrysosporium: an opportunistic fungal infection in a neutropenic patient

We report a case of an invasive infection with non-sporulating Chrysosporium species in a patient who was treated with chemotherapy for relapsed acute lymphoblastic leukemia. This patient presented with a persistent lobar pneumonia, skin lesions, and possible involvement of the central nervous system. The patient responded to treatment with amphotericin B and oral itraconazole.     

Seroepidemiology of toxoplasmosis among HIV-infected patients and healthy blood donors

A cross-sectional study was carried out in University of Malaya Medical Centre, Kuala Lumpur. Blood samples from 100 HIV-infected patients and 203 Healthy Blood Donors (HBD) were collected and anti-Toxoplasma antibodies were detected by using conventional ELISA. The seroprevalence of toxoplasmosis in HIV/AIDS and Healthy Blood Donors were found to be 21% and 28.1% respectively. There was no significant association between the seroprevalence of toxoplasmosis and various possible risk factors i.e. contact with cat, consumption of undercooked meat and history of blood transfusion in both groups. No significant differences between Toxoplasma seroprevalence in HIV/AIDS and Healthy Blood Donors in association with presence of single or multiple risk factors were found. The mean CD4 count among HIV/AIDS patients in this study was 202.23 cell/cumm. There was no significant association between CD4 count and seropositivity for Toxoplasma antibodies in HIV/AIDS patients.     

Immunological profiles of immune restoration disease presenting as mycobacterial lymphadenitis and cryptococcal meningitis

OBJECTIVES: A proportion of HIV patients beginning antiretroviral therapy (ART) develop immune restoration disease (IRD). Immunological characteristics of IRD were investigated in a cohort of HIV patients beginning therapy in Kuala Lumpur, Malaysia. METHODS: Peripheral blood mononuclear cells were collected at weeks 0, 6, 12, 24 and 48 of ART from five patients experiencing IRD [two with cryptococcal and three with Mycobacterium tuberculosis (Mtb) disease], eight non-IRD controls who had begun ART with CD4 T-cell counts of <100 cells/microL and 17 healthy controls. Leukocytes producing interferon-gamma (IFNgamma) were quantified by enzyme-linked immunospot assay after stimulation with purified protein derivative (PPD), early secretory antigenic target-6 (ESAT-6), Cryptococcus neoformans or Cytomegalovirus antigens. Plasma immunoglobulin (IgG) antibodies reactive with these antigens were assessed by enzyme-linked immunosorbent assay. Proportions of activated (HLA-DR(hi)) and regulatory (CD25 CD127(lo) and CTLA-4(+)) CD4 T-cells were quantified by flow cytometry. RESULTS: Plasma HIV RNA declined and CD4 T-cell counts rose within 8-27 weeks on ART. Mtb IRD patients displayed elevated IFNgamma responses and/or plasma IgG to PPD, but none responded to ESAT-6. Cryptococcal IRD occurred in patients with low baseline CD4 T-cell counts and involved clear IFNgamma and antibody responses to cryptococcal antigen. Proportions of activated and regulatory CD4 T-cells declined on ART, but remained higher in patients than in healthy controls. At the time of IRD, proportions of activated CD4 T-cells and regulatory CD4 T-cells were generally elevated relative to other patients. CONCLUSIONS: Cryptococcal and Mtb IRD generally coincide with peaks in the proportion of activated T-cells, pathogen-specific IFNgamma responses and reactive plasma IgG. IRD does not reflect a paucity of regulatory CD4 T-cells.     

Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection

Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis.