Leprosy and HIV coinfection: a critical approach

An increase in leprosy among HIV patients, similar to that observed in patients with TB, was expected approximately 20 years ago. Studies conducted in the 1990s together with those reported recently seemed to indicate that a coinfection with HIV did not alter the incidence and the clinical spectrum of leprosy and that each disease progressed as a single infection. By contrast, in countries with a high seroprevalence of HIV, TB was noted to increase. Explanations may be provided by the differences in the incubation time, the biology and toxicity of Mycobacterium leprae and Mycobacterium tuberculosis. After the introduction of HAART the leprosy–HIV coinfection manifested itself as an immune reconstitution inflammatory syndrome (IRIS), typically as paucibacillary leprosy with type 1 leprosy reaction. The incidence of leprosy in HIV-infected patients has never been properly investigated. IRIS-leprosy is probably underestimated and recent data showed that the incidence of leprosy in HIV patients under HAART was higher than previously thought.     

Risk Stratification for Dissemination of Tuberculosis in HIV-Infected Patients

The location of tuberculosis (TB) early in the course of HIV-inducedimmunosuppression was located, and an attempt was made to determinethe correlation between the degree of immune suppression andprognostic variables to stratify the risk for disseminationof TB in HIV-infected patients. Clinical and laboratory characteristicswere reviewed in 73 HIV-infected patients with TB admitted between1984 and 1990. The presence of Mycobacterium tuberculosis wasinvestigated in different clinical samples to verify the diagnosticyield of different sources. TB was extrapulmonary in 46.6 per cent of patients in whom itwas their first opportunistic infection, and in 46.7 per centof patients with previously diagnosed AIDS (p = NS). TB wasfrequently associated with other opportunistic infections, particularlyoesophageal candidiasis (p = 0.006). Patients with localizedextrapulmonary or disseminated TB presented more often withcytopenias, hypoalbuminaemia and oral thrush. The existenceof extrapulmonary TB or another opportunistic coinfection allowedAIDS to be diagnosed in the same admission in 30 patients anda mean of 8.4 months later in another eight. Extrapulmonary TB was found to be as common in early HIV infectionas in patients with established AIDS. Haematological derangementswere common in these patients, and cytopenias, hypoalbuminaemiaand oral thrush were useful predictors of TB dissemination.The location of TB and its dissemination were not significantlylinked to a more advanced CDC stage of HIV infection or a moreprofound fall in CD4 count. Mycobacterium tuberculosis couldbe detected in sputum, bronchoalveolar lavage fluid, urine,lymph node aspirates, stool and blood samples, and investigationis worthwhile even in HIV-infected patients with clinicallylocalized TB     

Risk stratification for dissemination of tuberculosis in HIV-infected patients.

The location of tuberculosis (TB) early in the course of HIV-induced immunosuppression was located, and an attempt was made to determine the correlation between the degree of immune suppression and prognostic variables to stratify the risk for dissemination of TB in HIV-infected patients. Clinical and laboratory characteristics were reviewed in 73 HIV-infected patients with TB admitted between 1984 and 1990. The presence of Mycobacterium tuberculosis was investigated in different clinical samples to verify the diagnostic yield of different sources. TB was extrapulmonary in 46.6 per cent of patients in whom it was their first opportunistic infection, and in 46.7 per cent of patients with previously diagnosed AIDS (p = NS). TB was frequently associated with other opportunistic infections, particularly oesophageal candidiasis (p = 0.006). Patients with localized extrapulmonary or disseminated TB presented more often with cytopenias, hypoalbuminaemia and oral thrush. The existence of extrapulmonary TB or another opportunistic coinfection allowed AIDS to be diagnosed in the same admission in 30 patients and a mean of 8.4 months later in another eight. Extrapulmonary TB was found to be as common in early HIV infection as in patients with established AIDS. Haematological derangements were common in these patients, and cytopenias, hypoalbuminaemia and oral thrush were useful predictors of TB dissemination. The location of TB and its dissemination were not significantly linked to a more advanced CDC stage of HIV infection or a more profound fall in CD4 count.(ABSTRACT TRUNCATED AT 250 WORDS)     

HIV/AIDS患者合并活动性结核病的诊断及方法探讨

目的 在HIV/AIDS患者中筛查活动性结核(TB),并对TB/HIV双重感染患者的活动性rrB诊断方法进行探讨.方法 2006年8月至2007年3月调查南宁市和柳州市4家AIDS定点诊疗机构的660例HIV/AIDS患者,对CD+4T淋巴细胞计数≤350/mm3或至少有TB可疑症状之一的HIV/AIDS患者进行胸部x线平片、痰抗酸染色涂片和液体快速培养检查.结果 CD+4T淋巴细胞计数≤200个/mm3的患者占76.1%(502/660).HIV/AIDS患者合并活动性结核病的比例为22.9%(151/660),其中肺结核占74.8%(113/151),1/3的患者有肺外累及,肺外TB以淋巴TB为主,占68.1%.在痰涂片和胸部X线平片均不支持活动性TB的患者中培养阳性的占20.1%(53/264).在培养阳性的病例中38.5%(35/91)是非结核分枝杆菌感染.结论 本研究HIV/AIDS患者中合并活动性结核病的比例为22.8%.痰的快速培养在HIV/AIDS患者中诊断结核病中起至关重要的作用.HIV/MDS患者合并非结核分枝杆菌以及肺外TB比例不容忽视.     

Clinical characteristics of IRIS syndrome in patients with HIV and tuberculosis

BACKGROUND: Some patients with HIV/tuberculosis (TB) coinfection who are on anti-TB treatment and highly active antiretroviral therapy (HAART) will develop an exacerbation of symptoms, signs or radiological manifestations of TB that are not due to relapse or recurrence of their TB. The aetiology of these immune reconstitution inflammatory syndrome (IRIS) reactions is unknown but it is presumed that they occur, at least in part, as a consequence of HAART-related reconstitution of immunity. METHODS: Patients who were diagnosed with their first episode of definitive or presumed TB between January 2001 and July 2003 were identified from the Chelsea and Westminster TB/HIV database. The patients were classified into those who developed IRIS and those who did not using a set definition of the syndrome. Demographic, clinical and laboratory data relating to both HIV and TB were compared between the two groups. RESULTS: A total of 55 cases of TB were identified, of which 45 cases were confirmed on culture or gene probe and 10 were presumed cases. Fourteen cases (25.5%) developed IRIS with a median (range) duration of 2.53 (0.53-14.97) months. The median baseline CD4 [interquartile range (IQR)] for the IRIS group was significantly lower at 80 (33-117) cells/mm3 (P = 0.05) than the non-IRIS group at 139 (77-284) cells/mm3. A significantly greater proportion of patients in the IRIS group [11/14 (78.60%), P = 0.011] had baseline CD4 < 100cells/mm3 compared with the non-IRIS group [16/41 (39.0%)]. There was no significant difference between the two groups when comparing the log10 baseline viral load (VL). Eight (57.0%) patients in the IRIS group had disseminated TB at baseline compared with seven (17.0%) in the non-IRIS group (P = 0.006). In those who had a detectable VL at baseline, the median fold change (IQR) in CD4 from baseline to 3 months was significantly higher in the IRIS group patients, 1.5 (0.6-5.6), compared with 0.7 (-0.2 to 1.0) for those in the non-IRIS group (P = 0.046). CONCLUSIONS: Patients who develop IRIS are more likely to present with disseminated TB, have a CD4 count < 100 cells/mm3 and have a prompt rise in CD4 count in the initial 3 months of HAART.     

艾滋病病毒感染者和艾滋病患者中结核病筛查结果分析

目的为掌握艾滋病病毒感染者和艾滋病患者中结核病的患病情况及发病趋势,以便对结核病和艾滋病双重感染者开展积极防治。方法对上蔡县登记在册的HIV/AIDS人群进行症状询问、胸部拍片、痰涂片试验和痰培养。结果应检对象6100人,实检5863人,受检率为96.1%。发现活动性肺结核28例,肺结核患病率为477.6/10万;其中男性检出率为793.6/10万,女性检出率为193.5/10万,经!2检验差异有统计学意义。30、40岁年龄组检出率最高,占总检出人数的78.6%。痰涂片阳性13例,涂阳患病率为221.0/10万。结论HIV/AIDS人群是感染结核病的高危人群,应定期进行结核病筛查,做到早期发现,早期治疗;加强对该人群的结核病预防宣传教育。     

Response to HAART and GB virus type C coinfection in a cohort of antiretroviral-naive HIV-infected individuals

The prognostic role of GB virus type C (GBV-C) viraemia in HIV-infected subjects treated with highly active antiretroviral therapy (HAART) is still undefined. The aim of this analysis is to assess the relationship between GBV-C infection and response to antiretroviral therapy among HIV-infected subjects initiating HAART when antiretroviral-naive. A prospective, observational study of 400 HIV-infected patients with measurements of GBV-C RNA, hepatitis C virus (HCV) antibodies and HCV RNA determined from plasma stored prior to HAART initiation. Time to virological (achieving HIV RNA < or =500 copies/ml) and immunological success (a CD4+ count increase of > or =200 cells/microl), and the time to virological relapse (confirmed HIV RNA >500 copies/ml) were assessed by Kaplan-Meier methods and Cox proportional hazard regression model. Of the subjects, 117 (29.3%) were GBV-C positive and, overall, 351 (87.8%) patients achieved virological success. After controlling for a number of confounders including HCV RNA, GBV-C viraemic patients experienced a significantly lower risk of HIV rebound than those who were GBV-C negative [relative hazard (RH)=0.56, 95% CI: 0.34-0.93, P=0.03]. Conversely, the probability of achieving initial virological success or CD4+ count response after HAART did not differ between GBV-C-negative and -positive subjects. These results suggest that GBV-C coinfection may play a role in determining the rate of HIV rebound possibly by competing with HIV replication after HIV load has been successfully suppressed by HAART.     

No implication of HIV coinfection on the plasma exposure to rifampicin,pyrazinamide, and ethambutol in tuberculosis patients

There are contrasting findings regarding the effect of HIV on the pharmacokinetics of first‐line anti‐tubercular drugs (FLATDs) due to a lack of prospective controlled clinical studies, including patients with tuberculosis (TB) and patients with TB living with HIV. This study aims to assess the effect of HIV coinfection and antiviral therapy on the plasma exposure to FLATDs in patients with TB. HIV negative (TB‐HIV− group; n = 15) and HIV positive (TB‐HIV+ group; n = 18) adult patients with TB were enrolled during the second month of FLATDs treatment. All TB‐HIV+ patients were on treatment with lamivudine, tenofovir (or zidovudine), and raltegravir (or efavirenz). Serial blood sampling was collected over 24 h and FLATDs pharmacokinetic parameters were evaluated using noncompartmental methods. In the TB‐HIV+ patients, dose‐normalized plasma exposure area under the curve from zero to 24 h (nAUC_0–24; geometric mean and 95% confidence interval [CI]) values at steady‐state to rifampicin, pyrazinamide, and ethambutol were 18.38 (95% CI 13.74–24.59), 238.21 (95% CI 191.09–296.95), and 18.33 (95% CI 14.56–23.09) µg∙h/ml, respectively. Similar plasma exposure was found in the TB‐HIV− patients. The geometric mean and 90% CI of the ratios between TB‐HIV− and TB‐HIV+ groups suggest no significant pharmacokinetic interaction between the selected antivirals and FLATDs. Likewise, HIV coinfection itself does not appear to have any effect on the plasma exposure to FLATDs.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

First‐line anti‐tubercular drugs (FLATDs) plasma exposure is an important variable of tuberculosis (TB) outcome; however, there are contrasting findings regarding the effect of HIV on the pharmacokinetics of FLATDs due to a lack of prospective controlled clinical studies, including HIV positive and HIV negative patients with TB.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study evaluates the effect of HIV coinfection on the pharmacokinetics of rifampicin, pyrazinamide, and ethambutol in patients who are on stable therapy in the second month of FLATDs treatment.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study shows no evidence that the pharmacokinetics of rifampicin, pyrazinamide, and ethambutol in patients with TB are affected by HIV coinfection or by any of the standard of care HIV comedications allowed in the study (lamivudine, zidovudine, tenofovir, efavirenz, or raltegravir).

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

HIV coinfection does not require dose adjustment of rifampicin, pyrazinamide, and ethambutol in patients with TB.     

Osteoarticular manifestations of Mycobacterium tuberculosis infection

Mycobacterium tuberculosis has affected humans for much of our existence. The incidence of global tuberculosis infection continues to rise, especially in concert with HIV coinfection. Many disease processes, such as diabetes, increase the likelihood of tuberculosis infection. Tuberculosis bacteria can infect any bone, joint, tendon, or bursa; however, the most common musculoskeletal site for infection includes the spine and weight-bearing joints of the hip and knee. Many patients who present with osteoarticular tuberculosis infection will have a gradual onset of pain at the site of infection. Many patients who develop a musculoskeletal tuberculosis infection will have no evidence of a pulmonary tuberculosis infection on x-ray film and many will have very mild symptoms with the initial infection. Healthcare providers must remember that many patients who develop tuberculosis infection do not progress to active tuberculosis disease; however, the latent infection may become active with immune compromise.     

Tuberculosis and HIV disease: Two decades of a dual epidemic

The HIV epidemic is currently in its third decade without any sign of abating. Tuberculosis (TB) is responsible for a third of all AIDS deaths, 99% of which occur in developing countries. The two epidemics fuel each other, together making up the leading infectious causes of mortality worldwide. Tuberculosis-HIV coinfection presents special diagnostic and therapeutic challenges and constitutes an immense burden on the health care systems of heavily infected countries. Despite major gains that have been made in the past two decades, important questions still remain. To cope with the challenge of TB-HIV coinfection, further research in the design of diagnostic tests for tuberculosis, detection of drug resistant Mycobacterium tuberculosis strains in HIV-positive people, as well as development of more effective therapeutic agents and vaccines are urgently needed. It has become evident that this dual epidemic will persist unless comprehensive measures are instituted through the provision of sufficient funding in addition to expanding and strengthening current control strategies adopted by governments and international organizations.     

Effect of antiretroviral therapy in thromboregulation through the hydrolysis of adenine nucleotides in platelets of HIV patients

The human immunodeficiency virus (HIV) infection results in biochemical and vascular dysfunctions. The highly active antiretroviral therapy (HAART) markedly reduces mortality and opportunistic diseases associated with acquired immunodeficiency syndrome (AIDS). This increased survival time predisposes the development of cardiovascular diseases. Platelets present purinergic system ectoenzymes such as E-NTPDase, E-5′-nucleotidase and E-ADA on its surface. In view of this, the aim of this study was to evaluate the activity of these ectoenzymes in platelets as well as the platelet aggregation and lipid profile of patients with HIV infection and also patients receiving HAART. The results showed an increase in the E-NTPDase activity for ATP hydrolysis in the HIV group compared with the control group and the HIV/HAART group. When assessing the activity E-NTPDase hydrolysis to ADP, the results revealed an increase in activity in the HIV group when compared to the control group, and a decrease in activity when in the HIV/HAART group when compared to the control and HIV groups. The activity of E-5′-nucleotidase revealed an increase in AMP hydrolysis in the HIV group, as the results from control and HIV/HAART groups showed no statistical difference. Regarding the E-ADA activity, the HIV and HIV/HAART groups revealed a decreased deamination of adenosine when compared with the control group. Furthermore, we observed an increased platelet aggregation of HIV/HAART group compared with the control group. Thus, our results suggest that antiretroviral treatment against HIV has a significant effect on the activity of purinergic system ectoenzymes demonstrating that thromboregulation is involved in the process.     

HIV合并结核分枝杆菌感染的探索研究

目的 了解该地区HIV合并结核分枝杆菌(TB)感染的发展状况.方法 随机选取2008年1月至2010年12月在该院检查并接受治疗的177例HIV感染者作为调查对象,统计这些病例中感染TB的例数,分析该地区HIV感染者合并TB感染的百分率,并进行TB药敏分析.结果 在177例HIV感染患者中有29例患者合并感染TB,占16.38%,其中男21例,占72.41%(21/29),女8例,占27.59%(8/29),差异有统计学意义(P<0.01).而在29例HIV合并TB感染患者中,TB对利福平、乙胺丁醇、链霉素、异烟肼的敏感性分别为100.00%、100.00%、89.65%、75.86%.结论 HIV合并TB感染是HIV患者死亡的最重要因素,在临床中应加强检测并合理使用抗菌药物和抗病毒药物,以减少HIV感染者的病死率.     

Human immunodeficiency virus infection, Part II

The acceptance of highly active antiretroviral therapy (HAART) among patients and health care providers has had a dramatic impact on the epidemiology and clinical characteristics of many opportunistic infections associated with human immunodeficiency virus (HIV). Previously intractable opportunistic infections and syndromes are now far less common. In addition, effective antibiotic prophylactic therapies have had a profound impact on the risk of patients developing particular infections and on the incidence of these infections overall. Most notable among these are Pneumocystis carinii, disseminated Mycobacterium avium complex, tuberculosis, and toxoplasmosis. Nevertheless, infections continue to cause significant morbidity and mortality among patients who are infected with HIVThe role of HAART in many clinical situations is unquestioned. Compelling data from clinical trials support the use of these therapies during pregnancy to prevent perinatal transmission of HIV HAART is also recommended for health care workers who have had a ‘significant’ exposure to the blood of an HIV infected patient. Both of these situations are discussed in detail in this article. In addition, although more controversial, increasing evidence supports the use of HAART during the acute HIV seroconversion syndrome. An “umnune reconstitution syndrome” has been newly described for patients in the early phases of treatment with HAART who develop tuberculosis, M avium complex, and cytomegalovirus disease.Accumulating data support the use of hydroxyurea, an agent with a long history in the field of myeloproliferative disorders, for the treatment of HIV Newer agents, particularly abacavir and adefovir dipivoxil, are available through expanded access protocols, and their roles are being defined and clarified.     

Incidence of and risk factors for insulin resistance in treatment-naive HIV-infected patients 48 weeks after starting highly active antiretroviral therapy

OBJECTIVES: to assess the incidence and risk factors for insulin resistance (IR) in a cohort of naive HIV-infected patients 48 weeks after starting highly active antiretroviral therapy (HAART). DESIGN: prospective, two centre, observational, cohort study. METHODS: One-hundred and thirty-seven patients who started HAART and maintained the same regimen for 48 weeks were included. IR was determined by the homeostasis model assessment (HOMA-IR) method. Individuals with a HOMA-IR value >3.8 were defined as insulin resistant. Independent associations with the development of IR at 48 weeks were evaluated. RESULTS: Seventeen (12.4%) individuals showed a HOMA-IR value >3.8 at baseline and were excluded for incidence analyses. Fifteen patients developed IR at 48 weeks of HAART, giving an incidence of 13%. Independent predictors of the development or IR were indinavir exposure (beta-coefficient 5.45, 95% confidence interval [CI] 1.30-22.8; P=0.02), and hepatitis C virus (HCV) antibody positivity (beta-coefficient 5.22, 95% CI 1.34-20.33; P=0.01). The appearance of IR was associated with a higher BMI (beta-coefficient 1.72 for each 2 kg/m2 increase, 95% CI 1.54-1.94; P=0.02) and with the presence of lipodystrophy at 48 weeks (beta-coefficient 5.59, 95% CI 1.45-21.5; P=0.01). CONCLUSIONS: HAART induces the development of IR in previously naive non-insulin-resistant HIV-infected individuals, with an incidence of 13% in the first year of therapy. Indinavir exposure, and HCV coinfection are associated with an increased risk of developing IR.     

Mycobacterium avium complex infection in HIV/AIDS patients

Disseminated Mycobacterium avium complex (MAC) infection is a severe complication of advanced HIV/AIDS disease. Disseminated infection due to MAC appeared later in the natural history of HIV disease and was an independent predictor of mortality in patients before the extended use of highly active antiretroviral therapy (HAART). The use of combination schemes, including three or four antimicrobial agents followed by secondary prophylaxis and HAARTs, improved the survival and reduced mortality rates. However, subjects who ignore their serological status for HIV, or who are not receiving or do not tolerate HAART, are at high risk of developing disseminated MAC disease. In addition, patients who show a good immunological and virological response to HAART can develop episodes of immune reconstitution inflammatory syndrome associated with MAC, including supurative lymphadenitis and subcutaneous or soft-tissue abscesses. In this article, we describe the epidemiological, clinical, immunological, therapeutic and preventive aspects of MAC infection in HIV-seropositive patients in the pre- and post-HAART era.     

Myocardial disease in human immunodeficiency virus (HIV) infection: a review

Heart muscle disease is the most important cardiovascular manifestation of HIV infection and is likely to become even more prevalent as HIV infected patients live longer. This may present as myocarditis, dilated cardiomyopathy or isolated left or right ventricular dysfunction. Myocardial involvement in HIV infection is multifactorial and may arise as a result of myocardial invasion with HIV itself, opportunistic infections, viral infections, autoimmune response to viral infection, drug-related cardiac toxicity, nutritional deficiencies, and prolonged immunosuppression. Both adults and children are affected with severity ranging from incidental microscopic inflammatory findings at autopsy to clinically significant cardiac disease with chronic cardiac dysfunction. It is associated with a poor prognosis, and results in symptomatic heart failure in up to 5% of HIV patients. Clinical pathological studies from the pre-HAART era show a 30% prevalence of cardiomyopathy in patients with AIDS. The introduction of highly active antiretroviral therapy (HAART) regimens has substantially modified the course of HIV disease by lengthening survival and improving quality of life of HIV-infected patients. There is also good evidence that HAART significantly reduces the incidence of cardiovascular manifestations of HIV infection. By preventing opportunistic infections and reducing the incidence of myocarditis, HAART regimens have reduced the prevalence of HIV-associated cardiomyopathy by almost 7-fold from the pre-HAART era. HAART is however only available to a minority of HIV infected individuals in most areas of the world and studies from the pre-HAART period still apply. In this review, the aetiopathogenesis and presentation of HIV related myocardial disease were reviewed and measures taken to improve survival discussed.     

Epidemiological and clinical features of 139 patients with tuberculosis at a teaching hospital in Italy (Pisa, 1996-2000).

In order to describe epidemiologic and clinical features of patients with tuberculosis (TB) identified recently in the hospital of Pisa (Tuscany, Italy), a retrospective study of all cases of TB notified to the Local Public Health Service during January 1996-December 2000 was performed. The diagnosis of TB was made following the criteria of the WHO. A total of 139 patients affected by TB were identified. Diagnosis was microbiologically proved in 81 patients. Mean age was 53.8+/-20.5 S.D. yrs. Thirty-five (25.2%) patients were extra European community citizens (mostly from Africa). The incidence of TB (N/100.000) was 8.4 in 1996 and 6.8 in 2000. Sixty-eight point three per cent of patients had pulmonary TB, 24.5% extrapulmonary and 7.2% mixed TB. The rate of extrapulmonary TB was 15.9% and 39.2% in the 1996-98 and in the 1999-2000 periods, respectively (p = 0.002). Extrapulmonary TB was more frequent in extra European community citizens (42.8%) than in Italian ones (18.3%), p = 0.003. Seven patients were presenting also advanced HIV infection. Microscopic examination for acid fast bacilli in sputum or bronchial secretion resulted negative in 17.4% of proved pulmonary TB (positive culture for Mycobacterium tuberculosis). The chest x-rays showed pleural effusion in 19 patients. Pulmonary cavitation was documented in 15 patients with negative chest x-rays. Fever was not present in 42.4% of the patients at the moment of diagnosis. Three point eight percent of the isolated strains of M. tuberculosis were in vitro multidrug-resistant. The data presented showed an important rate of TB in Pisa. We have yet to understand if the decreased rate observed in 2000 represents a new trend as reported in other North American and European countries. The rate of extrapulmonary TB shows a trend to increase accordingly to recent literature. The isolation rate of multidrug-resistant strains of M. tuberculosis in Pisa seems to be similar to the rates reported in other areas of Europe.     

News in Brief

Disseminated Mycobacterium avium complex (MAC) infection is a severe complication of advanced HIV/AIDS disease. Disseminated infection due to MAC appeared later in the natural history of HIV disease and was an independent predictor of mortality in patients before the extended use of highly active antiretroviral therapy (HAART). The use of combination schemes, including three or four antimicrobial agents followed by secondary prophylaxis and HAARTs, improved the survival and reduced mortality rates. However, subjects who ignore their serological status for HIV, or who are not receiving or do not tolerate HAART, are at high risk of developing disseminated MAC disease. In addition, patients who show a good immunological and virological response to HAART can develop episodes of immune reconstitution inflammatory syndrome associated with MAC, including supurative lymphadenitis and subcutaneous or soft-tissue abscesses. In this article, we describe the epidemiological, clinical, immunological, therapeutic and preventive aspects of MAC infection in HIV-seropositive patients in the pre- and post-HAART era.     

Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis

Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1–expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1–expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB.