Epidemiological and clinical profile of HIV-infected patients from Southwestern Goias State, Brazil.

Knowledge about epidemiological distribution patterns of HIV infection in different geographic regions is relevant to understand the dynamics of the disease in Brazil. This study aims to characterize the epidemiological and clinical profile of HIV-infected patients from Southwestern Goias State, from 2005 to 2015. A standardized questionnaire was used to collect clinical-epidemiological, virological, and immunological data from the medical records of all HIV-infected patients (n=539) who were followed at the regional reference center of Jatai, Goias State, Brazil, from 2005 to 2015. We detected the prevalence of male patients and the heterosexual route of transmission, as well as an expressive number of young women infected with HIV. The HIV infection was more prevalent in reproductive ages (55.3%). Most patients presented clinical manifestations related to HIV infection at the time of diagnosis. Twenty-four patients presented coinfection with hepatitis C virus, syphilis, hepatitis B virus, leprosy or Chagas disease. Pneumonia caused by Pneumocystis jirovecii was the most common opportunistic infection, followed by neurotoxoplasmosis, tuberculosis, and neurocryptococcosis. Combined antiretroviral therapy improved CD4+ T-cell counts: the mean CD4+ T-cell counts after treatment was twice as high as those found at the first medical appointment; and highly active antiretroviral therapy promoted viral suppression in a significant number of patients. Considering the increasing distribution of HIV infection to the interior of Brazil, this descriptive study outlines the clinical-epidemiological characteristics of HIV infection in Southwestern Goias and contributes to develop local prevention strategies and public service plans.

The magnitude and risk factors of intestinal parasitic infection in relation to Human Immunodeficiency Virus infection and immune status, at ALERT Hospital, Addis Ababa, Ethiopia.

Human Immunodeficiency Virus (HIV) and intestinal parasitic infections are among the main health problems in developing countries like Ethiopia. Particularly, co-infections of these diseases would worsen the progression of HIV to Acquired Immunodeficiency Syndrome (AIDS). The purpose of this study was to determine the magnitude and risk factors for intestinal parasites in relation to HIV infection and immune status. The study was conducted in (1) HIV positive on antiretroviral therapy (ART) and (2) ART naïve HIV positive patients, and (3) HIV-negative individuals, at All African Leprosy and Tuberculosis (TB) Eradication and Rehabilitation Training Center (ALERT) hospital in Addis Ababa, Ethiopia. Study participants were interviewed using structured questionnaires to obtain socio-demographic characteristics and assess risk factors associated with intestinal parasitic infection. Intestinal parasites were identified from fecal samples by direct wet mount, formol ether concentration, and modified Ziehl-Neelsen staining techniques. The immune status was assessed by measuring whole blood CD4 T-cell count. The overall magnitude of intestinal parasite was 35.08%. This proportion was different among study groups with 39.2% (69/176), 38.83% (40/103) and 27.14% (38/140) in ART naïve HIV positives patients, in HIV negatives, and in HIV positive on ART patients respectively. HIV positive patients on ART had significantly lower magnitude of intestinal parasitic infection compared to HIV negative individuals. Intestinal helminths were significantly lower in HIV positive on ART and ART naïve patients than HIV negatives. Low monthly income, and being married, divorced or widowed were among the socio-demographic characteristics associated with intestinal parasitic infection. No association was observed between the magnitude of intestinal parasites and CD4 T-cell count. However, Cryptosporidium parvum, and Isospora belli were exclusively identified in individuals with CD4 T-cell count of ≤ 350 cells/mm(3). Regular provision of mass preventive chemotherapy and extended health education will curb the burden of intestinal parasitic infection in the community. Emphasis should also be given to laboratory diagnosis and identification of opportunistic intestinal parasites in patients with lower CD4-Tcell count.

Polymorphisms assessment in the promoter region of IL12RB2 in Amazon leprosy patients.

Leprosy displays a wide clinical spectrum that is dependent of the type of immune response. We investigate here whether polymorphisms in the promoter region of the IL12RB2 gene are associated with susceptibility or resistance to clinical forms of leprosy. Nucleotide sequencing of the promoter region of IL12RB2 encompassing SNPs -1035 A/G, -1033 T/C, -1023 A/G, -650 del/G and -464 A/G was performed on DNA samples from 105 leprosy patients and 108 healthy controls. However, none of the SNPs were associated with susceptibility to the disease or any of its clinical forms. Similarly, haplotype analysis did not show any association. The haplotype -1035A/-1033T/-650G/-464A was prevalent, and homozygosity for this haplotype was associated to a lower distribution of CD4(+) T cells (p=0.041). Our data suggest that polymorphisms present in the promoter region of IL12RB2 may not be associated with susceptibility to leprosy or its clinical forms.

No association of cryptococcal antigenemia with poor outcomes among antiretroviral therapy-experienced HIV-infected patients in Addis Ababa, Ethiopia.

INTRODUCTION: There are limited data on clinical outcomes of ART-experienced patients with cryptococcal antigenemia. We assessed clinical outcomes of a predominantly asymptomatic, ART-experienced cohort of HIV+ patients previously found to have a high (8.4%) prevalence of cryptococcal antigenemia. METHODS: The study took place at All Africa Leprosy, Tuberculosis and Rehabilitative Training Centre and Black Lion Hospital HIV Clinics in Addis Ababa, Ethiopia. A retrospective study design was used to perform 12-month follow-up of 367 mostly asymptomatic HIV-infected patients (CD4<200 cells/µl) with high levels of antiretroviral therapy use (74%) who were previously screened for cryptococcal antigenemia. Medical chart abstraction was performed approximately one year after initial screening to obtain data on clinic visit history, ART use, CD4 count, opportunistic infections, and patient outcome. We evaluated the association of cryptococcal antigenemia and a composite poor outcome of death and loss to follow-up using logistic regression. RESULTS: Overall, 323 (88%) patients were alive, 8 (2%) dead, and 36 (10%) lost to follow-up. Among the 31 patients with a positive cryptococcal antigen test (titers ≥1∶8) at baseline, 28 were alive (all titers ≤1∶512), 1 dead and 2 lost to follow-up (titers ≥1∶1024). In multivariate analysis, cryptococcal antigenemia was not predictive of a poor outcome (aOR = 1.3, 95% CI 0.3-4.8). A baseline CD4 count <100 cells/µl was associated with an increased risk of a poor outcome (aOR 3.0, 95% CI 1.4-6.7) while an increasing CD4 count (aOR 0.1, 95% CI 0.1-0.3) and receiving antiretroviral therapy at last follow-up visit (aOR 0.1, 95% CI 0.02-0.2) were associated with a reduced risk of a poor outcome. CONCLUSIONS: Unlike prior ART-naïve cohorts, we found that among persons receiving ART and with CD4 counts <200 cells/µl, asymptomatic cryptococcal antigenemia was not predictive of a poor outcome.

Histopathological study of cutaneous manifestations in HIV and AIDS patients.

OBJECTIVES: Most human immunodeficiency virus (HIV)-infected patients develop various skin diseases. These skin manifestations not only act as markers but also reflect the patient's underlying immune status. Investigating CD4 counts is costly and not always possible. Thus, the potential value to be gained by using skin manifestations as predictors of low CD4 counts and disease progression should be explored. The present study attempted to correlate the association of various cutaneous disorders found in HIV patients with CD4 and CD8 counts, the CD4 : CD8 ratio and stage of HIV infection. METHODS: This was a prospective study involving 61 patients who were HIV-positive and demonstrated skin lesions. Punch biopsies of skin were taken for histopathological diagnosis. CD4 and CD8 T cell counts were performed. RESULTS: The study sample included a majority of male patients, most of whom were aged 21-40 years. Pruritic papular dermatitis was the most common skin manifestation, followed by molluscum contagiosum, eosinophilic folliculitis, and Hansen's disease. Most of the lesions were associated with CD4 counts of <220/µl (n = 38). All skin lesions associated with HIV or acquired immune deficiency syndrome (AIDS) showed a CD4 : CD8 ratio of <0.50. CONCLUSIONS: The study findings demonstrate an inverse relationship between CD4 counts and the occurrence of skin lesions. The majority of lesions were associated with stage 3 or stage 4 infection. Thus, specific cutaneous manifestations can be considered as good clinical indicators for predicting underlying immune status in resource-poor countries.

Increased frequency of CD4 and CD8 regulatory T cells in individuals under 15 years with multibacillary leprosy.

BACKGROUND: Leprosy is a chronic disease, caused by Mycobacterium leprae, which poses a serious public health problem worldwide. Its high incidence in people under 15 years old in Ceará state, Brazil, reflects the difficulty of its control. The spectrum of clinical manifestations is associated with the immune response developed, with the Th1 and Th2 responses being related to the paucibacillary and multibacillary forms, respectively. Regulatory T cells (Treg), which can suppress Th1 and Th2 response, have received special attention in the literature and have been associated with development of chronic infections. However, their role in leprosy in individuals under 15 years old has not yet been elucidated. We evaluated the frequency of CD4(+)/CD8(+)CD25(high)FOXP3(+) and CD4(+)/CD8(+)CD25(high)FOXP3(high) cells in leprosy patients and household contacts, in both cases under 15 years old. METHODOLOGY/PRINCIPAL FINDINGS: PBMC from 12 patients and 17 contacts were cultured for 72 hours with anti-CD3 and anti-CD28 (activators) or with activators associated with total sonicated fraction of M. leprae. After culture, the frequency of CD4(+)/CD8(+) Treg was identified by flow cytometry. Cells stimulated by activators and antigen from multibacillary patients showed Treg frequencies almost two times that of the contacts: CD4(+)FOXP3(+) (21.93±8.43 vs. 13.79±8.19%, p = 0.0500), CD4(+)FOXP3(high) (10.33±5.69 vs. 5.57±4.03%, p = 0.0362), CD8(+)FOXP3(+) (13.88±9.19 vs. 6.18±5.56%, p = 0.0230) and CD8(+)FOXP3(high) (5.36±4.17 vs. 2.23±2.68%, p = 0.0461). Furthermore, the mean fluorescence intensity of FOXP3 in Treg was higher in multibacillary patients than in the contacts. Interestingly, there was a positive correlation of the bacillary index and number of lesions with the frequency of all Treg evaluated in patients. CONCLUSIONS/SIGNIFICANCE: We have demonstrated for the first time that multibacillary leprosy patients under 15 years old have greater CD4(+) and CD8(+) Treg frequencies and these correlate with clinical and laboratorial aspects of disease. These findings suggest the involvement of these cells in the perpetuation of M. leprae infection.

Clinical and histological features of leprosy and human immunodeficiency virus co-infection in Brazil.

BACKGROUND: Both leprosy and human immunodeficiency virus (HIV) are infectious diseases, and are an important global health problem. Patients with leprosy who are co-infected with HIV seem to be at higher risk of developing leprosy reactions. AIM: To examine the histological features of leprosy in patients with HIV and leprosy co-infection, particularly to determine whether the typical leprosy histopathology is present in skin biopsies, and to assess the histological features of leprosy reactions in co-infected patients. METHODS: This was a matched cohort study with 11 co-infected patients and 31 HIV-negative patients with leprosy. A structured protocol for skin-biopsy evaluation was followed, focusing on inflammation of the skin and dermal nerves. RESULTS: Of the 11 HIV-positive patients, 7 (63%) had borderline tuberculoid (BT) leprosy and 5 (70%) of these 7 patients had developed a type 1 reaction. The lesions in these patients were immunologically active, with 100% of biopsies having evidence of compact granulomas, 90% evidence of oedema and 30% evidence of necrosis. CONCLUSIONS: In this study, patients co-infected with HIV and M. leprae had the typical histological lesions of leprosy. There was evidence of immune activation in patients who received combination antiretroviral therapy, and these patients had BT leprosy and leprosy-upgrading reactions.

Clinical and histological features of leprosy and human immunodeficiency virus co-infection in Brazil

BACKGROUND: Both leprosy and human immunodeficiency virus (HIV) are infectious diseases, and are an important global health problem. Patients with leprosy who are co-infected with HIV seem to be at higher risk of developing leprosy reactions. AIM: To examine the histological features of leprosy in patients with HIV and leprosy co-infection, particularly to determine whether the typical leprosy histopathology is present in skin biopsies, and to assess the histological features of leprosy reactions in co-infected patients. METHODS: This was a matched cohort study with 11 co-infected patients and 31 HIV-negative patients with leprosy. A structured protocol for skin-biopsy evaluation was followed, focusing on inflammation of the skin and dermal nerves. RESULTS: Of the 11 HIV-positive patients, 7 (63%) had borderline tuberculoid (BT) leprosy and 5 (70%) of these 7 patients had developed a type 1 reaction. The lesions in these patients were immunologically active, with 100% of biopsies having evidence of compact granulomas, 90% evidence of oedema and 30% evidence of necrosis. CONCLUSIONS: In this study, patients co-infected with HIV and M. leprae had the typical histological lesions of leprosy. There was evidence of immune activation in patients who received combination antiretroviral therapy, and these patients had BT leprosy and leprosy-upgrading reactions.

Immune reconstitution inflammatory syndrome in leprosy.

Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical deterioration in the clinical status of a patient infected with human immunodeficiency virus (HIV) on highly active antiretroviral treatment (HAART). The immune suppression caused by the virus can initially suppress the clinical manifestations of leprosy which can then be unmasked after treatment with HAART or an inflammatory reaction can occur in the initial months of therapy, resulting from dysregulated recovery of immunity to specific antigens. Both these conditions are identified as IRIS in leprosy. Though this syndrome is a widely recognized entity presently, there is still a lack of universally acceptable diagnostic criteria for the condition. The first case published case of leprosy- associated immune reconstitution disease was reported in 2003 and about 47 confirmed cases of IRIS in leprosy have been reported since then, mostly from Brazil and India. Anti-inflammatory drugs and steroids are the drugs of choice in inflammatory episodes with continuation of antiretroviral therapy. With increasing affordability of antiretroviral therapy, clinicians will put more and more number of human immunodeficiency virus infected patients on therapy and hence an increase in the incidence of IRIS is expected. Therefore, it is important to understand all facets of this syndrome which is becoming more prevalent with each passing day.

Type 2 lepra reaction with HIV1 co-infection: a case report with interesting management implications.

A patient co-infected with leprosy and Human Immunodeficiency Virus (HIV)-type 1 who developed type 2 lepra reaction in the absence of antiretroviral therapy is presented. The reaction responded only after initiating anti retroviral therapy (ART) despite normal CD4+ counts. The present report suggests that type 2 reactions in leprosy and HIV co-infected patients may not always be the typical manifestation of immune reconstitution inflammatory syndrome (IRIS) and stresses the importance of considering concomitant HIV infection in refractory lepra reactions. Extensive research is required into the manifestations of HIV in leprosy patients.

Outcome in a paediatric cohort receiving ART in Addis Abeba, Ethiopia.

AIM: To evaluate pediatric AntiRetroviral Treatment (ART) treatment in a resource-limited setting. METHODS: Data from a paediatric ART cohort at the All African Leprosy and Rehabilitation Centre, Addis Abeba, were analysed. Outcome measures included survival, age, gender, WHO stage, weight, regimen and CD4 cell count. RESULTS: From April 2005 to December 2008, 482 children initiated ART. Median age was 5.9 years (IQR 3.7-9.8), and median CD4 cell count was 236 cells per mm3. Median follow-up was 16 months (IQR=6-24 month). Among those followed for 24 months (n=188), 160 children were still receiving treatment, six had dropped out, eight had been transferred out, and 13 (7.5%) had died (4.0 deaths per 100 person-years). Mortality was highest in the first 6 months resulting in a 4.3% mortality rate. Lower age and immune suppression (low CD4) were associated with mortality, while sex, drug regimen, tuberculosis at treatment initiation, application of stavudine and/or zidovudine were not. CONCLUSION: ART treatment of children in resource-limited settings is possible as demonstrated by low attrition. The high proportion of malnourished children and children admitted at late stage of the disease calls for attention. Efforts to enrol more children and at an earlier stage of the disease should be promoted.

HIV testing and treatment among tuberculosis patients --- Kenya, 2006-2009.

In resource-limited settings, high case-fatality rates are seen among tuberculosis (TB) patients with human immunodeficiency virus (HIV) infection, especially during the early months of TB treatment. HIV prevalence among TB patients has been estimated to be as high as 80%--90% in some areas of sub-Saharan Africa. In 2004, the World Health Organization (WHO) recommended increasing collaboration between HIV and TB programs. Since then, many countries, including Kenya, have worked to increase TB/HIV collaborative activities. In 2005, the Kenya Division of Leprosy, Tuberculosis, and Lung Disease (DLTLD) added questions regarding HIV testing and treatment to the existing TB surveillance system.* This report summarizes HIV data collected from Kenya's extended TB surveillance system during 2006--2009. During this period, HIV testing among TB patients increased from 60% in 2006 to 88% in 2009, and the prevalence of HIV infection among TB patients tested decreased from 52% to 44%. In 2009, 92% of HIV-infected TB patients received cotrimoxazole prophylaxis for the prevention of opportunistic infections. Although these data highlight the increase in HIV services provided to TB patients, only 34% of HIV-infected TB patients started antiretroviral therapy (ART) while being treated for TB. Innovative interventions are needed to increase HIV treatment among TB patients in Kenya, especially considering the 2009 WHO guidelines recommending that all HIV-infected TB patients be started on ART as soon as possible, regardless of CD4 count. Although these guidelines have not yet been implemented in Kenya, officials are working to identify methods of increasing access to ART for TB patients.

Leprosy and HIV, where are we at?

The impact of leprosy and HIV co-infection is an evolving picture. Surprisingly the outcomes that were feared, of more lepromatous disease has not materialised. But with the roll-out of antiretroviral therapy, the emergence of leprosy as Immune Reconstitution Inflammatory Syndrome is re-focusing attention on the characteristics of this important co-infection.

Borderline tuberculoid leprosy with upgrading Type 1 reaction in a HIV seropositive patient, after antiretroviral therapy: an immune reconstitution inflammatory syndrome.

A case of borderline tuberculoid (BT) leprosy with upgrading Type 1 reaction, in a HIV seropositive patient, 7 weeks after starting highly active antiretroviral therapy, as an immune reconstitution inflammatory syndrome (IRIS), is reported.

Leprosy occurring as immune reconstitution syndrome.

Immune reconstitution inflammatory syndrome (IRIS) may occur in HIV-infected patients after starting highly active antiretroviral therapy (HAART). Since 2003, 19 cases were published as IRIS. Leprosy has been reported as an example of an IRIS, and it is important that this syndrome should be recognized in leprosy-endemic areas. The case definition of leprosy as IRIS is based on clinical presentation of leprosy, evidence of immune restoration and timing of onset. Case definition should include the following: (1) leprosy and/or leprosy type 1 reaction presenting within six months of starting HAART; (2) advanced HIV infection; (3) low CD4+ count before start HAART; (4) CD4+ count increasing after HAART has been started. Although pathogenic mechanisms are still unclear, it is likely that leprosy-associated IRIS will be increasingly reported in those countries endemic for both diseases and as access to HAART becomes more widely available.

Dermatologic immune restoration syndrome: report of five cases from a tertiary care center in north India.

BACKGROUND: Dermatologic conditions are often an early clue to human immunodeficiency virus (HIV) infection. As the disease progresses and the host immunity fails, patients may develop a number of skin conditions. At this point, they have a dominant T helper 2 immunologic response. After the initiation of antiretroviral therapy, the T helper 1 response is restored, and some skin problems, paradoxically, make their appearance then. CONCLUSION: Herpes zoster, mucocutaneous herpes, eosinophilic folliculitis, and mycobacterial infections have been known to occur at this stage. This may be because immune restoration of a host's immunity causes recognition of silent or latent infection and results in development of the condition. We report five cases that were seen at our center during a 2-year period.