Treatment outcome of tuberculosis among Human Immunodeficiency Virus positive patients in Eastern Ethiopia: a retrospective study.

INTRODUCTION: Tuberculosis is the leading cause of morbidity and mortality among people living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome worldwide. Although Human Immunodeficiency Virus related tuberculosis is both treatable and preventable, incidence rates continue to climb in developing countries where both infections are endemic. The aim of this study was to assess the treatment outcome of tuberculosis among Human Immunodeficiency Virus positive patients attending in three hospitals of Eastern Ethiopia. METHODS: A retrospective clinical record review was conducted for 627 Tuberculosis and Human immunodeficiency virus co-infected patients registered from January 2008 to January 2014 cards were reviewed in three hospitals of tuberculosis clinics of Eastern Ethiopia from December 2015 to February 2016. The three hospitals were selected based on their high patient load of TB-HIV co infection and the presence of ART and TB units. Data on patient's details and tuberculosis treatment outcome were collected using standardized report format of National Tuberculosis and Leprosy Control Programme (NTLCP). The collected data were analyzed by Statistical Package for Social Sciences (SPSS) software Version 16. RESULTS: The overall treatment success rate was 78.3%. Of the total TB-HIV co infected study participants, 17.9% cured, 60.4% treatment completed, 8.6% died, 0.6% failure, 1.8% defaulter and 10.7% transferred out. Those participants in the age groups of less than or equals to 18 years old (Adjusted Odds Ratio = 1.990, 95% Confidence Interval: 1.01, 3.350), extra pulmonary tuberculosis (Adjusted Odds Ratio = 1.51, 95% Confidence Interval = 1.12, 3.42), on antiretro viral therapy (Adjusted Odds Ratio = 1.54, 95% Confidence Interval = 1.252, 3.910) were more likely to have higher treatment outcome than each of the above variables counter parts. CONCLUSION: The rate of treatment success in this study was lower than recommended rate by World Health Organization. Thus this study recommends improving counseling during tuberculosis treatment, providing home visits and motivation of patients, improving defaulter tracing and health information dissemination in order to reduce treatment interruption.

Peripheral nerve abnormality in HIV leprosy patients.

BACKGROUND: The geographical overlap of HIV (human immunodeficiency virus) and leprosy infection has become increasingly frequent and worrying, bringing many clinical issues. Peripheral neuropathy is very frequent in leprosy because of the predilection of its etiologic agent by Schwann cells of the peripheral nervous system, and it also affects individuals with HIV as one of the most common neurological manifestations. METHODOLOGY/PRINCIPAL FINDINGS: The present study compared a cohort of 63 patients diagnosed with leprosy and coinfected with HIV with a cohort of 64 patients with leprosy alone, who were followed at the outpatient clinic of the Nucleus of Tropical Medicine of the Federal University of Pará, Brazil. We observed that HIV-coinfected leprosy patients presented greater odds of overall peripheral nerve damage (nerve function impairment-NFI) than patients with leprosy alone. More sensitive damage was observed, especially in patients coinfected with multibacillary forms. Leprosy patients coinfected with HIV presented higher chances of motor damage with improvement over time using multidrug therapy (MDT) and highly active antiretroviral therapy (HAART), along with a greater extent of damage and occurrence of neuritis. The data suggest that in addition to patients presenting possible damage caused by leprosy, they also had a greater damage gradient attributable to HIV disease, but not related to HAART because most of these patients had been on the treatment for less than a year. Neuritis was treated with prednisone at doses recommended by the WHO, and coinfected patients had the highest rate of clinical improvement in the first 60 days. CONCLUSIONS/SIGNIFICANCE: The clinical characteristics of the two diseases should be considered in leprosy patients coinfected with HIV for better diagnosis and treatment of peripheral neuropathy. We suggest that new simplified assessment tools that allow the evaluation of the NFI of these patients be developed for use in the service.

A case of histoid leprosy in a HIV infected person on HAART not responding to conventional MB-MDT.

A 46 year old male diagnosed case of Acquired Immune Deficiency Syndrome (AIDS) on Highly Active Anti Retroviral Therapy (HAART) presented with raised nodular skin lesions of two months duration which on skin biopsy was diagnosed as Histoid leprosy. Individual was put on standard Multi Bacillary Multi Drug Therapy (MB MDT) for two months has shown exacerbation of lesion and was later put on daily Rifampicin, Ofloxacin and Minocycline (ROM) for which he responded. Interesting feature is rarity of association of HIV with Histoid Leprosy where the patient did not respond to the conventional MB MDT and later responded to daily ROM.

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.

Public-private mix for TB and TB-HIV care in Lagos, Nigeria.

SETTING: Private and public tuberculosis (TB) treatment centres in Lagos State, Nigeria. OBJECTIVE: To assess the contribution of private health care providers to TB and TB-HIV (human immunodeficiency virus) case finding in Lagos State. DESIGN: A retrospective review of programme data submitted to the Lagos State TB and Leprosy Control Programme in 2011 by public, private for-profit (PFP) and private not-for-profit (PNFP) health care providers. RESULTS: A total of 8425 TB cases were notified by 31 private (11 PFP and 20 PNFP) and 99 public health facilities in Lagos State. Overall, the private facilities were responsible for 10.3% (866/8425) of the total TB cases notified. The proportion of TB patients tested for HIV was respectively 86.2%, 53.1% and 96.5% among public, PFP and PNFP facilities. Overall, 22.4% of the TB patients were HIV-positive. The HIV positivity rate among public, PFP and PNFP facilities was respectively 23.8%, 7.8% and 9.9%. Uptake of cotrimoxazole preventive therapy was respectively 69.6%, 25% and 38.2% among public, PFP and PNFP facilities, while that of antiretroviral therapy was respectively 23.8%, 8.3% and 9.1% in public, PFP and PNFP facilities. CONCLUSION: There is a need to scale up collaboration with the private sector, and particularly PNFP health providers.

Murabutide revisited: a review of its pleiotropic biological effects.

Despite the great efforts put into their development, the list of clinically approved immunological adjuvants is still very short. Evolution of the knowledge of the immune system has enabled for rational design of novel adjuvants and has led to the conclusion that more than one type of adjuvant will be required. Derivatives of muramyl dipeptide (MDP), the minimal immunomodulatory structure of bacterial cell wall peptidoglycan, have gained considerable attention in the past decades, because of their potent adjuvant effects. Murabutide is a safe derivative of MDP, which interacts with cells of the immune system, both innate and adaptive, and exerts its effect through activation of Nod2. The transcriptional response of murabutide-stimulated macrophages revealed enhanced expression of genes coding for various proteins such as immune mediators and their receptors, transcription factors and kinases, ion channels/transporters and proteins involved in cell metabolic activity, thus reflecting a broad spectrum of biological effects. In addition to its well recognized adjuvant effect, murabutide has also been shown to enhance the host's resistance against microbial infections, nonspecific resistance against tumors and the induction of cytokines and chemokines implicated in enhancing the immune response and hematopoesis. This article provides an insight into the mechanism of action of murabutide and its interactions with the cells of the immune system in vitro and in vivo. On account of its numerous biological effects, murabutide has been the subject of several clinical studies. Many of these have confirmed its potential to synergize with cytokines of therapeutic interest in potentiating the tumoricidal activity of macrophages or targeting chronic viral diseases, as well as reducing the cytokine dosage needed to achieve a therapeutic effect. This review covers the findings of all relevant studies and focuses on the role of murabutide and its potential in the treatment of several microbial diseases.

Combination prevention: new hope for stopping the epidemic.

HIV research has identified approaches that can be combined to be more effective in transmission reduction than any 1 modality alone: delayed adolescent sexual debut, mutual monogamy or sexual partner reduction, correct and consistent condom use, pre-exposure prophylaxis with oral antiretroviral drugs or vaginal microbicides, voluntary medical male circumcision, antiretroviral therapy (ART) for prevention (including prevention of mother to child HIV transmission [PMTCT]), treatment of sexually transmitted infections, use of clean needles for all injections, blood screening prior to donation, a future HIV prime/boost vaccine, and the female condom. The extent to which evidence-based modalities can be combined to prevent substantial HIV transmission is largely unknown, but combination approaches that are truly implementable in field conditions are likely to be far more effective than single interventions alone. Analogous to PMTCT, "treatment as prevention" for adult-to-adult transmission reduction includes expanded HIV testing, linkage to care, antiretroviral coverage, retention in care, adherence to therapy, and management of key co-morbidities such as depression and substance use. With successful viral suppression, persons with HIV are far less infectious to others, as we see in the fields of sexually transmitted infection control and mycobacterial disease control (tuberculosis and leprosy). Combination approaches are complex, may involve high program costs, and require substantial global commitments. We present a rationale for such investments and cite an ongoing research agenda that seeks to determine how feasible and cost-effective a combination prevention approach would be in a variety of epidemic contexts, notably that in a sub-Saharan Africa.

Incidence and predictors of mortality and the effect of tuberculosis immune reconstitution inflammatory syndrome in a cohort of TB/HIV patients commencing antiretroviral therapy.

BACKGROUND: Tuberculosis-HIV (TB-HIV) coinfection remains an important cause of mortality in antiretroviral therapy (ART) programs. In a cohort of TB-HIV-coinfected patients starting ART, we examined the incidence and predictors of early mortality. METHODS: Consecutive TB-HIV-coinfected patients eligible for ART were enrolled in a cohort study at the Mulago National Tuberculosis and Leprosy Program clinic in Kampala, Uganda. Predictors of mortality were assessed using Cox proportional hazards analysis. RESULTS: Three hundred and two patients [median CD4 count 53 cells/µL (interquartile range, 20-134)] were enrolled. Fifty-three patients died, 36 (68%) of these died within the first 6 months of TB diagnosis. Male sex [hazard (HR): 2.19; 95% confidence interval (CI): 1.19 to 4.03; P = 0.011], anergy to tuberculin skin test [HR: 2.59 (1.10 to 6.12); P = 0.030], a positive serum cryptococcal antigen result at enrollment (HR: 4.27; 95% CI: 1.50 to 12.13; P = 0.006) and no ART use (HR: 4.63; 95% CI: 2. 37 to 9.03; P < 0.001) were independent predictors of mortality by multivariate analysis. Six (10%) patients with TB immune reconstitution inflammatory syndrome died, and in most, an alternative contributing cause of death was identified. CONCLUSIONS: Mortality among these TB-HIV-coinfected patients was high particularly when presenting with advanced HIV disease and not starting ART, reinforcing the need for timely and joint treatment for both infections. Screening for a concomitant cryptococcal infection and antifungal treatment for patients with cryptococcal antigenemia may further improve clinical outcome.

Leprosy and HIV coinfection: a clinical, pathological, immunological, and therapeutic study of a cohort from a Brazilian referral center for infectious diseases.

BACKGROUND: Although awareness of the relevance of leprosy and human immunodeficiency virus (HIV) coinfection is increasing worldwide, several aspects of this co-occurrence are not fully understood. METHODS: We describe clinical, pathological, immunological, and therapeutic long-term follow-up of a cohort of 25 individuals with leprosy and HIV infection from Manaus, Amazonas. RESULTS: Careful description of our cohort indicates a higher prevalence of leprosy in an HIV-positive population than that in the general population. We also observed upgrading shifting of leprosy clinical forms after initiation of highly active antiretroviral therapy and multidrug therapy and an impact of HIV infection on leprosy granuloma formation, among other features. CONCLUSION: Taken together, these new insights allow the proposition of a classification system that includes (1) leprosy and HIV true coinfection, (2) opportunistic leprosy disease, and (3) leprosy related to highly active antiretroviral therapy.

Human immunodeficiency virus and leprosy coinfection in Pune, India.

We report eight cases and the incidence of leprosy in human immunodeficiency virus (HIV)-infected individuals after initiation of antiretroviral treatment (ART). The incidence of leprosy in patients on ART was 5.22 per 1,000 person-years (95% confidence interval, 2.25 to 10.28). This high incidence suggests that there should be regular examination of HIV-infected individuals for clinical signs of leprosy.

Presence of tropical spastic paraparesis/human T-cell lymphotropic virus type 1-associated myelopathy (TSP/HAM)-like among HIV-1-infected patients.

UNLABELLED: Human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and -2) are retroviruses that share similar routes of transmission and some individuals may have a dual infection. These co-infected subjects may be at increased risk for tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM)-like. To study the prevalence of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) among co-infected HIV-1/HTLV-1 subjects. Since July 1997, our group has been following a cohort to study the interaction of HTLV with HIV and/or hepatitis C virus (HCV), as well as HTLV-1-only infected asymptomatic carriers or those already presenting with TSP/HAM. During these 9 years, 296 HTLV-1-infected individuals were identified from a total of 538 patients who were referred to our clinic at the Institute of Infectious Diseases "Emílio Ribas," in São Paulo, Brazil. All subjects were evaluated by two neurologists, blinded to the HTLV status. TSP/HAM diagnosis was based on Kagoshima diagnostic criteria. RESULTS: A total of 38 HIV-1/HTLV-1 co-infected subjects were identified in this cohort: Twenty-six had already been diagnosed with AIDS and 12 remained asymptomatic. Six of 38 co-infected subjects (18%) were diagnosed as having TSP/HAM and also AIDS, and for 5 of them TSP/HAM was their first illness. One additional incident case was diagnosed after 2 years of follow-up. No modifications on HIV-1 viral load was seen. In contrast, the co-infected with TSP/HAM-like group showed higher HTLV-1 proviral load (505 +/- 380 vs. 97 +/- 149 copies/10(4) PBMC, P = 0.012) than asymptomatic co-infected subjects, respectively. The incidence of myelopathy among HIV-1/HTLV-1 co-infected subjects is probably higher than among patients infected only with HTLV-1, and related to a higher HTLV-1 proviral load. Thus, HTLV-1/2 screening should be done for all HIV-1-infected patients in areas where HTLV-1 infection is endemic.

Brazilian policy of universal access to AIDS treatment: sustainability challenges and perspectives.

INTRODUCTION: The Brazilian AIDS Programme success is recognized worldwide, due to its integrated approach of prevention, respect for human rights and to free of charge universal access to state of the art antiretrovirals. CURRENT SITUATION: As of 2006, 180,000 people living with AIDS are on HAART with 17 drugs available, receiving medical and laboratory care through the public health system. Costs for ART drugs reached US$ 400 million in 2006 and will increase steeply if the current trends are maintained: uptake of approximately 20,000 new patients/year and the need for more expensive, patent-protected second and third line drugs. DISCUSSION: We discuss the strengths and weaknesses of the programme, budgetary pressures, the need for more intense preventive efforts, for boosting local production of new drugs, for more investment in research and development and the issue of voluntary and compulsory licensing. There are many hurdles in pursuing long-term sustainability, which depends on country driven initiatives and international collaboration and participation. CONCLUSION: We conclude that the Brazilian experience demonstrated the capability of a developing country to treat people with equity, independently of race, gender or economic power and that this equality "seed" has already spread to other countries. Internally this experience must be used to tackle other endemic diseases, such as leprosy, malaria, dengue and leishmania. The Brazilian political will has been proven but, once again, there will be the need for concerted action by civil society, researchers, health professionals, people living with HIV/AIDS and the government to convince the world that health needs should not be treated as commercial issues, and that progress in research and development must be shared throughout the world if we expect to survive as a civilization.

Two patients coinfected with Mycobacterium leprae and human immunodeficiency virus type 1 and naive for antiretroviral therapy who exhibited type 1 leprosy reactions mimicking the immune reconstitution inflammatory syndrome.

Two case reports of patients with human immunodeficiency virus type 1 (HIV-1) infection who developed leprosy are presented. Both developed type 1 leprosy reactions in the absence of antiretroviral therapy. Reactions have been described for a number of HIV-1- and Mycobacterium leprae-coinfected patients and have been considered to be part of an immune reconstitution inflammatory syndrome (IRIS) since the reactions were usually linked to the administration of highly active antiretroviral therapy. The reports of our two patients suggest that the type 1 reactions in patients with leprosy and HIV may not always be an IRIS manifestation but may be akin to the classical reactional state described for the natural course of leprosy infection, which occurs in leprosy patients due to the fluctuations of the antimycobacterial immune response, whether they are coinfected with HIV or not.

Erythema nodosum leprosum and HIV infection: A therapeutic experience.

The relationship between leprosy and HIV infection is not yet fully understood, as not much is known about the natural history of the co-infected patients. The matter has become more confusing because of conflicting reports. Type-1 lepra reactions and neuritis appear to be severe and more frequent among them. But erythema nodosum leprosum too is not as uncommon among these patients as it was once thought. Management of these co-infected patients is often difficult for want of clear-cut guidelines on clinical care. We report here our experience of treating recurrent, severe erythema nodosum leprosum in a patient concurrently having leprosy and HIV infection. Early institution of antiretroviral therapy appears to provide an edge in improving the therapeutic outcome for him. It also suggests a direct and more complex interplay of HIV and Mycobacterium leprae infection.

Antiretroviral therapy in sub-Saharan Africa: adherence lessons from tuberculosis and leprosy.

Declining drug costs and increases in international donor interest are leading to greater availability of antiretroviral treatment programmes for persons living with the human immunodeficiency virus in parts of sub-Saharan Africa. Ensuring adequate adherence to antiretroviral drug therapy is one of the principal challenges facing successful implementation in Africa, where 70% of the world's infected persons live. Tuberculosis and leprosy are two diseases of global importance whose control programmes can provide important lessons for developing antiretroviral drug adherence strategies. This paper examines various approaches used in tuberculosis and leprosy control which could help enhance adherence to antiretroviral therapy in resource-limited settings.