Leprosy as immune reconstitution inflammatory syndrome in patients living with HIV: Description of French Guiana's cases over 20 years and systematic review of the literature.

BACKGROUND: HIV infection is highly prevalent in French Guiana, a territory where leprosy is also endemic. Since the introduction of Highly Active Antiretroviral Treatment (HAART) in the management of HIV, leprosy has been reported as part of the immune reconstitution inflammatory syndrome (IRIS). METHODOLOGY/PRINCIPAL FINDINGS: We aimed to present a general description of these forms of leprosy as IRIS, highlighting clinical and therapeutic specificities. A retrospective study was conducted in French Guiana, including patients living with HIV (PLHIV) with advanced infection (CD4 < 200/mm3) and developing leprosy or a leprosy reaction within six months of HAART initiation, from 2000 to 2020. Clinical, histological and biological data were collected for all these patients. Six patients were reported in French Guiana. A systematic review of the literature was conducted, and its results were added to an overall analysis. Overall, seventy-three PLHIV were included. They were mainly men (74%), aged 22-54 years (median 36 years), mainly from Brazil (46.5%) and India (32.8%). Most leprosy cases (56.2%) were borderline tuberculoid (BT). Leprosy reactions were frequent (74%), mainly type 1 reaction (T1R) (68.5%), sometimes intense with ulceration of skin lesions (22%). Neuritis was observed in 30.1% of patients. The outcome was always favorable under multidrug therapy (MDT), continuation of HAART and additional corticosteroid therapy in case of neuritis or ulceration. There was no relapse. CONCLUSION: Leprosy as IRIS in PLHIV mainly presents as a BT leprosy in a T1R state, sometimes with ulcerated skin lesions. Response to MDT is usually good. Systemic corticosteroids are necessary and efficient in case of neuritis.

Addressing the drug-resistant tuberculosis challenge through implementing a mixed model of care in Uganda.

Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and human immunodeficiency virus (HIV) status), on co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) statuses, culture results, smear results and treatment outcomes (6, 12, and 24 months) from 2012 to 2017 RR-TB/MDR-TB cohorts were collected from all the 15 DR-TB treatment initiation sites and descriptive analysis was done using STATA version 14.2. We presented outcomes as the number of patient backlog cleared, DR-TB initiation sites, RR-TB/DR-TB cumulative patients enrolled, percentage of co-infected patients on the six, twelve interim and 24 months treatment outcomes as per the Uganda NTLP 2016 Programmatic Management of drug-resistant Tuberculosis (PMDT) guidelines (NTLP, 2016). Over the period 2013-2015, the RR-TB/MDR-TB Treatment success rate (TSR) was sustained between 70.1% and 74.1%, a performance that is well above the global TSR average rate of 50%. Additionally, the cure rate increased from 48.8% to 66.8% (P = 0.03). The Uganda DR-TB mixed model of care coupled with early application of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges.

Case Report: Severe Visceral Leishmaniasis in a Patient with HIV Coinfection Undergoing Treatment for Erythema Nodosum Leprosum.

We report a case of visceral leishmaniasis (VL)/HIV coinfection in a patient undergoing regular antiretroviral therapy and treatment with thalidomide for erythema nodosum leprosum. He presented at a health service with high fever, chills, asthenia, pale skin, lower limb edema, hepatomegaly, and splenomegaly. Visceral leishmaniasis was confirmed by direct examination, and serological and molecular tests. Serum levels of Th1/Th2 cytokines were measured. The patient began treatment with liposomal amphotericin B, with good clinical response; however, VL recurred 6 months later. Treatment was reinitiated, maintaining secondary prophylaxis with liposomal amphotericin B. The patient showed clinical improvement with important recovery of CD4+ T-lymphocyte count.

Immune reconstitution inflammatory syndrome associated with bacterial infections.

INTRODUCTION: Immune reconstitution inflammatory syndrome (IRIS) is defined by various clinical manifestations following the initiation of antiretroviral treatment (ART) in HIV patients primarily infected with Mycobacteria. IRIS has clinical similarities with lepromatous reactions in patients with leprosy following antibiotic initiation. AREAS COVERED: Tuberculosis and more rarely lepromatous leprae and Whipple's disease are the main diseases caused by actinobacteria associated with IRIS, regardless of HIV status. The pathogenesis of this syndrome remains complex and partially understood. The treatment for IRIS is non-evidence-based, except for corticosteroids in tuberculosis-IRIS. Thalidomide and other immunomodulatory drugs have been successfully used in case series. EXPERT OPINION: IRIS is mainly observed during infections (viral, fungal or bacterial) which involve inefficient macrophages for the clearance of bacteria, namely Actinobacteria such as Mycobacterium leprae, M. tuberculosis and Tropheryma whipplei. The restoration of macrophage competence after ART or antibiotic initiation results from a complex mechanism, probably involving a sudden and violent immune reaction with a cytokine storm, such as TNF-α and IFN-γ. This overreaction might be controlled using corticosteroids and thalidomide.

Skewing of the CD4(+) T-cell pool toward monofunctional antigen-specific responses in patients with immune reconstitution inflammatory syndrome in The Gambia.

BACKGROUND: A common complication of starting antiretroviral therapy (ART) for human immunodeficiency virus (HIV) is the development of immune reconstitution inflammatory syndrome (IRIS) in approximately 25% of patients. Despite similarities with paradoxical reactions to tuberculosis and reversal reactions in leprosy, the exact mechanisms, and therefore potential determinants, of IRIS are still unknown. METHODS: In this longitudinal cohort study, we analyzed 20 patients who developed IRIS following initiation of ART and 16 patients who did not, matched for ART time point. Peripheral blood mononuclear cells were stimulated overnight with a positive control antigen and 2 tuberculosis-specific antigens (purified protein derivative [PPD] and ESAT-6/CFP10), followed by polychromatic flow cytometry for analysis of cytokine production from CD4(+) and CD8(+) T cells. RESULTS: Responses to PPD were significantly higher in IRIS patients compared to controls during the IRIS time point, but CD4(+) and CD8(+) T-cell responses to the positive control stimulation were significantly lower in IRIS patients at all time points. Furthermore, whereas control patients had rejuvenated polyfunctional T-cell responses by 3 months after ART, IRIS patients were strikingly monofunctional (generally interferon γ alone), even up to 6 months of ART in response to all stimulations. CONCLUSIONS: Our findings suggest that the peripheral T-cell responses to the underlying pathogen are exaggerated in IRIS patients but that the overall quality of the peripheral T-cell pool is significantly reduced compared to non-IRIS patients. Furthermore, these effects are apparent at least up to 3 months after cessation of IRIS.

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.

Two unusual cases of histoplasmosis in human immunodeficiency virus-infected individuals.

Histoplasmosis, also called as Darling's disease, is caused by the dimorphic fungus, Histoplasma capsulatum. In India, several cases of histoplasmosis have been reported since 1954, but in only a few cases could the diagnosis be confirmed by fungal culture. Disseminated histoplasmosis in adults is often associated with immunosuppression, as in human immunodeficiency virus (HIV) infection. Oral lesions are seen in 30-50% of the patients. Here, we are reporting two histoplasmosis cases, one with disseminated histoplasmosis with extensive skin and oral lesions in a known HIV-positive patient and the second case presenting with ulcer of the tongue, found to be HIV positive on investigation. It is important to consider histoplasmosis as one of the differential diagnosis of oral lesions in HIV-infected individuals.

Adverse effects of antiretroviral treatment.

BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) has led to significant reduction in acquired immune deficiency syndrome (AIDS)-related morbidity and mortality. Adverse drug reactions (ADRs) to antiretroviral treatment (ART) are however, major obstacles in its success. AIMS: We sought to study the adverse effects of ART in a resource-restricted setting in India. METHODS: Hundred patients on ART were studied prospectively over a period of two years. All patients were asked to visit the clinic if they developed any symptoms or on a monthly basis. They were screened clinically and investigated suitably for any ADRs. RESULT: Out of the 100 patients, ten patients did not come for follow-up; only 90 cases were available for evaluation. ADRs were observed in 64 cases (71.1%) - the maximal frequency of ADRs was seen with zidovudine (AZT) (50%) followed by stavudine (d4T) (47.9%), efavirenz (EFV) (45.4%) and finally, Nevirapine (NVP) (18.4%). Most common ADRs were cutaneous (44.4%) followed by hematological (32.2%), neurological (31.1%), metabolic (22.2%) and gastrointestinal (20%). Most common cutaneous ADRs observed were nail hyperpigmentation (14.4%) and rash (13.3%). Immune reconstitution inflammatory syndrome (IRIS) was observed as a paradoxical reaction to ART in 20 (22.2%) cases. CONCLUSION: To optimize adherence and thus, efficacy of ART, clinicians must focus on preventing adverse effects whenever possible, and distinguish those that are self-limited from those that are potentially serious.

National scale-up of HIV testing and provision of HIV care to tuberculosis patients in Kenya.

SETTING: Kenya, one of the 22 tuberculosis (TB) high-burden countries, whose TB burden is fuelled by the human immunodeficiency virus (HIV). OBJECTIVE: To monitor and evaluate the implementation of HIV testing and provision of HIV care to TB patients in Kenya through the establishment of a routine TB-HIV integrated surveillance system. DESIGN: A descriptive report of the status of implementation of HIV testing and provision of HIV interventions to TB patients one year after the introduction of the revised TB case recording and reporting system. RESULTS: From July 2005 to June 2006, 88% of 112835 TB patients were reported to the National Leprosy and TB Control Programme, 98773 (87.9%) of whom were reported using a revised recording and reporting system that included TB-HIV indicators. HIV testing of TB patients increased from 31.5% at the beginning of this period to 59% at the end. Of the 46428 patients tested for HIV, 25558 (55%) were found to be HIV-positive, 85% of whom were provided with cotrimoxazole preventive treatment and 28% with antiretroviral treatment. CONCLUSION: A country-wide integrated TB-HIV surveillance system in TB patients can be implemented and provides essential data to monitor and evaluate TB-HIV related interventions.

Immune reconstitution inflammatory syndrome.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical deterioration in clinical status in a patient on antiretroviral treatment (ART) despite satisfactory control of viral replication and improvement of CD4 count. AIM: To study development of IRIS as a part of ART. METHODS: Hundred patients on antiretroviral treatment were studied prospectively in the Department of Skin and VD over a period of 2 years. Patients were asked to come if they developed any symptoms or on a monthly basis. They were screened clinically and investigated suitably for evidence of opportunistic infections. RESULTS: Out of 100 patients, 10 patients did not come for follow-up. Twenty (22.2%) out of the 90 patients developed IRIS. Herpes zoster (HZ), herpes simplex virus (HSV), and tuberculosis (TB) were the cases of IRIS seen in the present study. CONCLUSIONS: IRIS in terms of HSV/TB is known to accelerate HIV disease progression. Hence early detection and prompt treatment, along with continuation of highly active ART, are of utmost importance.

Improving adherence to antiretroviral therapy.

Antiretroviral therapy (ART) has transformed HIV infection into a treatable, chronic condition. However, the need to continue treatment for decades rather than years, calls for a long-term perspective of ART. Adherence to the regimen is essential for successful treatment and sustained viral control. Studies have indicated that at least 95% adherence to ART regimens is optimal. It has been demonstrated that a 10% higher level of adherence results in a 21% reduction in disease progression. The various factors affecting success of ART are social aspects like motivation to begin therapy, ability to adhere to therapy, lifestyle pattern, financial support, family support, pros and cons of starting therapy and pharmacological aspects like tolerability of the regimen, availability of the drugs. Also, the regimen's pill burden, dosing frequency, food requirements, convenience, toxicity and drug interaction profile compared with other regimens are to be considered before starting ART. The lack of trust between clinician and patient, active drug and alcohol use, active mental illness (e.g. depression), lack of patient education and inability of patients to identify their medications, lack of reliable access to primary medical care or medication are considered to be predictors of inadequate adherence. Interventions at various levels, viz. patient level, medication level, healthcare level and community level, boost adherence and overall outcome of ART.