Evaluating the safety, tolerability, pharmacokinetics and efficacy of clofazimine in cryptosporidiosis (CRYPTOFAZ): study protocol for a randomized controlled trial.

BACKGROUND: Cryptosporidium infection and diarrhea (cryptosporidiosis) is a life-threatening infection in persons with HIV and also in children of 6-18 months of age in the developing world. To date, only nitazoxanide is licensed for treatment of cryptosporidiosis, and only in persons after the first year of life and with healthy immune systems. Clofazimine (CFZ: Lamprene®), an established drug that has been used for leprosy for more than 50 years, recently has been described as effective against Cryptosporidium in vitro and in mouse infections. The efficacy and pharmacokinetics of CFZ in vivo, in HIV-infected patients with cryptosporidial diarrhea are not known. METHODS: CRYPTOFAZ includes a randomized, double-blind, placebo-controlled study of the safety, tolerability and Cryptosporidium inhibitory activity of orally administered CFZ in subjects with HIV infection and chronic diarrhea with Cryptosporidium. An additional open label aspect of the study will compare the pharmacokinetics (PK) of orally administered CFZ in HIV-infected individuals with and without Cryptosporidium-associated diarrhea. The study will recruit a total of 66 subjects. Study participants will be given either CFZ or a placebo for 5 days while in hospital and will be followed up after discharge. Cryptosporidium will be diagnosed by quantitative PCR as the definitive test and by stool ELISA, which will also be used to quantify the shedding of Cryptosporidium in stool. PK will be studied on plasma and stool samples. Primary endpoints include reduction in the number of Cryptosporidium shed in stools over a 5-day period and compared to placebo recipients and the PK of CFZ in plasma assessed by area under the curve, peak plasma concentration, and half-life (T ½) determined after the last dose. DISCUSSION: This study provides an opportunity to explore a possible treatment option for HIV-infected patients with cryptosporidial diarrhea, who, as of now in Malawi and most of sub-Saharan Africa, do not have a definitive treatment apart from supportive care. The strength of this study lies in it being a randomized, double-blind, placebo-controlled trial. If shown to be effective and safe, the findings will also lay a foundation for a future study of the use of CFZ in children 6-18 months of age. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03341767 . Registered on 14 November 2017.

Nerve abscess in Hansen's disease as part of immune reconstitution inflammatory syndrome: a case report.

Immune reconstitution inflammatory syndrome is an inflammatory reaction in HIV-infected patients after initiation of antiretroviral therapy resulting from restored immunity to specific infectious or non-infectious antigens. A 36-year-old male patient on highly active antiretroviral therapy of six months duration, presented with reddish, tender lesions over medial aspect of arm and a single, anaesthetic patch. Tender fluctuant swellings were seen on the medial aspect of left forearm. A few of them had ruptured spontaneously discharging pus. A skin biopsy from the anaesthetic patch showed caseating epitheloid granulomas. A diagnosis of Hansen's disease borderline tuberculoid in type 1 reversal reaction, with formation of nerve abscess due to Immune Reconstitution Inflammatory Syndrome was made. The patient was started on multibacillary multidrug therapy as per WHO guidelines and highly active antiretroviral therapy was continued.

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.

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 Immuno 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.

Hansen's disease: a vanishing disease?

The introduction, implementation, successes and failures of multidrug therapy (MDT) in all Hansen's disease endemic countries are discussed in this paper. The high efficacy of leprosy treatment with MDT and the global reduction of prevalence led the World Health Organization, in 1991, to establish the goal of elimination of Hansen's disease (less than 1 patient per 10,000 inhabitants) to be accomplished by the year 2000. Brazil, Nepal and East Timor are among the few countries that didn't reach the elimination goal by the year 2000 or even 2005. The implications of these aspects are highlighted in this paper. Current data from endemic and previously endemic countries that carry a regular leprosy control programme show that the important fall in prevalence was not followed by the reduction of the incidence. This means that transmission of Mycobacterium leprae is still an issue. It is reasonable to conclude that we are still far from the most important goal of Hansen's disease control: the interruption of transmission and reduction of incidence. It is necessary to emphasize to health managers the need of keeping Hansen's disease control activities to better develop control programmes in the future. The recent international proposal to interrupt the transmission of leprosy by the year 2020 seems to unrealistic and it is discussed in this paper. The possibility of epidemiological impact related to the human immunodeficiency virus/Hansen's disease coinfection is also considered.

Hansen's disease: a vanishing disease?

The introduction, implementation, successes and failures of multidrug therapy (MDT) in all Hansen's disease endemic countries are discussed in this paper. The high efficacy of leprosy treatment with MDT and the global reduction of prevalence led the World Health Organization, in 1991, to establish the goal of elimination of Hansen's disease (less than 1 patient per 10,000 inhabitants) to be accomplished by the year 2000. Brazil, Nepal and East Timor are among the few countries that didn't reach the elimination goal by the year 2000 or even 2005. The implications of these aspects are highlighted in this paper. Current data from endemic and previously endemic countries that carry a regular leprosy control programme show that the important fall in prevalence was not followed by the reduction of the incidence. This means that transmission of Mycobacterium leprae is still an issue. It is reasonable to conclude that we are still far from the most important goal of Hansen's disease control: the interruption of transmission and reduction of incidence. It is necessary to emphasize to health managers the need of keeping Hansen's disease control activities to better develop control programmes in the future. The recent international proposal to interrupt the transmission of leprosy by the year 2020 seems to unrealistic and it is discussed in this paper. The possibility of epidemiological impact related to the human immunodeficiency virus/Hansen's disease coinfection is also considered.

[Infection due to Strongyloides stercoralis: epidemiological, clinical, diagnosis findings and outcome in 30 patients]. / Infección por Strongyloides stercoralis: estudio epidemiológico, clínico, diagnóstico y terapéutico en 30 pacientes.

BACKGROUND: Strongyloides stercoralis is a nematode parasite, which is endemic in tropical and subtropical regions. Infection usually remains asymptomatic, but in immunocompromised hosts severe and life-threatening manifestations such as hyperinfection syndrome and disseminated disease might occur. METHODS: We retrospectively analyzed the epidemiological and clinical characteristics, including HIV co-infection, microbiological findings, and outcome in 30 patients with strongyloidiasis, who attended in the Infectious Diseases F. J. Muñiz Hospital in Buenos Aires from January 2004 to December 2008. RESULTS: The study included 20 men and 10 women with an average age of 33 years. HIV co-infection was present in 21 patients (70%) with a median CD4 T cell count of 50 cells/mm³ (range 7-355) (average 56 cells/mm³). Among HIV negative patients the following comorbidities were detected: tuberculosis (n = 3) and chronic alcoholism, leprosy treated with corticosteroids, immunosuppressive treatment for psoriasis, and diabetes mellitus (each in one patient). Two patients did not have any predisposing diseases or immunosuppressive treatments. Seventeen patients presented with diarrhea and were classified as chronic intestinal strongyloidiasis (57%), asymptomatic infection with peripheral eosinophilia was diagnosed in 7 (23%), and 6 patients (20%) developed hyperinfection syndrome. Seventeen patients (57%) presented peripheral eosinophilia. Diagnosis was achieved by direct visualization of larvae in feces by Baermann technique (n = 20), by multiple stool smears examinations (n = 2), by combination of both (n = 1), by visualization of the filariform larvae in duodenal fluid and stool (n = 1), and in fecal and bronchoalveolar lavage specimens (n = 6). Overall mortality in this series was 20% (6/30). There was no significant correlation between age and mortality. A significant inverse correlation between the survival rate and CD4 T-cell count as well as eosinophilia was observed. There was also a significant correlation between HIV co-infection and mortality. Twenty-two patients responded favorably to treatment with ivermectin.

Infección por Strongyloides stercoralis: estudio epidemiológico, clínico, diagnóstico y terapéutico en 30 pacientes / Infection due to Strongyloides stercoralis: epidemiological, clinical, diagnosis findings and outcome in 30 patients

Background: Strongyloides stercoralis is a nematode parasite, which is endemic in tropical and subtropical regions. Infection usually remains asymptomatic, but in immunocompromised hosts severe and life-threatening manifestations such as hyperinfection syndrome and disseminated disease might occur. Methods: We retrospectively analyzed the epidemiological and clinical characteristics, including HIV co-infection, microbiological findings, and outcome in 30 patients with strongyloidiasis, who attended in the Infectious Diseases F. J. Muñiz Hospital in Buenos Aires from January 2004 to December 2008. Results: The study included 20 men and 10 women with an average age of 33 years. HIV co-infection was present in 21 patients (70 percent) with a median CD4 T cell count of 50 cells/mm³ (range 7-355) (average 56 cells/mm³). Among HIV negative patients the following comorbidities were detected: tuberculosis (n = 3) and chronic alcoholism, leprosy treated with corticosteroids, immunosuppressive treatment for psoriasis, and diabetes mellitus (each in one patient). Two patients did not have any predisposing diseases or immunosuppressive treatments. Seventeen patients presented with diarrhea and were classified as chronic intestinal strongyloidiasis (57 percent), asymptomatic infection with peripheral eosinophilia was diagnosed in 7 (23 percent), and 6 patients (20 percent) developed hyperinfection syndrome. Seventeen patients (57 percent) presented peripheral eosinophilia. Diagnosis was achieved by direct visualization of larvae in feces by Baermann technique (n = 20), by multiple stool smears examinations (n = 2), by combination of both (n = 1), by visualization of the filariform larvae in duodenal fluid and stool (n = 1), and in fecal and bronchoalveolar lavage specimens (n = 6). Overall mortality in this series was 20 percent (6/30). There was no significant correlation between age and mortality. A significant inverse correlation between the survival rate and CD4 T-cell count as well as eosinophilia was observed. There was also a significant correlation between HIV co-infection and mortality. Twenty-two patients responded favorably to treatment with ivermectin.

Antecedentes: Strongyloides stercoralis, parásito endémico de áreas tropicales y subtropicales del planeta, en sujetos inmunodeprimidos puede cursar con formas graves y aun mortales como el síndrome de hiperinfestación y la enfermedad diseminada. Métodos: Análisis retrospectivo de las características epidemiológicas, manifestaciones clínicas, co-infección por virus de inmunodeficiencia humana (VIH), hallazgos microbiológicos y evolución de 30 pacientes con estrongiloidiasis, atendidos en el Hospital de Enfermedades Infecciosas F. J. Muñiz de Buenos Aires, entre enero 2004 y diciembre 2008. Resultados: Se incluyeron en la evaluación 20 hombres y 10 mujeres con una mediana de edad de 33 años. Co-infección por VIH hubo en 21 pacientes (70 por ciento); la mediana de linfocitos T CD4+ en ellos al momento del diagnóstico de la parasitosis fue de 50 céls/mm³ (rango 7 a 355), (media de 56 céls/mm³). En los pacientes seronegativos para VIH, se comprobaron las siguientes co-morbilidades: tuberculosis (n: 3) y un caso de cada una de las siguientes afecciones: alcoholismo crónico, diabetes mellitus, reacción lepromatosa bajo corticotera-pia, y psoriasis en tratamiento inmunosupresor. Hubo dos pacientes sin aparentes enfermedades de base. Diecisiete pacientes presentaron enfermedad intestinal crónica con diarrea (57 por ciento), era asintomática y fue sospechada por la eosinofilia periférica (n: 7, 23 por ciento) y se clasificó como síndrome de hiperinfestación (n: 6, 20 por ciento) diagnosticado por la identificación de larvas en la materia fecal y secreciones broncopulmonares. Diecisiete pacientes (57 por ciento) presentaron eosinofilia periférica. El diagnóstico se efectuó por la visualización directa de las larvas en muestras de heces en fresco mediante la técnica de concentración de Baer-man (n: 20); por el examen copro-parasitológico seriado (n: 2) y por ambos métodos (n: 1); en líquido duodenal y materia fecal (n: 1) y por la identificación de larvas en materia fecal y secreciones respiratorias (n: 6). Letalidad global: 20 por ciento (6/30). Los pacientes con eosinofilia tuvieron una menor letalidad que aquellos sin esta respuesta (p < 0,001). No hubo correlación estadística entre la edad y la supervivencia. Sí fue significativa la correlación entre el recuento de CD4 y la letalidad, incluyendo 18 de los 21 pacientes seropositivos para VIH (p: 0,03). Finalmente, la correlación seropositividad para VIH y letalidad también fue significativa. Veintidós pacientes respondieron a la terapia antiparasitaria con ivermectina y evolucionaron favorablemente.

Unresponsive cutaneous leishmaniasis and HIV co-infection: report of three cases.

Cutaneous leishmaniasis (CL) is a vector borne disease caused by various species of Leishmania parasite. CL is endemic in the Thar desert of Rajasthan state and Himachal Pradesh in India. Immune suppression caused by human immunodeficiency virus (HIV) infection is associated with atypical clinical presentation of CL which responds poorly to the standard treatment and causes frequent relapses. We are reporting three cases of localized and disseminated CL due to Leishmania tropica which failed to respond to conventional intralesional/intramuscular sodium stibogluconate (SSG) injections. Initially, we did not think of HIV infection because CL is endemic in this region. When patients did not respond to SSG injections, we performed enzyme-linked immunosorbent assay (ELISA) tests for HIV and they turned out to be HIV positive. Our report showed that CL is emerging as an opportunistic infection associated with HIV/AIDS and may be the first manifestation in HIV positive patients in an endemic area.

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.

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.

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.

AIDS and HIV infections: uncommon presentations.

Infection with HIV or AIDS has a great impact on skin diseases, not only by affecting the immune system and thereby host defense against bacterial, viral, or mycotic infection, but also by changing tumor immune response and autoimmune reactivity. In the present review, emphasis will be made on infectious diseases, including sexually transmitted disease, inflammatory skin disease, and neoplasias. Knowledge of changing disease pattern with HIV/AIDS may help the clinical dermatologist and venerologist to identify dermatoses and act in the most appropriate manner to support the patient.

Leprosy and HIV co-infection in five patients.

In a retrospective study, five patients are reported who suffered from a Mycobacterium leprae/HIV co-infection and were treated for their HIV infection with HAART. In four patients, this revealed their leprosy and induced a type I leprosy reaction. Two patients who were lepromin negative at diagnosis were retested after about 1 year of anti-retroviral treatment, and found to be positive.

Penicillium marneffei infection: an AIDS-defining illness.

A 29-year-old HIV seropositive male patient from Manipur presented with fever, cough, weight loss and asymptomatic papules and nodules all over the body. Differential diagnoses of secondary syphilis, histoplasmosis, cryptococcosis and penicilliosis were considered. Histopathological and mycological study of the skin biopsy tissue, and blood culture confirmed the diagnosis of penicilliosis. Although penicilliosis, an AIDS-defining illness, is restricted to Southeast Asia, more and more cases are being recognized in non-endemic countries.

Immune reconstitution inflammatory syndrome associated with HIV and leprosy.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is an unusual inflammatory reaction to an opportunistic infection that occurs in human immunodeficiency virus (HIV)-positive patients with profound immunosuppression during the reconstitution of the immune system in the initial months of highly active antiretroviral treatment. OBSERVATIONS: We describe 3 cases of leprosy occurring in patients treated with a combination of 3 antiretroviral drugs who fulfilled the criteria for IRIS. A reactional state occurred in all 3 cases. Two of the 3 patients presented an unusual ulcerous progression of the lesions not generally observed in cases of leprosy. The outcome was favorable in all 3 cases. The frequency of IRIS associated with leprosy in French Guiana and Martinique is estimated at 3 cases per 1000 HIV-positive patients receiving highly active antiretroviral treatment. CONCLUSION: Leprosy should be recognized as an IRIS-associated infection with possibility of atypical presentation.

Leprosy and AIDS: two cases of increasing inflammatory reactions at the start of highly active antiretroviral therapy.

Reported here are the cases of two HIV-positive patients with skin lesions suggestive of leprosy, based on clinical and pathological analysis, which worsened during the few weeks following initiation of highly active antiretroviral therapy. The lesions improved after a few weeks of multidrug therapy for leprosy. Mycobacterium leprae was confirmed by polymerase chain reaction analysis of blood in case 1 and of a biopsy sample in case 2. Neither Mycobacterium avium complex nucleic acid, which is usually associated with immune restoration syndrome, nor mycobacterial cutaneous manifestations were detected in either case.