Monitoring and detection of leprosy patients in Southwest China: A retrospective study, 2010-2014.

More than 100 counties, mainly in southwest China, report incidence rates of leprosy >1/100,000. The current study analysed the epidemiology of leprosy in southwest China to improve our understanding of the transmission pattern and improve control programs. 207 counties were selected in southwest China. Leprosy patients and their household contacts were recruited. The data from the medical interview and the serological antileprosy antibody of the leprosy patients were analysed. A total of 2,353 new cases of leprosy were interviewed. The distribution of leprosy patients was partly associated with local natural and economic conditions, especially several pocket areas. A total of 53 from 6643 household contacts developed leprosy, and the incidence rate of leprosy in the household contacts was 364/100,000 person-years. We found that NDO-BSA attained higher positive rates than MMP-II and LID-1 regardless of clinical types, disability and infection time in leprosy patients. By means of combination of antigens, 88.4% patients of multibacillary leprosy were detected, in contrast to 59.9% in paucibacillary leprosy. Household contacts should be given close attention for the early diagnosis, disruption of disease transmission and precise control. Applications of serology for multi-antigens were recommended for effective coverage and monitoring in leprosy control.

Immune response to vaccination with DNA-Hsp65 in a phase I clinical trial with head and neck cancer patients.

DNA-hsp65, a DNA vaccine encoding the 65-kDa heat-shock protein of Mycobacterium leprae (Hsp65) is capable of inducing the reduction of established tumors in mouse models. We conducted a phase I clinical trial of DNA-hsp65 in patients with advanced head and neck carcinoma. In this article, we report on the vaccine's potential to induce immune responses to Hsp65 and to its human homologue, Hsp60, in these patients. Twenty-one patients with unresectable squamous cell carcinoma of the head and neck received three doses of 150, 400 or 600 microg naked DNA-hsp65 plasmid by ultrasound-guided intratumoral injection. Vaccination did not increase levels of circulating anti-hsp65 IgG or IgM antibody, or lead to detectable Hsp65-specific cell proliferation or interferon-gamma (IFN-gamma) production by blood mononuclear cells. Frequency of antigen-induced IL-10-producing cells increased after vaccination in 4 of 13 patients analyzed. Five patients showed disease stability or regression following immunization; however, we were unable to detect significant differences between these patients and those with disease progression using these parameters. There was also no increase in antibody or IFN-gamma responses to human Hsp60 in these patients. Our results suggest that although DNA-hsp65 was able to induce some degree of immunostimulation with no evidence of pathological autoimmunity, we were unable to differentiate between patients with different clinical outcomes based on the parameters measured. Future studies should focus on characterizing more reliable correlations between immune response parameters and clinical outcome that may be used as predictors of vaccine success in immunosuppressed individuals.

Leprosy: diagnostic and control challenges for a worldwide disease.

Leprosy is a curable disease with well-defined etiology, but lacks better diagnostic tools, preventive and therapeutic strategies. The continued application of the Ridley-Jopling clinical classification that recognizes the natural diversity of the immune response has provided the basis for understanding leprosy, and this review proposes its implementation in all Reference Centers in order to standardize the diagnostic resources, aiming at the improvement of the disease control. Due to the broad bioepidemiological aspects of infection its eradication is difficult, and proper diagnosis of the disease and the correct clinical classification are required to ensure proper treatment. Tools and markers for diagnosis and prognosis, and the novel use of nanotechnology, as well as strategies for disease control and monitoring populations at higher risk are still continuous challenges, which will be specifically reviewed with additional insights. The use of the current diagnostic tools, such as ELISA and PCR has a very limited approach for leprosy that has been considered as a marginal disease; therefore, the current diagnostic tools must be applied extensively in the routine to accumulate clinical experience in order to improve their precise application, like what has been done in many other infectious diseases. Since a vaccine for leprosy presents an unpredictable future, the proposed chemoprophylaxis of contacts (healthy carriers and/or with subclinical infection) must also be employed in referral centers of endemic countries not only to evaluate its efficacy, but also because of the favorable cost-benefit ratio, given that there is no other available approach, besides the multi-drug therapy of patients. This strategy should readily be applied as a public health policy, and may lead to a substantial breakage of the transmission chain aiming a world without leprosy.

El ML Flow test como técnica de diagnóstico inmediato para programas de control de la lepra: posible impacto sobre la clasificación de los pacientes / No disponible

Objetivo: Evaluar la utilidad de la técnica ML Flow como un instrumento adicional, de tipo serológico, para la clasificación en Brasil, Nepal y Nigeria, 2.632 pacientes de lepra mediante tres métodos: (1) como pacientes multibacilares (MB) o paucibacilares (PB) de acuerdo al número de lesiones (clasificación OMS), (2) mediante la baloscopia y (3) con serología utilizando el ML Flow Test que detecta anticuerpos IgM específicos frente al Mycobacterium leprae PGL-1. Resultados: La proporción de pacientes MB era del 39,5, 35,6 y 19,4% en Brasil, Nepaly Nigeria, respectivamente. La seropositividad mayor fue observada en los pacientes de Nigeria (62,9%), seguido por Brasil (50,8%) y Nepal (35,6%). Los resultados del ML Flor Test y baciloscopia resultaron negativos en el 69,1 y 82,7% de los pacientes PB, mientras que fueron positivos en el 58,6% de los pacientes MB de Brasil y 28,3% de Nepal. En los pacientes MB, tanto los frotis como el ML Flow Test resultaron negativos en el 15,6% de los pacientes de Brasil y 38,3% en Nepal. La evaluación de todos los pacientes PB con el ML Flow para prevenir un posible sub-tratamiento podría incrementar el grupo MB un 18, 11 y 46,2% para Brasil, Nepal y Nigeria, respectivamente. Con el ML Flow Test como único criterio para la clasificación, el incremento resultante sería del 11.3 y 43,5% de pacientes que requerirían tratamiento para la lepra MB en Brasil y Nigeria, respectivamente y una disminución del 3.7% en Nepal. Conclusiones: El test ML Flow puede ser útil para mejorar la clasificación, reducir el riesgo de sub-tratamiento con el consiguiente fracaso terapéutico y minimizar la necesidad de frotis cutáneos (AU)

Objective: To evaluate the use of the ML Flow test as an additional, serological, tool for the classification of new leprosy patients. Design: In Brazil, Nepal and Nigeria, 2.632 leprosy patients were classified by three metods: (1) as multibacillary (MB) or paucibacillary (PB) according to the number of lesions (WHO classification), (2) by slit skin smear examination, and (3) by serology using the ML Flow test detecting IgM antibodies to Mycobacterium leprae-specific phenolic glycolipid-I. Results: The proportion of MB leprosy patients was 39.5, 35,6 and 19,4% in Brazil, Nepal and Nigeria, respectively. The highest seropositivity in patients was observed in Nigeria (62,9%), followed by Brazil (50,8%) and Nepal (35,6%). ML Flow test results and smears were negative in 69.1 and 82,7% of PB patients, while smears were positive in 58.6% of MB patients in Brazil and 28.3% in Nepal. In MB patients, both smears and ML Flow test were negative in 15.6% in Brazil and 38.3% in Nepal. Testing all PB patients with the ML Flow test to prevent under-treatment would increase the MB group by 18, 11 and 46,2% for brazil, Nepal and Nigeria, respectively. Using the ML Flow test as the sole criterion for classification would result in an increase of 11.3 and 43,5% of patients requiring treatment for MB leprosy in Brazil and Nigeria, respectively, and a decrease of 3.7% for Nepal. Conclusions: The ML Flow test could be used to strengthen classification, reduce the risk of under-treatment and minimize the need for slit skin smears (AU)

Immunomodulación en la práctica pediátrica / Immunomodulation in pediatric practice

En los últimos años la inmunoterapia ha tomado un gran auge debido, primordialmente, a la variedad de alternativas descritas, fundamentadas en una gran cantidad de estudios clínicos, lo que ha permitido que enfermedades aparentemente poco complicadas, pero cuya resolución es frecuentemente problemática, como las infecciones recurrentes de las vías respiratorias, hasta enfermedades crónicas como tuberculosis, lepra, colagenopatías y enfermedades malignas, etc., ahora puedan tener un mejor pronostico. Es importante resaltar la importancia de conocer las características farmacologicas de estos medicamentos, así como sus indicaciones precisas. con el fin de no caer en el mal uso de los mismos y poder ofrecer a los pacientes un recurso valioso y eficaz de cara al nuevo milenio

An hypothesis to explain why cell-mediated immunity alone can contain infections by certain intracellular parasites and how immune class regulation of the response against such parasites can be subverted.

Cells with a low density of parasite-specific antigens on their surface are postulated to be susceptible to a cell-mediated attack but not to effector mechanisms normally activated following the binding of specific antibody to the infected cell. It is further postulated that such infected cells normally induce a cell-mediated response, and that cells infected with slow-growing intracellular parasites have a low density of parasite-specific antigens on their surface. Despite these general postulates, cell-mediated immunity is not invariably induced following natural infection by certain slow-growing parasites, such as those responsible for leprosy, tuberculosis, and the leishmaniases, and antibody can be induced that is exclusive of a strong, cell-mediated response. It is proposed that certain events in such cases subvert the normal regulatory processes that control the class of immunity induced. In these cases, the parasite-infected cells, bearing a low representation of parasite antigens, induce antibody even though they are not susceptible to antibody-dependent effector mechanisms, and so they are not eliminated. In this case, chronic infection and uncontrolled growth of the parasite occurs, often with fatal consequences.