Human T cell responses to peptides of the Mycobacterium leprae 45-kD serine-rich antigen.

In order to identify T cell epitopes within the Mycobacterium leprae 45-kD serine-rich antigen, we analysed responses to overlapping 17-mer peptides encompassing the whole antigen in non-exposed UK controls, Pakistani leprosy patients and tuberculosis patients in both the United Kingdom and Pakistan. This antigen has been described as M. leprae-specific, although it has a hypothetical homologue in M. tuberculosis. Human peripheral blood mononuclear cells were stimulated with peptide for 5 days and IFN-gamma measured in supernatants by ELISA. Some peptides were recognized more frequently by T cells from tuberculoid leprosy patients than those from UK controls, suggesting that such T cell epitopes might have diagnostic potential, while other peptides induced greater responses among UK control subjects. Short-term cell lines confirmed that these assays detected specific T cell recognition of these peptides. However, many tuberculosis patients also recognized these potentially specific peptides suggesting that there could be a true homologue present in M. tuberculosis.

Tratamiento del deterioro agudo de la función neural en la lepra: resultado de un estudio prospectivo de cohort en Bangladesch

Se informa del resultado de 132 pacientes con deterioro agudo de la función nwerviosa (NFI) a los nervios sensitivos y un 67% de los motores evidenciaron mejoría , sin diferencia estadísticamente significativo en la respuesta de varios nervios a la prednisolona. La duración y gravedad del deterioro no son indicadores significativos del resultado terapéutico. Un total de 32% de los nervios determinados no respondieron el tratamiento con prednisolona y un 12% de los nervios afectados continuaron con deterioro funcional a pesar del tratamiento. En el grupo tratado, el valor medio ojo-mano-pie (EHF) se incrementó desde 2.02 al 1.33 (el valor mediano pasó de 2 a 1). Aproximadamente un tercio de los pacientes no recibieron tratamiento con prednisolona, motivo suficiente para que algunos presentaron NFI nuevo frente a un historial de deterioro crónico y resultaron NFI omitidos. El grupo de pacientes "injustamente tratados" presentó una mejoría espontánea de la función nerviosa sensorial del NFI del 62% de la función motora a los 12 meses desde el inicio de NFI. El valor EHF no registró ninguma mejoría estadísticamente significativa.

A clinical prediction rule for nerve-function impairment in leprosy patients.

BACKGROUND: Nerve-function impairment (NFI) commonly occurs during or after chemotherapy in leprosy and is the key pathological process leading to disability and handicap. We describe the development of a simple clinical prediction rule for estimating the risk of NFI occurrence. METHODS: New leprosy cases who presented to a centre in Bangladesh were recruited and followed up for 2 years in a field setting. We used multivariable regression analysis by Cox's proportional hazards model to identify predictive variables for NFI. Discriminative ability was measured by a concordance statistic. Internal validity was assessed with bootstrap resampling techniques. FINDINGS: 2510 patients were followed up for 2 years, 166 developed NFI. A simple model was developed with leprosy group (either paucibacillary leprosy [PB] or multibacillary leprosy [MB]) and the presence of any nerve-function loss at registration as predictive variables. Patients with PB leprosy and no nerve-function loss had a 1.3% (95% CI 0.8-1.8%) risk of developing NFI within 2 years of registration; patients with PB leprosy and nerve-function loss, or patients with MB leprosy and no nerve-function loss had a 16.0% (12-20%) risk; and patients with MB leprosy with nerve-function loss had a 65% (56-73%) risk. INTERPRETATION: Our prediction rule can be used to plan surveillance of new leprosy patients. Patients at low risk of NFI may need no follow-up beyond their course of chemotherapy (6 months); patients with intermediate risk need a minimum of 1 year of surveillance; and patients with high risk should have at least 2 years of surveillance for new NFI. Current recommendations for surveillance of patients with leprosy (for the duration of chemotherapy only) exclude an important group of patients who are at risk of developing NFI after completion of treatment.

Tratamiento del deterioro agudo de la función neural en la lepra: resultado de un estudio prospectivo de cohorte en Bangladesh

Se informa del resultado de 132 pacientes con deterioro mudo de la función nerviosa (NFI) a los 4 y 12 meses de iniciar tratamiento con prednisolona. En total un 68 por ciento de los nervios sensitivos y un 67 por ciento de los motores evidenciaron mejoría, sin diferencia estadísticamente significativo en la respuesta de varios nervios a la prednisolona. La duración v gravedad del deterioro no son indicadores significativos del resultado terapéutico. Un total de 32 por ciento de los nervios determinados no respondieron al tratamiento con prednisolona y un 12 por ciento de los nervios afectados continuaron con deterioro funcional a pesar del tratamiento. En el grupo tratado, el valor medio ojo-mano-pie (EHF) se incrementó desde 2.02 al l.33 (el valor mediano pasó de 2 a 1). Aproximadamente un tercio de los pacientes no recibieron tratamiento con prednisolona, motivo suficiente para que algunos presentaran NFI nuevo frente a un historial de deterioro crónico y resultaran NFI omitidos, El grupo de pacientes "injustamente tratados" presentó una mejoría espontánea de la función nerviosa sensorial del NFI del 62 por ciento de la función motora a los 12 meses desde el inicio de NFI. El valor EHF no registró ninguna mejoría estadísticamente significativa (AU)

CLIMATE: A New Route Toward Limiting Climate Change?

Climate change mitigation strategies have focused on reductions in carbon dioxide and other long-lived greenhouse gases. Smith et al., investigate the viability of a different strategy, recently proposed by Hansen et al., which focuses on controlling short-lived pollutants such as soot and tropospheric ozone. They conclude that carbon dioxide must remain the primary focus of climate change mitigation strategies.

Thalidomide in children undergoing bone marrow transplantation: series at a single institution and review of the literature.

Thalidomide has one of the most notorious drug histories because of its teratogenicity. Its widespread use in the 1960s led to a worldwide epidemic of phocomelia in inborns; this in turn led to its complete ban in most of the world. However, it has now been licensed for selected indications including graft-versus-host-disease (GVHD) after bone marrow transplantation, wasting associated with tuberculosis and human immunodeficiency virus infection, and leprosy. Little is known, however, about its use in children in these settings. Therefore, we report our experience and review the literature on thalidomide in children for GVHD after bone marrow transplantation. We studied 6 patients, 2 with chronic GVHD, 2 with acute GVHD, and 2 with acute GVHD progressing into chronic disease. One patient with chronic GVHD had a complete response, whereas the other had a partial response. Side effects consisted primarily of sedation and constipation, which are reported previously and well known side effects. None had neuropathy. One patient had rash, eosinophilia, and early pancreatitis that began shortly after initiation of thalidomide, persisted, and resolved only after discontinuation of thalidomide. Eosinophilia and pancreatitis are both previously unreported side effects or associated findings of thalidomide treatment. Review of the literature reveals three major studies of thalidomide in GVHD; of these two included children and adults together, and one in which age range of patients was not mentioned. In addition, four series of children receiving only thalidomide are reported. These series contained 1 to 14 patients each. Results show efficacy in at least 50% of children with chronic GVHD and little or no efficacy in children with exclusively acute GVHD. Side effects are similar to those reported in adults and consisted mostly of sedation and constipation, both of which subsided over time and resolved after discontinuing the drug. We speculate on the reasons for which thalidomide is more effective in chronic, compared with acute, GVHD in children, and make recommendations for future study.

Protective efficacy of BCG vaccine against leprosy in southern Malawi.

This paper describes a matched case-control study to determine the efficacy of BCG vaccine in preventing the occurrence of leprosy in southern Malawi, a previously unstudied area. The BCG immunization rate amongst 145 individuals with leprosy was 44.8%, compared to 62.5% in 290 matched controls. The protective efficacy of BCG vaccine against leprosy in this region was estimated to be 63.6%; smallpox immunization had no effect. These findings support the view that BCG vaccine should be considered as a control measure in areas where leprosy is endemic.

Comparative study of functional bracing and plaster cast treatment of stable lateral malleolar fractures.

In a prospective, randomized study, the use of the Aircast pneumatic air stirrup was compared with a standard below-knee walking cast in the management of Lauge-Hansen supination-eversion, stage II ankle fractures. Forty patients were randomly allocated to the two treatment groups. The use of the air stirrup led to a significant improvement in early patient comfort, post-fracture swelling, range of ankle motion at union, and time to full rehabilitation. We advocate the use of pneumatic air stirrup in the cost-effective management of stable ankle fractures.

Association of amyloidosis with erythema nodosum leprosum reactions and recurrent neutrophil leucocytosis in leprosy.

Rectal biopsy in 190 inpatients at a leprosy hospital in the Highlands of Papua New Guinea disclosed 16 patients with secondary amyloidosis. This represented 20% of the patients who had had polar lepromatous leprosy (L.L.) for more than 2 years. Patients with amyloidosis characteristically had either a history of recurrent attacks of erythema nodosum leprosum (E.NH) reactions or chronic trophic ulcers. Levels of the serum component (protein SAA) antigenically related to the amyloid fibril protein AA were monitored, at varying intervals for three months, in lepromatous patients with E.N.L. reaction. The SAA levels rose during E.N.L. reactions in parallel with the neutrophil count. SAA occurred with greatest frequency among patients with LH, while most non-lepromatous patients with detectable SAA had chronic trophic ulcers. The correlation between raised neutrophil count and elevated SAA concentration, observed in this and other studies, suggests that neutrophils are associated with the production of SAA.

Association of amyloidosis with erythema nodosum leprosum reactions and recurrent neutrophil leucocytosis in leprosy

Rectal biopsy in 190 inpatients at a leprosy hospital in the Highlands of Papua New Guinea disclosed 16 patients with secondary amyloidosis. This represented 20% of the patients who had had polar lepromatous leprosy (L.L.) for more than 2 years. Patients with amyloidosis characteristically had either a history of recurrent attacks of erythema nodosum leprosum (E.NH) reactions or chronic trophic ulcers. Levels of the serum component (protein SAA) antigenically related to the amyloid fibril protein AA were monitored, at varying intervals for three months, in lepromatous patients with E.N.L. reaction. The SAA levels rose during E.N.L. reactions in parallel with the neutrophil count. SAA occurred with greatest frequency among patients with LH, while most non-lepromatous patients with detectable SAA had chronic trophic ulcers. The correlation between raised neutrophil count and elevated SAA concentration, observed in this and other studies, suggests that neutrophils are associated with the production of SAA.