The Prevalence of Previously Undiagnosed Leprosy in the General Population of Northwest Bangladesh

In order to estimate the level of leprosy in an area with many leprosy patients, we determined the prevalence of previously undiagnosed leprosy in the general population and compared this with the registered (or known) number of leprosy patients. We also compared it with the known prevalence of leprosy in contacts of leprosy patients. We examined 20 randomly selected geographical clusters of 1,000 persons each in two districts of Bangladesh, with over 4 million population. Physical examination was performed on all individuals. The number of newly found leprosy cases among 17,862 people above 5 years of age from the clusters was 27, giving a rate of previously undiagnosed leprosy of 15.1 per 10,000. This rate is six times higher than the registered prevalence, but three times lower than the rate in the most distant subgroup of contacts (neighbour of neighbour and social contacts) of leprosy patients in the same area. We conclude that in areas where leprosy is common, it may be preferable to do full village or neighbourhood surveys when a new leprosy patient is found, rather than to limit contact surveys to close contacts only, such as household members

Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy

Objective To determine the effectiveness of chemoprophylaxis using a single dose of rifampicin to prevent leprosy in close contacts. Design Single centre, double blind, cluster randomised, placebo controlled trial. SettingLeprosy control programme in two districts of northwest Bangladesh with a population of more than four million. Participants28 092 close contacts of 1037 patients with newly diagnosed leprosy. 21 711 contacts fulfilled the study requirements. Interventions A single dose of rifampicin or placebo given to close contacts in the second month of starting the index patient’s treatment, with follow-up for four years. Main outcome measure Development of clinical leprosy. Results 18 869 of the 21 711 contacts (86.9%) were followed-up at four years. Ninety one of 9452 contacts in the placebo group and 59 of 9417 in the rifampicin group had developed leprosy. The overall reduction in incidence of leprosy using a single dose of rifampicin in the first two years was 57% (95% confidence interval 33% to 72%). The groups did not differ between two and four years. The overall number needed to treat (NNT) to prevent a single case of leprosy among contacts was 297 (95% confidence interval 176 to 537). Differences were found between subgroups at two years, both in reduction of incidence and in NNT. ConclusionA single dose of rifampicin given to contacts of patients with newly diagnosed leprosy is effective at preventing the development of clinical leprosy at two years. The effect was maintained, but no difference was seen between the placebo and rifampicin groups beyond two years. Trial registration Current Controlled Trials ISRCTN61223447

Preventing Nerve Function Impairment in Leprosy: Validation and Updating of a Prediction Rule

Leprosy is caused by a bacterium that attacks the peripheral nerves. This may cause nerve function impairment (NFI), resulting in handicaps and disabilities. Therefore, prediction and prevention of NFI is extremely important in the management of leprosy. In 2000, a prediction rule for NFI was published, but circumstances have changed since the study was performed in the 1990s: the leprosy detection delay has shortened and the definition of NFI has changed. The original rule used ‘leprosy classification’ and ‘NFI present at diagnosis’ to predict future NFI. In the current patient population we studied an adjusted rule based on ‘leprosy classification’ and ‘presence of antibodies’. This adjusted rule predicted NFI more often than the original rule. With the adjusted rule it is now also possible to assess NFI risk before the first nerve damage event takes place. This may help doctors and health workers to improve surveillance for people at high risk. Early detection and treatment can then prevent permanent disabilities

The spatial distribution of leprosy cases during 15 years of a leprosy control program in Bangladesh: An observational study

BACKGROUND: An uneven spatial distribution of leprosy can be caused by the influence of geography on the distribution of risk factors over the area, or by population characteristics that are heterogeneously distributed over the area. We studied the distribution of leprosy cases detected by a control program to identify spatial and spatio-temporal patterns of occurrence and to search for environmental risk factors for leprosy. METHODS: The houses of 11,060 leprosy cases registered in the control area during a 15-year period (1989-2003) were traced back, added to a geographic database (GIS), and plotted on digital maps. We looked for clusters of cases in space and time. Furthermore, relationships with the proximity to geographic features, such as town center, roads, rivers, and clinics, were studied. RESULTS: Several spatio-temporal clusters were observed for voluntarily reported cases. The cases within and outside clusters did not differ in age at detection, percentage with multibacillary leprosy, or sex ratio. There was no indication of the spread from one point to other parts of the district, indicating a spatially stable endemic situation during the study period. The overall risk of leprosy in the district was not associated with roads, rivers, and leprosy clinics. The risk was highest within 1 kilometer of town centers and decreased with distance from town centers. CONCLUSION: The association of a risk of leprosy with the proximity to towns indicates that rural towns may play an important role in the epidemiology of leprosy in this district. Further research on the role of towns, particularly in rural areas, is warranted

Statins in Candidemia: clinical outcomes from a matched cohort study

<p>Abstract</p> <p>Background</p> <p>HMG CoA reductase inhibitors (statins) in patients with bacteremic sepsis have shown significant survival benefits in several studies. There is no data on the effect of statins in candidemic patients, however in-vitro models suggest that statins interfere with ergesterol formation in the wall of yeasts.</p> <p>Methods</p> <p>This retrospective matched- cohort study from 1/2003 to 12/2006 evaluated the effects of statins on patients with candidemia within intensive care units. Statin-users had candidemia as a cause of their systemic inflammatory response and were on statins throughout their antifungal therapy, while non-statin users were matched based on age +/- 5 years and co-morbid factors. Primary analysis was 30-day survival or discharge using bivariable comparisons. Multivariable comparisons were completed using conditional logistic regression. All variables with a p-value less than 0.10 in the bivariable comparisons were considered for inclusion in the conditional logistic model.</p> <p>Results</p> <p>There were 15 statin-users and 30 non-statin users that met inclusion criteria, all with similar demographics and co-morbid conditions except the statin group had more coronary artery disease (P < 0.01) and peripheral vascular disease (P = 0.03) and lower median APCAHE II scores (14.6 vs 17, p = 0.03). There were no differences in duration of candidemia, antifungal therapy or <it>Candida </it>species between the groups. Statins were associated with lower mortality on bivariable (OR 0.09, 95% CI 0.11-0.75, p = 0.03) and multivariable (OR 0.22, 95% CI 0.02-2.4, p = 0.21) analyses compared to controls; although, in the latter the protective effect lacked statistical signficance.</p> <p>Conclusion</p> <p>In our small, single-center matched-cohort study, statins may provide a survival benefit in candidemia, however further studies are warranted to validate and further explore this association.</p

HIV-1 Inhibits Autophagy in Bystander Macrophage/Monocytic Cells through Src-Akt and STAT3

Autophagy is a homeostatic mechanism of lysosomal degradation. Defective autophagy has been linked to various disorders such as impaired control of pathogens and neurodegeneration. Autophagy is regulated by a complex array of signaling pathways that act upstream of autophagy proteins. Little is known about the role of altered regulatory signaling in disorders associated with defective autophagy. In particular, it is not known if pathogens inhibit autophagy by modulation of upstream regulatory pathways. Cells infected with HIV-1 blocked rapamycin-induced autophagy and CD40-induced autophagic killing of Toxoplasma gondii in bystander (non-HIV-1 infected) macrophage/monocytic cells. Blockade of autophagy was dependent on Src-Akt and STAT3 triggered by HIV-1 Tat and IL-10. Neutralization of the upstream receptors VEGFR, β-integrin or CXCR4, as well as of HIV-1 Tat or IL-10 restored autophagy in macrophage/monocytic cells exposed to HIV-1-infected cells. Defective autophagic killing of T. gondii was detected in monocyte-derived macrophages from a subset of HIV-1+ patients. This defect was also reverted by neutralization of Tat or IL-10. These studies revealed that a pathogen can impair autophagy in non-infected cells by activating counter-regulatory pathways. The fact that pharmacologic manipulation of cell signaling restored autophagy in cells exposed to HIV-1-infected cells raises the possibility of therapeutic manipulation of cell signaling to restore autophagy in HIV-1 infection