Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy

Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis

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

A Novel Therapeutic and Prophylactic Vaccine (HVJ-Envelope / Hsp65 DNA + IL-12 DNA) against Tuberculosis Using the Cynomolgus Monkey Model

AbstractWe have developed a novel tuberculosis (TB) vaccine; a combination of the DNA vaccines expressing mycobacterial heat shock protein 65 (HSP65) and interleukin 12 (IL-12) delivered by the hemagglutinating virus of Japan (HVJ)-envelope and –liposome (HSP65 + IL-12/HVJ). An IL-12 expression vector (IL-12DNA) encoding single-chain IL-12 proteins comprised of p40 and p35 subunits were constructed. This vaccine provided remarkable protective efficacy in mouse and guinea pig models compared to the BCG vaccine on the basis of C.F.U of number of TB, survival, an induction of the CD8 positive CTL activity and improvement of the histopathological tuberculosis lesions. This vaccine also provided therapeutic efficacy against multi-drug resistant TB (MDR-TB) and extremely drug resistant TB (XDR-TB) (prolongation of survival time and the decrease in the number of TB in the lung) in murine models. Furthermore, we extended our studies to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis. This novel vaccine provided a higher level of the protective efficacy than BCG based upon the assessment of mortality, the ESR, body weight, chest X-ray findings and immune responses. All monkeys in the control group (saline) died within 8 months, while 50% of monkeys in the HSP65+hIL-12/HVJ group survived more than 14 months post-infection (the termination period of the experiment). Furthermore, the BCG priming and HSP65 + IL-12/HVJ vaccine (booster) by the priming-booster method showed a synergistic effect in the TB-infected cynomolgus monkey (100% survival). In contrast, 33% of monkeys from BCG Tokyo alone group were alive (33% survival). Furthermore, this vaccine exerted therapeutic efficacy (100% survival) and augmentation of immune responses in the TB-infected monkeys. These data indicate that our novel DNA vaccine might be useful against Mycobacterium tuberculosis including XDR-TB and MDR-TB for human therapeutic clinical trials

Improving access to lymphatic filariasis MMDP services through an enhanced evidence-based, cascaded training model for health worker capacity strengthening in Ghana: an evaluation study

IntroductionGhana has made significant progress in reducing the transmission rate of lymphatic filariasis. However, very little progress has been made in the provision of morbidity management and disability prevention (MMDP) services, which is one of the key requirements for certification of elimination as a disease of public health importance. This study was designed to compare pre-post- intervention to determine the feasibility and effectiveness of a cascade training model for health worker capacity strengthening in Ghana, using the WHO recommended minimum intervention package to improve access to MMDP services.MethodsThis study used a quasi-experimental design to assess the impact of evidence-based training of patients with lymphatic filariasis (LF) in the Upper West region of Ghana. All lymphedema patients who were available at the time of data collection participated in the study before and after the training.ResultsThe mean age of respondents was 54.67 years (SD ± 16.89 years) at baseline and 54.70 years (SD ± 15.80 years) at evaluation. The majority (i.e., 76.30% at baseline and 80.50% at evaluation) of the respondents were female. Most of the respondents had not completed primary school (83.82% at baseline and 85.40% at evaluation). We found an improvement in the quality of life among LF patients, that is, the proportion of respondents who reported having a high quality of life increased from 2.9% at baseline to 20.12% at evaluation (p < 0.001). The lymphedema management practice of “hygiene/washing and drying of affected limb” was reported by 73.17% of respondents at evaluation compared with only 32.95% of respondents at baseline (p < 0.001). The acute attack management technique of “cooling the affected limb in cool water/cold compress” was reported by 70.15% of respondents at evaluation compared with 23.70% of respondents at baseline (p < 0.001).ConclusionThe research confirmed that LF-related perceptions remained generally the same at baseline and evaluation among community members. The implementation of the LF-related morbidity management (MMDP) project has led to a significant improvement in the morbidity management practices among patients at evaluation compared with baseline. Our findings also showed that self-care led to an improvement in patients’ quality of life. This justifies the need for investment in morbidity management interventions in endemic communities

Mapping suitability for Buruli ulcer at fine spatial scales across Africa: A modelling study.

Buruli ulcer (BU) is a disabling and stigmatising neglected tropical disease (NTD). Its distribution and burden are unknown because of underdiagnosis and underreporting. It is caused by Mycobacterium ulcerans, an environmental pathogen whose environmental niche and transmission routes are not fully understood. The main control strategy is active surveillance to promote early treatment and thus limit morbidity, but these activities are mostly restricted to well-known endemic areas. A better understanding of environmental suitability for the bacterium and disease could inform targeted surveillance, and advance understanding of the ecology and burden of BU. We used previously compiled point-level datasets of BU and M. ulcerans occurrence, evidence for BU occurrence within national and sub-national areas, and a suite of relevant environmental covariates in a distribution modelling framework. We fitted relationships between BU and M. ulcerans occurrence and environmental predictors by applying regression and machine learning based algorithms, combined in an ensemble model to characterise the optimal ecological niche for the disease and bacterium across Africa at a resolution of 5km x 5km. Proximity to waterbodies was the strongest predictor of suitability for BU, followed potential evapotranspiration. The strongest predictors of suitability for M. ulcerans were deforestation and potential evapotranspiration. We identified patchy foci of suitability throughout West and Central Africa, including areas with no previous evidence of the disease. Predicted suitability for M. ulcerans was wider but overlapping with that of BU. The estimated population living in areas predicted suitable for the bacterium and disease was 46.1 million. These maps could be used to inform burden estimations and case searches which would generate a more complete understanding of the spatial distribution of BU in Africa, and may guide control programmes to identify cases beyond the well-known endemic areas

Measuring solar reflectance—Part I: Defining a metric that accurately predicts solar heat gain

Solar reflectance can vary with the spectral and angular distributions of incident sunlight, which in turn depend on surface orientation, solar position and atmospheric conditions. A widely used solar reflectance metric based on the ASTM Standard E891 beam-normal solar spectral irradiance underestimates the solar heat gain of a spectrally selective 'cool colored' surface because this irradiance contains a greater fraction of near-infrared light than typically found in ordinary (unconcentrated) global sunlight. At mainland U.S. latitudes, this metric RE891BN can underestimate the annual peak solar heat gain of a typical roof or pavement (slope {le} 5:12 [23{sup o}]) by as much as 89 W m{sup -2}, and underestimate its peak surface temperature by up to 5 K. Using R{sub E891BN} to characterize roofs in a building energy simulation can exaggerate the economic value N of annual cool-roof net energy savings by as much as 23%. We define clear-sky air mass one global horizontal ('AM1GH') solar reflectance R{sub g,0}, a simple and easily measured property that more accurately predicts solar heat gain. R{sub g,0} predicts the annual peak solar heat gain of a roof or pavement to within 2 W m{sup -2}, and overestimates N by no more than 3%. R{sub g,0} is well suited to rating the solar reflectances of roofs, pavements and walls. We show in Part II that R{sub g,0} can be easily and accurately measured with a pyranometer, a solar spectrophotometer or version 6 of the Solar Spectrum Reflectometer

Routine Surveillance Data as a Resource for Planning Integration of NTD Case Management

Background: There is a high burden of morbidity due to neglected tropical diseases. To help address this, the World Health Organization recommends integration of case management (CM). Here, we present a practical framework designed to identify areas that could benefit from an integrated CM strategy in Ghana. We also investigated the accessibility of primary health care (PHC) to CM cases, and the impact of this on morbidity at diagnosis. Methods: Routinely detected cases of Buruli ulcer (BU) and leprosy, and suspected lymphedema identified through morbidity surveys during mass drug administration campaigns in Ghana in 2014 were remotely georeferenced. We estimated distances from cases’ home communities to the nearest primary healthcare facility (PHC), and compared rates of reported disease, completeness of clinical information, and risk of more severe morbidity, relative to PHC accessibility. Results: We georeferenced communities of 295/350 reported leprosy cases, 240/333 BU cases, and 1,557/2383 instances of lymphedema. Overlap of these diseases was predominantly around Accra and in the Upper East Region. Rates of reported disease appeared higher in populations with higher accessibility to PHC, and leprosy cases living further from PHC had a higher risk of disability at diagnosis. Conclusions: This investigation demonstrates the feasibility and value of using routinely collected data to map CM-NTDs at low cost. The maps presented are intended to provide a resource for planning the implementation of integrated CM for NTDs in Ghana. This approach could be easily implemented by national health services in other endemic countries in the future

Psychometric Properties of the Participation Scale among Former Buruli Ulcer Patients in Ghana and Benin

Background: Buruli ulcer is a stigmatising disease treated with antibiotics and wound care, and sometimes surgical intervention is necessary. Permanent limitations in daily activities are a common long term consequence. It is unknown to what extent patients perceive problems in participation in social activities. The psychometric properties of the Participation Scale used in other disabling diseases, such as leprosy, was assessed for use in former Buruli ulcer patients. Methods: Former Buruli ulcer patients in Ghana and Benin, their relatives, and healthy community controls were interviewed using the Participation Scale, Buruli Ulcer Functional Limitation Score, and the Explanatory Model Interview Catalogue to measure stigma. The Participation Scale was tested for the following psychometric properties: discrimination, floor and ceiling effects, internal consistency, inter-item correlation, item-total correlation and construct validity. Results: In total 386 participants (143 former Buruli ulcer patients with their relatives (137) and 106 community controls) were included in the study. The Participation Scale displayed good discrimination between former Buruli ulcer patients and healthy community controls. No floor and ceiling effects were found. Internal consistency (Cronbach's alpha) was 0.88. In Ghana, mean inter-item correlation of 0.29 and item-total correlations ranging from 0.10 to 0.69 were found while in Benin, a mean inter-item correlation of 0.28 was reported with item-total correlations ranging from 20.08 to 0.79. With respect to construct validity, 4 out of 6 hypotheses were not rejected, though correlations between various constructs differed between countries. Conclusion: The results indicate the Participation Scale has acceptable psychometric properties and can be used for Buruli ulcer patients in Ghana and Benin. Future studies can use this Participation Scale to evaluate the long term restrictions in participation in daily social activities of former BU patients