[Show abstract][Hide abstract] ABSTRACT: Mycobacterium ulcerans disease (MUD), often called Buruli ulcer (BU), can result in severe disabling of affected persons. It affects all parts of the body with the upper and lower extremities as the most affected areas. BU causes disabilities such as scarring, limb contractures, disfigurements, as well as a great deal of distress if it affects the face. Patients with BU of the face encounter both physical and psychological problems that make their living difficult. The disease on the face can cause loss of eyes, nose, lips, repositioning of facial features and destruction of other soft tissues of the face. This study aims to discuss the fate of persons with MUD of the face. Patients with MUD of the face should be given physical, social, economic and emotional support. This form of support should span from healthcare providers, families and friends to enhance their quality of life. Physiotherapy is also of great importance to both patients and health workers, to achieve a better physical appearance and psychological well-being.
[Show abstract][Hide abstract] ABSTRACT: Cebu has been one of the most leprosy endemic areas in the Philippines. Despite the high coverage rates of multiple drug therapy (MDT) and high BCG-vaccine coverage in children, leprosy control authorities believe that leprosy transmission and incidence (as evidence by continuing new case detection in both adults and children) have not declined as expected, once leprosy had been eliminated. In response to the concerns communicated by the authorities regarding ongoing leprosy transmission in Cebu, this study aims to examine the evidence for the hypothesized ongoing transmission, both in children and adults. Furthermore, it will be assessed which groups and areas are experiencing a continuing risk of leprosy infection; this can form a starting point for more targeted approaches to leprosy control.
Case records from 2000-2010 were retrospectively collected from the Leonard Wood Memorial Clinic archives, and all other clinics on the island where leprosy was treated. Between 2000 and 2010, 3288 leprosy cases were detected. The overall five year case notification rate (CNR) dropped significantly from 47.35 (2001-2005) to 29.21 cases (2006-2010) per 100.000 population. Smaller CNRs were reported for children; however the decline in child-CNR over the same period was minimal. Furthermore, no increase in median age of notification in children or adults was found between 2000 and 2010. Population-adjusted clustering of leprosy cases was mainly detected in urban and peri-urban areas.
Although the overall CNR declined significantly, CNR seems to be rather static in lower risk populations and areas. Cases are mainly found in urban areas, however CNRs in these areas decline at a much faster rate than in the lower endemic rural areas. A similar situation was found when comparing adults and children: CNRs observed in children were lower than in adults, but further decline (and elimination) of these childhood CNRs was found to be difficult. Moreover, the median age of notification in children has remained stable, suggesting transmission is still on-going. It is unclear why many years of good MDT-coverage and a gradual decline in CNR have not been accompanied by evidence of reduced transmission, especially beyond a certain threshold level of case notification. We believe that a new approach to leprosy control is required to tackle transmission more directly. The most promising approach may involve chemoprophylaxis and/or immunoprophylaxis interventions, targeted at high risk (urban) areas and groups such as household contacts, followed by a different approach once decline in CNR starts to level off. Identified clusters and trends can form the starting point for implementing this approach.
[Show abstract][Hide abstract] ABSTRACT: Cutaneous infection by Mycobacterium ulcerans, also known as Buruli ulcer (BU), represents the third most common mycobacterial disease in the world after tuberculosis and leprosy. Data on the burden of BU disease in the Democratic Republic of Congo are scanty. This study aimed to estimate the prevalence rate and the distribution of BU in the Songololo Territory, and to assess the coverage of the existing hospital-based reporting system.
We conducted a cross-sectional survey (July-August 2008) using the door-to-door method simultaneously in the two rural health zones (RHZ) of the Songololo Territory (RHZ of Kimpese and Nsona-Mpangu), each containing twenty health areas. Cases were defined clinically as active BU and inactive BU in accordance with WHO-case definitions.
We detected 775 BU patients (259 active and 516 inactive) in a total population of 237,418 inhabitants. The overall prevalence of BU in Songololo Territory was 3.3/1000 inhabitants, varying from 0 to 27.5/1000 between health areas. Of the 259 patients with active BU, 18 (7%) had been reported in the hospital-based reporting system at Kimpese in the 6-8 months prior to the survey.
The survey demonstrated a huge variation of prevalence between health areas in Songololo Territory and gross underreporting of BU cases in the hospital-based reporting system. Data obtained may contribute to better targeted and improved BU control interventions, and serve as a baseline for future assessments of the control program.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Nerve damage in leprosy often causes disabilities and deformities. Prednisolone is used to treat nerve function impairment (NFI). However, optimal dose and duration of prednisolone treatment has not been established yet. Besides treating existing NFI it would be desirable to prevent NFI. Studies show that before NFI is clinically detectable, nerves often show subclinical damage. Within the 'Treatment of Early Neuropathy in LEProsy' (TENLEP) study two double blind randomized controlled trials (RCT) will be carried out: a trial to establish whether prednisolone treatment of 32 weeks duration is more effective than 20 weeks in restoring nerve function in leprosy patients with clinical NFI (Clinical trial) and a trial to determine whether prednisolone treatment of early sub-clinical NFI can prevent clinical NFI (Subclinical trial). METHODS: Two RCTs with a follow up of 18 months will be conducted in six centers in Asia. In the Clinical trial leprosy patients with recent (< 6 months) clinical NFI, as determined by Monofilament Test and Voluntary Muscle Test, are included. The primary outcomes are the proportion of patients with restored or improved nerve function. In the Subclinical trial leprosy patients with subclinical neuropathy, as determined by Nerve Conduction Studies (NCS) and/or Warm Detection Threshold (WDT), and without any clinical signs of NFI are randomly allocated to a placebo group or treatment group receiving 20 weeks prednisolone. The primary outcome is the proportion of patients developing clinical NFI. Reliability and normative studies are carried out before the start of the trial. DISCUSSION: This study is the first RCT testing a prednisolone regimen with a duration longer than 24 weeks. Also it is the first RCT assessing the effect of prednisolone in the prevention of clinical NFI in patients with established subclinical neuropathy. The TENLEP study will add to the current understanding of neuropathy due to leprosy and provide insight in the effectiveness of prednisolone on the prevention and recovery of NFI in leprosy patients. In this paper we present the research protocols for both Clinical and Subclinical trials and discuss the possible findings and implications.Trial registration: Netherlands Trial Register: NTR2300Clinical Trial Registry India: CTRI/2011/09/002022.
[Show abstract][Hide abstract] ABSTRACT: Purpose: Multi-drug resistant tuberculosis (MDR-TB) and extremely drug resistant (XDR) TB are big problems in the world. We have developed novel TB therapeutic vaccines, HVJ-Envelope/HSP65 + IL-12 DNA vaccine (HSP65-vaccine), granulysin vaccine and killer specific secretory protein of 37kDa (Ksp37) vaccine. Methods and Results: HSP65 vaccine showed strong therapeutic effect against both MDR-TB and XDR-TB in mice. Intradermal immunization of HSP65-vaccine showed stronger therapeutic effect against TB than intramuscular or subcutaneous immunization. Furthermore, the synergistic therapeutic effect was observed when the vaccine was administrated in combination with Isoniazid (INH), which is a first line drug for chemotherapy. The combination of types of vaccines (HSP65- and granulysin- vaccines) also showed synergistic therapeutic effect. In the monkey model, granulysin-vaccine prolonged the survival period after the infection of TB and long-term survival was observed in vaccine-treated group. We examined the potential of two kinds of novel DNA vaccines (Ksp37-vaccine and granulysin-vaccine). Both vaccines augmented in vivo differentiation of CTL against TB. We measured the amount of Ksp37 protein in human serum and revealed that the level of Ksp37 protein of patients with tuberculosis was lower than that of healthy volunteers. Therefore, we established Ksp37 transgenic mice as well as granulysin transgenic mice to elucidate the function of those proteins. Both transgenic mice were resistant to TB infection. Conclusion: These data indicate the potential of combinational therapy; the combination of two DNA vaccines or combination of DNA vaccine with antibiotic drug. Thus, it will provide a novel strategy for the treatment of MDR-TB.
Human vaccines & immunotherapeutics. 12/2012; 9(3).
[Show abstract][Hide abstract] ABSTRACT: Purpose and Methods: Emergence of the multi-drug resistant (MDR) Mycobacterium tuberculosis (TB) is a big problem in the world. We have developed novel TB vaccines [DNA vaccines encoding HSP65 + IL-12, granulysin or killer-specific secretory protein of 37kDa (Ksp37)] using Hemagglutinating virus of Japan -envelope (HVJ-E). It is suggested that the activity of the TB-specific CTL is one of the most important factor for the resistance to TB and immunity for TB in chronic human TB disease. Therefore, we examined the level of activation of the TB-specific CTL after the administration of these vaccines. Results: HSP65 + IL-12 DNA vaccine showed higher protective efficacy compared with BCG in both mouse and monkey models of TB. It induced the TB-specific CTL in the mouse model of TB, while little level of activity was observed after the injection of BCG. It also showed strong therapeutic efficacy against MDR-TB. In the monkey model, the vaccine augmented the production of IFN-γ and IL-2 from PBL and the therapeutic effect was correlated with the level of IL-2. We next evaluated the potential of DNA vaccine encoding a granulysin, which is an important defensive molecule expressed by human T cells. We found that granulysin-encoding vaccine induced the differentiation of the CTL in vitro and in vivo. It also showed therapeutic efficacy against TB in the monkey as well as the mouse model. The DNA vaccine encoding a Ksp37 also induced the TB-specific CTL in vitro and in vivo in the mouse model. It augmented the production of IL-2, IFN-γ and IL-6 from T cells and spleen cells. A synergistic effect on the activation of the TB-specific CTL was observed by the combination of Ksp37 DNA vaccine with granulysin DNA vaccine. Conclusion: These data indicate that our novel vaccines (HSP65 + IL-12 DNA, granulysin and Ksp37) have a capability to activate the TB-specific CTL and will be very strong protective and therapeutic vaccines against TB.
Human vaccines & immunotherapeutics. 12/2012; 9(3).
[Show abstract][Hide abstract] ABSTRACT: Despite the huge effort and massive advances toward the elimination of leprosy over the last two decades, the disease has proven stubborn; new case detection rates have stabilised over the last few years and leprosy remains endemic in a number of localised regions. The American Leprosy Missions and Infectious Disease Research Institute have undertaken a large research effort aimed at developing new tools and a vaccine to continue the push for leprosy elimination. In this paper, we outline our strategy for the integration of rapid diagnostic tests and lab-based assays to facilitate the detection of early or asymptomatic leprosy cases, as well as the efficient and focused implementation of chemoprophylaxis and immunisation to intervene in leprosy development and transmission.
Memórias do Instituto Oswaldo Cruz 12/2012; 107:190-196. · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although leprosy is curable with drug treatment, the identification of biomarkers of infection, disease progression and treatment efficacy would greatly help to reduce the overall prevalence of the disease. Reliable biomarkers would also reduce the incidence of grade-2 disability by ensuring that those who are most at risk are diagnosed and treated early or offered repeated treatments in the case of relapse. In this study, we examined the reactivity of sera from lepromatous and tuberculoid leprosy patients (LPs) against a panel of 12 recombinant Mycobacterium leprae proteins and found that six proteins were strongly recognised by multibacillary (MB) patients, while only three were consistently recognised by paucibacillary patients. To better understand the dynamics of patient antibody responses during and after drug therapy, we measured antibody titres to four recombinant proteins, phenolic glycolipid-I and lipoarabinomannan at baseline and up to two years after diagnosis to investigate the temporal changes in the antibody titres. Reactivity patterns to individual antigens and decreases in antibody titres were patient-specific. Antibody titres to proteins declined more rapidly vs. those to carbohydrate and glycolipid antigens. Compared to baseline values, increases in antibody titres were observed during reactional episodes in one individual. Additionally, antibody responses against a subset of antigens that provided a good prognostic indicator of disease progression were analysed in 51 household contacts of MB index cases for up to two years. Although the majority of these contacts showed no change or exhibited decreases in antibody titres, seven individuals developed higher titres towards one or more of these antigens and one individual with progressively higher titres was diagnosed with borderline lepromatous leprosy 19 months after enrolment. The results of this study indicate that antibody titres to specific M. leprae antigens can be used to monitor treatment efficacy in LPs and assess disease progression in those most at risk for developing this disease.
Memórias do Instituto Oswaldo Cruz 12/2012; 107:79-89. · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cynomolgus monkeys are a useful model for human tuberculosis, but susceptibility to M. leprae is unknown. A cynomolgus model of leprosy could increase understanding of pathogenesis-importantly, neuritis and nerve-damaging reactions. We administered viable Mycobacterium leprae to 24 cynomolgus monkeys by three routes, with a median follow-up period of 6 years (range = 1-19 years) involving biopsies, nasal smears, antiphenolic glycolipid-1 (PGL-1) antibody serology, and lepromin skin testing. Most developed evanescent papules at intradermal M. leprae inoculation sites that, on biopsy, showed a robust cellular immune response akin to a lepromin skin test reaction; many produced PGL-1 antibodies. At necropsy, four monkeys, without cutaneous or gross neurological signs of leprosy but with elevated PGL-1 antibodies, including three with nasal smears (+) for acid fast bacilli (AFB), showed histological features, including AFB, suggestive of leprosy at several sites. Overall, however, cynomolgus monkeys seem minimally susceptible to leprosy after experimental M. leprae administration.
The American journal of tropical medicine and hygiene 08/2012; 87(2):327-36. · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This review focuses on nerve damage in leprosy. We present evidence to support the argument that leprosy is best seen as a chronic neurological condition rather than a simple skin disease. Nerve damage affects small dermal nerves and peripheral nerve trunks. Perineural inflammation is a characteristic and hallmark of early leprosy. T cell-mediated inflammation is the main pathological process in leprosy nerve damage. The level of nerve damage in leprosy is high with up to 60% of multibacillary patients having clinically apparent nerve damage at the time of diagnosis; 30% of patents may develop further nerve damage during treatment and 10% may develop new nerve damage after drug treatment. Since the nerve damage is immune mediated, the antibiotics used to treat Mycobacterium leprae infection have little effect on the accompanying nerve damage. This requires treatment with immunosuppressants to stop the inflammation. Treatment of nerve damage with steroids can be effective but about 50% of patients relapse and require a further course of steroids. Research is needed to refine steroid regimens to be used and define appropriate alternatives. Neuropathic pain is now being recognised as another late complication for leprosy patients. There are also service challenges relating to how best to identify patients who need steroid treatment and how to manage patients with established neuropathy who may require health services for many years.
International Health 06/2012; 4(2):77-85. · 1.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives. To describe trends and category of disabilities caused by Buruli ulcer disease. Design. This retrospective study was set up to quantify information on the disability trends caused by Buruli ulcer (BU) using data on patients attending BU and chronic ulcer clinics from 2004 to 2009, at Global Evangelical Mission Hospital, Apromase. Methods. Data was retrieved from the WHO BU1 form, case registry book, surgical theatre register, and BU patients' records book of the hospital. Disability was measured as the incapability of patients to perform one or more daily activities due to his/her state of BU disease before treatment. Results. A total of 336 positive BU cases comprising 181 males (53.9%) were recorded of which 113 (33.6%) cases of disabilities were identified. A mean age of 52.5 (±1.32) years was recorded. For the trend of disabilities, the year 2009 recorded the highest (N = 34, 31.0%). The lesions were mostly located at the lower limbs (N = 65, 57.5%) region of the patients. Lesions with diameter >15 cm were the major (59.3%) category of lesions. Conclusion. Trend of disability reveals proportional increase over the years from 2004 to 2009. Contracture at the knee and ankle joints was the commonest disability recorded.
Plastic surgery international. 01/2012; 2012:752749.
[Show abstract][Hide abstract] ABSTRACT: Aims. This retrospective study was to identify some challenges in the treatment of Buruli ulcer (BU) and present a proposed treatment regime. Materials and Methods. Information from patients medical records, hospital database, and follow-up findings on BU treatment procedures from 1994 to 1998 and from 2004 to 2007 at three research sites in Ghana were reviewed to determine the treatment challenges encountered. Data needed were recorded and analyzed, and results presented using SPSS version 17.0. Results. A total of 489 BU patients information was selected for the study. A majority (56.90%, n = 278) of the patients were children (0-14 years), with a mean age of 12.8 years. Significant challenges in BU treatment in Ghana identified included sequelae (P = 0.041 ), delayed treatment (P = 0.012 ), and high treatment cost (P = 0.044 ). Duration of hospital stay was clearly correlated with the time spent at home prior to admission; spearman's rank correlation coefficient was 0.72 (95% CI 0.42-0.87). Conclusion. Delays in seeking treatment among BU patients were the main factor which resulted in most of the other factors contributing to the challenges in treatment. A combination of psychosocial and biomedical approach was proposed as holistic method to alleviate the challenges in BU treatment.
Journal of Tropical Medicine 01/2012; 2012:371915.
[Show abstract][Hide abstract] ABSTRACT: Buruli ulcer (BU) is a necrotizing bacterial infection of skin, subcutaneous tissue and bone caused by Mycobacterium ulcerans. Although the functional impairment caused by BU results in severe suffering and in socio-economic problems, the disease remains largely neglected in Africa. The province of Bas-Congo in Democratic Republic of Congo contains one of the most important BU foci of the country, i.e. the Songololo Territory in the District of Cataractes. This study aims to assess the impact of a BU control project launched in 2004 in the Songololo Territory.
We used a comparative non-randomized study design, comparing clinical profiles and outcomes of the group of patients admitted at the General Reference Hospital (GRH) of the "Institut Médical Evangélique" (IME) of Kimpese 3 years before the start of the project (2002-2004) with those admitted during the 3 years after the start of the project (2005-2007).
The BU control project was associated with a strong increase in the number of admitted BU cases at the GRH of IME/Kimpese and a fundamental change in the profile of those patients; more female patients presented with BU, the proportion of relapse cases amongst all admissions reduced, the proportion of early lesions and simple ulcerative forms increased, more patients healed without complications and the case fatality rate decreased substantially. The median duration since the onset of first symptoms however remained high, as well as the proportion of patients with osteomyelitis or limitations of joint movement, suggesting that the diagnostic delay remains substantial.
Implementing a specialized program for BU may be effective in improving clinical profiles and outcomes in BU. Despite these encouraging results, our study highlights the need of considering new strategies to better improve BU control in a low resources setting.
[Show abstract][Hide abstract] ABSTRACT: To compare the occurrence, duration and severity of ENL in leprosy patients treated with either 12 or 24 months of standard multi-drug therapy (MDT).
Study population: 296 patients treated with MDT for 2 years, between 1985 and 1992 and followed up as part of a relapse study; and 293 patients, treated between 1998 and 2004, with MDT for 1 year and also followed up as part of a relapse study. The Chi squared test and multiple logistic regression analysis were used to test for statistical significance.
ENL was not significantly more common, but it was longer-lasting and more severe in patients receiving only 12 months of MDT, as compared with those receiving 24 months treatment. A high BI at the start of treatment significantly increased the risk of severe ENL by a factor of between 6 and 12, while treatment with 12 instead of 24 months of MDT significantly increased the risk by a factor of between 3 and 10.
This study provides further evidence that a high initial BI is the key risk factor for ENL. It also suggests that the difference between these two cohorts in their experience of ENL as demonstrated in this study, may be related to the different amounts of clofazimine which the two cohorts were given in the early years of their treatment. Further studies are needed to determine whether clofazimine could be used more specifically to reduce the severity of ENL in the small group of patients at high risk for the condition.
[Show abstract][Hide abstract] ABSTRACT: This study examines factors that may enhance the control and holistic treatment of Buruli ulcer in an endemic area of the Ashanti Region in Ghana. A total of 189 Buruli ulcer patients from the Bomfa sub-district were treated at the Global Evangelical Mission Hospital, Apromase-Ashanti, Ghana, from January to December 2005. Diagnosis was based on clinical findings and confirmed by any two positives of Ziehl-Neelson test for acid fast bacilli, polymerase chain reaction and histopathology. Children up to age 14 made up 43.4% of the cases; male: female ratio was 3:2. The mean duration of hospitalization was 77 days and hospital stay was significantly correlated with the time spent at home with the disease prior to admission; also, 76.7% of the cases were late ulcers. Of the 189 patients, 145 (i.e. 76.7%) were treated with antibiotics and surgery which involved excision, skin grafting with or without contracture release. A follow-up survey after the introduction of the psychosocial approach recorded fewer (85) new Buruli ulcer (BU) cases of which, the majority (78.8%, 67) were nodules and only 21.2% (18) were ulcers. Health education plays a major role in the holistic treatment of BU. This paper proposes a further study in other endemic areas on the treatment of BU with emphasis on psychosocial approach for holistic treatment.
Transactions of the Royal Society of Tropical Medicine and Hygiene 06/2011; 105(8):459-65. · 1.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the frequency, time interval to relapse and the possible risk factors for relapse in multibacillary (MB) leprosy after 1 year's treatment with the standard multi-drug therapy (MDT).
Smear positive MB patients treated with MDT for 1 year were enrolled in a prospective relapse study between 1999 and 2005 at the Leonard Wood Memorial Center for Leprosy Research (LWM). After treatment completion, at yearly intervals, patients underwent slit-skin smear examination and were clinically monitored for possible signs of relapse.
300 patients were recruited, and by 2009, follow-up totaled 1,913 patient years, with a mean of 6.4 years per patient. Only one case of relapse was detected, with an absolute relapse rate of 0.3% (0.52 per 1000 patient-years at risk (PYAR)); among a subset with pre-treatment bacterial indices (BI) of > or = 4 +, the rate was 0.6%. Relapse occurred 7 years after MDT.
These data provide strong evidence of the long-term efficacy of the one year WHO-MDT for multibacillary (MB) leprosy patients, even in those with a high initial BI.