Ocular hypotension and hypotony in multibacillary leprosy patients; at diagnosis, during and after completion of multidrug therapy

The prevalence and incidence of ocular hypotony (IOP < 7 mm Hg) and factors associated with them were determined in a Leprosy Referral Centre at Tamilnadu, India. Applanation intraocular pressures were measured every six months in a cohort of newly diagnosed multibacillary (MB) leprosy patients who were followed-up during the two year period of multidrug therapy (MDT) and for five years thereafter. Transient hypotony was present in two patients at the time of diagnosis, in 3 patients during MDT and in 9 patients after MDT with a cumulative prevalence of 4.65%. Transient ocular hypotension was present in 24 patients (8%) at disease diagnosis. 25 patients developed hypotension during MDT that was associated with trichiasis (HR 8.83 95% CI 2.06, 37.78 p = 0.003) and flare or/and cells (HR 4.60 95% CI 1.08, 19.64 p = 0.039). 29 patients developed ocular hypotension after MDT that was associated with punctate keratitis and uveal involvement. In general, MB leprosy patients with hypotension had a mean IOP of 12.60 mm Hg which differed significantly (p < 0.0001) from the mean IOP of 14.9 mm Hg in those who did not have hypotension. Transient hypotension and hypotony in MB leprosy patients are associated with signs of intraocular inflammation.     

Leprosy in Guadeloupe (French West Indies): declining disease,increasing diagnosis delay

INTRODUCTION: Endemic for nearly three centuries, leprosy is declining in Guadeloupe: its prevalence has decreased by 75 p. 100 over the last decade. Because it has become rare, it may well be overlooked. PATIENTS AND METHODS: Retrospective study of all the new cases of leprosy diagnosed in Guadeloupe from May 1996 to May 2001. RESULTS: In 10 cases of the 41 reported in this study, diagnosis had been delayed by more than 6 months. Nine of these 10 cases presented with classical clinical signs. The mean delay before diagnosis in these 10 cases was of 22 months (range: 7-36 months); the mean number of consultations with a physician before the final diagnosis was of 3.2 (range: 2-8). The mean age at the time of diagnosis in patients in whom diagnosis was delayed was significantly greater than those in whom diagnosis was confirmed rapidly (55 vs. 37 years). DISCUSSION: In Guadeloupe, one patient out of 4 presenting with leprosy is diagnosed with a delay of more than 6 months, despite a classical clinical presentation. This is deleterious to the patients and health economics. The patients in whom diagnosis was delayed were older. This epidemiological tendency appears inherent to this form of "residual leprosy". The present rareness of the disease is responsible for a lack of knowledge of the disease by the physicians through lack of experience. This phenomenon is also observed for syphilis and measles. There is a real risk of underestimation or erroneous diagnosis.     

The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in north India

The aim of this study was to find predictors of neuropathy and reactions, determine the most sensitive methods for detecting peripheral neuropathy, study the pathogenesis of neuropathy and reactions and create a bank of specimen, backed up by detailed clinical documentation. A multi-centre cohort study of 303 multibacillary leprosy patients in Northern India was followed for 2 years. All newly registered MB patients requiring a full course of MDT, who were smear positive and/or had six or more skin lesions and/or had two or more nerve trunks involved, were eligible. A detailed history was taken and physical and neurological examinations were performed. Nerve function was assessed at each visit with nerve conduction testing, warm and cold detection thresholds, vibrometry, dynamometry, monofilaments and voluntary muscle testing. Because the latter two are widely used in leprosy clinics, they were used as 'gold standard' for sensory and motor impairment. Other outcome events were type 1 and 2 reactions and neuritis. All subjects had a skin biopsy at registration, repeated at the time of an outcome event, along with a nerve biopsy. These were examined using a variety of immunohistological techniques. Blood sampling for serological testing was done at every 4-weekly clinic visit. At diagnosis, 115 patients had an outcome event of recent onset. Many people had skin lesions overlying a major nerve trunk, which were shown to be significantly associated with an increased of sensory or motor impairment. The most important adjusted odds ratios for motor impairment were, facial 4.5 (1.3-16) and ulnar 3.5 (1.0-8.5); for sensory impairment they were, ulnar 2.9 (1.3-6.5), median 3.6 (1.1-12) and posterior tibial 4.0 (1.8-8.7). Nerve enlargement was found in 94% of patients, while only 24% and 3% had paraesthesia and nerve tenderness on palpation, respectively. These increased the risk of reactions only marginally. Seven subjects had abnormal tendon reflexes and seven abnormal joint position sense. In all but one case, these impairments were accompanied by abnormalities in two or more other nerve function tests and thus seemed to indicate more severe neuropathy. At diagnosis, 38% of a cohort of newly diagnosed MB leprosy patients had recent or new reactions or nerve damage at the time of intake into the study. The main risk factor for neuropathy found in this baseline analysis was the presence of skin lesions overlying nerve trunks. They increased the risk of sensory or motor impairment in the concerned nerve by 3-4 times. For some nerves, reactional signs in the lesions further increased this risk to 6-8 times the risk of those without such lesions. Patients with skin lesions overlying peripheral nerve trunks should be carefully monitored for development of sensory or motor impairment.     

Dapsone resistance in patients attending Central Leprosy Teaching and Research Institute, Chengalpattu (South India)

The Central Leprosy Teaching and Research Institute (C.L.T. & R.I.) Chengalpattu, took up studies on dapsone resistance in M. leprae from 1974. From 1978, the study was further strengthened by a project under THELEP (TDR) for eliciting information on the efficacy of certain drug regimens. The Thelep studies were to be conducted only on the dapsone sensitive untreated cases and, therefore, directed towards the detection of primary resistance, while the non-THELEP institutional studies were concentrated on secondary dapsone resistance problem. These two studies together detected 99 cases of dapsone resistance in the patients who attended CLTRI Hospital during 1974-81; 23 of them, were of primary origin, 16, 6 and 1 showing mild (RI), moderate (RII), and high (RIII) grades respectively. Of the remaining 76 cases of secondary resistance, 7 and 69 were of RII and RIII grades respectively. The need for vertical and horizontal monitoring of the drug resistance problem has been pointed out.     

Increased incidence of cytoplasmic ANCA (cANCA) and other autoantibodies in leprosy patients from western India

The prevalence of various autoantibodies was studied in 75 leprosy patients comprising eight patients with lepromatous leprosy (LL), 36 patients with borderline lepromatous leprosy (BL) and 31 patients with borderline tuberculoid leprosy (BT), along with 100 normal controls. Certain autoantibodies such as anti-nuclear antibodies (ANA), anti-single stranded DNA (anti-ssDNA) and anti-neutrophil cytoplasmic antibodies (ANCA) were raised among leprosy patients. When ANCA specificities to anti-myeloperoxidase (anti-MPO), anti-proteinase3 (anti-PR3) and anti-lactoferrin (anti-LF) were studied, it was found that the patterns of immunofluorescence such as perinuclear (p-ANCA), cytoplasmic (c-ANCA) and atypical (X-ANCA) and specificity by ELISA to anti-MPO, anti-PR3 and anti-LF varied in the LL, BL and BT groups. However, a higher amount of c-ANCA was observed in 62.5% of leprosy cases, while the incidences of p-ANCA and X-ANCA were lower. The LL group showed a higher incidence of autoantibodies as compared with the BL and BT groups, along with a male preponderance for autoantibody development. Some unusual antibody profiles such as 'X'-ANCA were also observed. The study suggests that autoantibody formation could be quite prevalent and also variable in the spectrum of leprosy cases, and there seems to be a serological overlap among leprosy and autoimmune disease, which could have pathogenetic importance in the leprosy patients developing complications.     

Modified leprosy elimination campaign (MLEC) in the State of Orissa, India

As part of a country-wide modified leprosy elimination campaign (MLEC) carried out in 21 selected States in India in 1998, the State of Orissa launched activities in early January of that year, during which 28.9 million people were examined, giving 85% coverage of the enumerated population. Using general health care staff and volunteers, 416,604 suspect cases were identified and 62,804 of these were confirmed as leprosy by experience observers. The period of intensive search activity lasted 1 week only, but this was preceded by several months of community mobilization and involvement, health education, training of government and voluntary staff, media messages and the involvement of all relevant health departments, officials and politicians. Both this and the intensive search period were characterized by a high level of interest and cooperation by all concerned. The total of new cases detected and put on treatment (multi-drug therapy; MDT) during the period of only 7 days was approximately equal to that which, on routine population survey by the leprosy services, would be recorded over a period of 2 years. The MLEC in Orissa is judged to have been not only an historic step forward in the control of leprosy in a State previously classified as highly endemic for leprosy, but also one of the most successful State health interventions ever mounted. In the 5 months after completion of the campaign, the voluntary reporting rate increased from 50 to 90%. As a direct result of the campaign, facilities for the diagnosis and treatment of leprosy are now available daily in an additional 1639 institutions, over and above those in existence before the campaign was launched. The achievements in terms of detecting hidden (and thus undiagnosed and untreated) cases exceeded the outset predictions, underlining the importance of continued vigilance and the need to maintain involvement of general health care staff. It is anticipated that the rise in prevalence due to the addition of 62,884 cases will be reduced by the implementation of MDT by 80% by about March 1999. Overall the results of the MLEC in Orissa strongly support the likelihood that an elimination level of less than 1 case per 10,000 of the population will be reached in this State by the year 2000.     

丙硫异菸胺合并利福平(或R761)和氨苯矾治疗多菌型麻风的毒副作用的观察

木文对丙硫异菸胺(PTH)合并利福平(RFP)和氨苯砜以及PTH合并异丁基呱嗪力复霉素(R₇₆₁)和氨笨砜(治疗组)治疗多菌型麻风的毒副作用进行了观察,并分别与不含PTH的相应对照组进行了比较.治疗期为半年.结果发现合并PTH的治疗组的毒性明显增加.与相应对照组相比有显著差异.主要毒副作用为肝脏损害.在PTH合并RFP和氨苯矶治疗组有一例在治疗6个月时因急性黄色肝萎缩而死亡.上述结果表明治疗组的毒性增加与PTH有关,因此PTH合并RFP或R₇₆₁和氨笨破不能广泛用于多菌型麻风的治疗.     

The ALERT MDT Field Evaluation Study (AMFES): a descriptive study of leprosy in Ethiopia. Patients, methods and baseline characteristics

The ALERT MDT Field Evaluation Study (AMFES) is a long-term prospective study of 650 patients (594 new cases and 56 relapses after dapsone monotherapy), treated with fixed-duration multiple-drug therapy (MDT), as recommended by WHO. Follow-up has continued for up to 11 years from the start of treatment. This paper presents the methodology of the study and the baseline characteristics of the cohort, while accompanying papers examine the incidence of, and possible risk factors for, the various complications of leprosy, including relapse, reactions and nerve function impairment. The methods of diagnosis, classification and treatment with MDT are described; nerve function was assessed at every visit to the clinic using a standardized methodology, so that reactions and new impairment could be detected early and treated. Eighty-four per cent of new case had at least one thickened nerve, with the ulnar nerve most commonly involved. Seventy-seven per cent of cases completed treatment and only one adverse reaction to the MDT drugs was noted. Twenty-eight per cent of all patients were given steroids at one time or another, almost always for new nerve function impairment, and 3% of these developed significant complications of steroid treatment. Twenty-nine patients (5%) received hospital care, including 14 patients who underwent major surgery. Sixty-one per cent of the women over 19 years of age had at least one pregnancy, but pregnancies were much less common after leprosy was diagnosed.     

The effect of corticosteroid usage on the bacterial killing, clearance and nerve damage in leprosy: a prospective cohort study: part 1--study design and baseline findings of 400 untreated multibacillary patients

OBJECTIVE: To investigate possible adverse effects of therapeutic usage of corticosteroids on the killing and clearance of M. leprae and the clearance of granuloma, in patients with multibacillary (MB) leprosy. DESIGN: A cohort of 400 untreated MB patients were sub-grouped into those to be treated with corticosteroids (prednisolone 40 mg daily tapered to 5 mg over 12 weeks) along with MB-MDT for reaction and/or neuritis or silent neuropathy (SN) of <6 months duration (group A), and those with no reaction and to be treated with MDT only (group B). Clinical, bacteriological, histopathological and neurological test findings at fixed time points were compared. Analysis was performed using SPSS version 10.0. The significance of association was tested using Chi-square test. In the current report, we describe the study design and baseline findings of 400 untreated MB patients, with special emphasis on differences between patients in groups A and B. RESULTS: At baseline, applying Ridley-Jopling classification, 39% patients were BT, 20% BB, 24% BL, 12% sub-polar LL and 5% pure neural (PN). Overall, 60% patients were slit skin smear (SSS) negative and 33% presented with disability either grades 1 or 2. Overall 140/400 (35%) patients presented with reaction and/or neuritis and 11/400 (3%) presented with SN of <6 months duration. Comparing groups A and B, the percentage of patients presenting with DG2 was significantly higher in group A (43%). By clinical tests, monofilaments (MF) and voluntary muscle testing (VMT), the percentage of patients and nerves showing functional impairment was also significantly higher in group A. However, in the more sensitive nerve conduction velocity (NCV) test, the percentage of patients that showed nerve abnormalities was closely comparable; 94% and 91% in groups A and B respectively while number of affected nerves was higher in group A. CONCLUSION: At baseline, as recorded by NCV, peripheral nerve function abnormality was observed in almost all the MB patients regardless of reaction; but among those presenting with reaction or neuritis, the nerve damage was more severe and extensive.     

Secondary and primary dapsone resistant leprosy: an analysis of 199 patients from St. Thomas Hospital and leprosy project, Chettupattu, South India

The occurrence of secondary and primary dapsone resistance in 199 patients in our control area and the influence of certain variables such as age, initial bacteriological and morphological indices, duration of regular dapsone monotherapy, on the emergence of dapsone resistance was investigated. Ninety one of 122 patients and 29 out of 77 showed secondary (SDR) and primary (PDR) resistance to dapsone respectively. Very low BI (BI:2.5) group also showed both SDR (60%) and PDR (40%). Low or high MI group exhibited the same degree of resistance. Multiplication of M. leprae was obtained even when the MI of the inocula was zero. Even in the group who had 1 to 5 years duration of regular dapsone treatment, 85% patients showed SDR. Significance of such results are discussed in relation to chemotherapy. The overall minimum prevalence of SDR was found to be 5.6% and 21% in the case of PDR in our control area.     

A pleiotropic effect of the APOE gene: association of APOE polymorphisms with multibacillary leprosy in Han Chinese from Southwest China

This is a study by investigators from the Chinese Academy of Sciences and Dermatology departments based in Yunnan province in China. Basing their research on a previous observation that patients with leprosy have a lower frequency of dementia due to Alzheimer's Disease than patients without, they investigated whether there was any link between the occurrence of leprosy and the human genes involved in the formation and breakdown of different lipids or fats, processes that are key steps in the development of both Alzheimer's disease as well as the invasion of skin and nerves in leprosy. They searched for a link between a gene called Apolipoprotein E (APOE) which is known to be involved in Alzheimer's and found that certain mutations in the gene were more common in patients with leprosy. They suggested that this might lead to an increase in a lipid binding protein found in blood plasma and that this in turn would aid the survival of the bacteria that cause leprosy, Mycobacterium leprae, thus allowing it to spread and the disease to develop.     

The frequency of drug resistance mutations in Mycobacterium leprae isolates in untreated and relapsed leprosy patients from Myanmar, Indonesia and the Philippines

INTRODUCTION: The magnitude of drug resistance in Mycobacterium leprae to dapsone, rifampicin, and ofloxacin was studied in three Southeast Asian countries with a high prevalence of leprosy. METHODS: M. leprae from the skin of leprosy patients was collected in North Maluku and North Sulawesi in Indonesia, Yangon in Myanmar, and Cebu in the Philippines. Mutations in the drug resistance determining regions in the folP1, rpoB, and gyrA genes, which have been proven to confer resistance, were analysed. In addition, samples from 51 newly diagnosed cases and 13 patients with leprosy relapse in Cebu were submitted for susceptibility testing in the mouse footpad. RESULTS: Of 252 isolates obtained from new cases, 3% were dapsone resistant and 2% were rifampicin resistant. In samples taken from patients with relapsed leprosy (n = 53), significantly more resistance mutations were detected: 15% had dapsone resistance mutations, and 8% had rifampicin resistance mutations. Two patients with relapsed leprosy had mutations for both dapsone and rifampicin resistance. No mutations conferring quinolone resistance were detected. No mutations were detected in the folP1 gene of M. leprae isolates with a low degree of resistance to dapsone. DISCUSSION: Detection of drug-resistant cases by mutation detection in the drug resistance determining region of the genome is a practical method for monitoring resistance. A comparison of the results obtained in this study with previous data obtained prior to the use of multidrug therapy (MDT), does not indicate clearly whether the magnitude of drug resistance has changed. Larger studies of resistance mutations in M. leprae isolated from patients with relapsed leprosy are needed to confirm our results. CONCLUSION: We recommend monitoring the magnitude of drug resistance globally, by testing M. leprae DNA from relapse cases and a representative sample of new cases.