Sequential monitoring of 724 sera for antibodies to a neoantigen based on phenolic glycolipid-I (PGL-I) and native lipoarabinomannan (LAM) in 90 leprosy patients undergoing therapy in San Francisco was conducted. Untreated lepromatous patients frequently (91%) had significant antibodies to both moieties. Antibodies were less frequently found in tuberculoid patients (74% to neoantigen and 37% to LAM). In the first 3 years of treatment, average serum antibodies to both moieties fell significantly. Antibodies to LAM fell during each of the first 4 years of therapy, but decreasing antibody levels to the PGL-I neoantigen did not appear to fall consistently after the third year of treatment. A wide variation in the rate of fall of serum antibodies was noted. Sequential changes in the amounts of serum antibodies to the neoantigen and LAM in general paralleled one another but were at times discrepant. Both in San Francisco and Malaysia, skin-smear negative, long-term treated, lepromatous leprosy patients frequently harbored significant antibodies to both PGL-I and LAM.
Leprosy continues to pose a significant challenge to public health, particularly in certain global regions. Accurate diagnosis and understanding of the disease's etiology are crucial for effective management and prevention. This study aimed to explore the contribution of Natural resistance-associated macrophage protein 1 (NRAMP1) and its genetic variations, as well as the levels of anti-PGL-1 antibodies, to the pathology of multibacillary leprosy in affected individuals and their household contacts. The study included 23 multibacillary leprosy patients and 28 household contacts. NRAMP1 protein expression and anti-PGL-1 IgG and IgM levels were measured using PCR and ELISA techniques, respectively. Genotypic variants of the NRAMP1 gene were also examined. Statistical analyses, including Mann-Whitney tests and univariate logistic regression, were employed to evaluate the data. Significant differences were observed in NRAMP1 protein expression and IgG and IgM levels between the patient and household contact groups. The study also highlighted the role of the NRAMP1 gene and its D543N and 3'UTR polymorphisms in leprosy susceptibility. No significant differences were observed in the genotype variants of INT4 between the two groups. These findings emphasize the potential of integrating PCR technology with serological tests to enhance diagnostic precision in leprosy. They also suggest the need for further research to clarify the role of NRAMP1 and its polymorphisms in leprosy susceptibility and resistance.
The proliferative responses of peripheral blood mononuclear cells (PBMC) to Mycobacterium leprae and BCG were studied in two groups of leprosy patients: a group of 8 lepromatous patients who had been on treatment for more than 20 years (TLL) and a group of 8 untreated lepromatous leprosy patients (ULL). The mean response to M. leprae of the TLL group was 6195 cpm with 5 of the 8 patients responding positively. The mean response to M. leprae of the ULL group was 617 cpm, with only 1 patient showing a positive response. The corresponding proliferative responses to BCG were 19,908 cpm in the TLL group and 7908 in the ULL group. Thirteen M. leprae reactive clones were established from 2 TLL patients and 5 M. leprae reactive clones were established from 2 tuberculoid leprosy patients. Seven of these clones, 4 from the TLL patients and 3 from the tuberculoid (TT) patients could be studied further. Three of the TLL clones responded specifically to M. leprae, while one of the clones exhibited a broad cross-reactivity to other mycobacteria. All of these clones were of the CD4+CD8- phenotype. Our findings suggest that responsiveness to M. leprae can be detected in vitro in a proportion of LL patients who have undergone prolonged chemotherapy, and that this response involves M. leprae reactive CD8+CD8- T cells, of which some appear to be specific to M. leprae.
Fifteen patients with pure lepromatous leprosy were treated for 12 months with DDS at 50 mgm. twice weekly. The drug was fully effective in this dose, and the incidence and severity of ENL were not less than on larger doses
Using a trial design previously evolved at Sungei Buloh Leprosarium, a pilot trial was performed of B.663, in the dosage of 100 mgm. twice weekly, in eight patients with previously untreated lepromatous leprosy. The therapeutic results, as measured by clinical, bacteriologic and histologic assessment, and especially by the rate of fall of the morphologic index, were similar to those obtained with sulfone therapy or with 0.663 in the dosage of 300 mgm. daily. Although B.663 pigmentation was produced in all eight patients, it developed more slowly and was less intense than with standard dosage. Difficulties resulting from skin discoloration in assessing the clinical progress of patients on B.663 are discussed.
Leprosy is a chronic infectious disease and is still a public health problem in Malaysia. In 1926, the Leper Enactment Act was established which required compulsory notification and isolation of leprosy patients. As a result, the National Leprosy Control Centre (NLCC) was built in Sungai Buloh, Selangor. In 1969, the National Leprosy Control programme was launched with the objective of early case finding and decentralisation of treatment of leprosy. The treatment of leprosy patients is integrated with basic Medical and Health services in Malaysia. With the implementation of multiple drug therapy in 1985, the National prevalence rate of leprosy has reduced from 5.7 per 10,000 in 1983 to 1.7 per 10,000 in 1992. The Research Unit in NLCC was established in 1950, where cultivation of Mycobacterium leprae using mouse foot-pad technique is done. This technique is used for assessment of efficacy of chemotherapeutic agents in leprosy. Research activites are also done in collaboration with the Institute for Medical Research in Kuala Lumpur such as isolation of Mycobacterium leprae antigen using T cell clones and phenolic glycolipid antigen.
Matched MeSH terms: Mycobacterium leprae/drug effects; Mycobacterium leprae/growth & development
An account is given of the first hundred consecutive proven cases of sulphone resistance in leprosy, detected in Malaysia between 1963 and 1974. Proof of resistance was clinical in eighty patients and was obtained by drug-sensitivity testing in mice in ninety-six patients; 76 cases were proved both clinically and experimentally, and there was no discrepancy between the two methods. Sulphone resistance was confined to patients with lepromatous-type leprosy--i.e., patients with a large bacterial population. Clinical evidence of relapse due to drug resistance appeared 5-24 years after the start of sulphone treatment. Low dosage favoured the appearance of resistance; therefore regular treatment of lepromatous leprosy with dapsone in full dosage is recommended. The attainment of "skin smears negative for leprosy bacilli" is no test of cure of lepromatous leprosy.
Proof that a patient is suffering from sulfone-resistant leprosy depends on demonstrating that his bacilli can multiply in the mouse foot pad even when the mice are fed sulfone in the diet. Hitherto the maximal dose of DDS tolerated by the mouse has been used in such tests. This paper concerns a patient whose bacilli multiplied in mice fed lower doses of DDS, but were inhibited when the maximal dose was used . His clinical features are distinctive and probably characteristic of this type of "partial" resistance. It is likely that more cases of this type will be found . Recommendations are made concerning the investigation of possible DDS-resistant leprosy patients and their treatment.
To differentiate the leprosy agents Mycobacterium leprae and Mycobacterium lepromatosis and correlate them with geographic distribution and clinicopathologic features.
Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae with predominant involvement of skin and nerves. We present a 70-year-old man with leprosy whose initial presentation resembled rheumatologic disease, due to leprae reaction. He presented with an 8-week history of worsening neuropathic pain in the right forearm, associated with necrotic skin lesions on his fingers that had ulcerated. Physical examination revealed two tender necrotic ulcers at the tip of the right middle finger and the dorsal aspect of the left middle finger. The patient had right wrist tenosynovitis and right elbow bursitis. Apart from raised inflammatory markers, the investigations for infection, connective tissue disease, vasculitis, thromboembolic disease and malignancy were negative. During the fourth week of hospitalization, we noticed a 2-cm hypoesthetic indurated plaque on the right inner arm. Further examination revealed thickened bilateral ulnar, radial and popliteal nerves. A slit skin smear was negative. Two skin biopsies and a biopsy of the olecranon bursa revealed granulomatous inflammation. He was diagnosed with paucibacillary leprosy with neuritis. He responded well to multidrug therapy and prednisolone; his symptoms resolved over a few weeks. This case illustrates the challenges in diagnosing a case of leprosy with atypical presentation in a non-endemic country.
Leprosy is a granulomatous disease primarily affecting the skin and peripheral nerves caused by Mycobacterium leprae, but also significantly involving sinonasal cavities and cranial nerves. It continues to be a significant public health problem, and despite multidrug therapy, it can still cause significant morbidity. The awareness of cranial nerve, intracranial and orbital apex involvement as in our case is important for appropriate treatment measures.