Lepromatous Patients Research Articles

HSP60 mimetic peptides from Mycobacterium leprae as new antigens for immunodiagnosis of Leprosy

The early diagnosis of leprosy serves as an important tool to reduce the incidence of this disease in the world. Phage display (PD) technology can be used for mapping new antigens to the development of immunodiagnostic platforms. Our objective was to identify peptides that mimic Mycobacterium leprae proteins as serological markers using phage display technology. The phages were obtained in the biopanning using negative and positive serum from household contacts and leprosy patients, respectively. Then, the peptides were synthesized and validated in silico and in vitro for detection of IgG from patients and contacts. To characterize the native protein of M. leprae, scFv antibodies were selected against the synthetic peptides by PD. The scFv binding protein was obtained by immunocapture and confirmed using mass spectrometry. We selected two phase-fused peptides, MPML12 and MPML14, which mimic the HSP60 protein from M. leprae. The peptides MPML12 and MPML14 obtained 100% and 92.85% positivity in lepromatous patients. MPML12 and MPM14 detect IgG, especially in the multibacillary forms. The MPML12 and MPML14 peptides had positivity of 11.1% and 16.6% in household contacts, respectively. There was no cross-reaction in patient’s samples with visceral leishmaniasis, tuberculosis and other mycobacteriosis for both peptides. Given these results and the easy obtainment of mimetic antigens, our peptides are promising markers for application in the diagnosis of leprosy, especially in endemic and hyperendemic regions.

Analysis Mycobacterium lepromatosis as the causative agent of diffuse lepromatous leprosy patient in Indonesia

Abstract. Adriaty D, Alinda MD, Karim A, Putra BHK, Agusni RI, Iswahyudi, Wahyuningtyas PA, Wahyuni R, Widayati E, Listiawan MY, Prakoeswa CR. 2023. Analysis Mycobacterium lepromatosis as the causative agent of diffuse lepromatous leprosy patient in Indonesia. Biodiversitas 24: 4521-4529. The present investigation deals with identifying, besides clinical signs, both microscopically and molecularly, to clearly differentiate the Mycobacterium lepromatosis genome against Mycobacterium leprae so that treatment can be carried out properly. To date, there has yet to be a report on this discovery in Indonesia. A 53-year-old Javanese man had ulceration on both legs that had been reoccurring in the past two years. Some of the ulcers were preceded by blisters that rapidly turned into a wound. The ulcers were described as wide and deep, covered with blackish crusts and some exudative areas with irregular edges. He had a history of recurrent epistaxis and had never been treated for leprosy. There was rapid progression and the development of new ulcers on his legs and hands for two weeks before hospitalization. There was body weakness, no fever, and the skin was shiny and ichthyosiform. On the face, diffuse infiltration will appear without nodules, and madarosis also occurs. Examination in this study used the BTA examination method, histopathological examination with HE and Wade-fite staining with biopsy material and the PCR method using skin slit smear material. The results of the BTA examination showed that BI was 3+, and MI showed 7%. Histopathology showed thinning of the epidermis with many foam cells containing BTA, including endnotes and perivascular tissues. Nested PCR examination with LERF2-MLER4 primers for detecting M. leprae showed a positive result with amplicon 135bp in size. Advanced PCR examination using LPMF2-MLER4 primers for detecting M. lepromatosis also showed a positive result with amplicons 142bp in size. The result of DNA sequencing was consistent with the order of nucleotides of M. lepromatosis. Based on the clinical and histopathological results, it was consistent with diffuse lepromatous leprosy and Lucio’s phenomenon. The DNA sequencing showed a suitable result with M. lepromatosis, which has been reported in Mexico. Thus, it can be concluded that in biomolecular strain, this bacterium is an M. lepromatosis that has never been reported in Indonesia.

Type 2 reaction associated sensorineural hearing loss in a drug resistant lepromatous leprosy patient: A case report

Rationale: Leprosy, a chronic granulomatous disease often present clinically as erythema nodosum leprosum, a type 2 reaction. The involvement of cochlear part of audiovestibular system is a rarity. Patient concerns: A 26-year-old male patient with lepromatous leprosy developed bilateral sensorineural hearing loss (SNHL) during type 2 reactional episode. Diagnosis: Recurrent erythema nodosum leprosum in rifampicin-resistant lepromatous leprosy. Interventions: Corticosteroids and second-line multidrug therapy. Outcomes: The patient improved significantly and was further referred for management of psychosocial impact due to sensorineural hearing loss. Lessons: The hearing impairment is a rare complication of type 2 reaction. Any patient with suspected cranial nerve involvement should essentially be screened by tuning fork tests for early detection of hearing impairment and offer timely intervention as required. All high bacteriological index cases should be investigated for antimicrobial resistance in high endemic areas.

Quantitative Real-Time Polymerase Chain Reaction for Detection of Mycobacterium leprae DNA in Tissue Specimens from Patients with Leprosy.

In leprosy, early diagnosis is crucial to prevent transmission and onset of disabilities of the disease. The purpose of this study was to determine usefulness of quantitative real-time polymerase chain reaction (PCR) in clinically diagnosed cases of leprosy. Thirty-two leprosy cases were included. The real-time PCR was performed using commercial kit targeting Mycobacterium leprae-specific insertion sequence element. The slit skin smear was positive in two (22.2%) borderline tuberculoid (BT) patients, five (83.3%) borderline lepromatous (BL) patients, and seven (50%) lepromatous leprosy (LL). The positivity of quantitative real-time PCR in BT, BL, LL, and pure neuritic leprosy were 77.8%, 83.3%, 100%, and 33.3%, respectively. Using histopathology as the gold standard, sensitivity of quantitative real-time PCR was 93.1%, and specificity was 100%. The DNA load was higher in LL (3,854.29/106 cells), followed by BL (140.37/106 cells), and BT (2.69/106 cells). Because of the high sensitivity and specificity of real-time PCR, our study strongly suggests the use of real-time PCR as a diagnostic tool for leprosy.

Evidencing leprosy neuronal inflammation by 18-Fluoro-deoxy-glucose.

Leprosy is caused by multiple interactions between Mycobacterium leprae (M. leprae) and the host's peripheral nerve cells. M. leprae primarily invades Schwann cells, causing nerve damage and consequent development of disabilities. Despite its long history, the pathophysiological mechanisms of nerve damage in the lepromatous pole of leprosy remain poorly understood. This study used the findings of 18F-FDG PET/CT on the peripheral nerves of eight lepromatous patients to evaluate the degree of glucose uptake by peripheral nerves and compared them with clinical, electrophysiological, and histopathological evaluations. Eight patients with lepromatous leprosy were included in this study. Six patients were evaluated up to three months after leprosy diagnosis using neurological examination, nerve conduction study, 18F-FDG PET/CT, and nerve biopsy. Two others were evaluated during an episode of acute neuritis, with clinical, neurophysiological, and PET-CT examinations to compare the images with the first six. Initially, six patients already had signs of peripheral nerve injury, regardless of symptoms; however, they did not present with signs of neuritis, and there was little or no uptake of 18F-FDG in the clinically and electrophysiologically affected nerves. Two patients with signs of acute neuritis had 18F-FDG uptake in the affected nerves. 18F-FDG uptake correlates with clinical neuritis in lepromatous leprosy patients but not in silent neuritis patients. 18F-FDG PET-CT could be a useful tool to confirm neuritis, especially in cases that are difficult to diagnose, such as for the differential diagnosis between a new episode of neuritis and chronic neuropathy.

Ocular Manifestations of Lepromatous Leprosy

This study was done during the study period November 2020 to September 2022, during which 47 patients of leprosy were examined of whom 36 were Lepromatous leprosy in Ophthalmology department if Rajah Muthiah Medical College and Hospital. In our study 80.06% of Lepromatous leprosy patients had ocular manifestations, of whom maximum prevalence was present in 61-75 age group. The major ocular manifestations present were Madarosis (61.11%), Iridocyclitis (50%), Lagophthalmos (11.11%), corneal anesthesia (22.22%), corneal Hypoesthesia (16.67%), exposure keratitis (8.33%) and corneal opacity (8.33). BCVA- 3/60 to PL (U/L) – 18.06% BCVA- 3/60 to PL (B/L)- 2.8% Most of the patients of Lepromatous leprosy had Bilateral Polyneuropathy. The most common nerve affected in Lepromatous leprosy was found to be ulnar nerve and Radial cutaneous nerve. The ocular symptoms occurred more in patients of WHO grade 2 Disability than grade 2 or grade 1. Ocular symptoms occurred mostly in patients who completed Leprosy treatment. Keywords: Lepromatous leprosy, ocular manifestations, leprosy.

A Pilot Study on Hypogonadism in Male Leprosy Patients in Rural Tertiary Care Hospital in Central India

Background: Leprosy is a chronic granulomatous infectious disease caused by Mycobacterium leprae. Besides the skin and peripheral nerves, it also involves many internal organs. Testicular involvement is mainly seen in leprosy. Hypogonadism in males with leprosy can occur due the involvement of testis. Aim: The aim was to evaluate the gonadal function impairment in males with leprosy and to analyze the relation of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone to the activity, duration, and disease classification in Central India. Patients and Methods: This was a prospective observational pilot study. We evaluated 30 patients of leprosy. They were subjected to careful history taking, dermatological and genital examination, assessment of FSH, LH, and testosterone levels, and slit skin smear for acid-fast bacilli. Diagnosis of leprosy was confirmed histopathologically. The collected data were encoded and entered electronically in a computer excel worksheet 2010 version. The statistical analysis was performed using SPSS version 17.0 for Windows. Pearson correlation coefficient was used to establish relationship between different variables. P ≤ 0.05 was considered statistically significant. Results: A positive correlation was found between FSH and LH hormones which was highly significant, whereas there was a negative correlation between testosterone and FSH and LH levels. There was a positive correlation between age, duration of disease, and reaction in leprosy with those of FSH and LH levels. There was a positive correlation between disease activity bacillary index (BI) and FSH, LH and a negative correlation between BI and testosterone. Conclusion: It is recommended that lepromatous leprosy patients should be routinely screened for hypogonadism using FSH, LH, and testosterone levels.

Strongyloidiasis infection in a borderline lepromatous leprosy patient with adrenocorticoid insufficiency undergoing corticosteroid treatment: a case report

Strongyloidiasis is a soil-transmitted helminthiasis mainly caused by Strongyloides stercoralis. It is endemic to the tropics and subtropics. Sri Lanka has a 0-1.6% prevalence rate. S. stercoralis infection was identified in a 33-year-old Sri Lankan male patient treated with corticosteroids for borderline lepromatous leprosy with adrenocortical dysfunction. In March 2020, a 33-year-old Sri Lankan (Sinhalese) male patient presented with watery diarrhea, lower abdominal pain, and post-prandial abdominal fullness. Previously, he was diagnosed with borderline lepromatous leprosy and was treated with rifampicin, clofazimine, and prednisolone 60mg daily since July 2019. After developing gastrointestinal symptoms, he had defaulted leprosy treatment including the prednisolone for 3months. Duodenal biopsy revealed numerous intraepithelial nematodes within the lumina of glands in the duodenum whose appearance favored Strongyloides. Fecal wet smear revealed numerous Strongyloidisstercoralis L1 rhabditiform larvae. Larval tracks were seen in the agar plate culture. L3 filariform larvae of Strongyloidis stercoralis were seen in the Harada-Mori culture. In addition, the short synacthen test revealed adrenocortical insufficiency, and oral hydrocortisone and fludrocortisone were started with albendazole treatment against strongyloidiasis. Fecal wet smear and culture repeated after treatment with albendazole were negative for Strongyloidisstercoralis. The patient was discharged in July 2020 on oral hydrocortisone. Onemonth later his condition was reviewed and the repeated fecal wet smear and agar plate culture was normal. He is being followed up every 3months. This is the first case of strongyloidiasis diagnosed in a patient with borderline lepromatous leprosy from Sri Lanka. The patient manifested symptoms of strongyloidiasis while on high-dose steroid therapy for his lepromatous reaction. Subsequently, the patient not only discontinued his steroid therapy, but also developed adrenocortical insufficiency as a complication of leprosy. Therefore, although diagnosis of strongyloidiasis was delayed, his subsequent low steroid levels probably protected him from disseminated disease. This is an interesting case where symptomatic strongyloidiasis was diagnosed in a patient who was initially treated with high-dose steroids but subsequently developed adrenocortical insufficiency. We emphasize the need to screen all patients prior to the commencement of immunosuppressive therapy.

Leptin Deficiency May Influence the Divergence of Cell-Mediated Immunity Between Lepromatous and Tuberculoid Leprosy Patients.

Leprosy is a disease caused by an intracellular bacillus bacterium called Mycobacterium leprae which lives and multiplies in the hosts' macrophages and Schwann cells. Depending on the degree of the host's cell-mediated immunity (CMI) response to the bacilli, the disease manifests itself in five clinical spectra ranging from polar tuberculoid (TT) to polar lepromatous leprosy (LL). A very high level of T helper 1 (Th1) driven bacilli-specific CMI is seen in the TT form, whereas this response is essentially nonexistent in the LL form. As a result, there is very low or absent bacillary load and localized nodular lesions in TT patients. On the contrary, LL patients presented with high bacillary load and generalized lesions due to low CMI response. The mechanism underlying this divergence of CMI response is not clearly elucidated yet. However, mounting evidence links it to an elevated number of Th1 and Th17 suppressing CD4+ CD25+ FOXP3+ T regulatory cells (Treg cells) which are abundantly found in LL than in TT patients. The predominance of these cells in LL patients is partly attributed to a deficiency of leptin, the cytokine-like peptide hormone, in these patients. Becausea normal level of leptin promotes the proliferation and preferential differentiation of effector T cells (Th1 and Th17) while inhibiting the growth and functional responsiveness of the Treg cells. In contrast, leptin deficiency or neutralization was reported to exert the opposite effect on Treg cells and effector T cells. Other smaller subsets of lymphocytes such as gamma delta (γδ) T cells and B regulatory cells are also modulated by leptin level in the pathogenesis of leprosy. Leptin may therefore regulate the divergence of CMI between TT and LL patients by regulating the homeostasis of effector T cells and Treg cells, and this review will examine the underlying mechanism for this.

ELISA Test Based on the Phenolic Glycolipid-I (PGL-I) of Mycobacterium leprae: A Reality of a Laboratory from a Non-Endemic Country

Background: Leprosy is a neglected tropical disease caused by Mycobacterium leprae, leading to disabilities if untreated. The ELISA based on phenolic glycolipid I (PGL-I), or its synthetic version ND-O-BSA, is almost universally positive in multibacillary leprosy and thus extensively used in endemic countries. Household contacts with a positive antibody titer have ~6-fold higher probability to develop the disease than those with a negative titer. Thus, the aim of the study was to evaluate the performance of this ELISA in the setting of a non-endemic country. Methods: We calculate the cut-off using optimized O.D. thresholds, generated by receiver operating characteristics (ROC) curve analysis, testing 39 well-characterized sera obtained from lepromatous leprosy patients with strongly positive ND-O-BSAELISA titer and 39 sera from healthy non-endemic patients never exposed to M. leprae or M. tuberculosis. Indeed, we tested a second set of sera from suspected or confirmed leprosy or household contacts (SLALT group, n=50), and patients with tuberculosis (control group, n=40). Results: We detected 56.4% of SLALT and 22.5% of tuberculosis as positive, consistent with the literature. Conclusion: The ELISA based on ND-O-BSA may thus be considered a good option to be used in a non-endemic area as a screening tool in at risk population usually coming to our center.

Grade 2 disability among leprosy patients: A pilot study from an endemic area of Central India.

Background and Aim:Deformities and disabilities in leprosy lead to significant morbidity to the individual and financial burden to the family. As the prevalence of leprosy is higher in central India, this study was conducted to know the burden of deformity and disability among leprosy patients in central India and the factors associated with it.Materials and methods:This was a hospital-based, cross-sectional study, conducted on 50 new or on treatment or released from treatment leprosy patients, attending the Dermatology OPD of a tertiary care institute in Central India. Disability was graded as per the WHO criteria for disability grading of hands and feet.Results:Grade 2 disability was found among 32% of the patients with leprosy, whereas a total of 60% of our patients had either grade 1 or grade 2 disabilities. Trophic ulcer was found among 20% and claw hand among 14% of leprosy patients. We found significant associations of lepromatous leprosy with trophic ulcer (p = 0.004) and grade 2 disability (p = 0.012). All patients with claw hands and 80% of the patients with trophic ulcers presented to the healthcare facility at least 6 months after the onset of symptoms.Conclusions:We found very high rates of disability and deformity among leprosy patients indicating possible huge burden of morbidity among leprosy patients in central India. The significant association of lepromatous leprosy with trophic ulcer and grade 2 disability indicated delayed presentation and diagnosis of lepromatous leprosy patients. Our results underlined the need for large scale community-based studies on disability and deformity among leprosy patients in Central India. These results also call for better training of primary level healthcare workers for early detection and management of deformities and disabilities as well as better patient education for leprosy patients regarding hand and foot care.

Associations Between the Purinergic Receptor P2X7 and Leprosy Disease

Leprosy is an infectious disease still highly prevalent in Brazil, having been detected around 27,863 new cases in 2019. Exposure to Mycobacterium leprae may not be sufficient to trigger the disease, which seems to be influenced by host immunogenetics to determine resistance or susceptibility. The purinergic receptor P2X7 plays a crucial role in immunity, inflammation, neurological function, bone homeostasis, and neoplasia and is associated with several infectious and non-infectious diseases. Here, we first compare the P2RX7 expression in RNA-seq experiments from 16 leprosy cases and 16 healthy controls to establish the magnitude of allele-specific expression for single-nucleotide polymorphisms of the gene P2RX7 and to determine the level of gene expression in healthy and diseased skin. In addition, we also evaluated the association of two P2RX7 single-nucleotide polymorphisms (c.1513A>C/rs3751143 and c.1068A>G/rs1718119) with leprosy risk. The expression of P2RX7 was found significantly upregulated at macrophage cells from leprosy patients compared with healthy controls, mainly in macrophages from lepromatous patients. Significant risk for leprosy disease was associated with loss function of rs3751143 homozygous mutant CC [CC vs. AA: p = 0.001; odds ratio (OR) = 1.676, 95% CI = 1.251–2.247] but not with heterozygous AC (AC vs. AA: p = 0.001; OR = 1.429, 95% CI = 1.260–1.621). Contrary, the polymorphic A allele from the gain function of rs1718119 was associated with protection for the development of leprosy, as observed in the dominant model (AA + AG × GG p = 0.0028; OR = 0.03516; CI = 0.1801–0.6864). So, our results suggest that the functional P2X7 purinergic receptor may exert a key role in the Mycobacterium death inside macrophages and inflammatory response, which is necessary to control the disease.

Analysis of the myeloid-derived suppressor cells and annexin A1 in multibacillary leprosy and reactional episodes

BackgroundLeprosy is a chronic infectious disease caused by Mycobacterium leprae. Patients have distinct clinical forms, and the host´s immunological response regulate those manifestations. In this work, the presence of the myeloid-derived suppressor cell and the regulatory protein annexin A1 is described in patients with multibacillary leprosy and with type 1 and 2 reactions.MethodsPatients were submitted to skin biopsy for histopathological analysis to obtain a bacilloscopic index. Immunofluorescence was used to detect myeloid-derived suppressor cells and annexin A1.ResultsThe data demonstrated that the presence of granulocytic and monocytic myeloid-derived suppressor cells in leprosy patients. A high number of monocytic myeloid-derived suppressor cells were observed in lepromatous leprosy and type 2 reactional patients. The presence of annexin A1 was observed in all myeloid-derived suppressor cells. In particular, the monocytic myeloid-derived suppressor cell in the lepromatous patients has higher levels of this protein when compared to the reactional patients. This data suggest that the higher expression of this protein may be related to regulatory response against a severe infection, contributing to anergic response. In type 1 reactional patients, the expression of annexin A1 was reduced.ConclusionsMyeloid-derived suppressor cell are present in leprosy patients and annexin A1 might be regulated the host response against Mycobacterium leprae.

Hepatitis B Virus Infection Among Leprosy Patients: A Case for Polymorphisms Compromising Activation of the Lectin Pathway and Complement Receptors.

Thousands of leprosy patients not only suffer from physical deformities, but also either have or have had hepatitis B virus (HBV) coinfection. Polymorphisms of the complement system modulate susceptibility to leprosy, but genetic susceptibility to past or present HBV infection is unknown. We used sequencing and multiplex sequence-specific PCR to genotype 72 polymorphisms of seven genes (MBL2, FCN1, FCN2, FCN3, MASP1, MASP2, C3) encoding components of the lectin pathway, and two genes encoding complement receptors (CR1, VSIG4) in 190 patients, of which 74 were positive for HBsAg and/or anti-HBc (HBV+, 93.2% with a resolved infection) and 116 lepromatous patients, and 408 HBV-blood donors. In addition, we tested for levels of proteins of the lectin pathway. We found no difference between serum concentrations of mannan-binding lectin (MBL), MBL-associated serine proteins (MASP-1, MASP-2, MASP-3, MAp44), ficolin-3 (FCN-3), soluble complement receptor 1 (sCR1) and MBL mediated C4 activation, measured by ELISA or TRIFMA in up to 167 HBV+ and HBV− patients. Haplotypes lowering protein levels or encoding dysfunctional proteins increased susceptibility to HBV infection: MBL2*LYQC (OR = 3.4, p = 0.02), MASP1*AC_CC (OR = 4.0, p = 0.015) and MASP2*1C2-l (OR = 5.4, p = 0.03). Conversely, FCN1*3C2 haplotype, associated with higher gene expression, was protective (OR = 0.56, P = 0.033). Other haplotypes associated with HBV susceptibility were: MASP2*2B1-i (OR = 19.25, P = 0.003), CR1*3A (OR = 2.65, P = 0.011) and VSIG4*TGGRCG (OR = 12.55, P = 0.014). Some polymorphisms in ficolin genes associated with lower protein levels increased susceptibility to leprosy/HBV infection: FCN*1 (OR = 1.66, P = 0.029), FCN2*GGGCAC (OR = 6.73, P = 0.008), and FCN3*del_del_C (OR = 12.54, P = 0.037), and to lepromatous disease/HBV infection: FCN2*TA (OR = 2.5, P = 0.009), whereas FCN2*MAG was associated with increased FCN-2 expression and resistance against coinfection (OR = 0.29, P = 0.026). These associations were independent of demographic factors and did not increase susceptibility to leprosy per se, except MASP2*1C2-l. Associations for FCN2, FCN3, MASP1, MASP2, and VSIG4 variants were also independent of each other. In conclusion, polymorphisms compromising activation of the lectin pathway of complement increase susceptibility to HBV infection, with ficolin polymorphisms playing a major role in modulating the susceptibility among leprosy patients.

Association of Testosterone Level among Lepromatous and Borderline Leprosy Male Patients: Experience of 30 Cases in Bangladesh

Background: Hormonal dysfunction is reported among the leprosy patients.
 Objective: The purpose of the present study was to see the association of testosterone level among male patients presented with lepromatous and borderline leprosy.
 Methodology: This cross-sectional study was conducted in the Leprosy Hospital, Dhaka, Bangladesh from January to December 2016 for a period of one year. All patients with a known diagnosis of leprosy under follow up at the hospital were included in the study. The serum concentration of testosterone was measured using an enzyme immunoassay technique (ELISA) (DiaMetra, Spello, Italy).
 Result: A total number of 30 cases of leprosy were recruited for this study. The mean with SD of the study population was 39.20±9.065 years. Among 30 cases of study population 26 cases were lepromatous leprosy patents and the rest 4 cases were Borderline Leprosy patients. The mean with the standard deviation of testosterone level in serum was 6.41±4.756 mg/dL and 4.71±2.396 mg/L in lepromatous leprosy and borderline leprosy respectively (p=0.497).
 Conclusion: In conclusion there is no statistically significant relationship between leprosy and testosterone; however, lower level of testosterone is found among the study population
 Bangladesh Journal of Infectious Diseases 2020;7(2):36-39

Serum Levels of Prostate Specific Antigen Parameters among Male Patients with Lepromatous Leprosy in Edo State, Nigeria

Aim: This study is aimed at determining the total PSA (tPSA), free PSA (fPSA) concentrations and free to total PSA ratio (f/tPSA) and their utility in prostate cancer (PCa) risk stratification among male lepromatous leprosy patients in Edo state, Nigeria. Methods: Forty participants and thirty controls participated in this study. A structured questionnaire was administered to each participant to elicit details such as their personal data, age, sex, residence, medications, alcohol consumption, smoking habit, length of time of diagnosis, sexual activities, as well as the history of any other underlying diseases. Blood samples were collected from the participants. Total and free PSA concentrations in the samples were measured using ELISA method. Results: Significantly (p = 0.042) higher serum fPSA among the leprosy patients (0.22 ± 0.12 ng/ml) compared with the healthy controls (0.17 ± 0.09 ng/ml). There were no significant (p = 0.055) difference in the mean tPSA between the leprosy patients (2.69 ± 2.25 ng/ml) compared with the control (1.95 ± 0.69 ng/ml). Similarly, no significant (p = 0.548) difference was observed in PSA ratio between the control (0.08 ± 0.04) and the leprosy patients (0.09 ± 0.03). Conclusion: Our study indicated no significant differences in tPSA and f/tPSA between the leprosy patients and their healthy control. Elevated tPSA as well as f/tPSA levels that fell within the high risk zones of PCa were more prevalent among patients aged ≥ 70 years, not married, who rarely had sexual intercourse and those with longer disease duration.

Soluble mediators of immune significance in sera of leprosy patients

Background: The disease leprosy is categorized by a wide spectrum of clinical forms imposed by the patient’s immune responses to the organism, Mycobacterium leprae. Soluble receptors and soluble mediators are important for regulation of immune responses. Objectives: As leprosy reactions are known immune inflammatory reactions during the disease process, the aim of the study was to screen nitrite, IL-6 cytokine and sTLR2 in sera samples to identify circulating biomarkers associated with leprosy and T1R and T2R among patients recruited from the Northern part of India. Methods: Leprosy patients recruited in our Institute were included in this study. We analysed the level of nitrite, soluble TLR2 and IL-6 in sera of leprosy patients, healthy controls and healthy household contacts by colorimetric assay and ELISA respectively. Results: The level of serum nitrite was observed to be higher in tuberculoid leprosy patients compared to lepromatous leprosy patients (p = 0.006). The level was also higher in healthy contacts of leprosy patients compared to lepromatous leprosy patients (p = 0.008). The sTLR2 level was significantly higher in healthy controls than leprosy patients (p = 0.002) and their healthy contacts (p = 0.001). The level of IL-6 in serum was significantly higher in leprosy patients than in healthy controls (p = 0.001). Conclusion: Nitrite, IL-6 cytokine and sTLR2 are shown to be potential circulating biomarkers associated with leprosy among patients recruited in Northern India.

Association of IL-10 Gene Polymorphism With IL-10 Secretion by CD4 and T Regulatory Cells in Human Leprosy.

Leprosy is a chronic bacterial disease caused by Mycobacterium leprae. Cytokines are known to play vital role as a peacekeeper during inflammatory and other immunocompromised conditions such as leprosy. This study has tried to bridge the gap of information on cytokine gene polymorphisms and its potential role in the pathogenesis of leprosy. Interleukin-10 (IL-10) is an immunosuppressive cytokine, found to be elevated in leprosy that accounted for the suppression of host’s immune system by regulating the functions of other immune cells. T helper cells and T regulatory (Tregs) cells are the major source of IL-10 in lepromatous leprosy patients. In this study, we have documented the association of IL-10 cytokine gene polymorphism with the disease progression. A total of 132 lepromatous leprosy patients and 120 healthy controls were analyzed for IL-10 cytokine gene polymorphisms using PCR-SSP assay and flow cytometry was used to analyze IL-10 secretion by CD4 and Tregs in various genotype of leprosy patients. The frequencies of IL-10 (-819) TT and IL-10 (-1082) GG genotypes were significantly higher in leprosy patients as compared to healthy controls. This observation advocates that these genotypes were associated with the susceptibility and development of the disease. In addition, flow cytometry analysis demonstrated an increased number of IL-10 producing CD4 and Treg cells in IL-10 (819) TT genotype compared to CT and CC genotypes. These observations were further supported by immunohistochemical studies. Therefore, we can conclude that IL-10 cytokine gene polymorphisms by affecting its production can determine the predilection and progression of leprosy in the study population.

Lesional fine needle aspiration (FNA) cytology in reactional and non-reactional leprosy patients

Fine needle aspiration cytology (FNAC) is a relatively simpler tool as compared to histopathology for the evaluation of the cytomorphology of skin lesions. Fifty consecutive leprosy patients diagnosed and classified according to Ridley Jopling scale1 were taken to study the cytomorphology of leprosy lesions in fine needle aspirates and correlate it with their histopathology by a skin biopsy from the same site for histopathological examination after H/E staining. Borderline leprosy patients with Type I reaction showed significantly more numbers of giant cells, collagen and elastin in their smears as compared to those without reaction. The smears were more heavily cellular with fragmented collagen and elastin along with significant increase in neutrophils in patients with Type II reaction while foamy macrophages with fatty background were common in non-reactional lepromatous leprosy patients. A complete correlation between histopathological and cytomorphological findings was observed in 79.4% of cases.

Endocrinological Testicular Dysfunction in Patients with Lepromatous Leprosy and the Impact of Disease on Patient's Quality of Life.

Introduction:Leprosy or Hansen's disease poses a drastic impact on the quality of life in affected patients even after successful completion of treatment. The involvement of the endocrine system in leprosy is usually insidious, silent, and under-reported, especially the testicular dysfunction.Aims and Objectives:The present study was aimed at evaluating the abnormalities of the primary testicular hormone testosterone and the gonadotrophins LH and FSH in male patients affected with lepromatous leprosy and assessing the impact of the disease on quality of life (QOL).Materials and Methods:The study included 43 married male patients diagnosed with lepromatous leprosy. Careful history taking and examination for symptoms of testicular dysfunction were done. Serum concentrations of total testosterone, FSH, and LH were noted. The QOL was evaluated using the WHO Quality of Life-BREF (WHOQoL-BREF).Results:The most common clinical manifestation of testicular dysfunction was reduced or loss of libido reported in 12 (27.9%) patients followed by gynaecomastia in 7 (16.3%). Ultrasonographic (USG) analysis revealed reduced testicular volume in 31 (72.1%) patients, and average testicular volume was 11.9 ± 4.9 mL each. Seventeen (39.5%) patients had low serum testosterone levels, 9 (20.9%) had high serum FSH level, and 11 (25.6%) high LH levels. There was a significant negative correlation between testosterone level and FSH as well as LH. There was also a significantly positive correlation between testicular volume and testosterone level. Symptomatic patients with gynaecomastia/gynaecothelia had higher hormonal derangement than those who had other symptoms. On QOL, most patients scored lowest on the domain of “social relationships” (including sexual wellbeing) followed by “psychological health”.Conclusion:We found a high rate of USG diagnosed testicular atrophy in lepromatous leprosy patients. Therefore, every leprosy patient should be thoroughly examined clinically to rule out features of testicular dysfunction. Testicular function tests should be routinely carried out in all leprosy patients to arrive at an early diagnosis. Leprosy is found to affect all domains of a patient's quality of life.