Anti-phenolic Glycolipid Research Articles

Impact of histopathological and serological assessments on early diagnosis of leprosy relapse.

This study aimed to identify laboratory factors predicting leprosy relapse (LR) after multi-drug therapy (MDT). A case-control study included 80 patients treated with MDT at a national reference center over 12 years. The Relapse Group had 40 patients who relapsed after an average of 89.2 months post-MDT, while the Control Group had 40 patients who remained asymptomatic for an average of 113.1 months. Significant predictors of LR included neural/perineural lymphocytic infiltrate (OR = 4.67; p = 0.0076) and foamy granulomas (OR = 15.55; p = 0.0005), increasing odds by 4.7 and 15.6 times, respectively. The Relapse Group had a mean histological bacillary index (hBI) of 3.23+ compared to 1.8 in the Control Group (p = 0.004). An hBI ≥3+ had 72% sensitivity and 65% specificity for detecting LR (AUC = 0.72; p = 0.0002). Elevated anti-phenolic glycolipid I (anti-PGL-I) IgM antibody levels (ELISA index, EI ≥1) were also associated with LR (OR = 4.67; p = 0.0031). An EI ≥3.6 had 71% sensitivity and 62% specificity (AUC = 0.70; p = 0.0012). Multivariate analysis indicated that neural/perineural infiltrate, foamy granulomas, hBI ≥ 1+, and EI ≥ 1 significantly predicted LR, with up to 94.32% probability. Conclusively, these factors can identify individuals at high probability of LR after MDT.

Models for predicting the risk of illness in leprosy contacts in Brazil: Leprosy prediction models in Brazilian contacts.

This study aims to develop and validate predictive models that assess the risk of leprosy development among contacts, contributing to an enhanced understanding of disease occurrence in this population. A cohort of 600 contacts of people with leprosy treated at the National Reference Center for Leprosy and Health Dermatology at the Federal University of Uberlândia (CREDESH/HC-UFU) was followed up between 2002 and 2022. The database was divided into two parts: two-third to construct the disease risk score and one-third to validate this score. Multivariate logistic regression models were used to construct the disease score. Of the four models constructed, model 3, which included the variables anti-phenolic glycolipid I immunoglobulin M positive, absence of Bacillus Calmette-Guérin vaccine scar and age ≥60 years, was considered the best for identifying a higher risk of illness, with a specificity of 89.2%, a positive predictive value of 60% and an accuracy of 78%. Risk prediction models can contribute to the management of leprosy contacts and the systematisation of contact surveillance protocols.

Levels of TGF- Serum Positively Correlated with Levels of IgM Anti PGL-1 In Household Contacts of Multibacillary Leprosy Patients

Background Leprosy is a chronic progressive infectious disease. Phenolic glycolipid-1 (PGL-1) is an antigen of Mycobacterium leprae, which can trigger the host’s antibody response. Transforming growth factorβ (TGF-β) plays an immunosuppressive role when the host is exposed to PGL-1 antigen or other M. leprae antigens. This study aims to determine the correlation of TGF-β levels with IgM anti-PGL-1 levels in patients with multibacillary leprosy household contacts. Methods Observational analytical study with a cross-sectional approach. The study subjects consisted of 48 household contact subjects and 24 non-household contact subjects aged 15-65 years old who were selected by consecutive sampling based on inclusion and exclusion criteria. 3 mL of venous blood samples were taken and then examined for IgM anti-PGL-1 and TGF-β with the ELISA kit. Data analysis was carried out using SPSS version 23, and a p-value <0.05 was significant. Results The mean level of IgM anti-PGL-1 in the household contact group was 685.46 ± 290.79 u/mL, while in the non-household contact group was 345.50 ± 206.58 u/mL. The mean TGF-β level in household contact groups was 256.69 ± 127.41 pg/mL, while in the non-household contact group was 144.85 ± 36.73 pg/mL (p<0.001). This study found a moderate positive relationship (r=0.450, p<0.001) between levels of TGF-β and IgM anti-PGL-1 household contacts and non-household contacts group. Conclusions The mean level of IgM anti-PGL-1 and TGF-β in household contacts is higher than in non-household contacts, with a significant difference. There is a moderate positive significant relationship between levels of TGF-β and IgM anti-PGL-1 household contacts and non-household contacts group.

Measurements and Accuracy of IgM and IgG Anti Phenolic Glycolipid-1 Levels in Blood Serum for Early Detection Mycobacterium leprae by using Enzyme-Linked Immunosorbent Assay (ELISA): A Reality of a Laboratory

Indonesia was the third most recent case of leprosy globally in 2020 with 11,173 people, after India and Brazil. Most of the leprosy manifestations are asymptomatic. This is possibly as subclinical leprosy which individuals without leprosy symptoms but have leprosy specific antibodies high levels, so it has the potential to become a transmission and disability. Therefore, an ELISA test need for early detection in preventing leprosy transmission. This study aims to measure IgM and IgG antibody levels in leprosy patients and assess the accuracy of the measurement results. This research is a cross-sectional study. Five patients' blood samples have analyzed for IgM and IgG anti-PGL-1 antibody levels by ELISA. Accuracy interpretation of this measurement based on the %CV. Antibody levels were classified based on the cut-off <605 u/ml as IgM seronegative or <630 u/ml as IgG seronegative, 605–1000 u/ml as low seropositive IgM or 630-1000 u/ml as low seropositive IgG, and >1000 u/ml as high seropositive IgM and IgG. Among five patients examined, 40% had high seropositive leprosy with anti-PGL-1 IgM and IgG antibody titers>1000 u/ml, and 60% of patients had seronegative leprosy. Accuracy in this ELISA test shows high accuracy with %CV <10% in the conversion of OD to antibody titer levels. IgM and IgG Anti PGL-1 antibody titers by ELISA as one of the parameters in identifying patients at higher risk of leprosy. A significant portion of patients with high seropositive leprosy with high accuracy.

Positive Correlation of Plasma Interleukin-6 Levels with Immunoglobulin M (IgM) Anti Phenolic Glycolipid-1 (PGL-1) Levels in Household Contacts of Multibacillary Leprosy Patients

Background/aim: Leprosy is a chronic infectious disease that can be cured but causes high morbidity because it causes disability. Leprosy is caused by the bacterium Mycobacterium leprae, an obligate intracellular virulence factor in the form of phenolic glycolipid-1 (PGL-1), a capsule component in M. leprae. This study aims for known Increased IL-6 correlation with IgM anti PGL-1 level in household contacts of multibacillary leprosy patient. Methods: Analytical observational study with a cross-sectional approach. The sample consisted of 42 household contact persons and 22 non-contact samples aged 18-65 years who were selected through consecutive sampling according to the inclusion and exclusion criteria. Samples of 3 millilitres of venous blood were taken, which would then be examined for PGL-1 and IL-6 with the ELISA kit. Data analysis with SPSS version 23 and p-value <0.05 was significant Results: The average anti-PGL-1 IgM level in the household contact group was 636.76±288.45 u/ml, while in the non-contact group, it was 211.00±237.43 u/ml. The average IL-6 level in the household contact group was 20.28 ± 12.54 pg/ml, while in the non-contact group, it was 8.29 ± 2.88 pg/ml. There was a significant difference in the levels of IL-6 and anti-PGL-1 IgM in the household contact and non-contact groups (p<0.001). This study found a strong positive relationship (r=0.620, p<0.001) between IL-6 levels and anti-PGL-1 IgM levels. Conclusion: IgM anti-PGL-1 and IL-6 levels in household contacts were higher than in non-contacts, with a significant difference. There is a significant positive relationship between IL-6 and anti-PGL-1 IgM levels. Keywords: leprosy, contacts, IgM anti-PGL-1, IL-6

Comparison of antiphenolic glycolipid-1 antibody levels in seropositive contacts of leprosy after 2 years of single-dose rifampicin as postexposure prophylaxis.

Leprosy is still a global problem, especially in developing countries, including Indonesia. Ineffective prevention of leprosy leads to active transmission of the disease. World Health Organization (WHO) recommend post-exposure prophylaxis (PEP) with single dose of rifampicin (SDR) for leprosy patients. Previous study showed protective effect of SDR against leprosy, especially for the first 2 years. Hence, the use of PEP and IgM anti PGL-1 examination are required to suspend the chain of leprosy transmission. This study evaluated the effectiveness of SDR administration by comparing IgM anti-PGL-1 antibody levels in seropositive household contacts before and after 2 years of SDR administration. Analytical observational laboratory study comparing IgM anti PGL-1 antibody levels before and after 2 years of SDR administration in leprosy contacts, with a prospective follow-up study design. We conducted this study from December 2022 to January 2023 at Dr. Mohammad Hoesin General Hospital Palembang. All seropositive household contacts of leprosy who had been administrated SDR 2 years ago were included, then PGL-1 antibody levels were examined. The use of SDR showed significant improvement in leprosy contacts after 2 years (P=0.000). The median antibody level before SDR administration was 1,209.20 (615.81 - 4,353.60), which decrease to 146.03 (0 - 2,487.80) U/mL after 2 years. There was statistically significant relationship between history of BCG vaccination (P=0.003) and IgM PGL-1 antibody levels after 2 years of SDR administration. There is a significant decrease in IgM anti PGL-1 antibody levels among leprosy contacts after 2 years of SDR chemoprophylaxis administration.

The role of anti-phenolic glycolipid-1 serological test in leprosy

The number of new leprosy cases in the world is surprisingly high, Indonesia is still at the third rank in the term of new leprosy cases over the world. Leprosy control strategies can be successful if early diagnosis and appropriate therapy are carried out. Currently, several serological tests have been developed which can help detecting subclinical leprosy, making the diagnosis,and monitoring therapy. One such serological tests is the anti-Phenolic Glycolipid-1 (PGL-1) serological test. The antibody response to PGl-1 is mainly IgM, the amount of this antibody is correlated to the number of bacteria; so, the titer is higher in lepromatous type compared with tuberculoid type, this causes serological tests still have limitation in diagnosing leprosy, especially in paucibacillary type leprosy.

Secondary syphilis mimicking mid-borderline leprosy in HIV-positive patient

Background: Syphilis increases the risk of HIV transmission. Coinfection of both infectious diseases potentially changes the presentation of mucocutaneous lesions and accelerates disease progression, complicating the diagnosis and treatment with standard regimens. In the case study, we present a case of secondary syphilis in an HIV-positive patient with clinical manifestations resembling mid-borderline leprosy. Case presentation: A 23-year-old male patient was referred to the emergency care unit of Dr. Soetomo General Hospital with red spots on the palms of the hands and soles of the feet for the past four months. The skin manifestation first appeared as a single spot, grew over time with itch and pain. The patient had lost 15 kg of body weight in the last three months which was confirmed as HIV-positive. He was also treated for leprosy based on the skin manifestations ever since. There was no history of direct contact with leprosy patients. The patient admitted that he had sex with men in the last 3-4 years. The laboratory examination showed negative results for Mycobacterium leprae through skin biopsy and negative for IgM and IgG of anti-phenolic glycolipid-1 (PGL-1). The patient however was positive for syphilis due to high titers of venereal disease research laboratory/rapid plasma regain (VDRL/RPR) and treponema pallidum hemagglutination (TPHA), supported by histological findings. The patient’s condition improved after receiving penicillin benzathine G, the definitive treatment for syphilis. Conclusion: Secondary syphilis is a great imitator to mid-borderline leprosy, especially in HIV patients. To avoid misdiagnosis and mistreatment, a careful physical and laboratory examination, including serology and histopathology, should be carried out.

Factors associated with the development of leprosy in Brazilian contacts: a systematic review.

ABSTRACTPeople who interact with leprosy patients in their environment, neighborhood, family, or social relationships are at risk to develop the disease. This systematic review investigated the risk and protective factors associated with the development of leprosy in Brazilian contacts. The studies were found in Cochrane Library, PubMed (MEDLINE), Embase, Virtual Health Library, grey literature and hand search until July 2021. The study selection, data extraction and quality assessment were independently performed by two investigators. The quality assessment was performed using the Newcastle-Ottawa Scale (NOS). This review was registered in PROSPERO (CRD42020160680). Seventeen articles fulfilled the inclusion criteria (n=544). The immunological and molecular factors, such as Anti-phenolic Glycolipid Antibodies (Anti-PGL-1) seropositivity, negative Mitsuda test, absence of Bacillus Calmette-Guérin (BCG) scar, positive Polymerase Chain Reaction (PCR) in blood; age and race; conviviality, education, contact time and type of contact, as well as elements related to the index case (bacilloscopic index; genetic conditions, family relationships), and some combined factors were shown to be relevant risk factors associated with the development of the disease in Brazilian leprosy contacts. The protective factors reported were the presence of one or more BCG scars, positive Mitsuda test, and education level. All selected studies were considered of high quality according to NOS. The knowledge of disease-related risk and protective factors provides the scientific basis for decision-making in the management of the disease in leprosy contacts.

Can anti-PGL-I antibody isotypes differentiate leprosy contacts and leprosy patients?

ABSTRACT Background: Serologicaltests for antibody measurement in leprosy have a series of limitations indiscriminating contacts and patients. The present paper intends to evaluate ifassociation of more than one antibody isotype in serum samples may be a usefultool in leprosy diagnosis. Methods: Thisstudy evaluated 395 leprosy contacts and 71leprosy index cases living in endemic municipalities in Northeastern Brazil.The participants were evaluated according to their anti-phenolic glycolipidantigen-I isotype (PGL-I) profile. Serum anti-PGL-I IgM, IgG, and IgA weremeasured by indirect ELISA. Results:A strong association was found for antibody positivity in MB leprosy indexcases. The odds ratios were 6.11 (95% CI 3.08 – 12.16) for IgM, 3.31 (1.66 –6.61) for IgG, and 16.97 (8.39 – 34.2) for IgA. For IgM associated with one ormore isotypes, the OR was 21.0 (95% CI 10.11 – 43.64), and for IgG + IgA, theOR was 17.58 (6.23 – 49.54). The highest diagnostic sensitivity of 76.0% (95%CI 61.8 – 86.9) was observed for IgM, and the lowest value was 24.1% (13.0 –38.2), which was observed for IgG + IgA isotypes. Regarding presumptivepositive predictive values, the lowest value was obtained for IgM at 24.7% (95%CI 18.1 – 32.3), and the highest values were observed for IgM+ one or moreisotypes and for IgG + IgA isotype at 60.0% (44.3 – 74.3) and 66.7% (41.0 –86.7), respectively. Conclusions: The present work demonstrated that by associating two or more positive antibody isotypes, the risk of facing a real case of leprosy may increase.

RELATIONSHIP BETWEEN SERUM LEVELS OF IMMUNOGLOBULIN M-ANTI PHENOLIC GLYCOLIPID 1 AND IMMUNOGLOBULIN G-ANTI PHENOLIC GLYCOLIPID 1 WITH BACTERIA INDEX VALUES IN MULTIBACILLARY LEPROSY

Objective: This study aims to determine the relationship of serum levels of anti-phenolic glycolipid (PGL-1), immunoglobulin M (IgM), and anti-PGL-1 immunoglobulin G (IgG) with bacterial index (BI) values in multibacillary (MB) leprosy. Methods: This study was an observational study with a cross-sectional design. A total of 30 study samples were examined for a Slit Skin Smear and examined serum levels of IgM and IgG Anti PGL-1 antibodies by ELISA method. Results: The results showed the higher the BI value, the serum levels of IgM anti-PGL-1 and IgG anti-PGL-1 increased. Conclusion: There was a significant relationship between IgM anti-PGL-1 with BI value in MB leprosy (p<0.05), but there was no significant relationship between IgG anti-PGL-1 with BI value in MB leprosy (p>0.05). IgM anti-PGL-1 has more role in increasing the value of BI in MB leprosy.

Mycobacterium indicus pranii vaccine immunoprophylaxis in anti-phenolic glycolipid-1-positive leprosy contacts - A pilot study from a tertiary care center in North India.

Contacts of leprosy patients have an increased risk of infection with Mycobacterium leprae. Contact tracing and chemo- or immunoprophylaxis are important means of preventing leprosy transmission. We aimed to evaluate the efficacy of immunoprophylaxis with Mycobacterium indicus pranii vaccine in reducing anti-phenolic glycolipid-1 titers in household contacts of leprosy patients. This prospective single-center study was conducted in a tertiary care center in North India from January 2015 to December 2016. Contacts of leprosy patients (both paucibacillary and multibacillary) were screened for anti-phenolic glycolipid-1 antibodies with enzyme-linked immunosorbent assay. Those found positive were given immunoprophylaxis with a single dose of Mycobacterium indicus pranii vaccine, and anti-phenolic glycolipid-1 titers were evaluated at six and 12 months. All contacts were clinically followed for three years. Of the 135 contacts of 98 leprosy patients that were screened, 128 were recruited. Seventeen of these contacts were positive for anti-phenolic glycolipid-1 antibodies and were given Mycobacterium indicus pranii vaccine. Two contacts were lost to follow-up. After immunoprophylaxis, anti-phenolic glycolipid-1 titers were negative in all patients at all intervals, and no contact developed any clinical signs or symptoms of leprosy during the three-year follow-up. The small number of contacts studied, the short follow-up period and the absence of a control group were limitations of this study. Dicussion: We could not find any papers on natural decline of PGL 1 titres in contacts, although in leprosy patients, these titres may even increase after completion of treatment. However the titres do correlate with bacterial load (reference: Int J Lepr Other Mycobact Dis. 1998 Sep;66(3):356-64) so if the tires decrease or become negative it may be considered as an indirect evidence of bacillary clearance. Hence we may suggest the protective efficacy. Furthermore, as the editor mentioned, considering the small number of positive patients, a control group was not possible in the present pilot study, but such studies may be carried out in the future. Immunoprophylaxis with Mycobacterium indicus pranii vaccine is effective and safe in preventing disease in contacts of leprosy patients. However, these findings need to be replicated in larger studies.

Serological evidence of Toxoplasma gondii infection as potential risk for the development of lepromatous leprosy in an endemic area for both neglected tropical diseases in Brazil

BackgroundMycobacterium leprae and Toxoplasma gondii infections are both neglected tropical diseases highly prevalent in Brazil. Infection with certain parasite species can significantly alter susceptibility to other important pathogens, and/or influence the development of pathology. Here we investigated the possible influence of M. leprae/T. gondii co-parasitism on the manifestation of leprosy and its clinical forms.MethodsParticipants (n = 291) were recruited in Campos dos Goytacazes city, Rio de Janeiro state, southeast Brazil, from August 2015 to December 2019 and clinically diagnosed for leprosy. Participants were selected based on the presence (patients) or absence (healthy controls) of the leprosy disease. Contacts of patients were also recruited for this study. Serum samples from patients (n = 199) with leprosy, contacts (n = 40) and healthy controls (n = 52) were investigated for levels of IgM and IgG anti-phenolic glycolipid-1 (PGL-1) by ELISA. Additionally, IgG antibody against soluble Toxoplasma antigen (STAg) was measured in sera samples from leprosy patients, contacts and healthy controls for Toxoplasma gondii serology by ELISA. Anti-PGL-1 IgG and IgM levels were compared using one-way ANOVA Kruskal-Wallis or Mann-Whitney, while Spearman test was used to correlate levels of IgG anti-STAg and IgM/IgG anti-PGL-1 from seropositive and seronegative individuals for T. gondii infection. The risk of T. gondii infection for leprosy disease was assessed using Fisher’s test.ResultsLevels of IgM anti-PGL-1 antibodies were significantly higher in multibacillary (MB) patients compared to paucibacillary (PB) patients (P = 0.0068). Higher IgM and IgG levels anti-PGL-1 were detected in patients with the lepromatous forms. The serologic prevalence for T. gondii infection was 74.9%. We detected increased anti-STAg antibody levels in leprosy patients (79.4%), reaching 88.8% within those with lepromatous form of this disease. The leprosy risk increase in T. gondii seropositive individuals was two-fold (odds ratio [OR] = 2.055; 95% confidence intervals [95% CI]: 1.18–3.51) higher than those seronegative, and considering the lepromatous leprosy risk this increase was even dramatic (OR = 4.33; 95% CI: 1.76–9.69) in T. gondii seropositive individuals. Moreover the leprosy risk in T. gondii seropositive individuals was weakly correlated to the levels of IgG anti-STAg and IgM/IgG anti-PGL-1.ConclusionsAltogether, our results suggest that T. gondii infection may exert immunomodulatory properties that influence to the susceptibility of leprosy, mainly on its more severe clinical form. A better understanding of parasite immunomodulation can ultimately contribute to the development of medical applications.

Prevention of transmission of leprosy: The current scenario.

With the worldwide implementation of WHO multidrug therapy in the 1980s, the global burden of leprosy has decreased. However, the annual new case detection rate around the world has remained nearly static over the past decade with India, Brazil, and Indonesia contributing the majority of these new cases. This has been attributed to the ongoing transmission of Mycobacterium leprae from existing untreated cases and partly to the intensive new case detection programs operative in endemic areas. The WHO has called for a "global interruption of transmission of leprosy by 2020". Targeted chemoprophylaxis of contacts may help bring down the number of new cases. The single-dose rifampicin currently in use for post-exposure prophylaxis (PEP) has limitations and so newer antileprosy drugs and regimens have been trialed for chemoprophylaxis. BCG re-vaccination in combination with chemoprophylaxis for the prevention of leprosy transmission has not been very encouraging. The use of the anti-phenolic glycolipid-1 (PGL-1) antibody test to detect subclinical cases and administer targeted chemoprophylaxis was unsuccessful owing to its low sensitivity and technical difficulties in a field setup. There is a pressing need for newer multidrug chemoprophylactic regimens using second-line antileprosy drugs. The Netherlands Leprosy Relief has proposed an enhanced PEP++ regimen. A simple but highly sensitive and specific serological test to detect subclinical cases at the field level needs to be developed. Although there are a number of challenges in the large-scale implementation of strategies to halt leprosy transmission, it is important to overcome these in order to move towards a "leprosy-free world."

The Correlation of Ig M Anti PGL-1 antibody between blood veins and dryed capillary blood on filter papers in household contact of leprosy patient

Delays of leprosy detection and treatment can lead to disability and potential transmission. Serologic examination has the advantage in detecting Subclinical Leprosy. The procedure of serologic test, which is one of its main limitation, could be simplified by the use filter paper. This study aims to assess the effectiveness of the use of capillary blood dropped on filter paper as a substitute for venous blood in household contact of leprosy patients. Seventeen samples of capillary blood dried on filter paper and venous blood samples from the same individual were examined by ELISA method to determine the levels of IgM anti-Phenolic glycolipid-1 (PGL-1). The mean of anti- PGL-1 IgM levels of filter paper samples 163.31±126.16; whereas the mean of levels from venous samples was 473.16±411.26. There was significant difference and correlation between these two groups. Samples on filter paper in household contact can be used to determine the level of anti-PGL-1 IgM in serum by converting on the regression basis. Further study is required to evaluate the potency of filter paper methods to conduct large-scale serological screening.

Can anti–PGL-1 and anti–NDO-LID-1 antibody titers be used to predict the risk of reactions in leprosy patients?

Leprosy patients may present reactional episodes classified as type I or reversal reaction and type II or erythema nodosum leprosum. Early diagnosis of these reactions is hampered by lack of diagnostic tests. This study aimed at evaluating anti–Mycobacterium leprae antibody levels in reactional and nonreactional leprosy patients at the time of diagnosis. Clinical data and serum samples of 224 patients diagnosed between 2009 and 2010 were collected in the municipality of Rondonópolis-MTBR. Quantification of anti–phenolic glycolipid-1 (PGL-1) IgM antibodies of M. leprae was obtained by the enzyme-linked immunosorbent assay method and anti–natural octyl disacharide-leprosy IDRI diagnostic (NDO-LID-1) IgM/IgG semiquantitative rapid test. We obtained low serological levels of anti–PGL-1 and anti–NDO-LID-1 for tuberculoid (T) (1.56% and 15.62%) and borderline tuberculoid (BT) patients (7.95% and 26.13%), medium levels in the borderline-borderline (BB) (47.91% and 68.75%), and high levels in lepromatous (LL) (93.33% and 100%) and borderline-lepromatous (BL) (88.0% and 100%). When comparing the reactional groups (RI and RII) with without reaction (WR) group at the time of diagnosis, we observed a statistically significant difference between the groups; patients with RII presented higher serological response: 66.66% anti–PGL-1 and 91.66% anti–NDO-LID-1. In respect to patients who developed a reaction after the initial diagnosis, they also showed significant positivity for both anti–PGL-1 and anti–NDO-LID-1 in comparison to the patients who stayed without reaction in the study period (P<0.0001). These results allow us to conclude that serological tests may contribute to an early diagnosis of RII and that the anti–NDO-LID-1 test was demonstrated to be a better indicator.

Serum anti-phenolic glycolipid-1 IgA correlates to IgM isotype in leprosy patients: a possible candidate for seroepidemiological surveys?

The aim of this study was to compare serum anti-phenolic glycolipid-1 IgA, IgG, and IgM levels in leprosy patients and controls. Analysis of anti-PGL-1 IgA, IgG, or IgM in serum samples from multibacillary (MB, n=32) and paucibacillary (PB, n=22) leprosy patients, and in non-endemic controls (n=17), using an indirect enzyme-linked immunosorbent assay. A strong correlation between serum IgM and IgA isotypes was found (r=.745, P<.0001) in MB patients. A moderate correlation was found in all analyses in PB patients. A moderate agreement was found between anti-PGL1 IgA and IgM tests. Based on the ROC curves, the cut-off values were selected and the parameters of validation were calculated. Considering the clinical forms altogether, the diagnostic sensitivities were 50.0% for IgA, 22.2% for IgG, and 74.1% for IgM. The positive (VPP) and negative (VPN) predictive values were estimated for each isotype. For IgA, the VPP and VPN were, respectively, 100.0% (87.0%-100.0%; 95% confidence interval) and 38.7% (24.4%-54.5%); for IgG, 100% (87.0%-100.0%) and 28.8% (17.8%-42.1%), respectively; and for IgM, 95.2% (83.8%-99.4%) and 51.7% (32.5%-70.6%), respectively. Despite the limiting factors, anti-PGL1 IgA correlates to IgM levels and it could be considered as a possible laboratorial tool to be also used, for instance, in serological follow-up studies.

Molecular Evidence for the Aerial Route of Infection of Mycobacterium leprae and the Role of Asymptomatic Carriers in the Persistence of Leprosy.

Leprosy persists as a public health problem. The chain of transmission and mechanism of infection are not completely understood. In the current study, we investigated the route of infection and of disease onset, from airway exposure, colonization, and bloodstream dissemination. Mycobacterium leprae DNA was detected through quantitative polymerase chain reaction in nasal vestibule, nasal turbinate mucosa, and peripheral blood samples, along with anti-phenolic glycolipid I serology and skin tests from the same individual, from 113 leprosy patients and 104 household contacts of patients (HHCs). Bivariate statistics and multiple correspondence analysis were employed. The rates of DNA positivity among patients were 66.4% (75 of 113) for nasal swab samples, 71.7% (81 of 113) for nasal turbinate biopsy samples, 19.5% (22 of 113) for blood samples, with seropositivity of 62.8% (71 of 113 samples) and with increasing incidences toward the multibacillary pole of the clinical spectrum. Positivity among HHCs were as follows: 49% (51 of 104) for nasal swab samples, 53.8% (56 of 104) for nasal biopsy samples, 6.7% (7 of 104) for blood samples, and 18.3% (19 of 104 samples) for anti-phenolic glycolipid I serology. During the follow-up of 5-7 years, out of 104 HHCs, 7 developed leprosy (6.7%). Risk for the disease outcome was estimated by comparing results in HHCs who develop leprosy with those not affected. Neither nasal passage nor mucosa positivity was determinant of later disease onset; however, blood presence increased the risk for disease development (relative risk/positive likelihood ratio, 5.54; 95% confidence interval, 1.30-23.62), as did seropositivity (positive likelihood ratio, 3.69 [1.67-8.16]; relative risk, 5.97 [1.45-24.5]). Our findings strongly suggest that the aerosol route of infection and transmission is predominant and that HHCs contribute to the infection risk to themselves and probably to others.

Risk-benefit assessment of Bacillus Calmette-Guérin vaccination, anti-phenolic glycolipid I serology, and Mitsuda test response: 10-year follow-up of household contacts of leprosy patients.

Despite multidrug therapy, leprosy remains a public health issue. The intradermal Bacillus Calmette-Guérin (BCG) vaccine, Mitsuda test (lepromin skin test), and anti-phenolic glycolipid I (PGL-I) serology are widely used in leprosy studies and have shown great epidemiological value. This longitudinal study evaluated the relative risks and benefits of these three tools by comparing results observed in household contacts (HHCs) of leprosy patients who developed leprosy with those of HHCs who did not in a population of 2,992 individuals monitored during a 10-year period. Seventy-five (2.5%) new leprosy cases were diagnosed, including 28 (0.9%) co-prevalent cases. Therefore, for the risk-benefit assessment, 47 (1.6%) HHCs were considered as truly diagnosed during follow-up. The comparison between healthy and affected contacts demonstrated that not only did BCG vaccination increase protection, but boosters also increased to 95% relative risk (RR) reduction when results for having two or more scars were compared with having no scars [RR, 0.0459; 95% confidence interval (CI), 0.006-0.338]. Similarly, Mitsuda reactions >7mm in induration presented 7-fold greater protection against disease development compared to reactions of 0-3mm (RR, 0.1446; 95% CI, 0.0566-0.3696). In contrast, anti-PGL-I ELISA seropositivity indicated a 5-fold RR increase for disease outcome (RR, 5.688; 95% CI, 3.2412-9.9824). The combined effect of no BCG scars, Mitsuda reaction of <7mm, and seropositivity to anti-PGL-I increased the risk for leprosy onset 8-fold (RR, 8.109; 95% CI, 5.1167-12.8511). The adoption of these combined assays may impose measures for leprosy control strategies.

Asymptomatic Leprosy Infection among Blood Donors May Predict Disease Development and Suggests a Potential Mode of Transmission.

Blood donor samples (1,007) were assessed for anti-phenolic glycolipid 1 (PGL-1) IgM antibodies and Mycobacterium leprae DNA presence, which had 3.8% and 0.3% positivity, respectively. After a 5-year follow-up period, six individuals with positive markers developed leprosy, raising the hypothesis that asymptomatic infection among blood donors may be an undisclosed mode of leprosy transmission via transfusion.