|Year : 2019 | Volume
| Issue : 2 | Page : 166-169
Detection of Anti-Phenolic Glycolipid-I antibody in sera from tuberculosis patients in Bandung, West Java, Indonesia
Hendra Gunawan1, Nina Roslina1, Jono Hadi Agusni1, Iceu Dimas Kulsum2, Kristina Makarti1, Reti Hindritiani1, Oki Suwarsa1
1 Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran-Dr. Hasan Sadikin Hospital, Bandung, Indonesia
2 Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran-Dr. Hasan Sadikin Hospital, Bandung, Indonesia
|Date of Web Publication||14-Jun-2019|
Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran-Dr. Hasan Sadikin Hospital, Jl. Pasteur No. 38, Bandung 40161
Source of Support: None, Conflict of Interest: None
Background: Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium leprae (M. leprae) are morphologically, immunologically, and pathologically similar. The incidence of simultaneous tuberculosis (TB) and leprosy is still controversial. The aim of this study was to detect anti-phenolic glycolipid-I (anti-PGL-I) antibody in sera from TB patients at Dr. Hasan Sadikin Hospital Bandung, West Java, Indonesia. The aim of this study is to detect anti-phenolic glycolipid-I (anti-PGL-I) antibody in sera from TB patients at Dr. Hasan Sadikin Hospital Bandung, West Java, Indonesia. Methods: We performed a cross-sectional descriptive study with consecutive sampling from 112 TB patients clinically diagnosed by internist from the Internal Medicine Department and confirmed through bacteriological, histological, and chest radiograph examinations. The specimens were taken from the blood serum of the patient. Furthermore, the anti-PGL-I immunoglobulin (Ig) M and IgG serum level were evaluated using the enzyme-linked immunosorbent assay. Results: The mean of anti-PGL-I IgM and IgG serum levels in TB patients of this study was 34.17 ± 21.94 pg/ml and 41.44 ± 18.93 pg/ml with the mean of optical density values was 0.18 ± 0.05 and 0.26 ± 0.07. The seropositivity of anti-PGL-I in TB patients was 27.68% for IgM and 41.96% for IgG. The seropositivity of anti-PGL-I IgM and IgG level based on clinical manifestation of TB in this study from the highest to the lowest were as follows: extrapulmonary TB patients (61.29% and 59.57%), pulmonary TB patients (29.03% and 36.17%), and pulmonary with extrapulmonary TB patients (9.68% and 4.26%), respectively. Conclusion: The seropositivity of anti-PGL-I antibody in sera from TB patients in Bandung, West Java, Indonesia was 27.68% for IgM and 41.96% for IgG. Furthermore, periodic observations are needed to determine the likelihood of clinical manifestation of leprosy in TB patients.
Keywords: Anti-phenolic glycolipid-I antibody, seropositivity, tuberculosis
|How to cite this article:|
Gunawan H, Roslina N, Agusni JH, Kulsum ID, Makarti K, Hindritiani R, Suwarsa O. Detection of Anti-Phenolic Glycolipid-I antibody in sera from tuberculosis patients in Bandung, West Java, Indonesia. Int J Mycobacteriol 2019;8:166-9
|How to cite this URL:|
Gunawan H, Roslina N, Agusni JH, Kulsum ID, Makarti K, Hindritiani R, Suwarsa O. Detection of Anti-Phenolic Glycolipid-I antibody in sera from tuberculosis patients in Bandung, West Java, Indonesia. Int J Mycobacteriol [serial online] 2019 [cited 2019 Sep 18];8:166-9. Available from: http://www.ijmyco.org/text.asp?2019/8/2/166/260385
| Introduction|| |
Tuberculosis (TB) and leprosy are infectious diseases that exist from time immemorial. Both of these diseases mainly occur in developing countries. Mycobacterium tuberculosis and Mycobacterium leprae are similar in morphology, immunology, and pathology.,, The incidence of simultaneous TB and leprosy occurrence is still controversial. Some researchers stated that the simultaneous occurrence of TB and leprosy is rare.
Phenolic glycolipid-I (PGL-I) is a specific antigen of M. leprae,,, which can stimulate the humoral immune response to form anti-PGL-I antibodies., The primary antibody that formed is immunoglobulin (Ig) M. Anti-PGL-I IgM will be detected 1–2 weeks after infection of M. leprae. Increased levels of IgM indicated that a person was infected with M. leprae. The detection of antibodies against M. leprae is very useful for early detection of new leprosy cases both in patients with subclinical infections and patients who have developed leprosy symptoms. The study by de Macedo et al. in 2018 which compare serum anti-PGL-I IgA, IgG, and IgM levels in leprosy patients and controls showed that the diagnostic sensitivities were 50.0% for IgA, 22.2% for IgG, and 74.1% for IgM. Therefore, IgM levels could be considered as a possible laboratory tool to be used in serological follow-up studies.
Directly observed treatment short-course (DOTS) is an international TB control strategy recommended by the World Health Organization. In 1995, a national TB control program in Indonesia began to establish the DOTS strategy and implemented in a community health center. Since 2000, the DOTS strategy has been performed nationwide across healthcare facilities. Our general hospital is the top referrals in our province which provide services for TB patients through the DOTS strategy with the establishment of the DOTS Clinic in Bandung, West Java, Indonesia.
Detection of anti-PGL-I antibody in sera from TB patients has never been done before. The aim of this study was to investigate anti-PGL-I antibody in sera from TB patients at DOTS Clinic, Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia. The results of this study will give useful information for finding the new cases of leprosy in TB patients. We planned to conduct periodic observations to discover the likelihood of clinical manifestation of leprosy in TB patients.
| Methods|| |
Population and inclusion criteria
The study was approved by the Institutional Review Board of Health Research Ethics Committee, Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia. One hundred and twelve patients were recruited and enrolled after informed consent was explained. The patients were male and female, ages ≥18 years old which clinically diagnosed with TB by internist from the Internal Medicine Department and confirmed through bacteriological, histological, and chest radiograph examinations.
A cross-sectional descriptive study with consecutive sampling was performed from July 27 to October 18, 2017. For all patients, the following data were collected: sex, age, administrative department of residence, education, occupation, date of TB diagnosis, type of TB, and Bacillus Calmette–Guérin (BCG) vaccination scar. The blood samples were taken from the patients during the treatment of TB. The detection of anti-PGL-I antibody in blood samples was carried out in the Immunology Laboratory of Health Research Unit of Universitas Padjadjaran. Serum was obtained by spinning the blood samples at 1.000 rpm for 15 min, diluted 1:5 and tested in Duplo with the average value counted as a final result. The presence of IgM and IgG antibodies against PGL-I was measured using the enzyme-linked immunosorbent assay (ELISA) kits offered by Glory Science Co., Ltd., (Del Rio, TX, USA). Measurement of anti-PGL-I IgM and IgG values using the ELISA were further carried out according to the manufacturer's instruction. The cutoff optical density (OD) value of anti-PGL-1 IgM in this study was 0.20.
Quantitative variables were described as a mean ± standard deviation, and qualitative data as n (%). All analyses were performed using SPSS 23 statistical package (IBM Corp, Armonk, NY, USA) for windows.
| Results|| |
Distribution of tuberculosis patient according to sex, age, education, occupation, Bacillus Calmette–Guérin vaccination scar, and type of tuberculosis
Of 112 patients, the number of female patients was 66 (58.93%) and male patients were 46 (41.07%). The patients were in the age group of 18–69 years old. Most of the patients were high school graduated (41.07%) and mostly work as a homemaker (36.61%). BCG vaccination scar was found in 75 patients (66.96%). The majority of patients (55.36%) had an extrapulmonary TB.
The seropositivity of anti-phenolic glycolipid-I immunoglobulin M and immunoglobulin G in tuberculosis patients
The mean of anti-PGL-I IgM and IgG serum levels in TB patients of this study was 34.17 ± 21.94 pg/ml and 41.44 ± 18.930 with the mean of OD values was 0.18 ± 0.05 and 0.26 ± 0.072, respectively. The seropositivity of anti-PGL-I in TB patients was 27.68% for IgM and 41.96% for IgG [Table 1].
|Table 1: Anti-phenolic glycolipid-I immunoglobulin M/immunoglobulin G seropositive of tuberculosis patients (n=112)|
Click here to view
Distribution of tuberculosis patients with seropositive anti-phenolic glycolipid-I immunoglobulin M and immunoglobulin G
The characteristic of TB patients with seropositive anti-PGL-I IgM and IgG was presented in [Table 2]. The seropositivity of anti-PGL-I IgM and IgG level based on clinical manifestation of TB in this study from the highest to the lowest were as follows: extrapulmonary TB patients (61.29% and 59.57%), pulmonary TB patients (29.03% and 36.17%), and pulmonary with extrapulmonary TB patients (9.68% and 4.26%), respectively.
|Table 2: Demographic characteristics of tuberculosis patients with anti-phenolic glycolipid-I immunoglobulin M/immunoglobulin G seropositive|
Click here to view
| Discussion|| |
The mean of anti-PGL-I IgM serum level in this study was 34.17 ± 21.94 pg/ml, with the average OD value was 0.18 ± 0.05. Bakker et al. in Flores Island, Indonesia (2005) conducted a study of seropositivity of anti-PGL-I IgM in leprosy and nonleprosy population. He reported that the cut-off OD value of anti-PGL-1 IgM was 0.20. A study by Sinha et al. in India (1989) was also used OD value as a cutoff point to measure the seropositivity of anti-PGL-I IgM at 0.20, that similar to our study. The seropositivity of anti-PGL-I IgM in TB patients of this study was accounted for 27.68% from 112 patients. The result was almost similar to another study by Parkash et al. He reported that the seropositivity of anti-PGL-I antibody in TB patients was 28.57%. However, the seropositivity of anti-PGL-I IgM in this study was higher when compared to a study conducted by Cardenas et al. which only 10% of latent TB patients had seropositive antibodies against PGL-I. The studies for detecting the seropositivity of anti-PGL-I antibodies in TB patients have not been generally practiced. More research were commonly done on leprosy patients or nonleprosy populations, such as the household contacts of leprosy patients and healthy populations. Bakker et al. and Sinha et al. presented the seropositivity of anti-PGL-I IgM from healthy populations was 3%–3.3%. Bazan-Furini et al., in Brazil (2010), conducted a study of seropositivity of anti-PGL-I IgM in leprosy patients and their household contacts. He reported that the seropositivity of anti-PGL-I IgM from the household contacts of leprosy patients was accounted for 43.1% of paucibacillary and 56.9% of multibacillary (MB). The different results of seropositivity of anti-PGL-I IgM depend on the method used, location, and the population of the study. The seropositivity of anti-PGL-I IgM results in a healthy population may be due to the exposure of M. leprae from the environment such as water and soil., The high seropositivity of IgM anti-PGL-I in leprosy contacts is due to close and prolonged contact with leprosy patients, especially MB leprosy patients. Risk factors for developing leprosy increase 4.6–7.2 times higher in MB leprosy contacts.,
Prakoeswa et al. conducted a study to detect the deoxyribonucleic acid (DNA) of M. leprae from blood sample of household contact using polymerase chain reaction (PCR) examination to ascertain that subclinical leprosy plays an important role in leprosy transmission. Systematic review and meta-analysis study by Penna et al. showed that contacts with anti-PGL-I IgM seropositivity were three times more likely to develop leprosy. A person with the seropositive result of anti-PGL-I IgM may be a source of future infections and required prophylactic intervention to break the chains of transmission. The seropositivity of anti-PGL-I IgM in TB patients showed that M. leprae coinfection in TB patients was possible; although, they often occur in the form of subclinical infections. Co-infection by two microorganisms was a common occurrence. Coinfection by M. tuberculosis appears likely in multibacillary leprosy patients which shown an impaired cell-mediated response to M. leprae. Several cases of TB that preceded leprosy have been reported.,, TB infection can occur in all leprosy spectrum. Donoghaue et al. showed the presence of M. leprae coinfection with M. tuberculosis from archaeological discoveries in Roman times using PCR examination. The result was proven by the finding of the DNA of M. tuberculosis and M. leprae in the human skeletal materials. It proved that both of the diseases can occur simultaneously.
The previous data about the seropositivity of anti-PGL-I IgM that related to gender and age only available in healthy and leprosy-contact populations., In this study, BCG vaccination scar was found in 75 patients (66.96%), but it is not the major driver for anti-PGL-I IgM seroprevalence. As mention in one randomized, double-blind vaccine trial in Venezuela, about 29,000 contacts of leprosy patients have been vaccinated with either a mixture of heat-killed M. leprae and BCG or BCG alone, and there was no clear association with the presence of BCG or lepromin scars with risk of developing leprosy. The seropositivity of anti-PGL-I IgM level based on clinical manifestations of TB in this study from the highest to lowest were as follows: extrapulmonary TB patients (61.29%), pulmonary TB patients (29.03%), and pulmonary with extrapulmonary TB patients (9.68%). To the author's knowledge, there were no data of the seropositivity of anti-PGL-I IgM based on the clinical manifestations of TB patients have been reported.
Rifampicin as the oral anti-TB drug is also one of the multidrug therapies for leprosy which has bactericidal effect against M. leprae. TB treatment may have had an upgrading immunological effect caused by the release of antigens from M. leprae organisms killed by the rifampicin.
| Conclusion|| |
The seropositivity of anti-PGL-I antibody in sera from TB patients at the DOTS Clinic Dr. Hasan Sadikin Hospital Bandung, West Java, Indonesia, in 2017, suggests that at least 27% of TB patients at DOTS Clinic, Dr. Hasan Sadikin Hospital Bandung have subclinical infection of leprosy. The data of demographic characteristics of TB patients with anti-PGL-I antibody seropositive are a novelty. More prospective cohort studies to determine the manifestations of leprosy in the subclinical form in TB patients with anti-PGL-I IgM seropositive are needed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Rawson TM, Anjum V, Hodgson J, Rao AK, Murthy K, Rao PS, et al.
Leprosy and tuberculosis concomitant infection: A poorly understood, age-old relationship. Lepr Rev 2014;85:288-95.
Maske AP, Sawant PA, Joseph S, Mahajan US, Kudale AM. Socio-cultural features and help-seeking preferences for leprosy and turbeculosis: A cultural epidemiological study in a tribal district of Maharashtra, India. Infect Dis Poverty 2015;4:33.
Lee HN, Embi CS, Vigeland KM, White CR Jr. Concomitant pulmonary tuberculosis and leprosy. J Am Acad Dermatol 2003;49:755-7.
Lietman T, Porco T, Blower S. Leprosy and tuberculosis: The epidemiological consequences of cross-immunity. Am J Public Health 1997;87:1923-7.
Witas HW, Donoghue HD, Kubiak D, Lewandowska M, Gładykowska-Rzeczycka JJ. Molecular studies on ancient M. tuberculosis
and M. leprae
: Methods of pathogen and host DNA analysis. Eur J Clin Microbiol Infect Dis 2015;34:1733-49.
Rees RJ, Young DB. The microbiology of leprosy. In: Hastings RC, Opromolla DV, editors. Leprosy. New York: Churcill Livingstone; 1994. p. 49-83.
Barreto JG, Guimarães Lde S, Leão MR, Ferreira DV, Lima RA, Salgado CG, et al.
Anti-PGL-I seroepidemiology in leprosy cases: Household contacts and school children from a hyperendemic municipality of the Brazilian Amazon. Lepr Rev 2011;82:358-70.
Bryceson A, Pfaltzgraff RE. Leprosy. 3rd
ed. London: Churchill Livingstone; 1990. p. 1-42.
Bonfitto NL, Motta AC, Furini RB, Komesu MC, Figueiredo JF, Foss NT. Determination of the salivary anti-phenolic glycolipid-1 antibody in leprosy patients as a tool to monitoring multidrugtherapy. Am J Infec Dis 2009;5:321-6.
Nagao-Dias AT, Almeida TL, Oliveira Mde F, Santos RC, Lima AL, Brasil M, et al.
Salivary anti-PGL IgM and IgA titers and serum antibody IgG titers and avidities in leprosy patients and their correlation with time of infection and antigen exposure. Braz J Infect Dis 2007;11:215-9.
de Macedo AC, Guimarães JA, Rodrigues RO, Araújo TD, Tavares CM, Cabral PB, et al
. Serum anti-phenolic glycolipid—1 IgA correlates to IgM isotype in leprosy patients: A possible candidate for seroepidemiological surveys?. J Clin Lab Anal 2018;32:e22276.
Directorate General of Disease Prevention and Control. Republic of Indonesia Department of Health. Handbook of National Tuberculosis Control. Jakarta: Bakti Husada; 2014. p. 13-20.
Bakker MI, Hatta M, Kwenang A, Van Mosseveld P, Faber WR, Klatser PR, et al.
Risk factors for developing leprosy – A population-based cohort study in Indonesia. Lepr Rev 2006;77:48-61.
Sinha S, Kannan S, Nagaraju B, Sengupta U, Gupte MD. Utility of serodiagnostic tests for leprosy: A study in an endemic population in South India. Lepr Rev 2004;75:266-73.
Parkash O, Chaturvedi V, Girdhar BK, Sengupta U. A study on performance of two serological assays for diagnosis of leprosy patients. Lepr Rev 1995;66:26-30.
Cardenas VM, Orloff MS, Kaminaga J, Cardenas IC, Brown J, Hainline-Williams S, et al.
Tuberculosis and leprosy infections in the Marshallese population of Arkansas, USA. Lepr Rev 2016;87:109-12.
Bazan-Furini R, Motta AC, Simão JC, Tarquínio DC, Marques W Jr., Barbosa MH, et al.
Early detection of leprosy by examination of household contacts, determination of serum anti-PGL-1 antibodies and consanguinity. Mem Inst Oswaldo Cruz 2011;106:536-40.
Meima A, Irgens LM, van Oortmarssen GJ, Richardus JH, Habbema JD. Disappearance of leprosy from Norway: An exploration of critical factors using an epidemiological modelling approach. Int J Epidemiol 2002;31:991-1000.
Prakoeswa CR, Agusni I, Izumi S. Detection of Mycobacterium leprae
DNA in blood of the subclinical leprosy. Folia Med Indones 2007;43:64-7.
Douglas JT, Cellona RV, Fajardo TT Jr. Abalos RM, Balagon MV, Klatser PR, et al.
Prospective study of serological conversion as a risk factor for development of leprosy among household contacts. Clin Diagn Lab Immunol 2004;11:897-900.
Penna ML, Penna GO, Iglesias PC, Natal S, Rodrigues LC. Anti-PGL-1 positivity as a risk marker for the development of leprosy among contacts of leprosy cases: Systematic review and meta-analysis. PLoS Negl Trop Dis 2016;10:e0004703.
Donoghue HD, Marcsik A, Matheson C, Vernon K, Nuorala E, Molto JE, et al
. Co–infection of Mycobacterium tuberculosis and Mycobacterium leprae in human archaeological samples: a possible explanation for the historical decline of leprosy. Proc R Soc B. 2005;272:389-94.
Trindade MÂ, Miyamoto D, Benard G, Sakai-Valente NY, Vasconcelos Dde M, Naafs B, et al.
Leprosy and tuberculosis co-infection: Clinical and immunological report of two cases and review of the literature. Am J Trop Med Hyg 2013;88:236-40.
Rajagopala S, Devaraj U, D'souza G, Aithal VV. Co-infection with M. tuberculosis and M. leprae-case report and systematic review. J Mycobac Dis 2012;2:1-5.
Agarwal DK, Mehta AR, Sharma AP, Sural S, Kumar A, Mehta B, et al.
Coinfection with leprosy and tuberculosis in a renal transplant recipient. Nephrol Dial Transplant 2000;15:1720-1.
Ulrich M, Smith PG, Sampson C, Zuniga M, Centeno M, Garcia V, et al.
IgM antibodies to native phenolic glycolipid-I in contacts of leprosy patients in Venezuela: Epidemiological observations and a prospective study of the risk of leprosy. Int J Lepr Other Mycobact Dis 1991;59:405-15.
Rees RJ, Pearson JM, Waters MF. Experimental and clinical studies on rifampicin in treatment of leprosy. Br Med J 1970;1:89-92.
[Table 1], [Table 2]