|Year : 2019 | Volume
| Issue : 1 | Page : 238-243
Relation between anti-phenolic glycolipid-1 seropositivity and other factors among the household contacts of Egyptian leprosy cases
Magda M Hagag1, Manal A Safan2, Dalia M Abdou3
1 Department of Dermatology and Venerology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Medical Biochemistry, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Dermatology and Venereology, Faculty of Medicine, Menoufia university, Shebin Elkom, Egypt
|Date of Submission||29-Apr-2017|
|Date of Acceptance||24-Jul-2017|
|Date of Web Publication||17-Apr-2019|
Dalia M Abdou
Source of Support: None, Conflict of Interest: None
The aim of this study was to evaluate the relationship between anti-phenolic glycolipid-1 (anti-PGL-1) seropositivity and the presence of other risk factors and signs suggestive of leprosy in household contacts (HCC) of leprosy cases.
Leprosy is a chronic infectious disease. Its prevalence has declined after the introduction of multidrug therapy; however, efforts are needed for early case identification. Relation of anti-PGL-1 antibody (Ab) levels in HCC and other risk factors is a point of concern.
Patients and methods
In this cross-sectional study, we studied serum anti-PGL-1 Ab levels among 90 HCC of leprosy cases that were reported during the period from January 2010 to May 2016 using enzyme-linked immunosorbent assay.
The mean serum level of anti-PGL-1 Ab was significantly higher in the children category with a mean of 71.98 ± 67.88 pg/ml and in those with positive signs suggestive of leprosy with a mean of 148.91 ± 62.01 pg/ml. The mean was significantly higher when the number of residents per bedroom was more than two with a mean of 80.78 ± 72.49 pg/ml, when the number of damaged nerves was two in the leprosy cases with a mean anti-PGL-1 Ab level of 117.22 ± 79.01 pg/ml, and when the cases were of grade 2 disability at the time of diagnosis with a mean of 104.53 ± 78.11 pg/ml.
High levels of anti-PGL-1 Ab may be considered as a risk factor for leprosy. Measurement and follow-up examination of its levels may contribute to early diagnosis of leprosy in parallel with clinical assessment.
Keywords: anti-phenolic glycolipid-1 antibody, household contacts, leprosy
|How to cite this article:|
Hagag MM, Safan MA, Abdou DM. Relation between anti-phenolic glycolipid-1 seropositivity and other factors among the household contacts of Egyptian leprosy cases. Menoufia Med J 2019;32:238-43
|How to cite this URL:|
Hagag MM, Safan MA, Abdou DM. Relation between anti-phenolic glycolipid-1 seropositivity and other factors among the household contacts of Egyptian leprosy cases. Menoufia Med J [serial online] 2019 [cited 2019 Aug 25];32:238-43. Available from: http://www.mmj.eg.net/text.asp?2019/32/1/238/256100
| Introduction|| |
Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae, which is an acid-fast bacillus and an intracellular parasite with predilection to Schwann cells and skin . It has a long incubation period with an average between 3 and 10 years .
Leprosy is transmitted by close and prolonged contact of susceptible individuals with untreated multibacillary (MB) leprosy patients through inhalation of the bacilli contained in the nasal secretions or through skin erosions. Nasal mucosa is the main route of transmission. Other routes include blood, vertical transmission, breast milk, and insect bites .
It is characterized by damage to the skin, peripheral nerves, and the lining of the upper respiratory tract. As a result of the nerve damage, there may be paralysis, deformity, and ulceration. The disease manifests itself as a clinical spectrum depending on the patient's immunological response and finally leads to peripheral nerve damage and deformities .
WHO classified leprosy simply into paucibacillary (having five or fewer skin lesions) and MB (having six or more skin lesions) disease states roughly according to the effectiveness of cellular immunity and the corresponding bacterial load .
Phenolic glycolipid-1 (PGL-1) is an M. leprae-specific antigen , and this dominant lipid in the cell wall is responsible for its immunological specificity. The most studied antibody (Ab) isotype is the serum anti-PGL-1 IgM . It is known that individuals seropositive for anti-PGL-1 antibodies have a 7.5-fold greater risk of acquiring leprosy compared to seronegative contacts .
The levels of PGL-1 in the serum are correlated with the bacteriological index (BI), with the highest levels detected in MB individuals. As the BI decreased, the ability to detect PGL-1 in individual samples was lower. Following the first administration of multidrug therapy, the levels of serum PGL-1 in patients show a dramatic decline in concentrations reflecting the rapid killing of bacilli and cessation of new PGL-1 synthesis .
The aim of the study was to evaluate the relationship between anti-PGL-1 seropositivity and the presence of other risk factors and signs suggestive of leprosy in household contacts (HCC) of leprosy cases to assess its importance as a screening test.
| Patients and Methods|| |
The study was approved by the ethical committee in Menoufia University. Informed consent was obtained from the studied group of HCC themselves or their parents if they were young before the beginning of the study. The cross-sectional study involved 90 HHC of leprosy cases that were reported during the period from January 2010 to May 2016, as well as those HCC of leprosy cases who were diagnosed during data collection.
This study had targeted HCC of leprosy patients who resided in the same house with the index leprosy case before diagnosis. Both sexes were included. Different degrees of consanguinity were chosen. HCC were 7 years old or greater. Those who hadn't resided with the index leprosy case at the time of diagnosis were excluded. The full history of all HCC were obtained including personal data on age, sex, address and occupation, Bacillus Calmette–Guérin vaccine, complete family history of leprosy, and data of cohabitation of the HCC with the index leprosy case. General clinical examination that included searching for clinical manifestations suggestive of leprosy was performed.
Dermatological examination was carried out as the whole body was inspected under good visual light for the presence of skin lesions (erythematous or hypopigmented patches, infiltrations or nodules, the number of lesions, if present, and its distribution (symmetrical or asymmetrical), hair growth over the lesions, presence or absence of sweating, and the presence of neurotrophic ulcers or visible deformities.
Right and left (ulnar, median, popliteal, great auricular, and posterior tibial) nerves were examined for nerve enlargement, symmetry, tenderness, and other complications of nerve affection. Sensation over hands, feet, skin lesions, and nerves in the vicinity of skin lesions were assessed.
For evaluation of serum level of PGL-1 Ab, venous blood was withdrawn from the cubital vein of HCC of the index leprosy cases under aseptic conditions and quantitative measurement of anti-PGL-1 Ab was performed utilizing reagents provided in the Human PGL-1 Ab ELISA Kit purchased from Glory Science Co., Ltd. (Del Rio, TX, USA) using enzyme-linked immunosorbent assay technique.
Data management and statistical analysis
Statistical analysis of the data 
Data were fed to the computer and analyzed using IBM SPSS software package version 20.0 (IBM Corp., Armonk, New York, USA) . Qualitative data were described as numbers and percentages. The Kolmogorov–Smirnov test was used to verify the normality of the distribution. Quantitative data were described using the range (minimum–maximum), mean, SD, and median. Significance of the obtained results was judged at the 5% level.
For abnormally distributed quantitative variables, the Mann–Whitney test was used for comparison between two studied groups, the Kruskal–Wallis test for comparison between more than two studied groups, and the Spearman coefficient for correlation.
| Results|| |
As regards HCC, the current study included 90 HCC of leprosy cases: 43 (47.8%) men and 47 (52.2%) women. Their ages ranged from 7 and 80 years with a mean age of 27.30 ± 16.83 years. BCG vaccination status was assessed based on the presence of a scar in the left shoulder. In all, 85 (94.4%) HCC were immune, whereas five (5.6%) HCC had no scars [Table 1].
|Table 1: Distribution of the studied cases according to household contact (n=90)|
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The difference in the anti-PGL-1 Ab levels between male contacts with a mean of 64.03 ± 66.09 pg/ml and female contacts with a mean of 54.70 ± 59.51 pg/ml was not significant (P = 0.144). There was no significant relationship between the immunological status and the Ab levels (P = 0.161) [Table 2].
|Table 2: Relation between anti-phenolic glycolipid-1 of contact with cases with different parameters|
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On complete general and clinical examination, different clinical signs suggestive of leprosy such as cording of the great auricular nerves, multiple hypopigmented patches, ulcers that are resistant to treatment, and some eye problems were present in 12 (13.3%) HCC who had anti-PGL-1 Ab levels with a mean of 148.91 ± 62.01 pg/ml. Although 78 HHC were clinically free with mean anti-PGL-1 Ab levels of 45.35 ± 50.25 pg/ml, there was a significant relationship between the presence of signs suggestive of leprosy and anti-PGL-1 Ab levels (P < 0.001) [Table 2].
According to the number of residents per room, 28 HCC had less than four (31.1%) residents per room, whereas 62 of them had more than four (68.9%) residents per room with a mean number of 5.06 ± 1.46 residents. There was a difference but it was not significant (P = 0.064). As regards the number of residents per bedroom, 52 (57.8%) HCC had less than two residents per bedroom who had anti-PGL-1 Ab at a mean level of 43.36 ± 49.13 pg/ml, whereas the remaining 38 (42.2%) HCC had more than residents per bedroom with anti-PGL-1 Ab level at a mean of 80.78 ± 72.49 pg/ml. There was a significant relationship between the number of residents per bedroom and anti-PGL-1 levels (P = 0.026) [Table 2].
According to the degree of consanguinity with the index leprosy case, 23 (25.6%) were partners of the case including 16 (17.8%) wives and seven (7.8%) husbands, 41 (45.6%) were children of the case including 23 (25.6%) sons and 18 (20%) daughters, and 26 (28.9%) were of other degrees of consanguinity [Table 1].
There was significant relationship between degree of consanguinity and anti-PGL-1 Ab levels (P = 0.045). Children were the category that had the highest mean at a level of 71.98 ± 67.88 pg/ml.
There was significant inverse relation between age and anti-PGL-1 levels (r = 0.288, P = 0.006). There was significant direct relation with the number of residents per bedroom (r = 0.268, P = 0.011) [Table 3].
|Table 3: Correlation between anti-phenolic glycolipid-1 of contact with cases with different parameters|
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Our study implies that there is a significant relationship between presence of clinical and dermatological signs suggestive of leprosy and anti-PGL-1 Ab levels. Similar results were recorded by Carvalho et al.  who stated that HHC who exhibited signs suggestive of leprosy displayed significantly higher anti-PGL-1 seropositivity than those who exhibited no characteristic signs of the disease.
As regards index leprosy cases, those HCC who are relatives of 34 index leprosy cases were registered during the period of 2010–2016; 19 (55.9%) leprosy cases were diagnosed after 2014; and15 cases were diagnosed during or before 2014. Regarding operational classification 31 (91.2%) cases were of lepromatous leprosy type who had more than five skin lesions and positive slit-skin smear test at the time of diagnosis, whereas three (8.8%) cases were of tuberculoid leprosy type. They had less than five skin lesions and a negative slit-skin smear at the time of diagnosis [Table 4].
|Table 4: Descriptive analysis of the studied cases according to registered index case (n=34)|
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HCC of leprosy cases who had + 5 BI had the highest mean level at 115.53 ± 77.94 pg/ml. As regards number of damaged nerves at the time of diagnosis, 23 were contacts of a case who had no damaged nerves at the time of diagnosis with a mean level of 33.32 ± 34.39 pg/ml, 54 were contacts of a case that had one damaged nerve at the time of diagnosis with a mean level of 56.19 ± 59.51 pg/ml, and 13 were contacts of a case that had two damaged nerves at the time of diagnosis with the highest mean level of 117.22 ± 79.01 pg/ml. There was a significant relationship between the number of damaged nerves and the level of anti-PGL-1 (P = 0.018) [Table 5].
|Table 5: Relation between anti-phenolic glycolipid-1 of contact with cases with different parameters|
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According to the degree of disability at the time of diagnosis, the highest mean level, which was 104.53 ± 78.11 pg/ml, was observed in contacts of cases who were of degree 2 disability at the time of diagnosis. There was a significant relationship between the degree of disability at the time of diagnosis and the anti-PGL-1 Ab levels of the HCC (P = 0.042) [Table 5].
| Discussion|| |
In this study we had fully examined HCC of leprosy patients and detected three new leprosy cases based on clinical examination. The diagnosis was confirmed later on with histopathological examination. Similar results were reported by Bazan-Furini et al.  who detected five cases of indeterminate leprosy and two cases of lepromatous leprosy. Therefore, we ascertain the importance of complete clinical examination of HCC for early diagnosis, especially in endemic areas.
There was a significant relationship between the degree of consanguinity and the anti-PGL-1 levels; we found that children had the highest mean level of 71.98 ± 67.88 pg/ml.
Seropositivity is directly related to genetic susceptibility and frequent exposure to M. leprae. This may be an explanation for seropositivity being high among siblings, as siblings who live in the same house are exposed to a similar mycobacterial load, and may have similar levels of susceptibility owing to similar genetic backgrounds.
A study with Vietnamese and Brazilian families showed an association of genetic factors that rendered some individuals more susceptible to clinically expressing M. leprae infections .
Consanguinity is the relationship between members of the same family and it is classified as linear or collateral. Linear type is the blood relationship that exists among persons, in which one person is descended from the other and proceeds upwards in a direct ascending line, whereas collateral consanguinity is the relation subsisting among persons who are descended from the same common ancestor, but not from each other. Affinity was considered to be a relationship by marriage.
The importance of consanguinity for the level of anti-PGL-1 antibodies should be emphasized as most of the contacts with seropositive titers had a family history of leprosy. In addition, the three cases that were diagnosed as leprosy had a confirmed linear consanguinity with the index case.
In the current study, as regards demographic criteria, the percentage of those at a young age was 45.6, who showed a significant inverse relation between age and the level of anti-PGL-1 (r = 0.288).
When clinical classification of the index cases was analyzed, there was a significant relationship between the number of damaged nerves in the index leprosy cases and the anti-PGL-1 Ab levels in the HHC. In all, 13 HHC of cases who had two damaged nerves at the time of diagnosis had the highest mean level of 117.22 ± 79.01 pg/ml. As regards the degree of disability of the index leprosy case at the time of diagnosis, HHC of cases with grade 2 disability had the highest mean level of 104.53 ± 78.11 pg/ml. The proportion of anti-PGL-1 seropositive HCC among the different clinical forms indicated a slight difference in the seropositivity between HHC of MB leprosy patients and the PB leprosy patients. Similar results were reported by Calado and colleagues ,,.
The results suggest a useful role for the measurement of serum M. leprae-specific anti-PGL-1 Ab. The measurement can be used as an easy, noninvasive, and inexpensive adjunct method for the detection of leprosy in the population.
Family health programs should perform an active search for cases, through examination of skin and through neurological examination during household visits to those people. The objectives are to increase the detection rate of suspected cases and, consequently, to increase rates of early diagnosis and treatment.
The results suggest a useful role for the measurement of serum M. leprae-specific anti-PGL-1 Ab as an easy, noninvasive, and inexpensive adjunct method for the detection of leprosy in the population. As seropositivity might be a risk factor for developing leprosy, those persons with seropositive results should be monitored via clinical examination, determination of the immune response, and bacteriological state for leprosy detection.
| Conclusion|| |
There is a considerable relation between anti-PGL-1 Ab levels and other risk factors and signs that seropositivity may be a risk factor for developing leprosy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Rodrigues LC, Lockwood DN. Leprosy now epidemiology, progress, challenges and research gaps. Lancet Infect Dis 2011; 11
Pinheiro R, de Souza Salles J, Sarno E, Sampaio E. Mycobacterium leprae
host cell interactions and genetic determinants in leprosy an over view. Future Microbiol 2011; 6
Lastòria JC, Morgado MA. Leprosy: review of epidemiological, clinical and etiopathogenic aspects – part 1. An Bras Dermatol 2014; 89
Scollard DM, Adams LB, Gillis TP, Krahenbuhl JL, Truman RW, Williams DL. The continuing challenges of leprosy. Clin Microbiol Rev 2006; 19
Monotoya D, Modlin R. Learning from leprosy: Insight into the human innate immune response. Adv Immunol 2010; 105
Jadhav R, Suneetha L, Kamble R, Shinde V, Devi K, Chaduvula MV, et al.
Analysis of antibody and cytokine markers for leprosy nerve damage and reactions in the INFIR cohort in India. PLoS Negl Trop Dis 2011; 5
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
Douglas JT, Cellona RV, Fajardo TTJr, Abalos RM, Balagon MV, Klatser PR. Prospective study of serological conversion as a risk factor for development of leprosy among household contacts. Clin Diagn Lab Immunol 2004; 11
Spencer JS, Brennan PJ. The role of Mycobacterium leprae
phenolic glycolipid-1 (PGL-1) in serodiagnosis and in the pathogenesis of leprosy. Lepr Rev 2011; 82
Kirkpatrick LA, Feeney BC. A simple guide to IBM SPSS statistics for version 20.0. Student ed
. Belmont, CA: Wadsworth, Cengage Learning; 2013.
Kotz S, Balakrishnan N, Read CB, Vidakovic B. Encyclopedia of statistical sciences
ed. Hoboken, NJ: Wiley InterScience; 2006.
Carvalho AP, da Conceição Oliveira Coelho Fabri A, Corrêa Oliveira R, Lana FC. Factors associated with anti-PGL-1 seropositivity among the household contacts of leprosy cases. BMC Infect Dis 2015; 15
Mira MT, Alcaïs A, Nguyen VT, Moraes MO, Di Flumeri C, Vu HT, et al.
Susceptibility to leprosy is associated with PARK2 and PACRG. Nature 2004; 427
Calado KLS, Vieira AG, Durães S, Sékula SB, Oliveira MLW. Seropositivity with anti-PGL-1 of household and neighbours contacts of leprosy patients in an urban area. An Bras Dermatol 2005; 80
Cardona-Castro N, Beltrán-Alzate JC, Manrique-Hernández R. Survey to identify Mycobacterium leprae
infected household contacts of patients from prevalent regions of leprosy in Colombia. Mem Inst Oswaldo Cruz 2008; 103
Frota CC, Freitas MVC, Foss NT, Lima LNC, Rodrigues LC, Barreto ML, et al.
Seropositivity to anti-phenolic glycolipid-I in leprosy cases, contacts and no known contacts of leprosy in an endemic and a non-endemic area in Northeast Brazil. Trans R Soc Trop Med Hyg 2010; 104
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]