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LEPROSY ROUND
Year : 2015  |  Volume : 60  |  Issue : 1  |  Page : 51-54
Comparison of bacillary index on slit skin smear with bacillary index of granuloma in leprosy and its relevance to present therapeutic regimens


1 Department of Dermatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Dermatology, St. John's Medical College and Hospital, Bangalore, Karnataka, India
3 Department of Pathology, St. John's Medical College and Hospital, Bangalore, Karnataka, India
4 Consultant Dermatologist, Bangalore, Karnataka, India

Date of Web Publication26-Dec-2014

Correspondence Address:
Ishwara P Bhat
Department of Dermatology, St. John's Medical College Hospital, Bangalore 560 034, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.147791

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   Abstract 

Background: As the world moves toward elimination of leprosy, persistence of infective cases in endemic pockets remains a significant problem. The use of clinical criteria to decide the paucibacillary (PB) versus multibacillary (MB) regimens has greatly simplified therapy at the field setting. However, a small but significant risk of under-treatment of so-called "PB" cases which actually have significant bacillary load exists. This study was undertaken to assess this risk and compare two methods of assessment of bacillary load, namely bacillary index on slit skin smear (BIS) versus bacillary index of granuloma (BIG). Aims: To compare BIS with BIG on skin biopsy in consecutive untreated cases of leprosy. Materials and Methods: This prospective study was conducted over a period of 12 months, wherein new untreated patients with leprosy were consecutively recruited. After a thorough clinical examination, each patient underwent slit skin smear (SSS) where the BIS was calculated. The same patient also underwent a skin biopsy from a clinical lesion where, the BIG was calculated. SSS and skin biopsy for BIS and BIG respectively were repeated for all patients at the end of therapy for comparison. All patients received therapy according to World Health Organization-Multidrug Therapy Guidelines. Results: The BIG was positive in all cases where the BIS was positive. Significantly, BIG was positive in three cases of borderline tuberculoid leprosy with <5 lesions who received PB regimen, whereas the BIS was negative in all three cases. Conclusion: This study suggests that BIG may be a better indicator of the true bacillary load in leprosy as compared to BIS. Its role in management is significant, at least in tertiary care centers to prevent "under-treatment" of so called PB cases, which may actually warrant MB regimens.


Keywords: Bacillary index of granuloma, multi-bacillary, paucibacillary, slit skin smears


How to cite this article:
Kumaran SM, Bhat IP, Madhukara J, Rout P, Elizabeth J. Comparison of bacillary index on slit skin smear with bacillary index of granuloma in leprosy and its relevance to present therapeutic regimens. Indian J Dermatol 2015;60:51-4

How to cite this URL:
Kumaran SM, Bhat IP, Madhukara J, Rout P, Elizabeth J. Comparison of bacillary index on slit skin smear with bacillary index of granuloma in leprosy and its relevance to present therapeutic regimens. Indian J Dermatol [serial online] 2015 [cited 2020 Jul 15];60:51-4. Available from: http://www.e-ijd.org/text.asp?2015/60/1/51/147791

What was known? Discrepancy between the bacillary index done in SSS versus that done in biopsy granuloma has been noted in earlier studies.



   Introduction Top


Leprosy is a chronic infectious disease; much of the damage it inflicts is irreversible leading to disability and stigmatisation. The global leprosy burden in early 2006 was 219,826 cases with only six countries having a prevalence rate of greater than 1 per 10,000. Although, India declared its elimination status in 2005, a large part of international figures still come from India. [1] Use of the cardinal signs is the single most powerful and time-tested tool in the diagnosis of leprosy when used carefully. Many programs use a single cardinal sign, i.e., presence of anesthetic skin patch for diagnosis and skin lesion count for classification of leprosy. [2] Laboratory based tools like slit skin smears (SSS) and histopathology, which are time tested, have been side lined as they are regarded not practical or do not reckon to the sensitivity of diagnosis. [3]

The demonstration of acid fast bacillus (AFB) through SSS is important for classification and management of leprosy, especially at places where the expertise is available. Its specificity is almost 100% as it directly demonstrates the AFB. The wide spread poor performance of SSS, however, has emphasized the importance of accurate histopathological assessment of the type of leprosy. [4] The World Health Organization (WHO) sixth committee report claimed the quality of skin smears and of microscope is probably the weakest link in most leprosy elimination programs. [5]

There is paucity of data comparing the bacillary index in the granuloma (BIG) with bacillary index on slit skin smear (BIS) in literature. [6],[7],[8] These studies have consistently demonstrated that most patients who were BIS negative at the time of presentation were actually positive on BIG. The aim of our study was to compare the discrepancy between BIS and BIG in our leprosy patients.


   Materials and Methods Top


This was a prospective study carried out over 12 month period after getting institutional ethical clearance. Consecutive untreated cases of leprosy patients proved clinically and histologically and attending our out-patient department were enrolled in the study. Patients with pure neuritic leprosy and those already on treatment or treated leprosy patients were excluded. Our hospital being a tertiary care center sees a lot of patients from the nearby states and around the country. Clinical findings in form of presenting complaints, morphology and the number of lesions, peripheral nerve involvement, presence or absence of lepra reactions and deformity were recorded on a specially prepared data sheet. The patients were classified using WHO classification.

All patients underwent routine SSS and skin biopsies for histopathological examination that were performed before and after complete treatment from the same infiltrated lesions for easy comparison. All patients were treated with multidrug therapy (MDT) as per standard WHO guidelines. Two different investigators, one each for SSS and histology, did the evaluation. None of these investigators were aware of the clinical details of the patients. The investigator doing SSS was blinded about the histological findings and vice versa. Ridley's logarithmic scale was used to evaluate the bacillary load on SSS and histology, designated as BIS and BIG respectively.


   Results Top


Overall, 50 consecutive leprosy patients attended the out-patient department during the 12-month study period of which only 45 were included and assessed (the remaining five patients were on treatment). Nearly 90% of the study cohort was migrant population from Bihar, Uttar Pradesh, and Andhra Pradesh.

The youngest patient studied was 10 years old and the oldest was 58 years old. The demographic details and distribution is shown in [Table 1]. A significant proportion (73%) of the subjects belonged to the borderline tuberculoid spectrum (BT) of leprosy, remaining belonged to borderline lepromatous (BL) and lepromatous leprosy (LL). For treatment and analysis purpose patients of BT group were further divided into two groups based on the number of lesions as ≤5 and >5 lesions respectively. We did not have any patients from tuberculoid and mid-borderline spectrum of leprosy.
Table 1: Demographic details and distribution


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Lepra reaction was seen in 10 patients (7 patients had type 1 and 3 patients had type 2 reaction respectively).

Pre-treatment analysis of BIS and BIG

BIS


Before the start of MDT all patients in the BL and LL spectrum were BI positive (BI ranged from 2+ to 6+) [Figure 1]. Among BT patients only four patients with more than five lesions were BI positive (BI 1+ to 2+).
Figure 1: Slit skin smear showing the acid fast bacilli (Modified Ziehl- Neelsen stain, ×1000)

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BIG

Pre-treatment analysis of tissue specimens using modified Fite Faraco stain demonstrated that all patients who were SSS positive were BIG positive [Figure 2]. In the BT group, three patients who had ≤5 lesions who were negative on SSS were found to be BIG positive, correlation between BI and BIG is shown in [Table 2]. Clinical examination in these patients showed two patients with three large lesions and one patient with four lesions. These lesions were large and distributed over more than two body parts. Histopathological examination in all these three patients revealed foamy macrophages, lymphocytes and diffuse granulomas suggestive of BL [Figure 3].
Figure 2: Acid fast bacilli in biopsy sample (Fite Faraco stain, ×1000)

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Figure 3: Granulomas diffusely involving dermis with early "Grenz zone" formation (H and E, ×400)

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Table 2: Correlation between bacillary index of slit skin smear and bacillary index of granuloma pre-treatment

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Post-treatment analysis

Only 40 patients completed the recommended duration of treatment, remaining five patients were lost to follow-up (two patients each from BT and LL spectrum and one patient from the BL spectrum). Among the 40 patients, correlation of BIS and BIG showed that patients who were BIS/BIG positive before the start of treatment remained so after the therapy period but there was a standard I log fall in BIS at the end of treatment period in all the treated patients. Histological examination from repeat skin biopsies of 3 BT patients (≤5 lesions) who were BIG positive showed absence of foamy macrophages and upgrading, however, the BIG remained positive on modified Fite Faraco stain, [Table 3]. On clinical examination of lesions in these three patients, infiltration of the plaques was still present at the end of treatment period.
Table 3: Post-treatment correlation between bacillary index of slit skin smear and bacillary index of granuloma

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   Discussion Top


With global leprosy elimination status being attained and burden of disease low, it becomes an increasingly tough task to maintain the achieved target. Number of new cases detected in India by August 2012 was 127,295 of which 63,562 were MB cases. [9]

The classification of leprosy into paucibacillary (PB) and multibacillary (MB) for the sake of treatment have undergone significant modifications during the past decades in order to simplify them at the field level as much as possible. The sixth WHO working committee decided that all BI positive leprosy patients be taken as MB which was later converted to the number of lesions in the late 90's. However, the heterogeneity of these classification systems often leads to ambiguity and misclassification.

Skin smears taken to detect intradermal AFB have high specificity but low sensitivity because about 70% of leprosy patients are smear negative. Nevertheless, skin smears are important because they identify the most infectious patients and those at higher risk of relapse. [10] Histological diagnosis, when available, is deemed the gold standard for diagnosis of leprosy.

Fewer studies conducted in the past although not exactly done to compare BIS and BIG have consistently demonstrated discrepancies, wherein BIG was consistently seen in more number of patients in comparison to BIS. [11],[12],[13],[14],[15]

Recently Bhushan et al., [16] found that among 141 patients evaluated, BIS was positive in only 43 cases as compared to 65 who were BIG positive. With the available few reports it is imperative that BIG is positive in significant number of patients with BT spectrum.

Ridley had observed higher values of bacillary index in skin biopsies (BIG) compared to SSS (BIS) in a study of 11 patients. He opined that the higher BIG in skin biopsies indicates that the BIS reflects density of bacilli in a given foci, while the BIG takes into account both the size of foci and bacterial density. In other words BIG is more accurate in assessing the bacterial status of the tissue specimen. [4],[17]

The results of our study correlate well with the above studies, 19/45 patients were BIG positive in comparison only 16 that were BIS positive. It was observed that among 18 BT patients who had less than 5 lesions, 3 were BIG positive in the biopsy all of whom were BIS negative on SSS and their histology was more suggestive of BL. After completion of treatment these three BT patients were still BIG positive. Clinical examination of these patients revealed a considerable activity in the lesions in form of persistence in infiltration. Also, the lesions were large and involving more than two body parts. As per recommendations, these three patients received PB regimen which may place them at a risk of relapse. In a disease wherein governments and health workers worldwide have worked really hard to achieve the elimination levels, as far as possible no gaps must be left unclosed to reverse things to the past.

Although the above studies disclosed the discrepancies between BIS and BIG, none has gone ahead and followed-up these patients and assessed their risk to relapse and outcome of leprosy. However, follow-up in leprosy patients has been problematic, especially due to the migratory nature of the general population and long incubation period of the disease.


   Conclusion Top


With a decreasing prevalence, there are more chances in future for the referral hospitals to be involved in the management of leprosy. Hence we surmise that utility of BIG in classifying and treating leprosy needs to be seriously considered as it forms the backbone of therapeutic regimen chosen at least at the referral centers.

It is important to highlight BT leprosy as this forms the commonest clinical spectrum which can present with lesser number of lesions (≤5 lesions). The significance of finding abundant AFB and MB histology in tissue biopsies of patients termed as PB leprosy must be resolved so that they get their deserved treatment, but in an era where researchers are already mulling over many leprosy patients receiving extended therapy due to the present classification, proper evidence needs to be given to consider this group for MB treatment.

Although skin biopsy/SSS is probably not feasible for every patient diagnosed in the field setting, it must be remembered that a significant number of BT patients with less than five patches may have significant bacillary loads, probably warranting the uniform introduction of 3 drug MB regimens in all patients with leprosy irrespective of the number of patches. Long-term follow-up and large scale studies may solve this present enigma.

 
   References Top

1.
Anonymous. World Health Organization. Global leprosy situation, 2006. Wkly Epidemiol Rec 2006;81:309-16. Available from: http://www.who.int/wer/en/ [Last accessed on 2011 May 31].  Back to cited text no. 1
    
2.
Shetty VP, Doshi RP. Detection and classification of leprosy: Future needs and strategies. Indian J Lepr 2008;80:139-47.  Back to cited text no. 2
    
3.
Saunderson P, Groenen G. Which physical signs help most in the diagnosis of leprosy? A proposal based on experience in the AMFES project, ALERT, Ethiopia. Lepr Rev 2000;71:34-42.  Back to cited text no. 3
    
4.
Lucas SB, Ridley DS. The use of histopathology in leprosy diagnosis and research. Lepr Rev 1989;60:257-62.  Back to cited text no. 4
    
5.
WHO Expert Committee on Leprosy. Sixth report. Geneva. World Health Organization. WHO Technical Report Series; 768. 1988.  Back to cited text no. 5
    
6.
Srinivas D, Rao PN, Lakshmi TS, Suneetha S. Bacterial index of granuloma and its relevance compared to BI of skin smears. Lepr Rev 2002;73:79-80.  Back to cited text no. 6
    
7.
Ridley DS. The bacteriological interpretation of skin smears and biopsies in leprosy. Trans R Soc Trop Med Hyg 1955;49:449-52.  Back to cited text no. 7
    
8.
Suneetha S, Arunthathi S, Chandi S, Kurian N, Chacko CJ. Histological studies in primary neuritic leprosy: Changes in the apparently normal skin. Lepr Rev 1998;69:351-7.  Back to cited text no. 8
    
9.
World Health Organization. Global leprosy situation, 2012. Wkly Epidemiol Rec 2012;87:317-28.  Back to cited text no. 9
    
10.
Lockwood, Diana NJ. Leprosy elimination-a virtual phenomenon or a reality? BMJ (Clinical research ed.) 2002;324:1516-8.  Back to cited text no. 10
    
11.
Pönnighaus JM. Diagnosis and management of single lesions in leprosy. Lepr Rev 1996;67:89-94.  Back to cited text no. 11
    
12.
Groenen G, Saha NG, Rashid MA, Hamid MA, Pattyn SR. Classification of leprosy cases under field conditions in Bangladesh. I. Usefulness of skin-smear examinations. Lepr Rev 1995;66:126-33.  Back to cited text no. 12
    
13.
Lever GS, Lever WF. Bacterial diseases. In: Lever GS, editor. Histopathology of Skin. 7 th ed. London: Lippincott Williams and Wilkins; 1990. p. 256.  Back to cited text no. 13
    
14.
Fleury RN, Aranda CM. Detection of AFB in tuberculoid biopsies. Int J Lepr Other Mycobact Dis 1995;63:103.  Back to cited text no. 14
    
15.
Nayak SV, Shivarudrappa AS, Nagarajappa AH, Sacchidanand S, Ahmed SM. Role of modified rapid AFB method in histopathological sections of Hansen′s disease. Indian J Dermatol Venereol Leprol 2003;69:173-4.  Back to cited text no. 15
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16.
Bhushan P, Sardana K, Koranne RV, Choudhary M, Manjul P. Diagnosing multibacillary leprosy: A comparative evaluation of diagnostic accuracy of slit-skin smear, bacterial index of granuloma and WHO operational classification. Indian J Dermatol Venereol Leprol 2008;74:322-6.  Back to cited text no. 16
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17.
Ridley DS. Skin biopsy in leprosy. Histological interpretation and clinical application. Documenta Geigy. Basle, Switzerland: CIBA-GEIGY Ltd. 1977.  Back to cited text no. 17
    

What is new?
Bacillary index of granuloma represents the bacillary load more accurately and suggests that even BT cases with less than five patches may have significant bacillary loads warranting MB regimens.


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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