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Preventing Nerve Function Impairment in Leprosy: Validation and Updating of a Prediction Rule

17 Sep 2008

Marcia Triunfol

Source: PLoS Neglected Tropical Diseases (see original article)

Citation: Schuring RP, Richardus JH, Steyerberg EW, Pahan D, Faber WR, et al (2008). Preventing Nerve Function Impairment in Leprosy: Validation and Updating of a Prediction Rule. PLoS Negl Trop Dis 2(8): e283.

Although 95% of people are immune to Mycobacterium leprae, the causative agent of leprosy, a small fraction of affected individuals may develop permanent nerve damage due to bacteria infiltration in the brain’s Schwann cells. Early detection and corticosteroid treatment may prevent the occurrence of nerve function impairment (NFI) seen in some leprosy patients.

Several risk factors have been associated with the development of NFI. Eight years ago, a study with data from Bangladesh, known as the Bands study, (1) formulated a prediction value that divided patients into NFI risk groups based on the WHO classification.

The WHO classification separates leprosy patients into two main groups: paucibacillary (PB) leprosy, which is characterized by one or more hypopigmented skin muscles and anaesthetic patches with no skin sensation; and multibacillary (MB) leprosy, which presents symmetric skin lesions, nodules, plaques, thickened dermis and nasal bleeding. In the Bands study, patients were further classified according to whether there was any nerve function loss at registration into the study.

Although the Bands study, and the prediction rule it suggests for NFI in leprosy patients, is only eight years old, a review of this rule is necessary for two main reasons. First, the definition of NFI has since changed and therefore patient classification may have changed as well and, second, a new and simple serological test for diagnosing leprosy has been developed.

The serological test detects anti-phenolic glycolipid I antibodies and is known as PGL-I. It can be performed in a mere 10 minutes. PGL-I has been used to evaluate community surveys, leprosy contacts, early diagnoses and for monitoring therapy. The test detects antibodies mainly of the IgM class.

In the present study, the authors validated the Bands NFI prediction rule and compared the performance of an adjusted NFI prediction rule in which the presence of anti-PGL-I antibodies is taken into account.

Data were analysed from 1,037 patients who participated in the Rural Health Programme (RHP) in northwest Bangladesh during the years of 2002 and 2003. The final group that took part in the study comprised a total of 864 patients, of whom 538 were males and 326 females, with a median age of 34 years.

NFI was defined according to a set of criteria based on the guidelines described in the rural health, programme which basically stated that NFI occurs when there is nerve function reduction by ≥2 points in sensory or motor functions, corneal anaesthesia and a nerve tenderness score of 2. Blood bacterial load was determined by the presence of IGM antibodies against M. leprae by Elisa.

In this study, the authors detected the occurrence of NFI in 115 of the 864 patients (13% of patients). They compared the Bands prediction rule (which defines NFI risk groups according to the WHO leprosy classification of PB and MB leprosy combined with the presence of any nerve function loss at diagnoses) with the new proposed prediction value, which replaces the value presence of any nerve function at diagnoses by anti-PGL-I antibodies. The cumulative incidence in the three resulting risk groups (lower risk, mild risk, and higher) were similar. The cumulative incidence of NFI for the risk groups was determined using Kaplan- Meier survival curves.

To identify independent variables that influenced the hazard ratio of NFI, the authors applied Cox proportional hazards regression, which considered sex, age, the WHO classification, presence of nerve-loss at diagnoses, bacterial load and anti-PGL-1 antibodies as variables. Of these, the WHO classification and the anti-PGL-I antibodies were significantly associated with NFI. Perhaps most important is that the new prediction rule suggested did not include the occurrence of nerve loss at diagnosis as a predictable value and therefore is more suitable to identify patients at risk of developing NFI at any moment during the course of disease.

Whereas Kaplan-Meier survival analyses were not able to differentiate between the medium and high- risk groups when using the Bands prediction rule, the adjusted prediction rule (Cox analysis) was able to distinguish three risk groups. Therefore, when the Bands prediction rule was replaced by the adjusted rule, patients were reassigned to either the high-risk group (212 patients) or to the lower risk (25 patients). Clearly, the application of the new adjusted prediction rule has major consequences for patients, as their classification, and therefore the choice for their treatment, may change.

Reference

1. Croft RP, Nicholls PG, Steyerberg EW, Richardus JH, Smith WCS (2000). A clinical prediction rule for nerve-function-impairment in leprosy patients. Lancet 355: 1603–1606. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10821364

2008. Schuring et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.