Can baseline ML Flow test results predict leprosy reactions? An investigation in a cohort of patients enrolled in the uniform multidrug therapy clinical trial for leprosy patients in Brazil

Abstract

BackgroundThe predictive value of the serology to detection of IgM against the Mycobacterium leprae-derived phenolic glycolipid-I/PGL-I to identify leprosy patients who are at higher risk of developing reactions remains controversial. Whether baseline results of the ML Flow test can predict leprosy reactions was investigated among a cohort of patients enrolled in The Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR).MethodsThis was a descriptive study focusing on the main clinical manifestations of leprosy patients enrolled in the U-MDT/CT-BR from March 2007 to February 2012 at two Brazilian leprosy reference centers. For research purposes, 753 leprosy patients were categorized according to a modified Ridley-Jopling (R&J) classification and according to the development of leprosy reactions (reversal reaction/RR and erythema nodosum leprosum/ENL), and whether they had a positive or negative bacillary index/BI.ResultsMore than half of the patients (55.5 %) reported leprosy reaction: 18.3 % (138/753) had a RR and 5.4 % (41/753) had ENL. Leprosy reactions were more frequent in the first year following diagnosis, as seen in 27 % (205/753) of patients, while 19 % (142/753) developed reactions during subsequent follow-up. Similar frequencies of leprosy reactions and other clinical manifestations were observed in paucibacillary (PB) and multibacillary (MB) leprosy patients treated with U-MDT and regular MDT (R-MDT) (P = 0.43 and P = 0.61, respectively). Compared with PB patients, leprosy reactions were significantly more frequent in MB patients with a high BI, and more patients developed RR than ENL. However, RR and neuritis were also reported in patients with a negative BI. At baseline, the highest rate of ML Flow positivity was observed in patients with a positive BI, especially those who developed ENL, followed by patients who had neuritis and RR. Among reaction-free patients, 81.9 % were ML Flow positive, however, the differences were not statistically significant compared to reactional patients (P = 0.45).ConclusionsMB and PB patients treated with R-MDT and U-MDT showed similar frequencies of RR and other clinical manifestations. Positive ML Flow tests were associated with MB leprosy and BI positivity. However, ML Flow test results at baseline showed limited sensitivity and specificity for predicting the development of leprosy reactions.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-016-0203-0) contains supplementary material, which is available to authorized users.

Differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum

“…In our cohort, we observed that only 4.6% of PB cases had a reaction during follow-up, which is likely related to the large number of TT cases, who only rarely develop RR. Among MB leprosy cases, the incidence of reactions was much higher, similar to that observed by Hungria et al in their cohort involving 753 cases of leprosy [32].…”

“…We saw elevated anti-LID-NDO antibodies, as determined by OD, in people at leprosy diagnosis who went on to develop RR or ENL in the next 2 years. The predictive value of anti-PGL-1 levels for leprosy immune reactions is unclear [32, 35–37]. However, we saw a high and statistically significant risk of reaction development with increase in anti-LID-NDO at leprosy diagnosis.…”

Perfil clínico-epidemiológico de pacientes com hanseníase atendidos em hospital universitário no Rio de Janeiro entre 2008 e 2017

“…Um trabalho realizado em dois centros de referência para hanseníase observou que 55,5% dos pacientes apresentaram pelo menos um estado reacional. 18 Outro estudo recente em que foram incluídos pacientes do Brasil, Filipinas e Nepal evidenciou uma frequência de reação de 22,1% (435/1972 pacientes). 19 A alta frequência de estados reacionais encontradas no presente estudo pode estar relacionada ao fato do HUGG ser um centro de referência para os casos mais graves da doença.…”

Mycobacterium leprae-Specific Antibodies in Multibacillary Leprosy Patients Decrease During and After Treatment With Either the Regular 12 Doses Multidrug Therapy (MDT) or the Uniform 6 Doses MDT

“…Previous studies have investigated the potential use of leprosy serology as a marker of reactional episodes ( 50 – 52 ). Two previous publications from our group using the U-MDT database and sera bank ( 40 , 41 ) have described the impact of baseline serology on the development of leprosy reactions. The baseline ML flow test results showed limited sensitivity and specificity as prognostic markers for the development of leprosy reactions during subsequent follow-up ( 40 ).…”

“…Two previous publications from our group using the U-MDT database and sera bank ( 40 , 41 ) have described the impact of baseline serology on the development of leprosy reactions. The baseline ML flow test results showed limited sensitivity and specificity as prognostic markers for the development of leprosy reactions during subsequent follow-up ( 40 ). Also, the analyses of anti-PGL-I, anti-LID-1, anti-ND-O-LID antibodies at diagnosis showed low sensitivity and specificity for predicting reversal reaction while anti-LID-1 serology at diagnosis showed prognostic value for the development of ENL in BI positive patients ( 41 ).…”