Genetic Susceptibility and Predictors of Paradoxical Reactions in Buruli Ulcer.
BACKGROUND
Buruli ulcer (BU) is the third most frequent mycobacterial disease in immunocompetent persons after tuberculosis and leprosy. During the last decade, eight weeks of antimicrobial treatment has become the standard of care. This treatment may be accompanied by transient clinical deterioration, known as paradoxical reaction. We investigate the incidence and the risks factors associated with paradoxical reaction in BU.


METHODS
The lesion size of participants was assessed by careful palpation and recorded by serial acetate sheet tracings. For every time point, surface area was compared with the previous assessment. All patients received antimicrobial treatment for 8 weeks. Serum concentration of 25-hydroxyvitamin D, the primary indicator of vitamin D status, was determined in duplex for blood samples at baseline by a radioimmunoassay. We genotyped four polymorphisms in the SLC11A1 gene, previously associated with susceptibility to BU. For testing the association of genetic variants with paradoxical responses, we used a binary logistic regression analysis with the occurrence of a paradoxical response as the dependent variable.


RESULTS
Paradoxical reaction occurred in 22% of the patients; the reaction was significantly associated with trunk localization (p = .039 by Χ(2)), larger lesions (p = .021 by Χ(2)) and genetic factors. The polymorphisms 3'UTR TGTG ins/ins (OR 7.19, p < .001) had a higher risk for developing paradoxical reaction compared to ins/del or del/del polymorphisms.


CONCLUSIONS
Paradoxical reactions are common in BU. They are associated with trunk localization, larger lesions and polymorphisms in the SLC11A1 gene.
Centre de Dépistage et de Traitement de l'Ulcère de Buruli de Lalo, Ministère de la Santé, Cotonou, Bénin.|Department of Internal Medicine, Infectious Diseases Service, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Yves Thierry
YT
Barogui
Department of Internal Medicine, Infectious Diseases Service, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Sandor-Adrian
SA
Klis
Centre Interfacultaire de Formation et de Recherche en Environnement pour le Développement Durable, Université d'Abomey-Calavi, Abomey-Calavi, Bénin.
Roch Christian
RC
Johnson
Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Richard O
RO
Phillips
Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Eveline
E
van der Veer
Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Cleo
C
van Diemen
Department of Internal Medicine, Infectious Diseases Service, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.|Department of Pulmonary Diseases & Tuberculosis, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Tjip S
TS
van der Werf
Department of Internal Medicine, Infectious Diseases Service, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Ymkje
Y
Stienstra
D000890:Anti-Infective Agents / Q000008:administration & dosage*; D054312:Buruli Ulcer / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D027682:Cation Transport Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011863:Radioimmunoassay; D016032:Randomized Controlled Trials as Topic; D017211:Treatment Failure; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D000099173:Natural Resistance-associated Macrophage Protein 1
D000890:Anti-Infective Agents; D027682:Cation Transport Proteins; D014807:Vitamin D; D000099173:Natural Resistance-associated Macrophage Protein 1; C104450:25-hydroxyvitamin D