Relapses <i>vs.</i> reactions in multibacillary leprosy: proposal of new relapse criteria

Linder, Katharina; Zia, Mutaher; Kern, Winfried V.; Pfau, Ruth K. M.; Wagner, Dirk

doi:10.1111/j.1365-3156.2008.02003.x

Cited by 16 publications

(22 citation statements)

References 15 publications

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“…The clinical signs, which are called infl ammatory episodes, may affect both paucibacillary and multibacillary cases, and when they appear following chemotherapy, they may be confounded with cases of recurrence. 3,9,11,20 According to Ximenes et al (2007) 21 and Shetty et al (2005), 18 patients who present reactional episodes are more likely to be treated as cases of recurrence. This indicates that there is a need for greater attention to the differential diagnosis between these two conditions.…”

Section: Discussionmentioning

confidence: 99%

Recidivas de casos de hanseníase no estado de Mato Grosso

Ferreira

Ignotti

Senigalia³

et al. 2010

Rev. Saúde Pública

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OBJECTIVE:To compare new registrations of recurrences of leprosy cases in primary healthcare units (PHUs) and in specialized units in the State of Mato Grosso. METHODS:This was a cross-sectional study based on all new registrations (N = 323) of recurrences of leprosy cases within the Notifi able Disease Information System (SINAN) between 2004 and 2006 that were made in the State of Mato Grosso, Central-West Brazil. The cases diagnosed were compared regarding sex, age, clinical-laboratory characteristics and geographical distribution among the municipalities. To compare and calculate the proportions of the variables, the chi-square test at the signifi cance level of 5% was used. RESULTS:Among the new registrations of recurrences, 20% were confi rmed at specialized units and 80% at PHUs. However, most of the diagnoses at PHUs presented negative bacilloscopy fi ndings (c2 = 12.34; p = 0.002). Seventyone per cent of the cases were among males; the mean age was 43 years. No differences in the percentages of registrations were observed between the healthcare units with regard to clinical form, operational classifi cation or degree of physical incapacity. Out of the total number of municipalities in the state, 64.7% presented recurrences and these accounted for 6 to 20% of all registrations. CONCLUSIONS:The new registrations of cases of recurrence in Mato Grosso were infl uenced by the diagnoses made at PHUs, thus suggesting that there is a defi ciency within the healthcare services in recognizing cases of recurrence.

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Section: Discussionmentioning

confidence: 99%

Recidivas de casos de hanseníase no estado de Mato Grosso

Ferreira

Ignotti

Senigalia³

et al. 2010

Rev. Saúde Pública

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“…Our data show that development of DR isolates of M. leprae is contributing to leprosy relapse in Brazil but that the following are alternative causes: (i) bacterial persistence, (ii) immunosuppression of the host, (iii) pregnancy, (iv) the presence of advanced leprosy, (v) reinfection, and (vi) factors associated with failures in operational health care, such as late diagnosis, inadequate or irregular treatment of the disease, and misclassification of earlier disease (11,18,19,20). We admit, however, that a limitation of this study is the use of PCR sequencing for SNP detection, with limitations regarding the detection of eventual minor mutant populations.…”

Section: Discussionmentioning

confidence: 99%

“…For good-quality data on relapse rates, in addition to laboratory technology, uniformity of clinical criteria relapse diagnosis is important and needs to be standardized within and among countries. Although it not so difficult to diagnose leprosy relapse during the late MB disease form, recognition of relapse is not so easy during early disease, especially in the borderline spectrum cases of disease and under field conditions (19,20).…”

Section: Discussionmentioning

confidence: 99%

Drug and Multidrug Resistance among Mycobacterium leprae Isolates from Brazilian Relapsed Leprosy Patients

et al. 2012

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h Skin biopsy samples from 145 relapse leprosy cases and from five different regions in Brazil were submitted for sequence analysis of part of the genes associated with Mycobacterium leprae drug resistance. Single nucleotide polymorphisms (SNPs) in these genes were observed in M. leprae from 4 out of 92 cases with positive amplification (4.3%) and included a case with a mutation in rpoB only, another sample with SNPs in both folP1 and rpoB, and two cases showing mutations in folP1, rpoB, and gyrA, suggesting the existence of multidrug resistance (MDR). The nature of the mutations was as reported in earlier studies, being CCC to CGC in codon 55 in folP (Pro to Arg), while in the case of rpoB, all mutations occurred at codon 531, with two being a transition of TCG to ATG (Ser to Met), one TCG to TTC (Ser to Phe), and one TCG to TTG (Ser to Leu). The two cases with mutations in gyrA changed from GCA to GTA (Ala to Val) in codon 91. The median time from cure to relapse diagnosis was 9.45 years but was significantly shorter in patients with mutations (3.26 years; P ‫؍‬ 0.0038). More than 70% of the relapses were multibacillary, including three of the mutation-carrying cases; one MDR relapse patient was paucibacillary. There is no doubt about the efficiency of the currently used multidrug therapy (MDT) scheme for treatment of leprosy, as demonstrated by the strong decrease in disease prevalence since its implementation and the low number of reported relapse cases (18). However, there has been a scarcity of in-depth studies of relapse occurrences in recent decades (27). As is known, differentiating diagnosis of relapse and reactional states poses some difficulties in the field, being responsible for under-or overdiagnosis of both disease stages. This is important because undiagnosed relapse cases could contribute to continuing disease transmission. In addition, hardly any data on the contribution of emergence of drug-resistant strains of Mycobacterium leprae to leprosy relapses exist.Diaminodiphenylsulfone (DDS), also called dapsone, was the first drug to be effective against leprosy worldwide, and the first cases of resistance to dapsone were detected in 1964 and involved two single nucleotide polymorphisms (SNPs) in the gene folP1, located in codons 53 and 55 (8, 9, 14, 29). Rifampin is the key component of the standard multidrug regimen used for treatment of leprosy, and it has been shown that PCR-based DNA sequence analysis of the rpoB gene of M. leprae was in full concordance with rifampin susceptibility testing in the mouse footpad system (17, 30). In addition to dapsone and rifampin, ofloxacin is also used for leprosy treatment and is a quinolone with an action mechanism based on interaction with DNA gyrase (2); SNPs in gyrA and gyrB confer resistance or hypersensitivity to quinolones (15). Although there is not yet an official definition of multidrug resistance (MDR) in leprosy, in parallel with tuberculosis, we adopt this terminology when we encounter resistance to rifampin and one other drug of the standard M...

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“…As new cases are considered a major indicator of the maintenance of disease transmission (Rinaldi, 2005), this shows that there is still a need for better measures to control leprosy (WHO, 2008). Relapsed cases could be a new source of disease transmission, but differentiating the diagnoses of disease relapse and of reactional state poses some difficulties in the field, contributing to continuing disease transmission in some situations (Linder et al, 2008;Shetty et al, 2005) or overdiagnosis of relapse in others.…”

Section: Introductionmentioning

confidence: 99%

Genotyping of Mycobacterium leprae from Brazilian leprosy patients suggests the occurrence of reinfection or of bacterial population shift during disease relapse

Rocha

Santos

Pignataro

et al. 2011

Journal of Medical Microbiology

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We performed genotyping of Mycobacterium leprae present in skin biopsy samples that were collected during the first and the second disease occurrences from eight leprosy patients, seven of whom were diagnosed as suffering from disease relapse. Sequence analysis of part of the M. leprae rpoB, folP1, gyrB and gyrA genes did not show genetic change that supported the presence of drug-resistant bacilli. However, we observed a synonymous nucleotide change at position 297 of gyrA among five of these patients, one presenting C to T (CgyrAT) and four presenting T to C (TgyrAC) at this position. Additional genotyping by analysis of the four short tandem repeats GAA, GTA9, AT17 and TA18 showed that the gyrA single nucleotide polymorphism change was accompanied by a change in short tandem repeat genotype. Our data suggest that leprosy relapse in these patients, living in an area endemic for leprosy, could be caused by M. leprae with a genotype different from the one that caused initial disease.

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Relapses vs. reactions in multibacillary leprosy: proposal of new relapse criteria

Cited by 16 publications

References 15 publications

Recidivas de casos de hanseníase no estado de Mato Grosso

Recidivas de casos de hanseníase no estado de Mato Grosso

Drug and Multidrug Resistance among Mycobacterium leprae Isolates from Brazilian Relapsed Leprosy Patients

Genotyping of Mycobacterium leprae from Brazilian leprosy patients suggests the occurrence of reinfection or of bacterial population shift during disease relapse

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