Leprosy in Colombia: A look from life experience.

Leprosy continues to be stigmatized, causing harm to fundamental rights, pain and hopelessness in those who have suffered from it and their families. From its relationship with public and mental health, effective strategies must be implemented to reduce stigma and unlearn myths and wrong perceptions, support families, and improve quality of life through early care and detection. This article shows that those affected by leprosy are capable, functional people with much to contribute to society anywhere in the world.

High seropositivity against NDO-LID in a group of household contacts of leprosy patients. Are we close to leprosy elimination in Colombia?

INTRODUCTION: Leprosy is a chronic infectious disease caused by two mycobacteria (Mycobacterium leprae and Mycobacterium lepromatosis). The household contacts (HHC) of leprosy index cases are at higher risk of being infected with these mycobacteria. Therefore, serological testing in HHC would be an effective strategy to eliminate leprosy in Colombia. OBJECTIVE: To determine the seroprevalence and factors associated with the infection by M. leprae in HHC. METHODS: An observational study was conducted in 428 HHC located in the Colombian Caribbean, Andean, Pacific, and Amazonian regions. We evaluated the seropositivity and titrations of IgM, IgG, and protein A against NDO-LID. RESULTS: The evaluated HHC showed high seropositivity, precisely 36.9% anti-NDO-LID IgM, 28.3% anti-NDO-LID IgG, and 47.7% protein A. Furthermore, Protein A showed a greater capacity to detect infected individuals than other anti-NDO-LID conjugates (p < 0.0001). This study did not show differences in the seropositivity according to sex or age of the HHC (p > 0.05). Higher seropositivity for IgM was evidenced mainly in HHC located in the Colombian Pacific region (p 0.001). This research did not show differences in the seropositivity for these serological tests between HHC of PB or MB leprosy patients (p > 0.05). CONCLUSION: Leprosy transmission is still active between Colombian HHC. Consequently, controlling leprosy transmission in this population is fundamental to eradicating this disease.

Association of the rs2111234, rs3135499, rs8057341 polymorphisms in the NOD2 gene with leprosy: A case-control study in the Norte de Santander, Colombia population.

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The development of leprosy involves several factors, including the causative agent, the individual host's immune response, environmental factors, and the genetic background of the host. Specifically, the host's innate immune response, encoded by genes, determines their susceptibility to developing leprosy post-infection. Polymorphic variants in the nucleotide-binding oligomerization domain 2 (NOD2) gene are associated with leprosy among populations in a variety of endemic areas around the world. Colombia, a country located in the tropical zone, has several leprosy-endemic regions, including Norte de Santander. The aim of this study was to analyze the rs7194886, rs2111234, rs3135499, and rs8057341 single nucleotide polymorphisms (SNPs) in the NOD2 gene using a case-control study to determine whether they confer greater or lesser susceptibility to the development of leprosy. METHODOLOGY: The TaqMan qPCR amplification system was used for SNPs detection. FINDINGS: An association between the A-rs8057341 SNP (p = 0,006286) and resistance to leprosy was found. However, the rs3135499 (p = 0,9063) and rs2111234 (p = 0.1492) were not found to be associated with leprosy susceptibility. In addition, the rs7194886 SNP was not found to be in Hardy-Weinberg equilibrium (HWE) in the study population. The GAG haplotype, consisting of SNPs rs2111234-G, rs3135499-A, and rs8057341G, acts as a susceptibility factor for the development of leprosy in women. SNPs rs3135499 and rs8057341 are functionally related to decreased NOD2 expression according to an in-silico analysis. CONCLUSIONS: The SNPs rs8057341-A was related with resistance to leprosy and the haplotype rs2111234-G, rs3135499-A and rs8057341-G SNPs was related with susceptibility in the Norte de Santander Colombia, studied population.

Mycobacterium lepromatosis as Cause of Leprosy, Colombia.

Leprosy is a granulomatous infection caused by infection with Mycobacterium leprae or M. lepromatosis. We evaluated skin biopsy and slit skin smear samples from 92 leprosy patients in Colombia by quantitative PCR. Five (5.4%) patients tested positive for M. lepromatosis, providing evidence of the presence of this pathogen in Colombia.

Detection of Mycobacterium leprae infection in family clusters from six leprosy-endemic regions in Colombia.

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which continues to be endemic in tropical countries, making it necessary to implement strategies for its elimination. The objective of the current article was to detect M. leprae infection and associated factors through serological and epidemiological evaluation in family clusters of leprosy patients. METHODS: Mycobacterium leprae infection was determined in 50 family clusters of leprosy patients from the departments of Bolívar, Atlántico, Santander, Boyacá, Chocó and Antioquia through the detection of antibodies (protein A, IgM, IgG) against anti-natural octyl disacharide-leprosy IDRI diagnostic (NDO-LID). RESULTS: Higher seroconversion and elevated titers of these antibodies against NDO-LID were observed in the population of Chocó and Atlántico (p<0.05). Additionally, a higher frequency of infection was observed in large family groups that consumed armadillo meat and belonged to a low socioeconomic stratum (p<0.05). Multivariate analysis established that the main associated factors for a family cluster experiencing this infection were belonging to a vulnerable economic stratum and a large family group. CONCLUSIONS: This study found that the set of social and demographic variables (i.e. armadillo consumption, geographic area, low socioeconomic status and belonging to a large family cluster) are related to the promotion of seropositivity in family clusters.

Clinical, histopathological, and molecular characterization of leprosy in an endemic area of the colombian caribbean.

Background: Mycobacterium leprae was considered the only causal agent of leprosy until Mycobacterium lepromatosis was identified' which it has been suggested has greater pathogenicity and is linked to diffuse lepromatous leprosy (DLL) and Lucio's phenomenon (LPh). Our objective is to identify Mycobacterium spp. in an endemic area of leprosy in Colombia. Methods: The study included cases with a diagnosis of leprosy by clinical and histopathological analysis. DNA extraction and two specific rounds of semi-nested polymerase chain reaction (PCR) were performed in paraffin biopsies skin to identify M. leprae and M. lepromatosis. Demographic, clinical, and histopathological data were extracted and tabulated for analysis. Results: Forty-one cases of leprosy were analyzed. The most frequent clinical diagnosis was lepromatous leprosy (36.6%); there was one case with DLL and two with LPh. The most common histopathological finding was tuberculoid leprosy (36.59%); three cases had negative histopathology. M. lepromatosis was not detected; all cases corresponded to M. leprae including cases with negative histopathology' DLL, and LPh. Conclusion: In this study, M. leprae was the causative agent of leprosy, encompassing even its most severe phenotypic forms. It is appropriate to consider PCR as an indispensable tool for the diagnosis of leprosy and to continue to carry out the active search for M. lepromatosis.

Stigma, participation restriction and mental distress in patients affected by leprosy, cutaneous leishmaniasis and Chagas disease: a pilot study in two co-endemic regions of eastern Colombia.

BACKGROUND: Leprosy, cutaneous leishmaniasis (CL) and Chagas disease (CD) are neglected tropical diseases with a high psychosocial burden (PSB). These conditions are endemic in Norte de Santander and Arauca in Colombia, but data on the related PSB are scarce. Therefore, we assessed mental distress, participation restriction and stigma among CD, CL and leprosy patients. METHODS: In 2018, 305 leprosy, CD or CL patients were interviewed using a self-report questionnaire to assess mental distress, participation scale for participation restriction and explanatory model interview catalogue (EMIC) for stigma. Descriptive statistics and the significance of median score differences were compared. RESULTS: Fifty percent of CD patients and 49% of leprosy patients exhibited mental distress, percentages which were significantly higher than that of CL (26%). Twenty-seven percent of leprosy patients experienced participation restriction, which was lower for CL (6%) and CD (12%). Median EMIC scores were significantly higher for leprosy patients than for CD (27%) and CL (17%) patients. CONCLUSIONS: We found high levels of PSB among leprosy, CD and CL patients. Mental distress was highest among CD patients. Participation restriction and stigma were more prevalent in leprosy patients. Rural residence or lower educational status may impact PSB. Further investigation is needed to formulate evidence-based, holistic interventions.

Inequalities in health by regime of affiliation to the health system in events of obligatory notification, Colombia, 2015 / Desigualdades en salud según régimen de afiliación y eventos notificados al Sistema de Vigilancia (Sivigila) en Colombia, 2015

Introduction: Inequalities in the health field are caused by the differences in the social and economic conditions, that influence the disease risk and the measures taken to treat the disease. Objective: We aimed to estimate the social inequalities in health in Colombia, according to the type of affiliation to the health system as a proxy of socioeconomic status. Materials and methods: We conducted a retrospective descriptive analysis calculating incidence rates age and sex adjusted for all mandatory reporting events using the affiliation regime (subsidized and contributory) as a socioeconomic proxy. Estimates were made at departmental level for 2015. Social inequalities were calculated in terms of absolute and relative gaps. Results: We found social inequalities in the occurrence of mandatory reporting events in population affiliated to the Colombian subsidized regime (poor population). In this population, 82.31 cases of Plasmodium falciparum malaria per 100,000 affiliates were reported more than those reported in the contributory regime. Regarding the relative gap, belonging to the subsidized regime increased by 31.74 times the risk of dying from malnutrition in children under 5 years of age. Other events such as those related to sexual and reproductive health (maternal mortality, gestational syphilis and congenital syphilis); neglected diseases and communicable diseases related to poverty (leprosy and tuberculosis), also showed profound inequalities. Conclusion: In Colombia there are inequalities by regime of affiliation to the health system. Measured socioeconomic status was a predictor of increased morbidity and premature mortality.

Introducción. Las desigualdades en salud se generan por diferencias en las condiciones sociales y económicas, lo cual influye en el riesgo de enfermar y la forma de enfrentar la enfermedad. Objetivo. Evaluar las desigualdades sociales en salud en Colombia, utilizando el tipo de afiliación al sistema de salud como un parámetro representativo (proxy) de la condición socioeconómica. Materiales y métodos. Se trata de un análisis descriptivo y retrospectivo en el que se calcularon las tasas específicas de incidencia, ajustadas por edad y sexo, para eventos de notificación obligatoria, utilizando el régimen de afiliación (subsidiado o contributivo) como variable representativa del nivel socioeconómico. Las estimaciones se hicieron a nivel departamental para el 2015. Las desigualdades sociales se calcularon en términos de brechas absolutas y relativas. Resultados. Se evidencian desigualdades sociales en la ocurrencia de eventos de notificación obligatoria, las cuales desfavorecen a la población afiliada al régimen subsidiado. En esta población, se reportaron 82,31 casos más de malaria Plasmodium falciparum por 100.000 afiliados, que los notificados en el régimen contributivo. Respecto a la brecha relativa, el pertenecer al régimen subsidiado se asocia con un aumento de 31,74 veces del riesgo de morir por desnutrición en menores de cinco años. Otros eventos también presentaron profundas desigualdades, como los relacionados con la salud sexual y reproductiva (mortalidad materna, sífilis gestacional y sífilis congénita), las enfermedades infecciosas y las enfermedades transmisibles relacionadas con la pobreza (lepra y tuberculosis). Conclusión. El tipo de afiliación al Sistema General de Seguridad Social en Salud en Colombia es un buen indicador del nivel socioeconómico, y es un factor predictor de mayor morbilidad y mortalidad prematura asociada con los factores determinantes sociales de la salud.

Social and environmental conditions related to Mycobacterium leprae infection in children and adolescents from three leprosy endemic regions of Colombia.

BACKGROUND: Leprosy is is still considered a public health issue and in Colombia 7-10% of new cases are found in children, indicating both active transmission and social inequality. We hypothesized that circulating antibodies against Natural Octyl Disaccharide-Leprosy IDRI Diagnostic (NDO-LID) (a combination of Mycobacterium leprae antigens) could reveal the social and environmental aspects associated with higher frequencies of M. leprae infection among children and adolescents in Colombia. METHODS: An observational cross-sectional study was conducted involving sampling from 82 children and adolescents (younger than 18 years of age) who had household contact with index leprosy patients diagnosed in the last 5 years. Data were analyzed through bivariate analysis made by applying a Pearson x2 test for qualitative variables, while quantitative variables, depending on their distribution, were analyzed using either a Student's t-test or Mann-Whitney U test. Multivariate analysis was performed using a multiple regression and binomial logistic approach. RESULTS: A bivariate analysis demonstrated that antibody titers against NDO-LID were significantly greater in children and adolescents with a low socioeconomic status that had: lived in vulnerable areas of the UAChR shared region; eaten armadillo meat; exposure of over 10 years to an index case and; not received BCG immunization. Moreover, a multivariate analysis showed that residing in the UAChR region has a strong association with a greater possibility of M. leprae infection. CONCLUSIONS: M. leprae transmission persists among young Colombians, and this is associated with social and environmental conditions. An intensification of efforts to identify new leprosy cases in vulnerable and forgotten populations where M. leprae transmission continues therefore appears necessary.

Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009-15.

OBJECTIVES: Antimicrobial resistance (AMR) is a priority for surveillance in bacterial infections. For leprosy, AMR has not been assessed because Mycobacterium leprae does not grow in vitro. We aim to obtain AMR data using molecular detection of resistance genes and to conduct a prospective open survey of resistance to antileprosy drugs in countries where leprosy is endemic through a WHO surveillance network. METHODS: From 2009 to 2015, multi-bacillary leprosy cases at sentinel sites of 19 countries were studied for resistance to rifampicin, dapsone and ofloxacin by PCR sequencing of the drug-resistance-determining regions of the genes rpoB, folP1 and gyrA. RESULTS: Among 1932 (1143 relapse and 789 new) cases studied, 154 (8.0%) M. leprae strains were found with mutations conferring resistance showing 182 resistance traits (74 for rifampicin, 87 for dapsone and 21 for ofloxacin). Twenty cases showed rifampicin and dapsone resistance, four showed ofloxacin and dapsone resistance, but no cases were resistant to rifampicin and ofloxacin. Rifampicin resistance was observed among relapse (58/1143, 5.1%) and new (16/789, 2.0%) cases in 12 countries. India, Brazil and Colombia reported more than five rifampicin-resistant cases. CONCLUSIONS: This is the first study reporting global data on AMR in leprosy. Rifampicin resistance emerged, stressing the need for expansion of surveillance. This is also a call for vigilance on the global use of antimicrobial agents, because ofloxacin resistance probably developed in relation to the general intake of antibiotics for other infections as it is not part of the multidrug combination used to treat leprosy.

Resistencia a la poliquimioterapia en pacientes con enfermedad de Hansen / Resistance to polychemotherapy in patients with Hansen's disease

RESUMEN Se describe un reporte de caso de un paciente del Sanatorio Agua de Dios Cundinamarca con diagnóstico de lepra lepromatosa histioide con sospecha de resistencia a la poliquimioterapia (PQT), evidenciando la importancia de los criterios clínicos para inicio de terapia alterna ante las limitaciones en los medios paraclínicos. La resistencia debe sospecharse y diagnosticarse tempranamente para evitar la progresión de la enfermedad; los criterios clínicos y paraclínicos ayudan a su confirmación diagnóstica, en los estudios bacteriológicos la escala semicuantitativa Colombiana debe reemplazarse por escala logarítmica de Ridley y Jopling, los estudios histopatológicos se practican en todo paciente con enfermedad de Hansen, los estudios de resistencia se están implementando en el país pero su acceso limita oportunidad para apoyo en el inicio terapéutico.(AU)

ABSTRACT This paper describes a case report of a patient from the Sanatorio Agua de Dios-Cundinamarca diagnosed with histioid lepromatous leprosy with suspected resistance to polychemotherapy (PQT), making evident the importance of clinical criteria for initiating an alternative therapy given the limitations of paraclinical examinations. Resistance should be suspected and diagnosed early to prevent the progression of the disease; clinical and paraclinical criteria help to confirm diagnosis. In bacteriological studies, the Colombian semiquantitative scale should be replaced by the Ridley-Jopling logarithmic scale. Histopathological studies are conducted on all patients with Hansen's disease. Research on resistance is being implemented in the country, but its access limits the opportunity for support in therapy initiation.(AU)

The impact of skin diseases on quality of life: a multicenter study / El impacto de las enfermedades cutáneas en la calidad de vida: un estudio multicéntrico

INTRODUCTION: To date, no formal study has been published regarding how Colombian patients with skin disorders could be affected according to their perception of disease. OBJECTIVE: To determine the impact in quality of life of skin diseases in a Colombian population. METHODS: This multicenter study included patients with skin disease from almost the whole country. Individuals >18 years old; of any gender; with any skin disease and who signed informed consent, were included. We applied the Colombian validated version of the Skindex-29 instrument. RESULTS: A total of 1896 questionnaires had sufficient information for the analyses. No significant differences in sociodemographic characteristics of patients who returned the questionnaire incomplete vs. complete, were found. Participants mean age was 41.5 years. There were no statistical differences in men vs. women regarding the global (p = 0.37), symptoms (p = 0.71) and emotions (p = 0.32) domains, whereas statistical differences were found in the function domain (p = 0.04; Mann-Whitney U test). Psoriasis, contact dermatitis, atopic dermatitis, urticaria, hair disorders, Hansen's disease, scars, hyperhidrosis and genital human papillomavirus disease scored the highest. Limitations. Skindex-29 score variability as a result of differences in the location of the skin lesions, their inflammatory or non-inflammatory nature, and the start of therapy. CONCLUSIONS: Even the most localized or asymptomatic skin lesion in our population leads to a disruption at some level of patient's wellness. This study adds well supported scientific data of the burden of skin diseases worldwide

INTRODUCCIÓN: En Colombia se carece de estudios que hayan evaluado formalmente el impacto de las enfermedades dermatológicas en la calidad de vida de los pacientes que las padecen. OBJETIVO: Determinar el impacto en la calidad de vida de las enfermedades cutáneas en una población colombiana. MÉTODOS: Estudio multicéntrico que incluyó a individuos>18 años de edad; de cualquier sexo, con cualquier trastorno cutáneo y que firmaron el consentimiento informado. Se aplicó la versión validada en Colombia del instrumento Skindex-29. RESULTADOS: Un total de 1.896 cuestionarios se incluyeron en el análisis. No se observaron diferencias significativas en las características sociodemográficas entre los que devolvieron el cuestionario incompleto vs. completo. La edad promedio fue de 41,5 años. No hubo diferencias significativas entre hombres y mujeres con respecto al puntaje global del instrumento, ni de los dominios sintomático o emocional, mientras que sí las hubo en el dominio funcional. Entre las enfermedades que más afectaron la calidad de vida se incluyen: psoriasis, dermatitis de contacto, dermatitis atópica, urticaria, trastornos capilares, lepra, cicatrices, hiperhidrosis y las verrugas genitales. Limitaciones. Las puntuaciones del Skindex-29 mostraron una gran variabilidad explicable por diferencias en la localización de las lesiones de la piel, su naturaleza inflamatoria/no inflamatoria, y la iniciación o no del tratamiento. CONCLUSIONES: Cualquier lesión dermatológica por más localizada o asintomática que sea, condujo a una alteración en algún grado de la calidad de vida dermatológica. Este estudio añade soporte científico a la carga de enfermedad que generan los trastornos cutáneos en el mundo

Evaluation and Monitoring of Mycobacterium leprae Transmission in Household Contacts of Patients with Hansen's Disease in Colombia.

Leprosy in Colombia is in a stage of post elimination-since 1997, prevalence of the disease is less than 1/10000. However, the incidence of leprosy has remained stable, with 400-500 new cases reported annually, with MB leprosy representing 70% of these case and 10% having grade 2 disability. Thus, leprosy transmission is still occurring, and household contacts (HHCs) of leprosy patients are a population at high risk of contracting and suffering from the effects of the disease during their lifetime. We performed a cross-sectional study with the aim of evaluating leprosy transmission within Family Groups (FGs) from four Colombian departments: Antioquia, Bolívar, Córdoba and Sucre. This study included 159 FGs formed by 543 HHCs; 45 FGs were monitored twice, first in 2003 and again in 2012. Migration, forced displacement by violence, loss of contact with the health center and the lack of an agreement to participate in the second monitoring were the primary reasons not all FGs were tested a second time. In each HHC, a clinical examination was performed, epidemiological data recorded, the bacillary index determined, DNA was isolated for M. leprae detection by nested PCR and IgM anti-phenolic glycolipid-I (PGL-I) titers were inspected. Further, DNA from M. leprae isolates were typed and compared among FGs. Twenty-two (4.1%) of the 543 HHCs had IgM anti-PGL-I positive antibody titers, indicating infection. Nasal swabs (NS) taken from 113 HHCs were tested by RLEP PCR; 18 (16%) were positive for M. leprae DNA and two new leprosy cases were detected among the HHCs. Of the confirmed HHCs with leprosy, it was possible to genotype the bacterial strains from both the index case and their HHCs. We found that the genotype of these two strains agreed at 9 markers, showing the individuals to be infected by the same strain, indicating familiar transmission. HHCs of leprosy patients not only are a high-risk population for M. leprae infection, they can act as M. leprae carriers and therefore serve as sources for transmission and infection. Our results confirm familiar leprosy transmission and suggest that follow-up of HHCs is a good strategy for early diagnosis of leprosy and to monitor its transmission.

Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country.

An active search for Mycobacterium leprae drug resistance was carried out, 243 multibacillary patients from endemic regions of Colombia were included from 2004 to 2013 in a surveillance program. This program was a World Health Organization initiative for drug resistance surveillance in leprosy, where Colombia is a sentinel country. M. leprae DNA from slit skin smear and/or skin biopsy samples was amplified and sequenced to identify mutations in the drug resistance determining region (DRDR) in rpoB, folP1, gyrA, and gyrB, the genes responsible for rifampicin, dapsone and ofloxacin drug-resistance, respectively. Three isolates exhibited mutations in the DRDR rpoB gene (Asp441Tyr, Ser456Leu, Ser458Met), two in the DRDR folP1 gene (Thr53Ala, Pro55Leu), and one isolate exhibited mutations in both DRDR rpoB (Ser456Met) and DRDR folP1 (Pro55Leu), suggesting multidrug resistance. One isolate had a double mutation in folP1 (Thr53Ala and Thr88Pro). Also, we detected mutations outside of DRDR that required in vivo evaluation of their association or not with drug resistance: rpoB Arg505Trp, folP1 Asp91His, Arg94Trp, and Thr88Pro, and gyrA Ala107Leu. Seventy percent of M. leprae mutations were related to drug resistance and were isolated from relapsed patients; the likelihood of relapse was significantly associated with the presence of confirmed resistance mutations (OR range 20.1-88.7, p < 0.05). Five of these relapsed patients received dapsone monotherapy as a primary treatment. In summary, the current study calls attention to M. leprae resistance in Colombia, especially the significant association between confirmed resistance mutations and relapse in leprosy patients. A high frequency of DRDR mutations for rifampicin was seen in a region where dapsone monotherapy was used extensively.

Human Genetic Ancestral Composition Correlates with the Origin of Mycobacterium leprae Strains in a Leprosy Endemic Population.

Recent reports have suggested that leprosy originated in Africa, extended to Asia and Europe, and arrived in the Americas during European colonization and the African slave trade. Due to colonization, the contemporary Colombian population is an admixture of Native-American, European and African ancestries. Because microorganisms are known to accompany humans during migrations, patterns of human migration can be traced by examining genomic changes in associated microbes. The current study analyzed 118 leprosy cases and 116 unrelated controls from two Colombian regions endemic for leprosy (Atlantic and Andean) in order to determine possible associations of leprosy with patient ancestral background (determined using 36 ancestry informative markers), Mycobacterium leprae genotype and/or patient geographical origin. We found significant differences between ancestral genetic composition. European components were predominant in Andean populations. In contrast, African components were higher in the Atlantic region. M. leprae genotypes were then analyzed for cluster associations and compared with the ancestral composition of leprosy patients. Two M. leprae principal clusters were found: haplotypes C54 and T45. Haplotype C54 associated with African origin and was more frequent in patients from the Atlantic region with a high African component. In contrast, haplotype T45 associated with European origin and was more frequent in Andean patients with a higher European component. These results suggest that the human and M. leprae genomes have co-existed since the African and European origins of the disease, with leprosy ultimately arriving in Colombia during colonization. Distinct M. leprae strains followed European and African settlement in the country and can be detected in contemporary Colombian populations.

Is drug-resistant Mycobacterium leprae a real cause for concern?: First approach to molecular monitoring of multibacillary Colombian patients with and without previous leprosy treatment.

INTRODUCTION: There is no information in Colombia on Mycobacterium leprae primary and secondary drug resistance in regards to the WHO-multidrug therapy regime. On the other hand, public health authorities around the world have issued various recommendations, one of which prompts for the immediate organization of resistance surveillance through simple molecular methods. OBJECTIVE: To determine the prevalence of Mycobacterium leprae drug resistance to rifampicin, ofloxacin and dapsone in untreated and previously treated patients at the Centro Dermatológico Federico Lleras Acosta during the 1985-2004 period. MATERIALS AND METHODS: We conducted a retrospective study which included multibacillary patient biopsies through elective sampling: 381 of them from new patients and 560 from previously treated patients. Using a microtome, we obtained six slides from each skin biopsy preserved in paraffin, and we extracted M. leprae DNA. We amplified three molecular targets through PCR and obtained the patterns of drug resistance to dapsone, rifampicin and ofloxacin by reverse hybridization. Finally, we collected epidemiological, clinical and demographical data for analyses. RESULTS: From 941 samples under study, 4.14% of them were resistant to one or more drugs, and 5.77 and 3.04% had resistant genotypes in new and previously treated patients, respectively. Total resistance for each drug was 0.43% for dapsone, 3.19% for rifampicin and 1.17% for ofloxacin. We found statistically significant differences for rifampicin and for the total population when comparing the results from untreated versus previously treated patients. Two thirds of the resistant samples were resistant to rifampicin alone or combined. CONCLUSIONS: The standard multidrug therapy schemes continue being effective for leprosy cases; however, it is necessary to guarantee adherence and regularity. Surveillance to drug resistance in new and previously treated leprosy cases should be established.

Is drug-resistant Mycobacterium leprae a real cause for concern?: First approach to molecular monitoring of multibacillary Colombian patients with and without previous leprosy treatment / ¿Es la resistencia de Mycobacterium leprae a los medicamentos un verdadero motivo de preocupación?: Primera aproximación a la vigilancia molecular de pacientes colombianos multibacilares con tratamiento previo para lepra y sin él

Introduction: There is no information in Colombia on Mycobacterium leprae primary and secondary drug resistance in regards to the WHO-multidrug therapy regime. On the other hand, public health authorities around the world have issued various recommendations, one of which prompts for the immediate organization of resistance surveillance through simple molecular methods. Objective: To determine the prevalence of Mycobacterium leprae drug resistance to rifampicin, ofloxacin and dapsone in untreated and previously treated patients at the Centro Dermatológico Federico Lleras Acosta during the 1985-2004 period. Materials and methods: We conducted a retrospective study which included multibacillary patient biopsies through elective sampling: 381 of them from new patients and 560 from previously treated patients. Using a microtome, we obtained six slides from each skin biopsy preserved in paraffin, and we extracted M. leprae DNA. We amplified three molecular targets through PCR and obtained the patterns of drug resistance to dapsone, rifampicin and ofloxacin by reverse hybridization. Finally, we collected epidemiological, clinical and demographical data for analyses. Results: From 941 samples under study, 4.14% of them were resistant to one or more drugs, and 5.77 and 3.04% had resistant genotypes in new and previously treated patients, respectively. Total resistance for each drug was 0.43% for dapsone, 3.19% for rifampicin and 1.17% for ofloxacin. We found statistically significant differences for rifampicin and for the total population when comparing the results from untreated versus previously treated patients. Two thirds of the resistant samples were resistant to rifampicin alone or combined. Conclusions: The standard multidrug therapy schemes continue being effective for leprosy cases; however, it is necessary to guarantee adherence and regularity. Surveillance to drug resistance in new and previously treated leprosy cases should be established.

Introducción. Colombia no dispone de información sobre farmacorresistencia primaria y secundaria de Mycobacterium leprae al esquema de terapia múltiple de la Organización Mundial de la Salud (OMS) y las autoridades de salud pública del mundo han emitido varias recomendaciones, entre las cuales está organizar de inmediato la vigilancia a la resistencia empleando métodos moleculares simples. Objetivo. Determinar la prevalencia de la resistencia de M. leprae a rifampicina, ofloxacina y dapsona en pacientes del Centro Dermatológico Federico Lleras Acosta con tratamiento previo y sin él durante el período de 1985 a 2004. Materiales y métodos. Se realizó un estudio retrospectivo. Mediante muestreo electivo se incluyeron biopsias de pacientes multibacilares: 381 de pacientes nuevos y 560 de pacientes previamente tratados. Se obtuvieron con micrótomo seis cortes de cada biopsia de piel incluida en parafina, y se realizó la extracción de ADN de M. leprae. Se llevó a cabo la amplificación de tres blancos moleculares mediante PCR y se obtuvieron los patrones de resistencia a los medicamentos dapsona, rifampicina y ofloxacina por hibridación inversa. Se recolectaron datos epidemiológicos, clínicos y demográficos para llevar a cabo los análisis. Resultados. De las 941 muestras estudiadas, 4,14 % era resistente a uno o más fármacos, y se detectaron 5,77 y 3,04 % con genotipos resistentes en pacientes nuevos y previamente tratados, respectivamente. La resistencia total para cada fármaco fue de 0,43 % a dapsona, 3,19 % a rifampicina y 1,17 % a ofloxacina. Se encontró una diferencia estadísticamente significativa para rifampicina y para la población total al comparar los resultados de los pacientes no tratados con los de los pacientes tratados previamente. Dos tercios de las muestras resistentes lo fueron a rifampicina sola o combinada. Conclusiones. Los esquemas de terapia múltiple estándar siguen siendo efectivos para los casos de lepra; sin embargo, es necesario garantizar el cumplimiento y la regularidad y establecer la vigilancia de la farmacorresistencia en pacientes nuevos y previamente tratados.

Lepra en Colombia: ¿Se encuentra en la fase de post-eliminación? / No disponible

Hace más de diez años que la lepra en Colombia no se considera un problema de salud pública, ya que la prevalencia es menor de 1/10.000. Si embargo, los informes de 2012 correspondientes a 11 de 27 Departamentos (48%) revelan incidencias de 0.12 a 4.73 casos por 100.000 habitantes. El Ministerio de Sanidad y el Instituto de Salud dirigen y organizan el Programa Nacional de la Lepra (PNL), que planifica las actividades de prevención, vigilancia y control a nivel nacional. La logística está delegada a nivel regional (municipios, distritos, Departamentos), sin embargo en muchas zonas la deficiente estructura hospitalaria, los elevados costes, la falta de personal sanitario formado, o el difícil acceso a los servicios sanitarios son algunas de las barreras que impiden el desarrollo y acceso a las actividades que el PNL publica en sus guías. Lo mencionado anteriormente tiene como consecuencia un diagnóstico tardío con un 30% de discapacidades (grado 1 y 2) en el momento del diagnóstico. Tampoco hay una gran percepción de la enfermedad en la población general ni en los profesionales sanitarios sobre la incidencia de la lepra en Colombia. Esta es una revisión de la situación de la lepra en Colombia, teniendo en cuenta no solamente los datos estadísticos, sino también algunos aspectos que influyen en el diagnóstico tardío y la discapacidad hallados en pacientes en el momento de su diagnóstico. Esta revisión contiene opiniones personales del autor que pueden diferir de las de otros

Leprosy in Colombia is not considering as a public health problem since a prevalence rate less tan 1/10000 was achieved more than ten years ago. Nevertheless, reports of 2012 from 11 of 27 departments 848%) showed incidence rates from 0.12 to 4.73 cases per 100000 inhabitants. The Ministry of Health and the National Institute of Health directs and organize the National Leprosy Program ( NLP), which plan the activities for prevention, surveillance and control at national level. The operational activities are delegated to the regional levels (municipalities, districts departments) however in many areas poor hospital infrastructure, high costs, lack of health personnel trained, difficult access to the health services are some of the barriers that impede the development and access to the activities that the NLP publishes in guides. The above mentioned facts have as consequence late case detection with 30% of disability rates (grade 1 and 2) at the time of diagnosis. Also, there is not awareness in general population neither in health professionals about the existence of leprosy cases in Colombia. This is a review of the situation of leprosy in Colombia, taking into account not only statistical data, but also some aspects that influence late diagnosis and disability found in patients at the time of diagnosis. In this review may appear author's personal perceptions that may differ from others

Pure neuritic leprosy in patients from a high endemic region of Colombia.

Agua de Dios was a leprosarium for leprosy patients' obligatory isolation (1872-1961). Its leprosy incidence is the highest in Colombia (1.5-7/10000). Relapses are common. Government grant of US$ 200 per month subsidy is available to patients with disabilities. Spontaneous consultation with neural symptoms is frequent and simulation to get the subsidy has to be considered. We studied 36 subjects (2007-2009), with ages from 29-78, 19 of them men, with neural symptoms of 6 months to 20 years evolution. All had clinical examination, bacteriological examination, skin and nerve biopsies, electromyography (EMG), PCR for M. leprae, IgM anti-PGL1, and lepromin A. All but two are household contacts of leprosy patients. Symptoms were hypoesthesia of the hands and feet, and difficulty using hands with loss of muscular strength. None had skin lesions. Three had thickening of ulnar nerve. Lepromin was positive in all; bacteriology and biopsies were negative in all. The speed and amplitude of neural conduction were altered in 34 patients; two women had normal EMG and were considered to be feigning the disease; 21 were diagnosed as PNL by clinical, epidemiological and EMG findings; five of them had a positive PCR and one, high titers for IgM anti PGL1. Nine other subjects had diabetes and six carpal tunnel syndrome (CTS). Slow progression of disease, the lack of neural enlargement and the neural biopsies without inflammation suggest that most of these patients could have spontaneously cured PNL, as happens with other cases of paucibacillary leprosy. Diabetes and CTS are important differential diagnoses of PNL. Patients were treated with MDT and received the state subsidy.

[Leprosy reactions in a Colombian national reference centre]. / Reacciones por lepra en un centro de referencia nacional en Colombia.

INTRODUCTION: Colombia is the country in America with the highest proportion of new cases leprosy with severe disability. To decrease such disability it is necessary to control these reactions, the main cause of nerve damage in leprosy. OBJECTIVE: To describe the clinical and epidemiological characteristics and the treatment of patients with type 1 and 2 leprosy reactions who consulted the Centro Dermatológico Federico Lleras Acosta. MATERIALS AND METHODS: It is a descriptive study which included patients with clinical diagnoses of type 1 and 2 reactions who were seen in the center between 2003 and 2009. The town of origin of the patients, their age, clinical features and treatments were analysed. RESULTS: We studied 96 reactions in 87 patients, 35 type 1 and 61 type 2 reactions; 75% of the patients came from the departments of Tolima, Cundinamarca, Santander and Boyacá; 77% of type 1 reaction occurred before the beginning of multidrug therapy for leprosy. The reactions that started after stopping the multidrug therapy were considered as a leprosy relapse. CONCLUSIONS: Correct identification of type 1 reaction by the general practitioner will allow the diagnosis of leprosy in a large percentage of patients. The type 1 reaction that begins after stopping the leprosy multidrug therapy may be a manifestation of a relapse of the disease.