RESUMO
OBJECTIVES: To introduce the Laboratory Quality Stepwise Implementation (LQSI) tool and provide data about its roll-out, usage and effectiveness in assisting laboratories with quality improvement. METHODS: The LQSI tool, a freely available stepwise guide, was developed by WHO to assist laboratories with efficiently implementing a quality management system. RESULTS: Since the tool's launch in 2014, it has been accessed by 130 986 unique users from 195 of 206 listed states. Of 35 respondents to a survey, 12 (34%) indicated that their laboratory had been able to achieve accreditation/certification/licensing as a result of using the tool. CONCLUSIONS: The LQSI tool, currently being used worldwide and available in English, French, Russian, Spanish, Arabic and Turkish, positively impacts the quality of services provided by clinical and public health laboratories, leading to improved clinical care and disease surveillance capacity as required by the IHR (2005) and envisioned by the Global Health Security Agenda.
Assuntos
Laboratórios/normas , Controle de Qualidade , Melhoria de Qualidade , Organização Mundial da Saúde , HumanosRESUMO
Socioeconomic and culturally defined social contact patterns are expected to be an important determinant in the continuing transmission of Mycobacterium leprae in leprosy-endemic areas. In a case-control study in two districts in Bangladesh, we assessed the association between social contact patterns and the risk of acquiring clinical leprosy. Social contacts of 90 recently diagnosed patients were compared to those of 199 controls. Leprosy was associated with a more intensive social contact pattern in the home [odds ratio (OR) 1·09, 95% confidence interval (CI) 1·00-1·19, P = 0·043] and in the nearby neighbourhood (OR 1·07, 95% CI 1·03-1·11, P = 0·001). Although it is known that M. leprae spreads most easily within households of infected persons, in endemic areas social contacts within the neighbourhood, village or urban ward, also appear to be important for transmission. We advise that disease control measures in leprosy-endemic areas should not be limited to households, but include high-risk groups in the nearby neighbourhood of patients.
Assuntos
Hanseníase/epidemiologia , Hanseníase/transmissão , Comportamento Social , Participação Social , Adolescente , Adulto , Bangladesh/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Hanseníase/prevenção & controle , Masculino , Características de Residência , Adulto JovemRESUMO
BACKGROUND: There is a higher case-detection rate for leprosy among spatially proximate contacts such as household members and neighbors. Spatial information regarding the clustering of leprosy can be used to improve intervention strategies. Identifying high-risk areas within villages around known cases can be helpful in finding new cases. METHODS: Using geographic information systems, we created digital maps of four villages in a highly endemic area in northwest Bangladesh. The villages were surveyed three times over four years. The spatial pattern of the compounds--a small group of houses--was analyzed, and we looked for spatial clusters of leprosy cases. RESULTS: The four villages had a total population of 4,123. There were 14 previously treated patients and we identified 19 new leprosy patients during the observation period. However, we found no spatial clusters with a probability significantly different from the null hypothesis of random occurrence. CONCLUSION: Spatial analysis at the microlevel of villages in highly endemic areas does not appear to be useful for identifying clusters of patients. The search for clustering should be extended to a higher aggregation level, such as the subdistrict or regional level. Additionally, in highly endemic areas, it appears to be more effective to target complete villages for contact tracing, rather than narrowly defined contact groups such as households.
Assuntos
Busca de Comunicante , Doenças Endêmicas , Hanseníase/epidemiologia , Vigilância da População , Adulto , Bangladesh/epidemiologia , Análise por Conglomerados , Demografia , Feminino , Sistemas de Informação Geográfica , Humanos , Incidência , Hanseníase/transmissão , Masculino , Mycobacterium leprae/isolamento & purificação , Prevalência , Fatores de RiscoRESUMO
We have developed a multiplex assay, based on multiplex ligation-dependent probe amplification (MLPA), that allows simultaneous detection of multiple drug resistance mutations and genotype-specific mutations at any location in the Mycobacterium tuberculosis genome. The assay was validated on a reference panel of well-characterized strains, and the results show that M. tuberculosis can be accurately characterized by our assay. Eighteen discriminatory markers identifying drug resistance (rpoB, katG, inhA, embB), members of the M. tuberculosis complex (16S rRNA, IS6110, TbD1), the principal genotypic group (katG, gyrA), and Haarlem and Beijing strains (ogt, mutT2, mutT4) were targeted. A sequence specificity of 100% was reached for 16 of the 18 selected genetic targets. In addition, a panel of 47 clinical M. tuberculosis isolates was tested by MLPA in order to determine the correlation between phenotypic drug resistance and MLPA and between spoligotyping and MLPA. Again, all mutations present in these isolates that were targeted by the 16 functional probes were identified. Resistance-associated mutations were detected by MLPA in 71% of the identified rifampin-resistant strains and in 80% of the phenotypically isoniazid-resistant strains. Furthermore, there was a perfect correlation between MLPA results and spoligotypes. When MLPA is used on confirmed M. tuberculosis clinical specimens, it can be a useful and informative instrument to aid in the detection of drug resistance, especially in laboratories where drug susceptibility testing is not common practice and where the rates of multidrug-resistant and extensively drug resistant tuberculosis are high. The flexibility and specificity of MLPA, along with the ability to simultaneously genotype and detect drug resistance mutations, make MLPA a promising tool for pathogen characterization.
Assuntos
Técnicas de Tipagem Bacteriana/métodos , Reação em Cadeia da Ligase/métodos , Mutação , Mycobacterium tuberculosis/genética , Tuberculose/microbiologia , Proteínas de Bactérias/genética , Primers do DNA/genética , Elementos de DNA Transponíveis , DNA Bacteriano/genética , DNA Ribossômico/genética , Farmacorresistência Bacteriana/genética , Genótipo , Testes de Sensibilidade Microbiana/métodos , Mycobacterium tuberculosis/isolamento & purificaçãoRESUMO
Identifying pathogen and host-related laboratory parameters are essential for the early diagnosis of leprosy reactions. The present study aimed to clarify the validity of measuring the profiles of serum cytokines [interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha], the soluble IL-6 receptor (sIL-6R), soluble T cell (sCD27) and macrophage (neopterin) activation markers and Mycobacterium leprae-specific anti-PGL-I IgM antibodies in relation to the leprosy spectrum and reactions. Serum samples from 131 Indonesian leprosy patients (82 non-reactional leprosy patients and 49 reactional) and 112 healthy controls (HC) from the same endemic region were investigated. Forty-four (89.8%) of the reactional patients had erythema nodosum leprosum (ENL) while only five (10.2%) had reversal reaction (RR). Follow-up serum samples after corticosteroid treatment were also obtained from 17 of the patients with ENL and one with RR. A wide variability in cytokine levels was observed in the patient groups. However, IFN-gamma and sIL-6R were elevated significantly in ENL compared to non-ENL patients. Levels of IFN-gamma, TNF-alpha and sIL-6R declined significantly upon corticosteroid treatment of ENL. Thus, although the present study suggests limited applicability of serial measurement of IFN-gamma, TNF-alpha and sIL-6R in monitoring treatment efficacy of ENL, reactions it recommends a search for a wider panel of more disease-specific markers in future studies.
Assuntos
Citocinas/sangue , Monitoramento de Medicamentos/métodos , Glucocorticoides/uso terapêutico , Hanseníase/tratamento farmacológico , Hanseníase/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Biomarcadores/sangue , Criança , Estudos Transversais , Feminino , Glicolipídeos/imunologia , Humanos , Imunoglobulina M/sangue , Mediadores da Inflamação/sangue , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-4/sangue , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Neopterina/sangue , Prednisolona/uso terapêutico , Receptores de Interleucina-6/sangue , Solubilidade , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangueRESUMO
In recent years a number of field trials have been carried out to assess the efficacy of rifampicin chemoprophylaxis for the prevention of leprosy in contacts of leprosy patients. Results from these trials are now being analysed and published. The aim of this one-day workshop was to review current evidence and discuss potential future courses of action with regard to the use of chemoprophylaxis to prevent leprosy. During the morning session the current evidence for the contribution that chemoprophylaxis may make to leprosy prevention was presented, both the results from trials (abstracts in section 1) and the outcome of modelling (abstract in section 2); in addition presentations were given on different aspects of the use of antibiotics for chemoprophylaxis (abstracts in section 3). The afternoon was devoted to discussions, a summary of which is presented in section 4 of this report. The conclusions and recommendations are given in section 5.
Assuntos
Hansenostáticos/uso terapêutico , Hanseníase/prevenção & controle , Quimioprevenção , HumanosRESUMO
BACKGROUND: Initial nerve damage in leprosy occurs in small myelinated and unmyelinated nerve fibers. Early detection of leprosy in the peripheral nervous system is challenging as extensive nerve damage may take place before clinical signs of leprosy become apparent. PATIENTS AND METHODS: In order to determine the prevalence of, and factors associated with, peripheral autonomic nerve dysfunction in newly diagnosed leprosy patients, 76 Brazilian patients were evaluated prior to treatment. Skin vasomotor reflex was tested by means of laser Doppler velocimetry. Blood perfusion and reflex vasoconstriction following an inspiratory gasp were registered on the second and fifth fingers. RESULTS: Vasomotor reflex was impaired in at least one finger in 33/76 (43%) patients. The fifth fingers were more frequently impaired and suffered more frequent bilateral alterations than the second fingers. Multivariate regression analysis showed that leprosy reaction (adjusted odds ratio = 8.11, 95% confidence interval: 1.4-48.2) was associated with overall impaired vasomotor reflex (average of the four fingers). In addition, palmar erythrocyanosis and an abnormal upper limb sensory score were associated with vasomotor reflex impairment in the second fingers, whereas anti-phenolic glycolipid-I antibodies, ulnar somatic neuropathy and a low finger skin temperature were associated with impairment in the fifth fingers. CONCLUSIONS: A high prevalence of peripheral autonomic dysfunction as measured by laser Doppler velocimetry was observed in newly diagnosed leprosy patients, which is clinically evident late in the disease. Autonomic nerve lesion was more frequent than somatic lesions and was strongly related to the immune-inflammatory reaction against M. leprae.
Assuntos
Doenças do Sistema Nervoso Autônomo/epidemiologia , Dedos/inervação , Hanseníase/fisiopatologia , Sistema Vasomotor/fisiopatologia , Adolescente , Adulto , Criança , Feminino , Humanos , Fluxometria por Laser-Doppler , Hanseníase/diagnóstico , Masculino , Pessoa de Meia-Idade , Reflexo AnormalRESUMO
Se revisan los conocimiento actuales sobre factores de riesgo para contraer lepra entre contactos de casos confirmados para intentar identificar los factores asociados con la enfermedad que entre los contactos presentan potencial para ser objetivos de intervenciones en los programas de control de la lepra. Se han utilizado distintas definiciones para el termino contacto aunque la mayoría de estudios emplean el de conviviente. Sin embargo, hay estudios que indican que otro tipo de contacto distinto al conviviente también esta en peligro de contraer la enfermedad. El tipo de lepra y su carga bacilar son los dos factores mas implicados en la transmisión pero los contactos de pacientes PB presentan mayor riesgo de contraer la lepra que los individuos de la población general. Los factores de contacto más importantes son: la cercanía e intensidad de contacto y la susceptibilidad heredada mientras que el sexo y la edad de los contactos junto a los factores socio-económicos no están muy claros. Tampoco están definidos los conceptos de marcadores inmunológicos y moleculares en cuanto al riesgo de transmitir o desarrollar la enfermedad pero existen evidencia de que contactos PGL1 seropositivos están en mayor riesgo. La presencia de cicatriz BCG parece apuntar hacia un menor riesgo. Las analogías con tuberculosis parecen indicar la similitud del concepto de ondas en el estanque en las dos enfermedades. Se sabe que pacientes esputo negativos pueden transmitir la tuberculosis, por tanto se debe extender este concepto de riesgo a los contactos de pacientes PB. La conclusión es que los contactos de pacientes MB y PB, tanto convivientes como no, deben ser objeto de intervenciones dirigidas sobre todo cuando están relacionadas genéticamente
Existing knowledge on risk factors the development of clinical leprosy among contacts of know leprosy patients is reviewed with the aim to identify factors associated with leprosy among contacts that have potential or developing effective targeted interventions in leprosy control. Different definitions of contact have been used and most study on this subject were among so-called household members. Yet several studies indicate that contacts found in other places that the household are also at risk of developing leprosy. The type of leprosy and the bacterial index are the main patient-related factors involved in transmission, but also contacts of PB patients have a higher risk of contracting leprosy as compared to general population. The most important contact-related factors are the closeness and intensity of the contact and inherited susceptibility, while the role of age and sex of the contacts is not clear. The role of socio-economic factors is also vague. The significance of immunological and molecular markers in relation to risk of transmitting or developing leprosy is not yet fully understood, but there is an indication that contacts who are sero-positive for anti-PGL-I antibodies are at increased risk of developing clinical leprosy. The presence of BCG scar is likely to be related to a lower risk. Analogies with tuberculosis suggest that the stone-in-the-pond approach to control may be applicable to leprosy too. Sputum smear negative tuberculosis patients are known to spread the bacteria to other. This analogy strengthens the suggestion that the contacts of paucibacillary leprosy cases should also be included in contact tracing and examination. It is included that targeted interventions should be aimed at close contacts of both MB and PB patients inside and outside the household, particularly when genetically related
Assuntos
Humanos , Masculino , Feminino , Fatores de Risco , Hanseníase/complicações , Hanseníase/diagnóstico , Mycobacterium leprae/isolamento & purificação , Mycobacterium leprae/patogenicidade , Estudos Retrospectivos , Hanseníase/genética , Hanseníase/imunologia , Hanseníase/microbiologiaRESUMO
En este trabajo se describe el modelo metodológico y hallazgos del estudio COLEP. Los objetivos del estudio son determinar la efectividad de la quimioprofilaxis con una dosis única de rifampicina e la prevención de la lepra entre contactos de pacientes de lepra y hallar características de los grupos de contacto en mayor riesgo de desarrollar lepra clínica. Estas características deben resultar útiles para los programas de control de lepra. El COLEP es un ensayo agrupado y aleatorio, a dobe ciego y controlado por placebo para determinar factores de riesgo que caracterizan los subgrupos en mayor riesgo entre el grupo contacto total de un paciente y un estudio de cohortes utilizando un grupo de referencia de entre la población general para determinar la prevalencia e incidencia de la lepra en la zona de la población estudiada. El período de seguimiento fue de 4 años. Se desarrolló un sistema de codificación explicando la distancia física y genética del contacto al paciente. Este estudio de Bangladesh incluye 1037 pacientes recién diagnosticados y sin tratamiento previo y sus 21,867 contactos. La prevalencia de la lepra entre los contactos era de 7-3 por 1000. Un total de 21,708 contactos sin rasgos ni síntomas de lepra clínica se incluyeron en un ensayo quimioprofiláctico con una dosis única de rifampicina y aleatorio a nivel del grupo de contacto en cuanto tratamiento y placebo. Los resultados de este ensayo estarán disponibles en algunos años
In this article, we describe the design, methodology and recruitment findings of the COLEP study. The objectives of this study were to determine the effective-ness of chemoprophylaxis with a single dose of rifampicin in the prevention of leprosy among contacts of leprosy patients, and to find characteristics of contact groups most at risk to develop clinical leprosy. These characteristics should be usable by routine leprosy control programmes. COLEP consists of a cluster randomized, double-blind and placebo-controlled trial, a cohort study to determine risk factors characterizing the sub-groups most at risk within the total contact group of a patient, and a cohort study using a reference group from the general population to determine the prevalence and incidence of leprosy in the total population of the study area. The follow-up period will be 4 years. A coding system was developed describing the physical and genetic distance of the contact person to the patient. This study in Bangladesh includes 1.037 newly diagnosed and previously untreated leprosy patients and their 21.867 contacts. The prevalence of leprosy among contacts was 7.3 per 1.000. a total of 21.708 contacts without sings and symptoms of clinical leprosy are included in a trial of chemoprophylaxis with single dose rifampicin, and randomized at contact group level in treatment and placebo arms. The results of this large field trial will become available in the years to come
Assuntos
Humanos , Masculino , Feminino , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/transmissão , Antibioticoprofilaxia/métodos , Hanseníase/epidemiologia , Hanseníase/prevenção & controleRESUMO
The direct detection of mRNAs from bacterial cultures on a DNA array without amplification and labelling would greatly extend the range of applications suitable for microarray analysis. Here we describe the direct detection of 23S rRNA and seven mRNA species from total Staphylococcus aureus RNA prepared using commercially available RNA purification columns followed by fluorescent detection on a flow through microarray. RNA hybridisation was detected using paired secondary labelled probes directly 5' and 3' to immobilised 60 mers. In this way, we were able to detect the effect of 30-min exposure to antimicrobials on mRNA levels within 3 h after column purification of total RNA without the need for enzymatic manipulation. Specifically the expression of mecA was confirmed in a highly resistant strain and induction of katA and ile-tRNA synthetase genes after exposure to mupirocin could be detected.
Assuntos
Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Bacteriano/isolamento & purificação , RNA Mensageiro/isolamento & purificação , Staphylococcus aureus/genética , Humanos , RNA Bacteriano/química , RNA Bacteriano/genética , RNA Mensageiro/química , RNA Mensageiro/genética , RNA Ribossômico 23S/química , RNA Ribossômico 23S/genéticaRESUMO
We conducted a population-based survey on 5 small island in South Sulawesi Province (Indonesia) to collect baseline data previous to a chemoprophylactic intervention study aiming at interrrupting the transmission of Mycobacterium leprae. Here we describe the present leprosy epidemiology on these geographically isolated islands. Of the 4774 inhabitants living in the study area 4140 were screened for leprosy (coverage: 87%). We identified 96 leprosy patients (85 new and 11 old patients), representing a new case detection rate (CDR) of 205/10,000 and prevelence rate 195/10,000. CDRs were similar for males and females. Male patients were more often classified as multibacillary (MB) than women. Of the new patients, 33 (39%) were classified as MB, 16 (19%) as paucibacillary (PB) 2-5 lesions and 36 (42%) as PB single lesion. In this area of high leprosy endemicity leprosy patients were extensively clustered, i.e. not equally distributed among the islands and within the islands among the houses
Assuntos
Humanos , Interpretação Estatística de Dados , Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Hanseníase/transmissão , InfectologiaRESUMO
Background: Not every leprosy patient is equally effective in transmitting Mycobacterium leprae. We studied the spatial distribution of infection (using seropositivity as a marker) in the population to identifity which disease characteristics of leprosy patients are important in transmission. Methods: Clinical data and blood samples for anti-M.leprae ELISA were collected during a cross-sectional survey on five Indonesian islands highly endemic for leprosy. A geographic information system (GIS) was used to define contacts of patients. We investigated spatial clustering of patients and seropositive people and used logist regression to determine risk factors for seropositivity. Results: Of the 3986 people examined for leprosy, 3271 gave blood. Seroprevalence varied between islands (1.7-8.7%) and correlated significantly with leprosy prevalence. Five clusters of patients and two clusters of seropositives were detected. In multivariate analysis, seropositivity significantly differed to be the best discriminator of contact groups with higher seroprevalence: contacts of seropositive patients had an adjusted odds ratio (aOR) of 1.75 (95% CI: 0.92-3,31). This increased seroprevalence was strongest for contact groups living _< 75 metres of two seropositive patients (aOR:3.07;95%CI:1.74-5.42). Conclusions: In this highly endemic area for leprosy, not only household contacts of seropositive patients, but also persons living in the vicinity of seropositive patient were more likely to harbour antibodies against M.leprae. Through measuring the serological status of patients and using a broader definition of contacts, higher risk groups can be more specifically identified
Assuntos
Humanos , Ensaio de Imunoadsorção Enzimática , Ensaio de Imunoadsorção Enzimática/normas , Hanseníase/epidemiologia , Modelos Logísticos , Mycobacterium leprae/crescimento & desenvolvimentoRESUMO
It is generally accepted that genetic factors play a role in susceptibility to both leprosy per se and leprosy type, but the strength of this effects has never been quantified. Estimating the contribution of genetic factors to clustering of leprosy within families is difficult since these persons often shave the same environment. Three correlation structures (genetic, household and spatial) were proposed for population data (n=560), collected on a geographically isolated Indonesian island highly endemic for leprosy, to explain the distribution of leprosy per se, leprosy type and Mycobacterium leprae-specific antibody. Heritability estimates and risk ratios for siblings were calculated to quantify the genetic effect. Leprosy was clinically diagnosed and specific anti-M.leprae antibodies were measured using ELISA. For leprosy per se in the total population the genetic correlation structure fitted best. In the population with relative stable household status (persons under 21 years and above 39 years) all structures were significant. For multibacillary leprosy (MB) genetic factors seemed more important than for paucibacillary leprosy. Seropositivity could be explained best by the apatial model, but the genetic model was also significant. Herediatry was 57% for leprosy per se and 31% for seropositivity. Genetic factors seem to play an important role in the clustering of leprosy patients, especially MB patients, and they could explain more then half of the toral phenotypic variance. This unique study population is very suitable to confirm the role of already known chromosome regions in controlling leprosy or to search for new susceptibility loci
Assuntos
Humanos , Hanseníase/classificação , Hanseníase/genética , Indonésia/epidemiologia , Vetores Genéticos/genéticaRESUMO
This study identified risk factors for developing leprosy through yearly incidence rates in five island populations. Personal factors, like age, sex, household size and the presence of M.leprae-specific antibodies as well as contact were studied. Of the 94 index patients (patients diagnosed in 2000) 43 (46%) were classified as multibacillary (MB), 17 (19%) were seropositive and 6 (7%) presented M.leprae DNA in nasal swabs as determined by polumerase chain reaction (PCR). All PCR positive patients were also seropositive. Forty-four of the 4903 persons initially without symptoms of leprosy developed leprosy in almost four years follow-up, giving an incidence rate of 2.98 per 1000 person-years. Men had a 2.2 times higher risk (95% Confidence Interval [CI]: 1.2-4.1) to developd leprosy than women. Persons living in households of more than 7 household members. Persons who were seropositive in 2000 had a 3.7 times higher risk (95% CI:1.1-12.4) than seronegative persons. Household contacts of MB patients had an adjusted hazard ratio (aHR) of 4.6 (95% CI:1.6-12.9) and household contacts of PCR positive patients an aHR of 9.36 (95% CI: 2.5-34.9) compared to non-contacts. Patients with PCR positive nasal swabs, suggesting nasal excretion of M.leprae, are probably the patients with the highest transmission patential. Since all index patients who were PCR positive were also seropositive, serology semms an adequate tool to identify these patients. Preventing seropositive persons to become seropositive patients and thus the main source of infection may break the chain of transmission
Assuntos
Humanos , Interpretação Estatística de Dados , Ensaio de Imunoadsorção Enzimática , Ensaio de Imunoadsorção Enzimática/normas , Hanseníase/complicações , Hanseníase/congênito , Hanseníase/diagnóstico , Reação em Cadeia da Polimerase , Reação em Cadeia da Polimerase/métodosRESUMO
An intervention study was implemented on five Indinesian island highly endemic for leprosy to determine whether rifampicin can be used as chemoprophylaxis to prevent leprosy. The population was actively screened before the intervention and subsequently once a year for three years. In the control group, no chemoprophylaxis was given. In the contact group, chemoprophylaxis was only given to contacts of leprosy patients and in the blanket group to all aligible persons. The cohort consited of 3,965 persons. The yearly incidence rate in the control group was 39/10,000; the cumulative incidence after three years was significantly lower in the blanket group (P=0.031). No difference was found between the contact and the control groups (P=0.93). Whether this apparent reduced leprosy incidence in the first three years in the blanket group is due to a delayed development of leprosy or a complete clearence of infections needs to be determined
Assuntos
Humanos , Dermatologia/estatística & dados numéricos , Hanseníase/prevenção & controle , Microscopia/métodosRESUMO
Existing knowledge on risk factors for the development of clinical leprosy among contacts of known leprosy patients is reviewed with the aim to identify factors associated with leprosy among contacts that have potential for developing effective targeted interventions in leprosy control. Different definitions of 'contact' have been used and most studies on this subject were among so-called household members. Yet several studies indicate that contacts found in other places than the household are also at risk of developing leprosy. The type of leprosy and the bacterial index are the main patient-related factors involved in transmission, but also contacts of PB patients have a higher risk of contracting leprosy as compared to the general population. The most important contact-related factors are the closeness and intensity of the contact and inherited susceptibility, while the role of age and sex of the contacts is not clear. The role of socio-economic factors is also vague. The significance of immunological and molecular markers in relation to risk of transmitting or developing leprosy is not yet fully understood, but there is an indication that contacts who are sero-positive for anti-PGL-I antibodies are at increased risk of developing clinical leprosy. The presence of a BCG scar is likely to be related to a lower risk. Analogies with tuberculosis suggest that the 'stone-in-the-pond' approach to control may be applicable to leprosy too. Sputum smear negative tuberculosis patients are known to spread the bacteria to others. This analogy strengthens the suggestion that the contacts of paucibacillary leprosy cases should also be included in contact tracing and examination. It is concluded that targeted interventions should be aimed at close contacts of both MB and PB patients inside and outside the household, particularly when genetically related.
Assuntos
Controle de Doenças Transmissíveis/organização & administração , Busca de Comunicante/métodos , Doenças Endêmicas/estatística & dados numéricos , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Criança , Pré-Escolar , Países em Desenvolvimento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Taxa de Sobrevida , Organização Mundial da SaúdeRESUMO
In this article, we describe the design, methodology and recruitment findings of the COLEP study. The objectives of this study were to determine the effectiveness of chemoprophylaxis with a single dose of rifampicin in the prevention of leprosy among close contacts of leprosy patients, and to find characteristics of contact groups most at risk to develop clinical leprosy. These characteristics should be usable by routine leprosy control programmes. COLEP consists of a cluster randomized, double-blind and placebo-controlled trial, a cohort study to determine risk factors characterizing the sub-groups most at risk within the total contact group of a patient, and a cohort study using a reference group from the general population to determine the prevalence and incidence of leprosy in the total population of the study area. The follow-up period will be 4 years. A coding system was developed describing the physical and genetic distance of the contact person to the patient. This study in Bangladesh includes 1037 newly diagnosed and previously untreated leprosy patients and their 21,867 contacts. The prevalence of leprosy among contacts was 7.3 per 1000. A total of 21,708 contacts without signs and symptoms of clinical leprosy are included in a trial of chemoprophylaxis with single dose rifampicin, and randomized at contact group level in treatment and placebo arms. The results of this large field trial will become available in the years to come.
Assuntos
Busca de Comunicante , Hanseníase/prevenção & controle , Hanseníase/transmissão , Mycobacterium leprae/efeitos dos fármacos , Rifampina/administração & dosagem , Adolescente , Adulto , Fatores Etários , Quimioprevenção/métodos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Índia/epidemiologia , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Valores de Referência , Medição de Risco , Fatores Sexuais , Resultado do TratamentoRESUMO
Oligonucleotide arrays capable of detecting single nucleotide polymorphisms (SNPs) from amplified nucleic acid have many applications. The expected SNP is usually placed approximately in the center of the probe to ensure the maximum shift in Tm between complementary and SNP sequences. Unfortunately, different short probes (< 30 bases) selected using widely accepted criteria do not perform consistently in this type of assay. Here we present a systematic study on the effect of secondary structure on the ability of oligonucleotide probes to detect an SNP, using real-time array monitoring of a porous microarray substrate that incorporates a novel intra-array mixing system. These results demonstrate that, although positioning of an SNP in the middle of the probe is highly destabilizing, the effect of stable secondary structure on the signal obtained is so dramatic that such probes may be very insensitive. Therefore, if the SNP flanking sequence contains significant secondary structure, then more sensitive probes with good specificity may be obtained by positioning the mutation towards one end of the probe.
Assuntos
Sondas de DNA/química , RNA Polimerases Dirigidas por DNA/genética , Membranas Artificiais , Conformação de Ácido Nucleico , Análise de Sequência com Séries de Oligonucleotídeos/instrumentação , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Polimorfismo de Nucleotídeo Único/genética , Artefatos , Sondas de DNA/classificação , Desenho de Equipamento , Análise de Falha de Equipamento , Porosidade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The interruption of leprosy transmission is one of the main challenges for leprosy control programs since no consistent evidence exists that transmission has been reduced after the introduction of multidrug therapy. Sources of infection are primarily people with high loads of bacteria with or without clinical signs of leprosy. The availability of a simple test system for the detection of antibodies to phenolic glycolipid-I (PGL-I) of Mycobacterium leprae to identify these individuals may be important in the prevention of transmission. We have developed a lateral flow assay, the ML Flow test, for the detection of antibodies to PGL-I which takes only 10 min to perform. An agreement of 91% was observed between enzyme-linked immunosorbent assay and our test; the agreement beyond chance (kappa value) was 0.77. We evaluated the use of whole blood by comparing 539 blood and serum samples from an area of high endemicity. The observed agreement was 85.9% (kappa = 0.70). Storage of the lateral flow test and the running buffer at 28 degrees C for up to 1 year did not influence the results of the assay. The sensitivity of the ML Flow test in correctly classifying MB patients was 97.4%. The specificity of the ML Flow test, based on the results of the control group, was 90.2%. The ML Flow test is a fast and easy-to-perform method for the detection of immunoglobulin M antibodies to PGL-I of M. leprae. It does not require any special equipment, and the highly stable reagents make the test robust and suitable for use in tropical countries.
Assuntos
Anticorpos Antibacterianos/sangue , Imunoensaio/métodos , Hanseníase/classificação , Hanseníase/imunologia , Mycobacterium leprae/imunologia , Antígenos de Bactérias/química , Sequência de Carboidratos , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Glicolipídeos/química , Glicolipídeos/imunologia , Humanos , Imunoensaio/estatística & dados numéricos , Imunoglobulina M/sangue , Hanseníase/prevenção & controle , Hanseníase/transmissão , Dados de Sequência Molecular , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The interruption of leprosy transmission is one of the main challenges for leprosy control programs since no consistent evidence exists that transmission has been reduced after the introduction of multidrug therapy. Sources of infection are primarily people with high loads of bacteria with or without clinical signs of leprosy. The availability of a simple test system for the detection of antibodies to phenolic glycolipid-I (PGL-I) of Mycobacterium leprae to identify these individuals may be important in the prevention of transmission. We have developed a lateral flow assay, the ML Flow test, for the detection of antibodies to PGL-I which takes only 10 min to perform. An agreement of 91% was observed between enzyme-linked immunosorbent assay and our test; the agreement beyond chance (kappa value) was 0.77. We evaluated the use of whole blood by comparing 539 blood and serum samples from an area of high endemicity. The observed agreement was 85.9% (kappa = 0.70). Storage of the lateral flow test and the running buffer at 28 degrees C for up to 1 year did not influence the results of the assay. The sensitivity of the ML Flow test in correctly classifying MB patients was 97.4%. The specificity of the ML Flow test, based on the results of the control group, was 90.2%. The ML Flow test is a fast and easy-to-perform method for the detection of immunoglobulin M antibodies to PGL-I of M. leprae. It does not require any special equipment, and the highly stable reagents make the test robust and suitable for use in tropical countries.