Levantamento de dados para estudo dos fatores associados à falha terapêutica em hanseníase / Data collection to study the factors associated with failure leprosy therapy

A Hanseníase é uma doença infectocontagiosa de caráter crônico, evolução lenta, causada pelo Mycobacterium leprae (M. leprae). A transmissão ocorre por meio do trato respiratório, e para o desenvolvimento da doença existe a necessidade da susceptibilidade, além do contato íntimo e prolongado. Para fins terapêuticos a Organização Mundial da Saúde (OMS) traz uma classificação mais simples que é baseada no número de lesões cutâneas. Os casos com até cinco lesões são considerados paucibacilares e aqueles com mais de cinco lesões são multibacilares. Apesar da implantação da poliquimioterapia (PQT) pela OMS ter sido um importante avanço técnico na história do controle da doença, em 2019 ainda foram notificados 202.185 novos casos no mundo, sendo o Brasil o segundo em concentração de casos. Um indicador importante para o controle da hanseníase são as taxas de retratamento, definido como nova notificação de hanseníase em paciente que já tenha recebido tratamento anterior, suas causas incluem abandono, insuficiência terapêutica, falência terapêutica, alteração de esquema por erro diagnóstico e recidiva. Embora um grande número de casos de recidivas seja detectado no Brasil, apenas 8,4%, 13,3% e 1,9% dos casos podem ser explicados por mutações que sabidamente conferem resistência bacilar aos medicamentos utilizados na PQT: rifampicina (RFP), dapsona (DDS) e ofloxacina (OFLO), respectivamente. Além dos aspectos relacionados ao patógeno, a contribuição do hospedeiro para esse cenário, apesar de pouco estudada, deve ser de grande importância. No geral a resposta ao medicamento é variável entre indivíduos, ocasionando falta de eficácia farmacológica ou reação adversas, em partes esses eventos podem ser explicados pela farmacogenética. Conhecer fatores genéticos que interferem no metabolismo dos medicamentos pode contribuir para melhores resultados terapêuticos. Dentre os desafios para atingir a eliminação da hanseníase estão a ausência de novas ferramentas de diagnóstico e de entendimento das causas associadas a recidiva e à não adesão a PQT, uma vez que a resistência medicamentosa explica pouco da reativação da doença, deste modo, o presente estudo teve como finalidade constituir banco de dados em hanseníase para estudos de associação do tipo caso-controle sobre os fatores associados com a falha terapêutica da PQT convencional. Dos 240 prontuários avaliados, 119 foram classificados como casos de falência terapêutica ou recidiva e 121 como sucesso terapêutico, aqui denominados como controles, a maioria dos pacientes era do sexo masculino, branco e procedente do estado de São Paulo; Em relação à faixa etária de diagnóstico, 18% foram diagnosticados com idade entre 40 e 49 anos, enquanto nos controles 14% tiveram diagnóstico com idade inferior a 19 anos; quanto à forma clínica da doença, 59% dos casos e 47% dos controles foram classificados como virchoviano. Dentre os casos de falência terapêutica ou recidiva, a resistência molecular explicou apenas 5,8 % dos casos de retratamento. Esse dado reforça a urgência de estudos que esclareçam as causas da falha terapêutica em hanseníase, contribuindo assim para o estabelecimento de medidas que visem o alcance de melhores índices relacionados aos desfechos terapêuticos.(AU)

Leprosy is a chronic infectious disease with insidious evolution, caused by Mycobacterium leprae (M. leprae). Transmission occurs through the respiratory tract, and the onset of the disease depends on susceptibility, in addition to intimate and prolonged contact with untreated patients. For therapeutic purposes, the World Health Organization's (WHO) classification is based on the number of skin lesions. Cases with up to five lesions are considered paucibacillary and those with more than five lesion are multibacillary. Although the implementation of multidrugtherapy (MDT) by WHO was an important technical advance in the history of disease control. In 2019, 202,185 new cases were reported in the world, with Brazil the second in the highest number of cases. An important indicator for the control of leprosy is retreatment rate, defined as a new notification of leprosy in a patient who has already received previous treatment. Its causes include abandonment, therapeutic failure, , alteration of the regimen due to diagnostic error and relapse. Although a large number of cases of relapses are detected in Brazil, only 8.4%, 13.3% and 1.9% of cases can be explained by mutations that are known to confer bacillary resistance to drugs used in the MDT: rifampicin (RFP), dapsone (DDS) and ofloxacin (OFLO), respectively. In addition to aspects related to the pathogen, the host's contribution to this scenario, although little studied, is highly important. In general, the response to the drug treatment is variable between individuals, causing a lack of pharmacological efficacy or adverse reactions. , These events may be explained by pharmacogenetics. Knowing genetic factors that interfere with drug metabolism can contribute to better therapeutic results. Among the challenges to achieve leprosy elimination are the absence of new diagnostic tools and understanding of the causes associated with relapse and non-adherence to MDT, since drug resistance explains little about the reactivation of the disease. Thus, the present study aimed at constituting a leprosy database for case-control association studies on factors associated with conventional MDT therapeutic failure. Of the 240 medical records evaluated, 119 were classified as cases of therapeutic failure or relapse and 121 as therapeutic success, here referred to as controls. The majority of patients were male, white and from the state of São Paulo. Regarding the age of diagnosis, 18% were diagnosed between 40 and 49 years, while in controls, 14% were diagnosed under 19 years; as to the clinical form of the disease, 59% of the cases and 47% of the controls were classified as lepromatous. Among the cases of therapeutic failure or relapse, molecular resistance explained only 5.8% of retreatment cases. This data reinforces the urgency of studies that clarify the causes of therapeutic failure in leprosy, thus contributing to the establishment of measures aimed at achieving better therapeutic outcomes(AU).

Primary multicentric cutaneous epithelioid angiosarcoma.

Cutaneous epithelioid angiosarcoma is a rare malignant vascular tumor, most commonly affecting elderly men, and is usually located on the extremities. We report a case of an 81-year-old lady who presented with two ulcerated plaques over the right temporal and parietal scalp of 1 year duration. The right submaxillary and submandibular lymph nodes were enlarged and tender. Computed tomography (CT) scan of the head showed soft tissue swelling over parietal and temporal areas and there was no intracranial extension. Ultrasonogram of the abdomen showed hyperechoic areas in liver suggestive of secondaries. Histopathology of the skin lesion showed the dermis and subcutis composed of clusters of atypical epithelioid cells with vesicular nuclei, prominent nucleoli and eosinophilic cytoplasm with increased mitotic figures. Immunohistochemical staining revealed CD-31, 33, 34 and vimentin positivity, while cytokeratin was negative confirming the diagnosis of epitheloid angiosarcoma. This case report highlights the unusual occurrence of multicentric epitheloid angiosarcoma on the scalp with secondaries in the liver.

A fatal case of Lucio phenomenon from India.

A 65-year-old man presented with cutaneous ulcerations involving the legs, hands, abdomen, buttocks, and pinna, along with fever, arthralgia, and anorexia for the prior 10 days. On cutaneous examination, dark, irregular-shaped bizarre erythematous purpuric spots and angulated ulcers were seen over bilateral, upper extremities and trunk including dorsum of hands, finger tips and the pinnae of both ears. Most striking were the presence of multiple deep ulcers covered with a blackish eschar and in some areas yellow slough eroding the subcutaneous tissue with ragged margins. These ulcers were distributed symmetrically over the thighs, lower legs and gluteal region. Slit-skin smear examination revealed a bacterial index (BI) of 6+ with globi from earlobes, ulcers 3+, eyebrows 3+ and normal skin 2+ and morphologically showed mainly solid (20-30%), fragmented (60-70%) and granular (5-10%) acid-fast bacilli. Biopsy from the ulcer margin revealed an ulcerated epidermis and dermis. The dermis had infiltrate of foamy macrophages, and evidence of ischemic necrotizing vasculitis, with fibrinoid necrosis and new vessel formation. There was presence of clumps of acid-fast bacilli (AFB) within macrophages, periadnexally, perivascularly, and also within endothelial cells. These clinical and histopathological features helped us to arrive at the diagnosis of Lucio phenomenon in an untreated case of Lucio leprosy which is rarely reported from areas other than Mexico.

Noncompliance with the world health organization-multidrug therapy among leprosy patients in Cebu, Philippines: its causes and implications on the leprosy control program.

The success of current World Health Organization (WHO) key strategy for leprosy elimination (ie, multidrug therapy [MDT] regimen) depends largely on the efficiency of health care delivery services and patient compliance. A high rate of noncompliance with this regimen has serious implications for the leprosy control program because it can set the stage for the emergence of drug resistance, eventually resulting in treatment failure and failure of the program. A community-based descriptive study using pretested interviews conducted in 12 leprosy endemic areas in Cebu, Philippines, showed that the noncompliance rate with the WHO-MDT regimen among 233 study subjects was 30%. The causes of noncompliance are drug-related, health care provider-triggered, or patient-inducted, or some combination of these. Recommendations on strategic interventions to obviate the cause for noncompliance are presented.

The treatment of unstable ankle fractures in patients over eighty years of age.

BACKGROUND: The current study examined the outcomes of operative treatment of unstable ankle fractures in patients at least 80 years old at the time of injury. METHODS: Of 2,682 patients who presented for treatment of ankle fractures, 17 patients met the study criteria. These patients had open reduction and internal fixation after sustaining 15 closed and two open unstable ankle fractures. There were 11 type B fractures and six type C fractures by the Danis-Weber classification, and 12 supination-external rotation and five pronation-external rotation fractures by the Laugen-Hansen classification systems. RESULTS: When noncompliant patients who developed complications were removed from analysis, the fixation failure and deep infection rates were 0% each. CONCLUSIONS: These results highlight the importance of patient compliance and non-weightbearing status in the treatment of ankle fractures in patients over 80 years.

Qué se debe hacer con un paciente que se rehúsa a recibir la terapia para una enfermedad infectocontagiosa? / What should be done with a patient that denies the acceptance of therapy for a communicable disease?

Algunas enfermedades infecciosas pueden requerir tratamiento farmacológico prolongado, con importante toxicidad o simplemente inconveniente. Se discute el caso de la lepra, su tratamiento y la toxicidad secundaria y se informan las alternativas disponibles en los casos en los que el paciente rehúsa el tratamiento médico

Experiencing leprosy: perceiving and coping with leprosy and its treatment. A qualitative study conducted in Nepal.

The way people interpret their disease and its treatment, or the meanings of these, has an impact on the way they deal with their disease and its treatment; meanings shape actions. In this article, the influence of the patients' interpretations on their coping with leprosy and its treatment, their help seeking and adherence behaviour is explored. This article describes the findings of a qualitative study, in which 29 people who discontinued treatment and 47 people who were released from treatment were interviewed in depth. All were registered at general health posts. Exploring the meanings of leprosy and its treatment in patients in Nepal resulted in the identification of six different categories of meanings. Each of these influenced the way people coped with leprosy and its treatment, their help seeking and adherence behaviour. These different categories are discussed. The main conclusion is that the explanatory models of the interviewees and of the health worker are different and that if we want to improve our leprosy services more health education has to be given whilst at the same time listening more carefully to those affected by this disease. This will give us greater insight into the way people understand their disease and its treatment and the measures we can take to prevent discontinuation of treatment.

Short report: Treatment failure in Hansen's disease.

Areas of low endemicity of Hansen's disease, such as Texas, California, and Hawaii, exist due to immigration and rare autochthonous infections. Managing this disease in these areas of low endemicity is difficult, especially in observing for relapse. The accurate diagnosis of relapse is imperative so that appropriate therapy can be promptly reinstituted and unnecessary treatment can be avoided. To assess treatment failures in an area of low endemicity, we retrospectively evaluated 113 patients with Hansen's disease treated in southern Texas. Of 57 patients who completed therapy, 11 were later restarted on medications for this disease for presumed relapse. However, nine of the 11 were found not to have true relapses of Hansen's disease. The accurate diagnosis of relapse of this disease is essential not only in the individual patient but also for prospective treatment trials to establish best practices.

MDT acompañada (AMDT) mas interrogantes que respuestas

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Short report: treatment failure in Hanse´ns disease

Areas of low endemicity of Hansen's disease, such as Texas, California, and Hawaii, exist due to immigration and rare autochthonous infections. Managing this disease in these areas of low endemicity is difficult, especially in observing for relapse. The accurate diagnosis of relapse is imperative so that appropriate therapy can be promptly reinstituted and unnecessary treatment can be avoided. To assess treatment failures in an area of low endemicity, we retrospectively evaluated 113 patients with Hansen's disease treated in southern Texas. Of 57 patients who completed therapy, 11 were later restarted on medications for this disease for presumed relapse. However, nine of the 11 were found not to have true relapses of Hansen's disease. The accurate diagnosis of relapse of this disease is essential not only in the individual patient but also for prospective treatment trials to establish best practices.

Defaulting patterns in a provincial leprosy control programme in Northern Mozambique.

Cohort-based multidrug therapy (MDT) completion rates are used to assess adherence to MDT. However this measure gives no information about when during the treatment period defaulting occurs. Two districts in Cabo Delgado province in Northern Mozambique were selected for evaluation of multibacillary patient defaulter data between 1993 and 1997 to examine when patients default during the treatment penod. In all, 548 (59.2%) of 926 MB patients completed treatment and 378 (40.8%) defaulted between 1993 to 1997. The percentage of defaulters fell steadily from 59.8% in 1993 to 23.2% in 1997. Of the 378 defaulters 57.7% defaulted treatment within 6 months and 83.1% within 1 year of starting treatment. It was observed that patients tend to default early rather than late in the treatment period and that this pattern is maintained over time despite a fall in defaulter rates. Patients established early into a treatment routine were more likely to complete treatment. A comprehensive effort to improve and maintain leprosy control services will probably influence adherence more than any single, specific strategy. Shortening MDT treatment from 2 years to 1 year is unlikely to affect the defaulter rate.

Estudo da adesäo ao tratamento da hanseníase no município de Duque de Caxias - Rio de Janeiro: abandonos ou abandonados / Study of adhesion to treatment of the leprosy in municipal district of Duque de Caxias - Rio de Janeiro: abandoning or abandoned?

Este estudo teve por objetivo analisar os fatores determinantes do abandono do tratamento da hanseníase no município de Duque de Caxias, regiäo metropolitana do Rio de Janeiro, área hiperendêmica com um dos maiores índices de abandono do tratamento no Estado nos últimos anos. Dos 855 casos notificados entre 1995 e 1997, construíram-se coortes administrativas com 483 pacientes, 160 casos multibacilares e 323 paucibacilares. Destes, 73 casos estavam classificados pelo nível local como em abandono de tratamento. Verificou-se que os casos multibacilares têm o dobro de chance de abandonar o trantamento em relaçäo aos casos paucibacilares (RPC= 2,07(1,21 - 3,55)). Este aspecto tem especial relevância quando consideramos que tais casos apresentam até cinco vezes mais incapacidades físicas que os casos paucibacilares. Na análise espacial observou-se que tanto a detecçäo quanto o abandono distribuem-se por toda área do município. Os resultados mostram que as taxas de abandono estäo superestimadas, quando avaliadas segundo o atual esquema terapêutico proposto para casos multibacilares. Além disso, ao se considerar o índice de adesäo, tais casos näo têm significado epidemiológico na manutençäo da transmissäo da hanseníase visto que apenas 3,5(por cento) dos pacientes receberam doses insuficientes. Para um maior sucesso no controle desta endemia recomenda-se que as estratégias adotadas sejam voltadas para a detecçäo precoce de casos, o que terá influência na reduçäo do abandono do tratamento

Towards an understanding of non-compliance. An assessment of risk factors for defaulting from leprosy treatment.

Within the Eastern Leprosy Control Project of Nepal, a retrospective case control study looked for simple factors that might be used operationally to predict non-compliant behaviour in patients. Patients with these factors would then become the targets of measures such as intensified health education messages and home visits in order to reduce the risk of defaulting. A study of 1442 patient cards (half defaulters, half treatment completed) revealed occasional small but significant demographic and clinical differences, but none was of a sufficient magnitude to be operationally useful. Review of the attendance of patients in the first few months of treatment suggested that eventual defaulting was strongly associated with irregularity from the commencement of treatment. It is possible that an early indicator based on attendance over the first months can be used to target patients who are in danger of non-completion of treatment.

Análise dos motivos para o abandono do tratamento: o caso dos pacientes hansenianos da Unidade de Saúde em Carapina/ES / Analysis of reasons for treatment droup put: the case of hansen's disease patient of the Health Unit at Carapina/ES

O abandono do tratamento entre pacientes hansenianos tem constituído um grave problema aos profissionais da área de saúde pública. Este trabalho tem por objetivo analisar os motivos alegados pelos pacientes para a falta e/ou abandono de seus tratamentos. Trata-se de um estudo retrospectivo, envolvendo uma amostra de 42 pacientes que faltaram e/ou abandonaram o tratamento no período de 1994 a 1996. Para coleta de dados utilizou-se roteiro semi-estruturado de entrevista. As respostas foram agrupadas em categorias gerais referentes a fatores intrínsecos e extrínsecos que caracterizaram o abandono e/ou falta. A relaçäo entre falta e abandono entre os pacientes multibacilares (MB) foi 0,8:1 e entre os paucibacilares (PB) 0,7:1. Entre os pacientes do tipo PB destacaram-se os fatores intrínsecos para justificar o abnadono do tratamento e, entre os pacientes MB, evidenciou-se uma prevalência de fatores extrínsecos como justificaçäo de suas faltas. Levando-se em consideraçäo os dados apresentados, há necessidade de maior aprofundamento nessa área, a fim de orientar a proposta metodológica do trabalho no Programa de Controle da Hanseníase

A recurrent case of BT leprosy with widely spread skin lesions showing a histopathology of indeterminate group after 4.5-years irregular treatment, Bangladesh.

A 29 year-old Bengali male case is presented in this paper which was a borderline tuberculoid leprosy (BT) at detection. His father contracted a lepromatous leprosy of G = 2 deformity. He took anti-leprosy drugs including MDT/MB regimen irregularly and had maculae widely-spread with anesthesia 16 months after being released from treatment (RFT). The histopathology of the maculae unexpectedly showed that of an indeterminate group of leprosy. The recurrent skin lesions were susceptive to a four-week regimen of Rifampicin and Ofloxacin. This case can not be defined as a relapsed case, because slit skin smears were always negative. It would be called a recurrent case after MDT/MB regimen. Though the reason recurrent skin lesions occur is unknown, it is reasonable to assume that the recurrent lesions are caused by dormant persisters which are originally drug sensitive. The recurrent skin lesions can not be classified because the clinical features can not be matched to their histology. Such recurrent cases might occur among the defaulters of MDT in future.

Abandonos ou abandonados? Aspectos da hanseníase no Município de Duque de Caxias, Rio de Janeiro / Abandonments or abandoned? Aspects of the hanseníase in the Municipal district of Duque de Caxias

Analisa os aspectos determinantes do abandono do tratamento da hanseníase numa perspectiva epidemiológica, com a sistematizaçäo dos registros do prontuário que puderam ser categorizados. Dos 855 casos notificados entre 1995 e 1997, fez-se a construçäo de coortes administrativas com 483 pacientes, 160 casos multibacilares e 323 paucibacilares. Destes, 73 casos foram registrados como em abandono de tratamento. Verificou-se que os casos multibacilares têm o dobro de chance de abandonar o tratamento em relaçäo aos casos paucibacilares (RPC=2,07 (1,21-3,55)). Este aspecto tem especial relevância quando consideramos que tais casos apresentam até cinco vezes mais incapacidades físicas que os casos paucibacilares. Observa que tanto a detecçäo quanto o abandono do tratamento distribuem-se por toda área do município. Conclui que as taxas de abandono do tratamento estäo superestimadas, quando avaliadas segundo o atual esquema terapêutico proposto para casos multibacilares. Além disso, considerando-se o índice de adesividade, tais casos nao têm significado epidemiológico na manutençao da transmissäo da hanseníase visto que apenas 3,5 por cento dos pacientes receberam doses insuficientes. Para um maior sucesso no controle da endemia recomenda-se que as estratégias adotadas sejam voltadas para a detecçäo precoce de casos, o que terá influência na reduçäo do abandono do tratamento.

[Determining factors of non-compliance among patients undergoing polychemotherapy in the district of Bamako (Mali)]. / Facteurs déterminants de l'irrégularité des malades sous PCT dans le district de Bamako (Mali).

In order to examine the factors determining irregularity among patients undergoing multidrug therapy in Bamako district, we conducted a non-experimental study based, in the first instance, on medical records and later on a questionnaire. One thousand one hundred and seventy-five (1,175) treatment cards were reviewed in this way. The results of our study show that 3.1% of the patients fail to attend treatment sessions regularly and that multibacillary patients have more irregular attendance than paucibacillary patients. We have not observed any statistically meaningful difference between old and new patients as far as irregularity in attending multidrug therapy sessions is concerned. The second part of our research based on a questionnaire targeting a group of cases (36 patients who did not attend regularly) and a random control group (50 patients who attended treatment regularly but had missed at least one treatment) has shown that it is only for Item VI ("Have you ever missed your appointment because you perhaps considered yourself cured?") that a statistically meaningful difference emerges between cases and controls regarding the rates of affirmative responses (p < 0.05).