Addressing the drug-resistant tuberculosis challenge through implementing a mixed model of care in Uganda.

Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and human immunodeficiency virus (HIV) status), on co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) statuses, culture results, smear results and treatment outcomes (6, 12, and 24 months) from 2012 to 2017 RR-TB/MDR-TB cohorts were collected from all the 15 DR-TB treatment initiation sites and descriptive analysis was done using STATA version 14.2. We presented outcomes as the number of patient backlog cleared, DR-TB initiation sites, RR-TB/DR-TB cumulative patients enrolled, percentage of co-infected patients on the six, twelve interim and 24 months treatment outcomes as per the Uganda NTLP 2016 Programmatic Management of drug-resistant Tuberculosis (PMDT) guidelines (NTLP, 2016). Over the period 2013-2015, the RR-TB/MDR-TB Treatment success rate (TSR) was sustained between 70.1% and 74.1%, a performance that is well above the global TSR average rate of 50%. Additionally, the cure rate increased from 48.8% to 66.8% (P = 0.03). The Uganda DR-TB mixed model of care coupled with early application of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges.

Leprosy New Case Detection Trends and the Future Effect of Preventive Interventions in Pará State, Brazil: A Modelling Study.

BACKGROUND: Leprosy remains a public health problem in Brazil. Although the overall number of new cases is declining, there are still areas with a high disease burden, such as Pará State in the north of the country. We aim to predict future trends in new case detection rate (NCDR) and explore the potential impact of contact tracing and chemoprophylaxis on NCDR in Pará State. METHODS: We used SIMCOLEP, an existing individual-based model for the transmission and control of M. leprae, in a population structured by households. The model was quantified to simulate the population and observed NCDR of leprosy in Pará State for the period 1990 to 2014. The baseline scenario was the current control program, consisting of multidrug therapy, passive case detection, and active case detection from 2003 onwards. Future projections of the NCDR were made until 2050 given the continuation of the current control program (i.e. baseline). We further investigated the potential impact of two scenarios for future control of leprosy: 1) discontinuation of contact tracing; and 2) continuation of current control in combination with chemoprophylaxis. Both scenarios started in 2015 and were projected until 2050. RESULTS: The modelled NCDR in Pará State after 2014 shows a continuous downward trend, reaching the official elimination target of 10 cases per 100,000 population by 2030. The cessation of systematic contact tracing would not result in a higher NCDR in the long run. Systematic contact tracing in combination with chemoprophylaxis for contacts would reduce the NCDR by 40% and bring attainment of the elimination target two years forward to 2028. CONCLUSION: The NCDR of leprosy continues to decrease in Pará State. Elimination of leprosy as a public health problem could possibly be achieved around 2030, if the current control program is maintained. Providing chemoprophylaxis would decrease the NCDR further and would bring elimination forward by two years.

Constatación del papel de la búsqueda de contactos y estrategias de prevención en a interrupción de la transmisión de la Lepra - quimio profilaxis: llamamiento para pedir una mayor investigación / No disponible

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Protecting people against leprosy: chemoprophylaxis and immunoprophylaxis.

Elimination of leprosy cannot be achieved by multidrug therapy alone, and new tools are needed to prevent leprosy. A randomized controlled trial with chemoprophylaxis for contacts of leprosy patients using a single dose of rifampicin (SDR) has shown an overall protective effect of approximately 60%, effective in the first 2 years after the intervention. When a contact who previously received bacillus Calmette-Guérin (BCG) vaccination also receives SDR, the protective effect is additive, approximating 80%. Vaccine trials have been conducted with BCG, often in combination with Mycobacterium leprae or related Mycobacterium vaccines as immunoprophylaxis for contacts of leprosy patients, with BCG giving the best results. Meta-analysis shows that the protective effect of BCG vaccination is larger in observational studies than in trials, 60% versus 41%, and is higher among contacts of leprosy patients than among the general population, 68% versus 53%. We believe that a future leprosy control strategy should include contact management, consisting of a contact survey, at which time preventive interventions could be added, such as chemoprophylaxis and immunoprophylaxis. Modeling studies have shown that both interventions will lower the incidence of leprosy in the population. Implementation studies of such contact-based strategy are now called for.

Protecting people against leprosy: chemoprophylaxis and immunoprophylaxis

Elimination of leprosy cannot be achieved by multidrug therapy alone, and new tools are needed to prevent leprosy. A randomized controlled trial with chemoprophylaxis for contacts of leprosy patients using a single dose of rifampicin (SDR) has shown an overall protective effect of approximately 60%, effective in the first 2 years after the intervention. When a contact who previously received bacillus Calmette-Guérin (BCG) vaccination also receives SDR, the protective effect is additive, approximating 80%. Vaccine trials have been conducted with BCG, often in combination with Mycobacterium leprae or related Mycobacterium vaccines as immunoprophylaxis for contacts of leprosy patients, with BCG giving the best results. Meta-analysis shows that the protective effect of BCG vaccination is larger in observational studies than in trials, 60% versus 41%, and is higher among contacts of leprosy patients than among the general population, 68% versus 53%. We believe that a future leprosy control strategy should include contact management, consisting of a contact survey, at which time preventive interventions could be added, such as chemoprophylaxis and immunoprophylaxis. Modeling studies have shown that both interventions will lower the incidence of leprosy in the population. Implementation studies of such contact-based strategy are now called for.

Patient-related factors predicting the effectiveness of rifampicin chemoprophylaxis in contacts: 6 year follow up of the COLEP cohort in Bangladesh.

OBJECTIVES: The COLEP trial in Bangladesh showed a 57% reduction in leprosy incidence among contacts of newly diagnosed patients in the first 2 years after chemoprophylaxis with single dose rifampicin (SDR). We assessed the impact of this intervention after 6 years and identified characteristics of the leprosy index patients predicting the effectiveness of this intervention. DESIGN: The cohort of 1037 patients and their 28 092 contacts that participated in the randomised placebo controlled field trial with single dose rifampicin was followed for 6 years. The leprosy status of contacts was established at 2, 4 and 6 years after the intervention. We assessed the association between characteristics of the index leprosy patients and the development of clinical leprosy among their contacts using logistic regression. RESULTS: The protective effect of SDR was seen only in the first 2 years, with no additional effect after 4 and 6 years. However, the total impact of the intervention was still statistically significant (P = 0.025) after 6 years and no excess cases were observed in the SDR arm at a later stage. The intervention prevented leprosy in contacts that actually received SDR, but did not offer protection to members of the same contact group who did not take chemoprophylaxis. The intervention was most effective in contact groups of female index patients, an enhanced effect was also observed in contact groups of patients belonging to a cluster of two or more leprosy patients at intake as well. CONCLUSION: These easy to recognise patient characteristics indicate a possible enhanced risk of transmission of Mycobacterium leprae to contacts in the vicinity of patients and are useful for deciding about preventive measures, such as early detection or chemoprophylaxis.

Prevención de la lepra: estudio convencional de contactos y quimioprofilaxis / No disponible

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Aceptación de quimioprofilaxis por los convivientes de pacientes de lepra en Bangladesh: estudio cualitativo / No disponible

Objetivos: La quimioprofilaxis con dosis única de rifampicina constituye una intervención prometedora para prevenir la lepra en los contactos de los pacientes. Sin embargo, su implementación en los programas de control requiere frecuentemente hacer público el diagnóstico de lepra, que en muchos países sigue siendo una infección estigmatizante. Promocionar el control y el tratamiento de la afecciones estigmatizantes sin contribuir a reducir el estigma de los individuos afectados puede resultar deficiente. El objetivo de este estudio era evaluar la aceptación social al revelar el diagnóstico y predisposición hacia la toma de medicamentos profilácticos en un área endémica de lepra de Bangladesh. Metodología: Estudio cualitativo a través de grupos de discusión con 136 hombres y mujeres sanos, de diferentes edades y religiones, procedente de dos aldeas rurales y un área urbana del noroeste de Bangladesh, y 14 trabajadores sanitarios con experiencia en tratar a paciente de lepra. Resultados: Los participantes no se opondrían a revelar el diagnóstico de lepra a los convivientes y parientes más cercanos si fueron diagnosticados de lepra. Sin embargo, muchos participantes no quisieron compartir esta información con sus vecinos y contactos sociales por el estigma de esta enfermedad. Todos los participantes estaban dispuestos a tomar quimioprofilaxis si cualquier contacto cercano a ellos resultara diagnosticado de lepra, incluso después de explicarles que no estaba garantizada la protección total contra la lepra. Conclusión: Se puede afirmar que la quimioprofilaxis para los convivientes de los pacientes de lepra es una condición efectiva y socialmente aceptable para los programas de control actuales. La quimioprofilaxis para otro tipo de contacto que podría beneficiarse sólo sería factible sin revelar la información sobre los pacientes, si se administra en forma de campañas para toda la población del área (AU)

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The long-term effect of current and new interventions on the new case detection of leprosy: a modeling study.

BACKGROUND: Although the number of newly detected leprosy cases has decreased globally, a quarter of a million new cases are detected annually and eradication remains far away. Current options for leprosy prevention are contact tracing and BCG vaccination of infants. Future options may include chemoprophylaxis and early diagnosis of subclinical infections. This study compared the predicted trends in leprosy case detection of future intervention strategies. METHODS: Seven leprosy intervention scenarios were investigated with a microsimulation model (SIMCOLEP) to predict future leprosy trends. The baseline scenario consisted of passive case detection, multidrug therapy, contact tracing, and BCG vaccination of infants. The other six scenarios were modifications of the baseline, as follows: no contact tracing; with chemoprophylaxis; with early diagnosis of subclinical infections; replacement of the BCG vaccine with a new tuberculosis vaccine ineffective against Mycobacterium leprae ("no BCG"); no BCG with chemoprophylaxis; and no BCG with early diagnosis. FINDINGS: Without contact tracing, the model predicted an initial drop in the new case detection rate due to a delay in detecting clinical cases among contacts. Eventually, this scenario would lead to new case detection rates higher than the baseline program. Both chemoprophylaxis and early diagnosis would prevent new cases due to a reduction of the infectious period of subclinical cases by detection and cure of these cases. Also, replacing BCG would increase the new case detection rate of leprosy, but this effect could be offset with either chemoprophylaxis or early diagnosis. CONCLUSIONS: This study showed that the leprosy incidence would be reduced substantially by good BCG vaccine coverage and the combined strategies of contact tracing, early diagnosis, and treatment of infection and/or chemoprophylaxis among household contacts. To effectively interrupt the transmission of M. leprae, it is crucial to continue developing immuno- and chemoprophylaxis strategies and an effective test for diagnosing subclinical infections.

Prospects, achievements, challenges and opportunities for scaling-up malaria chemoprevention in pregnancy in Tanzania: the perspective of national level officers.

OBJECTIVES: To describe the prospects, achievements, challenges and opportunities for implementing intermittent preventive treatment for malaria in pregnancy (IPTp) in Tanzania in light of national antenatal care (ANC) guidelines and ability of service providers to comply with them. METHODS: In-depth interviews were made with national level malaria control officers in 2006 and 2007. Data was analysed manually using a qualitative content analysis approach. RESULTS: IPTp has been under implementation countrywide since 2001 and the 2005 evaluation report showed increased coverage of women taking two doses of IPTp from 29% to 65% between 2001 and 2007. This achievement was acknowledged, however, several challenges were noted including (i) the national antenatal care (ANC) guidelines emphasizing two IPTp doses during a woman's pregnancy, while other agencies operating at district level were recommending three doses, this confuses frontline health workers (HWs); (ii) focused ANC guidelines have been revised, but printing and distribution to districts has often been delayed; (iii) reports from district management teams demonstrate constraints related to women's late booking, understaffing, inadequate skills of most HWs and their poor motivation. Other problems were unreliable supply of free SP at private clinics, clean and safe water shortage at many government ANC clinics limiting direct observation treatment and occasionally pregnant women asked to pay for ANC services. Finally, supervision of peripheral health facilities has been inadequate and national guidelines on district budgeting for health services have been inflexible. IPTp coverage is generally low partly because IPTp is not systematically enforced like programmes on immunization, tuberculosis, leprosy and other infectious diseases. Necessary concerted efforts towards fostering uptake and coverage of two IPTp doses were emphasized by the national level officers, who called for further action including operational health systems research to understand challenges and suggest ways forward for effective implementation and high coverage of IPTp. CONCLUSION: The benefit of IPTp is appreciated by national level officers who are encouraged by trends in the coverage of IPTp doses. However, their appeal for concerted efforts towards IPTp scaling-up through rectifying the systemic constraints and operational research is important and supported by suggestions by other authors.

Lepra: Comportamiento en el Área de salud “Julio Antonio Mella” en el período de Enero 1979 a Abril 2004 / No disponible

La lepra es una enfermedad que data de muy antiguo, ha sido considerada por centurias como incurable, mutilante y repulsiva, lo que motivó el que durante siglos a los enfermos se les arrojara de los enclaves urbanos y en el mejor de los casos se les confinara en áreas propias, si no eran perseguidos como enemigos. En la conciencia social esto motivó que hasta hoy, un caso de lepra resulta traumático en familia, barrios y centro de trabajo, por lo que se precisa una adecuada educación de la población, para el trato con estos enfermos. En Cuba, los primeros casos se reconocieron en las Actas del Cabildo celebrado en La Habana, en fecha tan temprana como 1613. En Puerto Príncipe, entre 1706 y 1715 las autoridades acordaron más de una vez recoger a los enfermos de ese mal que vagaban por la ciudad y ya en 1734 solicitaron un permiso a las autoridades eclesiásticas para construir una ermita dedicada a San Lázaro con una silo anexo de leprosos, que fue inaugurado en 1937 y que con altas y bajas duró en funcionamiento hasta el final del siglo XIX en que fue clausurado por el Gobierno Interventor norteamericano. Según el Dr. José Díaz Almeida, en 1900 “ las estadísticas de lepra en Las Antillas calcularon para Cuba una cifra de 1.000 enfermos y en 1961 alcanzó la cifra de 4.500 lo que determinó que el Ministerio de Salud Pública incluyera un Programa Nacional de Control de Lepra que comenzó en 1962, el cual desarrolló el examen sistemático de los enfermos y el chequeo de sus convivientes que en 1972 pasó a las áreas de salud, manteniendo la Dapsona como droga de primera línea(1). En 1977 se estableció un nuevo programa de control basado en el uso de la Rifampicina, droga bactericida, cuyo objetivo inmediato fue reducir progresivamente la morbilidad a cifras mínimas mediante la curación y corte de la cadena de transmisión (2). A partir de abril de 1989 se implantó en las provincias de Camagüey, Santiago de Cuba y Guantánamo, el Programa de Control de Lepra 1988, basado en la poliquimioterapia, con la administración de las drogas Rifampicina, Dapsone y Clofazimina (3). La evidencia epidemiológica sugiere que la fuente mayor de transmisión radica en los individuos que todavía no presentan síntomas, por lo que a través de los estudios inmunológicos se han logrado caracterizar antígenos específicos del micobacterium leprae, entre los que figuran el test inmunoenzimático ELISA que se utiliza para detectar AC específicos anti micobacterium leprae, de la clase IGM contra el glico lípido fenólico (PGI) obtenido del hígado del armadillo infectado con micobacterium leprae. Considerándose en la actualidad que las cifras mayores de 0,300 son propositivas, entre 0,2250 y 0,300 dudosas y las menores de 0,250 son seronegativas (4) y (5). En el área de salud “Julio A. Mella” de la ciudad de Camagüey, desde el año 1977 con la inauguración del policlínico, comenzó el seguimiento de los pacientes afectados en esa zona. El objetivo del presente trabajo es: Analizar los datos existentes del programa de lepra en nuestra área de salud durante los últimos 25 años para conocer su prevalencia y tendencia (AU)

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A study on transmission and a trial of chemoprophylaxis in contacts of leprosy patients: design, methodology and recruitment findings of COLEP.

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.