RESUMEN
With an estimated 9.4 million new cases globally, tuberculosis (TB) continues to be a major public health concern. Eighty percent of all cases worldwide occur in 22 high-burden, mainly resource-poor settings. This devastating impact of tuberculosis on vulnerable populations is also driven by its deadly synergy with HIV. Therefore, building capacity and enhancing universal access to rapid and accurate laboratory diagnostics are necessary to control TB and HIV-TB coinfections in resource-limited countries. The present review describes several new and established methods as well as the issues and challenges associated with implementing quality tuberculosis laboratory services in such countries. Recently, the WHO has endorsed some of these novel methods, and they have been made available at discounted prices for procurement by the public health sector of high-burden countries. In addition, international and national laboratory partners and donors are currently evaluating other new diagnostics that will allow further and more rapid testing in point-of-care settings. While some techniques are simple, others have complex requirements, and therefore, it is important to carefully determine how to link these new tests and incorporate them within a country's national diagnostic algorithm. Finally, the successful implementation of these methods is dependent on key partnerships in the international laboratory community and ensuring that adequate quality assurance programs are inherent in each country's laboratory network.
Asunto(s)
Técnicas de Laboratorio Clínico/métodos , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Países en Desarrollo , Humanos , Ciencia del Laboratorio Clínico/métodosRESUMEN
Rifapentine and its primary metabolite, 25-desacetyl rifapentine, are active against mycobacterium tuberculosis. The objectives of this study were to describe the population pharmacokinetics of rifapentine and 25-desacetyl rifapentine in fasting and fed states. Thirty-five male healthy volunteers were enrolled in an open-label, randomized, sequential, five-way crossover study. Participants received a single 900-mg dose of rifapentine after meals with high fat (meal A), bulk and low fat (meal B), bulk and high fat (meal C), high fluid and low fat (meal D), or 200 ml of water (meal E). Venous blood samples were collected over 72 h after each rifapentine dose, and plasma was analyzed for rifapentine and 25-desacetyl rifapentine using high-performance liquid chromatography. Pharmacokinetic data were analyzed by nonlinear mixed-effect modeling using NONMEM. Compared with the fasting state, meal A had the greatest effect on rifapentine oral bioavailability, increasing it by 86%. Meals B, C, and D resulted in 33%, 46%, and 49% increases in rifapentine oral bioavailability, respectively. Similar trends were observed for 25-desacetyl rifapentine. As meal behavior has a substantial impact on rifapentine exposure, it should be considered in the evaluation of optimal dosing approaches.
Asunto(s)
Antibióticos Antituberculosos/farmacocinética , Grasas de la Dieta/farmacología , Ayuno/metabolismo , Rifampin/análogos & derivados , Administración Oral , Adulto , Antibióticos Antituberculosos/administración & dosificación , Antibióticos Antituberculosos/química , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Humanos , Masculino , Rifampin/administración & dosificación , Rifampin/química , Rifampin/farmacología , Resultado del Tratamiento , Adulto JovenRESUMEN
Laboratory systems worldwide are challenged not only by the need to compete for scarce resources with other sections of national health care programmes, but also with the lack of understanding of the critical role that laboratories play in the accurate diagnosis and monitoring of patients suffering from high-burdens of disease. An effective approach to establishing cost-effective laboratory systems that provide rapid and accurate test results for optimal impact on patient care is to move away from disease-specific programmes and establish integrated laboratory services. An integrated laboratory network provides all primary diagnostic services needed for care and treatment without requiring patients to go to different laboratory facilities for specific tests. Such a network focuses on providing quality-assured basic laboratory testing through the use of common specimen collection, reporting and diagnostic platforms that can be used across diseases. An integrated laboratory system also provides specimen transport to specialised laboratories and an environment conducive to the introduction and use of new and more complex technologies that would benefit the patient population and public health systems as a whole. As such, this article described various strategies for, and practical examples of, the successful integration of laboratory services.
RESUMEN
The $63 billion comprehensive global health initiative (GHI) emphasizes health systems strengthening (HSS) to tackle challenges, including child and maternal health, HIV/AIDS, family planning, and neglected tropical diseases. GHI and other initiatives are critical to fighting emerging and reemerging diseases in resource-poor countries. HSS is also an increasing focus of the $49 billion program of the US President's Emergency Plan for AIDS Relief and the Global Fund to Fight AIDS, Tuberculosis and Malaria. Laboratory systems and services are often neglected in resource-poor settings, but the funding offers an opportunity to end the neglect. To sustainably strengthen national laboratory systems in resource-poor countries, the following approaches are needed: (1) developing integrative national laboratory strategic plans and policies and building systems to address multiple diseases; (2) establishing public-private partnerships; (3) ensuring effective leadership, commitment, and coordination by host governments of efforts of donors and partners; (4) establishing and/or strengthening centers of excellence and field epidemiology and laboratory training programs to meet short- and medium-term training and retention goals; and (5) establishing affordable, scalable, and effective laboratory accreditation schemes to ensure quality of laboratory tests and bridge the gap between clinicians and laboratory experts on the use of test results.
Asunto(s)
Enfermedades Transmisibles Emergentes/prevención & control , Salud Global , Laboratorios/organización & administración , Técnicas de Laboratorio Clínico/normas , Países en Desarrollo , Recursos en Salud , Humanos , Liderazgo , Personal de Laboratorio Clínico/educación , Programas Nacionales de SaludAsunto(s)
Investigación Biomédica/organización & administración , Técnicas de Laboratorio Clínico/economía , Técnicas de Laboratorio Clínico/métodos , Tamizaje Masivo/métodos , Tripanosomiasis Africana/diagnóstico , Tripanosomiasis Africana/epidemiología , Anticuerpos Antiprotozoarios/sangre , Investigación Biomédica/economía , Humanos , Inmunoensayo/métodos , Valor Predictivo de las Pruebas , Prevalencia , Sensibilidad y Especificidad , Tripanosomiasis Africana/prevención & controlRESUMEN
RATIONALE: Comparison of the early bactericidal activity (EBA) of rifapentine and its pharmacokinetics with those of rifampin to determine the cause of poor clinical response and regrowth between doses, leading to rifamycin monoresistance at relapse. OBJECTIVES: Determination of the dose size of rifapentine that gives sufficient drug exposure to prevent regrowth. METHODS: EBA study over initial 5 days of treatment of 123 patients, half at Durban and half at Cape Town, who received single rifapentine doses of 300, 600, 900, or 1,200 mg rifapentine or five daily doses of 150, 300, or 600 mg rifampin, with a pharmacokinetic study on 58 patients measuring standard parameters for each dose size of rifamycin and their desacetyl metabolites. RESULTS: The EBAs for both rifamycins were similar, with a linear relationship to log dose at lower doses and a curvilinear response at higher doses giving a plateau at 1,136 mg rifapentine. The area under the concentration-time curve (AUC) divided by the minimal inhibitory concentration (MIC) agreed well for both rifamycins on the assumption that the only free 2% of free rifapentine and the 14% of free rifampin after plasma binding were active in the lesions. CONCLUSIONS: Only the free proportions of the rifamycins were active in lesions. From consideration of the pulse size and the duration of the postantibiotic lag, a 1,200-mg dose of rifapentine seemed necessary to improve response and to prevent regrowth between doses, and hence rifamycin monoresistance.