Intra-individual effects of food upon the pharmacokinetics of rifampicin and isoniazid.

Background: Poor response to TB therapy might be attributable to subtherapeutic levels in drug-compliant patients. Pharmacokinetic parameters can be affected by comorbidities or the interaction of drugs with food. Objectives: This study aimed to determine the effect of food intake upon pharmacokinetics of rifampicin and isoniazid in a Peruvian population with TB. Methods: Rifampicin and isoniazid levels were analysed at 2, 4 and 6 h after drug intake in both fasting and non-fasting states using LC-MS methods. Results: Sixty patients participated in the study. The median rifampicin Cmax and AUC0-6 were higher during fasting than non-fasting: 7.02 versus 6.59 mg/L (P = 0.054) and 28.64 versus 24.31 mg·h/L (P = 0.002). There was a statistically significant delay overall of non-fasting Tmax compared with the fasting state Tmax (P = 0.005). In the multivariate analysis, besides the effect of fasting, Cmax for females was 20% higher than for males (P = 0.03). Concerning isoniazid, there were significant differences in the Cmax during non-fasting (median = 3.51 mg/L) compared with fasting (4.54 mg/L). The isoniazid dose received had an effect upon the isoniazid levels (1.26, P = 0.038). In the multivariate analysis, isoniazid exposure during fasting was found to be 14% higher than during non-fasting (CI = 1.02-1.28, P < 0.001). Neither radiological extent of the disease nor consumption of food with drug intake nor pharmacokinetics of rifampicin or isoniazid was associated with a poorer treatment outcome. Conclusions: Rifampicin in particular and isoniazid pharmacokinetics were significantly affected by the intake of the drug with food between and within individuals.

Supply-side interventions to improve health: Findings from the Salud Mesoamérica Initiative.

BACKGROUND: Results-based aid (RBA) is increasingly used to incentivize action in health. In Mesoamerica, the region consisting of southern Mexico and Central America, the RBA project known as the Salud Mesoamérica Initiative (SMI) was designed to target disparities in maternal and child health, focusing on the poorest 20% of the population across the region. METHODS AND FINDINGS: Data were first collected in 365 intervention health facilities to establish a baseline of indicators. For the first follow-up measure, 18 to 24 months later, 368 facilities were evaluated in these same areas. At both stages, we measured a near-identical set of supply-side performance indicators in line with country-specific priorities in maternal and child health. All countries showed progress in performance indicators, although with different levels. El Salvador, Honduras, Nicaragua, and Panama reached their 18-month targets, while the State of Chiapas in Mexico, Guatemala, and Belize did not. A second follow-up measurement in Chiapas and Guatemala showed continued progress, as they achieved previously missed targets nine to 12 months later, after implementing a performance improvement plan. CONCLUSIONS: Our findings show an initial success in the supply-side indicators of SMI. Our data suggest that the RBA approach can be a motivator to improve availability of drugs and services in poor areas. Moreover, our innovative monitoring and evaluation framework will allow health officials with limited resources to identify and target areas of greatest need.

Prevalencia de infección tuberculosa latente en trabajadores de salud de establecimientos del primer nivel de atención. Lima, Perú / Prevalence of latent tuberculosis infection in health workers from primary health care centers in Lima, Peru

RESUMEN Con el propósito de disponer de información sobre los riesgos para infección por tuberculosis, la Dirección General de Epidemiología del Ministerio de Salud, desarrolló una vigilancia centinela en establecimientos de salud de la Provincia constitucional del Callao, dicha vigilancia incluyó el diagnóstico de infección tuberculosa latente (ITL) mediante la aplicación del método IGRA. El objetivo del presente estudio fue estimar la prevalencia de ITL en trabajadores de salud de un área con alta carga de enfermedad de tuberculosis. La prevalencia de ITL en trabajadores de salud fue 56%. En trabajadores con más de 10 años de servicio la prevalencia se incrementó a 63% y en trabajadores con más de 35 años de servicio se encontraron prevalencias entre 58 y 60%. Existe una alta prevalencia de ITL en trabajadores de salud de establecimientos del primer nivel de atención, identificándose al mayor tiempo de servicio, como uno de los principales factores de riesgo.

ABSTRACT To evaluate the risk of tuberculosis (TB) infection, the General Directorate of Epidemiology of the Ministry of Health developed a sentinel surveillance system in health centers located in the Constitutional Province of Callao. This surveillance system included the diagnosis of latent tuberculosis infection (LTI) using interferon gamma release assays. The objective of the present study was to estimate the prevalence of LTI in health workers in a region with a high burden of TB. The prevalence of LTI in health workers was 56%. The prevalence of LTI was 63% in workers with more than 10 years of service and 58-60% in workers with more than 35 years of service. The prevalence of LTI in health workers from primary health care centers was high, and longer service time was one of the main risk factors.

[Prevalence of latent tuberculosis infection in health workers from primary health care centers in Lima, Peru]. / Prevalencia de infección tuberculosa latente en trabajadores de salud de establecimientos del primer nivel de atención. Lima, Perú.

To evaluate the risk of tuberculosis (TB) infection, the General Directorate of Epidemiology of the Ministry of Health developed a sentinel surveillance system in health centers located in the Constitutional Province of Callao. This surveillance system included the diagnosis of latent tuberculosis infection (LTI) using interferon gamma release assays. The objective of the present study was to estimate the prevalence of LTI in health workers in a region with a high burden of TB. The prevalence of LTI in health workers was 56%. The prevalence of LTI was 63% in workers with more than 10 years of service and 58-60% in workers with more than 35 years of service. The prevalence of LTI in health workers from primary health care centers was high, and longer service time was one of the main risk factors.

Con el propósito de disponer de información sobre los riesgos para infección por tuberculosis, la Dirección General de Epidemiología del Ministerio de Salud, desarrolló una vigilancia centinela en establecimientos de salud de la Provincia constitucional del Callao, dicha vigilancia incluyó el diagnóstico de infección tuberculosa latente (ITL) mediante la aplicación del método IGRA. El objetivo del presente estudio fue estimar la prevalencia de ITL en trabajadores de salud de un área con alta carga de enfermedad de tuberculosis. La prevalencia de ITL en trabajadores de salud fue 56%. En trabajadores con más de 10 años de servicio la prevalencia se incrementó a 63% y en trabajadores con más de 35 años de servicio se encontraron prevalencias entre 58 y 60%. Existe una alta prevalencia de ITL en trabajadores de salud de establecimientos del primer nivel de atención, identificándose al mayor tiempo de servicio, como uno de los principales factores de riesgo.

Effects of dosage, comorbidities, and food on isoniazid pharmacokinetics in Peruvian tuberculosis patients.

Poor response to tuberculosis (TB) therapy might be attributable to subtherapeutic levels in drug-compliant patients. Pharmacokinetic (PK) parameters can be affected by several factors, such as comorbidities or the interaction of TB drugs with food. This study aimed to determine the PK of isoniazid (INH) in a Peruvian TB population under observed daily and twice-weekly (i.e., biweekly) therapy. Isoniazid levels were analyzed at 2 and 6 h after drug intake using liquid chromatography mass spectrometric methods. A total of 107 recruited patients had available PK data; of these 107 patients, 42.1% received biweekly isoniazid. The mean biweekly dose (12.8 mg/kg of body weight/day) was significantly lower than the nominal dose of 15 mg/kg/day (P < 0.001), and this effect was particularly marked in patients with concurrent diabetes and in males. The median maximum plasma concentration (Cmax) and area under the concentration-time curve from 0 to 6 h (AUC0-6) were 2.77 mg/liter and 9.71 mg · h/liter, respectively, for daily administration and 8.74 mg/liter and 37.8 mg · h/liter, respectively, for biweekly administration. There were no differences in the Cmax with respect to gender, diabetes mellitus (DM) status, or HIV status. Food was weakly associated with lower levels of isoniazid during the continuation phase. Overall, 34% of patients during the intensive phase and 33.3% during the continuation phase did not reach the Cmax reference value. However, low levels of INH were not associated with poorer clinical outcomes. In our population, INH exposure was affected by weight-adjusted dose and by food, but comorbidities did not indicate any effect on PK. We were unable to demonstrate a clear relationship between the Cmax and treatment outcome in this data set. Twice-weekly weight-adjusted dosing of INH appears to be quite robust with respect to important potentially influential patient factors under program conditions.

Pharmacokinetics of rifampin in Peruvian tuberculosis patients with and without comorbid diabetes or HIV.

For drug-compliant patients, poor responses to tuberculosis (TB) treatment might be attributable to subtherapeutic drug concentrations. An impaired absorption of rifampin was previously reported for patients with diabetes mellitus (DM) or HIV. The objectives of this study were to determine whether TB drug pharmacokinetics differed in Peruvian TB patients with DM or HIV. In this cross-sectional study, TB patients, recruited from health centers in Lima, Peru, had blood samples taken at 2 and 6 h after directly observed TB drug ingestion, to determine plasma concentrations of rifampin. Of 105 patients, 50 had TB without a comorbidity, 26 had coexistent DM, and 29 had coexistent HIV. Unexpectedly, the overall median 2- and 6-h levels of rifampin were 1.6 and 3.2 mg/liter, respectively, and the time to the peak concentration was 6 h (slow absorber) instead of 2 h (fast absorber) for 61 patients (62.2%). The geometric mean peak concentration of drug in serum (C(max)) was significantly higher in fast absorbers than in slow absorbers (5.0 versus 3.8 mg/liter; P = 0.05). The rifampin C(max) was significantly lower in male patients than in female patients (3.3 versus 6.3 mg/liter; P < 0.001). Neither slow nor fast absorbers with comorbidities (DM or HIV) had significantly different C(max) results compared to those of TB patients without comorbidities. An analysis of variance regression analysis showed that female gender (P < 0.001) and the time to maximum concentration of drug in serum (T(max)) at 2 h (P = 0.012) were independently correlated with increased exposure to rifampin. Most of this Peruvian study population exhibited rifampin pharmacokinetics different from those conventionally reported, with delayed absorption and low plasma concentrations, independent of the presence of an HIV or DM comorbidity.

Domestic poultry-raising practices in a Peruvian shantytown: implications for control of Campylobacter jejuni-associated diarrhea.

Raising poultry at home is common in many periurban communities in low-income countries. Studies demonstrate that free-range domestic poultry increase children's risk of infection with diarrhea-causing organisms such as Campylobacter jejuni. Corralling might reduce risk, but research on the socioeconomic acceptability of corralling is lacking. To explore this issue, we studied local knowledge and practices related to poultry-raising in a Peruvian shantytown. Our objectives were to understand: (1). motives for raising domestic poultry; (2). economic and cultural factors that affect the feasibility of corralling; and (3). local perceptions about the relationship between domestic poultry and disease. During 1999-2000, we met with community health volunteers and conducted ethnographic and structured interviews with residents about poultry-raising practices. We then enrolled 12 families in a 2-month trial of corral use during which field workers made biweekly surveillance visits to each family. Most participants reported that they raise birds because home-grown poultry and eggs taste better and are more nutritious and because they enjoy living around animals. Some want to teach their children about raising animals. To prevent theft, many residents shut their birds in provisional enclosures at night, but most stated that birds are healthier, happier, and produce better meat and eggs when let loose by day. Many view bird feces in the house and yard as dirty, but few see a connection to illness. Residents consider chicks and ducklings more innocuous than adult birds and are more likely to allow them inside the house and permit children to play with them. After extensive orientation and technical assistance, participants were willing to corral birds more often. But due to perceived disadvantages, many kept birds penned only intermittently. Additional food and water costs were a significant obstacle for some. Adequate space, bird care and corral hygiene would also need to be addressed to make this intervention viable. Developing a secure, acceptable and affordable corral remains a challenge in this population.