Pharmacokinetic Evidence from the HIRIF Trial To Support Increased Doses of Rifampin for Tuberculosis.

Rifamycins exhibit concentration-dependent killing of Mycobacterium tuberculosis; higher exposures potentially induce better outcomes. We randomized 180 tuberculosis patients in Peru to receive rifampin at 10, 15, or 20 mg/kg/day. A total of 168 had noncompartmental pharmacokinetic analyses; 67% were sampled twice, and 33% were sampled six times. The doses administered were well tolerated. The median area under the concentration-time curve from 0 to 6 h (interquartile range) was 24.9 (17.6 to 32.1), 43.1 (30.3 to 57.5), or 55.5 (35.7 to 73.2) h · µg/ml. The median maximum drug concentration in serum in the experimental arms reached the target of 8 µg/ml. Continued investigation of higher rifampin doses is warranted. (This study has been registered at ClinicalTrials.gov under registration no. NCT01408914.).

Barriers to the treatment of childhood tuberculous infection and tuberculosis disease: a qualitative study.

SETTING: In 2012, Peru's National TB Program (NTP) reported approximately 2400 incident cases of tuberculosis (TB) disease in children aged <15 years. Peru's TB burden is concentrated in the Lima metropolitan area, particularly in poor districts such as El Agustino and La Victoria, where this study was conducted. OBJECTIVE: To identify barriers to the treatment of childhood tuberculous infection and TB disease in Lima from the perspective of front-line providers and patients' families. DESIGN: We conducted 10 semi-structured focus groups with 53 purposefully sampled primary care providers, community health workers, and parents/guardians of pediatric TB patients. We also completed nine in-depth interviews with National TB Program administrators and pulmonologists specializing in TB. Two authors performed inductive thematic analysis and identified emerging themes. RESULTS: Four main treatment barriers emerged from the data: 1) dosing errors, 2) time- and labor-intensive preparation and administration of medications, 3) provider concern that isoniazid preventive therapy (IPT) generates isoniazid resistance, and 4) poor adherence to IPT. CONCLUSION: Our findings highlight the urgent need for child-friendly formulations, provider and parent/guardian education about IPT, and strategies to promote adherence to IPT, including support and supervision by health workers and/or regimens with fewer doses.

American tegumentary leishmaniasis: antigen-gene polymorphism, taxonomy and clinical pleomorphism.

Multi-locus enzyme electrophoresis is the current gold standard for the genetic characterisation of Leishmania. However, this method is time-consuming and, more importantly, cannot be directly applied to parasites present in host tissue. PCR-based methods represent an ideal alternative but, to date, a multi-locus analysis has not been applied to the same sample. This has now been achieved with a sample of 55 neotropical isolates (Leishmania (Viannia) braziliensis, L. (V.) peruviana, L. (V.) guyanensis, L. (V.) lainsoni and L. (L.) amazonensis), using five different genes as targets, four of which encoded major Leishmania antigens (gp63, Hsp70, H2B and Cpb). Our multi-locus approach strongly supports the current taxonomy and demonstrates a highly robust method of distinguishing different strains. Within L. (V.) braziliensis, we did not encounter so far specific genetic differences between parasites isolated from cutaneous and mucosal lesions. Interestingly, results provided by each of the different antigen-genes in the species considered, were different, suggesting different selective pressures. Our work emphasises the need for a multi-disciplinary approach to study the clinical pleomorphism of leishmaniasis.