Dose reduction of efavirenz: an observational study describing cost-effectiveness, pharmacokinetics and pharmacogenetics.

AIM: Antiretroviral treatment implies a high cost to the healthcare system. The aim of this study was to evaluate the clinical and economic impact of efavirenz (EFV) dose adjustment by monitoring plasma concentrations and pharmacogenetic analysis of the 516G>T CYP2B6 polymorphism. MATERIALS & METHODS: One hundred and ninety HIV patients treated with EFV were studied. Plasma EFV concentrations were measured by HPLC with ultraviolet detection, and pharmacogenetic analysis was performed by Real Time (RT)-PCR. RESULTS: One hundred and ninety patients initially treated with a standard dose of EFV (600 mg/day) were studied. In 31 (16.3%) patients, EFV dose was reduced. A total of 87.1% of patients were heterozygous/homozygous carriers (GT/TT). CD4(+) count increased while the minimum steady-state plasma concentration and adverse effects decreased significantly after dose adjustment. Considering only the dose reduction, the adjustments accounted for a saving of 43,539 €/year. CONCLUSION: The individualization of EFV dosage guided by genotyping 516G>T CYP2B6 and therapeutic drug monitoring could increase the efficiency of EFV use in antiretroviral treatment.

Development of a highly sensitive loop-mediated isothermal amplification (LAMP) method for the detection of Loa loa.

The filarial parasite Loa loa, the causative agent of loiasis, is endemic in Central and Western Africa infecting 3-13 million people. L. loa has been associated with fatal encephalopathic reactions in high Loa-infected individuals receiving ivermectin during mass drug administration programs for the control of onchocerciasis and lymphatic filariasis. In endemic areas, the only diagnostic method routinely used is the microscopic examination of mid-day blood samples by thick blood film. Improved methods for detection of L. loa are needed in endemic regions with limited resources, where delayed diagnosis results in high mortality. We have investigated the use of a loop-mediated isothermal amplification (LAMP) assay to facilitate rapid, inexpensive, molecular diagnosis of loiasis. Primers for LAMP were designed from a species-specific repetitive DNA sequence from L. loa retrieved from GenBank. Genomic DNA of a L. loa adult worm was used to optimize the LAMP conditions using a thermocycler or a conventional heating block. Amplification of DNA in the LAMP mixture was visually inspected for turbidity as well as addition of fluorescent dye. LAMP specificity was evaluated using DNA from other parasites; sensitivity was evaluated using DNA from L. loa 10-fold serially diluted. Simulated human blood samples spiked with DNA from L. loa were also tested for sensitivity. Upon addition of fluorescent dye, all positive reactions turned green while the negative controls remained orange under ambient light. After electrophoresis on agarose gels, a ladder of multiple bands of different sizes could be observed in positive samples. The detection limit of the assay was found to be as little as 0.5 ag of L. loa genomic DNA when using a heating block. We have designed, for the first time, a highly sensitive LAMP assay for the detection of L. loa which is potentially adaptable for field diagnosis and disease surveillance in loiasis-endemic areas.

Fever of unknown origin as the first manifestation of colonic pathology.

Fever of unknown origin (FUO) is an entity caused by more than 200 diseases. Haematologic neoplasms are the most common malignant cause of FUO. Fever as a first symptom of colonic tumour pathology, both benign and malignant, is a rare form of presentation. Our work is a descriptive study of a series of 23 patients with colonic tumoral pathology who presented with fever of unknown origin. The mean age was 67.6 years; 56.5% of patients were men and 43.5% were women. Primary malignant neoplasia was the most common diagnosis. Blood cultures were positive in 45% of the samples. Coagulase-negative staphylococci were the most common cause of bacteraemia. Nine of 10 faecal occult blood tests performed were positive. Fever secondary to colon neoplasms, both benign and malignant, usually presents with a bacteraemic pattern, with positive results for blood-culture tests in a high percentage of cases.

Primary super-infection of hydatid cyst--clinical setting and microbiology in 37 cases.

The clinical and microbiological characteristics of super-infected hydatid cysts are described. In our cohort, 7.3% of 503 patients had a super-infected cyst. Four patients developed severe sepsis, and two of them died. Escherichia coli, viridans group streptococci, and Enterococcus species in liver cysts and Aspergillus fumigatus in lung cysts were the microorganisms most frequent involved.