Validation of microscopic observation drug susceptibility testing for rapid, direct rifampicin and isoniazid drug susceptibility testing in patients receiving tuberculosis treatment.

Drug susceptibility testing (DST) is often needed in patients clinically failing tuberculosis (TB) therapy. Most studies of phenotypic direct drug susceptibility tests, such as microscopic observation drug susceptibility (MODS) tests, have been performed in patients not receiving TB treatment. The effect of ongoing TB treatment on the performance of MODS direct DST has not been previously explored, but patients failing such therapy constitute an important target group. The aim of this study was to determine the performance of MODS direct rifampicin and isoniazid DST in patients clinically failing first-line TB treatment, and to compare MODS direct DST with indirect proportion method DST. Sputa from 264 TB patients were cultured in parallel in Lowenstein-Jensen (LJ) and MODS assays; strains were tested for rifampicin and isoniazid susceptibility by the proportion method at the national reference laboratory. Ninety-three samples were culture-positive by LJ and MODS (concordance of 96%; kappa 0.92). With conventional MODS plate DST reading (performed on the same day as the sample is classified as culture-positive), the isoniazid DST concordance was 96.8% (kappa 0.89), and the concordance for rifampicin susceptibility testing was 92.6% (kappa 0.80). Reading of MODS DST plates 1 week after cultures had been determined to be culture-positive improved overall performance marginally-the isoniazid DST concordance was 95.7% (kappa 0.85); and the rifampicin DST concordance was 96.8% (kappa 0.91). Sensitivity for detection of multidrug-resistant TB was 95.8%. MODS testing provided reliable rifampicin and isoniazid DST results for samples obtained from patients receiving TB therapy. A modified DST reading schedule for such samples, with a final reading 1 week after a MODS culture turns positive, marginally improves the concordance with reference DST.

Missed opportunities for tuberculosis diagnosis.

BACKGROUND: In high tuberculosis (TB) burden, resource-poor countries, sputum smear microscopy remains the mainstay of diagnosis. The low sensitivity of this test means that patients with smear-negative but culture-positive TB pass undetected through the health care system. Such clinical episodes are missed opportunities for diagnosis and interruption of transmission, which might be averted through the application of more sensitive diagnostic tests. OBJECTIVES: To estimate the proportion of incident TB cases that might have been detected earlier than the actual date of diagnosis if a test more sensitive than smear microscopy had been used at an earlier presentation episode. METHOD: Retrospective cohort study in urban Peru, investigating health care facility interactions for symptoms suggestive of TB prior to TB diagnosis through patient interviews and a review of clinical records. RESULTS: Of 212 participants enrolled, 58% had one or more clinical interactions prior to their diagnostic episode. Of those with a prior episode, the median number of episodes was three. The median delay to diagnosis from first presentation was 26 days. CONCLUSION: There are clear missed opportunities for earlier TB diagnosis, delaying treatment initiation and continued spread of Mycobacterium tuberculosis to the community. The implementation of sensitive diagnostic tests appropriate to resource-poor settings should be given high priority.

The epidemiology of malaria in an epidemic area of the Peruvian Amazon.

A longitudinal study of malariometric indicators and their association with potential risk factors was conducted during August 1997-July 1998 at Padre Cocha, a village of 1,400 residents in the Peruvian Amazon. The incidence of Plasmodium falciparum infections during the study year was 166/1,000 persons; that of P. vivax was 826/1,000 persons. The mean duration of symptoms prior to diagnosis was 2 days; presenting geometric mean parasite densities were 3,976 parasites/microl for P. falciparum infections and 2,282 parasites/microl for P. vivax. There were no malaria-associated deaths. Consistent with the epidemic nature of malaria in the area, the incidence of both parasite species increased with age and there were no age-specific differences in mean parasite densities. No specific occupational risks for malaria were identified. Activities significantly associated with malaria risk reflected local vector behavior and included strolling outdoors after 6:00 PM and arising before 6:00 AM for adults, and attending evening church services for children.

Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen.

Combined hepatocellular injury and renal tubular necrosis developed in five alcoholic patients who were receiving acetaminophen therapeutically. Two patients were taking doses prescribed by a physician. The hepatitis was characterized by extremely high serum transaminase values that were maximal on admission. Two patients died, and autopsy disclosed hepatic centrizonal necrosis and acute renal tubular necrosis. The three who survived had clinical features typical of acute tubular necrosis. All five had measurable concentrations of acetaminophen in plasma, although measurements were requested on admission only in two patients. When an alcoholic presents with combined hepatic and renal insufficiency, acetaminophen should be considered as a possible inciting agent. This diagnosis should be considered when serum transaminase levels are markedly elevated and when renal failure is due to acute tubular necrosis.