Publications

To determine the proportion and distribution of drug-resistant Mycobacterium tuberculosis in California, we surveyed all California counties for drug-susceptibility test results for initial isolates from tuberculosis cases counted during the first quarters of 1991 and 1992. Overall, drug-susceptibility test results were not available for 17% of isolates. Among isolates with available test results, the proportion with resistance to isoniazid averaged 8.7%, and the proportion with resistance to at least 2 drugs, multidrug resistance, averaged 5.9% during these two quarters. The proportion of isolates with drug resistance did not change substantially during these time periods. The proportion with combined isoniazid and rifampin resistance remained stable at about 1.1%. Among persons whose isolates were tested for drug resistance, those with a known previous diagnosis of tuberculosis (relative risk [RR] = 2.6; 95% confidence interval [CI], 1.6 to 4.3; P < .01) and persons who were foreign born (RR = 1.7; 95% CI, 1.1 to 2.7; P = .014) were more likely to have isoniazid-resistant organisms. These statewide data suggest that the initial tuberculosis treatment regimen in California should include 4 antituberculosis drugs, as recommended by the American Thoracic Society and the Centers for Disease Control and Prevention for areas with a prevalence of isoniazid resistance of 4% or greater. The lack of test results for 1 in 6 patients with tuberculosis suggests the need for improved physician and laboratorian education to implement the recommendations that drug susceptibility be tested on all initial isolates.

Neonatal alloimmune thrombocytopenia (NATP) and post-transfusion purpura (PTP) are acquired bleeding disorders caused by alloimmune thrombocytopenia. In most cases, the thrombocytopenia is due to an alloantibody directed against the platelet glycoprotein IIb-IIIa (GPIIb-IIIa) complex. During the course of routine studies on the role of GPIIb-IIIa in inherited and acquired bleeding and thrombotic disorders, we unexpectedly identified an individual whose platelets reacted by non-reduced Western blot analysis with anti-GPIIIa polyclonal antisera, but did not react with a commercially available monoclonal antibody (SZ21) specific for GPIIIa. We screened all 14 GPIIIa exons for possible nucleotide changes which might alter amino acids and found variations in only exons 3 and 10. Nucleotide sequencing revealed that only the exon 3 alteration changed the predicted amino acid sequence. This variation was caused by homozygosity for the uncommon P1A2 allele of the GPIIIa gene. Platelets from two additional unrelated normal individuals known to be homozygous for P1A2 also lacked reactivity with SZ21 by Western blot. Using flow cytometry with intact platelets, we observed a markedly reduced binding of SZ21 to platelets with the P1A2 genotype. Scatchard analyses indicated that SZ21 bound to P1A1/A1 platelets with a Kd of approximately 8.26 x 10(-10) M, and to P1A2/A2 platelets with a Kd of approximately 5.58 x 10(-9) M. Thus, we have characterized a readily available monoclonal antibody able to distinguish between the two P1A alleles of the GPIIIa gene. Because incompatibility for this platelet polymorphism is the most common cause of neonatal alloimmune thrombocytopenia and posttransfusion purpura, and because platelet immunophenotyping reagents lack specificity and are not easily available, this monoclonal antibody could facilitate the management of patients with these disorders.