In addition to other programmatic activities, the Division of Communicable Disease Control (DCDC) is engaged in many research projects that contribute to local, state, national and international knowledge of infectious diseases. The following research highlights demonstrate the role of science in CDPH programs.
Rapid detection of extensively drug-resistant tuberculosis (XDR TB): The Microbial Diseases Laboratory (MDL) has developed a pyrosequencing method for rapid detection of mutations associated with resistance to injectable drugs and fluoroquinolones. For multidrug-resistant strains of Mycobacterium tuberculosis, extensive drug resistance is defined by resistance to a fluoroquinolone drug as well as one or more of the injectable drugs such as amikacin, kanamycin, or capreomycin. Resistance to these drugs can be detected quickly if the tuberculosis bacteria have specific known mutations in the gyrA gene (for fluoroquinolones), or the rrs gene (for injectable drugs). Pyro-sequencing enables detection of these mutations rapidly from an acid-fast smear-positive sputum sediment or from a culture. Culture-based confirmation of susceptibility or resistance is always recommended, but the pyrosequencing provides useful preliminary results to guide therapy during the period of several weeks when tuberculosis cultures are growing and culture-based drug susceptibility testing is being performed. Improved patient outcomes and a reduction in the spread of drug-resistant disease are expected to result from the application of this technology.
Tuberculosis screening among persons with HIV infection: The Tuberculosis Control Branch (TBCB) is investigating the policies, procedures, and actual practices of tuberculosis (TB) screening among HIV-infected clients at two Ryan White Part III-funded clinics as part of a study funded by the Centers for Disease Control and Prevention (CDC). The objective of the study is to identify practices that enhance and/or serve as barriers to prevention and treatment of TB infection in this population. Findings will be shared with national, state, and local partners to inform improved TB screening and treatment practice.
Treatment practices and costs of Multi Drug-Resistant TB (MDR-TB) in the United States: The Tuberculosis Control Branch is participating in a national study of multi drug-resistant tuberculosis (MDR-TB) to provide detailed observational data on the diagnosis, treatment and management practices, outcomes, and costs of MDR and XDR TB patients in the United States. Data from this study will be used for future clinical trials of MDR/XDR TB treatment regimens and case management procedures, and for financial planning for TB program budgets.
Tuberculosis deaths: Almost 10 percent of persons with TB will die. TBCB is participating in a national study to determine the proportion of deaths that are attributable to TB and to identify areas of intervention to prevent TB deaths. Study findings will be used to create the evidence-basis for public health interventions aimed at reducing TB deaths in the United States.
DRUG RESISTANT BACTERIA
Enhanced laboratory capacity to detect Carbapenemase-producing Enterobacteriaceae: Carbapenemase-producing Enterobacteriaceae (CPE) are emerging as a significant public health threat worldwide and are becoming increasingly more prevalent as a source of morbidity and mortality in the healthcare setting. Carbapenemases represent a diverse group of enzymes that hydrolyze most β-lactam antibiotics and are often associated with extensively-drug resistant bacteria. The detection of CPE is critical because of the limited therapeutic options associated with these infections and the importance of avoiding treatment failures through the empiric selection of antibiotics. The Microbial Diseases Laboratory (MDL) has recently implemented a molecular diagnostic testing service for detecting the most prevalent carbapenemase, Klebsiella pneumoniae carbapenemase or KPC. In addition to KPC, MDL plans to develop molecular diagnostic tests to screen CPE for additional carbapenemase genes including the newly-described New Delhi metallo-β-lactamase 1 (NDM-1). It is hoped that the availability of these new tests will assist in monitoring antimicrobial resistance trends and the potential of CPE expansion in the healthcare setting.
Influenza and 2009 H1N1: The influenza A 2009 H1N1 virus was first identified in California before spreading worldwide. In order to better characterize the epidemiology and clinical manifestations of the outbreak, including identifying populations at highest risk, the California Department of Public Health (CDPH) initiated surveillance for all severely ill and fatal cases with laboratory confirmed H1N1. To date, data from over 3,500 cases have been reviewed and analyzed. In the post-pandemic phase, CDPH is working with local health departments (LHDs) to monitor the H1N1 virus as well as other influenza viruses through review of intensive care unit (ICU) and fatal cases under age 65 years reportable. This work has resulted in several publications in nationally peer reviewed medical journals. Some of these publications have informed influenza vaccination recommendations for high risk groups such as pregnant women and adults with obesity.
Guillain-Barré Syndrome (GBS) surveillance and the H1N1 vaccine: The Immunization (IZ) and Communicable Disease Emergency Response (CDER) Branches of CDPH initiated surveillance for Guillain-Barré Syndrome (GBS) in the fall of 2009 due to concerns about the association of GBS and H1N1 vaccine. Reports of GBS were received from physicians and hospital discharge data to ensure that all cases were captured. A total of 704 suspected GBS cases were reported from 2009 to 2011. Preliminary data from this project found similar rates of GBS in patients who received seasonal flu vaccine as compared to H1N1 vaccine.
The California Encephalitis Project (CEP) was initiated in 1998 to better understand human encephalitis, including risk factors, clinical features, causative agents, outcomes and epidemiologic features. A number of important public health issues have arisen from this project since 1998. Highlights from the past year include:
Rabies: Detailed laboratory and clinical evaluation of a human rabies case who ultimately survived. Manuscripts describing this case are in preparation.
Encephalitis outcomes: A retrospective cohort study focusing on patients with encephalitis referred to CEP from Children’s Hospital & Research Center Oakland (CHRCO) from January 1, 1998 to December 31, 2009. Asian ethnicity, abnormal neuroimaging, and Glasgow Coma Score (GCS) were found to be significantly associated with outcomes at discharge. This study is unique in identification of ethnicity as an independent predictor of pediatric encephalitis outcomes. Additional variables examined in this study may be useful ancillary tools to aid in predicting outcomes among children hospitalized with encephalitis. An abstract was submitted and accepted to IDSA’s 49th Annual Meeting.
Basal ganglia/thalamic lesions: CEP and CDER conducted a follow-up study of a subset of cases with Basal ganglia/thalamic lesions. Six percent (183) of CEP cases reported T/BG neuroimaging abnormalities; with an etiology identified in 138 cases (75 percent) including 67 infectious cases (37 percent), 29 post-infectious/acute disseminated encephalomyelitis (ADEM) cases (16 percent), and 42 non-infectious cases (23 percent). Identified infectious agents included 20 cases (30 percent) of respiratory virus, 9 cases (13 percent) of Creutzfeldt-Jakob disease, 7 cases (10 percent) of arbovirus, and 7 cases (10 percent) of Mycobacterium tuberculosis. Identified non-infectious etiologies included 13 cases (31 percent) of ischemic events and 8 cases (19 percent) of neoplasm. Infectious and post-infectious cases were younger compared with non-infectious cases. Infectious etiologies had a higher median cerebrospinal fluid (CSF) white blood cell count compared with non-infectious etiologies. T/BG neuroimaging characteristics were associated with distinct etiologies. T/BG abnormalities in encephalitis patients can aid in identifying the underlying etiology with patient age, CSF findings, and neuroimaging characteristics helping to narrow the etiological scope and guide testing.
WEST NILE VIRUS
West Nile Virus (WNV) and organ transplants: In late fall of 2010, a case of West Nile Virus (WNV) encephalitis was identified in an organ transplant patient. The identification of this case led to an investigation that identified additional WNV cases. Transmission of WNV via transfusion and organ transplant has been reported since 2002. However, organ donors are not routinely screened (unlike blood) for WNV. Because of the identification of this cluster, the transplant community is re-evaluating the need to universally screen organ donors. An abstract describing this WNV cluster was submitted to the Infectious Diseases Society of America (IDSA) and accepted for presentation.
SEXUALLY TRANSMITTED DISEASES
Syphilis: In conjunction with the Kaiser Permanente Northern California Regional Laboratory, the Sexually Transmitted Diseases (STD) Control Branch conducted an evaluation of a novel chemiluminescence immunoassay to screen for syphilis. The evaluation described demographic and clinical factors associated with discordant syphilis serology results. The results of this evaluation will be published in the Journal of Infectious Diseases later this year.
Chlamydia and Gonorrhea: The STD Control Branch is conducting research to evaluate interventions to improve adherence to clinical practice guidelines for re-testing for chlamydia and gonorrhea. In addition to implementing clinical-level systems to reduce missed opportunities for re-testing, client options for text and email message reminders and home collection test kits will be evaluated. This research project is funded by a grant from the Office of Population Affairs: http://www.intouch4health.org/
Human Papillomavirus (HPV) Vaccine Impact: The STD Control Branch, in collaboration with the California Emerging Infections Program (CEIP), is evaluating the population-based impact of the HPV vaccines through surveillance of pre-cancerous cervical disease in Alameda County. To monitor changes in HPV types associated with disease, CDC performs molecular testing on tissue specimens submitted by the 5 sentinel sites.
This research project is part of the CDC-funded Emerging Infections Program: http://ceip.us/cd_hpv.htm