Healthcare Investigation Guide

A. Acute hepatitis B virus infection:

Presence of symptoms is a key factor in differentiating acute infections from chronic infections and should be assessed. Symptoms may include jaundice, dark urine, nausea, vomiting, abdominal pain, loss of appetite, fatigue, and joint pain. However, the majority of acute HBV infections are asymptomatic. To consider a case as acute, health departments should rely on medical history and information obtained from case investigation along with serologic findings with or without symptom onset.

Serologic markers indicating acute infection:
positive hepatitis B surface antigen (HBsAg) and
positive hepatitis B IgM core antibody (IgM anti-HBc).

B. Acute hepatitis C virus infection:

There are no serologic markers to differentiate between acute and chronic hepatitis C infection. Presence of symptoms is a key factor in differentiating acute infections from chronic infections and should be assessed. Symptoms may include jaundice, dark urine, nausea, vomiting, abdominal pain, loss of appetite, fatigue, and joint pain. However, the majority of acute HCV infections are asymptomatic. Therefore, health departments should also consider medical history and information obtained from case investigation along with a new finding of hepatitis C antibody or RNA positivity in a person not previously known positive (whether or not symptoms or ALT elevation are present).

A. Generate a chronologic listing of all healthcare encounters during the index patient’s likely exposure period.

B. Determine the nature and types of procedures performed during each healthcare encounter, especially those involving percutaneous exposures or invasive procedures (e.g., injections, infusions, skin puncture with a needle/lancet)

C. Review healthcare investigation database (see item 3) and regulatory/medical board reports/complaints to determine if the healthcare facility and/or providers have been under investigation. Enter the facility/provider(s) into the healthcare investigation database (step 3)

D. Contact the healthcare facility to inform them of the investigation and determine if they were aware of the current case(s) under investigation or any additional infections.

E. Evaluate the healthcare facility

1. Steps to follow if a single healthcare encounter is identified:
   1. Conduct a site visit at the facility.
      1. Gather general information about the types of services/procedures provided by the facility.
      2. Review facility records for the index patient.
         Information to assess includes whether patient was previously known to be infected, how many visits occurred during the exposure period, procedures performed during visits including healthcare personnel involved in care, equipment used, medications administered, room(s) where procedure(s) were performed.
      3. Review infection prevention and control practices at the facility.
         Observe the same procedures as those performed on the index patient, ideally by the same healthcare personnel. Focus on medication handling and equipment that is used for more than one patient (see infection prevention and control check-list). Evaluation of infection prevention and control practices should also assess the potential for facility staff to be the source of infection (e.g., through diversion of narcotics, sexual abuse of residents).
         If actual procedures are not being performed during the site visit, consider having healthcare personnel perform mock procedures so typical practices can be observed and assessed.
   2. Obtain patient list.
      Obtain a list of patients seen on the same day and an appropriate time period before and after the index patient to develop a chronologic listing of patients who may represent additional cases or sources of infection for the index patient.
      The appropriate time period before and after the index patient visit is typically 1-2 days, but the cohort selected will depend on a number of factors including number of visits the index patient had at the facility, the volume of patients seen at the facility, the types of procedures being performed, and the infection prevention practices observed during the site visit. For example, if the facility was a hospital, the list might only include patients from the relevant unit or patients who overlapped in the same operating room.
   3. Use appropriate methods to identify additional cases
      Cross-match patient list obtained from the facility with acute and chronic disease registries or hepatitis laboratory reports to identify additional cases and/or potential sources for the index patient’s infection. Please note that if the index patient’s exposure was recent, cross-match might not be efficient as infected patients may not have been reported and entered into the system. Also, the viral hepatitis disease registries, which rely upon voluntary reporting, may not be complete and do not include undetected cases. Recent studies estimate that about half of chronic HCV cases and one fifth or more of chronic HBV cases nationwide remain undiagnosed*. Additionally, patients who were present during the exposure period may have left the facility. Given these circumstances, targeted testing of patients to identify additional cases may be preferable. CDC is available for assistance or consultation on best practices for conducting patient screening.
2. If multiple healthcare encounters are identified, health departments should prioritize the investigation of encounters based on the following:

• information obtained on the facilities/providers from review of their healthcare investigation database (step 3) and regulatory/medical board complaints
• types of procedures the facility performed on the index patient (prioritize those involving percutaneous exposures e.g., injections, infusions, skin puncture with a needle/lancet)
• timing of procedures the facility performed on the index patient in relation to symptom onset within the likely exposure period (see step 1 – Verify the diagnosis)
• settings and procedures where outbreaks have been previously documented.

If a complete investigation (e.g., site visit, cross-matching patient lists) of all healthcare encounters is not possible, then health departments should, at a minimum, consider the following for each of the healthcare facilities identified:

1. Send a follow-up letter to all healthcare facilities and/or providers identified during the investigation to remind them that this is an opportunity to review their infection prevention practices. A letter based upon one used by the New York State Department of Health has been provided as one example [DOC - 2 pages].
2. Continue to monitor state/local health department surveillance data for the next several months to ensure no additional cases are identified/reported which are linked to any of the facilities/providers in question.

A. Site visit identifies major breaches in infection prevention and control that are high-risk for bloodborne pathogen transmission (e.g., syringe reuse from patient to patient or to reenter medication vials used for more than one patient). Health departments can consult these resources (Annals.org resource, CDC.gov resource) for information on high-risk breaches.

1. Facility should be immediately advised to stop unsafe practices.
2. A patient notification recommending bloodborne pathogen testing should be conducted for all potentially exposed patients, even if additional cases and/or a source-patient are not identified.  The scope of the patient notification will depend largely on how long the unsafe practice had been occurring in the facility. CDC is available for consultation on best practices for conducting a patient notification.
3. The facility/provider(s) should be reported to the appropriate regulatory authority (e.g., medical or state licensing board).

B. If the site visit does not identify major breaches in infection prevention and control, then results obtained from case finding, cross-matching, record review and targeted notification, and testing to identify potential sources should guide next steps.

1. Additional cases are identified
   1. Evaluate cases’ temporal and geographic overlap in the healthcare facility and use of shared medications and/or equipment as well as common exposures unrelated to healthcare.
   2. Pursue additional case finding through targeted notification and testing of patients. The time frame of targeted notification and testing will depend on findings/possible mechanism of transmission identified during the site visit.
   3. Consider obtaining blood specimens to allow for genotyping or viral sequencing of cases. However, depending on the mechanisms of transmission, viruses from cases may not be related to each other, despite transmission occurring in the facility. For example, there may be more than one source patient for the identified cases. In addition, source patients may not be identified for all cases. We recommend that these and other limitations be discussed with CDC before pursuing laboratory testing in this context.
2. Potential source patient(s) identified but not additional cases
   1. Assess relatedness of samples from index patient and potential source patient(s).
      1. If available, viral genotype information should be determined from available medical records.
      2. Alternatively, attempt to arrange for testing of index patient and potential source patient samples, to be performed locally (e.g., by the state/local health department laboratory).
      3. If genotypes match, consider the potential benefit of additional viral sequencing additional viral sequencing (for more information see DS Campo et al, J Infect Dis 2016).

         If warranted, coordinate with the CDC Division of Viral Hepatitis or other laboratory capable of HBV/HCV viral sequencing to ship specimens for testing. If collecting new samples, aliquot into multiple 0.5ml aliquots. For potential long-term storage, store frozen between -20°C – -70°C. Serum and plasma (red top tubes) are generally acceptable, avoid heparinized (purple top) tubes.

   2. If test results indicate relatedness between the viruses from the potential source and index patient (either through genotype or viral sequencing) consider additional case finding through targeted notification and testing of patients. When transmission is identified (e.g., additional cases or a source patient), absent recognized breaches in infection control, it can be challenging to determine if additional patients may have been exposed or infected.  Please note that potential source patients may only present sporadically to a health care facility, and infection control breaches may be variably intermittent or continuous; in many past investigations two or more transmission clusters separated widely in time have been detected.  For example, investigation of an HCV outbreak in an outpatient cardiology clinic detected two separate transmission clusters in June and December of the same year (see Z. Moore et al, Am J Cardiol 2011), and an outbreak in a dialysis center included cases spanning more than five years (see D. Nguyen et al, Infect Control Hosp Epidemiol 2016).  CDC is available for consultation on best practices for conducting a patient notification and to share lessons learned from previous investigations.
   3. If either of the patients refuse or do not have sufficient sample available for additional testing, targeted notification and testing of patients can also be used to find additional cases.
   4. If test results indicate that the virus from the potential source(s) and index patient are not related,
      1. send a follow-up letter to all healthcare facilities and/or providers identified during the investigation to remind them that this is an opportunity to review their infection prevention practices. A letter based upon one used by the New York State Department of Health has been provided as one example [DOC - 2 pages].
      2. Continue to monitor state/local health department surveillance data for the next several months to ensure no additional cases are identified/reported which are linked to any of the facilities/providers in question.
3. If additional cases or potential source patients are not immediately identified
   Consider sending a follow-up letter to the healthcare facilities and/or providers identified during the investigation and continue to monitor surveillance data.

* References

• Spradling PR, Rupp L, Moorman AC, et al.Hepatitis B and C virus infection among 1.2 million persons with access to care: factors associated with testing and infection prevalence.
  Clin Infect Dis 2012;55:1047-55.
• Denniston MM, Klevens RM, McQuillan GM, Jiles RB. Awareness of infection, knowledge of hepatitis C, and medical follow-up among individuals testing positive for hepatitis C: National Health and Nutrition Examination Survey 2001-2008.
  Hepatology 2012; 55:1652-61.
• Centers for Disease Control and Prevention. Completeness of reporting of chronic hepatitis B and C virus infections — Michigan, 1995-2008.
  Morbid Mortal Weekly Rpt 2013; 62: 99-102.
• Vijayadeva V, Spradling P, Moorman A, Rupp L, Lu M, Gordon S, Henkle E, Boscarino J, Teshale E, Homberg S, Nakasato C, for the CHeCS Investigators. Hepatitis B virus testing and prevalence by country of origin among Asian/Pacific Islanders. In press; Am J Managed Care, April 2014.

Acknowledgement: We would like to thank the health departments who graciously reviewed and provided comment on this algorithm.