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Treatment of latent tuberculosis & Ebola & Anencephaly in Central Washington

Today’s topics:

  • Treatment of latent tuberculosis infection
  • Ebola virus disease
  • Anencephaly


Action requested
: Consider short course therapy for latent tuberculosis infection (LTBI).

Background: The standard treatment for LTBI has been nine months of isoniazid.  Although effective, the prolonged treatment course and potential for drug-induced hepatitis can lead to lower completion rates.  Recently, evidence has confirmed the safety and effectiveness of shorter courses of treatment: rifampin daily for four months (4R) or isoniazid-plus-rifapentine once weekly for 12 weeks (3HP).  These regimens offer equivalent efficacy to isoniazid given for nine months (9H), as well as other benefits:

  • These shorter regimens are likely to provide higher effectiveness in clinical practice due to the higher completion rates associated with the shorter regimens (e.g., 80% vs 50% completion, respectively) and they have been demonstrated to be more cost-effective than 9H.
  • 4R circumvents loss in effectiveness created by the relatively high prevalence of isoniazid resistance among M. tuberculosis isolates (~15%).
  • 4R and 3HP offer reduced risk of drug induced liver injury compared to 9H and similar or better overall rates of discontinuation due to adverse effects despite a slightly higher risk of treatment interruption due to hypersensitivity.

Rifampin-based regimens for LTBI do have some limitations:

  • Estimated private-sector wholesale drug price is higher for 4R and 3HP than 9H (e.g., ~$300-500 per course versus ~$50).
  • The Centers for Disease Control and Prevention (CDC) recommends directly observed therapy for use of 3HP.  This may not be feasible due to provider resource constraints, scheduling incompatibility, or patient refusal.  However, heightened modes of adherence reminders and safety monitoring (e.g., weekly text messaging or phone calls) are being successfully implemented in some settings. 
  • Rifamycins, especially rifampin, induce the hepatic microsomal oxidase system (particularly CYP3A) that is involved in the catabolism of many other drugs. Affected drug classes include beta-blockers, calcium channel blockers, statins, some oral hypoglycemics, corticosteroids, anti-epileptics, and protease inhibitors, among others.  In some cases, the interaction only warrants clinical or laboratory monitoring for effect on the other drug.  In other situations increasing the dose of the other drug is necessary, and in some cases (e.g., tacrolimus, azoles) the interaction presents an absolute contraindication to rifamycin use.
  • CDC recommends 3HP be used for patients aged ≥12 years, although the lower age limit for use may be reduced to 2 years when the likelihood of completing another regimen is very low. 
  • No lower age limit exists for 4R; however, the American Academy of Pediatrics recommends using a 6-month course rather than 4 months.
  • Rifamycin-based regimens for LTBI treatment are not recommended for people with HIV/AIDS who are taking protease inhibitors, people presumed to be infected with rifamycin-resistant M. tuberculosis, and pregnant women.   3HP also cannot be used for patients with presumed isoniazid-resistant infection. 

Note that testing and treatment for LTBI should be reserved for patients with a reasonably high likelihood of infection (i.e., foreign birth, recent exposure to a contagious case) and/or a medical risk factor for reactivation (e.g., immunosuppression, diabetes mellitus, fibronodular scarring on chest radiography).  In healthy patients over 60 years of age who are not recent contacts, not refugees, and have no medical risk factors for reactivation, the cumulative lifetime risk of active disease (0.1% per life-year) is unlikely to exceed the risks of LTBI treatment.  Contact the Tuberculosis Program (425-339-5225) if you have specific questions about LTBI testing or treatment. 


  1. Confirm that LTBI treatment is indicated.
  2. Verify that an LTBI patient is eligible for short course therapy and, if so, which is most appropriate based on age and other factors noted above.
  3. Assess for potential drug interactions before starting 4R or 3HP therapy.
  4. Dosing:




    3HP (once weekly dose x 12)

    4R (daily dose x 120)






























    Consult the link below or call the Tuberculosis Program at 425-339-5225


  6. Contact the Tuberculosis Program (425-339-5225) for guidance on pediatric dosing.
  7. Monitor for signs and symptoms of adverse drug reactions, including: unexplained anorexia, fatigue, nausea or vomiting, dark urine, or icterus; persistent paresthesia of hands or feet; persistent weakness, fatigue, fever, or abdominal tenderness; or easy bruising or bleeding.  Baseline and routine liver function monitoring during treatment of LTBI are recommended by CDC only when there is a history of liver disease, HIV infection, chronic viral hepatitis, pregnancy (or within 3 months post-delivery), regular alcohol use, or concurrent ingestion of other potentially hepatotoxic drugs.
For more detailed information on LTBI treatment regimen selection, dosing, and safety monitoring, see

For an interactive online TST/IGRA interpreter that provides estimated lifetime risk of reactivation based on patient factors and LTBI test results, see



Action requested
: Be aware of resources to address management of patients at risk for or diagnosed with Ebola Virus Disease (EVD).

Background: As of August 28, 3069 suspected and confirmed cases of EVD had been reported to the World Health Organization; 1552 (51%) deaths have been attributed to EVD.  The actual number of cases is believed to be much greater than those reported.  This is the largest EVD outbreak in history.  Complicating control efforts are local burial customs, public fear that health care workers are spreading the disease, and lack of health care infrastructure to treat patients.  Two Americans who were infected and returned to the U.S. for treatment have now recovered.

Recommendations: For detailed updates on the outbreak or management of patients at risk for or diagnosed with EVD, see  Also, Public Health—Seattle & King County has produced a flow chart to guide evaluation of patients suspected of having EVD. Here is a version of the Ebola Evaluation Guidance (PDF) with local contact information.



Action requested
: Assure adequate folic acid intake for women of childbearing age. 

Background: The incidence of anencephaly in the south central Washington region is unusually elevated, about four times higher than expected. The Yakima Health District (YHD), Benton Franklin Health District (BFHD), and Washington State Department of Health (DOH) are actively investigating this public health issue.  Although the underlying cause of the increased incidence of anencephaly remains unknown, we do know that folic acid deficiency during pregnancy (even before pregnancy is recognized) can result in neural tube defects.  Thus, the situation is a good reminder of the need to assure adequate folic acid intake for all women of childbearing age.  Because this situation is occurring in a rural setting, concerns have also been raised about water from private wells.

Recommendations: Healthcare providers should recommend that all women of childbearing age:

  • Take 400 micrograms of folic acid daily (for women who have already had a pregnancy affected with any neural tube defect, increase from 400 micrograms daily to 4000 micrograms daily beginning one month prior to attempting to conceive)
  • Seek early prenatal care, and
  • Test water from private wells annually for nitrates and bacteria.

For more information about folic acid, see