1ºCare Exchange

A Reader-Directed Journal from the Oklahoma Center for Family Medicine Research at
The University of Oklahoma Health Sciences Center

Volume 1, Number 2 April 1999

In this issue... Emerging Infectious Diseases

Hepatitis C
Lyme Disease
Hantavirus
Plague
Human Ehrlichiosis

ormone Replacement Therapy

EMERGING INFECTIOUS DISEASES

by James W. Mold, MD & Mike Crutcher, MD, MPH

• Hepatitis C • Lyme Disease • Hanta Pulmonary Syndrome

• Plague • Human Ehrlichiosis

Despite an increasing array of vaccines and antibiotics, we find that our battle with microbes and the illnesses that they cause rages on. A decade ago, we were feeling very good about our successes. Today, a whole new set of organisms and infectious diseases threatens to outstrip our ability to respond. This issue of 1º Care Exchange summarizes pertinent information about several emerging infections of relevance to primary care physicians practicing in Oklahoma. While the number of new cases of Hepatitis C is declining, the prevalence of chronic infection is high, leading to predictions that the rate at which physicians will see the long term complications of this infection will continue to increase over the next 20 years at least. Both Hantavirus Pulmonary Syndrome and Plague are extremely serious infections associated with rodents that are quickly making their way eastward from Arizona and New Mexico. Early diagnosis, particularly in the case of Plague, can significantly reduce mortality. Ehrlichiosis is a tick-borne infection similar in many ways to Rocky Mountain Spotted Fever and is endemic in parts of our state. Lyme Disease was included because it is over-diagnosed in Oklahoma (see prevalence map, page 3).

Hepatitis C

Key Facts:

• Most common reason for liver transplantation in U.S. adults
• Responsible for 40% of chronic liver disease in U.S.
• New infections decreasing; complications of existing chronic infections expected to triple during the next 20 years

Populations at risk:

1. Recipients of blood transfusions before 1992
2. Recipients of organ or bone marrow transplants before 1992
3. IV drug abusers
4. People with high risk sexual practices and multiple sex partners, although the incidence is low (this is controversial and needs to be studied)
5. EMTs, paramedics, and public safety workers exposed to blood at accident scenes
6. Infants of HCV infected mothers (wait until >1 year of age to screen)
7. Clinical laboratory workers exposed to blood and blood products
8. Health care workers with unintentional needle or sharps injuries (1.8% risk from single stick from an HCV positive source)
9. Long-term sexual partners (e.g. spouses) of HCV positive patients (risk: 1.5%)

Clinical Features:

• Initial infection asymptomatic in 60-70% of cases
• 85% of infections become chronic
• chronic HCV infection often asymptomatic for decades; fatigue is common
• 60-70% of chronic infections cause intermittent or persistent elevations of ALT
• 10-20% of chronic infections result in cirrhosis and 1-5% in hepatocellular carcinoma

Diagnostic Testing:

Screening:

• EIA-2 (2^nd generation enzyme immunoassay) for antibodies to HCV ($80)
• + test means: false +, past infection resolved, or chronic HCV

To R/O false + test:

• RIBA-2 (2^nd generation recombinant immunoblot assay) ($190)
• (All positive EIA results should be confirmed with RIBA).

To confirm chronic active infection:

• HCV RNA (by polymerase chain reaction) ($200-250)

Treatment:

• HAV vaccine is generally recommended for all persons with chronic hepatitis C, unless they have already had hepatitis A. HBV vaccine is recommended for persons at risk for hepatitis B. Patients should avoid alcohol and other hepatotoxins
• HCV infected patients without contraindications should be considered for treatment
• Patients with less severe disease are more likely to respond
• Serum transaminase levels don't correlate well with liver pathology; biopsy is generally performed before treatment though it may not be essential
• Treatment with interferon SC alpha 2b 3X/wk for 18-24 months induces an initial ALT response in 50%; long-term (>5 year) remission is achieved in 20-25%
• Other treatment options include: interferon alpha 2a, interferon alphacon-1, and combination therapy with interferon alpha 2b and ribavirin
• Contraindications to interferon treatment include: major depressive illness, cytopenias, hyperthyroidism, renal transplantation, autoimmune disease, pregnancy, and advanced cirrhosis.

References:

1. MMWR Oct. 16, 1998, 47:1-39.
2. Oklahoma State Dept. of Health Epidemiology Bulletin, Winter 1997, 97(4): 1-2.
3. Wong JB, et al. Pretreatment evaluation of chronic hepatitis C: Risks, benefits, and costs. JAMA 1998, 280(24): 2088-2093.
4. Moyer LA, Mast EE. Hepatitis C: Part I. Routine serologic testing and diagnosis. AFP 1999, 59(1): 79-88.
5. Raymond RS, Fallon MB, Abrams GA. Oral thymic extract for chronic Hepatitis C in patients previously treated with interferon: a randomized, double-blind, placebo-controlled trial. Ann Int Med 1998 129:797-800.

Lyme Disease

Lyme Disease is not native to Oklahoma although the organism has been found in rabbits and ticks. The map on page 3 shows the areas where Lyme Disease is known to exist in the US. If symptoms suggest Lyme Disease, ask if your patient has traveled outside the state.

Key Facts:

• First identified in 1975; now the most common vector-borne disease in the U.S.
• Most common in New England, the upper Midwest; and on the West Coast
• Common in Europe, especially in Germany, Austria, Switzerland, France, Sweden
• Caused by Borellia bergdorferi, a spirochete
• The main vector in the northeast is the nymphal stage of the deer tick which feeds May-September
• Tick is very small, the size of a pencil point.
• Median incubation period (tick bite to symptoms) is 14 days
• First reported case in Oklahoma occurred in 1985
• True Lyme disease cases from exposure within Oklahoma are probably rare; most reports are from the eastern part of the state
• A vaccine (LYMErix; SmithKline Beecham) is now available for persons at high risk of exposure; after 3 doses given in months 0,1, and 12, the protection rate was 76%. By 8 months after the 3rd injection, antibody levels drop dramatically, however.

Populations at risk:

• Individuals who have been outdoors or in contact with outdoor animals in endemic areas (see map, page 3).

Clinical Features:

• Similar to syphilis, this spirochetal infection has three distinct stages:

Stage 1

• Erythema migrans (EM) usually at site of tick bite (present in 80% of cases).
• Regional adenopathy and minor constitutional symptoms

Stage 2 (begins within days or weeks of Stage 1)

• Secondary annular skin lesions
• Fever, chills, arthralgias, myalgias, stiffness, palpitations, headache, extreme fatigue
• Atrioventricular conduction defects, myocarditis, pericarditis
• Meningoencephalitis, cranial nerve palsies, motor and sensory radiculitis, chorea, ataxia, myelitis

Stage 3

• Acrodermatitis chronica atrophicans, primarily lower arms and legs
• Subtle encephalopathy (memory and mood disturbance) and/or polyneuropathy
• Recurrent relatively brief attacks of acute poly- or oligoarticular arthritis involving large joints, most often knees

Diagnostic Testing:

• Serum: ELISA (enzyme linked immunoabsorbant assay) for the antibody
• Western blot test – in Oklahoma, should always be done to confirm positive ELISA
• These tests don't distinguish between recent and past infection.
• They are also less sensitive during the first 3 weeks of illness.
• May see false positives with syphilis, RMSF, relapsing fever, leptospirosis, mononucleosis, SLE, and RA

Culture: A skin culture may be done from a punch biopsy or saline lavage of the leading edge of an EM lesion

Treatment:

For Stage 1 Lyme disease:

• Doxycycline 100 mg BID for 14-21 days or
• Amoxicillin 500 mg TID for 14-21 days +/- probenecid 500 mg TID or
• Cefuroxime 500 mg BID for 21 days or
• Clarithromycin 500 mg BID for 14-21 days

For Stage 2 Lyme disease:

• Ceftriaxone 2 gm IV QD for 14-21 days or
• Penicillin G, 24 mu IV QD for 14-21 days

For Stage 3 Lyme disease:

• Doxycycline 100 mg BID for 14-28 days or
• Amoxicillin 500 mg QID for 14-28 days +/- probenecid 500 mg TID or
• Ceftriaxone or Pen G IV QD as for Stage 2

References:

1. Steere AC. Current understanding of Lyme disease. Hospital Practice April 15, 1993: 37-44.
2. Tugwell P, et al. Guidelines for laboratory evaluation in the diagnosis of Lyme Disease (Part 1). Ann Int Med 1997, 127:1106-1108.
3. Tugwell P, et al. Laboratory evaluation in the diagnosis of Lyme Disease (Part 2). Ann Int Med 1997, 127: 1109-1123.
4. Reiner KL, Huycke MM, McNabb SJN. The descriptive epidemiology of Lyme Disease in Oklahoma. JOSMA 1991, 84: 503-509.
5. Lyme Disease Vaccine. Medical Letter March 26, 1999, 41 (1049).

Hantavirus Pulmonary Syndrome
(Sin Nombre virus)

Hantavirus Pulmonary Syndrome cases by state of residence, United States, Aug. 3, 1998 (N=188).

Source: Graves T, Crutcher JM. J Okla State Med Assoc 1996, 91(6):327

Key Facts:

• First cases in the U.S. in New Mexico and Arizona (“4 corners area”) in 1993
• 205 confirmed cases in 29 states as of January 1999
• First documented case in Oklahoma occurred in Guymon in 1996
• Case-fatality rate is 45%
• Infection occurs via inhalation of aerosolized “Sin Nombre” virus (SNV)
• Virus present in feces, urine, and saliva of asymptomatic rodents (esp. deer mice)
• Transmission by rodent bite possible; person to person transmission very unlikely
• Another hantavirus (Bayou type) carried by the rice rat (present in SE OK) causes a similar illness but with renal involvement in addition to the pulmonary syndrome.

Populations at Risk:

1. People living in rural and semi-rural areas.
2. People who have cleaned or otherwise disturbed rodent-inhabited barns, sheds, vehicles, or abandoned dwellings.
3. People who work in enclosed areas inhabited by rodents.
4. Hikers and campers who have disturbed rodent nests/burrows.

Clinical Features:

• 3-6 day flu-like illness (fever, HA, severe myalgias, dizziness, GI symptoms, non-productive cough)
• Then rapid progression to hypoxia from non-cardiac pulmonary edema (ARDS)
• Left-shifted leukocytosis, thrombocytopenia, hemoconcentration, acidosis
• CXR – bilateral interstitial edema and possibly pleural effusions

Diagnostic Testing:

Serum:

• IgM ELISA test for antibodies to SNV (Contact OSDH: 405-271-4060)
• + result if >1:400
• Test is + even during prodrome

Pathologic specimens:

• Formalin-fixed tissue specimens can be sent to the OSDH for processing before being sent to the CDC.

Treatment:

1. Supportive treatment, as is given for ARDS.
2. IV ribavirin can be tried but has not been proven effective.
3. No evidence that corticosteroids help.

References:

1. Graves T and Crutcher JM. First reported case of hantavirus pulmonary syndrome in Oklahoma. JOSMA 1998, 91(6): 327-330.

Plague

Key Facts:

• Increasing incidence in 13 western states: 299 cases in past 20 years; only one case in Oklahoma so far
• Caused by Yersinia pestis, a gram-negative non-motile cocco-bacillis
• Transmission to humans occurs through the bite of an infected rodent flea, by direct contact with the blood or tissues of an infected rodent, or by inhalation of organisms aerosolized by an infected rodent or human.
• Recent rise in number of cases transmitted from domestic cats carrying infected fleas
• Incubation period is 1-3 days
• Incidence highest during summer months
• Mortality rates are 50-60% for untreated bubonic and 100% for untreated pneumonic plague; early antibiotic treatment is effective.

Populations at Risk:

1. People in endemic areas exposed to rodents or to domestic cats exposed to rodents
2. Hunters who skin infected animals without gloves
3. People who have handled sick or dying rodents (e.g. mice, rats, squirrels)

Clinical Features:

• Three forms: bubonic, septicemic, and pneumonic
• Signs and symptoms tend to be mild at first despite seriousness of illness.
• Enlarged, tender lymph nodes (“bubos”); often absent in septicemic and pneumonic forms
• Skin mottling (esp. chest, abdomen, face)
• Apprehension out of proportion to apparent severity of illness
• Fever is not universal; WBC may be elevated or depressed
• Thrombocytopenia is common
• Rapid development of septic shock, ARDS, and DIC

Diagnostic Testing:

• Aspiration of bubo: Wayson, Giemsa, or Gram stain for organisms; fluorescent antibody (FA) testing; and culture on blood agar
• Blood: culture
• Sputum: FA testing; culture
• Throat swab: FA testing

Treatment:

Antibiotics are effective if started early enough. Effective agents include

• streptomycin
• chloramphenicol
• tetracycline (not doxycycline)
• gentamycin

References:

1. Human Plague—United States, 1993-1994. MMWR 43(13):242-246, 1994.
2. Kelty TK. Plaque. AFP 1986 33(6):159-164.

Human Ehrlichiosis

Key Facts:

• First case worldwide 1954 in Japan
• First documented U.S. case in 1986 in Arkansas
• Appears to be common in eastern Oklahoma
• Highest reported incidence is in men 60-69 years old; occurs at all ages/ both genders
• Responsible organism is Ehrlichia chaffeensis (after Fort Chaffee, Arkansas), an obligate intracellular cocco-bacillus resembling rickettsia
• Most common vector is the “Lone Star” tick
• Predominantly occurs April – September.
• Median incubation period after tick bite 9 days
• Case fatality rate is 5%, but higher in the elderly

Populations at Risk:

• Anyone at risk for tick bites

Clinical Features:

• Fever, rigors, headache, arthralgias, myalgias, nausea, vomiting, malaise, fatigue
• Leukopenia, thrombocytopenia; slowly progressive anemia
• Mild hepatitis
• Rash in 36%; variable appearance, most often on trunk, legs, and/or arms
• Complications include: DIC, renal failure, seizures, coma (generally 7-10 days into illness)

Diagnostic Testing:

Serologic tests:

• Acute and convalescent sera for antibody testing (only helpful after the fact)
• Ehrlichia DNA by polymerase chain reaction (PCR) may be helpful acutely if available.

Treatment:

• Treatment should not be delayed until the diagnosis is confirmed serologically
• Tetracycline and doxycycline are effective.
• Chloramphenicol is probably effective (though less so in vitro).

References:

1. Schaffner W, Standaert SM. Ehrlichiosis – In pursuit of an emerging infection. NEJM 1996, 334(4): 262-263.
2. Fishbein DB, et al. Human Ehrlichiosis in the United States, 1985 to 1990. Ann Int Med 1994, 120(9): 736-743.
3. Walker DH, Dumler JS. Emergence of the Ehrlichioses as Human Health Problems. EID 1996 2(1). (http://www.cdc.gov/ncidod/EID/vol2no1/walker1.htm)

On the Web...

http://www.cdc.gov/

The major web site for information about infectious diseases is the Centers for Disease Control and Prevention's site. This site has an excellent search engine, which will help you find up-to-date information about emerging infections nation- and world-wide

http://www.Lyme.org/

The Lyme Disease Foundation. An excellent site for sufferers of the disease and for individuals interested in research.