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Published Date: 2009-11-20 15:00:04
Subject: PRO/AH/EDR> Murine typhus - USA (04): (TX) 2008-2009
Archive Number: 20091120.3995

MURINE TYPHUS - USA (04): (TEXAS) 2008-2009
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Date: Thu 19 Nov 2009
Source: CDC. MMWR Morb Mortal Wkly Rep 2009; 58(45); 1267-70 [edited]
<http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5845a4.htm>

Outbreak of _Rickettsia typhi_ infection - Austin, Texas, 2008
--------------------------------------------------------------
Murine typhus is a flea borne rickettsial disease caused by the
organism _Rickettsia typhi_. Symptoms include fever, headache,
chills, vomiting, nausea, myalgia, and rash. Although murine typhus
is endemic in southern Texas, only 2 cases had been reported during
the past 10 years from Austin, located in central Texas (Figure 1
[for figure, see original report at the source URL above. - Mod.LL])

On 8 Aug 2008, the Austin/Travis County Department of Health and
Human Services (ATCDHHS) contacted the Texas Department of State
Health Services (TDSHS) concerning a cluster of 14 illnesses with
serologic findings indicative of murine typhus. On 12 Aug 2008, TDSHS
initiated an investigation with assistance from CDC to characterize
the magnitude of the outbreak and assess potential animal reservoirs
and peridomestic factors that might have contributed to disease. This
report summarizes the clinical and environmental findings of that
investigation. 33 confirmed cases involved illness comparable to that
associated with previous outbreaks of murine typhus. Illness ranged
from mild to severe, with 73 percent of patients requiring
hospitalization. Delayed diagnosis and administration of no or
inappropriate antibiotics might have contributed to illness severity.
Environmental investigation suggested that opossums and domestic
animals likely played a role in the maintenance and spread of _R.
typhi_; however, their precise role in the outbreak has not been
determined. These findings underscore the need to increase awareness
of murine typhus and communicate appropriate treatment and prevention
measures through the distribution of typhus alerts before and
throughout the peak vector season of March to November.

Murine typhus is a reportable condition in Texas, and health-care
providers are required to report any suspected cases to the local
health department through the National Electronic Disease
Surveillance System within 1 week of detection. The 1st 2 case
reports associated with this outbreak were received in April 2008. 14
more reports were received in May and June [2008]. Receipt of 8
additional case reports in July 2008 prompted ATCDHHS to seek
assistance from TDSHS. On 8 Aug 2008, CDC was requested to assist in
the investigation. An additional 29 cases were reported during the
course of the investigation, which concluded on 1 Dec 2008.

Clinical and laboratory investigation
-------------------------------------
Of the 53 cases reported during 2008, 33 (62 percent) were laboratory
confirmed. _R. typhi_ infection was confirmed by PCR and sequence
analysis of DNA for 1 patient. Illness onset dates for confirmed
cases ranged from March to November [2008], with the highest number
of cases occurring in June (n = 7; 21 percent). Most confirmed cases
occurred during May-August (70 percent). The median age of patients
was 37 years (range: 7-64 years). More males (55 percent) than
females (45 percent) had confirmed illness. Patients were
predominantly white (97 percent); 3 percent were black. Because data
on ethnicity were not consistently available in the patient charts,
ethnicity was not included in the analyses. The most commonly
reported symptoms in confirmed cases were fever (100 percent),
malaise (76 percent), headache (73 percent), chills (61 percent),
myalgia (61 percent), anorexia (58 percent), nausea (52 percent),
rash (46 percent), vomiting (42 percent), and diarrhea (36 percent).

No deaths were attributed to murine typhus; however, 73 percent of
the confirmed patients were hospitalized, and 27 percent were
admitted to intensive care units. Only 51 percent (n = 17) of
confirmed patients were prescribed antibiotics. 15 (88 percent)
patients who received antibiotics received the recommended treatment
with doxycycline; 2 received an antibiotic other than doxycycline.
The median time from symptom onset to prescription of antibiotics was
8 days (range: 1-19 days).

Blood chemistry results revealed that 70 percent of confirmed
patients experienced impaired liver function, as indicated by
elevated aspartate aminotransferase, alanine transaminase, alkaline
phosphate, bilirubin, and/or lactate dehydrogenase levels. Elevated
creatinine and/or decreased albumin or serum protein levels indicated
impaired kidney function in 21 percent of patients. Among the 33
patients 24 percent had low platelet counts, and 24 percent had
anemia. Leukocytosis and leukopenia were each observed in 6 percent
of patients.

Among the 12 confirmed patients whose discharge/outpatient follow-up
laboratory results were available during the clinical investigation
(12 Aug-1 Dec 2008), most laboratory values were normal for
leukocytes (80 percent), bilirubin (77 percent), and creatinine (92
percent). However, low albumin and serum protein levels persisted in
58 percent of cases, and impaired liver function persisted in most
cases; aspartate aminotransferase levels remained elevated in 83
percent of cases, and alanine transaminase levels remained elevated
in 92 percent. No additional follow-up by TDSHS or CDC is anticipated.

Confirmed patients were clustered in central Austin (Figure 2 [for
figure, see original report at the source URL above. - Mod.LL]). 2
patients resided north of Austin but worked or engaged in
recreational activities in central Austin. Among the 33 confirmed
cases, only 2 patients (6 percent) noted flea bites or flea exposure
during the 2 weeks before illness onset. Recent close exposure to
opossums or rats was reported by 18 percent and 15 percent of
patients, respectively.

Environmental investigation
---------------------------
During 12-19 Aug 2008, CDC conducted an environmental investigation
with assistance from ATCDHHS. Environmental site assessments were
conducted at the homes of 20 patients with confirmed cases. Blood and
arthropod specimens were collected from 26 domestic pets (cats and
dogs), and postmortem blood and tissue specimens were collected from
31 wild animals trapped at patients' home sites. Separate blood
samples were obtained from each animal for serologic and PCR testing.

On average, 5 fleas were collected from each opossum, and 1 or 2 from
each raccoon, cat, and dog. All animal and arthropod specimens were
tested for evidence of _R. typhi_ and _Rickettsia felis_ DNA by PCR
and for seroreactive antibodies to _R. typhi_ antigen using
immunofluorescence assay.

Most patients with confirmed cases (n = 27; 82 percent) resided in
homes with yards bordered by thick vegetation; 79 percent owned a dog
or cat, but only 42 percent (n = 14) reported regularly administering
flea or tick preventatives. 19 (95 percent) of the 20 households
assessed had obvious evidence of wildlife or wildlife attractants on
the property (such as, pet food or water dishes outside the home or
unsealed outdoor garbage containers). Among the 57 animals assessed,
only 33 percent (n = 19) had evidence of active murine typhus
infection by serology, as determined using a 1:32 titer threshold.
Antibodies (IgG) to _R. typhi_ were detected in 3 feral cats, 4
domestic dogs, and 12 opossums; none of 4 wild rats or 9 raccoons
tested positive. None of the animal tissue (n = 57) or flea specimens
(n = 139) tested positive for _R. typhi_ or _R. felis_ DNA by PCR.
Seropositive animals were from 5 different postal code areas. Most
seropositive animals (68 percent) were found in the 2 contiguous
postal code areas where the most human cases (36 percent) were reported.

In response to this outbreak, ATCDHHS increased public awareness of
flea borne rickettsiosis via alerts posted on its Internet website.
The alerts included a definition of murine typhus and its symptoms in
addition to descriptions of how the disease is transmitted, treated,
and prevented. Recommended prevention and control measures included
using dog and cat flea preventatives, exterminating household
rodents, eliminating rodent habitats in or near homes, using
pesticides to limit flea infestations, avoiding wild animals
(including feral cats and opossums), and using insect repellents
containing DEET.

[Reported by: Campbell J, Eremeeva ME, Nicholson WL, et al]

Editorial note
--------------
Contemporary reports of murine typhus in the USA are sporadic and
usually limited to southern Texas, southern California, and Hawaii,
where enzootic foci remain and where the disease is reportable. This
cluster of _R. typhi_ cases in Austin during 2008 might represent the
emergence of murine typhus in a new area. Alternatively, _R. typhi_
might have been present in this area in reservoir species but at
levels below a threshold for transmission and detection. In addition,
recent changes in local ecology or transmission dynamics might have
caused the emergence of clinical human cases. The low prevalence of
active murine typhus infection among the animals assessed versus that
in previous studies (33 percent versus 63 percent - 94 percent) (1)
precludes making conclusions about the reservoir species associated
with this outbreak.

Rats are the primary animal reservoir of _R. typhi_ (1); however,
other mammals (including opossums and domestic dogs and cats) can
maintain the disease, as was observed in this outbreak. Few rats were
sampled and evidence of active infection was not found; however, the
67 percent prevalence of seropositivity among opossums points to
their possible role in propagation. Domestic animals also were found
to be seropositive; however, further studies would be needed to
ascertain whether they played a role in propagation of the outbreak.
Although fleas on opossums and cats can be infected with _R. typhi_,
they are more often infected with the related organism _Rickettsia
felis_ (2,3). However, only 1 case of _R. felis_ has been reported in
the USA since 1994 (4). Furthermore, PCR and serologic evidence, in
addition to the moderate to severe clinical course for most cases,
suggest that _R. typhi_ was the cause of this outbreak. Thus, this
outbreak provides documentation of an atypical reservoir and vector
in a suburban murine typhus cycle.

Based on patient symptoms and laboratory findings, the severity of
illness associated with this outbreak appears comparable to previous
murine typhus outbreaks in other areas (5-8). Illness severity ranged
from mild to severe, with complications that required
hospitalization. The patients described in this report experienced
substantial delays in diagnosis, antibiotic initiation (on average 8
days after symptom onset), or lack of antibiotic therapy, which
likely contributed to the high rate of hospitalizations and might
have contributed to illness severity. Delays in murine typhus
treatment can increase duration of symptoms and risk for
complications (such as, seizures, respiratory failure, and persistent
frontal and temporal lobe dysfunction) or death (5,6). Elevated liver
enzymes and decreased platelet counts in a patient with rash illness
should be evaluated for rickettsiosis (5-7). All suspected murine
typhus patients should be treated with doxycycline, with a minimum
recommended course of 7-10 days or at least 3 days after resolution
of fever (9). Health-care providers in emerging or established areas
where murine typhus occurs should initiate treatment for suspected
murine typhus cases on clinical and
epidemiologic considerations without waiting for laboratory
confirmation of the diagnosis (9).

Murine typhus might now be established in the Austin and Travis
County area and should be considered an ongoing public health threat.
As of 14 Sep 2009, a total of 24 new suspected cases had been
reported to ATCDHHS. Illness onsets ranged from 29 Apr 2009 to 29
July 2009. The median age of patients (37 years; range: 3-67 years)
and symptom profile has been similar to 2008 cases. The rate of
hospitalization (54 percent) has been lower, which might be
attributable to increased knowledge of the presentation and
appropriate treatment of the disease as a result of notices from
Texas Medical Society and ATCDHHS public health education web-based
campaigns. Health-care providers should be aware of the potential for
travel-associated exposures among visitors to Austin or other endemic
areas and notify their local or state health officials of suspected
cases of murine typhus.

References
----------
1. Azad AF: Epidemiology of murine typhus. Annu Rev Entomol 1990;35: 553-659.
2. Karpathy SE, Hayes EK, Williams AM, et al: Detection of
_Rickettsia felis_ and _Rickettsia typhi_ in areas of California
endemic for murine typhus. Clin Microbiol Infect. In press 2009.
3. Wiggers RJ, Martin MC, Bouyer D: _Rickettsia felis_ infection
rates in an east Texas population. Tex Med. 2005 Feb; 101(2): 56-8
[abstract available at
<http://www.ncbi.nlm.nih.gov/pubmed/16130886>].
4. Schrieffer ME, Sacci JB Jr, Dumler JS, Bullen MG, Azad AF:
Identification of a novel rickettsial infection in a patient
diagnosed with murine typhus. J Clin Microbiol. 1994 Apr; 32(4):
949-54. [available at
<http://jcm.asm.org/cgi/reprint/32/4/949?view=long&pmid=8027348>].
5. Dumler JS, Taylor JP, Walker DH: Clinical and laboratory features
of murine typhus in south Texas, 1980 through 1987. JAMA. 1991 Sep
11; 266(10): 1365-70 [available at
<http://jama.ama-assn.org/cgi/reprint/266/10/1365>].
6. CDC: Murine typhus - Hawaii, 2002. MMWR 2003; 52: 1224-6 [available at
<http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5250a2.htm>].
7. Whiteford SF, Taylor JP, Dumler SJ: Clinical, laboratory, and
epidemiologic features of murine typhus in 97 Texas children. Arch
Pediatr Adolesc Med. 2001 Mar; 155(3): 396-400 [available at
<http://archpedi.ama-assn.org/cgi/content/full/155/3/396>].
8. Fergie JE, Purcell K, Wanat P, Wanat D: Murine typhus in South
Texas children. Pediatr Infect Dis J. 2000 Jun; 19(6): 535-8
[abstract available at
<http://www.ncbi.nlm.nih.gov/pubmed/10877169>].
9. Dumler JS, Walker DH: _Rickettsia typhi_ (murine typhus). In:
Mandell GL, Bennett JE, Dolin R, eds. Principles and practices of
infectious diseases. 6th ed. Philadelphia, PA: Elsevier Churchill
Livingstone; 2005:2306-2309.

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[Murine typhus is distributed widely throughout the world, especially
in the warm and humid coastal environments of tropic and subtropical
climes. In the developed world, the infection is found along the
eastern coasts of the south Atlantic states in the USA, the
Caribbean, the Pacific coasts of the southwestern USA, as well as
Hawaii. In Europe, it is distributed along the Mediterranean coast as
well as the Atlantic and Mediterranean coasts of Africa.

It is a zoonosis, in which rats function as the disease's
asymptomatic reservoir, and the Oriental rat flea _Xenopsylla
cheopis_ is the most common vector. Although generally coastal in
distribution, the disease may well spread away from the coast via
major routes of transportation. Although rickettsia-infected flea
feces being rubbed into a flea bite appears to be the major vehicle
of transmission to man, flea bites themselves, and aerosolization of
flea feces, may transmit infection as well. - Mod.LL]

[Austin, the seat of Travis County and the capital of the state of
Texas in the South Central United States can be located on the
HealthMap/ProMED-mail interactive map at
<http://healthmap.org/r/00-M>
Travis County can be seen on the map at
<http://en.wikipedia.org/wiki/Travis_County,_Texas>. - Sr.Tech.Ed.MJ]

See Also