LOUSE-BORNE RELAPSING FEVER - NETHERLANDS: ASYLUM SEEKERS, ex ERITREA
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International Society for Infectious Diseases
http://www.isid.orgDate: Thu 30 Jul 2015
Source: Eurosurveillance edition 2015; 20(30) [edited]
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21196Louse-borne relapsing fever (_Borrelia recurrentis_) in asylum seekers from Eritrea, the Netherlands, July 2015
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[Authors: Wilting KR, Stienstra Y, Sinha B, Braks M, Cornish D, Grundmann H]
Two
patients from Eritrea, recently arrived in the Netherlands, presented
with fever and were investigated for malaria. Bloodfilms showed
spirochetes but no blood parasites. Louse-borne relapsing fever caused
by _Borrelia recurrentis_ was diagnosed. Treatment was complicated by
severe Jarisch-Herxheimer reactions [inflammatory reaction observed
after antimicrobial treatment of several infectious diseases] in both
patients. Physicians should be aware of the possibility of _B.
recurrentis_ infection in migrant populations who travel under crowded
conditions, especially after passing through endemic areas such as
Ethiopia and neighbouring countries.
_Borrelia recurrentis_ has
for many centuries caused infections of often epidemic proportions known
as relapsing fever. Since the infection is exclusively transmitted by
body lice and humans are their only host, large scale outbreaks are only
expected under circumstances conducive to louse infestation. We here
report the 1st introduction of louse-borne relapsing fever into the
Netherlands after World War II.
Case descriptions
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Patient 1
On
4 Jul 2015, a young adult from Eritrea was referred from the National
Reception Centre for Asylum Seekers (Asielzoekercentrum, AZC) to a
regional hospital in the northern Netherlands with a 5-day history of
headache, dizziness, right upper quadrant pain, myalgia, and fever (39.3
deg C [102.7 deg F]). Malaria was suspected. The patient had been in
the Netherlands for only 2 days after arriving in Europe 14 days
earlier. En route to Europe, they travelled through Ethiopia, Sudan, and
Libya. Previously, they had noticed chills while sheltering in an
unofficial street camp in Rome where they stayed with a small group of
fellow Eritreans before travelling to the Netherlands.
Thick and
thin bloodfilms did not show malaria parasites and commercial malaria
antigen tests were negative. However, filamentous unidentified
structures were reported in the thick film by the laboratory of the
peripheral hospital. The patient received empirical treatment with a
single dose of ceftriaxone (2000 mg intravenously) for suspected
bacterial septicaemia. After administration, their condition
deteriorated and the patient was transferred within the next 2 hours to
the University Medical Center Groningen (UMCG) where they arrived at the
emergency department with headache, peripheral hypothermia (35.3 deg C
[95.5 deg F]), hypotension (systolic/diastolic blood pressure 78/52
mmHg, heart rate of 106 beats per minute), abdominal pain but no
hepatosplenomegaly, and shortness of breath (respiratory rate 23
breaths/min). Laboratory analysis showed leucocytopenia (leucocytes: 1.6
x 10(9)/L, norm: 4.5-10 x 10(9)/L), anaemia (haemoglobin: 6.5mmol/L,
norm: 8.6-11.2 mmol/L) and thrombocytopenia (thrombocytes: 16x10(9)/L,
norm: 150-450x10(9)/L). C-reactive protein (CRP) was 254 mg/L (norm:
less than 1 mg/L). Kidney function was normal. The patient's liver
function tests showed mildly elevated transaminases (alanine
transaminase: 58 U/L, norm: 7-56 U/L; aspartate transaminase: 108 U/L,
norm: 10-40 U/L; alkaline phosphatase: 124 U/L, norm 20-140 U/L;
gamma-glutamyl transferase: 93 U/L, norm 0-51 U/L) and total bilirubin
levels of 38 micromole/L (norm: less than 26 micromol/L) and direct
bilirubin 35 micromol/L (norm: less than 7 micromol/L). Oxygen
saturation was 91 percent (norm: 95-100 percent). Giemsa-stained thick
and thin films revealed spirochetes in large numbers (Figure 1
[available at the source URL]) and no malaria parasites.
Given
the patient's travel history, louse-borne relapsing fever was suspected.
The clinical deterioration was provoked by the ceftriaxone
administration leading to a severe Jarisch-Herxheimer reaction [1].
Treatment was switched to doxycyline 200 mg per day intravenously
intravenously to reduce the risk of relapse [2]. The patient was
transferred to the intensive care unit (ICU) for fluid resuscitation,
cardiac support with noradrenalin, and supportive oxygen delivery via
high flow nose mask.
_B. recurrentis_ was confirmed by 16S rDNA
PCR and sequencing directly from blood 2 days later. The patient stayed
at the ICU for 2 days, made a full recovery and was discharged after 6
days. The body louse _Pediculus humanus humanus_ was recovered from [the
patient's clothing (Figure 2 [available at the source URL]).
Patient 2
On
9 Jul 2015, a 2nd young adult from Eritrea was directly referred by the
responsible physician at the AZC to the UMCG. On arrival, the patient
presented with general malaise, headache, fever (38.5 deg C [101.3 deg
F]) and cough. Blood tests showed elevated inflammatory parameters
(leucocytes: leucocytes: 12.7 x 10(9)/L, CRP: 320 mg/L), normal kidney
function and slightly elevated transaminases, but the blood sample was
haemolytic. Thick and thin films showed spirochetes and treatment was
started with doxycyline 200 mg orally. 2 hours later the patient
developed a severe Jarisch-Herxheimer reaction [that] required admission
to intensive care where they received fluid resuscitation, inotropic
treatment with noradrenalin, and oxygen via a face-mask. _B.
recurrentis_ was confirmed by 16S rDNA sequencing.
The patient
reported symptoms of chills and fever 2 weeks before presentation at our
hospital. Their journey through North Africa followed the same route as
that of Patient 1, but Patient 2 had arrived in Europe a week earlier.
Patient 2 had camped out in the streets for 5 days in Rome (as had
Patient 1). Patient 2 arrived in the Netherlands 2 weeks before
presenting at our hospitals after travelling through Austria and
Germany. The patient made a full recovery and was discharged after 5
days. Lice could not be recovered from the clothing.
Discussion
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_B.
recurrentis_ should be suspected in patients presenting with fever and a
recent history of migration from or through endemic countries
(Ethiopia, Sudan, Eritrea, and Somalia). The infection is transmitted
through body lice (_P. humanus humanus_, formally known as _P. humanus
corporis_), which typically lives and breeds in the seams of clothes but
can occasionally also be found in bed linens. Immigrants may share
their clothing and that can pose an additional risk of transmission. The
incubation period for relapsing fever is usually 4 to 8 days with a
range of 2 to 15 days [3]. It should be noted that head lice (_P.
humanus capitis_), which are not uncommon in Northern Europe, are
incompetent vectors and cannot transmit _B. recurrentis_. The
spirochetes are easily visible under a microscope in a Giemsa-stained
thick or thin blood film as used for the diagnosis of _Plasmodium_ spp
[4]. In our patients, the diagnosis was confirmed in both cases by 16S
rDNA PCR and sequencing from blood.
Published evidence supports a
single dose of tetracycline 500 mg intravenously as the conventional
treatment, but considering the limited availability of this drug,
doxycycline 200 mg can be used as an effective alternative [2,5]. In
young children, pregnant women, or patients with a tetracycline allergy,
erythromycin 500 mg can be used instead [6].
Both patients had
travelled independently along a similar route before arriving in the
Netherlands. Given the incubation period, it cannot be ruled out that
the infection was acquired within Europe. Crucial information about risk
factors such as exact travel history, recollection of louse infestation
or bites and onset of symptoms was, however, impossible to obtain from
our patients. Apart from being very sick and the fact that communication
required an interpreter versed in Tigre our patients appeared to be
traumatised and intimidated and not eager to volunteer information for
fear of legal consequences.
Both patients developed a severe
Jarisch-Herxheimer reaction after starting antibiotic treatment. _B.
recurrentis_ evades host immune defences, resulting in very high
bacterial loads (10(6)-10(8)/microl), and effective antibiotic therapy
is followed by severe reactions characterised by sudden rigors, fever,
and hypotension in virtually all treated patients [3]. Clinical symptoms
are associated with increased plasma concentrations of tumour necrosis
factor alpha (TNF-alpha), interleukin-6 and interleukin-8 [7]. Treating
physicians should be aware of this complication and the chances that ICU
admission may be warranted. It is advised that patients receive 2
well-placed intravenous lines for rapid fluid resuscitation. Treatment
of Jarisch-Herxheimer reaction consists mainly of supportive care.
Corticosteroids seem to have limited beneficial effect but studies
suggests that TNF-alpha blockers may be useful [8].
An ad hoc
survey at the AZC on [16 Jul 2015] found body lice on 2 newly arrived
Eritreans. Since then, all asylum seekers arriving from endemic
countries to the AZC have been segregated into a different compound,
where they turn over all of their personal clothes in exchange for
disposable overalls. Personal clothes are then washed and returned on
the next day. Used overalls and bed linen are subsequently destroyed. In
addition to delousing, all arrivals receive a single dose of ivermectin
as pre-emptive treatment against scabies and Eritreans who arrive with
clinically manifest scabies (about 80 percent of all new arrivals)
receive a 2nd dose a week later. No new cases of _B. recurrentis_
infection have been identified since mandatory delousing was
implemented.
Conclusion
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Because infections with
_B. recurrentis_ pose a significant health risk to other migrants, aid
workers, healthcare personnel, and arguably to the general population,
screening and delousing should be considered for arriving migrants
already at ports of entry into the European Union. Our patients may have
acquired body lice before arriving in Europe but transmission of
infected lice between migrants after arrival in Europe cannot be ruled
out and could pose an additional public health challenge.
[Figures and references are available at the source URL above.]
--
Communicated by:
ProMED-mail
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[Relapsing
fever is a bacterial infection caused certain species of the spirochete
_Borrelia_. These organisms are able to periodically change their
surface protein molecules to evade the host's immune response, thus
causing a relapsing illness. Following an incubation period of about 7
days, the illness is characterized by recurring episodes of high fever,
headache, muscle and joint pain, nausea and vomiting, each episode
lasting several days, followed by a several-day asymptomatic interval.
There may be up to 3-4 recurrences. Complications may include
involvement of the lungs (ARDS; acute respiratory distress syndrome),
central nervous system, spinal cord, eyes, heart, and liver. The
bacteremia is intense (more than 10 000 organisms per ml of blood)
during febrile episodes, which allows detection of organisms on a
Wright-Giemsa stained blood smear. Thick blood smears are more sensitive
than thin smears.
There are 2 types of relapsing fever:
Tick-borne relapsing fever (TBRF) and louse-borne relapsing fever
(LBRF). LBRF is more severe than TBRF, with case-fatality rates without
antimicrobial treatment of 30 to 70 percent in outbreaks. TBRF occurs in
the Western hemisphere, Africa, Asia, the Mediterranean region and the
Middle East. In the western United States, TBRF is usually associated
with sleeping in rustic, rodent-infested cabins in mountainous areas. In
the United States, 3 species, _Borrelia hermsii_, _B. parkerii_, and
_B. turicatae_, transmitted by the bite of soft-bodied ticks (genus
_Ornithodoros_) cause TBRF. A recently discovered _Borrelia_ species,
_B. miyamotoi_, has been found in hard-bodied ticks (_Ixodes_) in
regions where Lyme disease is endemic.
LBRF is caused by a single
species, _B. recurrentis_, transmitted through abraded skin when the
body louse is crushed during scratching. LBRF is endemic in Ethiopia,
Sudan, Eritrea, and Somalia. Outbreaks are found in developing regions
affected by war and in refugee camps characterized by overcrowding and
poor personal hygiene. While mammals and reptiles may serve as a
reservoir for tick-borne _Borrelia_ species, humans are the only host of
_B. recurrentis_.
Treatment of relapsing fever consists of
either a tetracycline (such as, doxycycline), a macrolide (such as,
erythromycin), penicillin, or other beta-lactam antibiotics (such as,
ceftriaxone). LBRF can be treated effectively with a single dose of the
antibiotic (
http://jid.oxfordjournals.org/content/137/5/573),
whereas treatment of TBRF requires 7-10 days to prevent relapse. When
initiating antibiotic therapy, all patients should be observed for a
Jarisch-Herxheimer reaction. The reaction, caused by massive release of
tumor necrosis factor alpha (TNF-alpha), interleukin-6, interleukin-8,
and other cytokines, is manifest by a worsening of symptoms with rigors,
tachycardia, sweating, hypotension, and high fever, occurs in over 50
percent of cases. The Jarisch-Herxheimer reaction can be fatal.
Pretreatment with anti TNF-alpha antibody has been found to suppress
Jarisch-Herxheimer reactions (
http://www.nejm.org/doi/full/10.1056/NEJM199608013350503). Corticosteroids and antipyretic agents have little or no effect (
http://jid.oxfordjournals.org/content/137/5/573 and
http://www.ncbi.nlm.nih.gov/pubmed/6132178), whereas meptazinol, an opioid agonist-antagonist, has been reported to reduce the severity of the reaction (
http://www.ncbi.nlm.nih.gov/pubmed/6132178). Treatment with intravenous fluids and vasopressors to maintain adequate blood pressure may be required. - Mod.ML
