LOUSE-BORNE RELAPSING FEVER - NETHERLANDS: ASYLUM SEEKERS, ex ERITREA
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Date: Thu 30 Jul 2015
Source: Eurosurveillance edition 2015; 20(30) [edited]
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21196


Louse-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.]

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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