Tick-borne infections in children in North America.

PURPOSE OF REVIEW: Because both incidence and awareness of tick-borne infections is increasing, review of major infections and recent advances related to their diagnosis and management is important. RECENT FINDINGS: A new algorithm, termed modified two-tier testing, for testing for antibodies to Borrelia burgdorferi , the cause of Lyme disease, has been approved and may replace traditional two-tier testing. In addition, doxycycline is now acceptable to use for treatment of and/or prophylaxis for Lyme disease for up to 21 days in children of any age. Borrelia miyamotoi , a bacterium in the relapsing fever type of Borrelia, is the first of this type of Borrelia that is transmitted by hard-bodied ticks such as Ixodes scapularis. SUMMARY: Awareness of these infections and advances in their diagnosis and treatment is important to assure the best outcomes for affected patients. Table 1 contains a summary of infections discussed.

Soft Tick Relapsing Fever - United States, 2012-2021.

Soft tick relapsing fever (STRF) (also known as tickborne relapsing fever) is a rare infection caused by certain Borrelia spirochetes and transmitted to humans by soft-bodied Ornithodoros ticks. In the United States, acquisition of STRF is commonly associated with exposure to rustic cabins, camping, and caves. Antibiotic treatment is highly effective for STRF, but without timely treatment, STRF can result in severe complications, including death. No nationally standardized case definition for STRF exists; however, the disease is reportable in 12 states. This report summarizes demographic and clinical information for STRF cases reported during 2012-2021 from states where STRF is reportable. During this period, 251 cases were identified in 11 states. The median annual case count was 24. Most patients with STRF (55%) were hospitalized; no fatalities were reported. The geographic distribution and seasonal pattern of STRF have remained relatively constant since the 1990s. Persons should avoid rodent-infested structures and rodent habitats, such as caves, in areas where STRF is endemic. STRF surveillance, prevention, and control efforts would benefit from a standardized case definition and increased awareness of the disease among the public and clinicians.

Bioactive phytocompounds against specific target proteins of Borrelia recurrentis responsible for louse-borne relapsing fever: Genomics and structural bioinformatics evidence.

Louse-borne relapsing fever (LBRF) with high untreated mortality caused by spirochete Borrelia recurrentis is predominantly endemic to Sub-Saharan Africa and has re-emerged in parts of Eastern Europe, Asia and Latin America due to population migrations. Despite subtractive evolution of lice-borne pathogenic Borrelia spp. from tick-borne species, there has been no comprehensive report on conservation of protein targets across tick and lice-borne pathogenic Borrelia nor exploration of phytocompounds that are toxic to tick against lice. From the 19 available whole genomes including B. recurrentis, B. burgdorferi, B. hermsii, B. parkeri and B. miyamotoi, conservation of seven drug targets (>80% domain identity) viz. 30 S ribosomal subunit proteins (RSP) S3, S7, S8, S14, S19, penicillin-binding protein-2 and 50 S RSP L16 were deciphered through multiple sequence alignments. Twelve phytocompounds (hydroxy-tyrosol, baicalein, cis-2-decanoic acid, morin, oenin, rosemarinic acid, kaempferol, piceatannol, rottlerin, luteolin, fisetin and monolaurin) previously explored against Lyme disease spirochete B. burgdorferi when targeted against LBRF-causing B. recurrentis protein targets revealed high multi-target affinity (2%-20% higher than conventional antibiotics) through molecular docking. However, based on high binding affinity against all target proteins, stable coarse-grained dynamics (fluctuations <1 Å) and safe pharmacological profile, luteolin was prioritized. The study encourages experimental evaluation of the potent phytocompounds and similar protocols for investigating other emerging vector-borne diseases.

When to Think About Other Borreliae:: Hard Tick Relapsing Fever (Borrelia miyamotoi), Borrelia mayonii, and Beyond.

In North America, several hard tick-transmitted Borrelia species other than Borrelia burgdorferi cause human disease, including Borrelia miyamotoi, Borrelia mayonii, and possibly Borrelia bissettii. Due to overlapping clinical syndromes, nonspecific tickborne disease (TBD) testing strategies, and shared treatment approaches, infections with these lesser known Borrelia are likely under-reported. In this article, we describe the epidemiology, clinical manifestations, diagnosis, and treatment of these less common Borrelia pathogens.

Tick borne relapsing fever - a systematic review and analysis of the literature.

Tick borne relapsing fever (TBRF) is a zoonosis caused by various Borrelia species transmitted to humans by both soft-bodied and (more recently recognized) hard-bodied ticks. In recent years, molecular diagnostic techniques have allowed to extend our knowledge on the global epidemiological picture of this neglected disease. Nevertheless, due to the patchy occurrence of the disease and the lack of large clinical studies, the knowledge on several clinical aspects of the disease remains limited. In order to shed light on some of these aspects, we have systematically reviewed the literature on TBRF and summarized the existing data on epidemiology and clinical aspects of the disease. Publications were identified by using a predefined search strategy on electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of TBRF published in English, French, Italian, German, and Hungarian were included. Maps showing the epidemiogeographic mosaic of the different TBRF Borrelia species were compiled and data on clinical aspects of TBRF were analysed. The epidemiogeographic mosaic of TBRF is complex and still continues to evolve. Ticks harbouring TBRF Borrelia have been reported worldwide, with the exception of Antarctica and Australia. Although only molecular diagnostic methods allow for species identification, microscopy remains the diagnostic gold standard in most clinical settings. The most suggestive symptom in TBRF is the eponymous relapsing fever (present in 100% of the cases). Thrombocytopenia is the most suggestive laboratory finding in TBRF. Neurological complications are frequent in TBRF. Treatment is with beta-lactams, tetracyclines or macrolids. The risk of Jarisch-Herxheimer reaction (JHR) appears to be lower in TBRF (19.3%) compared to louse-borne relapsing fever (LBRF) (55.8%). The overall case fatality rate of TBRF (6.5%) and LBRF (4-10.2%) appears to not differ. Unlike LBRF, where perinatal fatalities are primarily attributable to abortion, TBRF-related perinatal fatalities appear to primarily affect newborns.

Borrelia miyamotoi - another emerging tick-borne pathogen.

Borrelia miyamotoi is an emerging tick-borne pathogen phylogenetically belonging to spirochaetes causing relapsing fever. It is primarily transmitted by ticks from the Ixodes ricinus complex, similarly to borreliae causing Lyme borreliosis. Small rodents can serve as reservoir hosts. It is widespread in mild climate areas of the northern hemisphere, with constant low prevalence in ticks, in the range of units of percent. To date more than 200 human cases have been described including five cases of meningoencephalitis in immunocompromised patients. Clinical features of illness are non-specific, characterized by fever, fatigue, chills, headaches, muscles and joint pains. It can be treated with antibiotics. The diagnostic approach includes mainly PCR and serological methods. This review summarizes current knowledge on B. miyamotoi with an emphasis on taxonomy, ecology of vectors and reservoir hosts, geographical distribution, diagnosis and treatment of the disease. The review also highlights the need for an accurate determination of the etiology of the disease and its differentiation from Lyme borreliosis and human granulocytic anaplasmosis.

Louse-borne relapsing fever-A systematic review and analysis of the literature: Part 2-Mortality, Jarisch-Herxheimer reaction, impact on pregnancy.

Louse-borne relapsing fever (LBRF) is a classical epidemic disease, which in the past was associated with war, famine, poverty, forced migration, and crowding under poor hygienic conditions around the world. The disease's causative pathogen, the spirochete bacterium Borrelia recurrentis, is confined to humans and transmitted by a single vector, the human body louse Pediculus humanus corporis. Since the disease was at its peak before the days of modern medicine, many of its aspects have never been formally studied and to date remain incompletely understood. In order to shed light on some of these aspects, we have systematically reviewed the accessible literature on LBRF since the recognition of its mode of transmission in 1907, and summarized the existing data on mortality, Jarisch-Herxheimer reaction (JHR), and impact on pregnancy. Publications were identified by using a predefined search strategy of electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of LBRF published in English, French, German, and Spanish since 1907 were included. Data extraction followed a predefined protocol and included a grading system to judge the certainty of the diagnosis of reported cases. The high mortality rates often found in literature are confined to extreme scenarios. The case fatality rate (CFR) of untreated cases is on average significantly lower than frequently assumed. In recent years, a rise in the overall CFRs is documented, for which reasons remain unknown. Lacking standardized criteria, a clear diagnostic threshold defining antibiotic treatment-induced JHR does not exist. This explains the wide range of occurrence rates found in literature. Pre-antibiotic era data suggest the existence of a JHR-like reaction also in cases treated with arsenicals and even in untreated cases. LBRF-related adverse outcomes are observed in 3 out of 4 pregnancies.

[Borreliosis and relapsing fever]. / Borrélioses et fièvres récurrentes.

BORRELIOSIS AND RELAPSING feverrelapsing fevers borreliosis (RFB) are caused by bacteria of the genus Borrelia, within the spirochete's family, transmitted to Humans by arthropods (lice Pediculus humanus, soft ticks of the genus Ornithodoros, or hard ticks for one of them). The RFB transmitted by body lice is cosmopolitan and occurs during epidemics in the context of major crises (promiscuity, precarious hygiene conditions, food crises, etc.). RFB transmitted by ticks are distributed by region, according to the Borrelia species and the geographical repartition of the tick involved (sporadic transmission). The incubation period varies from 3 to 20 days. The first febrile phase lasts 3 days (1-14 days), followed by a phase of apyrexia with persistence of other clinical signs (skin rash, petechiae, headaches, agitation, polyarthromyalgia, abdominal pain, nausea/vomiting, etc.). The recurrence of fever occurs every 7 days on average. Bacteremia in the blood is abundant during fever allowing direct diagnosis by microscopy, Borrelia PCR or culture on a specific medium when available. The first-line treatment is doxycycline, except in case of neurological involvement (ceftriaxone). The mortality Rate varies from 2 to 5 % depending on the Borrelia Species involved. The outcome is usually good after treatment.

Borrélioses et fièvres récurrentes Les borrélioses récurrentes (br) ou fièvres récurrentes sont dues à des bactéries du genre borrelia, de la famille des spirochètes, transmises à l'homme par des arthro¬podes vecteurs (poux de corps, tiques molles, et tiques dures pour l'une d'entre elles). La br à poux est cosmo¬polite et transmise lors d'épidémies survenant dans le contexte de crises majeures (promiscuité, conditions d'hygiène précaires, crise alimentaire, etc.). Les br à tiques se répartissent par région, selon la borrelia en cause et la distribution géographique de leur tique vec¬trice. Le temps d'incubation varie de 3 à 20jours. La première phase fébrile dure 3jours (1-14jours), suivie d'une phase d'apyrexie avec persistance des autres signes cliniques (rash cutané, pétéchies, céphalées in¬tenses, agitation, polyarthromyalgies, douleurs abdomi¬nales, nausées/vomissements, etc.). La récurrence de la fièvre décrit une périodicité de 7jours en moyenne. La bactériémie est abondante lors des pics fébriles, permet¬tant de poser un diagnostic par examen direct en mi¬croscopie, pcr borrelia ou culture sur milieu spécial, quand celle-ci est possible. Le traitement repose sur la doxycycline, sauf pour les formes neurologiques (ceftriaxone). Le taux de mortalité varie de 2 à 5 % selon la borrelia incriminée. L'évolution est le plus souvent favorable après traitement.

Aggregation of data from 4 clinical studies demonstrating efficacy of single-dose doxycycline postexposure for prevention of the spirochetal infections: Lyme disease, syphilis, and tick-borne relapsing fever.

Single-dose doxycycline, given within 72 hours of exposure, has been evaluated in 4 clinical studies for postexposure prophylaxis of 3 spirochetal infections: Lyme disease, syphilis, and tick-borne relapsing fever. In this study, data from the 4 studies were aggregated using a meta-analytic random-effects approach, with the DerSimonian-Laird method for variance estimation, analyzing a total of 2468 subjects. The findings of this analysis demonstrated an overall efficacy rate for prevention of the 3 spirochetal infections of 78% (95% confidence interval: 50%-91%).

Tick-Borne Relapsing Fever Caused by Borrelia persica in Traveler to Central Asia, 2019.

We report a case of tick-borne relapsing fever caused by Borrelia persica in a traveler returning to Switzerland from central Asia. After the disease was diagnosed by blood smear microscopy, the causative Borrelia species was confirmed by shotgun metagenomics sequencing. PCR and sequencing techniques provide highly sensitive diagnostic tools superior to microscopy.

Doxycycline for Prevention of Spirochetal Infections: Status Report.

Important human infections caused by spirochetal microorganisms include Lyme disease, syphilis, leptospirosis, and tick-borne relapsing fever. Doxycycline prophylactic regimens have been shown to significantly reduce the risk for developing all of these infections in potentially exposed individuals, which is highly clinically relevant as no vaccines to prevent these infections in humans are currently available. Additional data, however, are needed to define more precisely the level of efficacy of the doxycycline prophylactic regimens, especially for Lyme disease and syphilis, infections that can be potentially prevented by a single 200-mg dose of doxycycline given within 72 hours postexposure.

[Relapsing fever after travelling in the tropics; a story with a twist]. / Terugkerende koorts na een reis in de tropen.

BACKGROUND: Relapsing fever is an infectious disease caused by Spirochaetes. The presentation is characterised by recurrent episodes of fever. CASE DESCRIPTION: At the end of her trip through South Africa and Botswana, a 54-year-old woman had symptoms of fever and dry cough. Back in the Netherlands, physical examination at the emergency department did not reveal any abnormalities besides fever. Laboratory investigation found thrombocytopenia and elevated infection markers. Thick blood smear revealed the presence of Spirochaetes. Following a working diagnosis of 'relapsing fever', the patient was treated with doxycycline. There was no Jarisch-Herxheimer reaction. At a follow-up outpatient appointment two weeks later, the patient had fully recovered. CONCLUSION: Relapsing fever is a rare disease without specific symptoms. The diagnosis is therefore easily overlooked. Untreated, mortality is high. During episodes of fever, the diagnosis can be established with a thick blood smear.

Louse-borne relapsing fever (Borrelia recurrentis infection).

Louse-borne relapsing fever (LBRF) is an epidemic disease with a fascinating history from Hippocrates' times, through the 6th century 'Yellow Plague', to epidemics in Ireland, Scotland and England in the 19th century and two large Afro-Middle Eastern pandemics in the 20th century. An endemic focus persists in Ethiopia and adjacent territories in the Horn of Africa. Since 2015, awareness of LBRF in Europe, as a re-emerging disease, has been increased dramatically by the discovery of this infection in dozens of refugees arriving from Africa.The causative spirochaete, Borrelia recurrentis, has a genome so similar to B. duttonii and B. crocidurae (causes of East and West African tick-borne relapsing fever), that they are now regarded as merely ecotypes of a single genomospecies. Transmission is confined to the human body louse Pediculus humanus corporis, and, perhaps, the head louse P. humanus capitis, although the latter has not been proved. Infection is by inoculation of louse coelomic fluid or faeces by scratching. Nosocomial infections are possible from contamination by infected blood. Between blood meals, body lice live in clothing until the host's body temperature rises or falls, when they seek a new abode.The most distinctive feature of LBRF, the relapse phenomenon, is attributable to antigenic variation of borrelial outer-membrane lipoprotein. High fever, rigors, headache, pain and prostration start abruptly, 2-18 days after infection. Petechial rash, epistaxis, jaundice, hepatosplenomegaly and liver dysfunction are common. Severe features include hyperpyrexia, shock, myocarditis causing acute pulmonary oedema, acute respiratory distress syndrome, cerebral or gastrointestinal bleeding, ruptured spleen, hepatic failure, Jarisch-Herxheimer reactions (J-HR) and opportunistic typhoid or other complicating bacterial infections. Pregnant women are at high risk of aborting and perinatal mortality is high.Rapid diagnosis is by microscopy of blood films, but polymerase chain reaction is used increasingly for species diagnosis. Severe falciparum malaria and leptospirosis are urgent differential diagnoses in residents and travellers from appropriate geographical regions.High untreated case-fatality, exceeding 40% in some historic epidemics, can be reduced to less than 5% by antibiotic treatment, but elimination of spirochaetaemia is often accompanied by a severe J-HR.Epidemics are controlled by sterilising clothing to eliminate lice, using pediculicides and by improving personal hygiene.

Síndrome PFAPA: Causa de fiebre recurrente también en adultos / PFAPA síndrome: a cayse of recurrent fever also in adults

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Human Borreliosis Caused by a New World Relapsing Fever Borrelia-like Organism in the Old World.

BACKGROUND: Relapsing fever is an infectious disease previously neglected in Africa, which imposes a large public health burden in the country. We aimed to investigate and report on a case of relapsing fever borreliosis in Zambia. METHODS: A previously unknown Borrelia species was isolated from the blood of a febrile patient. Investigations of the presumptive vector ticks and natural hosts for the Borrelia species were conducted by culture isolation and/or DNA detection by Borrelia-specific polymerase chain reaction. Using culture isolates from the patient and bat specimens, genetic characterization was performed by multilocus sequence analysis based on the draft genome sequences. RESULTS: The febrile patient was diagnosed with relapsing fever. The isolated Borrelia species was frequently detected in Ornithodoros faini (n = 20/50 [40%]) and bats (n = 64/237 [27%]). Multilocus sequence analysis based on a draft genome sequence revealed that the Borrelia species isolates from the patient and presumptive reservoir host (bats) formed a monophyletic lineage that clustered with relapsing fever borreliae found in the United States. CONCLUSIONS: A febrile illness caused by a Borrelia species that was treatable with erythromycin was identified in Zambia. This is the first study to report on relapsing fever Borrelia in Zambia and suggesting the likely natural reservoir hosts of the isolated Borrelia species. Interestingly, the isolated Borrelia species was more closely related to New World relapsing fever borreliae, despite being detected in the Afrotropic ecozone.