An outbreak of relapsing fever unmasked by microbial paleoserology, 16th century, France.

OBJECTIVES: Depicting past epidemics currently relies on DNA-based detection of pathogens, an approach limited to pathogens with well-preserved DNA sequences. We used paleoserology as a complementary approach detecting specific antibodies under a mini line-blot format including positive and negative control antigens. METHODS: Mini line blot assay incorporated skim milk as negative control, Staphylococcus aureus as positive control, and antigens prepared from lice-borne pathogens Rickettsia prowazekii, Borrelia recurrentis, Bartonella quintana, and Yersinia pestis. Paleoserums were extracted from rehydrated dental pulp recovered from buried individuals. Mini line blots observed with the naked eye, were quantified using a scanner and appropriate software. Paleoserology was applied to the indirect detection of lice-borne pathogens in seven skeletons exhumed from a 16th-17th century suspected military burial site (Auxi-le-Château); and 14 civils exhumed from a 5th-13th century burial site (Saint-Mont). Direct detection of pathogens was performed using quantitative real-time PCR. RESULTS: In Auxi-le-Château, paleoserology yielded 7/7 interpretable paleoserums including 7/7 positives for B. recurrentis including one also positive for B. quintana. In Saint-Mont, paleoserology yielded 8/14 interpretable paleoserums and none reacted against any of the four pathogens. Antibodies against R. prowazekii and Y. pestis were not detected. The seroprevalence was significantly higher in the military burial site of Auxi-le-Château than in the civil burial site of Saint-Mont. Real-time PCR detection of B. quintana yielded 5/21 positive (3 at Saint-Mont and 2 at Auxi-le-Château) whereas B. recurrentis was not detected. CONCLUSIONS: Paleoserology unmasked an outbreak of relapsing B. recurrentis fever in one 16th - 17th century military garrison, missed by real-time PCR. Paleoserology offers a new tool for investigating past epidemics, in complement to DNA sequence-based approaches.

Tick-Borne Relapsing Fever in the White Mountains, Arizona, USA, 2013-2018.

Tick-borne relapsing fever (TBRF) is a bacterial infection transmitted by tick bites that occurs in several different parts of the world, including the western United States. We describe 6 cases of TBRF acquired in the White Mountains of Arizona, USA, and diagnosed during 2013-2018. All but 1 case-patient had recurrent fever, and some had marked laboratory abnormalities, including leukopenia, thrombocytopenia, hyperbilirubinemia, and elevated aminotransaminases. One patient had uveitis. Diagnosis was delayed in 5 of the cases; all case-patients responded to therapy with doxycycline. Two patients had Jarisch-Herxheimer reactions. The White Mountains of Arizona have not been previously considered a region of high incidence for TBRF. These 6 cases likely represent a larger number of cases that might have been undiagnosed. Clinicians should be aware of TBRF in patients who reside, recreate, or travel to this area and especially for those who sleep overnight in cabins there.

Genomic blueprint of a relapsing fever pathogen in 15th century Scandinavia.

Louse-borne relapsing fever (LBRF) is known to have killed millions of people over the course of European history and remains a major cause of mortality in parts of the world. Its pathogen, Borrelia recurrentis, shares a common vector with global killers such as typhus and plague and is known for its involvement in devastating historical epidemics such as the Irish potato famine. Here, we describe a European and historical genome of Brecurrentis, recovered from a 15th century skeleton from Oslo. Our distinct European lineage has a discrete genomic makeup, displaying an ancestral oppA-1 gene and gene loss in antigenic variation sites. Our results illustrate the potential of ancient DNA research to elucidate dynamics of reductive evolution in a specialized human pathogen and to uncover aspects of human health usually invisible to the archaeological record.

The centenary of the discovery of trench fever, an emerging infectious disease of World War 1.

In 1915, a British medical officer on the Western Front reported on a soldier with relapsing fever, headache, dizziness, lumbago, and shin pain. Within months, additional cases were described, mostly in frontline troops, and the new disease was called trench fever. More than 1 million troops were infected with trench fever during World War 1, with each affected soldier unfit for duty for more than 60 days. Diagnosis was challenging, because there were no pathognomonic signs and symptoms and the causative organism could not be cultured. For 3 years, the transmission and cause of trench fever were hotly debated. In 1918, two commissions identified that the disease was louse-borne. The bacterium Rickettsia quintana was consistently found in the gut and faeces of lice that had fed on patients with trench fever and its causative role was accepted in the 1920s. The organism was cultured in the 1960s and reclassified as Bartonella quintana; it was also found to cause endocarditis, peliosis hepatis, and bacillary angiomatosis. Subsequently, B quintana infection has been identified in new populations in the Andes, in homeless people in urban areas, and in individuals with HIV. The story of trench fever shows how war can lead to the recrudescence of an infectious disease and how medicine approached an emerging infection a century ago.

Relapsing fever--a forgotten disease revealed.

Borrelial relapsing fever was once a major worldwide epidemic disease that made a significant impact on Livingstone during his epic travels through Africa and throughout Europe. Indeed, the term 'relapsing fever' was first used to describe clinical cases of this disease in Edinburgh. During the last century, we have witnessed the demise of the louse-borne infection, largely through improving standards of living resulting in a reduction in body lice, the vector for Borrelia recurrentis [louse-borne relapsing fever (LBRF)]. The tick-borne zoonotic form of the disease persists in endemic foci around the world [tick-borne relapsing fever (TBRF)]. Indeed, TBRF is reportedly the most common bacterial infection from Senegal and listed within the top ten causes of mortality in children under five in Tanzania. In Ethiopia, LBRF is again within the top ten causes of hospital admission, associated with significant morbidity and mortality. Despite these figures, many now regard relapsing fever as an unusual tropical disease. Certainly, recent cases have been imported following travel from endemic zones. More surprisingly, cases have been reported following family reunions in Colorado, USA. A further case was reported from the Mt Wilson observatory in Los Angeles, USA. In many regions, the infection is zoonotic with natural reservoirs in several vertebrate species. In West Africa, infection is again primarily zoonotic. Whether those species found predominantly in East Africa are zoonoses or are infections of humans alone is still debated, however, the life cycle may be determined by the feeding preferences of their arthropod vectors.

Tick-borne relapsing fever in North America.

Relapsing fever is characterized by recurring episodes of fever and nonspecific symptoms (e.g., headache, myalgia, arthralgia, shaking chills, and abdominal complaints). The illness is caused by an infection from the Borrelia species (spirochetes) that may be acquired through the bite of an infected tick (Ornithodoros species) or contact with the hemolymph of an infected human body louse (Pediculus humanus). In North America, most cases have been acquired in the western United States, southern British Columbia, and few cases have been reported from Mexico. Most cases have been acquired from exposure to rustic tick-infested cabins and caves. This article reviews relapsing fever, especially tick-borne relapsing fever in North America.

[Joseph Désiré Tholozan and the Persian relapsing fever]. / Joseph Désiré Tholozan et la fièvre récurrente de Perse.

In the year 1879, Tholozan seems to have been convinced of the danger caused by the bites of ornithodores in Persia, as a result of very careful observations of sick persons suffering from iranian relapsing fever due to Borrelia persica. Among the ticks collected by him and sent to entomologists in France was the true vector, named Argas (presently Ornithodoros) tholozani by Laboulbene and Megnin. Tholozan's contribution to our knowledge on persian relapsing fever is really important. He was one of the first to provide a good clinical description of the disease and to involve an argasid tick in its transmission. He discovered the real vector species which is now called after him.

[Henry Foley and the discovery in 1908 of the role played by the louse in the transmission of relapsing fever]. / Henry Foley et la découverte du rôle du pou dans la transmission de la fièvre récurrente et du typhus exanthématique.

The author recalls the very fine clinical, epidemiological and experimental work undertaken since 1907 at Beni Ounif de Figuig, south of Oran near the algerian-moroccan border which led Henry Foley and Edmond Sergent to suspect and later demonstrate the exclusive role played by the louse (Pediculus corporis or more precisely P. vestimenti) in the transmission of relapsing fever of which they studied an important epidemic occurring there between 1907-1910. This discovery led them to incriminate also the louse in the transmission of exanthematic typhus of which the epidemiology is practically similar. On the occasion of a tunisian epidemic of relapsing fever Charles Nicolle resumed Sergent's and Foley's work which he contested without any justification. Trying to attribute to himself all the merit of the discovery of the role of the louse in the transmission of relapsing fever, Charles Nicolle quotes Sergent's and Foley's works contesting them with a certain bad faith. In 1912 he mentions only Sergent's and Foley's 1910 works (posterior of only one year to his confirmation of the role of the louse in the transmission of exanthematic typhus) and ignores totally their 1908 preliminary paper. One must therefore give full credit to Henry Foley associated with Edmond Sergent for this essential discovery of the role of the louse in human pathology in which they occupy the first place.

[How the epidemics of typhus and relapsing fever were stopped in Serbia in 1915 year]. / Kako je zaustavljena epidemija pegavog i povratnog tifusa u Srbiji 1915. godine.

Eighty years are passed after the catastrophic epidemics of Typhus and Relapsing Fever in 1915 in Serbia was stopped and put under control. This remarkable achievment was realized in cooperation of the British Military Mission and Serbian health services, one month before the usual seasonal maximum of epidemic wave. The cutting of epidemics was made possible by introducing famous "Serbian barrel" (constructed by Dr Stammers). However, the epidemics of Typhus fever present in the same time in several european countries lasted throughout the whole First World War.

The enlarging spectrum of tick-borne spirochetoses: R. R. Parker Memorial Address.

The author reviews his changing interest in tick-borne spirochetoses during his career (1951-1985) as a medical entomologist at the U.S. Public Health Service's Rocky Mountain Laboratory. The discoveries of relapsing fevers in the western United States in the 1930s and 1940s led to well-supported epidemiologic research, including studies on the relationships between vectors and spirochetes. When tick-borne relapsing fever in the United States was shown to be a relatively rare and readily treatable disease, financial support was withdrawn, and ongoing research was limited or terminated. Interest in relapsing fever spirochetes, particularly the relation to the relapse phenomenon in animal hosts, resurfaced in the 1960s and 1970s with the introduction of immunofluorescence assays and with the development of Kelly's medium for continuous cultivation of certain spirochetes. This interest increased significantly in 1981 when the author discovered a tick-borne spirochete to be the causative agent of Lyme disease and of several clinically related disorders in Europe. The discovery of this agent, now known as Borrelia burgdorferi, has led not only to intensive clinical, epidemiologic, and ecologic investigations in the United States and abroad but also to the identification of molecular and immunochemical techniques necessary for the study of the complex biology of tick-borne spirochetes. Reference is also made to a new species of Borrelia that may be the etiologic agent of epizootic bovine abortion in the western United States.