# 76 - 190 Relapsing Fever

### 190 Relapsing Fever

TABLE 189-1  Treatment and Chemoprophylaxis of Leptospirosis in 
Adultsa
INDICATION
REGIMEN
Treatment
Mild leptospirosis
Doxycyclineb (100 mg PO bid) or
Amoxicillin (500 mg PO tid) or
Ampicillin (500 mg PO tid)
Moderate/severe 
leptospirosis
Penicillin (1.5 million units IV or IM q6h) or
Ceftriaxone (2 g/d IV) or
Cefotaxime (1 g IV q6h) or
Doxycyclineb (loading dose of 200 mg IV, then 100 mg IV 
q12h)
Chemoprophylaxis
 
Doxycyclineb (200 mg PO once a week) or
Azithromycin (250 mg PO once or twice a week)
aAll regimens are given for 7 days. bDoxycycline should not be given to pregnant 
women or children. cThe efficacy of doxycycline prophylaxis in endemic or epidemic 
settings remains unclear. Experiments in animal models and a cost-effectiveness 
model indicate that azithromycin has a number of characteristics that may make it 
efficacious in treatment and prophylaxis.
of major organ-system failure or lessen its severity. Although stud­
ies supporting antibiotic therapy have produced conflicting results, 
clinical trials are difficult to perform in settings patients frequently 
present for medical care in the later stages of disease. Antibiotics 
are less likely to benefit patients in whom organ damage has already 
occurred. Two open-label randomized studies comparing penicillin 
with parenteral cefotaxime, parenteral ceftriaxone, and doxycycline 
showed no significant differences among the antibiotics with regard 
to complications and mortality risk. Thus ceftriaxone, cefotaxime, 
or doxycycline is a satisfactory alternative to penicillin for the treat­
ment of severe leptospirosis. Antimicrobial susceptibility testing 
is not routine practice in individual cases of leptospirosis; to date, 
however, antibiotic resistance has not been reported in isolates from 
patients or the environment.
PART 5
Infectious Diseases
In mild cases, oral treatment with doxycycline, azithromycin, 
ampicillin, or amoxicillin is recommended. In regions where rick­
ettsial diseases are coendemic, doxycycline or azithromycin is the 
drug of choice. In rare instances, a Jarisch-Herxheimer reaction 
develops within hours after the initiation of antimicrobial therapy.
Aggressive supportive care for leptospirosis is essential and can 
be life-saving. Patients with nonoliguric renal dysfunction require 
aggressive fluid and electrolyte resuscitation to prevent dehydra­
tion and precipitation of oliguric renal failure. Peritoneal dialysis 
or hemodialysis should be provided to patients with oliguric renal 
failure. Rapid initiation of hemodialysis has been shown to reduce 
mortality risk and typically is necessary only for short periods. 
Patients with pulmonary hemorrhage may have reduced pulmonary 
compliance (as seen in ARDS) and may benefit from mechanical 
ventilation with low tidal volumes to avoid high ventilation pres­
sures. Evidence is contradictory for the use of glucocorticoids and 
desmopressin as adjunct therapy for pulmonary involvement asso­
ciated with severe leptospirosis.
■
■PROGNOSIS
Most patients with leptospirosis recover. However, post-leptospirosis 
symptoms, mainly of a depression-like nature, may occur and persist 
for years after the acute disease. Mortality rates are highest among 
patients who are elderly and those who have severe disease (pulmo­
nary hemorrhage, Weil’s syndrome). Leptospirosis during pregnancy 
is associated with high fetal mortality rates. Long-term follow-up of 
patients with renal failure and hepatic dysfunction has documented 
good recovery of both renal and hepatic function.
■
■PREVENTION
Individuals who may be exposed to Leptospira through their occupa­
tions or their involvement in recreational freshwater activities should 

be informed about the risks. Measures for controlling leptospirosis 
include avoidance of exposure to urine and tissues from infected 
animals through proper eyewear, footwear, and other protective equip­
ment. Targeted rodent control strategies have a potential benefit.
Vaccines for agricultural and companion animals are generally 
available, and their use should be encouraged. The veterinary vaccine 
used in each area should contain the serovars known to be present in 
that area in order to prevent vaccine serovar mismatch. Unfortunately, 
some vaccinated animals potentially still excrete leptospires in their 
urine. Commercial vaccines for human leptospirosis are available in 
Japan, China, Cuba, and France. These vaccines, made with bacterins—
inactivated Leptospira—provide short-term, serovar-specific immunity 
but cause strong adverse side effects; both usability and availability 
remain problematic. One of the largest-scale trials of vaccine efficacy 
for leptospirosis in humans has been reported from Cuba. However, 
no conclusions can be drawn about efficacy and adverse reactions 
because of insufficient study design and outcome details. The effi­
cacy of chemoprophylaxis with doxycycline (200 mg once a week) or 
azithromycin (in pregnant women and children) is being disputed, but 
focused pre- and postexposure administration is indicated in instances 
of well-defined short-term exposure (Table 189-1).
Acknowledgment
The authors gratefully acknowledge Dr. Marga G. A. Goris for her sub­
stantial contributions to this chapter in previous editions.
■
■FURTHER READING
Adler A: Leptospira and Leptospirosis. Berlin Heidelberg, SpringerVerlag, 2015.
Azevedo IR et al: Human leptospirosis: In search for a better vaccine. 
Scand J Immunol 98:1, 2023.
de Vries SG et al: Leptospirosis among returned travelers: A GeoSentinel 
Site Survey and Multicenter Analysis−1997−2016. Am J Trop Med 
Hyg 99:127, 2018.
Haake DA, Levett PN: Leptospirosis in humans. Curr Top Microbiol 
Immunol 387:65, 2015.
Levett PN: Leptospirosis. Clin Microbiol Rev 14:296, 2001.
Petakh P et al: Current treatment options for leptospirosis: A minireview. Front Microbiol 15:1403765, 2024.
Sykes JE et al: A global one health perspective on leptospirosis in 
humans and animals. J Am Vet Med Assoc 260:1589,2022.
van Samkar A et al: Suspected leptospiral meningitis in adults: Report 
of four cases and review of the literature. Neth J Med 73:464, 2015.
Vincent AT et al: Revisiting the taxonomy and evolution of pathoge­
nicity of the genus Leptospira through the prism of genomics. PLoS 
Negl Trop Dis 13:e0007270, 2019.
Alan G. Barbour

Relapsing Fever
Relapsing fever is caused by infection with any of several species of 
Borrelia spirochetes. It occurs in three different clinical and epide­
miologic forms: louse-borne relapsing fever (LBRF), soft tick relaps­
ing fever (STRF), and hard tick relapsing fever (HTRF). Physicians in 
ancient Greece distinguished LBRF from other febrile disorders by its 
characteristic clinical presentation: two or more fever episodes sepa­
rated by varying periods of well-being. In the nineteenth century, LBRF 
was one of the first diseases to be associated with a specific microbe 
by virtue of its characteristic laboratory finding: the presence of large 
numbers of spirochetes of the genus Borrelia in the blood.
The host responds with systemic inflammation that results in an 
illness ranging from a flulike syndrome to sepsis. Other manifestations

are the consequences of central nervous system (CNS) involvement 
and disordered hemostasis. Antigenic variation of the spirochetes’ 
surface proteins accounts for the infection’s relapsing course. Acquired 
immunity follows the serial development of antibodies to each of the 
several variants appearing during an infection. Treatment with antibi­
otics results in rapid cure but at the risk of a moderate to severe JarischHerxheimer reaction.
LBRF caused large epidemics well into the twentieth century and 
currently occurs in northeastern Africa and among migrants from that 
area. At present, however, most cases of relapsing fever are tick-borne 
in origin, with transmission from either soft-bodied ticks or hardbodied ticks. Sporadic cases and small outbreaks of STRF are focally 
distributed on most continents, with Africa and Central Asia most 
affected. In North America, the majority of reports of relapsing fever 
have been from the western United States and Canada and northern 
Mexico.
Two other members of the genus, Borrelia miyamotoi and B. lonestari, 
are causes of HTRF, an acute febrile illness with nonspecific constitu­
tional symptoms and occasionally meningoencephalitis.
■
■ETIOLOGIC AGENT
Coiled, thin microscopic filaments that swim in one direction and 
then coil up before heading in another were first observed in the 
blood of patients with relapsing fever in the 1880s. These microbes 
were categorized as spirochetes and assigned to the genus Borrelia. 
The breakthrough cultivation medium was rich in ingredients, ranging 
from simple (e.g., N-acetylglucosamine) to more complex (e.g., serum). 
The limited biosynthetic capacity of Borrelia cells is accounted for by a 
genome content one-quarter that of Escherichia coli.
Like other spirochetes, the helix-shaped Borrelia cells have two 
membranes, the outer of which is more loosely secured than in 
other double-membrane bacteria, such as E. coli. As a consequence, 
fixed organisms with damaged membranes can assume a variety of 
morphologies in smears and histologic preparations. The flagella of 
spirochetes run between the two membranes and are not on the cell 
surface. Although technically gram-negative, the 10- to 20-μm-long 
Borrelia cells, with a diameter of 0.2–0.3 μm, are too narrow to be seen 
by microscopy of Gram-stained slides.
■
■EPIDEMIOLOGY
Borrelia recurrentis, unlike the other relapsing fever Borrelia species, is 
acquired from an insect, the body louse (Pediculus humanus corporis), 
with humans serving as the sole reservoir in its life cycle (Table 190-1). 
Acquisition occurs not from the bite itself but from either rubbing the 
crushed insect’s hemolymph into the bite site or auto-inoculation into 
the conjunctivae or a wound. Although LBRF transmission is currently 
limited to Ethiopia, Eritrea, and Somalia, the disease has had a global 
TABLE 190-1  Relapsing Fever Borrelia Species, by RF Type, Geographic Region, and Vector
SPECIES
RELAPSING FEVER TYPE
REGION(S)
ARTHROPOD VECTOR(S)
B. crocidurae
Soft tick RF (STRF)
West Africa
Ornithodoros sonrai
B. duttonii
STRF
East Africa, southern and central Africa
O. moubata
B. hermsii
STRF
Western North America
O. hermsi
B. hispanica
STRF
North Africa, southern Europe
O. erraticus
B. kalaharica
STRF
West Africa, southern Africa
O. savignyi
B. lonestari
Hard tick RF (HTRF)
Southern and eastern United States
Amblyomma americanum
B. mazzotti
STRF
Mexico, Central America
O. talaje
B. miyamotoi
HTRF
North America, Asia, Europe
Ixodes pacificus, I. persulcatus, I. ricinus, I. scapularis
B. nietonii
STRF
Western North America
O. hermsii
B. persica
STRF
Central Asia, Middle East
O. tholozani
B. puertoricensis
STRF
Central America
O. puertoricensis
B. recurrentis
Louse-borne RF
Africa, globala
Pediculus humanus corporis (human body louse)
B. turicatae
STRF
Southwestern United States, northern Mexico
O. turicata
B. venezuelensis
STRF
Central America, South America
O. rudis
aAlthough transmission is currently limited to Ethiopia and adjacent countries, B. recurrentis infection has had a global distribution in the past, and that potential remains.

FIGURE 190-1  Ornithodoros turicata soft ticks of different ages.
distribution in the past, and that potential remains. Outbreaks of 
LBRF, often in association with typhus, can occur under circumstances 
of famine, refugee migration, war, homelessness, and incarceration. 
LBRF can occur in camps of migrants at a distance from their home 
countries.
The several species of Borrelia that cause STRF have geographic 
distributions that correspond with those of their vectors: soft ticks of 
the genus Ornithodoros (Fig. 190-1). STRF is found on most continents 
but is absent in arctic environments. For most species, the reservoirs 
of infection are small to medium-sized mammals, usually rodents, but 
also pigs and other domestic animals living around human habitats. 
However, one species, Borrelia duttonii in sub-Saharan Africa, is largely 
maintained by tick transmission between human hosts. In North 
America, STRF occurs as single cases or small case clusters through 
transient exposure of persons to tick-infested buildings or caves 
where mammals have nests or sleep. The two main Borrelia species 
involved in North America are Borrelia hermsii and Borrelia nietonii 
in the mountainous west and Borrelia turicatae in arid southwestern 
and south-central regions. The soft tick vectors typically feed for no 
more than 30 min, usually while the victim is sleeping, and then leave 
undetected. Transovarial transmission from one generation of ticks to 
the next means that infection risk may persist in a dwelling long after 
incriminated mammalian reservoirs have been removed.
CHAPTER 190
Borrelia miyamotoi is transmitted to humans from other mammals 
by different species of Ixodes hard ticks (e.g., I. scapularis in the eastern 
United States and I. ricinus in Europe) that also transmit Lyme dis­
ease, babesiosis, anaplasmosis, and a viral encephalitis. B. miyamotoi 
is acquired through outdoor activities and through contact with ticks 
in forested and shrubby areas during recreation, work, or activities 
around the home, similarly to Lyme disease (Chap. 191). Among 
residents of most areas where B. miyamotoi and Borreliella (also called 
Borrelia) burgdorferi coexist, the prevalence of antibodies to the former 
is about one-fourth of that to the latter. In contrast to B. burgdorferi, 
B. miyamotoi is transmitted to the host soon after the tick begins to 
feed, and it may be acquired from tick larvae as well as nymphs and 
adults. A less common cause of HTRF is B. lonestari, which is trans­
mitted by Amblyomma americanum ticks of the southern and eastern 
United States.
Relapsing Fever

■
■PATHOGENESIS AND IMMUNITY
STRF and HTRF spirochetes enter the body in the tick’s saliva with the 
onset of feeding. From an inoculum of a few cells, STRF spirochetes 
proliferate in the blood, doubling every 6 h to numbers of 106–107/mL 
or more. HTRF spirochetes grow more slowly in a mammalian host and 
attain lower peak concentrations in the blood. Borrelia species are extra­
cellular pathogens; their presence inside cells connotes dead bacteria 
after phagocytosis. Binding of the spirochetes to erythrocytes leads to 
aggregation of red blood cells, their sequestration in the spleen and liver, 
and hepatosplenomegaly and anemia. A bleeding disorder is probably 
the consequence of thrombocytopenia, impaired hepatic production of 
clotting factors, and/or blockage of small vessels by aggregates of spiro­
chetes, erythrocytes, and platelets. Some species (e.g., B. turicatae) are 
neurotropic and enter the brain, where they are comparatively sheltered 
from host immunity. Relapsing fever spirochetes can cross the maternalfetal barrier and cause placental damage and inflammation, leading to 
intrauterine growth retardation and congenital infection.

Although Borrelia species do not have potent exotoxins or a lipo­
polysaccharide endotoxin, they have abundant lipoproteins that acti­
vate Toll-like receptors on host cells, which leads to a proinflammatory 
process similar to that in endotoxemia, with elevations of tumor necro­
sis factor α, interleukin 6, and interleukin 8 concentrations.
IgM antibodies specific for the serotype-defining surface lipoprotein 
appear after a few days of infection and soon reach a concentration that 
causes lysis of bacteria in the blood through either direct bactericidal 
action or opsonization. The release of lipoproteins and other bacterial 
products from dying bacteria provokes a “crisis,” during which there can 
be an increase in temperature, hypotension, and other signs of shock. A 
similar phenomenon occurring in some patients soon after the initiation 
of antibiotic treatment is characterized by an abrupt worsening of the 
patient’s condition, which is called a Jarisch-Herxheimer reaction (JHR).
PART 5
Infectious Diseases
■
■CLINICAL MANIFESTATIONS
STRF and LBRF present with the sudden onset of fever. Febrile periods 
are punctuated by intervening afebrile periods of a few days; this pat­
tern occurs at least twice in STRF. The patient’s temperature is ≥39°C 
and may be as high as 43°C. The first fever episode often ends in a 
crisis lasting ~15–30 min and consisting of rigors, a further elevation 
in temperature, and increases in pulse and blood pressure. The crisis 
phase is followed by profuse diaphoresis, falling temperature, and 
hypotension, which usually persist for several hours. In LBRF, the first 
episode of fever is unremitting for 3–6 days; it is usually followed by a 
single milder episode. In STRF, multiple febrile periods last 1–3 days 
each. In both forms, the interval between fevers ranges from 4 to 
14 days, sometimes with symptoms of malaise and fatigue.
The symptoms that accompany the fevers are usually nonspecific. 
Headache, neck stiffness, arthralgia, myalgia, and vomiting may 
accompany the first and subsequent febrile episodes. An enlarging 
spleen and liver cause abdominal pain. A nonproductive cough is com­
mon during LBRF and—in combination with fever and myalgias—may 
suggest influenza. Acute respiratory distress syndrome may occur dur­
ing LBRF or STRF.
On physical examination, the patient with LBRF or STRF may be 
delirious or apathetic. There may be body lice in the patient’s clothes or 
signs of insect bites. In regions with B. miyamotoi or B. lonestari infection, 
a hard tick may be embedded in the skin. Jaundice, epistaxis, and sub­
conjunctival hemorrhages are common during LBRF but not in STRF or 
HTRF. Splenomegaly or spleen tenderness is common in LBRF and STRF.
Localizing neurologic findings are more common in STRF than in 
LBRF or HTRF. In North America, B. turicatae infection has neuro­
logic manifestations, including aseptic meningitis and cranial neuri­
tis, more often than B. hermsii or B. nietonii infection. Unilateral or 
bilateral Bell’s palsy is the most common form of cranial neuritis and 
typically presents in the second or third febrile episode, not the first. 
Visual impairment from unilateral or bilateral iridocyclitis or panoph­
thalmitis may be permanent. In LBRF, neurologic manifestations such 
as altered mental state are thought to be secondary to systemic inflam­
mation or small hemorrhages in the brain rather than to direct invasion 
of the nervous system.

Myocarditis in STRF or LBRF is evidenced by gallops on cardiac 
auscultation, a prolonged QTc interval, and cardiomegaly and pulmo­
nary edema on chest radiography.
General laboratory studies in all forms of relapsing fever are not 
specific. Mild to moderate normocytic anemia is common, but frank 
hemolysis and hemoglobinuria do not develop. Leukocyte counts 
range from slightly elevated to leukopenic. Mild to moderate throm­
bocytopenia is common; platelet counts may fall below 50,000/μL in 
some cases. C-reactive protein and procalcitonin levels are elevated. 
Laboratory evidence of hepatitis can be found, with elevated serum 
concentrations of aminotransferases; the prothrombin and partial 
thromboplastin times may be moderately prolonged.
Analysis of the cerebrospinal fluid (CSF) is indicated in all cases of 
suspected relapsing fever with signs of meningitis or meningoencepha­
litis. The presence of mononuclear pleocytosis and mildly to moder­
ately elevated protein levels justifies intravenous antibiotic therapy in 
relapsing fever.
The manifestations and course of B. miyamotoi disease are not as 
distinctive as those of relapsing fever. The most common presentation 
is acute onset of fever with chills, headache, and myalgias starting 
1–2 weeks after a tick bite. Patients have been hospitalized with a pre­
sumptive diagnosis of undifferentiated sepsis. There may be a second 
fever episode in untreated patients. Meningoencephalitis or meningitis 
was documented in adults with deficiencies in humoral immunity, 
including the effects of anti–B cell antibodies such as rituximab. If 
the patient has coexisting early Lyme disease, there may be erythema 
migrans, the localized skin rash.
■
■DIAGNOSIS
STRF or LBRF should be considered in a patient with the characteristic 
fever pattern and a history of recent exposure—i.e., within 1–2 weeks 
before illness onset—to body lice or soft ticks in geographic areas with 
documented current or past transmission. Because of the longevity 
of the ticks and the transovarial transmission of the pathogen in the 
ticks, a case of relapsing fever may be diagnosed many years after the 
last case reported in that locale. The lice may be on the clothes of a 
migrant, refugee, or unhoused person. While the epidemiologic risks 
for B. miyamotoi HTRF are similar to those for Lyme disease, prompt 
removal of an embedded tick upon discovery may not reduce the risk 
of infection of this pathogen.
The bedrock for laboratory diagnosis of LBRF and STRF remains 
direct detection of the spirochetes by microscopy of the blood. Manual 
differential counts of white blood cells by Wright, Giemsa, or GiemsaWright stain usually reveal spirochetes in thin blood smears if their 
concentration is ≥105/mL and several oil-immersion fields are exam­
ined (Fig. 190-2). The peak density of B. miyamotoi or B. lonestari in 
the blood may not be high enough for use of a blood smear alone for 
diagnosis. For LBRF and STRF, the preferred time to obtain a blood 
specimen is at or just before fever’s peak. Lower concentrations of 
spirochetes may be revealed by a thick blood smear that is treated 
with 0.5% acetic acid before staining. An alternative is a wet mount of 
citrated blood mixed with saline and examined by phase-contrast or 
dark-field microscopy for motile spirochetes.
Polymerase chain reaction (PCR) and similar nucleic acid amplifica­
tion test (NAAT) procedures are increasingly used for examination of 
blood or CSF in cases of suspected relapsing fever. Overall, NAAT is 
more sensitive than thin blood smear, particularly for samples obtained 
between febrile episodes. PCR is the preferred procedure for direct 
detection of B. miyamotoi or B. lonestari in blood or CSF. Culture of 
blood or CSF in Barbour-Stoenner-Kelly broth medium or equivalent 
is an option for isolation of Borrelia species. However, visible growth 
takes several days, and few laboratories offer this service.
Options for serologic confirmation of infection are limited, and 
results may be misleading. Whole cell–based assays, such as enzymelinked immunosorbent assay (ELISA) and the C6 peptide ELISA for 
Lyme disease, may be positive in relapsing fever through antigenic 
cross-reactivities among these spirochetes. A commercially available 
assay based on GlpQ—a protein antigen of STRF, HTRF, and LBRF 
Borrelia species but not of any Lyme disease species—has better

FIGURE 190-2  Photomicrograph of tick-borne relapsing fever spirochete (Borrelia 
turicatae) in a Giemsa-Wright–stained thin blood smear. Included in the figure are a 
polymorphonuclear leukocyte and two platelets.
specificity but commonly is negative at a time when a blood smear or 
PCR assay would be positive. The results of a GlpQ-based assay or an 
indirect immunofluorescence assay of whole cells cannot be used to 
differentiate between different Borrelia species as to etiology. A positive 
IgG immunoassay of a single specimen may be the consequence of a 
past infection and not the present illness.
■
■DIFFERENTIAL DIAGNOSIS
Depending on the patient’s history of residential, occupational, travel, 
and recreational exposures, the differential diagnosis of STRF includes 
one or more of the following infections that feature either periodicity in 
Tick-borne relapsing fever
Louse-borne relapsing fever
Meningitis/encephalitis
Oral
therapy
Sequential
therapy
Intravenous ceftriaxone 2 g qd
or Na penicillin G, 5 million U
q6h for 14 days
First choice
 Age ≥9 years, not pregnant:
  doxcycline, 100 mg bid
 Age <9 years: erythromycin,
  12.5 mg/kg per day
Second choice
 Age ≥9 years, not pregnant:
  tetracycline 500 mg qid
Third choice
 Age ≥9 years: erythromycin,
  500 mg qid
Duration: 10 days
FIGURE 190-3  Algorithm for treatment of relapsing fever. If it is not known whether the patient has tick-borne or louse-borne relapsing fever, the patient should be treated 
for the tick-borne form. The dashed line indicates that central nervous system invasion in louse-borne relapsing fever is uncommon.

the fever pattern or an extended single febrile period with nonspecific 
constitutional symptoms: Rocky Mountain spotted fever and other 
rickettsioses, ehrlichiosis, anaplasmosis, tick-borne viral infection, and 
babesiosis in North America, Europe, Russia, and northeastern Asia. 
STRF with Bell’s palsy may be misdiagnosed as Lyme disease in areas 
endemic for both diseases. Elsewhere in the Americas and Asia and 
in most of Africa, malaria, typhoid fever, typhus and other rickettsio­
ses, dengue, and leptospirosis also may be considered. Other agents 
transmitted by the body louse are Rickettsia prowazekii, the cause of 
typhus, and Bartonella quintana, the cause of trench fever. There may 
be co-infections of malaria, typhus, or typhoid with STRF or LBRF. 

B. miyamotoi infection may coexist with Lyme disease.

TREATMENT
Relapsing Fever
Penicillin and tetracyclines have been the antibiotics of choice for 
LBRF and STRF for several decades. Erythromycin has been a 
long-standing alternative choice. There is no evidence of acquired 
resistance to these antibiotics. Borrelia species are also susceptible 
to second- and third-generation cephalosporins. These spirochetes 
are relatively resistant to rifampin, sulfonamides, and aminoglyco­
sides. Spirochetes are no longer detectable in the blood within a few 
hours after the first dose of an effective antibiotic.
Under conditions of limited resources or in the midst of an 
epidemic, a single dose of antibiotic usually suffices for successful 
treatment of LBRF (Fig. 190-3). For adults, a single dose of oral 
doxycycline (200 mg), oral tetracycline (500 mg), or intramuscular 
ceftriaxone 250 mg for adults and 125 mg for children is effective. The 
corresponding doses for children are oral tetracycline at 12.5 mg/kg, 
oral doxycycline at 5 mg/kg, and intramuscular penicillin G pro­
caine at 200,000–400,000 units. When an adult patient is stuporous 
or nauseated, the intravenous dose of tetracycline is 250–500 mg. 
Tetracyclines are contraindicated in pregnant and nursing women; 
for individuals in these groups who are allergic to penicillin, oral 
erythromycin (500 mg for adults and 12.5 mg/kg for children) is 
an alternative. While there is little reported experience with other 
macrolides, such as azithromycin, these are likely to be as effective 
as erythromycin.
CHAPTER 190
Relapsing Fever
First choice
 Single dose of penicillin G ceftriaxone
   IM 250 mg adults and 125 mg children
  800,000 U adults
  200,000–400,000 U children
 then (4–12 h later)
 Age ≥9 years, not pregnant:
  doxycycline, 100 mg bid or
  tetracycline 500 mg qid
 Age <9 years or pregnant:
  erythromycin, 12.5 mg/kg per day
  or 500 mg qid
Duration: 7 days
Second choice (penicillin allergy):
 erythromycin, 500 mg qid ≥9 years
 or 12.5 mg/kg per day <9 years
Duration: 7 days