Jarisch-Herxheimer Research Articles

Tick‐Borne Relapsing Fever in the Northwestern United States and Southwestern Canada

Records from 182 cases of tick-borne relapsing fever (TBRF) were reviewed. In confirmed cases, there was febrile illness, and spirochetes were identified on peripheral blood preparations. In probable cases, there were clinical features of TBRF and either the same exposure as a confirmed case or serological (indirect fluorescent antibody test and western blotting [WB]) evidence of infection with Borrelia hermisii. Sera also were tested for antibody to Borrelia burgdorferi. We identified 133 confirmed and 49 probable cases of TBRF. A Jarisch-Herxheimer reaction was reported in 33 (54.1%) of 61 cases for which this information was available. Most patients who had antibodies to B. hermsii were serologically positive for B. burgdorferi, and WB demonstrated false positivity of testing for B. burgdorferi. Thirty-five (21%) of 166 cases were unreported to public health authorities. In 52 cases, there were more than two relapses before the diagnosis. This study demonstrates that TBRF is underrecognized and underreported and may be falsely identified as Lyme disease.

Tick-borne relapsing fever and pregnancy outcome in rural Tanzania.

To assess the impact of tick-borne relapsing fever (TBRF) on the outcome of pregnancy. Case control study of 137 pregnant women (cases) and 120 non-pregnant women (controls) with TBRF between 1985 and 1995. A rural hospital in Tabora Region, Tanzania. Risk of birth during the attack of TBRF was 58.0%, with an extremely high perinatal mortality of 436 per 1000 births. The total loss of pregnancies including abortions was 475. per 1000. Case-fatality rate in pregnant women was 1.5%, compared to 1.7% in the non-pregnant women. A Jarisch-Herxheimer reaction was seen in 1.5% of the cases and in 1.7% of controls. Relapse rate was 3.6%, compared to 1.7% in non-pregnant women. Pregnant women with TBRF show higher densities of spirochetes than non-pregnant women (p < 0.001). The risk of delivery during the attack was positively correlated to increasing density of the spirochetemia (p < 0.001) and to gestational age (p < 0.001). Perinatal death was related to low birthweight (p < 0.001) and low gestational age (p < 0.001) and not to degree of spirochetemia. The extremely high perinatal mortality rate during an attack asks for prevention and early effective management of TBRF. This is a challenge where access to health services in rural areas of developing countries is hampered by many factors.

Systemic Reaction in patients Treated with Cefotaxime for Lyme Disease

Starting in 1989, adverse reaction reports from the United States noted the occurrence of a new systemic reaction, also referred to as “delayed Jarisch-Herxheimer reaction,” in patients treated with cefotaxime for Lyme disease. This study was undertaken to investigate whether this reported systemic reaction could be considered a new adverse drug reaction to cefotaxime or expression of the underlying Lyme disease. All spontaneous adverse reaction reports received by Hoechst AG from the United States within the period January 1, 1987, to December 31, 1993, were reviewed. An operational definition of the observed systemic reaction was established, and reports were classified in five categories according to probability of representing a case of the reaction: certain, possible, unlikely, highly unlikely, or excluded. A strong association between Lyme disease as the indication for cefotaxime treatment and the systemic reaction was detected: 30 (97%) of 31 cases identified as certain were treated for Lyme disease, as opposed to 27 (90%) of 30, 31 (69%) of 45, 65 (39%) of 167, and 42 (11%) of 392 of those identified, respectively, as possible, unlikely, highly unlikely, and excluded (P < .001 and significant linear trend). This suggests that the new reported systemic adverse event may not be due to cefotaxime on its own but that it may represent either a combined effect of the drug and disease or persistent symptoms of the underlying Lyme disease not resolved by antibiotic therapy. The possibility of an effect of long treatment duration of cefotaxime cannot be completely ruled out but remains very unlikely.

The incidence of the jarisch-herxheimer reaction and fetal monitoring changes in pregnant patients receiving syphilotherapy

The incidence of the jarisch-herxheimer reaction and fetal monitoring changes in pregnant patients receiving syphilotherapy

Prevention of Jarisch–Herxheimer Reactions by Treatment with Antibodies against Tumor Necrosis Factor α

In patients with louse-borne relapsing fever (Borrelia recurrentis infection), antimicrobial treatment is often followed by sudden fever, rigors, and persistent hypotension (Jarisch-Herxheimer reactions) that are associated with increases in plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-6, and interleukin-8. We attempted to determine whether sheep polyclonal Fab antibody fragments against TNF-alpha (anti-TNF-alpha Fab) could suppress the Jarisch-Herxheimer reaction. We conducted a randomized, double-blind, placebo-controlled trial in 49 patients with proven louse-borne relapsing fever. Immediately before the intramuscular injection of penicillin, the patients received an intravenous infusion of either anti-TNF-alpha Fab or a control solution. Ten of the 20 patients given anti-TNF-alpha Fab had Jarisch-Herxheimer reactions with rigors, as compared with 26 of the 29 control patients (P = 0.006). The controls had significantly greater mean maximal increases in temperature (1.5 vs. 0.8 degrees C, P < 0.001), pulse rate (31 vs. 13 per minute, P < 0.001), and systolic blood pressure (25 vs. 15 mm Hg, P < 0.003), as well as higher mean peak plasma concentrations of interleukin-6 (50 vs. 17 micrograms per liter) and interleukin-8 (2000 vs 205 ng per liter) (P < 0.001 for both comparisons). Levels of TNF-alpha were undetectable after treatment with anti-TNF-alpha Fab. Pretreatment with sheep anti-TNF-alpha Fab suppresses Jarisch-Herxheimer reactions that occur after penicillin treatment for louse-borne relapsing fever, reduces the associated increases in plasma concentrations of interleukin-6 and interleukin-8, and may be useful in other forms of sepsis.

The Jarisch-Herxheimer Reaction In Pregnancy: A Nursing Perspective

The Jarisch-Herxheimer reaction is a systemic event that can occur after the first dose of penicillin administration during treatment of syphilis. This article presents a case report of the Jarisch-Herxheimer reaction in a woman who was treated for syphilis at 27 weeks gestation. The proposed pathophysiology of the reaction is described, and complications of this reaction during pregnancy are reviewed. Recommendations for the nursing care of women treated for syphilis are provided.

Ocular manifestations and treatment of Lyme disease.

Ocular manifestations in Lyme disease have been considered rare. In surveys and epidemiologic studies the possibility of ocular Lyme disease has usually not been taken into account. Patients with late ocular. Lyme disease may be seronegative by routine enzyme-linked immunosorbent assays, but immunoblot or detection of Borrelia DNA by polymerase chain reaction may help in diagnosing those cases. An ophthalmologist may suspect the diagnosis of Lyme disease in inflammatory ocular syndromes with unusual biomicroscopic or angiographic findings. Intraocular Lyme disease is usually treated with intravenous ceftriaxone or cefotaxime. Jarisch-Herxheimer reaction may occasionally complicate the antibiotic treatment of ocular manifestations. Overtreatment with ceftriaxone should be avoided because of a possibility of biliary complications.

Reactivation of healed primary syphilitic ulcer: a manifestation of febrile Herxheimer reaction in secondary syphilis.

No abstract available.

Evaluation of the detection of Borrelia burgdorferi DNA in urine samples by polymerase chain reaction.

It is difficult in some cases to identify an infection caused by Borrelia burgdorferi and to monitor the effect of therapy. Seropositivity will persist even after successful treatment and therefore may suggest ongoing infection. For direct detection of B. burgdorferi DNA in human urine samples, the polymerase chain reaction (PCR) was evaluated. A published primer system was selected, which amplifies a 259 bp fragment from the gene encoding the 23S rRNA. The lower detection limit of the primer system was 10 fg of extracted B. burgdorferi DNA. Several methods for the pretreatment of urine samples were tested. Of these, the Geneclean kit (Bio 101, USA) showed the best results. A total of 114 urine samples from 74 patients belonging to three clinical groups was investigated: (i) 51 samples from 26 patients with active Lyme disease, (ii) 36 samples from 27 patients with previous infection but no symptoms at the time the urine was collected, and (iii) 27 samples from 21 seronegative control patients without Lyme disease. B. burgdorferi DNA was detected in 25 urine samples of 17 patients with active disease, whereas 26 samples from this group of patients were negative. Only one asymptomatic case with previous infection showed a positive result, and the urine samples of the patients without Lyme disease were uniformly negative. Two of four patients from whom samples before and directly after onset of therapy were available converted from negative to positive PCR results after initiation of therapy, accompanied by the symptoms of a Jarisch-Herxheimer reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibiotic-Induced Release of Endotoxin A therapeutic Paradox

There is clear experimental evidence that antibiotics increase the bioavailability of endotoxin from Gram-negative bacteria. In this review, data for 2 variables, level of endotoxin and level of bacteria, at the time point closest to 2 hours post-antibiotic exposure were abstracted as a change from baseline readings from each available study, to enable presentation in a graphical overview. This overview indicates that the phenomenon is not limited to beta-lactam agents nor is it apparent only for the more rapidly bactericidal agents. However, evidence that this phenomenon is of clinical importance is scant. With the Jarisch-Herxheimer reaction (JHR), there is clear evidence for an acute deterioration with the initiation of antibiotic therapy and yet uncertainty as to the nature of the bacterial mediator(s) of this reaction. There is no evidence to support the commonly stated concern that therapy with antibiotics with a more rapid bactericidal action may result in the sudden lysis of bacteria with the release of cell wall components and cause a deterioration that might be avoidable through the use of antibiotics with a slower time course of action.

Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans

A randomized, multicenter, investigator-blinded clinical trial was undertaken in order to compare the efficacies of cefuroxime axetil and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans. A total of 232 patients with physician-documented erythema migrans were treated orally for 20 days with either cefuroxime axetil, 500 mg twice daily (119 patients), or doxycycline, 100 mg three times daily (113 patients), and clinical evaluations were conducted during treatment (8 to 12 days) and at 1 to 5 days and 1, 3, 6, 9, and 12 months posttreatment. Patients were assessed as to the resolution of erythema migrans and of the signs and symptoms related to early Lyme disease as well as to the prevention of late Lyme disease. A satisfactory clinical outcome (success or improvement) was achieved in 90 of 100 (90%) evaluable patients treated with cefuroxime axetil and in 89 of 94 (95%) patients treated with doxycycline (difference, -5%; 95% confidence interval, -12 to 3%). Patients with paresthesia, arthralgia, or irritability at enrollment were at higher risk for an unsatisfactory clinical outcome at 1 month posttreatment. Of the patients with satisfactory outcomes at 1 month posttreatment who were evaluable at 1 year posttreatment, a satisfactory outcome was achieved in 62 of 65 (95%) and in 53 of 53 (100%) patients treated with cefuroxime axetil and doxycycline, respectively (difference, -5%; 95% confidence interval, -10 to 4%). Twenty-eight percent of patients treated with doxycycline and 17% of those treated with cefuroxime axetil had one or more drug-related adverse events (P = 0.041). Doxycycline was associated with more photosensitivity reactions (6% compared with 0% for patients treated with cefuroxime axetil; P=0.006), and cefuroxime axetil was associated with more cases of diarrhea (5% compared with 0% for patients treated with doxycycline; P=0.030). Jarisch-Herxheimer reactions occurred in 12% of the patients in each treatment group. In summary, cefuroxime axetil is well tolerated and appears to be equally as effective as doxycycline in the treatment of early Lyme disease and in preventing the subsequent development of late Lyme disease.

Sustained cellular immune responses to Borrelia burgdorferi: lack of correlation with clinical presentation and serology

Fifty-one patients with erythema migrans were followed up prospectively with serial clinical evaluations, serologic determinations for antiborrelial antibodies, and lymphocyte stimulation responses to Borrelia burgdorferi antigens to determine (i) the factors associated with sustained cellular immune responses and (ii) whether lymphocyte stimulation is a good indicator of prior exposure to B. burgdorferi in patients treated early after erythema migrans. Positive lymphocyte stimulation responses ( > 2 standard deviations above normal control values) were found in 15 (29%) of 51 patients 3 months after treatment for erythema migrans and in 8 (18%) of 44 patients 1 year posttreatment. Heightened lymphocyte responses were not associated with the number or duration of erythema migrans lesions prior to treatment, the mean size of the largest erythema migrans lesion, or the number of symptoms at the time of presentation. The development of Jarisch-Herxheimer reaction, choice of antibiotic, and clinical outcome also were not associated with a positive lymphoproliferation assay result. Changes in the lymphocyte stimulation indices between the two time points assessed (3 months and 1 year posttreatment) also did not correlate with the above variables. When serologic results and lymphoproliferative responses were evaluated as categorical or continuous variables, there were no correlations between values. One year after treatment for early Lyme disease, lymphocyte reactivity is not a good indicator of prior infection with B. burgdorferi.

Leptospirosis Complicated by a Jarisch-Herxheimer Reaction and Adult Respiratory Distress Syndrome: Case Report

Leptospirosis, severe infection due to Leptospira interrogans, is a potentially lethal disease that causes multiple organ failure. In addition to hepatic, renal, and CNS involvement, which are classic complications of leptospirosis, the disease may also be complicated by adult respiratory distress syndrome. Treatment with penicillin may precipitate a severe Jarisch-Herxheimer reaction. The mechanisms of Leptospira-induced toxicity remain obscure. We report a near-fatal case of leptospirosis in a patient who developed a JHR and respiratory failure immediately after initiation of therapy.

Transient Worsening of Optic Neuropathy as a Sequela of the Jarisch-Herxheimer Reaction in the Treatment of Lyme Disease

A 58-year-old woman developed neurologic and neuroophthalmologic manifestations of Lyme disease, including a radiculomyelitis, cranial neuritis and mild right optic neuropathy. Upon treatment with intravenous ceftriaxone a Jarisch-Herxheimer reaction occurred with encephalopathy, mild fever, worsening radiculomyelitis, and deterioration of her visual acuity. Intravenous methylprednisolone was given, and the visual acuity recovered over 72 hours. This case suggests that transient worsening of optic neuropathy can develop as a sequela of the Jarisch-Herxheimer reaction in the treatment of Lyme disease.

Syphilitic Pneumonitis in an HIV-Infected Patient

Pneumonitis and symptomatic hepatitis are very rare complications of syphilis. Symptomatic hepatitis and subclinical reticulonodular pulmonary infiltrates were observed when an HIV-infected patient presented with secondary syphilis. The Jarisch-Herxheimer reaction included a flare of hepatitis symptoms, resembling cholangitis. In a patient with syphilis, it may be appropriate to delay an aggressive evaluation for suspected pneumonitis or cholangitis pending the outcome of specific antitreponemal therapy.

Changes in circulating immune complexes during the Jarisch Herxheimer reaction in secondary syphilis.

A cohort of 16 patients with early secondary syphilis were recruited to investigate the role of circulating immune complexes in the pathogenesis of the Jarisch Herxheimer reaction. Eleven of 16 patients had a reaction (68.75%) following initial therapy, characterised by rash potentiation, pyrexia, cardiovascular changes and a number of less specific symptoms. Circulating immune complexes were measured by a standard polyethylene glycol precipitation method and a new sensitive conglutinin binding assay that measured the proportion of IgG, IgM and IgA in complexes, in the first 8 hours after initial therapy. In the latter assay, resting levels of IgG (range 46-700 micrograms/ml) and IgM (range 100-410 micrograms/ml) containing complexes were raised in all patients prior to treatment, but levels were not predictive of those who subsequently had a Jarisch Herxheimer reaction. All patients having a reaction demonstrated a mean fourfold or greater rise in IgG (mean rise 712 micrograms/ml; range 180-1506 micrograms/ml) and IgM (mean rise 804 micrograms/ml; range 200-1120 micrograms/ml) containing complexes between two and eight hours after initial therapy. No such effect was seen in the five patients having no reaction or in a control subject. All these results were confirmed using the polyethylene glycol precipitation method for complex detection.

Louse-borne relapsing fever in Ethiopian children: a clinical study

An outbreak of louse-borne relapsing fever, caused by the return to their original recruitment areas of soldiers at the end of 30 years of fighting in northern Ethiopia, was reported in the Arsi region. We studied 103 infants and children with louse-borne relapsing fever who were admitted to Asella Hospital between 1 May 1991 and 30 April 1992. Twenty-one per cent of the patients had a clear history of contact with sick ex-soldiers; 42% were students admitted to the hospital following the re-opening of schools after the summer vacation. The common clinical features of the disease were fever in 100%, headache in 84.5%, chills in 74%, abdominal pain in 51%, epistaxis in 20%, hepatomegaly in 26%, splenomegaly in 14%, petechial rash in 34% and jaundice in 10%. Differences in symptoms and signs according to age are described. Observed complications were pneumonia in 14% and central nervous system involvement in 10%. Four children went into deep coma, and two of them died. Severe disease was associated with a high density of spirochaetes in blood smears. Patients were treated with two low doses of penicillin or one dose of penicillin followed by, according to age, chloramphenicol or tetracycline, and with intravenous fluids. The case fatality rate was 1.9%. Jarisch-Herxheimer reactions occurred in 61% of patients. There were relapses in 2.9% of treated patients.

Antibiotic-induced release of endotoxin: a reappraisal.

A three- to 20-fold increase in the total concentration of endotoxin occurs as a consequence of antibiotic action on gram-negative bacteria both in vitro and in vivo. There is considerable overlap between the effect of beta-lactam antibiotics and non-beta-lactam antibiotics. Moreover, there is an unexplained delay between the lethal activity of antibiotics and the release of endotoxin. Hence, the mechanism whereby antibiotic action leads to the release of endotoxin is unclear, and mechanisms other than bacterial lysis warrant consideration. The evidence that the release of endotoxin has clinical importance is conflicting, and the issue is unresolved. However, nonlytic release may have implications for the therapeutic efficacy of antiendotoxin immunotherapy. Although frequently cited in the context of the antibiotic-induced release of endotoxin, a number of important differences pertain to conditions, such as the Jarisch-Herxheimer reaction and the tumor lysis syndrome, for which there is clear evidence of an initial deterioration with effective therapy.

Detection of plasma tumor necrosis factor, interleukins 6, and 8 during the Jarisch-Herxheimer Reaction of relapsing fever.

The Jarisch-Herxheimer Reaction (J-HR) is a clinical syndrome occurring soon after the first adequate dose of an antimicrobial drug to treat infectious diseases such as Lyme disease, syphilis, and relapsing fever. Previous attempts to identify factors mediating this reaction, that may cause death, have been unsuccessful. We conducted a prospective trial in Addis Ababa, Ethiopia on 17 patients treated with penicillin for proven louse-borne relapsing fever due to Borrelia recurrentis to evaluate the association of symptoms with plasma levels of tumor necrosis factor (TNF), interleukins 6, and 8 (IL-6 and -8). 14 of the 17 (82%) patients experienced a typical J-HR consisting of rigors, a rise in body temperature (1.06 +/- 0.2 degrees C) peaking at 2 h, leukopenia (7.4 +/- 0.6 x 10(-3) cells/mm3) at 4 h, a slight decrease, and then rise of mean arterial blood pressure. Spirochetes were cleared from blood in 5 +/- 1 h after penicillin. There were no fatalities, but constitutional symptoms were severe during J-HR. Plasma TNF, IL-6, and -8 were raised in several patients on admission, but a seven-, six-, and fourfold elevation of these plasma cytokine concentrations over admission levels was detected, respectively, occurring in transient form coincidental with observed pathophysiological changes of J-HR. Elevated plasma cytokine levels were not detected in the three patients who did not suffer J-HR. We conclude that the severe pathophysiological changes characterizing the J-HR occurring on penicillin treatment of louse-borne relapsing fever are closely associated with transient elevation of plasma TNF, IL-6, and -8 concentrations.

Doppler systolic-diastolic ratios in pregnancies complicated by syphilis

Maternal infection with syphilis can result in focal areas of vasculitis and, similarly, placental villitis and obliterative arteritis. We hypothesized that Doppler systolic-diastolic ratios (S/Ds) in pregnancies complicated by maternal syphilis infection might reflect an increased resistance to placental perfusion. Doppler velocity waveform analysis was used to study the uterine and umbilical arteries in third-trimester pregnancies complicated by maternal syphilis infection. A control group of similarly studied normal pregnancies was used for comparison. Statistically significant increases were found in the mean S/Ds of both the uterine and umbilical arteries in the syphilis group compared with the normal group, indicating an increased resistance to perfusion of the placenta in pregnancies complicated by syphilis. This difference was even greater in association with the identification of spirochetes in the amniotic fluid by dark-field microscopy, indicating that the S/D results are related to the presence of intrauterine infection. Serial S/Ds in a small subgroup of patients correlated with the clinical courses, including an apparent acute vascular-resistance change associated with treatment, probably due to the Jarisch-Herxheimer reaction. Because of these post-treatment vascular events, the pre-treatment S/D alone may have a limited clinical predictive value for treatment efficacy in congenital syphilis.