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.

RELAPSING FEVER, A DISAPPEARING CAUSE OF FEVER AND MATERNAL DEATH IN SENGEREMA, TANZANIA, EAST AFRICA.

OBJECTIVE: To study the incidence of tick borne relapsing fever (TBRF) during the last 50 years, once like malaria an endemic disease in Sengerema, Tanzania. DESIGN: By analyzing the annual reports, focusing on the number of admissions, maternal deaths, blood smears of patients with fever for Borrelia. SETTING: Sengerema district, Tanzania. SUBJECT: Admissions in Sengerema Hospital due to TBRF. MAIN OUTCOME MEASURES: From 1960 to 2010, we analyzed the incidence of TBRF. RESULT: Forty annual admissions in the sixties/seventies, 200 in the eighties (range from 37 in 1964 to 455 in 1988), dropping to 30 in the nineties. For the last nine years no Borrelia spirochetes were found in blood smears at the laboratory anymore and no admissions for TBRF were registered. The number of maternal deaths due to relapsing fever decreased simultaneously; the last one recordedwas in 2002. CONCLUSION: During the last century, we have witnessed the disappearing of tick borne relapsing fever in Sengerema. Increase of gold mining, improved local economy, housing and standards of living after the nineties resulted in an almost complete eradication of the incidence of TBRF.

Louse-borne relapsing fever in Ethiopian children: experience of a rural hospital.

We describe the epidemiological and clinical aspects of louse-borne relapsing fever (LBRF) in a series of children attending in a rural hospital in Ethiopia during 1997-2007. From a total of 249 cases of LBRF, 154 (61.4%) were children (<15 years). The most frequent symptoms were: fever, headache, dizziness and musculoskeletal pains. The overall case fatality rate was 2.4 (10% for patients <1.1 years; 3.4% for 1.1 to 4.0 years; and 0% >4.0 years [P = 0.05]). The mortality in children was less than in adults (13.2%) (P = 0.003).

Coinfection with Borrelia turicatae serotype 2 prevents the severe vestibular dysfunction and earlier mortality caused by serotype 1.

BACKGROUND: Relapsing fever (RF) is a multisystemic spirochetal infection caused by different Borrelia species. Studies in our laboratory have shown that disease severity varies depending on the infecting serotype. However, the relative contribution of each serotype to pathogenesis during mixed infections is not known. To investigate this, we compared the outcome of infection with isogenic serotypes 1 (Bt1) or 2 (Bt2) of the RF agent B. turicatae alone or in combination. METHODS: B cell-deficient mice were used for these experiments, to avoid serotype clearance by the host's variable membrane protein-specific antibodies. Observers masked to infection status examined infected and uninfected control mice for clinical disease and functional impairment for up to 65 days. RESULTS: All mice developed persistent infection with the serotypes with which they were originally inoculated. Severe vestibular dysfunction developed in mice infected with Bt1 alone and was associated with increased morbidity and mortality. However, coinfection with Bt2 significantly reduced the severity of vestibular dysfunction and prevented earlier mortality. In contrast, coinfection with Bt1 had little effect on the severe arthritis caused by Bt2 infection. CONCLUSIONS: The manifestations of infection with B. turicatae are significantly influenced by the combination of serotypes present during mixed infection.

Characteristics of louse-borne relapsing fever in Ethiopian children and adults.

Louse-borne relapsing fever (LBRF) is endemic in Ethiopia. The epidemiological and clinical aspects of LBRF and the differences between the infection in children and that in adults were investigated in a rural hospital in Ethiopia. During the 5-year study (1997-2002), 197 patients had a confirmed diagnosis of LBRF. Most (62.1%) of the cases were children under 15 years of age. The adult cases (i.e. those aged > or =15 years) were far more likely to present with headache (76.9% v. 40%; P <0.001), musculo-skeletal pains (61.5% v. 30.5%; P <0.001), dizziness (64% v. 39%; P =0.002) and bleeding (16.9% v. 3.8%; P =0.005) than the paediatric. The overall level of case fatality was 6.4%. Death appeared to be significantly associated with adulthood (P =0.01), delay in consultation (P =0.026) and the presence of vomiting (P =0.023). LBRF is clearly still a public-health problem in Ethiopia, where the clinical manifestations of the disease differ according to the age of the case.

Relapsing fever in Gondar, Ethiopia.

OBJECTIVE: To determine the magnitude of relapsing fever, the rate of Jarisch-Herxheimer reaction (JHR) and its outcome and compare these parameters between adults and children in the same setting, time period and more or less similar management. DESIGN: A retrospective descriptive record analysis. SETTING: Gondar College of Medical Sciences (GCMS) hospital, paediatric ward and medical wards, northwest Ethiopia. SUBJECTS: Clinical records of 262 patients discharged with confirmed diagnosis of primary relapsing fever admitted between September 1995 and August 2000. RESULTS: Of the 13,177 patients admitted during the study period, 262 (1.99%) had a primary diagnosis of relapsing fever of which 70.6% were males. Children below 14 years of age comprised 41.2%. Of the total admissions, 83.6% were from Gondar town and the rest from outside. JHR was observed in 31.7% of the patients. The overall case fatality rate was 4.6%. Bad outcome was observed more frequently in adult patients. CONCLUSIONS AND RECOMMENDATIONS: Relapsing fever is still a public health problem. Because of the potential danger of the epidemic and its outcome it should not be neglected. Preventive programmes must be integrated with other services. Though the JHR is the most feared part of the management of relapsing fever, if health personnel are trained and competent, the management of relapsing fever can be delegated to the peripheral health workers, especially when it occurs in children. Moreover, the reason for bad outcome in adult patients than in children needs to be established.

Tetracycline versus penicillin in the treatment of louse-borne relapsing fever.

A prospective study of 120 louse-borne relapsing fever (LBRF) patient admitted to Mekele Regional Hospital, Tigray, Ethiopia from September to November 1991 was done. The patients were assigned systematically to a single dose of either tetracycline or procaine penicillin (sixty each). Doses given were oral tetracycline 250 mg or intramuscular procaine penicillin 200,000 units for children ages 12 years or less, and 500 mg or 600,000 IU for adults, respectively. The aim of this study was to compare the clinical effectiveness of tetracycline to that of procaine penicillin. Both drugs induced a Jarisch-Herxheimer (JH) like reaction, which was clinically similar in the two treatment groups, but peaked later and was more prolonged in the patients treated with procaine penicillin. Spirochaetes cleared more slowly and relapses were noticed only in the procaine penicillin treated group. Thus, tetracycline is recommended as first choice therapy and a single dose is sufficient for treatment of LBRF patients.

Mortality in high risk patients with tick-borne relapsing fever analysed by the Borrelia-index.

Clinical findings on 25 patients with a high spirochaetemia are presented. The diagnosis was established by demonstration of Borrelia spirochaetes in the thick blood smear and a Borrelia-index was estimated to calculate the density of the spirochaetemia. Causes of death were septicaemia (3x), severe spirochaetemia in a neonate (1x), and successive relapses in complicated cases without adequate treatment (2x). The results show a positive correlation between the degree of spirochaetemia and severity of complications and the Borrelia-index shows to have a prognostic value.

Louse-borne relapsing fever: I. A clinical and laboratory study of 363 cases in the Sudan.

Louse-borne relapsing fever seems to have become endemic in the southern Sudan. The epidemic history of the disease in the Sudan is reviewed. We have studied 363 Sudanese patients involved in an outbreak of louse-borne relapsing fever in Khartoum (Sudan) between January and June 1974. 318 of the 363 patients were new immigrants from the soughern Sudan to Khartoum. The clinical presentation varied. The common clinical fetures of the disease were: fever (94%), headache (85%), hepatosplenomegaly (74%), body and joint pains (66%), abdominal pain and tenderness (63%), jaundice (46%) and epistaxis (40%). Thrombocytopenia was common. Biochemical evidence of hepatocellular and renal damage was present in most patients. The mortality rate was 5-5% with treatment. Post-mortem examination was performed on six cases. The organs predominantly involved were the liver, spleen, brain and lungs. The common causes of death were severe hepatic damage, lobar pneumonia, subarachnoid haemorrhage and splenic rupture.