Leif Dotevall

Intravenous ceftriaxone compared with oral doxycycline for the treatment of Lyme neuroborreliosis

This prospective, open-label, non-randomized trial at the University Departments of Infectious Diseases in Ljubljana, Slovenia, and Göteborg, Sweden, was conducted to compare the kinetics of the cerebrospinal fluid (CSF) mononuclear cell count after 10–14 d of ceftriaxone or doxycycline for treatment of Lyme neuroborreliosis. 29 patients were treated with intravenous ceftriaxone 2 g daily in Ljubljana and 36 patients with oral doxycycline 400 mg daily in Göteborg. The study protocol included lumbar puncture before and 6–8 weeks after treatment initiation. There was a marked decrease (1.2 log10×106/l) of the median CSF mononuclear cell count following treatment. With the assumption of a linear regression of the logarithmic mononuclear cell counts between the 2 lumbar punctures, no significant difference between the 2 antibiotic treatments could be found. All patients were clinically much improved after treatment. At 6 months follow-up 23 (79%) of the ceftriaxone- and 26 (72%) of the doxycycline-treated patients were completely recovered. Intravenous ceftriaxone or oral doxycycline was found to be effective, safe, and convenient for treatment of Lyme neuroborreliosis.

Late-Onset Posttraumatic Skin and Soft-Tissue Infections Caused by Rapid-Growing Mycobacteria in Tsunami Survivors

BACKGROUND In the tsunami catastrophe in Thailand in 2004, several thousand Swedish tourists were injured, with contaminated crush trauma of the legs being the main cause of injury among the survivors. METHODS Patient and laboratory data for those who received hospital care in Stockholm and Gothenburg and contracted late-onset infections due to rapid-growing mycobacteria were reviewed retrospectively. Also, concomitant infections were recorded. RESULTS Fifteen patients with late-onset skin and soft-tissue infections due to rapid-growing mycobacteria are described here. Mycobacterium abscessus was isolated in 7 cases, Mycobacterium fortuitum was isolated in 6 cases, and Mycobacterium peregrinum and Mycobacterium mageritense were isolated in 1 case each. The infections appeared after a delay of 20-105 days (median, 60 days) after the trauma, targeting undamaged skin located near primary sutured wounds or skin grafts. Antimycobacterial drugs were given to 9 (60%) of the patients. The course of infection was protracted, but all infections due to rapid-growing mycobacteria healed within 12 months. Concomitant subcutaneous infections due to other microorganisms, such as Burkholderia pseudomallei or Cladophialophora bantiana, appeared early or late after the trauma. CONCLUSIONS Repeated cultures of abscess and wound specimens for Mycobacterium species may be needed to find the etiologic agents causing contaminated skin and soft-tissue infections, such as those that developed after traumas that occurred during the tsunami. These cultures are especially necessary when symptoms appear late and when conventional bacterial culture results are negative. A biopsy is recommended for the best yield and for complementary histopathological examination.

Astroglial and neuronal proteins in cerebrospinal fluid as markers of CNS involvement in Lyme neuroborreliosis

Is Lyme neuroborreliosis, even in its early phase, a parenchymatous disorder in the central nervous system (CNS), and not merely a meningitic process? We quantified cerebrospinal fluid (CSF) levels of four nerve and glial cell marker proteins in Lyme neuroborreliosis patients with pretreatment durations of 7–240 days. AH 23 patients had meningo‐radiculitis, and six had objective signs of encephalopathy. Glial fibrillary acidic protein (GFAp) pretreatment levels in CSF, and the light subunit of neurofilament protein (NFL) levels were related to clinical outcome and declined significantly after treatment (P < 0.001 and P < 0.01, respectively). NFL was detectable in 11 out of 22 patients, and pre‐and post‐treatment NFL levels were associated with the duration of neurological symptoms within 100 days prior to treatment. Neuron‐specific enolase (NSE) concentrations also decreased after therapy (P < 0.001), while CSF levels of glial S‐100 protein remained unchanged. The pretreatment duration of disease was related to postinfectious sequelae. GFAp, NSE and NFL levels in CSF are unspecific indicators of astroglial and neuronal involvement in CNS disease. The findings in the present study are in agreement with the hypothesis that early and late stages of Lyme neuroborreliosis damage the CNS parenchyma.

Cerebrospinal fluid and serum neopterin levels in patients with Lyme neuroborreliosis.

SummaryElevated (>3.0 nmol/l) cerebrospinal fluid neopterin concentrations were observed in 20 of 21 patients with Lyme neuroborreliosis compared with three of 11 control patients with headache, back pain or psychoneurotic disorders. Neopterin concentrations were correlated to mononuclear cell counts and protein concentrations in the cerebrospinal fluid (CSF). Following antibiotic treatment, CSF neopterin levels decreased. Serum neopterin levels were not significantly raised in patients with neuroborreliosis when compared to control subjects. Neopterin levels as well as cell count and protein concentration in the CSF are valuable inflammation markers of disease activity in Lyme neuroborreliosis.ZusammenfassungBei 20 von 21 Patienten mit Lyme Neuroborreliose fanden sich erhöhte Spiegel (>3,0 nMol/l) von Neopterin im Liquor; bei Patienten mit Kopfschmerzen, Rückenschmerzen oder neurotischen Störungen war dies nur in drei von elf Fällen nachzuweisen. Es bestand eine Korrelation zwischen dem Liquorgehalt an mononukleären Zellen und Eiweiß. Nach Antibiotikatherapie gingen die Neopterinspiegel zurück. Im Vergleich zu den Kontrollpersonen war bei den Patienten mit Neuroborreliose keine signifikante Erhöhung der Neopterinspiegel im Serum festzustellen. Die Neopterinspiegel im Liquor sind neben den Zellzahlen und der Eiweißkonzentration wertvolle unspezifische Entzündungsmarker und Parameter für die Krankheitsaktivität bei Neuroborreliose.Elevated (>3.0 nmol/l) cerebrospinal fluid neopterin concentrations were observed in 20 of 21 patients with Lyme neuroborreliosis compared with three of 11 control patients with headache, back pain or psychoneurotic disorders. Neopterin concentrations were correlated to mononuclear cell counts and protein concentrations in the cerebrospinal fluid (CSF). Following antibiotic treatment, CSF neopterin levels decreased. Serum neopterin levels were not significantly raised in patients with neuroborreliosis when compared to control subjects. Neopterin levels as well as cell count and protein concentration in the CSF are valuable inflammation markers of disease activity in Lyme neuroborreliosis. Bei 20 von 21 Patienten mit Lyme Neuroborreliose fanden sich erhöhte Spiegel (>3,0 nMol/l) von Neopterin im Liquor; bei Patienten mit Kopfschmerzen, Rückenschmerzen oder neurotischen Störungen war dies nur in drei von elf Fällen nachzuweisen. Es bestand eine Korrelation zwischen dem Liquorgehalt an mononukleären Zellen und Eiweiß. Nach Antibiotikatherapie gingen die Neopterinspiegel zurück. Im Vergleich zu den Kontrollpersonen war bei den Patienten mit Neuroborreliose keine signifikante Erhöhung der Neopterinspiegel im Serum festzustellen. Die Neopterinspiegel im Liquor sind neben den Zellzahlen und der Eiweißkonzentration wertvolle unspezifische Entzündungsmarker und Parameter für die Krankheitsaktivität bei Neuroborreliose.

Pain as presenting symptom in Lyme neuroborreliosis

Neurogenic pain with radiculitis is often the starting symptom in adult patients with tick‐borne Lyme neuroborreliosis and in some cases the only clinical manifestation. Cranial paresis and other neurologic signs usually occur after the onset of pain. The present paper describes four patients who had severe pain as the main presenting symptom of Lyme neuroborreliosis. Opioids had good short‐term effect in two of the cases. Oral doxycycline treatment was used successfully to eliminate the infection.

A food-borne streptococcal sore throat outbreak in a small community

Beta-haemolytic group A streptococci (GAS) is a common cause of sore throat, usually spread person-to-person. Outbreaks related to infected food have more seldom been reported. The bacteria may originate from the throat or from wounds on the hands of persons handling the food. An outbreak in Sätila, Sweden, in April/May 2003 involving 153 individuals who fell ill after eating contaminated ‘sandwich-layer cakes’ was investigated in a descriptive, retrospective cohort study. Questionnaires were distributed, one immediately after the outbreak and one 3 months later. The average attack rate was 72%. 143 individuals sought medical care and 137 were treated with antibiotics. 76 individuals were ill for more than 4days. GAS isolates of identical T-type were obtained from the throats of the patients, wounds on the caterers fingers and also from the cakes. PFGE banding patterns of 14 representative isolates were identical, as well as the emm-sequence type, emm 89, of 3 chosen isolates. The study shows that GAS from a small wound on a finger can cause illness in a large number of individuals. To prevent further outbreaks, it is important to increase public awareness of this type of transmission.

Imported Case of Lassa Fever in Sweden With Encephalopathy and Sensorineural Hearing Deficit

We describe an imported case of Lassa fever with both encephalopathy and bilateral sensorineural hearing deficit. Absence of fever during hospitalization, initially nonspecific symptoms, and onset of hearing deficit in a late stage of disease probably contributed to delayed diagnosis (14 days after admittance to hospital). The pathogenesis of neurological manifestations of Lassa fever is poorly understood and no specific treatment was given. A total of 118 personnel had close contact with the patient, but no secondary cases occurred. This case highlights the importance of considering Lassa fever as a differential diagnosis in patients with recent travel to endemic areas.

Late bacille Calmette-Guérin infection with a large focal urinary bladder ulceration as a complication of bladder cancer treatment.

Study Type – Therapy (case series) 
Level of Evidence 4

Spread of tuberculosis in a high school.

Pulmonary tuberculosis (TB) is a disease of relatively low contagiousness. Close contact for a long period of time is usually required. Children before adolescence rarely spread the disease because they are less likely than adults to have cavitary disease and productive cough. Besides, they lack the tussive force of adults needed to aerosolise Mycobacterium tuberculosis and spread the organism to the surroundings (1 –3). When children reach adolescence, they tend to get more ‘adult-like’ TB and often become more contagious (1). A British study showed a considerably increased risk for both active and latent TB in schoolmates of a 16-year-old index case but not in children in other age groups in the same school (4). Spread from preadolescent children and even an infant have also, but rarely, been described (5–7). With the increasing immigration from endemic to low-incidence countries in Europe spread of TB from active cases to susceptible contacts must always be considered. We describe here spread of TB in a school class. The report is based on work, in all parts performed according to the Swedish Communicable Diseases Act and the declaration of Helsinki. The specific rules and regulations for ethical vetting of research projects were not applicable. The index case was a 15-year-old girl who had moved to Sweden from a high-incidence country a few years earlier. She became ill with a productive cough, which became blood-tinged. Her general condition was relatively good, and she attended classes until admittance to hospital about 1 month after onset of the cough. She had a pulmonary infiltrate in the upper left lobe, and acid-fast bacilli were demonstrated by microscopy of sputum. The diagnosis was confirmed by isolation of M. tuberculosis from sputum. She had no BCG scar, and her mother did not know if she had been vaccinated. Health examination including a tuberculin skin test (TST), which is offered to children and adults coming to Sweden, had not been performed. She was part of a large class with another 48 adolescents of the same age as herself (14–15 years old). The class was divided into four groups depending on subject taught, but the index spent time with all 48 classmates several times every week. Thirty children were of northern European ethnicity (Sweden or Finland), nine had one parent from Sweden or Finland and the other from other countries with higher TB incidence and nine were not of northern European ethnicity. Forty-six children were born in Sweden and two in Southeast Asia. Thirteen of the children born in Sweden (all of mixed or non-Swedish/Finnish ethnicity) had documented BCG vaccination performed in Sweden during the first year of life but only 10 had BCG scars. The two children born in Southeast Asia had typical BCG scars. Thus, 15 children were BCG vaccinated. Due to the higher specificity of interferon-gamma-release assays (IGRA) over TST in particular in vaccinated individuals (8,9), the first author (BT) made the decision to perform an IGRA (Quantiferon-TB Gold in tube, QFT)) instead of TST. The analyses were performed according to the instructions of the manufacturer (Cellestis Ltd, Chadstone, Vic., Australia). One millilitre of blood was collected into each of three different collection tubes, which include Nil Control tube, TB Antigen tube and Mitogen tube (positive control). The sampleswere transported to the laboratory the sameday. At the laboratory, the collection tubeswere incubated at 37°C for 16–20 h and subsequently centrifuged at 2300 g for 15 min. The concentration of interferon gamma in the resulting plasma in the tubes was measured by ELISA and related to a concentration standard. The absorbance was measured in Vmax Kinetic Microplate Reader (Molecular Devices, Sunnyvale, CA, USA), and the OD-values were evaluated using the QFT-TB Gold Analysis Software version 2.50 (Cellestis Ltd, Chadstone, Vic., Australia). Four days after it was known that the index case had smear positive pulmonary TB, the examination of all 48 classmates started. Within 2 weeks, all had been seen at the hospital. All were healthy. Three had positive QFT. Two months later, all initially negative children were tested anew.

Ophthalmological findings in neuroborreliosis - a prospective study performed in western Sweden

To evaluate and follow‐up ophthalmological findings in individuals diagnosed with neuroborreliosis, confirmed by cerebrospinal fluid (CSF) analysis.