Outlook for a dengue vaccine.

Dengue is an increasing medical problem in subtropical and tropical countries. The search for a safe and effective vaccine is complicated by the fact that there are four types of dengue virus and that, if a vaccine is live attenuated, it should be proven not to cause the life-threatening form of dengue, dengue haemorrhagic fever. So far one vaccine candidate, a four-valent chimeric vaccine constructed from a yellow fever vaccine strain, has reached large clinical trials and has been shown to offer protection against dengue types 1, 3 and 54 but not against dengue type 2. It is highly likely that an effective vaccine will be available in the next decade.

Linezolid--a review of the first oxazolidinone.

Linezolid is the first of a truly new class of antibiotics, the oxazolidinones. It acts as an inhibitor of bacterial protein synthesis by blocking the formation of the 70S ribosomal initiation complex. Its activity is bacteriostatic against some species (e.g., enterococci) and bactericidal against others (e.g., pneumococci). The antibacterial spectrum of linezolid includes Gram-positive pathogens and some Gram-negative anaerobic species but not Gram-negative aerobes. Importantly, multi-drug resistant organisms such as methicillin-resistant staphylococci, staphylococci with reduced susceptibility to vancomycin, penicillin- and macrolide-resistant pneumococci and vancomycin-resistant enterococci are fully susceptible to linezolid. Linezolid has almost 100% bioavailability and the area under the plasma concentration curve is identical after oral and iv. administration. This enables initial oral administration of linezolid in those patients who can absorb the drug normally and also an early step-down therapy from iv. to oral. Controlled, randomised clinical studies have documented efficacy and safety of linezolid in hospital- and community-acquired pneumonia, uncomplicated and complicated skin and soft tissue infections and infections caused by vancomycin-resistant enterococci. The safety and tolerability of linezolid are advantageous. Linezolid is a weak and reversible monoamine oxidase (MAO) inhibitor and although no increased frequency of adrenergic or serotonergic adverse events has been reported, it is recommended that linezolid is used with caution in patients treated with other MAO inhibitors.

Characterization of Lyme borreliosis isolates from patients with erythema migrans and neuroborreliosis in southern Sweden.

Southern Sweden is an area of Lyme borreliosis (LB) endemicity, with an incidence of 69 cases per 100,000 inhabitants. The most frequent clinical manifestations are erythema migrans (77%) and neuroborreliosis (16%). There was no record of human Borrelia strains being isolated from patients in this region before the prospective study reported here. Borrelia spirochetes were isolated from skin and cerebrospinal fluid (CSF) from LB patients living in the region. A total of 39 strains were characterized by OspA serotype analysis, species-specific PCR, and signature nucleotide analysis of the 16S rRNA gene. Of 33 skin isolates, 31 (93.9%) were Borrelia afzelii strains and 2 (6.1%) were Borrelia garinii strains. Of six CSF isolates, five (83.3%) were B. garinii and one (16.7%) was B. afzelii. Neither Borrelia burgdorferi sensu stricto strains nor multiple infections were observed. The B. afzelii isolates were of OspA serotype 2. Three B. garinii strains were of OspA serotype 5, and the remaining four strains were of OspA serotype 6. All of the B. garinii strains belonged to the same 16S ribosomal DNA ribotype class. Our findings agree with earlier findings from other geographic regions in Europe where B. afzelii and B. garinii have been recovered predominantly from skin and CSF cultures, respectively. To further study the possible presence in Sweden of the genotype B. burgdorferi sensu stricto, which is known to be present in Europe and to occur predominantly in patients with Lyme arthritis, molecular detection of Borrelia-specific DNA in synovial samples from Lyme arthritis patients should be performed.

Supernatants from Staphylococcus epidermidis grown in the presence of different antibiotics induce differential release of tumor necrosis factor alpha from human monocytes.

Bacterial products from gram-positive bacteria, such as peptidoglycan, teichoic acid, and toxins, activate mononuclear cells to produce tumor necrosis factor alpha (TNF). The present study evaluated the release of soluble cell wall components from Staphylococcus epidermidis capable of inducing TNF after exposure of the bacteria to various antibiotics. A clinical S. epidermidis isolate (694) was incubated with either penicillin, oxacillin, vancomycin, or clindamycin at five times the MIC. Supernatants of the cultures obtained by filtration were added to plastic adherent monocytes in the absence or presence of human serum. After 18 h of incubation, monocyte supernatants were tested for the presence of TNF by enzyme-linked immunosorbent assay (ELISA). Supernatants from bacteria incubated with beta-lactam antibiotics induced higher TNF levels than those obtained from bacteria incubated with culture medium only (no antibiotics), vancomycin, or clindamycin. Human serum potentiated supernatant-induced TNF release, especially in beta-lactam supernatants. The soluble peptidoglycan and teichoic acid contents of supernatants, as estimated by inhibition ELISA and, for peptidoglycan, also by affinity depletion with vancomycin-Sepharose gel, were proportional to TNF release. Differences in the ability of individual antibiotics to generate TNF-releasing products from S. epidermidis were observed, the most potent antibiotics being penicillin and oxacillin.

Symptomatic urinary tract infection in women in primary health care. Bacteriological, clinical and diagnostic aspects in relation to host response to infection.

OBJECTIVE: To evaluate rapid diagnostic tests for bacteriuria in women with symptoms of urinary tract infection (UTI), and to analyse bacteriological and clinical findings in relation to host response to infection. DESIGN: Prospective study of symptomatic UTI in women. SETTING: Primary health care centres. PATIENTS: 819 women with signs and symptoms suggestive of UTI. MAIN OUTCOME MEASURES: History of UTI and clinical findings were recorded. After randomization but before antibiotic treatment, urine specimens were analysed for pyuria by sediment microscopy and for nitrite using a test strip, and cultures were performed. The systemic inflammatory response was assessed by C-reactive protein (CRP), erythrocyte sedimentation rate, and total white blood cell count. RESULTS: The combined use of tests for pyuria and nitrite resulted in a high sensitivity (0.93) and efficacy (0.85) when the prevalence of bacteriuria was 0.89. Escherichia coli and Staphylococcus saprophyticus accounted for 93% of the urinary isolates. Significantly more patients infected with S. saprophyticus than E. coli complained of dysuria (p < 0.05), frequency (p < 0.05) or flank pain (p < 0.01). CRP agreed best with the clinical diagnosis of acute pyelonephritis. CONCLUSIONS: In women with a high probability of bacteriuria, i.e. those with symptoms of lower UTI, examination for pyuria and urinary nitrite offers high diagnostic efficacy. If either or both tests are positive urine cultures can be omitted.

An epidemiologic study of Lyme disease in southern Sweden.

BACKGROUND: Lyme disease is the most common vector-borne infection in some temperate regions of the Northern Hemisphere. However, for most areas of endemic disease reliable epidemiologic data are sparse. METHODS: Over a one-year period, we conducted a prospective, population-based survey of cases of Lyme disease in southern Sweden. The diagnosis was made on the basis of the presence of erythema migrans at least 5 cm in diameter or characteristic clinical manifestations such as arthritis, neuroborreliosis, and carditis. RESULTS: We identified 1471 patients with Lyme disease, for an overall annual incidence of 69 cases per 100,000 inhabitants. The incidence varied markedly according to geographic region, and there were several areas where disease was widely prevalent. The incidence varied according to age, with the highest rates among people 5 to 9 and 60 to 74 years of age, but not according to sex. The most frequent clinical manifestation was erythema migrans (seen in 77 percent of all cases), followed by neuroborreliosis (16 percent) and arthritis (7 percent). Carditis was rare. A preceding tick bite was reported by 79 percent of the patients. Bites in the head and neck region were more common among children than among adults and were associated with an increased risk of neuroborreliosis. CONCLUSIONS: Lyme disease is very common in southern Sweden, with a relatively high frequency of neurologic complications and arthritis. With the exception of the low incidence of carditis, the pattern of disease we found in Sweden was similar to that reported in the United States.

Diagnosis of pneumonia by cultures, bacterial and viral antigen detection tests, and serology with special reference to antibodies against pneumococcal antigens.

In a prospective study of the etiology of pneumonia 196 adult patients were included. One of the following criteria was required for diagnosis of pneumococcal pneumonia: isolation of pneumococci from blood; isolation from transtracheal aspirate; isolation from sputum or nasopharynx or detection of capsular antigen in sputum in combination with a significant increase in antibodies against at least one pneumococcal antigen (type-specific capsular polysaccharide, C-polysaccharide, pneumolysin); or increase in antibodies against two pneumococcal antigens. Pneumococcal pneumonia was diagnosed in 63 patients (32%). Other diagnoses were nonencapsulated Haemophilus influenzae isolated from transtracheal aspirates, 9; Mycoplasma pneumoniae diagnosed by serology, 17; Chlamydia psittaci, 6; and viral infections, 42. Twenty-two patients (11%) had evidence of infection with more than one agent. The pathogen could not be determined in 70 (36%). Many patients were given antibiotics before admittance to the study, and in some cases a convalescent serum sample was not available.