Modified two-tier testing (MTTT) for Lyme borreliosis (i.e. confirmation with an EIA instead of an immunoblot) has been shown to have improved sensitivity compared with standard two-tier testing ...(STTT) in samples from American patients, without losing specificity. The current study assesses the sensitivity and specificity of various algorithms of MTTT in European patients with erythema migrans (EM) as a model disease for early Lyme borreliosis, and in appropriate controls. Four different immunoassays were used in the first tier, followed by either an immunoblot or the C6-EIA, or were used as standalone single-tier test. These tests were performed on consecutively collected sera of 228 Dutch patients with physician-diagnosed EM in the setting of general practice, 231 controls from the general population, and 50 controls with potentially cross-reactive antibodies. All the variants of MTTT that were studied had significantly higher sensitivity compared with their equivalent STTT, while retaining comparable specificity. Within the MTTT algorithms, classifying equivocal results as positive yielded better diagnostic parameters than classifying equivocal results as negative. The best diagnostic parameters were found using the Enzygnost-2 assay in the first tier, followed by a C6-ELISA in the second tier (sensitivity 77.6%, 95% CI 71.7–82.9; specificity 96.1%, 95% CI 92.7–98.2). This algorithm performed significantly better than the equivalent STTT algorithm in terms of sensitivity (
p
< 0.001), while maintaining comparable specificity (population controls
p
= 0.617). Our results show that MTTT can be a useful tool for the serodiagnosis of European patients with early Lyme borreliosis.
Borrelia burgdorferi sensu lato, the spirochete that causes human Lyme borreliosis (LB), is a genetically and phenotypically divergent species. In the past several years, various molecular approaches ...have been developed and used to determine the phenotypic and genetic heterogeneity within the LB-related spirochetes and their potential association with distinct clinical syndromes. These methods include serotyping, multilocus enzyme electrophoresis, DNA-DNA reassociation analysis, rRNA gene restriction analysis (ribotyping), pulsed-field gel electrophoresis, plasmid fingerprinting, randomly amplified polymorphic DNA fingerprinting analysis, species-specific PCR and PCR-based restriction fragment length polymorphism (RFLP) analysis, and sequence analysis of 16S rRNA and other conserved genes. On the basis of DNA-DNA reassociation analysis, 10 different Borrelia species have been described within the B. burgdorferi sensu lato complex: B. burgdorferi sensu stricto, Borrelia garinii, Borrelia afzelii, Borrelia japonica, Borrelia andersonii, Borrelia valaisiana, Borrelia lusitaniae, Borrelia tanukii, Borrelia turdi, and Borrelia bissettii sp. nov. To date, only B. burgdorferi sensu stricto, B. garinii, and B. afzelii are well known to be responsible for causing human disease. Different Borrelia species have been associated with distinct clinical manifestations of LB. In addition, Borrelia species are differentially distributed worldwide and may be maintained through different transmission cycles in nature. In this paper, the molecular methods used for typing of B. burgdorferi sensu lato are reviewed. The current taxonomic status of B. burgdorferi sensu lato and its epidemiological and clinical implications, especiallly correlation between the variable clinical presentations and the infecting Borrelia species, are discussed in detail.
One third of travellers to low- and middle-income regions of the tropics and subtropics become colonized by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). The risk varies by ...destination and, for each traveller, may be substantially further increased by travellers' diarrhoea (TD) and antibiotic use. Despite the risk of TD in Africa, ESBL-PE acquisition rates in all studies are lower there than in Asia. Africa has become increasingly popular as a destination for international travellers, yet minimal data are available from the continent's subregions and countries.
We analysed subregion- and country-specific data on carriage and risk factors for ESBL-PE colonization pooled from three prospective studies conducted between 2009 and 2013 among Finnish and Dutch travellers. The data were subjected to multivariable analysis of risk factors. In addition, we compared our data to two recent large investigations reporting data by subregion and country.
Our joint analysis comprised data on 396 travellers. The ESBL-PE colonization rate was highest in Northern Africa, followed by Middle and Eastern Africa, and lowest in Southern and Western Africa. Of individual countries with more than 15 visitors, the highest rates were seen for Egypt (12/17; 70.6%), Ghana (6/23; 26.1%), and Tanzania (14/81; 17.3%); the rates among travellers to Egypt were comparable to those reported in South and Southeast Asia. In a pooled multivariable analysis, travel destination, age, overnight hospitalisation abroad, TD, and use of fluoroquinolones were independently associated with increased ESBL-PE colonization rates.
Even in areas with relatively low risk of colonization, antimicrobials clearly predispose to colonization with ESBL-PE. Travellers to Africa should be cautioned against unnecessary use of antibiotics.
The differential diagnosis of stroke in Africa in areas with high HIV prevalence includes brain infections. We studied causes of stroke in Blantyre, Malawi, where HIV prevalence among medical ...inpatients is 70%.
In a descriptive study of 8-month duration, all patients presenting at Queen Elizabeth Central Hospital, Blantyre, with central neurological deficit of acute onset (<24 hours) had baseline investigations, including full blood count, blood glucose, serology for toxoplasmosis, syphilis, and HIV, ECG, echocardiogram, ultrasound of the carotid arteries, and computerized tomography scan of the brain. A lumbar puncture was performed unless contraindicated.
Ninety-eight consecutive patients (49 males) were studied. In those who were HIV positive (48%), the mean age was 37.5 years; ischemic stroke was the commonest diagnosis (n=25; 58%), followed by infection (n=11; 23%; including tuberculous n=4 and cryptococcal n=2 meningitis; toxoplasmic encephalitis n=1; neurocysticercosis n=1; brain abscess n=1; and progressive multifocal leucoencephalopathy n=2). No clinical or laboratory parameters could be identified as predictors for infection, but 3 of 5 patients with fever on admission had tuberculous meningitis. In HIV-negative patients (mean age 58.6 years), 55% had ischemic stroke and 31% had intracerebral hemorrhage; no brain infection was diagnosed. Presence of vascular disease correlated with age but not with HIV status.
Ischemic stroke was found in half of patients irrespective of HIV status. In those who are HIV positive, brain infection should be considered for which the presence of fever and examination of cerebrospinal fluid seem most useful in diagnosis.
IntroductionPerforming a test of cure (TOC) could demonstrate success or failure of antimicrobial treatment of C. trachomatis (CT) infection, but the value of using a nuclear acid amplification test ...(NAAT) based TOC after treatment is subject to discussion, as the presence of CT nucleic acids after treatment may be prolonged and intermittent without the presence of infectious bacteria. We used cell culture to assess if a NAAT positive TOC indicates the presence of viable CT.MethodsWe analysed follow up (FU) data from women with a CT infection who visited the STI clinic of Amsterdam, the Netherlands, from September 2015 through June 2016. After giving informed consent, participants underwent baseline and three FU speculum examinations to obtain cervical swabs for both CT culture and NAAT testing. Speculum examinations were scheduled at 7, 21 and 49 days after treatment (single dose 1000 mg azithromycin). Collected samples were analysed using a RNA and DNA-based NAAT. CT cell culture was performed on all samples at baseline, and in FU samples that were NAAT-positive. Clearance was defined as conversion to negative NAAT results at any FU visit.ResultsWe included 78 women with NAAT proven CT infection prior to receiving treatment of whom 58 (74%) were also culture positive. At the first visit after treatment (median 7 days; IQR 7–8) 44 (47%) women were NAAT positive, of whom three tested also positive by culture. CT infection was cleared in 73 women (94%), of whom 61 (78%) at their second FU visit (median 21 days; IQR 21–25). Of the five women who did not clear their infection, three were also culture positive indicating a viable infection. All five reported unprotected sexual contact after inclusion prior to their last FU visit, indicating potentially new infections.ConclusionWe observed prolonged and intermittent positive results over time for both NAAT tests. For three participants (4%) viable CT infections were detected 49 days after treatment. All three cases reported new sexual contacts. In conclusion, persisting infections or treatment failure were rare. Support: Hologic provided Aptima test materials and kits in-kind. Roche provided Cobas test materials and kits in- kind. Copan provided Universal Transport Medium in-kind
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