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Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Haemophilus influenzae type b (Hib) are three most common pathogens accounting for most bacterial meningitis, a serious global infectious disease with high fatality, especially in developing nations. Because the treatment and antibiotics differ among each type, the identification of the exact bacteria causing the disease is vital. Herein, we report a polymer/paper hybrid microfluidic biochip integrated with loop-mediated isothermal amplification (LAMP) for multiplexed instrument-free diagnosis of these three major types of bacterial meningitis, with high sensitivity and specificity. Results can be visually observed by the naked eye or imaged by a smartphone camera under a portable UV light source. Without using any specialized laboratory instrument, the limits of detection of a few DNA copies per LAMP zone for N. meningitidis, S. pneumoniae and Hib were achieved within 1 hour. In addition, these three types of microorganisms spiked in artificial cerebrospinal fluid (ACSF) were directly detected simultaneously, avoiding cumbersome sample preparation procedures in conventional methods. Compared with the paper-free non-hybrid microfluidic biochip over a period of three months, the hybrid microfluidic biochip was found to have a much longer shelf life. Hence, this rapid, instrument-free and highly sensitive microfluidic approach has great potential for point-of-care (POC) diagnosis of multiple infectious diseases simultaneously, especially in resource-limited settings.

Objectives To describe the presentation, influence of previous treatment and diagnosis in juvenile dogs presenting with pyrexia to a UK referral centre. Materials and Methods Clinical records of dogs aged 1 to 18 months presenting with a problem list including pyrexia (≥⃒39∙2°C) that was reproducible during referral hospitalisation were retrospectively reviewed. Signalment, history ‐ including previous treatment, clinical examination findings and diagnosis were recorded. Diagnoses were categorised as non‐infectious inflammatory, infectious, congenital, neoplastic and miscellaneous. The influence of previous treatment on the ability to reach a final diagnosis was analysed. Results A total of 140 cases was identified. Diagnosis was reached in 115 cases. Non‐infectious inflammatory disease was identified in 91 cases (79%), infectious disease in 19 cases (17%), a congenital disorder in four dogs (3%) and neoplasia in one dog (1%). Breeds most commonly identified were Border collies (17/140; 12%), beagles (16/140; 11%), Labrador retrievers (11/140; 8%), springer spaniels (9/140; 6%) and cocker spaniels (8/140; 6%). Before presentation, most dogs had received antibiotics (83/140; 59%), non‐steroidal anti‐inflammatory drugs (84/140; 60%) or steroids (9/140; 6%), either alone or in combination. Neither antibiotics nor non‐steroidal anti‐inflammatory drugs influenced the ability to reach a diagnosis. Steroid‐responsive meningitis‐arteritis comprised 55 of 91 (60%) individuals of the non‐infectious inflammatory cohort. All four dogs diagnosed with congenital disorders were Border collies. Clinical significance Non‐infectious inflammatory disease, particularly steroid‐responsive meningitis‐arteritis, immune‐mediated polyarthritis and metaphyseal osteopathy, was commonly diagnosed in this population of pyrexic juvenile dogs.

We investigated whether dried cerebrospinal fluid (CSF) conserved on filter paper can be used as a substrate for accurate PCR diagnosis of important causes of bacterial meningitis in the Lao PDR. Using mock CSF, we investigated and optimized filter paper varieties, paper punch sizes, elution volumes and quantities of DNA template to achieve sensitive and reliable detection of bacterial DNA from filter paper specimens. FTA Elute Micro Card™ (Whatman, Maidstone, UK) was the most sensitive, consistent and practical variety of filter paper. Following optimization, the lower limit of detection for Streptococcus pneumoniae from dried mock CSF spots was 14 genomic equivalents (GE)/μL (interquartile range 5.5 GE/μL) or 230 (IQR 65) colony forming units/mL. A prospective clinical evaluation for S. pneumoniae, S. suis and Neisseria meningitidis was performed. Culture and PCR performed on fresh liquid CSF from patients admitted with a clinical diagnosis of meningitis (n = 73) were compared with results derived from dried CSF spots. Four of five fresh PCR-positive CSF samples also tested PCR positive from dried CSF spots, with one patient under the limit of detection. In a retrospective study of S. pneumoniae samples (n = 20), the median (IQR; range) CSF S. pneumoniae bacterial load was 1.1 × 104 GE/μL (1.2 × 105; 1 to 6.1 × 106 DNA GE/μL). Utilizing the optimized methodology, we estimate an extrapolated sensitivity of 90%, based on the range of CSF genome counts found in Laos. Dried CSF filter paper spots could potentially help us to better understand the epidemiology of bacterial meningitis in resource-poor settings and guide empirical treatments and vaccination policies. © 2013 The Authors. Clinical Microbiology and Infection published by John Wiley and Sons Ltd on behalf of the European Society of Clinical Microbiology and Infectious Disease.

Contains fulltext : 51936.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To evaluate cognitive outcome in adult survivors of bacterial meningitis. METHODS: Data from three prospective multicentre studies were pooled and reanalysed, involving 155 adults surviving bacterial meningitis (79 after pneumococcal and 76 after meningococcal meningitis) and 72 healthy controls. RESULTS: Cognitive impairment was found in 32% of patients and this proportion was similar for survivors of pneumococcal and meningococcal meningitis. Survivors of pneumococcal meningitis performed worse on memory tasks (p

OBJECTIVE: To study cerebrospinal fluid (CSF) and serum samples from 34 consecutive patients suspected of having varicella-zoster virus (VZV) infection of the central nervous system (CNS). Population and METHODS: The patients were divided into three groups. The first group consisted of 27 patients with a rash in one to three dermatomes and clinical suspicion of meningitis and radiculitis; among them, three subgroups were distinguished according to the affected dermatome: ophthalmicus (n = 9), oticus (n = 11) and cervico-thoraco-lumbar zoster (n = 7). Four cases of zoster sine herpete (ZSH) were included in the second group: these patients presented with either radiculitis (n = 2) or meningoencephalitis (n = 2), without cutaneous eruption. The third group consisted of three patients with a generalised rash and encephalitis. A polymerase chain reaction (PCR) for VZV DNA and antigen-driven immunoblots for oligoclonal anti-VZV antibodies were carried out on all CSF samples. RESULTS: PCR of the CSF was positive in 44% of the patients from the first group, mainly within the first 7 days after eruption. In addition, intrathecal synthesis of anti-VZV antibodies was detected in 37% of patients, always after an interval of 7 days (p

Objective: To report the nature of stroke in patients infected with human immunodeficiency virus (HIV) in a region with high HIV seroprevalence and describe HIV associated vasculopathy. Methods: Patients with first ever stroke, infected with HIV and prospectively included in the stroke register of the Groote Schuur Hospital/University of Cape Town stroke unit were identified and reviewed. Results: Between 2000 and 2006, 67 of the 1087 (6,1%) stroke patients were HIV infected. Of these, 91% (n = 61) were younger than 46 years. Cerebral infarction occurred in 96% (n = 64) of the HIV positive patients and intracerebral haemorrhage in 4% (n = 3). HIV infected young stroke patients did not demonstrate hypertension, diabetes, hyperlipidaemia or smoking as significant risk factors for ischaemic stroke. Infection as a risk factor for stroke was significantly more common in HIV positive patients (p = 0.018, OR 6.4, CI 3.1 to 13.2). In 52 (81%) patients with ischaemic stroke, an aetiology was determined. Primary aetiologies comprised infectious meningitides/vasculitides in 18 (28%) patients, coagulopathy in 12 (19%) patients and cardioembolism in nine (14%) patients. Multiple aetiologies were present in seven (11%) patients with ischaemic stroke. HIV associated vasculopathy was identified in 13 (20%) patients. The HIV associated vasculopathy manifested either extracranially (seven patients) as total or significant carotid occlusion or intracranially (six patients) as medium vessel occlusion, with or without fusiform aneurysmal dilation, stenosis and vessel calibre variation. Conclusion: Investigation of HIV infected patients presenting with stroke will determine an aetiology in the majority of patients. In our cohort, 20% of patients demonstrated evidence of an HIV associated vasculopathy.

Background: In Latvia and other endemic regions, a single tick bite has the potential to transmit both tick-borne encephalitis (TBE) and Lyme borreliosis. Objective: To analyse both the clinical features and differential diagnosis of combined tick-borne infection with TBE and Lyme borreliosis, in 51 patients with serological evidence, of whom 69% had tick bites. Results: Biphasic fever suggestive of TBE occurred in 55% of the patients. Meningitis occurred in 92%, with painful radicular symptoms in 39%. Muscle weakness occurred in 41%; in 29% the flaccid paralysis was compatible with TBE. Only two patients presented with the bulbar palsy typical of TBE. Typical Lyme borreliosis facial palsy occurred in three patients. Typical TBE oculomotor disturbances occurred in two. Other features typical of Lyme borreliosis detected in our patients were distal peripheral neuropathy (n = 4), arthralgia (n = 9), local erythema 1–12 days after tick bite (n = 7) and erythema chronicum migrans (n = 1). Echocardiogram abnormalities occurred in 15. Conclusions: Patients with double infection with TBE and Lyme borreliosis fell into three main clinical groups: febrile illness, 3 (6%); meningitis, 15 (30%); central or peripheral neurological deficit (meningoencephalitis, meningomyelitis, meningoradiculitis and polyradiculoneuritis), 33 (65%). Systemic features pointing to Lyme borreliosis were found in 25 patients (49%); immunoglobulin (Ig)M antibodies to borreliosis were present in 18 of them. The clinical occurrence of both Lyme borreliosis and TBE vary after exposure to tick bite, and the neurological manifestations of each disorder vary widely, with considerable overlap. This observational study provides no evidence that co-infection produces unusual manifestations due to unpredicted interaction between the two diseases. Patients with tick exposure presenting with acute neurological symptoms in areas endemic for both Lyme borreliosis and TBE should be investigated for both conditions. The threshold for simultaneous treatment of both conditions should be low, given the possibility of co-occurrence and the difficulty in ascribing individual neurological manifestations to one condition or the other.

Objective: To evaluate the safety and efficacy of removing large acoustic neurinomas (⩾3 cm) by the retrosigmoid approach. Methods: Large acoustic neurinomas (mean (SD), 4.1 (0.6) cm) were removed from 50 consecutive patients by the retrosigmoid suboccipital approach while monitoring the facial nerve using a facial stimulator-monitor. Excision began with the large extrameatal portion of the tumour, followed by removal of the intrameatal tumour, and then removal of the residual tumour in the extrameatal region just outside the porus acusticus. The last pieces of tumour were removed by sharp dissection from the facial nerve bidirectionally, and resected cautiously in a piecemeal fashion. Results: There were no postoperative deaths. The tumour was removed completely in 43 of 50 patients (86%). The facial nerve was anatomically preserved in 92% of the patients and 84% had excellent facial nerve function (House-Brackmann grade 1/2). One patient recovered useful hearing after tumour removal. Cerebrospinal fluid leak occurred in 4%, but there were no cases of meningitis. All but two patients (96%) had a good functional outcome. Conclusions: The method resulted in a high rate of functional facial nerve preservation, a low incidence of complications, and good functional outcomes, with no mortality and minimal morbidity. Very favourable results can be obtained using the retrosigmoid approach for the removal of large acoustic neurinomas.