Emerging souvenirs-clinical presentation of the returning traveller with imported arbovirus infections in Europe.

BACKGROUND: Arboviruses are an emerging group of viruses that are causing increasing health concerns globally, including in Europe. Clinical presentation usually consists of a nonspecific febrile illness that may be accompanied by rash, arthralgia and arthritis, with or without neurological or haemorrhagic syndromes. The range of differential diagnoses of other infectious and noninfectious aetiologies is broad, presenting a challenge for physicians. While knowledge of the geographical distribution of pathogens and the current epidemiological situation, incubation periods, exposure risk factors and vaccination history can help guide the diagnostic approach, the nonspecific and variable clinical presentation can delay final diagnosis. AIMS AND SOURCES: This narrative review aims to summarize the main clinical and laboratory-based findings of the three most common imported arboviruses in Europe. Evidence is extracted from published literature and clinical expertise of European arbovirus experts. CONTENT: We present three cases that highlight similarities and differences between some of the most common travel-related arboviruses imported to Europe. These include a patient with chikungunya virus infection presenting in Greece, a case of dengue fever in Turkey and a travel-related case of Zika virus infection in Romania. IMPLICATIONS: Early diagnosis of travel-imported cases is important to reduce the risk of localized outbreaks of tropical arboviruses such as dengue and chikungunya and the risk of local transmission from body fluids or vertical transmission. Given the global relevance of arboviruses and the continuous risk of (re)emerging arbovirus events, clinicians should be aware of the clinical syndromes of arbovirus fevers and the potential pitfalls in diagnosis.

Current epidemiology of tetanus in England, 2001-2014.

Public Health England conducts enhanced national surveillance of tetanus, a potentially life-threatening vaccine-preventable disease. A standardized questionnaire was used to ascertain clinical and demographic details of individuals reported with clinically suspected tetanus. The 96 cases identified between 2001 and 2014 were analysed. The average annual incidence was 0·13/million (95% confidence interval 0·10-0·16) of which 50·0% were male. Where reported, 70·3% of injuries occurred in the home/garden (45/64). Overall, 40·3% (31/77) cases were in people who inject drugs (PWID), including a cluster of 22 cases during 2003-2004. Where known (n = 68), only 8·8% were age-appropriately immunized. The overall case-fatality rate was 11·0% (9/82). All tetanus-associated deaths occurred in adults aged >45 years, none of whom were fully immunized. Due to the success of the childhood immunization programme, tetanus remains a rare disease in England with the majority of cases occurring in older unimmunized or partially immunized adults. Minor injuries in the home/garden were the most commonly reported likely sources of infection, although cases in PWID increased during this period. It is essential that high routine vaccine coverage is maintained and that susceptible individuals, particularly older adults, are protected through vaccination and are offered timely post-exposure management following a tetanus-prone wound.

The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults.

Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients.

Healthcare-associated Crimean-Congo haemorrhagic fever in Turkey, 2002-2014: a multicentre retrospective cross-sectional study.

Healthcare-related transmission of Crimean-Congo haemorrhagic fever (CCHF) is a well-recognized hazard. We report a multicentre retrospective cross-sectional study undertaken in Turkey in 2014 in nine hospitals, regional reference centres for CCHF, covering the years 2002 to 2014 inclusive. Data were systematically extracted from charts of all personnel with a reported health care injury/accident related to CCHF. Blood samples were tested for CCHF IgM/IgG by enzyme-linked immunosorbent assay and/or viral nucleic acid detection by PCR after the injury. Fifty-one healthcare-related exposures were identified. Twenty-five (49%) of 51 resulted in laboratory-confirmed infection, with a 16% (4/25) overall mortality. The main route of exposure was needlestick injury in 32/51 (62.7%). A potential benefit of post-exposure prophylaxis with ribavirin was identified.

Managing potential drug-drug interactions between gastric acid-reducing agents and antiretroviral therapy: experience from a large HIV-positive cohort.

Drug-drug interactions between antiretroviral therapy and other drugs are well described. Gastric acid-reducing agents are one such class. However, few data exist regarding the frequency of and indications for prescription, nor risk assessment in the setting of an HIV cohort receiving antiretroviral therapy. To assess prevalence of prescription of gastric acid-reducing agents and drug-drug interaction within a UK HIV cohort, we reviewed patient records for the whole cohort, assessing demographic data, frequency and reason for prescription of gastric acid-reducing therapy. Furthermore, we noted potential drug-drug interaction and whether risk had been documented and mitigated. Of 701 patients on antiretroviral therapy, 67 (9.6%) were prescribed gastric acid-reducing therapy. Of these, the majority (59/67 [88.1%]) were prescribed proton pump inhibitors. We identified four potential drug-drug interactions, which were appropriately managed by temporally separating the administration of gastric acid-reducing agent and antiretroviral therapy, and all four of these patients remained virally suppressed. Gastric acid-reducing therapy, in particular proton pump inhibitor therapy, appears common in patients prescribed antiretroviral therapy. Whilst there remains a paucity of published data, our findings are comparable to those in other European cohorts. Pharmacovigilance of drug-drug interactions in HIV-positive patients is vital. Education of patients and staff, and accurate data-gathering tools, will enhance patient safety.

Malaria.

Malaria is a life-threatening disease, with its largest impact being due to Plasmodium falciparum infection in Africa. Military populations continue to be at a high risk of malaria and reported case series have frequently revealed poor compliance with preventative measures. The symptoms of malaria are non-specific and its management depends on awareness of the diagnosis and early recognition and treatment. This is aided by new and simple rapid diagnostic tests, but these should not replace the examination of blood films if these are available. Artemisinin combination therapy provides a more rapid and dependable cure of uncomplicated P falciparum infection, with artesunate now being the drug of choice in severe infection.

Mycobacterium chelonae hand infection following ferret bite.

We present a case of hand infection caused by Mycobacterium chelonae. The patient was a 58-year-old woman with Type II diabetes mellitus and stage 4 chronic kidney disease. The infection occurred following a ferret bite and had not responded to oral antibiotics in the primary care setting. She developed signs of pyogenic flexor tenosynovitis of the index and middle fingers of her left hand. Laboratory parameters showed high C-reactive protein, raised erythrocyte sedimentation rate and leucocytosis. Ultrasound imaging confirmed the clinical diagnosis. Plain radiographs showed no osseous involvement. The infection was treated with surgical debridement and broad spectrum parenteral antibiotics. The intra-operative tissue specimens were initially negative on aerobic and anaerobic cultures. Following transient improvement of her inflammatory parameters and clinical signs, she developed a recurrence with added features of osteomyelitis of the index and middle finger metacarpal heads on repeat radiographs. A revision surgical debridement of the flexor tenosynovitis and osteomyelitis with specific long-term antibiotic cover has led to resolution of the infection. Extended cultures of the tissue specimens at the regional laboratory confirmed the causative organism to be M. chelonae. To our knowledge, this is the first reported case of M. chelonae infection resulting from a ferret bite. This case reminds us of the need for a high index of suspicion for infection with uncommon pathogens following animal bites, especially in patients with altered immune status.

Patients accessing HIV treatment via sexual health services: what are the risks of the dual case-note system?

In many British hospitals, HIV-positive patients access care via genitourinary (GU) medicine services. As a result of National Health Service (NHS) legislation, such patients may have information concerning HIV treatment filed separately from their general clinical records. We sought to evaluate accuracy of medication records of patients with both GU medicine and general hospital case-notes, and to assess clinical risk arising from incorrect or incomplete recording. In this retrospective review, 156 episodes of care from 100 HIV-positive patients with separate HIV case-notes were evaluated for accuracy of medication recording, when paired with clinical notes from attendances in other hospital departments. Discrepancies were observed in 52.6% of care episodes; significant discrepancies were apparent in 7.8%. The dual case-note system represents significant risk to patient care. We recommend that hospitals that continue to operate this system urgently consider amalgamation of HIV care records into hospital case sheets, in line with current national standards.

Lyme disease in a British referral clinic.

BACKGROUND: Concerns about over-diagnosis and inappropriate management of Lyme disease (LD) are well documented in North America and supported by clinical data. There are few parallel data on the situation in the UK. AIM: To describe the patterns of referral, investigation, diagnosis and treatment of patients with suspected LD referred to an infectious disease unit in Liverpool, UK. Previous management by National Health Service (NHS) and non-NHS practitioners was reviewed. DESIGN: Descriptive study conducted by retrospective casenotes review. METHODS: Retrospective casenotes review of adults referred with possible LD to an infectious disease unit in Liverpool, UK, over 5 years (2006-2010). RESULTS: Of 115 patients, 27 (23%) were diagnosed with LD, 38 (33%) with chronic fatigue syndrome (CFS) and 13 (11%) with other medical conditions. No specific diagnosis could be made in 38 (33%). At least 53 unnecessary antibiotic courses had been given by non-NHS practitioners; 21 unnecessary courses had been prescribed by NHS practitioners. Among 38 patients, 17 (45%) with CFS had been misdiagnosed as having LD by non-NHS practitioners. CONCLUSION: A minority of referred patients had LD, while a third had CFS. LD is over-diagnosed by non-specialists, reflecting the complexities of clinical and/or laboratory diagnosis. Patients with CFS were susceptible to misdiagnosis in non-NHS settings, reinforcing concerns about missed opportunities for appropriate treatment for this group and about the use of inappropriate diagnostic modalities and anti-microbials in non-NHS settings.

Outbreak of zoonotic cutaneous leishmaniasis with local dissemination in Balkh, Afghanistan.

OBJECTIVES: In Afghanistan zoonotic cutaneous leishmaniasis (CL) due to Leishmania major has been less widely reported than anthroponotic CL due to L. tropica. However, an outbreak of zoonotic CL occurred amongst a group of British soldiers at a military camp near Mazar-e-Sharif in the Balkh province of northern Afghanistan in 2004. METHODS: A study was performed to assess the epidemiology, clinical features, parasitology results, treatment outcomes and environmental health measures associated with this incident. RESULTS: Twenty (17%) of 120 soldiers developed CL due to L. major and the risk of infection increased with the proximity of their accommodation to an area of recently cleared scrub, where many wild rodents were observed. Most cases had features of local dissemination, including secondary lesions from the pseudo-Koebner phenomenon, sporotrichoid lymphatic spread, lymphadenopathy and satellite papules or milia formation around healing lesions. Several cases responded poorly to fluconazole and low dose (10 mg/kg) sodium stibogluconate, which were considered suitable treatments at the time. Environmental health measures at the military camp were found to be deficient. CONCLUSIONS: Zoonotic CL due to L. major is a significant threat for foreign troops based in Balkh, Afghanistan and may present with unusually severe clinical features and be resistant to previously recommended treatments.

Management of suspected viral encephalitis in adults--Association of British Neurologists and British Infection Association National Guidelines.

In the 1980s the outcome of patients with herpes simplex encephalitis was shown to be dramatically improved with aciclovir treatment. Delays in starting treatment, particularly beyond 48 h after hospital admission, are associated with a worse prognosis. Several comprehensive reviews of the investigation and management of encephalitis have been published. However, their impact on day-to day clinical practice appears to be limited. The emergency management of meningitis in children and adults was revolutionised by the introduction of a simple algorithm as part of management guidelines. In February 2008 a group of clinicians met in Liverpool to begin the development process for clinical care guidelines based around a similar simple algorithm, supported by an evidence base, whose implementation is hoped would improve the management of patients with suspected encephalitis.

HIV post-exposure prophylaxis programmes in the developed and developing world: can we learn from each other?

In an audit of HIV post-exposure prophylaxis (PEP) programmes in Blantyre, Malawi, and Liverpool, UK, a striking common deficiency was poor attendance of follow-up visits and of HIV testing to determine efficacy of PEP. Causes of poor follow-up after PEP need to be explored in both settings.

Candida pelliculosa meningitis as an opportunistic infection in HIV: the first reported case.

We describe the first reported case of Candida pelliculosa meningitis in HIV infection. This case highlights the risk of uncommon opportunistic infections in association with the immunocompromised and the importance of autopsy as a diagnostic tool in HIV infection. We discuss the epidemiology, diagnosis and management of C. pelliculosa, a non-albicans species which is rarely associated with disease, and review current literature.

Acute presentations of HIV are still missed in low prevalence areas.

OBJECTIVES: To evaluate missed opportunities and delays in the diagnosis of HIV in a low prevalence setting over a 24 year period. METHODS: Patients with acute presentations of HIV were included in a retrospective note based review. Data were compared from acute presentations in 1985-2001 (88/241 new patients) with 2005-2007 (99/136 new patients). The number of recorded clinical and laboratory clues to infection and subsequent time delays to diagnosis of HIV were evaluated. RESULTS: The findings reflect the shifting demographics of HIV in the UK over the past two decades, exemplified by an eightfold increase in tuberculosis at presentation. Despite recording clinical stigmata of HIV (clues) in the notes, the number of missed clues increased, and many clinicians failed to request HIV testing. The median delay between presentation and diagnosis reduced from 5 to 1 day (p<0.001), and mortality dropped from 14% to 4% among patients presenting with acute symptoms. However, there was still a delay of more than 30 days before diagnosis for almost one in five patients. CONCLUSIONS: Despite some improvement and better awareness, there are still significant delays before hospital doctors consider the diagnosis of HIV for patients in low prevalence areas, even among some patient groups with high risk. Hospitals should consider moving to opt-out routine HIV testing of all medical admissions.

Acute central nervous system infections in adults--a retrospective cohort study in the NHS North West region.

BACKGROUND: Over the last 15 years, bacterial meningitis has received considerable attention, including national guidelines, whilst viral central nervous system (CNS) infections have been relatively neglected. A recent pilot study suggested that management of patients with suspected viral encephalitis was often suboptimal. AIM: To examine the relative incidence, clinical features and management of suspected acute CNS infections in adults across the NHS North West Region. DESIGN: A multicentre cross-sectional retrospective cohort study at 10 hospitals across the region over 3 months (from September to December 2007). Following a screen of all patients who had cerebrospinal fluid (CSF) analysis or received intravenous aciclovir and/or third-generation cephalosporin, those with clinical features suspicious of a CNS infection were included. Management was compared with the national meningitis and regional encephalitis guidelines. RESULTS: Three hundred and eighty-five patients were screened; 217 patients had a suspected CNS infection and 44 (20%) had a CNS infection: 18 aseptic meningitis (one herpes simplex virus [HSV]-2), 13 purulent meningitis (four Streptococcus pneumoniae) and 13 encephalitis (three HSV-1). The median (range) time from admission to suspicion of CNS infection and to LP was longer for patients with encephalitis than meningitis [4 (0.3-312) vs. 0.3 (0.1-12) h, P<0.001, and 23 (4-360) vs. 12 (2-48) h, P=0.042, respectively]; and the median time to treatment was longer for aciclovir than cephalosporin [7 (0.5-312) vs. 3 (0.3-312) h, P=0.002]. DISCUSSION: Encephalitis was as common as purulent meningitis, and HSV as common as Streptococcus pneumoniae. However, the management of patients with encephalitis was worse than meningitis. National encephalitis guidelines are needed.

Favourable one-year ART outcomes in adult Malawians with hepatitis B and C co-infection.

BACKGROUND: Few studies have investigated the impact of chronic hepatitis B and C infection on antiretroviral therapy (ART) outcomes in sub-Saharan Africa. Hepatotoxicity may be a particular concern in co-infected patients taking nevirapine-stavudine-lamivudine. METHODS: We conducted a prospective cohort study of 300 Malawian adults starting ART and describe one-year ART outcomes according to viral hepatitis status. RESULTS: At baseline, patients had advanced HIV disease (29.3% were in WHO stage 4; mean CD4 = 157 cells/microL; mean log(10)HIV-1 RNA = 5.24 copies/ml). Co-infection with hepatitis B, C and B + C were present in 6.7%, 5.7% and 1.7% respectively. At 50 weeks, all-cause mortality was 43 (14.3%). Sixteen (5.3%) had transferred to another unit. Eight (2.7%) were lost to follow up. Sixteen (5.3%) had stopped ART. 217 (72.3%) were alive on ART, of whom 82.5% had an HIV-1 RNA <400 copies/ml at week 50. During the first 50 weeks of ART, severe hepatotoxicity (liver enzyme values >5 times upper level of normal) occurred in 9%, but did not result in any ART discontinuations. Clinical hepatitis or jaundice was not observed. There were no significant differences in occurrence of hepatotoxicity, other side effects, mortality, severe morbidity, immune reconstitution or virological failure between hepatitis B and/or C co-infected patients and those who were not. Viral hepatitis co-infection was not associated with severe hepatotoxicity, mortality, severe morbidity or virological failure in multivariate analyses. CONCLUSION: Our data suggest that screening for viral hepatitis B and C and liver enzyme monitoring may not require high priority in ART programmes in sub-Saharan Africa.

Leukocytosis as a predictor for non-infective mortality and morbidity.

Leukocytosis (raised concentration of white cells in the blood) is commonly associated with infection or inflammation, but can occur in a wide variety of other conditions. Leukocytosis has also been linked with increased mortality and morbidity in a number of studies. We have systematically reviewed the relevant literature, which clearly demonstrates an association between leukocytosis and mortality-particularly due to cardiovascular or cerebrovascular causes. The mechanisms of this effect are uncertain but, when combined with other markers predictive of death, leukocytosis may contribute to modelling systems to predict in-patient mortality risk.

Reliability of rapid testing for hepatitis B in a region of high HIV endemicity.

Hepatitis B (HBV) and HIV co-infection is common in resource-poor settings. A recent study from Malawi revealed poor correlation between hepatitis B surface antigen (HBsAg) point-of-care tests and reference tests in patients co-infected with HIV. We studied a cohort of 300 Malawian adults entering a treatment programme for HIV. Sera were tested for HBsAg first using the Determine rapid test and re-tested using a commercial enzyme immunoassay (EIA). All tests were done under optimal conditions in Liverpool, UK. Sera from all 25 patients positive for HBsAg using the rapid test and from 50 who were negative, were re-tested using the EIA, with complete concordance of results. The kappa correlation was 1, specificity 100% (93-100%) and sensitivity 100% (86-100%) compared to the reference test. Patients had advanced immune suppression (mean CD4=175 cells x 10(6)/l). In a non-field setting, the results of point-of-care Determine rapid hepatitis B tests appear reliable in patients with HIV-1 co-infection.