Persistence of SARS-CoV-2 N-Antibody Response in Healthcare Workers, London, UK.

Prospective serosurveillance of severe acute respiratory syndrome coronavirus 2 in 1,069 healthcare workers in London, UK, demonstrated that nucleocapsid antibody titers were stable and sustained for <12 weeks in 312 seropositive participants. This finding was consistent across demographic and clinical variables and contrasts with reports of short-term antibody waning.

Good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) in adults in the UK: a consensus statement.

These good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) are an update to a previous consensus statement on OPAT in the UK published in 1998. They are based on previous national and international guidelines, but have been further developed through an extensive consultation process, and are underpinned by evidence from published literature on OPAT. They provide pragmatic guidance on the development and delivery of OPAT services, looking at all aspects of service design, care delivery, outcome monitoring and quality assurance, with the aim of ensuring that OPAT services provide high-quality, low-risk care, whatever the healthcare setting. They will provide a useful resource for teams developing new services, as well as a practical set of quality indicators for existing services.

Pituitary hCG production and cerebral tuberculosis mimicking disease progression during chemotherapy for an advanced ovarian germ cell tumour.

BACKGROUND: Ovarian germ cell tumours (OGCT) are rare but are usually curable with chemotherapy, even when presenting with advanced disease. The majority of OGCT produce the tumour markers, hCG and/or AFP which can be helpful in the diagnosis and monitoring the response to treatment. CASE PRESENTATION: In this case of a 36 year old woman, the elevated hCG level at presentation was helpful in making a clinical diagnosis of OGCT in a patient too unwell to permit a tissue diagnosis. Cisplatin based combination chemotherapy produced an initial normalisation of the hCG level, but later in treatment the patient developed new cerebral lesions and a rising serum hCG suggestive of disease progression. Further investigations suggested that the CNS lesions were cerebral TB and that the low levels of hCG elevations was likely to be pituitary in origin. Chemotherapy treatment was continued along with anti-tuberculous therapy and 24 months after successful completion of therapy the patient remains disease free. CONCLUSIONS: In the treatment of cancer patients it may be helpful to consider the potential non-malignant causes of new CNS lesions and that low hCG elevations may result from physiology rather than pathology in selected cases.

Factors associated with successful completion of outpatient parenteral antibiotic therapy (OPAT): A 10-year review from a large West London service.

Outpatient parenteral antibiotic therapy (OPAT) is an established antimicrobial delivery method in the UK. OPAT services differ nationwide, with a paucity of high-quality outcome data to enable benchmarking. A retrospective review of clinical outcomes and adverse events (AEs) of all patients treated during 2008-2017 was performed to identify factors associated with success and failure. Regression models were used to identify factors associated with OPAT success, and AEs were described for the study population using definitions recommended by BSAC. In the 10-year period, 2870 patient episodes resulted in 69 610 days of treatment, with a 91.7% rate of successful therapy completion and 92.0% of infections cured or improved. We encountered 196 AEs, including 1 case of Clostridium difficile-associated diarrhoea. AEs occurred in 10.9% of patient episodes. Adverse drug and line events occurred at a rate of 3.3 and 1.78 per 1000 treatment days, respectively. Rashes, blood dyscrasias and hepatitis were the most common drug AEs. The odds of OPAT success was greater for patients who spent more time (>14 days) on OPAT therapy (OR = 2.32; P < 0.01), utilised a peripheral line (OR = 1.83; P < 0.01), were treated in the clinic compared with self-administration (OR = 2.1; P < 0.02) and did not experience an AE (OR = 0.23; P < 0.01). In our setting, the odds of a successful OPAT episode were associated with longer treatment course, OPAT delivered via a peripheral line, administration in an OPAT clinic setting, and no adverse line or drug events.

A black mould death: A case of fatal cerebral phaeohyphomycosis caused by Cladophialophora bantiana.

Cladophialophora bantiana is a neurotropic mould and primary cause of cerebral phaeohyphomycoses, which presents with brain abscesses in both immunocompromised and immunocompetent individuals. It is associated with high mortality due to delay in diagnosis and absence of standardised therapy. We present a case of fatal cerebral phaeohyphomycosis in a 67-year-old Caucasian man. Diagnosis was achieved by histopathological examination of brain tissue followed by conventional culture and molecular identification. We highlight diagnostic and treatment challenges involved.

Community-acquired Pseudomonas aeruginosa meningitis.

Gram-negative bacilli such as Pseudomonas aeruginosa are a rare cause of meningitis. Patients developing P. aeruginosa meningitis most commonly have a history of neurosurgical procedures. We report a patient who presented with community-acquired chronic meningitis secondary to P. aeruginosa, related to surgery for otosclerosis 5 years previously.

Thick blood film examination for Plasmodium falciparum malaria has reduced sensitivity and underestimates parasite density.

BACKGROUND: Thick blood films are routinely used to diagnose Plasmodium falciparum malaria. Here, they were used to diagnose volunteers exposed to experimental malaria challenge. METHODS: The frequency with which blood films were positive at given parasite densities measured by PCR were analysed. The poisson distribution was used to calculate the theoretical likelihood of diagnosis. Further in vitro studies used serial dilutions to prepare thick films from malaria cultures at known parasitaemia. RESULTS: Even in expert hands, thick blood films were considerably less sensitive than might have been expected from the parasite numbers measured by quantitative PCR. In vitro work showed that thick films prepared from malaria cultures at known parasitaemia consistently underestimated parasite densities. CONCLUSION: It appears large numbers of parasites are lost during staining. This limits their sensitivity, and leads to erroneous estimates of parasite density.

Quantitative real-time polymerase chain reaction for malaria diagnosis and its use in malaria vaccine clinical trials.

The demand for an effective malaria vaccine is high, with millions of people being affected by the disease every year. A large variety of potential vaccines are under investigation worldwide, and when tested in clinical trials, researchers need to extract as much data as possible from every vaccinated and control volunteer. The use of quantitative real-time polymerase chain reaction (PCR), carried out in real-time during the clinical trials of vaccines designed to act against the liver stage of the parasite's life cycle, provides more information than the gold standard method of microscopy alone and increases both safety and accuracy. PCR can detect malaria parasites in the blood up to 5 days before experienced microscopists see parasites on blood films, with a sensitivity of 20 parasites/mL blood. This PCR method has so far been used to follow 137 vaccinee and control volunteers in Phase IIa trials in Oxford and on 220 volunteer samples during a Phase IIb field trial in The Gambia.

Mortality and malnutrition among populations living in South Darfur, Sudan: results of 3 surveys, September 2004.

CONTEXT: Mass violence against civilians in the west of Sudan has resulted in the displacement of more than 1.5 million people (25% of the population of the Darfur region). Most of these people are camped in 142 settlements. There has been increasing international concern about the health status of the displaced population. OBJECTIVE: To perform rapid epidemiological assessments of mortality and nutritional status at 3 sites in South Darfur for relief efforts. DESIGN, SETTING, AND PARTICIPANTS: In August and September 2004, mortality surveys were conducted among 137,000 internally displaced persons (IDPs) in 3 sites in South Darfur (Kass [n = 900 households], Kalma [n = 893 households], and Muhajiria [n = 900 households]). A nutritional survey was performed concomitantly among children aged 6 to 59 months using weight for height as an index of acute malnutrition (Kass [n = 894], Kalma [n = 888], and Muhajiria [n = 896]). A questionnaire detailing access to food and basic services was administered to a subset of households (n = 210 in each site). MAIN OUTCOME MEASURES: Crude and under 5-year mortality rates and nutritional status of IDPs in Kass, Kalma, and Muhajiria, South Darfur. RESULTS: Crude mortality rates, expressed as deaths per 10,000 per day, were 3.2 (95% confidence interval [CI], 2.2-4.1) in Kass, 2.0 (95% CI, 1.3-2.7) in Kalma, and 2.3 (95% CI, 1.2-3.4) in Muhajiria. Under 5-year mortality rates were 5.9 (95% CI, 3.8-8.0) in Kass, 3.5 (95% CI, 1.5-5.7) in Kalma, and 1.0 (95% CI, 0.03-1.9) in Muhajiria. During the period of displacement covered by our survey in Muhajiria, violence was reported to be responsible for 72% of deaths, mainly among young men. Diarrheal disease was reported to cause between 25% and 47% of deaths in camp residents and mainly affected the youngest and oldest age groups. Acute malnutrition was common, affecting 14.1% of the target population in Kass, 23.6% in Kalma, and 10.7% in Muhajiria. CONCLUSION: This study provides epidemiological evidence of the high rates of mortality and malnutrition among the displaced population in South Darfur and reinforces the need to mount appropriate and timely humanitarian responses.

Acute transverse myelitis as a rare manifestation of Campylobacter diarrhoea with concomitant disruption of the blood brain barrier.

We describe a case of acute transverse myelitis following Campylobacter diarrhoea in an adult. The patient presented with diplegia due to a longitudinal spinal cord lesion. The CSF demonstrated an aseptic meningitis. Oligoclonal bands and C. jejuni-specific IgG were detected in serum and cerebrospinal fluid at the beginning of the neurological illness. The patient was treated with antimicrobial therapy and steroids. A near full recovery was made and there were no relapses. C. jejuni is strongly implicated in the aetiology of acute motor axonal neuropathy and Miller Fisher syndrome through molecular mimicry of neuronal gangliosides. These gangliosides are expressed throughout the nervous system yet C. jejuni related central nervous system disease is exceedingly rare. We conclude that disruption of the blood-brain barrier was the key event in the pathogenesis of immune mediated post-infectious myelitis in our patient.

Outpatient parenteral antimicrobial therapy: Recent developments and future prospects.

Patients with serious infections requiring parenteral antimicrobial therapy are usually hospitalized for treatment. For certain conditions, however, administration of parenteral antibiotics outside the hospital setting may be safe, efficacious, convenient for patients and cost-beneficial. Outpatient parenteral antimicrobial therapy (OPAT) was developed in the US initially and its use has expanded globally during the past three decades. A wide variety of infections are amenable to treatment by OPAT. Once-daily agents such as ceftriaxone or teicoplanin and, more recently, antimicrobials such as ertapenem or daptomycin have been used for OPAT. The use of higher doses and less-frequent dosing of existing agents is being explored, and exciting new developments include the emergence of agents with broader-spectrum activity against drug-resistant organisms and the use of antifungal agents in the OPAT setting. Future prospects in OPAT include the use of more recently launched drugs such as telavancin, as well as drugs in development, including dalbavancin (Durata Therapeutics Inc) and omadacycline (PTK-0796; Novartis AG/PARATEK Pharmaceuticals Inc). This review outlines recent developments in, and future prospects for, the antimicrobial agents used in OPAT.

Eosinophilia in returning travellers and migrants from the tropics: UK recommendations for investigation and initial management.

Eosinophilia is a common finding in returning travellers and migrants, and in this group it often indicates an underlying helminth infection. Infections are frequently either asymptomatic or associated with non-specific symptoms, but some can cause severe disease. Here the British Infection Society guidelines group reviews common and serious infectious causes of eosinophilia, and outlines a scheme for investigating returning travellers and migrants. All returning travellers and migrants with eosinophilia should be investigated with concentrated stool microscopy and strongyloides serology, in addition to tests specific to the region they have visited. Terminal urine microscopy and serology for schistosomiasis should also be performed in those returning from Africa. Eosinophilia is also a feature of significant non-infective conditions, which should be considered.

Fever in returned travellers presenting in the United Kingdom: recommendations for investigation and initial management.

International travel is increasing. Most physicians and general practitioners will encounter returned travellers with fever and the majority of travel-related infection is associated with travel to the tropics. In those returning from the tropics malaria must always be excluded, and HIV considered, from all settings. Common causes of non-malarial fever include from Africa rickettsial diseases, amoebic liver abscess and Katayama syndrome; from South and South East Asia, enteric fever and arboviral infection; from the Middle East, brucellosis and from the Horn of Africa visceral leishmaniasis. Other rare but important diseases from particular geographical areas include leptospirosis, trypanosomiasis and viral haemorrhagic fever. North and South America, Europe and Australia also have infections which are geographically concentrated. Empirical treatment may have to be started based on epidemiological probability of infection whilst waiting for results to return. The evidence base for much of the management of tropical infections is limited. These recommendations provide a pragmatic approach to the initial diagnosis and management of fever in returned travellers, based on evidence where it is available and on consensus of expert opinion where it is not. With early diagnosis and treatment the majority of patients with a potentially fatal infection related to travel will make a rapid and full recovery.

Blood-stage challenge for malaria vaccine efficacy trials: a pilot study with discussion of safety and potential value.

There is increasing interest in malaria vaccines targeting the asexual blood stage of Plasmodium falciparum. Without accepted immunologic correlates of clinical protection, challenge studies are useful for assessing the efficacy of candidate vaccines in vivo in healthy volunteers. We report a pilot study of a safe and robust challenge protocol using a blood-stage inoculum. We have applied well-validated trial endpoints and twice daily real-time quantitative polymerase chain reaction monitoring of parasitemia to blood-stage challenge, which enabled direct comparison with sporozoite challenge. We found that greater accuracy in quantification of blood-stage growth rates can be achieved with blood-stage challenge. This finding may provide greater power to detect partial efficacy of many blood-stage candidate vaccines. We discuss the potential utility of blood-stage challenge studies in accelerating malaria vaccine development.