COVID-19: public health management of the first two confirmed cases identified in the UK.

We report key learning from the public health management of the first two confirmed cases of COVID-19 identified in the UK. The first case imported, and the second associated with probable person-to-person transmission within the UK. Contact tracing was complex and fast-moving. Potential exposures for both cases were reviewed, and 52 contacts were identified. No further confirmed COVID-19 cases have been linked epidemiologically to these two cases. As steps are made to enhance contact tracing across the UK, the lessons learned from earlier contact tracing during the country's containment phase are particularly important and timely.

HIV-associated fatigue in the era of highly active antiretroviral therapy: novel biological mechanisms?

OBJECTIVE: The aim of the study was to determine the prevalence and risk factors for HIV-associated fatigue in the era of highly active antiretroviral therapy (HAART). METHODS: A cross-sectional survey of 100 stable HIV-infected out-patients was carried out. Severity of fatigue was measured using the Fatigue Impact Scale (FIS). Symptoms of orthostatic intolerance (dysautonomia) were evaluated using the Orthostatic Grading Scale (OGS). Data for HIV-infected patients were compared with those for 166 uninfected controls and 74 patients with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (encephalopathy) (ME). RESULTS: Ninety-one per cent of HIV-infected patients were on HAART and 78% had suppressed plasma HIV viral load (≤ 40 HIV-1 RNA copies/mL). Fifty-one per cent of HIV-infected patients reported excessive symptomatic fatigue (FIS ≥ 40), and 28% reported severe fatigue symptoms (FIS ≥ 80). The mean FIS score among HIV-infected patients was 50.8 [standard deviation (SD) 41.9] compared with 13.0 (SD 17.6) in uninfected control subjects, and 92.9 (SD 29.0) in CFS patients (P < 0.001 for comparison of HIV-infected patients and uninfected controls). Among HIV-infected patients, fatigue severity was not significantly associated with current or nadir CD4 lymphocyte count, HIV plasma viral load, or whether on HAART. Prior dideoxynucleoside analogue (d-drug) exposure (P = 0.016) and the presence of clinical lipodystrophy syndrome (P = 0.011) were associated with fatigue. Additionally, fatigue severity correlated strongly with symptomatic orthostatic intolerance (r = 0.65; P < 0.001). CONCLUSIONS: Fatigue is very common and often severe in HIV-infected out-patients, despite viral suppression and good immune function. In a subgroup of patients, prior d-drug exposure may contribute to fatigue, suggesting a metabolic basis. Dysautonomia may also drive fatigue associated with HIV infection, as in other chronic diseases, and CFS/ME, and should be further evaluated with the potential for a shared therapeutic approach.

An audit of cervical cytology in HIV-positive women.

OBJECTIVE: To investigate whether a cohort of human immunodeficiency virus-positive (HIV+) women were having annual cervical cytology as recommended by the English National Health Service cervical screening programme (NHSCSP) guidelines. METHODS: An audit of cervical cytology in an HIV+ cohort of 187 women by obtaining their last cervical cytology result and recall from local cytology services. RESULTS: Of the 187 women in the audit, two were ineligible, leaving 185 women, 167 (90.3%) of whom were aged 25-64 years and eligible for screening. Of the 185 women, 126 (68.1%) had a cytology history, 50 (27%) had never had cervical cytology and nine (4.9%) had inadequate details to ascertain whether or not they had a cytology history. Of the 126 with a cytology record, 34 (27%) had a current cytological abnormality, which was low grade in 25 (19.8%) and high grade in nine (7.1%). Among women aged 25-64 years attending the clinic, these percentages were significantly higher than expected for England as a whole (P < 0.001). Of 126 women with a cytology record, 29 (23%) were overdue for their recall date and of these the previous test was abnormal in 14 (48.3%). Cytology tests were taken within the community setting in 61 (48.4%), whereas 65 (51.6%) were seen either at an HIV sexual health clinic or were under colposcopy follow-up. Of 91 women with negative cytology only 50 (54.9%) were recommended for repeat in 12 months. CONCLUSION: This audit demonstrates a high rate of cytological abnormalities among HIV+ women compared with the screening population at large. Implementation of NHSCSP guidelines has been difficult and requires improved care pathways between HIV clinics, primary care and laboratories.

Missed opportunities to diagnose syphilis prior to the development of sight-losing uveitis.

The incidence of syphilis in the UK is rapidly rising. Uveitis (intraocular inflammation) usually occurs in the secondary or later stages of syphilis infection and is sight-threatening. Methods A retrospective analysis of the demographics, presentation, diagnosis, treatment and outcomes of patients with syphilitic uveitis managed in Newcastle from 2005-2016 was carried out. Results Ten males (19 eyes) with syphilitic uveitis had a generally good visual and serological response to penicillin treatment. In eight of the patients there had been a failure to test for syphilis during assessments by various medical practitioners for unexplained symptoms that were attributable to syphilis prior to the eye involvement. Conclusion Uveitis associated with syphilis can be sight-threatening but responds well to treatment. In our case series there were multiple missed opportunities to diagnose syphilis prior to presentation with eye disease, with a general failure of healthcare professionals to take an adequate sexual history.

Audit of the use of benzathine penicillin, post-treatment syphilis serology and partner notification of patients with early infectious syphilis.

Recent increases in the incidence of early infectious syphilis have been particularly noted in men who have sex with men (MSM). Case-notes of 40 consecutive patients with infectious syphilis and follow-up data for one year were audited. Of the 40 patients, six were HIV co-infected. In all, 31 men received benzathine penicillin as first line while the remaining had other treatments. About 17 (42.5%) failed to attend for any post-treatment serological tests. Of the remainder, 17 (42.5%) attended for the first appointment and only 13 (32.5%) attended for the full one year follow-up. In all, 40 men in the study had 362 sexual contacts of which only 44 (12.2%) elected to be screened. This study illustrates the successful use of benzathine penicillin as first-line treatment, lack of patient compliance with post-treatment serological follow-up and difficulty with partner notification.

Age as a risk factor for severe manifestations and fatal outcome of falciparum malaria in European patients: observations from TropNetEurop and SIMPID Surveillance Data.

Previous studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or diseases.

Imported Falciparum malaria in Europe: sentinel surveillance data from the European network on surveillance of imported infectious diseases.

Malaria continues to have a high morbidity rate associated among European travelers. Thorough recording of epidemiological and clinical aspects of imported malaria has been helpful in the detection of new outbreaks and areas of developing drug resistance. Sentinel surveillance of data collected prospectively since 1999 has begun within TropNetEurop, a European network focusing on imported infectious diseases. TropNetEurop appears to cover approximately 10% of all patients with malaria seen in Europe. Reports of 1659 immigrants and European patients with Plasmodium falciparum malaria were analyzed for epidemiological information and data on clinical features. Regional data were quite diverse, reflecting local patterns of immigration and international travel. By far, the most infections were imported from West Africa. Europeans had more clinical complications; consequently, all deaths occurred in this group. Compared with European standards, the mortality rate was low (0.6% in Europeans). Data from TropNetEurop member sites can contribute to our understanding of the epidemiological and clinical findings regarding imported falciparum malaria.

Epidemiology and clinical features of vivax malaria imported to Europe: sentinel surveillance data from TropNetEurop.

BACKGROUND: Plasmodium vivax is the second most common species among malaria patients diagnosed in Europe, but epidemiological and clinical data on imported P. vivax malaria are limited. The TropNetEurop surveillance network has monitored the importation of vivax malaria into Europe since 1999. OBJECTIVES: To present epidemiological and clinical data on imported P. vivax malaria collected at European level. MATERIAL AND METHODS: Data of primary cases of P. vivax malaria reported between January 1999 and September 2003 were analysed, focusing on disease frequency, patient characteristics, place of infection, course of disease, treatment and differences between network-member countries. RESULTS: Within the surveillance period 4,801 cases of imported malaria were reported. 618 (12.9%) were attributed to P. vivax. European travellers and immigrants were the largest patient groups, but their proportion varied among the reporting countries. The main regions of infection in descending order were the Indian subcontinent, Indonesia, South America and Western and Eastern Africa, as a group accounting for more than 60% of the cases. Regular use of malaria chemoprophylaxis was reported by 118 patients. With 86 (inter-quartile range 41-158) versus 31 days (inter-quartile range 4-133) the median symptom onset was significantly delayed in patients with chemoprophylaxis (p < 0.0001). Common complaints were fever, headache, fatigue, and musculo-skeletal symptoms. All patients survived and severe clinical complications were rare. Hospitalization was provided for 60% and primaquine treatment administered to 83.8% of the patients, but frequencies varied strongly among reporting countries. CONCLUSIONS: TropNetEurop data can contribute to the harmonization of European treatment policies.

Burden and cost of imported infections admitted to infectious diseases units in England and Wales in 1998 and 1999.

BACKGROUND: International travel from the UK has been rising, and the number of imported infections has increased. This study aimed to describe the number, nature, origin, clinical burden and cost of imported infections treated in infectious disease units (IDU) in England and Wales. METHOD: Information about all admissions in 1998 and 1999 with illnesses considered to have been acquired during their most recent travel abroad was collected retrospectively by IDUs using a pre-piloted questionnaire. RESULTS AND ANALYSIS: Four of the 23 IDUs in England and Wales were able to complete the questionnaires. They reported a total of 421 travel related admissions during the 2-year period. Three hundred and ninety-two of these cases were attributed to infectious causes, and of these a discharge diagnosis was made for 340 cases. The total number of bed days used to treat cases of imported infection was 2918. The most common diagnosis was malaria. The odds ratio that cases of imported infection were malaria was highest following visits to Africa. The average cost per bed day on the IDUs was around pound sterling 100, and on this basis, the total cost of treating imported infections on the four IDUs in 2 years was around pound sterling 289,000. The relative risk of acquiring an imported infection requiring treatment on an IDU was greatest for travellers to Africa. CONCLUSIONS: From this study, the estimate of the total annual cost of IDU treatment for imported infections in England and Wales is in excess of pound sterling 800,000. Many cases may be preventable with prophylactic medication and vaccination and travel advice on risk reduction. Further information about imported infections would be useful to inform travel medicine services, other clinicians and travellers about the health risks associated with travel to specific areas, and help to target and assess the cost effectiveness of preventative measures.

Honeymoon malaria and "herbal" therapy: A case report.

A marked rise in the number of cases of malaria in the UK contracted in east Africa has been reported in 1998. This may be explained by the "Lariam"-media hype, poor understanding, poverty of health education, or increase in travel to more exotic destinations. European centers have experienced changes in the pattern of imported malaria and constant up-dates are essential. However even the best informed may still acquire malaria.

Two simultaneous cases of Cyclospora cayatensis enteritis returning from the Dominican Republic.

According to the "International Passenger Survey," published in 1996 by the Office of Trading Standards, 534,000 British people traveled to the Caribbean area (personal communication, ABTA, 1998). The Dominican Republic, the eastern end of a large Caribbean island, has become in recent years one of the most popular destinations for UK holidaymakers as well as for travelers from many other countries. Cyclospora cayatensis has been firmly identified as a cause of gastroenteritis among international travelers,1 including human immunodeficiency virus (HIV)-positive individuals,2 but it has not been previously reported in the literature in British individuals returning from this increasingly popular vacation destination.

Imported schistosomiasis in Europe: sentinel surveillance data from TropNetEurop.

BACKGROUND: Schistosomiasis is a major parasitic disease, increasingly imported into temperate climates by immigrants from and travelers to endemic areas. METHOD: To generate valid data on imported infectious diseases to Europe and to recognize trends over time, the European Network on Imported Infectious Diseases Surveillance (TropNetEurop) was founded in 1999. Three hundred and thirty-three reports of schistosomiasis were analyzed for epidemiologic and clinical features. RESULTS: Male patients accounted for 64% of all cases. The average age of all patients was 29.5 years. The majority of patients were of European origin (53%). Europeans traveled predominantly for tourism (52%). Main reasons for travel for people from endemic areas were immigration and refuge (51%) and visits to relatives and friends (28%). The majority of infections were acquired in Africa; 92 infections were clearly attributable to Schistosoma haematobium, 130 to Schistosoma mansoni, and 4 to Schistosoma intercalatum. Praziquantel was the only treatment used. No deaths were recorded. CONCLUSION: TropNetEurop sentinel provides valuable epidemiologic and clinical data on imported schistosomiasis to Europe.

A hoarse voice: atypical mycobacterial infection of the larynx.

Myobacterium malmoense is a non-tuberculous mycobacterium that most commonly causes pulmonary infection, particularly in patients with underlying pulmonary disease or immunodeficiency. We describe a case of Mycobacterium malmoense infection of the larynx in a previously well middle-aged woman, which has previously not been reported. The case highlights the importance of considering atypical mycobacterial infection in the differential diagnosis of laryngeal lesions.

Apolipoprotein B-associated cholesterol is a determinant of treatment outcome in patients with chronic hepatitis C virus infection receiving anti-viral agents interferon-alpha and ribavirin.

BACKGROUND: Hepatitis C virus (HCV) co-opts very-low-density lipoprotein (VLDL) pathways for replication, secretion and entry into hepatocytes and associates with apolipoprotein B (apoB) in plasma. Each VLDL contains apoB-100 and variable amounts of apolipoproteins E and C, cholesterol and triglycerides. AIM: To determine whether baseline lipid levels predicted treatment outcome. METHODS: Retrospective analysis was performed of 250 chronic hepatitis C (CHC) patients who had received anti-viral agents interferon-alpha and ribavirin; 165 had a sustained virological response (SVR). Pre- and post-treatment nonfasting lipid profiles were measured and non-high-density lipoprotein (non-HDL) cholesterol (i.e. apoB-associated) was calculated. Binary logistic regression analysis assessed factors independently associated with treatment outcome. RESULTS: There was an independent association between higher apoB-associated cholesterol (non-HDL-C) and increased odds of SVR (odds ratio 2.09, P = 0.042). In multivariate analysis, non-HDL-C was significantly lower in HCV genotype 3 (g3) than genotype 1 (P = 0.007); this was reversible upon eradication of HCVg3 (pre-treatment non-HDL-C = 2.8 mmol/L, SVR = 3.6 mmol/L, P < 0.001). CONCLUSIONS: Higher apoB-associated cholesterol is positively associated with treatment outcome in CHC patients receiving anti-viral therapy, possibly due to competition between apoB-containing lipoproteins and infectious low-density HCV lipo-viral particles for hepatocyte entry via shared lipoprotein receptors.

Apolipoprotein epsilon3 allele is associated with persistent hepatitis C virus infection.

BACKGROUND: Host genetic factors may significantly influence the ability to clear hepatitis C virus (HCV) following infection. HCV is associated with very low density lipoproteins (VLDL) and low density lipoproteins (LDL) in the host's circulation. Apolipoprotein E (APOE) is found in VLDL and binds to potential receptors involved in HCV entry into cells, the LDL receptor, and the scavenger receptor protein SR-B1. The APOE gene is polymorphic with three alleles coding for three isoforms: Apo-epsilon2, Apo-epsilon3, and Apo-epsilon4. The aim of this study was to assess if these functional polymorphisms determine disease outcome in HCV infected individuals. METHODS: The APOE genotype was determined in 420 Northern European patients with evidence of exposure to HCV. Genotype and allele distribution were compared with those of 288 healthy controls and progression of liver disease and viral clearance were analysed according to APOE allele status. RESULTS: The APOE*E2 and APOE*E4 alleles were both associated with a reduced likelihood of chronic infection (odds ratio (OR) 0.39 (95% confidence interval (CI) 0.211-0.728), p = 0.003; and OR 0.6 (95% CI 0.38-0.96), p = 0.032) and there was a notable absence of the E2E2 genotype in the HCV antibody positive group compared with the control population (p = 0.0067). Overall the genotypes carrying the E2 allele (E2,E3 and E2,E4) were associated with the equivalent of a 3-5-fold reduction in the risk of chronic HCV infection (genotype relative risk 0.36 and 0.20, respectively). CONCLUSION: This study indicates that functional APOE gene polymorphisms may be a determinant of outcome in HCV infection. We hypothesise that the E2 allele may protect against viral persistence via defective binding of HCV lipoviral particles to the cellular receptors involved in entry of these infectious particles.

Pancreatic exocrine insufficiency in HIV-positive patients.

OBJECTIVES: We describe the management of a cohort of eight HIV-positive patients on antiretroviral medication with evidence of pancreatic insufficiency consisting of chronic diarrhoea and a low faecal elastase measurement. PATIENTS AND METHODS: Twenty-two patients with chronic diarrhoea for whom a faecal elastase measurement was available were identified retrospectively. We compared baseline demographic characteristics, antiretroviral treatment and symptoms of steatorrhea between patients with evidence of pancreatic insufficiency, i.e. a low faecal elastase measurement of <200 microg/g (cases), and patients with evidence of normal pancreatic function, i.e. a normal faecal elastase measurement of >200 microg/g (controls). We describe the management of the patients with evidence of pancreatic insufficiency. RESULTS: Of the 22 patients, eight had evidence of pancreatic insufficiency, i.e. a low faecal elastase measurement. Comparing cases with controls, cases were more likely to have symptoms of steatorrhea (P=0.03) or to have lost weight (P=0.02). Cases were also significantly more likely to have taken didanosine (ddI) as part of their antiretroviral treatment when their symptoms started. Seven cases were treated with oral pancreatic supplements and all had symptomatic improvement of their diarrhoea. One patient stopped treatment with oral pancreatic supplements because of side effects without a relapse of symptoms; he had also stopped zalcitabine (ddC). CONCLUSIONS: We believe that measurement of faecal elastase to detect pancreatic insufficiency should be part of the standard investigation of HIV-positive patients with chronic diarrhoea alongside assessment for other causes of diarrhoea. Faecal elastase measurements should be requested, in particular, in all patients with diarrhoea and weight loss, or symptoms of steatorrhea, and in those on treatment with an antiretroviral regime containing ddI. If the faecal elastase level is low, a switch of antiretroviral medication to a nonddI/ddC-containing regime should be considered and treatment with oral pancreatic enzyme therapy should be instituted.