Emerging and re-emerging viral infections in Europe

Emerging viral infections are becoming a serious problem in Europe in the recent years. This is particularly true for severe acute respiratory syndrome (SARS), West Nile virus (WNV) disease, Toscana virus (TOSV) disease, and potentially for avian influenza virus (H5N1). In contrast, emergence or re-emergence of severe viral infections, including tick borne encephalitis virus, and viral haemorrhagic fever caused by Hantavirus and dengue virus have been frequently reported in several European countries. Laboratory diagnosis of these viral infections based on viral isolation or detection by immune electron microscopy, immunoassay and polymerase chain reaction (PCR) has dramatically improved in the recent years, and SARS represents a good example of a diagnostic approach to emerging viral infections. Finally, old and new promising agents are in the pipeline of pharmaceutical companies to treat emerging viral infections. However only prevention based on large epidemiological studies, and research and development of new vaccines may be able to control and eventually eradicate these deadly viral infections.     

Surgical audit: Comparison of the work load and results of two hospitals in the same district.

Surgical audit is being undertaken to monitor and compare (by computer) the type of patient, work load, and results of two similar surgical units. Both units are in the City and Hackney District of London, one at St Bartholomew''s Hospital and the other at Hackney Hospital. During 1978, 736 patients were admitted by the unit at St Bartholomew''s Hospital and 902 by the unit at Hackney. At St Bartholomew''s 70% of admissions were elective compared with 49% at Hackney, where 86% of patients lived within the district compared with only 36% at St Bartholomew''s. The wound was the commonest site for complications, infection affecting 9% of those at Hackney and 6% at St Bartholomew''s, despite identical antibiotic policies. There were six post-operative deaths at St Bartholomew''s and 32 at Hackney. In both hospitals the length of stay was similar, 50% of patients being discharged within one week and 80% within two weeks. As a result of the audit a vigorous venous thrombosis prophylactic regimen has been instituted, and at Hackney the anaesthetic department has been strengthened and a new intensive care unit opened.     

Hemophagocytic syndrome associated with dengue hemorrhagic fever

The haemophagocytic syndrome is characterised by systemic proliferation of non-neoplastic histiocytes showing haemophagocytosis resulting in blood cytopenia. It has been described in relation to several viruses earlier. We present three patients with haemophagocytic syndrome (HFS) secondary to dengue haemorrhagic fever (DHF) confirmed by standard laboratory tests. The patients were hospitalized at the University Hospital (Hospital Universitario Ramón González Valencia-HURGV) in Bucaramanga, Colombia, during the past two years. They were all school-aged patients who presented DHF with intense abdominal pain, prolonged fever, hypotension and painful hepatomegaly. Laboratory tests showed thrombocytopenia, anaemia and leukopenia. A calculous cholecystitis was observed in the abdominal ultrasonography, and all bone marrow aspirations showed that platelets, red and white blood cells were phagocyted by histiocytes. According to the International Society of Histiocytosis, SHF is defined and classified in three major categories; the reported cases corresponded to histiocytosis class II, specifically to secondary SHF. Diverse associations of this syndrome correspond to viral infections and some other non-infectious diseases. A difference has been established between primary SHF and secondary SHF. Finally, we emphasize that these three patients had an atypical evolution of FHD, being prolonged fever and persistent abdominal pain the most important symptoms. The authors recommend that a bone marrow aspiration should be carried out as part of the differential diagnosis study in prolonged fever associated with dengue, as there is a possibility that this complication could be secondary SHF.     

Viral haemorrhagic fevers--evolution of the epidemic potential

In this review modern data on dangerous and particularly dangerous viral haemorrhagic fevers caused by a group of viruses belonging to the families of phylo-, arena-, flavi-, bunya- and togaviruses are presented. Morbidity rates and epidemics caused by Marburg virus, Ebola fever virus, Lassa fever virus, Argentinian and Bolivian haemorrhagic fever viruses, dengue haemorrhagic fever virus, Crimean haemorrhagic fever virus, Hantaviruses are analyzed. Mechanisms of the evolution of the epidemic manifestation of these infections are considered. The importance of the development of tools and methods of diagnosis, rapid prevention and treatment of exotic haemorrhagic fevers is emphasized.     

Immunological and viral determinants of dengue severity in hospitalized adults in Ha Noi, Viet Nam

Background

The relationships between the infecting dengue serotype, primary and secondary infection, viremia and dengue severity remain unclear. This cross-sectional study examined these interactions in adult patients hospitalized with dengue in Ha Noi.

Methods and Findings

158 patients were enrolled between September 16 and November 11, 2008. Quantitative RT-PCR, serology and NS1 detection were used to confirm dengue infection, determine the serotype and plasma viral RNA concentration, and categorize infections as primary or secondary. 130 (82%) were laboratory confirmed. Serology was consistent with primary and secondary infection in 34% and 61%, respectively. The infecting serotype was DENV-1 in 42 (32%), DENV-2 in 39 (30%) and unknown in 49 (38%). Secondary infection was more common in DENV-2 infections (79%) compared to DENV-1 (36%, p<0.001). The proportion that developed dengue haemorrhagic fever (DHF) was 32% for secondary infection compared to 18% for primary infection (p = 0.14), and 26% for DENV-1 compared to 28% for DENV-2. The time until NS1 and plasma viral RNA were undetectable was shorter for DENV-2 compared to DENV-1 (p≤0.001) and plasma viral RNA concentration on day 5 was higher for DENV-1 (p = 0.03). Plasma viral RNA concentration was higher in secondary infection on day 5 of illness (p = 0.046). We didn''t find an association between plasma viral RNA concentration and clinical severity.

Conclusion

Dengue is emerging as a major public health problem in Ha Noi. DENV-1 and DENV-2 were the prevalent serotypes with similar numbers and clinical presentation. Secondary infection may be more common amongst DENV-2 than DENV-1 infections because DENV-2 infections resulted in lower plasma viral RNA concentrations and viral RNA concentrations were higher in secondary infection. The drivers of dengue emergence in northern Viet Nam need to be elucidated and public health measures instituted.     

A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy.

Several viral infections have been reported to result in more severe disease in pregnant than non-pregnant women, but the relative risks have not been well characterised. This has now been done for Lassa fever in a prospective study of 68 pregnant and 79 non-pregnant women who were admitted to hospital in Sierra Leone with confirmed Lassa fever. Lassa fever was the main cause of maternal mortality in the hospital, accounting for 25% of maternal deaths. Twelve of 40 patients in the third trimester died, compared with two of 28 in the first two trimesters and 10 of 79 non-pregnant women. The odds ratio for death in the third trimester compared with the first two trimesters was 5.57 (95% confidence intervals 1.02 to 30.26). The condition of the mother improved rapidly after evacuation of the uterus, whether by spontaneous abortion, evacuation of retained products of conception, or normal delivery; 10 of 26 women without uterine evacuation died, but only four of 39 women with evacuation died (p = 0.0016). The odds ratio for death with pregnancy intact was 5.47 (95% confidence interval 1.35 to 22.16). Fetal and neonatal loss was 87%. The risk of death from Lassa fever in the third trimester is significantly higher than that in the first two trimesters and higher than that for non-pregnant women, but evacuation of the uterus can significantly improve the mother''s chance of survival.     

Admissions to a Provincial Psychiatric Hospital: The Effects of Opening a Second In-patient Facility

Until 1955, the Saskatchewan Hospital, North Battleford, was the only facility designated for in-patient psychiatric treatment of the northern half of Saskatchewan''s population. In that year the University Hospital''s 39-bed psychiatric unit was opened in Saskatoon, but the number of Saskatoon patients referred to North Battleford have continued to increase.A statistical study of changes in the annual admission rates (patients/1000 population) to the Saskatchewan Hospital shows that the opening of the University Hospital unit has reduced the rate of intake of Saskatoon residents to the Saskatchewan Hospital. This decrease is related to specific diagnostic groups. There have also been changes in methods of referral.     

Isolation and identification of Crimean-Congo hemorrhagic fever virus in the Stavropol territory

The results of the isolation and identification of the causative agent of a haemorrhagic fever outbreak in the Stavropol Territory are presented. The virus isolated from blood of haemorrhagic fever patients by virological methods was identified in serological and molecular tests as Crimean haemorrhagic fever virus. This epidemiological analysis testify to increased activity of the natural focus of Crimean-Congo haemorrhagic fever in this area due to a number of natural and other factors leading to intensification of its epidemic realization.     

Laboratory Surveillance of Dengue in Rio Grande do Sul,Brazil, from 2007 to 2013

Background

According to official records, dengue was introduced in Brazil in the 80''s; since then several epidemics have occurred. Meanwhile, in Rio Grande do Sul (RS, Southern Brazil) the first autochthonous case occurred only in 2007.

Methodology and Principal Findings

In this study we report laboratory surveillance of dengue cases and seasonality of positive cases, describe serotypes and characterize the epidemiological pattern of dengue in RS from 2007 to 2013. A total of 9,779 serum samples from patients with suspected dengue fever were collected and submitted to molecular and/or serological analyses for dengue virus identification and serotyping, based on viral isolation, NS1 antigen detection and qRT-PCR, or Dengue IgM capture ELISA and MAC-ELISA. The first autochthonous dengue case in RS was confirmed in 2007 (DENV-3). While in 2008 and 2009 only imported cases were registered, autochthonous infection waves have been occurring since 2010. The highest number of dengue infections occurred in 2010, with DENV-1 and DENV-2 outbreaks in Northwestern RS. In 2011, another DENV-1 and DENV-2 outbreak occurred in the Northwestern region; moreover, DENV-4 was detected in travelers. In 2012, DENV-1 and DENV-4 co-circulated. DENV-2 circulation was only detected again in 2013, in high frequency (56.7%), co-circulating with DENV-4 (35%). Most infections occur in adults during summer. Differences in prevalence between genders were observed in 2007 (60% females), 2008 (60.8% males) and 2009 (77.5% males).

Conclusions

According to results of dengue surveillance, there was an increase in the number of dengue cases in RS and of cities infested with Aedes aegypti, possibly as a consequence of introduction of new serotypes and the difficulty of health programs to control the vector.     

Use of computer program for diagnosing jaundice in district hospitals and specialized liver unit.

A computer-assisted model for diagnosing jaundice has been adapted for use on the University of London C.D.C. 7600 computer via an on-line terminal at King''s College Hospital to provide a rapid turn-round time. The model was used prospectively in the diagnosis of 219 patients--135 seen in a specialized liver unit and 84 seen in one of four district hospitals in south-east London--with an overall accuracy in distinguishing among 11 different causes of jaundice of 69% and 62% respectively. These figures rose to 77% and 88% respectively when only those patients in whom the final diagnosis reached a "certain" probability were considered. When used to distinguish between a medical and a surgical cause of jaundice the accuracy was 86% in the liver unit and 77% in the district hospitals, rising to 95% in both series for those with a diagnosis of certain probability. The proposed improvements to the model--namely, the use of two deparate data bases and more diagnoses within the matrix--should be improve the accuracy even further. In practice the rapid feedback to the clinicians looking after patients provided help in managing difficult cases.     

Severe acquired immunodeficiency in European homosexual men.

Four previously healthy Danish homosexual men developed Kaposi''s sarcoma or opportunistic infections with fever of unknown origin and lymphadenopathy. One patient died of a Pneumocystis carinii pneumonia. Three patients had defective cell-mediated immunity with absent leucocyte interferon production and decreased proliferative response to mitogens and antigens. T lymphocyte helper subsets and natural killer cell activity were reduced. Unstimulated mononuclear cells produced leucocyte migration inhibitor factor. Two patients were sexual partners and three had never been to the USA, where cases of severe acquired immunodeficiency have been reported. Thus, the syndrome must also be suspected in European homosexual men who present with fever of unknown origin, opportunistic infections, or Kaposi''s sarcoma.     

Can Inpatient Hospital Experiences Predict Central Line-Associated Bloodstream Infections?

Background

Factors that increase the risk of central line-associated bloodstream infections (CLABSIs) are not fully understood. Recently, Hospital Compare began compiling data from hospital-required reporting to the CDC''s National Healthcare Safety Network on CLABSIs in intensive care units (ICUs), at over 4,000 Medicare-certified hospitals in the United States, and made this data accessible on a central website. Also available on the same website are results from the Hospital Consumer Assessment of Healthcare Providers and Systems survey of patients'' hospital experiences. Utilizing both databases, our objective was to determine whether patients'' hospital experiences were significantly associated with increased risk for reported ICU CLABSI.

Methods and Findings

We conducted a zero-inflated Poisson regression analysis at the hospital level on CLABSI-observed cases by ICUs in acute care hospitals (n = 1987) in the United States between January 1, 2011, and December 31, 2011. During this period there were a total of 10,866 CLABSI cases and 9,543,765 central line days. In our final model, the percent of patients who reported that they “sometimes” or “never” received help as soon as they wanted was significantly associated with an increased risk for CLABSIs.

Conclusions

Using national datasets, we found that inpatients'' hospital experiences were significantly associated with an increased risk of ICU reported CLABSIs. This study suggests that hospitals with lower staff responsiveness, perhaps because of an understaffing of nurse and supportive personnel, are at an increased risk for CLABSIs. This study bolsters the evidence that patient surveys may be a useful surrogate to predicting the incidence of hospital acquired conditions, including CLABSIs. Moreover, our study found that poor staff responsiveness may be indicative of greater hospital problems and generally poorly performing hospitals; and that this finding may be a symptom of hospitals with a multitude of problems, including patient safety problems, and not a direct cause.     

Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study

Introduction

The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes.

Methods and Findings

We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis.

Conclusions

Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts.     

Organ donation from intensive care units in England.

OBJECTIVE--To audit all deaths in intensive care units (excepting coronary care only and neonatal intensive care units) in England to assess potential for organ procurement. DESIGN--An audit in which 14 regional health authorities and London special health authorities each designated a regional liaison officer to identify intensive care units and liaise with Department of Health and the Medical Research Council''s biostatistics unit in distribution, return, and checking of audit forms. Audit took place from 1 January to 31 March 1989 and will continue to 31 December 1990. SETTING--278 Intensive care units in England. PARTICIPANTS--Colleagues in intensive care units (doctors, nurses, coordinators, and others), who completed serially numbered audit forms for all patients who died in intensive care. RESULTS--The estimated number of deaths in intensive care units was 3085, and validated audit forms were received for 2853 deaths (92%). Brain stem death was a possible diagnosis in only 407 (14%) patients (about 1700 cases a year) and was confirmed in 282 (10%) patients (an estimated 1200 cases a year). Half the patients (95% confidence interval 45% to 57%) in whom brain stem death was confirmed became actual donors of solid organs. Tests for brain stem death were not performed in 106 (26%) of 407 patients with brain stem death as a possible diagnosis, and general medical contraindication to organ donation was recorded for 48 (17%) of 282 patients who fulfilled brain stem death criteria before cessation of heart beat. The criteria were fulfilled before cessation of heart beat and in the absence of any general medical contraindication to organ donation in 234 patients, 8% of those dying in intensive care (an estimated 1000 cases a year). Consent for organ donation was given in 152 (70%) of 218 cases (64% to 76%) when the possibility of organ donation was suggested to relatives. In only 14 out of 232 families (6%; 3% to 9%) was there no discussion of organ donation with relatives. Corneal suitability was recorded as "not known" in a high proportion (1271; 45%) of all deaths and intensive care units reported only 123 corneal donors (4% of all audited deaths). CONCLUSION--When brain stem death is a possible diagnosis tests should always be carried out for confirmation. Early referral to the transplant team or coordinator should occur in all cases of brain stem death to check contraindications to organ donation. There should be increased use of asystolic kidney donation, and patients should be routinely assessed for suitability for corneal donation. Finally, more publicity and education are necessary to promote consent.     

Diagnostic capacity for viral haemorrhagic septicaemia virus (VHSV) infection in rainbow trout (Oncorhynchus mykiss) is greatly increased by combining viral isolation with specific antibody detection

Detection of disease specific antibodies in farmed rainbow trout (Oncorhynchus mykiss) has been proposed as an alternative or supplement to the currently approved procedures for diagnosis and surveillance in this species. In samples from natural outbreaks of the disease viral haemorrhagic septicaemia (VHS) at two freshwater farms in southern Denmark serologic testing was used to broaden the diagnostic window from outbreak to diagnosis in the laboratory as compared to traditional procedures of isolation and identification of the virus. The serologic assay clearly increased the chance of detecting present or previous infections where the pathogen could not be isolated by standard methods (indicating older infections where the virus had been cleared). Our data allowed us to monitor the levels of neutralising antibodies in relation to the presence of the virus in fish experiencing two different types of outbreaks at two different farms. By sequence analysis of the viral glycoprotein from selected isolates we found no evidence for escape mutants having developed in the fish showing high titres of neutralising antibodies.     

Review of cases of nosocomial Lassa fever in Nigeria: the high price of poor medical practice.

OBJECTIVE--To investigate two hospital outbreaks of Lassa fever in southern central Nigeria. SETTING--Hospitals and clinics in urban and rural areas of Imo State, Nigeria. DESIGN--Medical records were reviewed in hospitals and clinics in both areas. Patients with presumed and laboratory confirmed Lassa fever were identified and contracts traced. Hospital staff, patients, and local residents were questioned, records were carefully reviewed, and serum samples were taken. Serum samples were assayed for antibody specific to Lassa virus, and isolates of Lassa virus were obtained. RESULTS--Among 34 patients with Lassa fever, including 20 patients, six nurses, two surgeons, one physician, and the son of a patient, there were 22 deaths (65% fatality rate). Eleven cases were laboratory confirmed, five by isolation of virus. Most patients had been exposed in hospitals (attack rate in patients in one hospital 55%). Both outbreak hospitals were inadequately equipped and staffed, with poor medical practice. Compelling, indirect evidence revealed that parenteral drug rounds with sharing of syringes, conducted by minimally educated and supervised staff, fuelled the epidemic among patients. Staff were subsequently infected during emergency surgery and while caring for nosocomially infected patients. CONCLUSION--This outbreak illustrates the high price exacted by the practice of modern medicine, particularly use of parenteral injections and surgery, without due attention to good medical practice. High priority must be given to education of medical staff in developing countries and to guidelines for safe operation of clinics and hospitals. Failure to do so will have far reaching, costly, and ultimately devastating consequences.     

Acute renal failure in tropical Africa.

Between 1972 and 1975, 55 adult patients with acute renal failure were admitted to the renal unit of Korle Bu Hospital. Fourteen patients died, giving an overall death rate of 25%. Massive intravascular haemolysis after a short febrile illness was the commonest cause of acute renal failure. Clinically these patients presented with blackwater fever but in only one could Plasmodium falciparum malaria be confidently diagnosed. In half the patients various bacterial and viral infections (especially typhoid) could be incriminated as causing this blackwater fever syndrome. The incidence of glucose-6-phosphate dehydrogenase deficiency was 22.5%, but we could not confirm the impression of a greater predisposition to acute renal failure in patients with this enzyme defect.     

Development and evaluation of a PCR method for diagnosis of Salmonella enteric fever, based on DNA sequences of the hilA gene

Typically, diagnosis of enteric fever due to Salmonella spp. is by bacterial isolation from blood culture; however, the blood culture method is slow, not always available, and not informative in patients with antibiotic treatment. Salmonella spp. uses the hilA gene (component of the pathogenicity island I) to invade epithelial cells and produce infection. Using the hilA gene sequence a PCR test was designed to detect Salmonella in blood samples. The sensitivity (S), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) of the PCR method were obtained by testing the blood samples from 34 patients with suspected of enteric fever. Presence of S. typhi was confirmed by blood culture. Blood samples were also tested from 35 patients with infections due to other non-Salmonella pathogens, again corroborated by blood culture (Klebsiella pneumoniae, 9; Serratia marcescens, 5; Escherichia coli, 4; Pseudomonas aeruginosa, 9; Providencia alcalifaciens, 4; Enterobacter cloacae, 4). Control samples were obtained from 150 healthy volunteers. The S, SP, PPV and NPV for the PCR method were all 100%. The lowest number of colony forming units/ml detected by PCR in blood samples was 10.     

A familial syndrome of susceptibility to chronic active Epstein-Barr virus infection.

In two members of a family (daughter and father) active Epstein-Barr virus (EBV) infections persisted over periods of 4 and 3 years respectively (possibly 10 years in the father). Both had persistent splenomegaly and occasional bouts of unexplained fever but lived otherwise normal lives. The other members of the family (mother and son) were healthy. The titres of antibody to the EBV viral capsid antigen (VCA) and early antigen (EA) were extremely high in the daughter''s blood, whereas the titres of antibody to the Epstein-Barr nuclear antigen were low in the daughter''s blood and undetectable in the father''s. Target cells of the EBV infection that were obtained from the daughter''s blood were established in culture with great difficulty and showed increased expression of VCA and EA. Other immunologic investigations in the two patients revealed that the ratio of helper to suppressor T lymphocytes was inverted, natural killer-cell activity was abnormally low, lymphocyte responses to certain mitogens were depressed and there was a serum factor blocking mitogen-induced transformation. The possibility that the patients'' unusual susceptibility to EBV infection represented an inherited syndrome (perhaps X-linked) is discussed.