The use of a mobile laboratory unit in support of patient management and epidemiological surveillance during the 2005 Marburg Outbreak in Angola

Background

Marburg virus (MARV), a zoonotic pathogen causing severe hemorrhagic fever in man, has emerged in Angola resulting in the largest outbreak of Marburg hemorrhagic fever (MHF) with the highest case fatality rate to date.

Methodology/Principal Findings

A mobile laboratory unit (MLU) was deployed as part of the World Health Organization outbreak response. Utilizing quantitative real-time PCR assays, this laboratory provided specific MARV diagnostics in Uige, the epicentre of the outbreak. The MLU operated over a period of 88 days and tested 620 specimens from 388 individuals. Specimens included mainly oral swabs and EDTA blood. Following establishing on site, the MLU operation allowed a diagnostic response in <4 hours from sample receiving. Most cases were found among females in the child-bearing age and in children less than five years of age. The outbreak had a high number of paediatric cases and breastfeeding may have been a factor in MARV transmission as indicated by the epidemiology and MARV positive breast milk specimens. Oral swabs were a useful alternative specimen source to whole blood/serum allowing testing of patients in circumstances of resistance to invasive procedures but limited diagnostic testing to molecular approaches. There was a high concordance in test results between the MLU and the reference laboratory in Luanda operated by the US Centers for Disease Control and Prevention.

Conclusions/Significance

The MLU was an important outbreak response asset providing support in patient management and epidemiological surveillance. Field laboratory capacity should be expanded and made an essential part of any future outbreak investigation.     

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.     

Cases of legionellosis infection in Tbilisi

The epidemic outbreak of Legionella infection at two industrial enterprises during the period of July-August 1988 is described. The results of the epidemiological study, the clinical course and the serological diagnosis of the outbreak are presented. For the first time in the USSR a new form of the disease has been described at the territory of Georgia. This form, named Legionella fever, is manifested mainly by skin eruptions.     

On the epidemiological situation in quarantine, natural focal and other infections on the territory of the Southern Federal District

The data on the sanitary and epidemiological situation in the Southern Federal District are presented. The analysis of morbidity in tuberculosis, measles, HIV infection, viral hepatitis A, typhoid fever, cholera and quarantine infections, Crimean hemorrhagic fever, West Nile fever, rabies, malaria has been carried out. Special attention has been given to "new and newly returning infections", and among them to the spread of SARS ("atypical pneumonia"). The role of regional epidemiological safety programs, in particular such program as "The prophylaxis of quarantine and natural focal infections and the sanitary protection of the territory of the Southern Federal District of the Russian Federation from the import and spread infectious diseases in 2003-2005", has been substantiated.     

Specific features of the typhoid fever epidemic process in organized collective

During the chronic water epidemic of typhoid fever in Tajikistan in 1996-1997 specific features of the epidemic process dynamics in groups of servicemen were studied in several cities. The infective agent was proved to be transmitted by the alimentary route and through everyday contacts, the water route of transmission playing the most important role. The early clinical and epidemiological signs of the water outbreak of typhoid fever and the risk factors were established. The clinical and epidemiological aspects of vaccination were analyzed.     

An explosive outbreak of respiratory streptococcal infection with a droplet transmission mechanism

The data obtained in the study of an explosive outbreak of acute respiratory diseases, tonsillitis and scarlet fever in one of schools in Moscow have made it possible to exclude the alimentary mechanism of its development and to demonstrate the role of the droplet mechanism of transmission in the appearance of its outbreak. The epidemiological analysis of the outbreak has permitted the formulation of the hypothesis on the conditions of the formation and spread of the epidemic variant of the infective agent; this hypothesis corresponds to the available data in literature on the qualitative changes of the infective agent in the course of the epidemic process. The study has shown that the prophylaxis of the explosive outbreaks of respiratory streptococcal infections must be ensured by the system of epidemiological surveillance with timely intervention into the epidemiological process at its early stages.     

Clinical Features and Patient Management of Lujo Hemorrhagic Fever

Background

In 2008 a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, Lujo virus, occurred in Johannesburg, South Africa. Lujo virus is only the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa and the first in over 40 years. Because of the remote, resource-poor, and often politically unstable regions where Lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options typically available in industrialized countries.

Methods and Findings

We describe the clinical features of five cases of Lujo hemorrhagic fever and summarize their clinical management, as well as providing additional epidemiologic detail regarding the 2008 outbreak. Illness typically began with the abrupt onset of fever, malaise, headache, and myalgias followed successively by sore throat, chest pain, gastrointestinal symptoms, rash, minor hemorrhage, subconjunctival injection, and neck and facial swelling over the first week of illness. No major hemorrhage was noted. Neurological signs were sometimes seen in the late stages. Shock and multi-organ system failure, often with evidence of disseminated intravascular coagulopathy, ensued in the second week, with death in four of the five cases. Distinctive treatment components of the one surviving patient included rapid commencement of the antiviral drug ribavirin and administration of HMG-CoA reductase inhibitors (statins), N-acetylcysteine, and recombinant factor VIIa.

Conclusions

Lujo virus causes a clinical syndrome remarkably similar to Lassa fever. Considering the high case-fatality and significant logistical impediments to controlled treatment efficacy trials for viral hemorrhagic fever, it is both logical and ethical to explore the use of the various compounds used in the treatment of the surviving case reported here in future outbreaks. Clinical observations should be systematically recorded to facilitate objective evaluation of treatment efficacy. Due to the risk of secondary transmission, viral hemorrhagic fever precautions should be implemented for all cases of Lujo virus infection, with specialized precautions to protect against aerosols when performing enhanced-risk procedures such as endotracheal intubation.     

Transmission Potential and Design of Adequate Control Measures for Marburg Hemorrhagic Fever

Marburg hemorrhagic fever is rare yet among the most severe diseases affecting humans, with case fatality ratio even higher than 80%. By analyzing the largest documented Marburg hemorrhagic fever epidemic, which occurred in Angola in 2005 and caused 329 deaths, and data on viral load over time in non-human primates, we make an assessment of transmissibility and severity of the disease. We also give insight into the control of new Marburg hemorrhagic fever epidemics to inform appropriate health responses. We estimated the distribution of the generation time to have mean 9 days (95%CI: 8.2–10 days) and standard deviation 5.4 days (95%CI: 3.9–8.6 days), and the basic reproduction number to be  = 1.59 (95%CI: 1.53–1.66). Model simulations suggest that a timely isolation of cases, starting no later than 2–3 days after symptoms onset, is sufficient to contain an outbreak. Our analysis reveals that Marburg hemorrhagic fever is characterized by a relatively small reproduction number and by a relatively long generation time. Such factors, along with the extremely high severity and fatality, support the rare occurrence of large epidemics in human populations. Our results also support the effectiveness of social distancing measures - case isolation in particular - to contain or at least to mitigate an emerging outbreak. This work represents an advance in the knowledge required to manage a potential Marburg hemorrhagic fever epidemic.     

An outbreak of dengue fever in St. Croix (US Virgin Islands), 2005

Background

Periodic outbreaks of dengue fever occur in the United States Virgin Islands. In June 2005, an outbreak of dengue virus (DENV) serotype-2 with cases of dengue hemorrhagic fever (DHF) was detected in St. Croix, US Virgin Islands. The objective of this report is to describe this outbreak of DENV-2 and the findings of a case-control study examining risk factors for DHF.

Methodology/Principal Findings

This is the largest dengue outbreak ever recorded in St. Croix, with 331 suspected dengue cases reported island-wide during 2005 (62.2 cases/10,000 population); 54% were hospitalized, 21% had at least one hemorrhagic manifestation, 28% had thrombocytopenia, 5% had DHF and 1 patient died. Eighty-nine laboratory-positive hospitalized patients were identified. Of these, there were 15 (17%) who met the WHO criteria for DHF (cases) and 74 (83%) who did not (controls). The only variable significantly associated with DHF on bivariate or multivariable analysis was age, with an adjusted odds ratio (95% confidence interval) of 1.033 (1.003,1.064).

Conclusions/Significance

During this outbreak of DENV-2, a high proportion of cases developed DHF and increasing age was significantly associated with DHF.     

Single-nucleotide-polymorphism genotyping of Coxiella burnetii during a Q fever outbreak in The Netherlands

Coxiella burnetii is the etiological agent of Q fever. Currently, the Netherlands is facing the largest Q fever epidemic ever, with almost 4,000 notified human cases. Although the presence of a hypervirulent strain is hypothesized, epidemiological evidence, such as the animal reservoir(s) and genotype of the C. burnetii strain(s) involved, is still lacking. We developed a single-nucleotide-polymorphism (SNP) genotyping assay directly applicable to clinical samples. Ten discriminatory SNPs were carefully selected and detected by real-time PCR. SNP genotyping appeared to be highly suitable for discrimination of C. burnetii strains and easy to perform with clinical samples. With this new method, we show that the Dutch outbreak is caused by at least 5 different C. burnetii genotypes. SNP typing of 14 human samples from the outbreak revealed the presence of 3 dissimilar genotypes. Two genotypes were also present in livestock at 9 farms in the outbreak area. SNP analyses of bulk milk from 5 other farms, commercial cow milk, and cow colostrum revealed 2 additional genotypes that were not detected in humans. SNP genotyping data from clinical samples clearly demonstrate that at least 5 different C. burnetii genotypes are involved in the Dutch outbreak.     

Early onset of neurological features differentiates two outbreaks of Lassa fever in Ebonyi state,Nigeria during 2017–2018

Lassa fever (LF) is an acute viral haemorrhagic illness with various non-specific clinical manifestations. Neurological symptoms are rare at the early stage of the disease, but may be seen in late stages, in severely ill patients.The aim of this study was to describe the epidemiological evolution, socio-demographic profiles, clinical characteristics, and outcomes of patients seen during two Lassa fever outbreaks in Ebonyi State, between December 2017 and December 2018.Routinely collected clinical data from all patients admitted to the Virology Centre of the hospital during the period were analysed retrospectively. Out of a total of 83 cases, 70(84.3%) were RT-PCR confirmed while 13 (15.7%) were probable cases. Sixty-nine (83.1%) patients were seen in outbreak 1 of whom 53.6% were urban residents, while 19%, 15%, and 10% were farmers, students and health workers respectively. There were 14 (16.8%) patients, seen in second outbreak with 92.9% rural residents. There were differences in clinical symptoms, signs and laboratory findings between the two outbreaks. The case fatality rates were 29.9% in outbreak 1 and 85.7% for outbreak 2. Neurological features and abnormal laboratory test results were associated with higher mortality rate, seen in outbreak 2. This study revealed significant differences between the two outbreaks. Of particular concern was the higher case fatality during the outbreak 2 which may be from a more virulent strain of the Lassa virus. This has important public health implications and further molecular studies are needed to better define its characteristics.     

Ngari virus is a Bunyamwera virus reassortant that can be associated with large outbreaks of hemorrhagic fever in Africa

Two isolates of a virus of the genus Orthobunyavirus (family Bunyaviridae) were obtained from hemorrhagic fever cases during a large disease outbreak in East Africa in 1997 and 1998. Sequence analysis of regions of the three genomic RNA segments of the virus (provisionally referred to as Garissa virus) suggested that it was a genetic reassortant virus with S and L segments derived from Bunyamwera virus but an M segment from an unidentified virus of the genus Orthobunyavirus. While high genetic diversity (52%) was revealed by analysis of virus M segment nucleotide sequences obtained from 21 members of the genus Orthobunyavirus, the Garissa and Ngari virus M segments were almost identical. Surprisingly, the Ngari virus L and S segments showed high sequence identity with those of Bunyamwera virus, showing that Garissa virus is an isolate of Ngari virus, which in turn is a Bunyamwera virus reassortant. Ngari virus should be considered when investigating hemorrhagic fever outbreaks throughout sub-Saharan Africa.     

Prediction of foci of Crimean hemorrhagic fever by means of a computer]

Districts of the Osh region were classified by a number of signs with the aid of a computer for the purpose of epidemiological prognosis of the foci of Crimean hemorrhagic fever (CHF). The results obtained were compared with the data of virological study for CHF in these districts. This work showed that there were future prospects in using the computer program for prognostication of infections with natural nidality with the aid of a computer.     

Dengue 2 virus enhancement in asthmatic and non asthmatic individual.

During the 1981 dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) Cuban epidemic, bronchial asthma (BA) was frequently found as a personal or family antecedent in dengue hemorrhagic fever patients. Considering that antibody dependent enhancement (ADE) plays an important role in the etiopathogenic mechanism of DHF/DSS, we decide to study the Dengue 2 virus (D2V) capability of replication in peripheral blood leukocytes (PBL) from asthmatic patients and healthy persons. In 90% of asthmatic patients and 53.8% of control group it was obtained PBL with a significant D2V enhancing activity (X2 p < 0.01). Power enhancement was higher in asthmatic group. This is the first in vitro study relating BA and the dengue 2 virus immuno enhancement. The results obtained support the role of BA as a risk factor for DHF/DSS as already described on epidemiological data.     

Serial Expression of the Truncated Fragments of the Nucleocapsid Protein of CCHFV and Identification of the Epitope Region

The Crimean-congo hemorrhagic fever virus(CCHFV)is a geographically widespread fatal pathogen. Identification of the epitope regions of the virus is important for the diagnosis and epidemiological studies of CCHFV infections.In this study,expression vectors carrying series truncated fragments of the NP(nucleocapsid protein)gene from the S fragment of CCHFV strain YL04057 were constructed.The recombinant proteins were expressed in E.coli and purified for detection.The antigenic of the truncated fragments of ...     

Etiological relation between Korean hemorrhagic fever and epidemic hemorrhagic fever in Japan.

The first case of epidemic hemorrhagic fever in Japan was seen in Osaka in 1960. The etiologic agent of this disease has not yet been isolated, but a close etiologic relation between Korean hemorrhagic fever and epidemic hemorrhagic fever in Japan has been suspected because of similarities in the clinical and pathological pictures of the two diseases. This relation has now been confirmed serologically by demonstrating specific immunofluorescent antibodies to Korean hemorrhagic fever virus in 19 of 20 sera obtained from subjects 7 to 17 years after an acute attack of epidemic hemorrhagic fever.     

拉沙病毒分子流行病学特征和跨境传播风险

拉沙热主要流行于西非,经鼠传播,人群普遍易感,病死率高,暴发疫情频发,跨境传播时有发生。拉沙病毒易于传播,病毒分离、培养需在生物安全四级实验室(BSL-4)。2018年,世界卫生组织将其列为年度重点关注传染病,需加快研制防治关键技术手段。随着中非关系的日益紧密,贸易往来频繁,中国面临拉沙热的威胁显著增加。本文检索20世纪50年代首例拉沙热病例报道以来公开发表的主要文献,归纳拉沙热临床表现、病原学特征、流行病学特征、实验室检测以及跨境传播风险等,并对GenBank发布的全部287条拉沙病毒S基因编码区全长序列进行复核分析,以加强人们对拉沙热的了解,提高防控意识。     

Newly recognized mosquito-associated viruses in mainland China, in the last two decades

There are four principal arboviruses in mainland China. Two kinds of them are mosquito-borne viruses, namely Japanese encephalitis virus and dengue virus, which lead to Japanese encephalitis, and dengue fever/dengue hemorrhagic fever respectively; the other two are tick-borne viruses, namely tick-borne encephalitis virus and Crimean-Congo hemorrhagic fever virus (also known as Xinjiang hemorrhagic fever virus), which contribute to tick-borne encephalitis and Xinjiang hemorrhagic fever respectively. With exception of these four main arboviruses, many other mosquito-associated viruses have been isolated and identified in recent years. These newly isolated and identified mosquito-associated viruses are probably responsible for human and animal infections and diseases. The purpose of this review is to describe the newly isolated mosquito-associated viruses in mainland China which belong to five viral families, including their virological properties, phylogenetic relationships, serological evidence, as well as to appeal the public health concentration worldwide.