Novel paramyxovirus associated with severe acute febrile disease, South Sudan and Uganda, 2012.
ABSTRACT: In 2012, a female wildlife biologist experienced fever, malaise, headache, generalized myalgia and arthralgia, neck stiffness, and a sore throat shortly after returning to the United States from a 6-week field expedition to South Sudan and Uganda. She was hospitalized, after which a maculopapular rash developed and became confluent. When the patient was discharged from the hospital on day 14, arthralgia and myalgia had improved, oropharynx ulcerations had healed, the rash had resolved without desquamation, and blood counts and hepatic enzyme levels were returning to reference levels. After several known suspect pathogens were ruled out as the cause of her illness, deep sequencing and metagenomics analysis revealed a novel paramyxovirus related to rubula-like viruses isolated from fruit bats.
Project description:In August 2012, a wildlife biologist became ill immediately following a 6-wk field trip to collect bats and rodents in South Sudan and Uganda. After returning to the US, the biologist was admitted to the hospital with multiple symptoms including fever, malaise, headache, generalized myalgia and arthralgia, stiffness in the neck, and sore throat. Soon after admission, the patient developed a maculopapular rash and oropharynx ulcerations. The patient remained hospitalized for 14 d. Several suspect pathogens, including viral hemorrhagic fever viruses such as Ebola viruses and Marburg viruses, were ruled out through standard diagnostic testing. However, deep sequencing and metagenomic analyses identified a novel paramyxovirus, later named Sosuga virus, in the patient's blood. To determine the potential source, bat tissues collected during the 3-wk period just prior to the onset of symptoms were tested for Sosuga virus, and several Egyptian rousette bats (Rousettus aegyptiacus) were found to be positive. Further analysis of archived Egyptian rousette tissues collected at other localities in Uganda found additional Sosuga virus-positive bats, suggesting this species could be a potential natural reservoir for this novel paramyxovirus.
Project description:Australia has 4 rickettsial diseases: murine typhus, Queensland tick typhus, Flinders Island spotted fever, and scrub typhus. We describe 7 cases of a rickettsiosis with an acute onset and symptoms of fever (100%), headache (71%), arthralgia (43%), myalgia (43%), cough (43%), maculopapular/petechial rash (43%), nausea (29%), pharyngitis (29%), lymphadenopathy (29%), and eschar (29%). Cases were most prevalent in autumn and from eastern Australia, including Queensland, Tasmania, and South Australia. One patient had a history of tick bite (Haemaphysalis novaeguineae). An isolate shared 99.2%, 99.8%, 99.8%, 99.9%, and 100% homology with the 17 kDa, ompA, gltA, 16S rRNA, and Sca4 genes, respectively, of Rickettsia honei. This Australian rickettsiosis has similar symptoms to Flinders Island spotted fever, and the strain is genetically related to R. honei. It has been designated the "marmionii" strain of R. honei, in honor of Australian physician and scientist Barrie Marmion.
Project description:Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disease characterized by symptoms including spiking fever, arthralgia, myalgia, maculopapular rash, and pharyngitis. The lack of diagnostic biomarker, non-specific clinical presentation, and the rarity of AOSD often result in a significant delay in diagnosis and treatment. While the average time of initial presentation to diagnosis is four months, we present a case of AOSD diagnosis three years after initial onset of classical symptoms. By reporting the case of delayed diagnosis for AOSD, we hope to raise awareness in our medical community about the diagnostic difficulty in AOSD. The present case describes an otherwise healthy male who presented with typical symptoms of AOSD, but the diagnosis of AOSD was missed during his first presentation. In the second flaring episode, the diagnosis of AOSD was established. He had an excellent therapeutic response to anakinra and prednisone during the acute flaring episode. He is currently in complete remission on methotrexate as maintenance therapy.
Project description:Zika virus is an Aedes-borne Flavivirus causing fever, arthralgia, myalgia rash, associated with Guillain-Barré syndrome and suspected to induce microcephaly in the fetus. We report here the complete coding sequence of the first characterized Caribbean Zika virus strain, isolated from a patient from Martinique in December, 2015.
Project description:Reported cases of dengue are rising in South Australia (SA) in travellers returning from dengue-endemic regions. We have undertaken a retrospective analysis to identify the clinical and laboratory characteristics of patients returning to SA with suspected dengue virus (DENV) infection. From 488 requests, 49 (10%) were defined by serology as acute dengue, with the majority of patients (75%) testing as non-structural protein 1 (NS1) and/or IgM positive. Dengue was most commonly acquired in Indonesia (42.9%) with clinical features of fever (95%), headache (41%) and myalgia/arthralgia (56%). The presence of rash (36%) and laboratory findings of neutropenia, leukopenia, thrombocytopenia, but not elevated C-reactive protein, were distinct from findings in DENV-seronegative patients. Available dengue seropositive samples were analysed by RT-PCR, with 14/32 (43.8%) positive by a serotype non-specific DENV assay, but 28/32 positive (87.5%) when also assessed by serotype-specific RT-PCR. Serotype analysis revealed the predominance of DENV-1 and DENV-2 and the presence of DENV-3, but not DENV-4 or Zika virus (ZIKV). Thus, dengue in returned travellers in SA presents in a manner consistent with World Health Organization (WHO) definitions, with symptoms, travel history and laboratory results useful in prioritising the likelihood of dengue. This definition will assist the future management in DENV-non-endemic regions, such as SA.
Project description:OBJECTIVE:Zika virus (ZIKV) infection is a vector-borne disease that can be transmitted sexually and vertically. The vertical transmission of the virus may lead to congenital Zika syndrome in infants. The aim of this study is to conduct a systematic review and meta-analysis of published reports documenting the prevalence of congenital Zika-related disorders in infants of mothers infected with ZIKV during pregnancy. METHODS:We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of print, Embase, Embase Classic and Web of Science databases to identify human studies reporting prevalence of congenital disorders in infants of ZIKV-infected mothers. RESULTS:We identified 25 reports selected for inclusion in the current study (n?=?4683 subjects). The majority of the studies were from South American high-risk countries. Only one third of the identified studies were conducted in the United States. Clinical maternal symptoms included maculopapular rash (76.9%), arthralgia (46.4%), fever (45.5%) and headache (31.8%) with myalgia and conjunctivitis only presented in 25% of the cases. The most prevalent congenital disorder in the newborns was brain calcifications (42.6; 95% CI, 30.8-54.4), followed by ventriculomegaly (21.8; 95% CI, 15.2-28.4), joint abnormalities (13.2; 95% CI, 9.4-18.2), ocular abnormalities (4.2; 95% CI, 1.0-7.5) and microcephaly (3.9; 95% CI, 2.4-5.4). CONCLUSION:The current study highlights the high prevalence of a range of congenital disorders in newborns of mothers infected with ZIKV. It warrants developing studies to further clarify the mechanisms by which each of these disorders occurs in response to the viral infection during pregnancy and its vertical transmission to the infants.
Project description:BACKGROUND:Measles is a recurrent health problem in both advanced and developed countries. The World Health Organization (WHO) recommends anti-measles immunoglobulin M (Ig M) as the standard method of detecting the virus; however, many areas still present the inability to perform a serology test of anti-measles IgM. Therefore, a typical clinical feature is necessary to establish the diagnosis of measles. The objective of this study was to evaluate hyperpigmented rash and other clinical features as the diagnostic tools with respect to measles, especially in an outbreak setting. METHODS:In this observational diagnostic study, the inclusion criteria were as follows: between 6 and 144?months of age, fever, maculopapular rash for 3 days or more, accompanied by a cough, or coryza, or conjunctivitis. Those with a prior history of measles vaccination (1-6?weeks) were excluded, in addition to those with histories of corticosteroid for 2 weeks or more and immunocompromised conditions. The samples were taken from Dr. Soetomo General Academic Hospital in Surabaya, Indonesia. We evaluated the sensitivity, specificity, the positive predictive value, and the negative predictive value of such clinical features. Hyperpigmented rash was validated using Kappa and Mc Nemar tests. Anti-measles Ig M was considered as the gold standard. RESULTS:This study gathered 82 participants. The clinical manifestations of all subjects included fever, cough, coryza, conjunctivitis, Koplik spots, and maculopapular rash (which turns into hyperpigmented rash along the course of the illness). Most maculopapular rashes turn out to be hyperpigmented (89%). Sensitivity, specificity, positive predictive value, and negative predictive values ??of the combination of fever, maculopapular rash, and hyperpigmented rash were found to be at 90.7, 28.6, 93.2, and 22.2%, respectively. The Mc Nemar and Kappa tests showed p values of 0.774 and 0.119, respectively. CONCLUSION:The combination of fever, maculopapular rash, and hyperpigmented rash can be used as a screening tool regarding measles infection in an outbreak setting, which can then be confirmed by anti-measles Ig M. Cough, coryza, and Koplik's spot can be added to this combination, albeit with a slight reduction of sensitivity value.
Project description:During pregnancy, the organization of complex tolerance mechanisms occurs to assure non-rejection of the semiallogeneic fetus. Pregnancy is a period of vulnerability to some viral infections, mainly during the first and second trimesters, that may cause congenital damage to the fetus. Recently, Zika virus (ZIKV) infection has gained great notoriety due to the occurrence of congenital ZIKV syndrome, characterized by fetal microcephaly, which results from the ability of ZIKV to infect placental cells and neural precursors in the fetus. Importantly, in addition to the congenital effects, studies have shown that perinatal ZIKV infection causes a number of disorders, including maculopapular rash, conjunctivitis, and arthralgia. In this paper, we contextualize the immunological aspects involved in the maternal-fetal interface and vulnerability to ZIKV infection, especially the alterations resulting in perinatal outcomes. This highlights the need to develop protective maternal vaccine strategies or interventions that are capable of preventing fetal or even neonatal infection.
Project description:Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the Flavivirus genus of the Flaviviridae family. Since the large outbreaks in French Polynesia in 2013-2014 and in Brazil in 2015, ZIKV has been considered a new public health threat. Similar to other related flavivirus, ZIKV is associated with mild and self-limiting symptoms such as rash, pruritus, prostration, headache, arthralgia, myalgia, conjunctivitis, lower back pain and, when present, a short-term low grade fever. In addition, ZIKV has been implicated in neurological complications such as neonatal microcephaly and Guillain-Barré syndrome in adults. Herein, serum lipidomic analysis was used to identify possible alterations in lipid metabolism triggered by ZIKV infection. Patients who presented virus-like symptoms such as fever, arthralgia, headache, exanthema, myalgia and pruritus were selected as the control group. Our study reveals increased levels of several phosphatidylethanolamine (PE) lipid species in the serum of ZIKV patients, the majority of them plasmenyl-phosphatidylethanolamine (pPE) (or plasmalogens) linked to polyunsaturated fatty acids. Constituting up to 20% of total phospholipids in humans, plasmalogens linked to polyunsaturated fatty acids are particularly enriched in neural membranes of the brain. The biosynthesis of plasmalogens requires functional peroxisomes, which are important sites for viral replication, including ZIKV. Thus, increased levels of plasmalogens in serum of ZIKV infected subjects suggest a link between ZIKV life cycle and peroxisomes. Our data provide important insights into specific host cellular lipids that are likely associated with ZIKV replication and may serve as platform for antiviral strategy against ZIKV.
Project description:Zika virus (ZIKV) infection is typically characterized by a mild self-limiting disease presenting with fever, rash, myalgia and arthralgia and severe fetal complications during pregnancy such as microcephaly, subcortical calcifications and arthrogyropsis. Virus-induced arthralgia due to perturbed osteoblast function has been described for other arboviruses. In case of ZIKV infection, the role of osteoblasts in ZIKV pathogenesis and bone related pathology remains unknown. Here, we study the effect of ZIKV infection on osteoblast differentiation, maturation and function by quantifying activity and gene expression of key biomarkers, using human bone marrow-derived mesenchymal stromal cells (MSCs, osteoblast precursors). MSCs were induced to differentiate into osteoblasts and we found that osteoblasts were highly susceptible to ZIKV infection. While infection did not cause a cytopathic effect, a significant reduction of key osteogenic markers such as ALP, RUNX2, calcium contents and increased expression of IL6 in ZIKV-infected MSCs implicated a delay in osteoblast development and maturation, as compared to uninfected controls. In conclusion, we have developed and characterized a new in vitro model to study the role of bone development in ZIKV pathogenesis, which will help to identify possible new targets for developing therapeutic and preventive measures.