- Cerebral toxoplasmosis with fever and erythematous macular rash: An initial presentation in an advanced HIV infection. [Journal Article]
- TPTrop Parasitol 2018 Jan-Jun; 8(1):41-44
- The MTase-like domain of chikungunya virus nsP2 inhibits the interferon response by promoting the nuclear export of STAT1. [Journal Article]
- JVJ Virol 2018 Jun 20
- Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has evolved effective mechanisms to counteract the type I interferon (IFN) response. Upon viral recognition, cells secrete IFNs which sig...
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has evolved effective mechanisms to counteract the type I interferon (IFN) response. Upon viral recognition, cells secrete IFNs which signal through transmembrane receptors (IFNAR) to phosphorylate STAT proteins (pSTAT). pSTAT dimers are transported into the nucleus by importin-α5 and activate the transcription of IFN stimulated genes (ISGs) increasing cellular resistance to infection. Subsequently, STAT proteins are shuttled back into the cytoplasm by exportin CRM1. CHIKV non-structural protein 2 (nsP2) reduces ISG expression by inhibiting general host-cell transcription and by specifically reducing the levels of nuclear pSTAT1 via an unknown mechanism. To systematically examine where nsP2 acts within the JAK/STAT signalling cascade we used two well characterized mutants of nsP2, P718S and KR649AA. Both mutations abrogate nsP2's ability to shutoff host transcription, but only the KR649AA mutant localizes exclusively to the cytoplasm and no longer specifically inhibits JAK/STAT signalling. These mutant nsP2 proteins did not differentially affect IFNAR expression levels, or STAT1 phosphorylation in response to IFNs. Co-immunoprecipitation experiments showed that in the presence of nsP2, STAT1 still effectively binds importin-α5. Chemically blocking CRM1-mediated nuclear export in the presence of nsP2 additionally showed that nuclear translocation of STAT1 is not affected by nsP2. NsP2 debatably has five domains. Redirecting the nsP2 KR649AA mutant or just nsP2's C-terminal methyltransferase-like domain into the nucleus strongly reduced nuclear pSTAT in response to IFN stimulation. This demonstrates that the C-terminal domain of nuclear nsP2 specifically inhibits the IFN response by promoting the nuclear export of STAT1.IMPORTANCE Chikungunya virus is an emerging pathogen associated with large outbreaks on the African, Asian, European and American continents. In most patients infection results in high fever, rash and incapacitating (chronic) arthralgia. CHIKV effectively inhibits the first line of defence, the innate immune response. As a result, stimulation of the innate immune response with interferons (IFNs) is ineffective as treatment for CHIKV disease. The IFN response requires an intact downstream signalling cascade called the JAK/STAT signalling pathway which is effectively inhibited by CHIKV non-structural protein 2 (nsP2) via an unknown mechanism. The research described here specifies where in the JAK/STAT signalling cascade the IFN response is inhibited and which protein domain of nsP2 is responsible for IFN inhibition. The results illuminate new aspects of antiviral defence and CHIKV counter defence strategies and will direct the search for novel antiviral compounds.
- A case of nickel allergy after endovascular aortic repair. [Journal Article]
- ACAsian Cardiovasc Thorac Ann 2018 Jan 01; :218492318784736
- A 78-year-old man with no history of allergy, underwent endovascular aortic repair for abdominal aortic aneurysm rupture. Postoperatively, he had low-grade fever and persistently raised white blood c...
A 78-year-old man with no history of allergy, underwent endovascular aortic repair for abdominal aortic aneurysm rupture. Postoperatively, he had low-grade fever and persistently raised white blood cell counts, but tests showed no infection. A skin rash appeared on the trunk and upper arms; we suspected a drug allergy. Despite withdrawal and/or change of medications, the symptoms remained. Finally, a patch test for nickel showed a strongly positive result. Oral prednisone 5 mg·day-1 was started, and the clinical findings resolved thereafter. No recurrence of allergy, infection, or exacerbation of the treated abdominal aortic aneurysm was noted at the 2-year follow-up.
- Pediatric systemic lupus erythematosus. Retrospective analysis of clinico-laboratory parameters and their association with Systemic Lupus Erythematosus Disease Activity Index score. [Journal Article]
- SMSaudi Med J 2018; 39(6):627-631
- CONCLUSIONS: Pediatric systemic lupus erythematosus patients with higher SLEDAI score were most significantly associated with pyuria, high ANA titers, and elevated ESR.
- Atypical clinical presentation of flavivirus. Case report [Journal Article]
- RMRev Med Inst Mex Seguro Soc 2018 Mar-Apr; 56(2):198-202
- The first report of chikungunya virus (CHIKV) in Mexico was in may 2014, in Jalisco, and has disseminated along the country in such a way that now is considered a relevant emergent vector-transmitted...
The first report of chikungunya virus (CHIKV) in Mexico was in may 2014, in Jalisco, and has disseminated along the country in such a way that now is considered a relevant emergent vector-transmitted infection. It is clinically diagnosed by abrupt onset fever, asthenia, arthralgias, myalgias, headache and rash. In the clinical case, we described a women from Guerrero that had pulmonary symptomatology associated to CHIKV, which is an atypical clinical presentation that has been reported only in a hundred cases worldwide. In the epidemiological context the only known tool that we have to prevent the disease is the eradication of vectors because we lack population immunity, thus the importance of avoiding water accumulation and using protective gear. In Mexico we are acting through media advertisements in order to avoid, in first place the acute infection, which in severe cases can cause death, and in second place the chronic complications.
- Diagnosis and outcomes of pregnant women with Zika virus infection in two municipalities of Risaralda, Colombia: Second report of the ZIKERNCOL study. [Journal Article]
- TMTravel Med Infect Dis 2018 Jun 09
- CONCLUSIONS: The rate of microcephaly in our cohort was consistent with other studies. Pregnant women in endemic areas should be followed and tested according to standard protocols, and asymptomatic ZIKV infection should be considered. Long-term follow-up of children is required in the congenital Zika syndrome (CZS) assessment.
- Keystone Virus Isolated from a Florida Teenager with Rash and Subjective Fever: Another Endemic Arbovirus in the Southeastern United States? [Journal Article]
- CIClin Infect Dis 2018 Jun 09
- Keystone virus, a California-serogroup orthobunyavirus, was first isolated in 1964 from mosquitoes in Keystone, Florida. There are no reports of isolation from humans, despite studies suggesting that...
Keystone virus, a California-serogroup orthobunyavirus, was first isolated in 1964 from mosquitoes in Keystone, Florida. There are no reports of isolation from humans, despite studies suggesting that ~20% of persons living in the region are seropositive. We report virus isolation from a Florida teenager with a rash and fever.
- Investigation of laboratory confirmed Dengue outbreak in North-eastern Kenya, 2011. [Journal Article]
- PlosPLoS One 2018; 13(6):e0198556
- The first laboratory confirmed dengue outbreak in Kenya was reported in coastal towns of Malindi and Kilifi in 1982. Since then, no other outbreak had been confirmed in Kenya. Dengue outbreak was con...
The first laboratory confirmed dengue outbreak in Kenya was reported in coastal towns of Malindi and Kilifi in 1982. Since then, no other outbreak had been confirmed in Kenya. Dengue outbreak was confirmed among African Mission soldiers in Somalia (AMISOM) between May to October 2011. From September 2011, an upsurge of febrile patients who were negative for malaria on microscopy were reported in several health facilities in Mandera town, an adjacent area to Somalia in northern Kenya. We investigated a suspected dengue outbreak in Mandera town from 26th September 2011 to 5th October 2011. A suspected case was defined as acute onset of fever with two or more of the following: headache, arthralgia, myalgia, rash and hemorrhages and negative malaria microscopy results in a person presenting to a health facility in Mandera town from 1st August to 2nd October 2011. We prospectively identified new cases meeting the suspect case definition from 2nd October to 5th October 2011 and we collected blood samples from consenting patients. Blood was collected into plastic vacutainers and stored in dry shipper at -80oc to laboratory for dengue virus testing using real time reverse transcriptase polymerase chain reaction (rRT-PCR). We administered a standardized form to obtain clinical information. We calculated descriptive statistics to describe the outbreak. A total of 1,332 patients had been line listed by the district surveillance team, of which 381 (29%) met our suspect case definition of dengue. Cases peaked between 10th September and 1st October 2011 and thereafter declined. We prospectively identified 33 cases meeting the suspect case definition, of whom 30 (91%) were positive for dengue virus serotype 3 by PCR. Among the 30 laboratory confirmed patients, 20 (67%) required hospitalization (Median hospitalization period, two days with a range: 1-4 days)). And of these, 26 (86%) patients reported aches and pain, 16 (53%) reported vomiting, and four (13%) gingival bleeding. Twenty-three (77%) received anti-malarial therapy. Among laboratory-confirmed dengue patients, seven (23%) had malaria co-infection. This was the second confirmed Dengue outbreak in Kenya, and highlighted the need for improved surveillance to better define disease burden and continuous education to medical personnel to improve detection and clinical management. We also recommended enhanced community education for disease prevention.
- Capillary leak syndrome and aseptic meningitis in a patient with Kawasaki disease: A case report. [Case Reports]
- MMedicine (Baltimore) 2018; 97(23):e10716
- CONCLUSIONS: The incidence of KD has recently increased and cardiovascular complications are frequently reported. This may be combined with systemic damage, however, the combination of SCLS and aseptic meningitis is rarely reported, therefor, children who have SCLS, aseptic meningitis and unexplained fever >5 days, KD should be taken into account. Early diagnosis and timely treatment can reduce complications induced by KD.
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- A Case of Pulmonary Hemorrhaging as a Fatal Complication of IgA Vasculitis. [Journal Article]
- IMIntern Med 2018 Jun 06
- A 64-year-old man was admitted to our hospital for purpuric rash, joint pain, and a fever. He had earlier undergone a follow-up examination for interstitial lung disease. At the current visit, the di...
A 64-year-old man was admitted to our hospital for purpuric rash, joint pain, and a fever. He had earlier undergone a follow-up examination for interstitial lung disease. At the current visit, the diagnosis was immunoglobulin A (IgA) vasculitis, based on skin and renal biopsy findings. He developed sudden breathlessness and hemoptysis. Chest computed tomography revealed ground glass opacity in the right lower lung fields, suggesting pulmonary hemorrhaging associated with IgA vasculitis. Despite steroid and cyclophosphamide therapy, and plasma exchange, he died 52 days after admission. Early aggressive therapies may be recommended for old patients with IgA vasculitis who have an additional comorbidities.