Seroconversion to Islet Autoantibodies After Enterovirus Infection in Early Pregnancy.

Gestational enterovirus (EV) infections have been associated with an increased risk for type 1 diabetes in the offspring. We therefore analyzed non-diabetic mothers for EV exposure in early pregnancy in relation to type 1 diabetes HLA-DQ risk genotypes and seroconversion to islet autoantibodies during pregnancy. Non-diabetic mothers who had islet autoantibodies (n=365) against glutamic acid decarboxylase (GADA), islet antigen-2 autoantibodies (IA-2A), or insulin autoantibodies (IAA), in early pregnancy and at delivery were compared to islet autoantibody-negative mothers (n=1457) matched for age and sampling date. Mothers were genotyped for HLA-DQ and analyzed for both EV-RNA and EV-IgM. EV-IgM, but not EV-RNA, was detected during early pregnancy in 12% of islet autoantibody-positive mothers compared to 11% of the controls. In early pregnancy, mothers with HLA-DQ 2/2 or 2/X genotypes showed an increased risk for islet autoantibodies at delivery (OR 1.85; p=0.001). After adjusting for parity, maternal age, year of birth, and season of early pregnancy, early pregnancy EV-IgM combined with DQ2/2 or 2/X increased the risk for islet autoantibodies (OR 3.10; 95% CI 1; p=0.008). EV-IgM in early pregnancy increased the risk for islet autoantibodies at delivery in non-diabetic mothers with HLA-DQ 2/2 or 2/X type 1 diabetes risk genotypes

Acute flaccid paralysis with anterior myelitis - California, June 2012-June 2014.

In August 2012, the California Department of Public Health (CDPH) was contacted by a San Francisco Bay area clinician who requested poliovirus testing for an unvaccinated man aged 29 years with acute flaccid paralysis (AFP) associated with anterior myelitis (i.e., evidence of inflammation of the spinal cord involving the grey matter including anterior horn cell bodies) and no history of international travel during the month before symptom onset. Within 2 weeks, CDPH had received reports of two additional cases of AFP with anterior myelitis of unknown etiology. Testing at CDPH's Viral and Rickettsial Disease Laboratory for stool, nasopharyngeal swab, and cerebrospinal fluid (CSF) did not detect the presence of an enterovirus (EV), the genus of the family Picornaviridae that includes poliovirus. Additional laboratory testing for infectious diseases conducted at the CDPH Viral and Rickettsial Disease Laboratory did not identify a causative agent to explain the observed clinical syndrome reported among the patients. To identify other cases of AFP with anterior myelitis and elucidate possible common etiologies, CDPH posted alerts in official communications for California local health departments during December 2012, July 2013, and February 2014. Reports of cases of neurologic illness received by CDPH were investigated throughout this period, and clinicians were encouraged to submit clinical samples for testing. A total of 23 cases of AFP with anterior myelitis of unknown etiology were identified. Epidemiologic and laboratory investigation did not identify poliovirus infection as a possible cause for the observed cases. No common etiology was identified to explain the reported cases, although EV-D68 was identified in upper respiratory tract specimens of two patients. EV infection, including poliovirus infection, should be considered in the differential diagnosis in cases of AFP with anterior myelitis and testing performed per CDC guidelines

Acute flaccid paralysis with anterior myelitis - California, June 2012-June 2014.

In August 2012, the California Department of Public Health (CDPH) was contacted by a San Francisco Bay area clinician who requested poliovirus testing for an unvaccinated man aged 29 years with acute flaccid paralysis (AFP) associated with anterior myelitis (i.e., evidence of inflammation of the spinal cord involving the grey matter including anterior horn cell bodies) and no history of international travel during the month before symptom onset. Within 2 weeks, CDPH had received reports of two additional cases of AFP with anterior myelitis of unknown etiology. Testing at CDPH's Viral and Rickettsial Disease Laboratory for stool, nasopharyngeal swab, and cerebrospinal fluid (CSF) did not detect the presence of an enterovirus (EV), the genus of the family Picornaviridae that includes poliovirus. Additional laboratory testing for infectious diseases conducted at the CDPH Viral and Rickettsial Disease Laboratory did not identify a causative agent to explain the observed clinical syndrome reported among the patients. To identify other cases of AFP with anterior myelitis and elucidate possible common etiologies, CDPH posted alerts in official communications for California local health departments during December 2012, July 2013, and February 2014. Reports of cases of neurologic illness received by CDPH were investigated throughout this period, and clinicians were encouraged to submit clinical samples for testing. A total of 23 cases of AFP with anterior myelitis of unknown etiology were identified. Epidemiologic and laboratory investigation did not identify poliovirus infection as a possible cause for the observed cases. No common etiology was identified to explain the reported cases, although EV-D68 was identified in upper respiratory tract specimens of two patients. EV infection, including poliovirus infection, should be considered in the differential diagnosis in cases of AFP with anterior myelitis and testing performed per CDC guidelines

Distinguishing patients with laboratory-confirmed chikungunya from dengue and other acute febrile illnesses, Puerto Rico, 2012-2015.

Chikungunya, a mosquito-borne viral, acute febrile illness (AFI) is associated with polyarthralgia and polyarthritis. Differentiation from other AFI is difficult due to the non-specific presentation and limited availability of diagnostics. This 3-year study identified independent clinical predictors by day post-illness onset (DPO) at presentation and age-group that distinguish chikungunya cases from two groups: other AFI and dengue. Specimens collected from participants with fever ≤7 days were tested for chikungunya, dengue viruses 1-4, and 20 other pathogens. Of 8,996 participants, 18.2% had chikungunya, and 10.8% had dengue. Chikungunya cases were more likely than other groups to be older, report a chronic condition, and present <3 DPO. Regardless of timing of presentation, significant positive predictors for chikungunya versus other AFI were: joint pain, muscle, bone or back pain, skin rash, and red conjunctiva; with dengue as the comparator, red swollen joints (arthritis), joint pain, skin rash, any bleeding, and irritability were predictors. Chikungunya cases were less likely than AFI and dengue to present with thrombocytopenia, signs of poor circulation, diarrhea, headache, and cough. Among participants presenting <3 DPO, predictors for chikungunya versus other AFI included: joint pain, skin rash, and muscle, bone or back pain, and absence of thrombocytopenia, poor circulation and respiratory or gastrointestinal symptoms; when the comparator was dengue, joint pain and arthritis, and absence of thrombocytopenia, leukopenia, and nausea were early predictors. Among all groups presenting 3-5 DPO, pruritic skin became a predictor for chikungunya, joint, muscle, bone or back pain were no longer predictive, while arthritis became predictive in all age-groups. Absence of thrombocytopenia was a significant predictor regardless of DPO or comparison group. This study identified robust clinical indicators such as joint pain, skin rash and absence of thrombocytopenia that can allow early identification of and accurate differentiation between patients with chikungunya and other common causes of AFI

Number and proportion of enrolled participants by pathogens detected, overall and by age group, acute febrile illness study, May 7, 2012–May 6, 2015, Puerto Rico.

<p>Number and proportion of enrolled participants by pathogens detected, overall and by age group, acute febrile illness study, May 7, 2012–May 6, 2015, Puerto Rico.</p

Number of laboratory-positive dengue, chikungunya, influenza and other respiratory viral illness by month of illness onset, acute febrile illness study, May 7, 2012–May 6, 2015, Puerto Rico.

<p>Number of laboratory-positive dengue, chikungunya, influenza and other respiratory viral illness by month of illness onset, acute febrile illness study, May 7, 2012–May 6, 2015, Puerto Rico.</p

Characteristics and clinical features of participants at study enrollment by pathogen detected, acute febrile illness study, May 7, 2012–May 6, 2015, Puerto Rico.

<p>Characteristics and clinical features of participants at study enrollment by pathogen detected, acute febrile illness study, May 7, 2012–May 6, 2015, Puerto Rico.</p

Clinical and epidemiologic characteristics of dengue and other etiologic agents among patients with acute febrile illness, Puerto Rico, 2012–2015

<div><p>Identifying etiologies of acute febrile illnesses (AFI) is challenging due to non-specific presentation and limited availability of diagnostics. Prospective AFI studies provide a methodology to describe the syndrome by age and etiology, findings that can be used to develop case definitions and multiplexed diagnostics to optimize management. We conducted a 3-year prospective AFI study in Puerto Rico. Patients with fever ≤7 days were offered enrollment, and clinical data and specimens were collected at enrollment and upon discharge or follow-up. Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1–4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, <i>Leptospira</i> spp., and <i>Burkholderia pseudomallei</i>. Clinical presentation and laboratory findings of participants infected with DENV were compared to those infected with CHIKV, FLU A/B, and ORV. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. Of 8,996 participants enrolled from May 7, 2012 through May 6, 2015, more than half (54.8%, 4,930) had a pathogen detected. Pathogens most frequently detected were CHIKV (1,635, 18.2%), FLU A/B (1,074, 11.9%), DENV 1–4 (970, 10.8%), and ORV (904, 10.3%). Participants with DENV infection presented later and a higher proportion were hospitalized than those with other diagnoses (46.7% versus 27.3% with ORV, 18.8% with FLU A/B, and 11.2% with CHIKV). Predictors of dengue in participants presenting <3 DPO included leukopenia, thrombocytopenia, headache, eye pain, nausea, and dizziness, while negative predictors were irritability and rhinorrhea. Predictors of dengue in participants presenting 3–5 DPO were leukopenia, thrombocytopenia, facial/neck erythema, nausea, eye pain, signs of poor circulation, and diarrhea; presence of rhinorrhea, cough, and red conjunctiva predicted non-dengue AFI. By enrolling febrile patients at clinical presentation, we identified unbiased predictors of laboratory-positive dengue as compared to other common causes of AFI. These findings can be used to assist in early identification of dengue patients, as well as direct anticipatory guidance and timely initiation of correct clinical management.</p></div

Early predictors of laboratory-positive dengue versus all other acute febrile illnesses by age group, acute febrile illness study, May 7, 2012–May 6, 2015, Puerto Rico.

<p>Early predictors of laboratory-positive dengue versus all other acute febrile illnesses by age group, acute febrile illness study, May 7, 2012–May 6, 2015, Puerto Rico.</p