Surveillance For Acute Febrile Illness Research Articles

Effect of single-dose, live, attenuated dengue vaccine in children with or without previous dengue on risk of subsequent, virologically confirmed dengue in Cebu, the Philippines: a longitudinal, prospective, population-based cohort study.

A three-dose dengue vaccine (CYD-TDV) was licensed for use in children aged 9 years and older starting in 2015 in several dengue-endemic countries. In 2016, the Philippine Department of Health implemented a dengue vaccination programme, which was discontinued because of safety concerns. We assessed the relative risk of developing virologically confirmed dengue among children who did or did not receive a single dose of CYD-TDV by previous dengue virus (DENV) infections at baseline classified as none, one, and two or more infections. In this longitudinal, prospective, population-based cohort study, we enrolled healthy children (aged 9-14 years) residing in Bogo or Balamban, Cebu, Philippines, between May 2, and June 2, 2017, before a mass dengue vaccination campaign, via the Rural Health Unit in Bogo and three Rural Health Units in Balamban. We collected demographic information and sera for baseline DENV serostatus and conducted active surveillance for acute febrile illness. Children who developed acute febrile illness were identified, clinical data were collected, and blood was drawn for confirmation of dengue by RT-PCR. The primary outcome was the relative risk of developing virologically confirmed dengue among children who received or did not receive a single dose of CYD-TDV by DENV serostatus at baseline. A single dose of CYD-TDV did not confer protection against virologically confirmed dengue in children who had none or one previous DENV infection at baseline. One dose conferred significant protection against hospital admission for virologically confirmed dengue among participants who had two or more previous DENV infections at baseline during the first 3 years (70%, 95% CI 20-88; p=0·017) and the entire follow-up period (67%, 19-87; p=0·016). The risk of developing virologically confirmed dengue after a single dose of CYD-TDV varied by baseline DENV serostatus. Since the study assessed the effect of only a single dose, the findings cannot inform decisions on vaccination by public health officers. However, the findings have implications for children who receive an incomplete vaccination regimen and these results should prompt more detailed analyses in future trials on dengue vaccines. The Philippine Department of Health, Hanako Foundation, WHO, Swedish International Development Cooperation Agency, International Vaccine Institute, University of North Carolina, and US National Institute of Allergy and Infectious Diseases.

Sociodemographic factors associated with Kyasanur forest disease in India - a retrospective study

ObjectivesKyasanur forest disease (KFD) is a tick-borne disease in India affecting humans and two local non-human primate species. A critical knowledge gap in the scientific literature is the lack of information on how people's sociodemographic factors influence KFD occurrence. MethodsWe analyzed available data on KFD from three data sources: (a) 104 peer-reviewed articles using keyword searches on PubMed Central and Google Scholar, (b) 116 Program for Monitoring Emerging Diseases reports, and (c) an acute febrile illness surveillance data set on KFD from a report by the government of India. We performed statistical analyses to calculate the prevalence of KFD by state and differences in KFD cases by sex and age group. ResultsAll three data sets used indicate that KFD cases and deaths have occurred predominantly in the 15-64 years age group (literature: 87% cases and 95% deaths, Program for Monitoring Emerging Diseases: 78% cases and 78% deaths, acute febrile illness: 96% cases [no breakdown for acute febrile illness death data]). Data reporting varies across states and is non-standardized. ConclusionsThe inconsistent reporting of sociodemographic data on KFD in India has created a gap in our understanding of its impact on different social groups. Collecting and reporting data on sociodemographic factors is critical to understanding the epidemiology of KFD and designing effective public health interventions.

Burden of Typhoid and Paratyphoid Fever in India

BackgroundIn 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is unclear whether declining trends of hospitalization for typhoid in India reflect increased antibiotic treatment or a true reduction in infection.MethodsFrom 2017 through 2020, we conducted weekly surveillance for acute febrile illness and measured the incidence of typhoid fever (as confirmed on blood culture) in a prospective cohort of children between the ages of 6 months and 14 years at three urban sites and one rural site in India. At an additional urban site and five rural sites, we combined blood-culture testing of hospitalized patients who had a fever with survey data regarding health care use to estimate incidence in the community.ResultsA total of 24,062 children who were enrolled in four cohorts contributed 46,959 child-years of observation. Among these children, 299 culture-confirmed typhoid cases were recorded, with an incidence per 100,000 child-years of 576 to 1173 cases in urban sites and 35 in rural Pune. The estimated incidence of typhoid fever from hospital surveillance ranged from 12 to 1622 cases per 100,000 child-years among children between the ages of 6 months and 14 years and from 108 to 970 cases per 100,000 person-years among those who were 15 years of age or older. Salmonella enterica serovar Paratyphi was isolated from 33 children, for an overall incidence of 68 cases per 100,000 child-years after adjustment for age.ConclusionsThe incidence of typhoid fever in urban India remains high, with generally lower estimates of incidence in most rural areas. (Funded by the Bill and Melinda Gates Foundation; NSSEFI Clinical Trials Registry of India number, CTRI/2017/09/009719; ISRCTN registry number, ISRCTN72938224.)

The emergence of human metapneumovirus G gene duplication in hospitalized patients with respiratory tract infection, India, 2016–2018

BackgroundHuman metapneumovirus (HMPV) belongs to the family Pneumoviridae. It is one of the emerging respiratory viruses causing both upper and lower respiratory tract illnesses. HMPV has two genotypes: A and B. These genotypes are classified into lineage A1, A2, B1 and B2. Lineage-A2 is further classified as A2a, A2b and A2c. Similarly, B2 is classified as B2a and B2b. Studies have shown the circulation of A2b, B1 and B2 lineages in India. However, a limited amount of data is available on the current circulating genotypes of HMPV in India.MethodsThroat swab samples positive for HMPV by real-time RT- PCR, archived at Manipal Institute of Virology as a part of a hospital-based acute febrile illness surveillance study, was used from April 2016 to August 2018 by purposive sampling method. We performed the conventional reverse transcriptase-polymerase chain reaction for twenty samples targeting the G gene and then subjected them to sequencing. Phylogenetic analysis was done using MEGA X software by the Maximum Likelihood method.ResultsAll the twenty sequences belonged to the A2c subgroup. Phylogenetic analysis showed that strains from the study have genetic relation with circulating strains in Japan, China and Croatia. Seven out of the twenty sequences showed 180-nucleotide duplication and eleven sequences showed 111-nucleotide duplication. Two sequences did not show any duplications.ConclusionIn the current study, we report that A2c is the sub-lineage in India from April 2016 to August 2018. This study is the first retrospective study reporting the circulation of the A2c sub-lineage among adults in India with 180- and 111-nucleotide duplications in the G gene of human metapneumovirus.

Setting the stage for Acute Febrile Illness Surveillance Network in West Africa: Report of a Regional Experts and Stakeholders Workshop in Accra, Ghana, April 2021

A three-day regional workshop of stakeholders, partners, and experts from the West African countries was held from April 14 -16, 2021 in Accra, Ghana to conduct a situational analysis on the existing knowledge, expertise, previous accomplishments, and current activities in laboratory and syndrome based Acute Febrile Illness (AFI) surveillance that will guide a regional strategy for AFI surveillance. Technical presentations were made by participants from ministries of health, national public health institutes, West African Health Organization, Food Agricultural Organization, and the United States Centers for Disease Control and Prevention (USCDC) on existing AFI surveillance activities and infrastructure. In groups, the participants conducted Strength, Weaknesses, Opportunities and Threat (SWOT) analysis on AFI surveillance followed by a prioritization of actionable steps. Thirty-eight participants from 9 West African countries attended the meeting. The strengths recognized from the SWOT analysis include the existence and implementation of Integrated Disease Surveillance and Response (IDSR) within the region for priority diseases and a regional collaborative platform. However, there was inadequate information and data sharing platforms, non-availability of accurate diagnostic tools, knowledge gap on AFI and lack of harmonized framework. The opportunities that can be tapped into include supporting partners and global bodies, existing laboratory networks in Africa and infrastructure built during the COVID-19 pandemic. The meeting unveiled opportunities and challenges associated with establishing a regional AFI surveillance framework. It provided opportunity for stakeholders and experts to discuss the way forward on laying a foundation for a regional AFI surveillance system in the region.

Epidemiological and Clinical Characteristics of Acute Dengue Virus Infections Detected through Acute Febrile Illness Surveillance, Belize 2020.

The Acute Febrile Illness (AFI) Surveillance Network in Belize is a country-wide active surveillance program aimed at diagnosing vector-borne, respiratory, and enteric pathogens among patients presenting to 11 participating hospitals and clinics with new onset fever. This study describes the epidemiology of dengue virus (DENV) infections in Belize diagnosed through AFI surveillance in 2020. Of the 894 patients enrolled and PCR-tested for DENV in this period, 44 DENV-positive cases (5%) were identified. All four DENV serotypes were detected, with two cases testing positive for DENV serotype 4, which is the first report of this serotype in Belize since 2004. The majority of DENV cases (66%) were diagnosed in the Belize District, which contains the largest urban center in the country (Belize City). Positive cases were detected between January 2020 and September 2020, with the majority (89%) diagnosed during the dry season between January and April, unlike years prior when cases were more often diagnosed during the wet season. Clinical signs and symptoms varied slightly between DENV serotypes. Active surveillance of DENV among AFI cases provides insight into the epidemiologic and clinical characteristics of DENV in Belize. This information is important for informing public health interventions to mitigate DENV transmission.

Incorporating COVID-19 into Acute Febrile Illness Surveillance Systems, Belize, Kenya, Ethiopia, Peru, and Liberia, 2020-2021.

Existing acute febrile illness (AFI) surveillance systems can be leveraged to identify and characterize emerging pathogens, such as SARS-CoV-2, which causes COVID-19. The US Centers for Disease Control and Prevention collaborated with ministries of health and implementing partners in Belize, Ethiopia, Kenya, Liberia, and Peru to adapt AFI surveillance systems to generate COVID-19 response information. Staff at sentinel sites collected epidemiologic data from persons meeting AFI criteria and specimens for SARS-CoV-2 testing. A total of 5,501 patients with AFI were enrolled during March 2020-October 2021; >69% underwent SARS-CoV-2 testing. Percentage positivity for SARS-CoV-2 ranged from 4% (87/2,151, Kenya) to 19% (22/115, Ethiopia). We show SARS-CoV-2 testing was successfully integrated into AFI surveillance in 5 low- to middle-income countries to detect COVID-19 within AFI care-seeking populations. AFI surveillance systems can be used to build capacity to detect and respond to both emerging and endemic infectious disease threats.

Currently circulating genotypes of Hepatitis A virus in South West, East and North East India, 2017–2018

BackgroundThis study was carried out to understand the circulating genotypes of Hepatitis A virus (HAV) in South West, East and North East India during the period 2017–2018 as a part of acute febrile illness surveillance at the Manipal Institute of Virology. MethodsArchived serum samples of 48 Hepatitis A confirmed cases were subjected to RNA extraction using QIAamp® Viral RNA Mini Kit (QIAGEN, Germany). The samples with molecular confirmation for HAV by reverse transcriptase real-Time PCR (Real Star® HAV RT-PCR Kit 2.0, Altona Diagnostics, GmbH, Hamburg, Germany) were further subjected to nested conventional PCR targeting the 5′ UTR region. The purified PCR products were sequenced using Big Dye Terminator Kit (Applied Biosystems, USA), in a 3500 XL genetic analyzer (Applied Biosystems, USA). The edited sequences by means of MEGA X (MEGA version 10.1) were compared with reference sequences in the NCBI nucleotide database. ResultsFrom states of Assam, Goa, Gujarat, Karnataka, Kerala, Maharashtra, Odisha, Tamil Nadu and Tripura, 139 Hepatitis A and 33 Hepatitis E cases were reported during the study period. The median age of the acute Hepatitis A cases was 19 years (IQR 12.8–24) and most of the affected individuals were students between 10 and 19 years (52.5%). In the present study, 14 samples from Assam, Goa, Gujarat, Karnataka, Odisha, Kerala, Maharashtra and Tamil Nadu were genotyped as genotype IIIA by nested conventional polymerase chain reaction. ConclusionThe circulating HAV genotype in South West, North East and East India between 2017 and 2018 was IIIA.

1521. Risk factors associated with complications of influenza A or B infection, southern Puerto Rico, 2016-2019

BackgroundInfluenza is one of the most common viral respiratory diseases in the United States with 9–45 million cases per year. In Puerto Rico, more than 18,000 cases of influenza were reported during the 2019/20 season. The Sentinel Enhanced Dengue Surveillance System (SEDSS) conducts acute febrile illness surveillance for inpatient and outpatients at a southern Puerto Rico tertiary care hospital.MethodsWe performed a retrospective analysis of disease severity among laboratory-confirmed influenza cases enrolled in SEDSS. Cases with complications such as pneumonia or bronchitis evidenced by chest x-ray or clinical diagnosis were classified as severe.ResultsBetween January 2016 and December 2019, there were 2,835 laboratory-confirmed influenza cases. More than half (1,662, 59%) were aged 0–20 years, 51% (n=1,447)were female, and 4% (n=124)required hospital admission. Among all influenza cases, influenza A virus was most common (n = 1,963, 69%) followed by influenza B virus (n = 872, 31%). Odds of having influenza A were higher among adults (OR=1.62; 95% CI:1.38-1.92). Chronic disease history among influenza cases included: asthma (n= 507, 18%), hypertension (n = 337, 12%), hypercholesterolemia (n = 157, 6%), coronary heart disease (n = 79, 3%), immunodeficiency (n = 11, 1%), and kidney disease (n = 10, 1%). Overall, 61(2%) influenza cases developed complications, 21 developed pneumonia of which 85% had chest x-ray performed. One-third of influenza cases with pneumonia or bronchitis had preexisting conditions like asthma (33%) and hypertension (34%). Seventy five percent of Influenza A cases with asthma developed bronchitis or pneumonia. The odds of having severe Influenza were higher among patients with underlying hypertension compared to those without hypertension (OR= 3.8; 95% CI:2.0–7.1). Moreover, influenza cases with asthma had a higher odd of developing pneumonia or bronchitis as compared to those without asthma (OR=2.3; 95% CI: 1.3–4.0). While asthma is a recognized risk factor for influenza complications, isolated hypertension is not.ConclusionIdentifying people at risk for influenza complications provides a guide for clinicians and public health officials to implement preventive measures and improve clinical outcomes.Disclosures All Authors: No reported disclosures

Evaluation of two commercially available chikungunya virus IgM enzyme-linked immunoassays (ELISA) in a setting of concomitant transmission of chikungunya, dengue and Zika viruses

ObjectiveTo evaluate the diagnostic performance of the Inbios (Seattle, US) and Euroimmun (Luebeck, Germany) chikungunya virus (CHIKV) IgM enzyme-linked immunoassays (ELISAs). MethodsWe evaluated the tests’ accuracy on sera from 372 patients enrolled in an acute febrile illness surveillance study performed in Salvador, Brazil from Sept/2014 to Jul/2016, a period of simultaneous CHIKV, dengue (DENV), and Zika (ZIKV) virus transmission. We assessed the sensitivity on acute and paired convalescent sera from RT-PCR-confirmed CHIKV cases (collected at median one and 19 days post-onset of symptoms, respectively), and the specificity on sera of RT-PCR-confirmed DENV and ZIKV cases, and on negative patients. ResultsThe Inbios and Euroimmun tests’ sensitivities for acute samples were 4.0% and 10.3%, while for convalescent samples they were 92.4% and 96.9%, respectively. Overall, Inbios IgM ELISA specificities for acute and convalescent samples were 97.7% and 90.5%, respectively, and Euroimmun specificities were 88.5% and 83.9%, respectively. ConclusionsBoth tests presented high sensitivity for convalescent samples. However, the Euroimmun test returned more equivocal results and presented a slightly lower specificity, which might result in a higher rate of false positives if the test is used in scenarios of low CHIKV transmission, when the chance of CHIKV infection is lower.

Estimating the seroprevalence of chikungunya virus exposure in Shimoga district, Karnataka state: A hospital-based study during 2014-2018.

Chikungunya fever is a viral disease transmitted to humans by the bite of infected mosquitoes. The disease is characterized by fever, headache, rash, severe joint, and muscle pain. To evaluate the disease burden in the population and the effectiveness of public health measures, periodic seroprevalence surveys are essential. Chikungunya outbreaks were reported from many Asian countries since 2005, after more than three decades of disappearance. The study aimed to estimate the seroprevalence of the chikungunya virus in southern parts of Karnataka state, through demonstrating chikungunya virus-specific neutralizing antibodies. A cross-sectional study was carried out using 509 archived blood samples from a hospital-based acute febrile illness surveillance project, representative of the period between June 2014 and 2018. The study reported a 3.7% seroprevalence of chikungunya virus-neutralizing antibodies in Thirthahalli and Hosanagara taluks of South Karnataka. The low prevalence of chikungunya-neutralizing antibodies indicates that a major population is unexposed and prone to future outbreaks.

Evaluation of a Acute Febrile Illness Surveillance Network (GAFINet), South Korea.

ObjectiveThe purpose of this study is to describe and evaluate the results of the GAFINET(Gyeonggi Acute Febrile Illness Surveillance Network) operated for one year.IntroductionAfter MERS outbreak in 2015, the provincial government and infectious disease control center (GIDCC) initiated an emergency department (ED) based Gyeonggi-do provincial acute febrile illness (AFI) surveillance network (GAFINet) to monitor for a subsequent outbreak of emerging or imported infectious diseases since September 2016. Following pilot operation from September to December 2016, the operation was run for one year from June 2017 to May 2018.GAFINet Initiative involves ten hospitals, consisted of four university-affiliated hospitals and six provincial medical centers in Gyeonggi-do province. These hospitals participated in this network voluntarily.MethodsPeriodic surveillance for finding AFI patients in ED of participating hospitals was performed prospectively (Figure 2). AFI was definedas 1) fever: body temperature ≥38 °C at admission, or 2) chief complaint of febrile or chilling sensation. Demography of patientsand chief complaints were investigated in this first step. Cases were classified into six categories based on their clinicaldiagnoses: 1) respiratory AFI [AFRI], 2) gastroenteric AFI [AFGI], 3) exanthematic AFI [AFEI], 4) other infectious AFI, 5) non-infectiousAFI, and 6) unclassified AFI.Participating infectious diseases specialists regularly reviewed and reformed this classification via web based system.Nosocomial AFI cases or the patients transferred from another hospital were excluded. When a patient had a history of international travel or he/she were undiagnosed in three days after ED admission, more comprehensive information including history and final diagnosis were obtained. For a baseline data, age- and sex-stratified ED visits were also gathered weekly. The proportion of AFI cases per 1000 visits was determined for one week period and analyzed by febrile diseases categories with age-stratification. Characteristics of cases with international travel histories or undiagnosed cases were also described separately.The results were presented to participating researchers as visualized dashboards in Web-based systems.Also we compared the trend and peak time of GAFINET data with the surveillance data of KCDC for influenza, hand foot and mouth disease, and Tsutsugamushi disease.ResultsThe total number of patients in the emergency room in 10 hospitals was 366,695 for one year. Among them, 40,897 patients were diagnosed with acute febrile illness (11.2%). 47.8% were under 10 years of age, and 508 - 1,769 patients were fever - related patients per weak. The number of patients with foreign travel was 0 - 11 in each week, and the number of patients with unknown fever in the week was 0 - 6.1 to 9 years of age accounted for the largest proportion (27.6% - 48.3%) of acute febrile patients. The most common infectious diseases were acute febrile respiratory disease, and other acute febrile infections and acute febrile gastrointestinal disease are followed. In acute febrile respiratory disease and acute febrile illness, seasonal pattern was seen.A total of 157 patients with acute febrile illnesses with overseas travel ability, 0 - 11 persons per week, consistently occurred. Acute gastroenteritis (AGE) was the most frequent diagnosis in 28 patients (17.8%), fever of unkonwn origin(FUO) was 25(15.9%), Acute pharyngotonsilitis 17(10.8%), viral infection 17 (10.8%), Influenza 7 (4.5%) and colitis 5 (3.2%). The cause of fever was not found in 30 of the acute febrile patients with overseas travel ability. A total of 77 patients with acute febrile disease were admitted to the hospital.In comparison with national surveillance data, the trend of occurrence of influenza in GAFINet and national data was similar. Both data peaked in the first week of 2018. Also trend of hand-foot and mouth disease(HFMD) was similar in two data. But peak weak was little different in both data(CDC at 30 weeks, GAFINett at 29 weeks in 2017). In GAFINet, the final diagnosis was confirmed as Tsutsugamushi disease in total 43 cases. The number of reported cases was small, and the epidemic peaked at the same time as the CDC surveillance data, but the outbreak occurred in the same period (October to November).ConclusionsGAFINet has both the characteristics of indicator based surveillance and event based surveillance.Data were collected over a period of one year to examine the feasibility and applicability of the indicator based surveillance. In comparison with national surveillance data, some feasibility was verified by similar trends, but the necessity of operating regional surveillance data still needs to be discussed. It should also be noted that some diseases have different peak times of one week.The role of event based surveillance is mainly aimed at surveillance of fever patients with international travel history. The advantage of the GAFINet's classification system in the emergency room of participating hospitals is that the patient's cases of fever were constantly monitored. However, there is still a limit to the lack of budget and manpower in the samping and labaratory test.Real time visual feedback of surveillance data helped to increase participation and discuss the results.

Circulation of Asian-I and Cosmopolitan genotypes of Dengue-2 virus in northeast India, 2016-2017.

Dengue is a major public health problem in northeast India where the majority of the cases go unreported and undiagnosed. Even though all four dengue serotypes are reported, there is a dearth of information on genetic diversity. The present cross-sectional study was undertaken during 2016-17 to determine the genetic variance of dengue virus serotype 2 (DENV-2) based on the envelope (E) glycoprotein gene. The serum samples collected from the northeast parts of India, as a part of hospital-based acute febrile illness surveillance, were serotyped. Viral RNA was extracted from DENV-2 serum samples using QIAquick® RNA Extraction Kit. The E gene was amplified by conventional reverse-transcriptase polymerase chain reaction (RT-PCR) and the PCR products were sequenced. The E glycoprotein gene of nine serum samples with high viral RNA concentration (Ct <25) was sequenced. The E gene sequences of eight DENV-2 strains from Assam and Meghalaya aligned with genotype IV (Cosmopolitan) and one strain from Tripura segregated with Asian-I genotype. Ongoing laboratory-based surveillance is mandatory to understand the transmission dynamics of dengue in endemic countries. This study concluded that in northeast India, presently two distinct genotypes of DENV-2, namely genotype IVb (Cosmopolitan) and Asian-I genotype are in circulation.

Concomitant Transmission of Dengue, Chikungunya, and Zika Viruses in Brazil: Clinical and Epidemiological Findings From Surveillance for Acute Febrile Illness.

Since their emergence in the Americas, chikungunya (CHIKV) and Zika (ZIKV) viruses co-circulate with dengue virus (DENV), hampering clinical diagnosis. We investigated clinical and epidemiological characteristics of arboviral infections during the introduction and spread of CHIKV and ZIKV through northeastern Brazil. Surveillance for arboviral diseases among febrile patients was performed at an emergency health unit of Salvador, Brazil, between September 2014 and July 2016. We interviewed patients to collect data on symptoms, reviewed medical records to obtain the presumptive diagnoses, and performed molecular and serological testing to confirm DENV, CHIKV, ZIKV, or nonspecific flavivirus (FLAV) diagnosis. Of 948 participants, 247 (26.1%) had an acute infection, of which 224 (23.6%) were single infections (DENV, 32 [3.4%]; CHIKV, 159 [16.7%]; ZIKV, 13 [1.4%]; and FLAV, 20 [2.1%]) and 23 (2.4%) coinfections (DENV/CHIKV, 13 [1.4%]; CHIKV/FLAV, 9 [0.9%]; and DENV/ZIKV, 1 [0.1%]). An additional 133 (14.0%) patients had serological evidence for a recent arboviral infection. Patients with ZIKV presented with rash and pruritus (69.2% each) more frequently than those with DENV (37.5% and 31.2%, respectively) and CHIKV (22.9% and 14.7%, respectively) (P < .001 for both comparisons). Conversely, arthralgia was more common in CHIKV (94.9%) and FLAV/CHIKV (100.0%) than in DENV (59.4%) and ZIKV (53.8%) (P < .001). A correct presumptive clinical diagnosis was made for 9%-23% of the confirmed patients. Arboviral infections are frequent causes of febrile illness. Coinfections are not rare events during periods of intense, concomitant arboviral transmission. Given the challenge to clinically distinguish these infections, there is an urgent need for rapid, point-of-care, multiplex diagnostics.

Clinical and Epidemiological Status of Leptospirosis in a Tropical Caribbean Area of Colombia.

Objective To describe and analyze the clinical and epidemiological status in 28 confirmed cases of human leptospirosis at the main public hospital of Cordoba. Methods Between 2012 and 2013, we conducted an active surveillance at the main hospital of Cordoba to establish the etiologic diagnosis of the undifferentiated tropical febrile illness (UTFI) cases. UTFI is defined as a fever without an infection focus in the initial physical examination or in basic laboratory tests. Patients in acute phase were accompanied by prodromal symptoms, including myalgia, arthralgia, headache, asthenia, chills, icterus, dyspnea, abdominal pain, rash, and nausea. Samples were collected on admission and at discharge. Clinical and epidemiological data were collected for each patient. Microscopic agglutination test (MAT) was performed. Results The 28 leptospirosis cases presented the following gender distribution: male (n=24) and female (n=4). The duration of hospitalization was 10.39 days. The main symptoms and clinical manifestations were fever, headache and nausea, vomiting, and abdominal pain, all of which occurred in up to 60% of patients. Of the 28 cases studied, 4 were fatal. The most frequent infecting serogroups were Ballum and Canicola. Conclusion Leptospirosis is a common cause of undifferentiated tropical febrile illness in Colombia; it is important to establish ongoing and accurate surveillance for acute febrile illness to facilitate the detection of cases of leptospirosis.

Symptomatic Zika Virus Infection in Infants, Children, and Adolescents Living in Puerto Rico

Little information is available regarding Zika virus (ZIKV) infection in children. To describe patients younger than 18 years who were infected with ZIKV and were enrolled in the Sentinel Enhanced Dengue and Acute Febrile Illness Surveillance System (SEDSS). Children infected with ZIKV with 7 or fewer days of fever or emancipated minors aged 14 to 17 years with a generalized maculopapular rash, arthritis or arthralgia, or nonpurulent conjunctivitis were eligible for enrollment on or before December 31, 2016, in Puerto Rico. Patients were evaluated using ZIKV polymerase chain reaction testing at 7 or fewer days after the onset of symptoms. Available ZIKV polymerase chain reaction-positive specimens were evaluated to determine viral loads. Confirmed polymerase chain reaction-positive ZIKV infection. Clinical characteristics and viral loads of symptomatic children with confirmed ZIKV infection. Of 7191 children enrolled in SEDSS on or before December 31, 2016, only those with confirmed ZIKV infection (351 participants) were included in this study. Participants who had confirmed ZIKV infection included 25 infants (7.1%), 69 children (19.7%) aged 1 to 4 years, 95 (27.1%) aged 5 to 9 years, and 162 (46.1%) aged 10 to 17 years. Among these, 260 patients (74.1%) presented for evaluation of ZIKV infection at fewer than 3 days after the onset of symptoms, 340 (96.9%) were discharged to home after evaluation, and 349 (99.4%) had fever, 280 (79.8%) had a rash, 243 (69.2%) had facial or neck erythema, 234 (66.7%) had fatigue, 223 (63.5%) had headache, 212 (60.4%) had chills, 206 (58.7%) had pruritus, and 204 (58.1%) had conjunctival hyperemia. Of 480 specimens collected (317 serum and 163 urine specimens) from 349 children, the median number of days after the onset of symptoms was lower for children who had serum specimens (1 day [interquartile range (IQR), 1-2 days]) than for children who had urine specimens (2 [1-3] days) (P < .001). Of 131 children who had both serum and urine specimens collected on the same day, the median viral load was higher in serum than in urine (median [IQR], 23 098 [8784-88 242] copies/mL for serum vs 9966 [2815-52 774] copies/mL for urine; P = .02). When a single serum sample from each of 317 patients was analyzed, there were no statistically significant differences in median viral loads according to age, sex, or disposition. However, the median serum viral load varied significantly according to the number of days after the onset of symptoms (0 days, 106 778 [IQR, 9772-1 571 718] copies/mL; 1 day, 46 299 [10 663-255 030] copies/mL; 2 days, 20 678 [8763-42 458] copies/mL; and ≥3 days, 15 901 [5135-49 248] copies/mL; P = .001). This study represents the largest study to date of ZIKV infection in the pediatric population. Most children infected with ZIKV had fever, rash, and conjunctival hyperemia. The children usually presented for evaluation at fewer than 3 days after the onset of symptoms. Viral loads for ZIKV were higher in serum vs urine specimens. Median viral loads in serum specimens differed significantly according to the number of days after the onset of symptoms.

Dengue IgG Seropositivity and Zika Viral Load

BackgroundSecondary dengue virus (DENV) infections are typically more severe than primary infections. It is not known whether previous DENV infection is associated with higher Zika virus (ZIKV) quantitative RT-PCR results (viral loads (VLs)) in areas endemic for DENV such as Puerto Rico. Our objective was to analyze the association between previous DENV infection (DENV IgG-positive) and ZIKV VL among children with symptomatic ZIKV infection enrolled in the Sentinel Enhanced Dengue and Acute Febrile Illness Surveillance System (SEDSS) in Puerto Rico.MethodsThe study population for this analysis comprised individuals <18 years of age enrolled in SEDSS during 2016 who were ZIKV PCR-positive in serum (using the CDC Trioplex RT-polymerase chain reaction (RT-PCR) assay) within 5 days post-onset (DPO) of symptoms. ZIKV VLs (genome copies/mL) were determined using an RNA standard curve generated from the RT-PCR assay target amplicons. An in-house ELISA was used to ascertain the presence or absence of serum DENV IgG. Trends were assessed using Jonckheere-Terpstra and Chi-square for proportions tests. The Mann–Whitney-Wilcoxon test was used to compare medians. Linear regression modeling was used to determine the association between DENV IgG and ZIKV VL.ResultsOf the 319 individuals who met inclusion criteria, 163 have dengue IgG assays completed to date. Of these, 90/163 (55%) were DENV IgG-positive and 73/163 (45%) were DENV IgG-negative, and did not vary by sex (P = 1.00). However, the proportion of patients with DENV IgG-positivity increased with age (P < 0.001) (Figure). Overall, the median (interquartile range, IQR) ZIKV VL was 23,110 (7,452–84,003), and did not vary by age (P = 0.11) or sex (P = 0.33). However, the median ZIKV VL varied by DPO: 26,230 (DPO<3; n = 117), 15,159 (DPO≥ 3; n = 46), P = 0.002. The median (IQR) ZIKV VLs were: 24,073 (10,938–73,130) in DENV IgG-negative specimens and 22,658 (7,332–89,322) in DENV IgG-positive specimens (P = 0.91). Linear regression indicated no association between DENV IgG and ZIKV VL (P = 0.54).ConclusionDENV IgG-positivity increased with age among children with symptomatic ZIKV infection. ZIKV VLs did not vary by age, but decreased with increasing DPO. There was no association between DENV IgG and ZIKV VL.Disclosures All authors: No reported disclosures.

Scrub Typhus as an Etiology of Acute Febrile Illness in Gorakhpur, Uttar Pradesh, India, 2016.

Seasonal outbreaks of acute encephalitis syndrome (AES) with high mortality occur every year in Gorakhpur region of Uttar Pradesh, India. Earlier studies indicated the role of scrub typhus as the important etiology of AES in the region. AES cases were hospitalized late in the course of their illness. We established surveillance for acute febrile illness (AFI) (fever ≥ 4 days duration) in peripheral health facilities in Gorakhpur district to understand the relative contribution of scrub typhus. Of the 224 patients enrolled during the 3-month period corresponding to the peak of AES cases in the region, about one-fifth had immunoglobulin M (IgM) antibodies against Orientia tsutsugamushi. Dengue and leptospira accounted for 8% and 3% of febrile illness cases. Treating patients with AFI attending the peripheral health facilities with doxycycline could prevent development of AES and thereby reduce deaths due to AES in Gorakhpur region.

Enhanced Surveillance for Fatal Dengue-Like Acute Febrile Illness in Puerto Rico, 2010-2012.

BackgroundDengue is a leading cause of morbidity throughout the tropics; however, accurate population-based estimates of mortality rates are not available.Methods/Principal FindingsWe established the Enhanced Fatal Acute Febrile Illness Surveillance System (EFASS) to estimate dengue mortality rates in Puerto Rico. Healthcare professionals submitted serum and tissue specimens from patients who died from a dengue-like acute febrile illness, and death certificates were reviewed to identify additional cases. Specimens were tested for markers of dengue virus (DENV) infection by molecular, immunologic, and immunohistochemical methods, and were also tested for West Nile virus, Leptospira spp., and other pathogens based on histopathologic findings. Medical records were reviewed and clinical data abstracted. A total of 311 deaths were identified, of which 58 (19%) were DENV laboratory-positive. Dengue mortality rates were 1.05 per 100,000 population in 2010, 0.16 in 2011 and 0.36 in 2012. Dengue mortality was highest among adults 19–64 years and seniors ≥65 years (1.17 and 1.66 deaths per 100,000, respectively). Other pathogens identified included 34 Leptospira spp. cases and one case of Burkholderia pseudomallei and Neisseria meningitidis.Conclusions/SignificanceEFASS showed that dengue mortality rates among adults were higher than reported for influenza, and identified a leptospirosis outbreak and index cases of melioidosis and meningitis.

High rate of subclinical chikungunya virus infection and association of neutralizing antibody with protection in a prospective cohort in the Philippines.

BackgroundChikungunya virus (CHIKV) is a globally re-emerging arbovirus for which previous studies have indicated the majority of infections result in symptomatic febrile illness. We sought to characterize the proportion of subclinical and symptomatic CHIKV infections in a prospective cohort study in a country with known CHIKV circulation.Methods/FindingsA prospective longitudinal cohort of subjects ≥6 months old underwent community-based active surveillance for acute febrile illness in Cebu City, Philippines from 2012-13. Subjects with fever history were clinically evaluated at acute, 2, 5, and 8 day visits, and at a 3-week convalescent visit. Blood was collected at the acute and 3-week convalescent visits. Symptomatic CHIKV infections were identified by positive CHIKV PCR in acute blood samples and/or CHIKV IgM/IgG ELISA seroconversion in paired acute/convalescent samples. Enrollment and 12-month blood samples underwent plaque reduction neutralization test (PRNT) using CHIKV attenuated strain 181/clone25. Subclinical CHIKV infections were identified by ≥8-fold rise from a baseline enrollment PRNT titer <10 without symptomatic infection detected during the intervening surveillance period. Selected CHIKV PCR-positive samples underwent viral isolation and envelope protein-1 gene sequencing. Of 853 subjects who completed all study procedures at 12 months, 19 symptomatic infections (2.19 per 100 person-years) and 87 subclinical infections (10.03 per 100 person-years) occurred. The ratio of subclinical-to-symptomatic infections was 4.6:1 varying with age from 2:1 in 6 month-5 year olds to 12:1 in those >50 years old. Baseline CHIKV PRNT titer ≥10 was associated with 100% (95%CI: 46.1, 100.0) protection from symptomatic CHIKV infection. Phylogenetic analysis demonstrated Asian genotype closely related to strains from Asia and the Caribbean.ConclusionsSubclinical infections accounted for a majority of total CHIKV infections. A positive baseline CHIKV PRNT titer was associated with protection from symptomatic CHIKV infection. These findings have implications for assessing disease burden, understanding virus transmission, and supporting vaccine development.