Changing Disease Course of Crimean-Congo Hemorrhagic Fever in Children, Turkey.

Crimean-Congo hemorrhagic fever (CCHF), endemic in certain regions of the world, is listed as a priority disease with pandemic potential. Since CCHF was first identified in Turkey, children have been known to experience milder disease than adults. However, during the COVID-19 pandemic, we observed an unusually severe disease course, including hemophagocytic lymphohistiocytosis (HLH). We examined cytokine/chemokine profiles of 9/12 case-patients compared with healthy controls at 3 time intervals. Interferon pathway-related cytokines/chemokines, including interleukin (IL) 18, macrophage inflammatory protein 3α, and IL-33, were elevated, but tumor necrosis factor-α, IL-6, CXCL8 (formerly IL-8), and cytokines acting through C-C chemokine receptor 2 and CCR5 were lower among case-patients than controls. Interferon pathway activation and cytokines/chemokines acting through CCR2 and CCR5 improved health results among children with severe CCHF. Children can experience severe CCHF, including HLH, and HLH secondary to CCHF can be successfully treated with intravenous immunoglobulin and steroid therapy.

Investigation and long-term monitoring of the presence of neutralizing antibody in patients with COVID-19 disease of different clinical severity.

Understanding the immune responses elicited by severe acute respiratory syndrome virus (SARS-CoV-2) infection is critical to public health policy and vaccine development and prevention of reinfections for COVID-19. It is important to know the neutralizing capacity of antibodies and to monitor their persistence. Patients with COVID-19 were divided into four groups (severe-critical, moderate, mild, and asymptomatic) according to their clinical severity. Antibodies against SARS-CoV-2 spike viral surface protein were investigated by ELISA method 3 and 9 months after the onset of the disease. Neutralizing antibody (NAb) response was evaluated by microneutralization test. Patients who received at least two doses of COVID-19 vaccine after illness were enrolled. SARS-CoV-2 immunoglobulin G (IgG) and NAb titers were shown to be strongly correlated with disease severity. Anti-SARS-CoV-2 IgG and NAb levels were found to be compatible with each other. After 9 months of follow-up, both IgG and NAb levels continued unabated in individuals who had the disease. In individuals who received at least two doses of the vaccine, these levels increased, except for severe-critical patients. High levels of anti-SARS-CoV-2 IgG are indicative, as it is difficult to investigate NAb in routine laboratories. At the same time, it can be predicted that this period may be much longer if it continues for at least 9 months and is reinforced with vaccination.

Should a third booster dose be scheduled after two doses of CoronaVac? A single-center experience.

In the 10th month of the pandemic, coronavirus disease 2019 (COVID-19) vaccination was given first to healthcare workers in Turkey after receiving emergency use approval from the Ministry of Health. This study, which was performed at the COVID-19 reference center in Ankara (the capital of Turkey) aimed to evaluate the seroconversion rate of the CoronaVac vaccine. The anti-spike immunoglobulin G response to the two-dose vaccination was retrospectively examined in healthcare workers who had no previous history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The postvaccine seroconversion rate was investigated by measuring the antibody levels of healthcare workers who had received CoronaVac. Vaccination was administered as 600 SU in 28-day intervals. The healthcare workers' anti-SARS-CoV-2 immunoglobulin G levels were used to determine the seroconversion rate 2 months after the second dose of the vaccine. Of the healthcare workers, 22.9% (n = 155) were seronegative. The younger the age of the participant, the higher the level of anti-SARS-CoV-2 immunoglobulin G. Furthermore, anti-SARS-CoV-2 immunoglobulin G levels were much higher in women than men.

Higher viral loads in asymptomatic COVID-19 patients might be the invisible part of the iceberg.

PURPOSE: SARS-CoV-2 virus dynamics in different hosts and different samples and their relationship with disease severity have not been clearly revealed. The aim of this study is to evaluate the viral loads of 6 different sample types (nasopharyngeal/oropharyngeal combined, oral cavity, saliva, rectal, urine, and blood) of patients with different ages and clinics, to reveal the relationship between disease course and SARS-CoV-2 viral load, and differences in viral loads of asymptomatic and symptomatic patients. METHODS: Nasopharyngeal/oropharyngeal, oral cavity, saliva, rectal, urine, and blood samples are collected from patients who were hospitalized with diagnosis of COVID-19 on admission. Laboratory analysis were carried out at Public Health Institute of Turkey Virology Reference and Research Laboratory. RESULTS: A total of 360 samples from 60 patients were obtained on admission. Fifteen (25%) of the patients were asymptomatic while 45 (75%) were symptomatic. A significant difference was found between mean ages of asymptomatic vs symptomatic patients (26.4 and 36.4, respectively, p = 0.0248). No PCR positivity were found in blood. Only one asymptomatic patient had positive PCR result for urine sample. Viral loads of asymptomatic patients were found to be significantly higher (p = 0.0141) when compared with symptomatic patients. Viral load had a significant negative trend with increasing age. A significant decrease in viral load was observed with increasing disease severity. CONCLUSION: In conclusion, this study demonstrates that asymptomatic patients have higher SARSCoV-2 viral loads than symptomatic patients and unlike in the few study in the literature, a significant decrease in viral load of nasopharyngeal/oropharyngeal samples was observed with increasing disease severity. Factors associated with poor prognosis are found to be significantly correlated with low viral load.

Etiological and Clinical Profile of Acute Nonbacterial Encephalitis in Children: A Single-Center Prospective Study.

Encephalitis is a serious neurological syndrome caused by inflammation of the brain. The diagnosis can be challenging and etiology remains unidentified in about half of the pediatric cases. We aimed to investigate demographic, clinical, laboratory, electroencephalographic and neuroimaging findings, and outcome of acute encephalitis of nonbacterial etiology. This prospective study included children hospitalized with the diagnosis of acute encephalitis between 2017 and 2019. Microbiological investigations of the cerebrospinal fluid (CSF) were recorded. All CSF specimens were tested for anti-N methyl D-aspartate receptor (NMDAR) antibodies. In total, 31 children aged 10 months to 17 years (median = 6 years) were included. Pathogens were confirmed in CSF in three patients (9.7%): varicella zoster virus, herpes simplex virus type 1 (HSV-1), and both HSV-1 and NMDAR antibodies. Presenting features included encephalopathy (100%), fever (80.6%), seizure (45.2%), focal neurological signs (29%), and ataxia (19.4%). On clinical follow-up of median 9 (6-24) months, six patients showed neurological deficits: together with two patients who died in hospital, total eight (25.8%) patients were considered to have unfavorable outcome. Need for intubation, receiving immunomodulatory treatment, prolonged hospitalization, and high erythrocyte sedimentation rate at admission were associated with unfavorable outcome. The etiology of encephalitis remains unexplained in the majority of children. HSV-1 is the most frequently detected virus, consistent with the literature. The fact that anti-NMDAR encephalitis was detected in one child suggests autoimmune encephalitis not being rare in our center. The outcome is favorable in the majority while about one-fifth of cases suffer from sequelae.

Detection of non-polio and polio enteroviruses in Acute Flaccid Paralysis surveillance in Turkey.

Poliomyelitis was a disease feared worldwide, striking suddenly and paralysing mainly children for life. Monitoring of suspected cases of poliomyelitis is carried out with Acute Flaccid Paralysis (AFP) surveillance in Turkey. This study examines national data of AFP surveillance and the epidemiology of enteroviruses (EV) in Turkey from 2000 to 2019 and gives an overview of the detected serotypes of EVs. A total of 13,640 samples collected from patients with 5216 AFP pre-diagnosed cases (2 samples from each patient) and 3,208 contacts, during a 20-year period (2000-2019) were investigated. All isolated polioviruses were tested for their wild or vaccine origin according to the WHO recommended protocol by PCR and sequencing analysis were performed. Enterovirus positivity was detected in a total of 915 cases, which were identified as 204 Sabin-like polio virus (SLPV) and 711 non-polio enterovirus (NPEV). Of the 204 SLPV, 141 (69.1%) AFP were detected in patients and 63 (30.9%) were detected in samples taken from their contacts. Of the 711 NPEVs, 516 (72.5%) were from AFP cases and 195 (27.5%) were detected in samples taken from their contacts. It is concluded that the reason for the higher detection rate of NPEV in samples from AFP pre-diagnosed cases is attributed to the polio vaccination rates reaching 97% between 2008 and 2019 in Turkey. The most frequently detected NPEV serotypes were Coxackie A24, B3, and Echo 30. This retrospective study is the first comprehensive study in Turkey to evaluate the results of the AFP surveillance in the last 20 years.

Identification of potential microRNA markers related to Crimean-Congo hemorrhagic fever disease.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the arbovirus Crimean-Congo hemorrhagic fever virus (CCHFV). The CCHFV has a single-stranded RNA genome of negative sense. MicroRNAs (miRNAs) are key players in virus-host interactions and viral pathogenesis. We investigated the miRNA gene expression profiles in patients with CCHF using microarray for the first time in the world. Microarray analysis was performed using mirBase Ver 21 (Agilent Technologies, Santa Clara, CA). All statistical analyses were performed across the case-control, fatal-control, and fatal-nonfatal case groups using Genespring (Ver 3.0). Fifteen miRNAs were statistical significant in patients with CCHF compared with the controls (5 were upregulated, 10 were downregulated). Seventy-five and sixty-six miRNAs are in fatal compared with control and nonfatal case, respectively (fold change ([FC] ≥50) were statistically significant. In this study, the target genes of important miRNAs were identified and Gene Ontology analyses were performed across all groups. As a result of this study, we propose that the detection of miRNAs in patients with CCHF will allow the determination of therapeutic targets in diseases. CCHF is an important public health problem that can often be fatal. In this study, we investigated miRNA expression in case-control, fatal-control, and fatal-nonfatal case groups. Significant miRNAs associated with fatality were detected in CCHF. This study will serve as a source of data for the development of an antagomir-based therapy against CCHF using miRNAs in the future.

[Travel Related Fever and Rash: Two Cases of Dengue Fever]. / Seyahat Iliskili Ates ve Döküntü: Iki Dengue Atesi Olgusu.

The frequency of travel-related infections in the world has increased due to the easily and widespread use of travel facilities in the 21st century. Vector-borne diseases are an important part of infectious diseases. Dengue fever is one of the travel-related infections that has been reported increasingly in recent years through the development of diagnostic methods. The aim of this report was to present two Dengue fever cases originating from travel. There was a story of mosquito bite during a trip to Sri Lanka travel in our first case. The patient was 30 years old and maculopapular rash appeared on the fifth day of contact. Three days after the onset of the rash, she has admitted to our clinic, complaining with fever and chills. Increased leukopenia and muscle enzymes were detected in the laboratory analysis. Real-time reverse transcriptase polimerase chain reaction (RT-PCR) was positive in the serum sample. The patient was followed up with supportive care and discharged by improvement. The second case, a 24-year-old male, had a story of mosquito bite during his trip to Malaysia. After the patient complained of fever, chills, fever, nausea, vomiting and muscle pain, the Dengue virus (DENV) NS1 antigen test performed in this country was found to be positive. In the second case, there was no maculopapular rash and laboratory analysis showed an increase in leukopenia, thrombocytopenia and muscle enzymes. RT-PCR positivity was detected in the serum sample. The patient was followed up with supportive treatment and discharged with cure. DENV infections are caused by DENV which is common in the tropical areas of the world. There are four DENV-1, DENV-2, DENV-3 and DENV-4 serotypes. DENV infections can present different clinical manifestations such as asymptomatic disease, viral syndrome, Dengue haemorrhagic fever, and Dengue shock syndrome. Dengue fever is often accompanied by arthritis, maculopapular rash and high fever. Our cases were defined as Dengue fever according to this definition. In the diagnosis of the disease, it is necessary first to be suspicious of the disease and the travel history must be questioned. In the definitive diagnosis, virus isolation, antigen, nucleic acid detection and serological tests are used. The virus can be isolated from blood, serum, urine and tissues. In the first five days after beginning of the symptoms associated with DENV infections, serum RT-PCR and Dengue NS1 antigen test may be positive.

Evaluation of measles immunity in Turkey: is it still a threat?

Background/aim: Measles is one of the important vaccine-preventable diseases with many complications in childhood. This study presents cross-sectional seroepidemiological data, beginning from neonatal cord blood in infants to children under 6 years of age, about waning of measles antibody and tries to suggest the proper time for measles immunization. Materials and methods: A total of 564 blood samples consisting of neonatal cord blood and samples taken from infants and children at ages of 6, 9, 24­48, and 49­72 months were analyzed for measles seropositivity in a period of 6 months. Results: Measles seropositivity rate was 72.5% in 109 cord blood samples, 2.6% in 117 infants of 6 months of age, and 3.6% in 111 infants of 9 months of age. Seropositivity was determined in 118 children at 24­48 months and in 109 children at 49­72 months and was 80.5% and 66%, respectively (P = 0.001). These children were vaccinated in the 12th month. Conclusion: Though measles immunization coverage is 97% in Turkey, population immunity is somewhat lower than expected. Increases of measles cases in Europe and the refugee problem in the country could easily lead to outbreaks. Implementing the first dose of the immunization at 9 months may be an option.

Genetic variability human respiratory syncytial virus subgroups A and B in Turkey during six successive epidemic seasons, 2009-2015.

Human respiratory syncytial virus (HRSV) is most important viral respiratory pathogen of acute lower respiratory tract infections in infants and young children worldwide. The circulating pattern and genetic characteristics in the HRSV attachment glycoprotein gene were investigated in Turkey during six consecutive seasons from 2009 to 2015. HRSVA was dominant in the all epidemic seasons except 2011-2012 season. Partial sequences of the HVR2 region of the G gene of 479 HRSVA and 135 HRSVB were obtained. Most Turkish strains belonged to NA1, ON1, and BA9, which were the predominant genotypes circulating worldwide. Although three novel genotypes, TR-A, TR-BA1, and TR-BA2, were identified, they were not predominant. Clinical data were available for 69 HRSV-positive patients who were monitored due to acute lower respiratory tract illness. There were no significant differences in the clinical diagnosis, hospitalization rates, laboratory findings and treatment observed between the HRSVA and HRSVB groups, and co-infections in this study. The major population afflicted by HRSV infections included infants and children between 13 and 24 months of age. We detected that the CB1, GB5, and THB strains clustered in the same branch with a bootstrap value of 100%. CB-B and BA12 strains clustered in the same branch with a bootstrap value of 65%. The BA11 genotype was clustered in the BA9 genotype in our study. The present study may contribute on the molecular epidemiology of HRSV in Turkey and provide data for HRSV strains circulating in local communities and other regions worldwide.