Prevalence of Polypharmacy and Potential Drug-Drug Interactions Associated with Risk Factors in the Era of HIV Integrase Inhibitors: A Prospective Clinical Study.

People living with human immunodeficiency virus (PLWH), with the availability of modern antiretroviral drugs, have multiple comorbidities, which increase the risk of polypharmacy and potential drug-drug interactions (PDDIs). This is a particularly important issue for the aging population of PLWH. This study aims to review the prevalence and risk factors for PDDIs and polypharmacy in the era of HIV integrase inhibitors. A cross-sectional, two-center, prospective observational study was conducted on Turkish outpatients between October 2021 and April 2022. Polypharmacy was defined as the use of ≥5 non-HIV medications, excluding over-the-counter (OTC) drugs, and PDDIs were classified using the University of Liverpool HIV Drug Interaction Database (harmful/red flagged and potentially clinically relevant/amber flagged). The median age of the 502 PLWH included in the study was 42 ± 12.4 years and 86.1% were males. Most individuals (96.4%) were given integrase-based regimens (unboosted 68.7% and boosted 27.7%). In total, 30.7% of individuals were taking at least one OTC drug. The prevalence of polypharmacy was 6.8% (9.2% when OTC drugs were included). During the study period, the prevalence of PDDIs was 1.2% for red flag PDDIs and 16% for amber flag PDDIs. CD4+ T cell count >500 cells/mm3, number of comorbidities ≥3, comedication with drugs affecting blood and blood-forming organs, cardiovascular drugs, and vitamin/mineral supplements were associated with red flag or amber flag PDDIs. Drug interaction prevention is still important in HIV care. Individuals with multiple comorbidities should be closely monitored for non-HIV medications to prevent PDDIs.

Factors Associated with 28-day Critical Illness Development During the First Wave of COVID-19.

Objective: This study aimed to define the predictors of critical illness development within 28 days postadmission during the first wave of the COVID-19 pandemic. Materials and Methods: We conducted a prospective cohort study including 477 PCR-positive COVID-19 patients admitted to a tertiary care hospital in Istanbul from March 12 to May 12, 2020. Results: The most common presenting symptoms were cough, dyspnea, and fatigue. Critical illness developed in 45 (9.4%; 95% CI=7.0%-12.4%) patients. In the multivariable analysis, age (hazard ratio (HR)=1.05, p<0.001), number of comorbidities (HR=1.33, p=0.02), procalcitonin ≥0.25 µg/L (HR=2.12, p=0.03) and lactate dehydrogenase (LDH) ≥350 U/L (HR=2.04, p=0.03) were independently associated with critical illness development. The World Health Organization (WHO) ordinal scale for clinical improvement on admission was the strongest predictor of critical illness (HR=4.15, p<0.001). The patients hospitalized at the end of the study period had a much better prognosis compared to the patients hospitalized at the beginning (HR=0.14; p=0.02). The C-index of the model was 0.92. Conclusion: Age, comorbidity number, the WHO scale, LDH, and procalcitonin were independently associated with critical illness development. Mortality from COVID-19 seemed to be decreasing as the first wave of the pandemic advanced. Graphic Abstract: Graphic Abstract.

Monitoring Crimean-Congo haemorrhagic fever virus RNA shedding in body secretions and serological status in hospitalised patients, Turkey, 2015.

IntroductionCrimean-Congo haemorrhagic fever (CCHF) is a tick-borne disease in Africa, Asia, the Balkan peninsula, the south-east of Europe and the Middle East, with mortality rates of 3-30%. Transmission can also occur through contact with infected animals or humans.AimThis observational, prospective case series aimed to investigate detectable viral genomic RNA in whole-body fluids and antibody dynamics in consecutive daily samples of patients diagnosed with CCHF until discharge from hospital.MethodsWe tested 18 patients and 824 swabs and sera with RT-PCR and 125 serum samples serologically.ResultsThe longest duration until clearance of viral RNA was 18 days from serum collection and 18, 15, 13, 19 and 17 days, respectively, from nasal, oral, genital (urethral or vaginal) and faecal swab, and urine. In seven patients, viral load decreased in serum at the same time as it increased in urine or persisted at the same logarithmic values. Despite clearance in serum, viral RNA was detected in faeces and genital swabs in two and three patients, respectively. Viral clearance from body fluids occurred earlier than from serum in eight patients on ribavirin treatment. The shortest seroconversion time was 3 days after symptom onset for IgM and IgG. Seroconversion of IgG occurred until Day 14 of symptoms.ConclusionWe report persistence of viral RNA in urine, faeces and genital swabs despite serum clearance. This may indicate a need for extending isolation precautions, re-evaluating discharge criteria and transmission risk after discharge, and considering oral swabs as a less invasive diagnostic alternative.

Crucial parameter of the outcome in Crimean Congo hemorrhagic fever: Viral load.

BACKGROUND: Crimean Congo hemorrhagic fever (CCHF) is a fatal disease with a mortality rate of 5-30%. CCHF can be asymptomatic or it may progress with bleeding and cause mortality. OBJECTIVES: To evaluate relation of viral load with mortality, clinical and laboratory findings in CCHF. STUDY DESIGN: A total of 126 CCHF patients were included. Serum samples obtained from all patients on admission for measurement of viral load. RESULTS: In our study, mortality rate was 11.1%. The most important prognostic factor was viral load. Mean viral load was 8.3×10(7)copy/ml and 4.6×10(9)copy/ml in survived and dead patients, respectively (p<0.005). Probability of survival is found to be significantly reduced where AST >1130U/l, ALT >490U/l, CPK >505U/l, LDH >980U/l, platelet count <23×10(3)/l, creatinine >1.4mg/dl, INR >1.3, d-dimer >7100ng/dl, and viral load >1.03×10(8)copy/ml. Patients with 10(8)copy/ml or higher viral load had diarrhea, headache, unconsciousness, bleeding, and seizure significantly more frequently (p<0.05). WBC, hemoglobin, platelet counts were significantly lower whereas AST, ALT, CPK, LDH, creatinine levels, PT and aPTT time, d-dimer levels, and INR were found to be significantly higher in these group. CONCLUSIONS: There are several severity criteria for prognosis of CCHF. In addition to these parameters, we introduce creatinine as a predictive factor for prognosis. Our study, which has the largest number of patients among studies that evaluate viral load on CCHF shows that viral load is the most effective parameter on mortality.

Crimean-Congo hemorrhagic fever with hyperbilirubinemia and ascites: An unusual presentation.

Crimean-Congo hemorrhagic fever (CCHF) is a fatal systemic viral infection which is an important health problem in Turkey. Many systemic symptoms have been reported including fever, hemorrhage, headache, fatigue, muscle ache, abdominal pain, nausea and vomiting. A 45-year-old male farmer with CCHF presented with massive peritoneal effusion and hyperbilirubinemia. To our knowledge, this is the first case of peritoneal effusion and hyperbilirubinemia in an adult patient with CCHF. His clinical symptoms successfully improved with supportive therapy. In patients who live in endemic areas with atypical presentation for the diagnosis of CCHF should be kept in mind.

Crimean-Congo hemorrhagic fever: CXCL10 correlates with the viral load.

Crimean-Congo hemorrhagic fever (CCHF) is a human disease with high fatality rate. Although its pathogenesis is not elucidated yet, it is considered that cytokines play a significant role in the progression and outcome of the disease. Serum CXCL10 levels were estimated in 35 patients with acute CCHF and were correlated with the viral load, and various demographic and clinical parameters. The mean CXCL10 concentration in the patients' group was higher compared to the respective value in the control group (4421.74 pg/ml vs. 28.47 pg/ml, P < 0.05). A strong positive correlation between CXCL10 and viral load was seen (rs = 0.57, P < 0.001), while the outcome of the disease was related with the viral load (rs = 0.47, P = 0.004) and the presence of hemorrhagic manifestations (P < 0.001). The study provides an insight into the strong correlation between CXCL10 and viral load in acute CCHF cases suggesting that it plays an important role in CCHF pathogenesis.

Seroprevalence and risk factors of Crimean-Congo hemorrhagic fever in selected seven provinces in Turkey.

Turkey has been one of the most endemic regions since 2002, when Crimean-Congo hemorrhagic fever emerged worldwide. The aim of the present study was to estimate the seroprevelance of CCHF virus in humans who reside in rural and urban areas of known endemic and nonendemic selected provinces of Turkey by using commercial ELISA kit. CCHFV IgG antibodies were detected in 2.3% of the population. The most important risk factors for CCHF seropositivity, were older age, male gender, illiterate, farmer, animal husbandry, living in rural residence in adobe houses, and a previous tick bite history.

[An imported dengue Fever case in Turkey and review of the literature]. / Yurt Disi Kaynakli Bir Dang Atesi Olgusu ve Literatürün Gözden Geçirilmesi.

Dengue fever is an acute viral disease that can affect all age groups in tropical and subtropical countries. The predominant vectors are the mosquitoes namely Aedes aegypti and A.albopictus. Although there have been no case reports in Turkey due to DF, there is seroepidemiological evidence indicating the presence of Dengue virus (DENV) in Turkey. In this case report we presented an imported dengue fever case. The patient was 40 years old, previously healthy male, Switzerland citizen. He had immigrated from Dubai to India two weeks ago and after one week from immigration he attended to a hospital in India because of high fever. The NS1 antigen test (Bio-Rad Laboratories, USA) was found positive and the patient was followed-up with diagnosis of dengue fever in India. During his visit to Turkey, he attended to the hospital for a routine control and his analysis revealed thrombocytopenia (PLT: 48.000/µl), leukopenia (white blood cell: 2800/µL) and elevated liver enzymes (AST: 76 U/L, ALT: 83 U/L). Fever was not detected in follow-up. The patient had petechial rash on his lower extremities. white blood cell and PLT count increased to 4100/µl and 93.000/µl, respectively. Liver function tests revealed a decrease in AST (63 U/L) and ALT (78 U/L) on the third day. The PLT count increased to 150.000/ml. Since the patient had no fever and had normal physical and laboratory findings, he was discharged from the hospital. For the confirmation of dengue fever diagnosis the serum sample was sent to National Public Health Center, Virology Reference and Research Laboratory where IgM and IgG antibodies against DENV types 1-4 were investigated by indirect immunofluorescence method (Euroimmun, Germany). The serum sample yielded positive result at the dilutions of 1/1000 for IgM and 1/10.000 for IgG. The last dilution of type 3 DENV IgM and IgG were determined high density of fluorescein, thus the serotype was identified as "DENV type 3". Travel-related diseases become important with increasing travel opportunities, globalization and transportation, recently. As a result, this imported case with foreign nationality was the first dengue fever case confirmed by clinical and laboratory tests in Turkey.

Human puumala and dobrava hantavirus infections in the Black Sea region of Turkey: a cross-sectional study.

This study was carried out to better understand the epidemiology of hantaviruses in a province of Turkey (Giresun) where human hantavirus disease has recently been detected. In this cross-sectional study, a total of 626 blood samples from healthy people aged 15 and 84 years old were collected both in urban and rural areas in 2009. The sera were tested by enzyme-linked immunosorbent assay (ELISA), immunoblotting assay, and the focus reduction neutralization test (FRNT). We screened the samples by an ELISA and found that 65/626 samples reacted positively for the presence of hantavirus-reactive immunoglobulin G (IgG). Twenty of the 65 ELISA-positive samples could be confirmed by an immunobloting assay, and the overall seroprevalence was thereby calculated to 3.2% (20/626). The seroprevalence of the people living in wood areas or adobe houses 9/17 (52.9%) was significantly higher than among people living in concrete houses 10/47 (21.3%) (p=0.014). Finally, 3 of the 20 immunoblot-positive sera were confirmed as specific for the Puumala hantavirus serotype by FRNT, 1 serum was confirmed as Dobrava virus-specific, whereas 1 serum was found to be equally reactive to Dobrava and Saaremaa viruses. We will now focus on further investigations of the ecology and epidemiology of hantaviruses in humans and their carrier animals in Turkey, studies that have already been started and will be further intensified.

[A fatal case of West Nile virus encephalitis]. / Ölümcül Seyreden Bati Nil Virusu Ensefaliti Olgusu.

Although West Nile virus (WNV) serologic evidence has been well demonstrated throghout Turkey in the last 40 years; the first symptomatic WNV infection was reported in 2009 and increased number of cases were reported during August 2010. In that period WNV encephalitis was diagnosed serologically (WNV IgM positivity in serum sample detected by ELISA and IFA) and confirmed by plaque reduction neutralization test in a 76-year-old man who was admitted to Baskent University Faculty of Medicine with complaints of fever, impaired consciousness and generalized tremors. Despite all supportive treatment, he died on the 9th day of hospitalization. In this report, detailed clinical course, laboratory features and diagnosis of this mortal case of WNV encephalitis were described. WNV encephalitis should be considered in the differential diagnosis of patients with fever of unknown origin and loss of consciousness especially in summer and early fall in Turkey.

[An imported Chikungunya fever case from New Delhi, India to Ankara, Turkey: the first imported case of Turkey and review of the literature]. / Ankara'ya Hindistan Yeni Delhi'den Gelen Bir Chikungunya Atesi Olgusu: Türkiye'nin Ilk Yurt Disi Kaynakli Olgusu ve Literatürün Gözden Geçirilmesi.

Chikungunya virus (CHIKV) is an arthropod-borne alphavirus that causes an acute febrile illness, chikungunya fever. CHIKV virus is geographically distributed in Africa, India, and South-East Asia. Chikungunya fever outbreaks have been reported from India since 2006. The incubation period is 3-7 days, and the disease is characterized by sudden onset of high fever and severe arthralgia. Other symptoms can be rash, headache, fatigue, nausea-vomiting, and myalgias. Here, we report the first Chikungunya case imported from India, New-Delhi to Ankara, Turkey. In December 2010, a 55-year-old female Turkish government employee living in urban area of New Delhi for the last 3 years had sudden onset fever up to 38.4°C for 2 days. Itching rash and arthralgia also developed. Symptomatic treatment was given to patient in New Delhi. She returned to Turkey and was admitted to Hacettepe University Medical Faculty, Department of Internal Medicine, Infectious Diseases Unit, since arthralgia has continued on the 26th day of her complaints. Hepatomegaly and tenosynovitis were detected in her physical examination. Serum sample sent to Refik Saydam National Public Health Agency, Virology Reference and Research Laboratory, yielded negative results for specific IgM and IgG antibodies against Hantavirus and Dengue virus types 1-4; however, the results were positive for CHIKV specific IgM and IgG antibodies by commercial immunofluorescence method (Euroimmun, Germany). CHIKV RNA which was searched by in-house real-time RT-PCR was negative. The second serum sample obtained three weeks later also found positive for CHIKV specific IgM and IgG antibodies. This was the first laboratory confirmed imported Chikungunya case in Turkey. There are predictions regarding the presence of Aedes species mosquitos that can transmit this virus in Turkey. This case report will be an alarming signal for the clinicians in our country to consider Chikungunya fever in the differential diagnosis of patients presenting with fever, arthralgia and rash.

[Sandfly fever outbreak in a province at Central Anatolia, Turkey]. / Kirikkale ilinde saptanan tatarcik hummasi salgini

Sandfly fever virus (SFV), which is classified in Phlebovirus genus, Bunyaviridae family, is widely seen in the Middle East and Mediterranean basin. SFV has four serotypes known as Sicilian (SFSV), Cyprus (SFCV), Naples (SFNV) and Toscana virus (TOSV). Sandfly fever, which is transmitted to human by different species of sandflies, especially Phlebotomus spp., starts with acute onset of high fever and lasts for three days. Headache, anorexia and myalgia are the most common symptoms. The aim of this study was to present the clinical and laboratory findings of the patients who were diagnosed during sandfly fever outbreak in Kirikkale province (located in central Anatolia in Turkey) during July 2009. A total of 20 patients from different districts of Kirikkale province with the history of fly bite and with the clinical findings of fever, myalgia-arthralgia, headache, conjunctival hyperemia and gastrointestinal symptoms such as diarrhea and nausea-vomiting were admitted to the Infectious Disease Unit of State Hospital. All the patients were followed up after hospitalization. A sandfly fever outbreak has been considered in the area since the cases shared a common history of insect bite, similar clinical and laboratory features in a particular time interval. The first patients from each different districts were accepted as the "index case" and 11 patients' serum samples have been sent to Refik Saydam National Public Health Agency, Virology Reference and Research Laboratory, Ankara. Serum samples were analyzed by using a commercial mosaic immunofluorescence test (IFT) (Euroimmun, Germany) to detect IgM and IgG antibodies against SFSV, SFCV, SFNV and TOSV. SFV-IgM positivity was demonstrated in 8 out of 11 patients (Naples virus in 5, Sicilian virus in 3 cases), while all of the cases were IgG negative. Of seropositive patients, two were female and six were male with a mean age of 30.7 (age range: 16-53) years. Sandfly fever was diagnosed in five cases by the positive IgM results and in three cases by the detection of IgM seroconversion in the second samples collected 6 days later. Clinically, fever and myalgia-arthralgia were detected in all of the cases, diarrhea and nausea-vomiting in 7, headache in 5 and conjunctival hyperemia in 1 of 8 seropositive patients. The evaluation of laboratory findings revealed leukopenia (1800-3800 cell/µl) in all cases, thrombocytopenia (69000-140.000 cell/µl) in 7, elevated AST (42-271 IU/L) in 7, elevated ALT (46-173 IU/L) in 5, elevated CK (185-1560 U/L) in 6 and elevated CRP (5.18-83.6 mg/L in 5 of 8 patients. All the patients were treated symptomatically without any sequella and discharged with complete cure. Turkey is a country in the Mediterranean basin and it is known that there is a favorable sandfly fauna in Anatolia. Therefore sandfly fever should be considered in patients presenting with fever and arthralgia-myalgia and with a history of insect bite especially during summer months.

[Hantavirus infection: two case reports from a province in the Eastern Black Sea Region, Turkey]. / Dogu Karadeniz, Giresun ilinde tespit edilen iki hantavirus enfeksiyonu olgusu.

Hantaviruses which are the members of Bunyaviridae, differ from other members of this family since they are transmitted to humans by rodents. More than 200.000 cases of hantavirus infections are reported annually worldwide. Hantaviruses can lead to two different types of infection in humans, namely, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is the most common type of hantavirus infection in Europe and Asia and the most common virus types are Dobrava, Puumala, Hantaan and Seoul. A total of 25 hantavirus suspected cases have been reported from the Western Black Sea region of Turkey and 12 of these were confirmed serologically as "Puumala" subtype. Serological tests such as indirect immunofluorescence assay (IFA), are used for diagnosis and typing of the hantaviruses, however, since cross-reactions are common between the subtypes, the results of these tests should be confirmed by other methods. In this report two cases with hantavirus infection defined serologically were presented. Two male patients, 55 and 50 years old, respectively, living in Giresun province of Eastern Black Sea region, Turkey, were admitted to the State Hospital with the complaints of fever, sweating and diarrhoea without blood or mucus. Since thrombocytopenia and renal failure were detected in these two cases, they were transferred to the University Hospital. Presence of fever, thrombocytopenia and renal failure, with no laboratory findings of a bacterial infection and no growth of microoorganisms in the clinical specimens, admittance of the patients during summer and history of being present in the fields, necessitated to rule out leptospirosis, Crimean Kongo hemorrhagic fever and hantavirus infection which were all endemic in our area. Further investigation of the serum samples at the National Reference Virology Laboratory by IFA (Hantavirus Mosaic-1, Euroimmun, Germany) revealed hantavirus IgM and IgG antibodies ≥ 1:100 titer and the results were confirmed by immunoblot test (Hantavirus Profile 1 EUROLINE IgG and IgM, Euroimmun, Germany). Hantavirus Dobrava subtype was determined in both of the cases. Reverse transcriptase real-time PCR (Hantavirus Renal Syndrome General-type I&II Real Time RT-PCR; Shanghai ZJ Bio-Tech, China) revealed negative result. The first case was discharged with complete cure, however, the second case died. These cases which were the first cases from the Eastern Black Sea Region emphasized that hantavirus infections should be taken into consideration in patients presenting with fever, thrombocytopenia and renal function disturbance.