The relation between concentration of the proinflamatory cytokines in serum and clinical, parasitological and hematological changes during the imported malaria

REZIME: Malarija je multisistemska, potencijalno letalna bolest uzrokovana parazitima roda Plasmodium. Dokazano je da kod malarije oslobadanje proinflamatornih citokina produkuje sistemski, inflamatorni odgovor i da su njihove koncentracije povecane, posebno kod teških formi. Smatra se da su citokini odgovorni za pojavu temperature, povracanja, proliva, mialgija, trombocitopenije, imunospupresije, koagulopatije i neuroloških manifestacija. U Klinici za infektivne i tropske bolesti u periodu 2000- 2010. godine je leceno 103 bolesnika sa importovanom malarijom. U ukupnom uzorku bolesnika odredivani su najznacajniji klinicki i laboratorijski parametri, sa posebnim osvrtom na stepen parazitemije.U prospektivnom delu istraživanja koje je ukljucivalo 34 bolesnika uzeti su citokini: TNF- i IL-6. Najvažniji cilj disertacije je da se odredi nivo citokina TNF- i IL-6 u dve faze: pre i posle terapije, i ustanovi njihova korelacija sa klinickim, parazitološkim i hematološkim parametrima. Prema kriterijumima SZO za teške forme malarije formirana je grupa od 22 bolesnika i odredivane su njihove najucestalije komplikacije, kao i razlike u odnosu na ukupan uzorak bolesnika. Ustanovljeno je da su u prvoj fazi povišeni nivoi citokina TNF- i IL-6, i da postoji njihova jaka medusobna korelacija, kao i korelacija sa stepenom parazitemije, povišenim vrednostima d-dimera i laktata, leukopenijom i trombocitopenijom. Sem toga, utvrdeno je da je znacajno veci broj bolesnika imao falciparum malariju, parazitemiju manju od 5%, da nije uzimao hemoprofilaksu, a trombocitopenija je bila najcešca laboratorijska abnormalnost. Bolesnici sa hiperparazitemijom imali su znacajno vece vrednosti bilirubina i cešcu pojavu neuroloških komplikacija, dok su kod teških formi malarije ustanovljene znacajno više vrednosti TNF- i niže vrednosti trombocita.ABSTRACT: Malaria is a multisystemic, potentially lethal disease caused by parasites of the genus Plasmodium. It has been proven that the release of proinflammatory cytokines in malaria produces systemic inflammatory response and that their concentrations are increased, especially in severe forms. It is considered that the cytokines are responsible for the occurrence of fever, vomiting, diarrhea, myalgia, thrombocytopenia, immunosuppression, coagulopathy and neurological manifestations. At the Clinic of Infectious and Tropical Diseases, 103 patients with imported malaria were treated during the period 2000-2010. The most important clinical and laboratory parameters were determined in the total sample of patients, with special reference to the degree of parasitemia. In the prospective part of the study that included 34 patients, the cytokines TNF- and IL-6 have been taken. The main aim of the doctorate is to determine the levels of cytokines TNF- and IL-6 in two phases: before and after treatment, and to establish their correlation with clinical, parasitological and hematological parameters. According to the WHO criteria for severe forms of malaria, a group of 22 patients was formed, and their most common complications were determined, as well as the comparasion to the total sample of patients. It was confirmed that in the first phase, the levels of cytokines TNF and IL-6 are elevated and that there is their strong mutual correlation and correlation with the degree of parasitemia,elevated d-dimer and lactate levels, leukopenia and thrombocytopenia. In addition, it was found that a significantly greater number of these patients had falciparum malaria, as well as parasitemia less than 5%, that they did not take chemoprophylaxis, and the thrombocytopenia was the most common laboratory abnormality. Patients with hyperparasitemia had significantly higher values of bilirubin and more frequent occurrence of neurological complications, while in severe forms of malaria has been found significantly higher levels of TNF- and the lower number of thrombocytes

An exceptional case report of disseminated cryptococcosis in a hitherto immunocompetent patient

Cryptococcosis is an opportunistic fungal infection causes significant disease predominantly in immunocompromised patients. Here we present an excepcional case of disseminated cryptococcosis with pulmonary and cerebral involvement in an immunocompetent patient with no apparent predisposing factors at the time of hospital admission. We described a case of an apparently immunocompetent 66-years old man admitted to hospital with a one-month history of cough, fever and vertigo. During hospitalization, thorax imaging was suggestive of lung metastasis, therefore, he went through several investigations. During hospitalization, he developed neurological symptoms and subsequently underwent a lumbar puncture. Cerebrospinal fluid (CSF) culture was positive for Cryptococcus spp. isolated on Sabouraud’s dextrose agar and bird seed agar. In addition, the direct microscopy examination was positive for the India ink test, as well as with the latex agglutination test for cryptococcal polysaccharide antigen (CrAg) in CSF, while serum CrAg was negative. Despite the absence of classic immunocompromising features, he was treated with amphotericin B and fluconazole due to suspected disseminated cryptococcal infection. Later, he was diagnosed with prostatic adenocarcinoma. Upon successful completion of treatment for disseminated cryptococcosis, the patient underwent radical prostate ablation surgery as a treatment forprostatic adenocarcinoma. This exceptional case emphasizes the high degree of suspicion of atypical infections, and in these cases, it is particularly important to consider fungal infections in hitherto healthy patients with no apparent predisposing factors. Although Cryptococcus spp. is predominantly reported in patients with hematological malignancies, cryptococcosis investigation should also be considered as part of the initial workup of patients with a new diagnosis of a solid tumour prior to chemotherapy or radiotherapy.Publisher PDFPeer reviewe

Knowledge, Attitudes, and Practices on Tick-Borne Encephalitis Virus and Tick-Borne Diseases within Professionally Tick-Exposed Persons, Health Care Workers, and General Population in Serbia: A Questionnaire-Based Study

This study assessed the level of knowledge, attitudes, and practices (KAP) regarding tick-borne encephalitis virus (TBEV) and tick-borne diseases (TBDs) among different groups of people in Serbia. Professionally tick-exposed persons (PTEPs), health care workers (HCWs), and the general population (GP) were subjected to an anonymous, voluntary, online questionnaire using Microsoft Forms. A total of 663 questionnaire responses were collected (February–March 2021), while 642 were included in the analysis. The significant difference in knowledge in TBDs existed between GP and PTEPs, and HCWs (p < 0.001). The perception of risk-to-tick exposure and TBDs was generally high (42.4 (95% CI: 33.6–51.2) within GP, 44.9 (95% CI: 35.8–53.9) within PTEPs and 46.2 (95% CI: 38.0–54.5) within HCWs), while fear was low (13.7 (95% CI: 7.9–19.5) within GP, 12.6 (95% CI: 7.3–19.9) within PTEPs, and 13.5 (95% CI: 7.4–19.5) within HCWs). Protective practices differed across groups (F (2639) = 12.920, p < 0.001, η2 = 0.039), with both PTEPs (t = 3.621, Cohen d = 0.332, p < 0.001) and HCWs (t = 4.644, Cohen d = 0.468, p < 0.001) adhering to more protective practices than the GP, without differences between PTEPs and HCWs (t = 1.256, Cohen d = 0.137, p = 0.421). Further education about TBDs in Serbia is required and critical points were identified in this study

Increased tumor necrosis factor alpha and interleukin-6 serum levels and their correlation with laboratory parameters in patients with imported malaria

In malaria, blood concentrations of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6, are increased. In a study which included 34 patients, TNF-α and IL-6 were examined in two phases, immediately after the admission of patients, and at the end of antimalarial therapy, when the parasitemia was negative. The results show a significant increase of TNF-α and IL-6 in the first phase, before the effects of antimalarial therapy. A very strong correlation between TNF-α and IL-6 is also confirmed, which suggests their coordinated production. Increased TNF-α values were correlated with an older age, the level of parasitemia, the number of platelets and leukocytes, elevated values of procalcitonin, D-dimer and lactate dehydrogenasе, and lower values of serum iron and antithrombin. Increased values of IL-6 were correlated with the level of parasitemia, the number of platelets and leukocytes, and elevated values of D-dimer and lactates

Ekologija komaraca roda Anopheles na području Beograda u proceni vektorskog potencijala za ponovno uspostavljanje transmisije malarije

Belgrade is situated in the area that is potentially at risk from malaria outbrakes. Until eradication, the main vector of malaria in this area was Anopheles maculipennis s. s. (previous name An. typicus) and secondary vectors were An. messeae and An. atroparvus. In this study we examined the distribution and ecology of Anopheles mosquitoes (Diptera, Culicidae) in Belgrade. Females of Anopheles mosquitoes were collected from animal shelters in Belgrade at eight locations during 2003. Egg morphology was used to identify the specimens. A total of 3704 females deposited eggs ready for identification. Three species of An. maculipennis complex were identified: An. messeae, An. atroparvus and An. maculipennis s. s.. The most abundant species were An. messeae (64%). The relative frequency of three species varied depending on the site of collection. Seasonal fluctuations of mosquitoes' species varied. Each develops in a distinct type of water, too. The three species of the An. maculipennis complex, particularly An. messeae and An. atroparvus, are considered as potential vectors of malaria in Belgrade. With the possible reintroduction of Plasmodium species due to climatic changes and increased travel to and from the countries where malaria is endemic, a more efficient vector control is necessary.Beograd je smešten u području koje je potencijalno rizično za ponovno uspostavljanje transmisije malarije. Do eradikacije malarije, glavni vektor malarije na području Beograda bio je An. maculipennis s. s. (raniji naziv An. typicus) a sekundarni vektori bili su An. messeae i An. atroparvus. Mi smo analizirali distribuciju i ekologiju komaraca roda Anopheles (Diptera, Culicidae) na području Beograda. Ženke komaraca roda Anopheles sakupljali smo tokom 2003. godine na 8 lokaliteta šireg područja Beograda. Identifikaciju vrsta vršili smo na osnovu morfologije položenih jaja. Od ukupnog broja izlovljenih ženki komaraca roda Anopheles, njih 3704 je položilo jaja, a njihovom identifikacijom nađene su tri vrste komaraca roda Anopheles, svi pripadnici Anopheles maculipennis kompleksa: An. messeae, An. atroparvus i An. maculipennis s. s.. U ukupnoj populaciji najzastupljeniji je bio An. messeae 64%, zatim An. atroparvus 21%, a najmanje Anopheles maculipennis s. s. 8%. Postojala je razlika u procentualnoj zastupljenosti ovih vrsta u ukupnoj Anopheles populaciji prema lokalitetima, po mesecima, prema izboru vodenih staništa. Prisutne vrste Anopheles komaraca, posebno An. messeae i An. atroparvus ukazuju da je Beograd receptivan za transmisiju malarije, a klimatski uslovi tokom leta pogodni su za kompletiranje sporogoničnog razvoja pripadnika roda Plasmodium

Seasonality of trichinellosis in patients hospitalized in Belgrade, Serbia

A retrospective study of the course and outcome of trichinellosis in a series of 50 patients hospitalized at the Institute for Infectious and Tropical Diseases in Belgrade between 2001 and 2008 was performed. Clinical diagnosis of trichinellosis was based upon the patients' clinical history, symptoms and signs, and eosinophilia. The occurrence of cases showed a strong seasonality (P lt 0.00011. The incubation period ranged between one and 33 days. The mean time between onset of symptoms and admission was nine days. Family outbreaks were the most frequent. Smoked pork products were the dominant source of infection (76 %). Fever was the most frequent clinical manifestation (90 %), followed by myalgia (80 %) and periorbital edema (76 %). 43 patients were examined serologically and 72 % of them had anti-Trichinella antibodies. Eosinophilia and elevated levels of serum CK and LDH were detected in 94, 50 and 56 % of the patients, respectively. All patients responded favorably to treatment with mebendazole or albendazole, but eight developed transient complications. Trichinellosis remains a major public health issue in Serbia

Risk factors associated with poor clinical outcome in pyogenic spinal infections : 5-years’ intensive care experience

Introduction: Management of pyogenic spinal infections (PSI) after the development of neurological deficit has not been specifically addressed in the literature. We aimed to describe real-life clinical outcomes of PSI in patients admitted to an intensive care unit with neurological deficit and identify factors associated with good prognosis. Methodology: Consecutive patients admitted to ICU with a possible diagnosis of spinal infection over five years’ period were included. Descriptive statistics were performed to examine the demographics and clinical parameters. Results: The majority (71%) of patients were male. The mean age was 57.4 years (27-79), and 71% were > 50 years old. At least one underlying risk factor was identified in 68% of the patients; the most common comorbidity was diabetes mellitus (DM). All patients have presented with fever accompanied by a neurological deficit (86%) and back pain (79%). A complete recovery was achieved in 25% of patients. However, the majority of patients had adverse outcomes with 21.4% mortality, and 43% remaining neurological sequelae. Increased age with a cut-off of 65 years and pre-existing DM were identified as being associated with poor outcome. Conclusion: Mortality among patients admitted to ICU with PSI was significantly higher than reported in the literature. The residual neurological deficit was common, one-third of patients had remaining neurological sequelae, and only one-fourth had complete recovery. Increased age and background DM were the most important determinants of poor clinical outcome. The impact of DM appears to be much more important than currently recognised in this population.Publisher PDFPeer reviewe

Isolation of Borrelia lusitaniae from the blood of a patient with multiple erythema migrans

Tropical Diseases of the University Clinical Centre of Serbia with a clinical presentation of disseminated erythema migrans. The patient and the mother could not recall if there had been a tick bite. A sample of blood was taken, and antibiotic therapy with amoxicillin was started immediately. Human serum sample was checked for the presence of IgM antibody against Borrelia burgdorferi sensu lato by commercial ELISA test and the sample was positive for IgM. Blood was collected into the sterile K2EDTA tube, immediately transported to the Laboratory at the Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade, and centrifuged twice at 2200 rpm for 17 min at room temperature. After centrifugation, one part of the serum was served for DNA extraction using ammonium hydroxide, ethanol, and sodium acetate while the sediment was inoculated into a 6 mL tube with Barbour-Stoenner-Kelly-H (BSK-H) medium under aseptic conditions and incubated as 33°C. After 16 days of incubation, viable, motile, and spiral-shaped microorganisms were observed in the initial BSK-H culture under dark-field microscopy, and incubation was prolonged for 29 days. DNA from the culture was extracted using centrifugation, dissolving the sediment in the water, and heating at 95°C for 10 minutes. After extracting DNA from the human serum and the culture, rrf-rrl rDNA intergenic spacer and flagellin gene (flaB) were amplified by conventional PCR, and sequencing of obtained PCR products was performed commercially (Macrogen, Amsterdam, the Netherlands). After analysis of the sequences obtained, Borrelia lusitaniae was confirmed in human serum and culture. This is the first isolate of B. lusitaniae from a human blood sample that confirms that B. lusitaniae can disseminate via the hematogenous route

Epidemiologija i dijagnostika fascioloze ljudi

Fasciolosis is a zoonotic infection caused by the trematoda Fasciola hepatica and Fasciola gigantica. Human fasciolosis is endemic in some parts of South America, Africa, Eastern Asia and Europe. High prevalence of human fasciolosis does not necessarily occur in areas where fasciolosis is a major veterinary problem. Infection with Fasciola hepatica has not been reported in humans in Serbia and former Yugoslavia, although a large variety of animals, such as sheep and cattle show infection rates that may reach significant proportions in some areas. Humans can become accidental hosts of this parasite by ingesting contaminated drinking water or plants in an endemic area. Infection with Fasciola hepatica has a variable clinical presentation depending on the stage of the disease. Typical symptoms that may be associated with fascioliasis can be divided by the phases of the disease including the acute or liver phase, the chronic or biliary phase, the obstructive phase, and ectopic or pharyngeal fascioliasis. The diagnosis of human fasciolosis may be problematical and delayed, especially in non-endemic areas, because physicians rarely encounter this disease and a long list of other diseases must be included in the differential diagnosis. The diagnosis of fasciolosis is complex and requires the application of direct an indirect methods of diagnostics: clinical diagnosis, haematological and biochemical findings, parasitological diagnosis, immuno-diagnosis, imaging procedures, liver biopsy. At the Clinic for Infectious and Tropical Diseases in 2005, we recorded the first case of human fasciolosis in a woman from Belgrade, a citizen of Serbia, who developed clinical symptoms of acute fasciolosis after several months of living in Bosnia-Herzegovina. This article reviews the epidemiology and diagnostics of human fasciolosis. .Fascioloza je zoonozna infekcija izazvana trematodama Fasciola hepatica i Fasciola gigantica. Fascioloza ljudi je endemska bolest u pojedinim delovima Južne Amerike, Afrike, istočne Azije i Evrope. Visoka prevalencija fascioloze ljudi nije uvek povezana sa visokom prevalencijom animalne fascioloze. Iako je fascioloza domaćih životinja, pre svega ovaca i goveda, značajno prisutna u pojedinim krajevima Srbije i bivše Jugoslavije, nema dokumentacije, odnosno objavljenih slučajeva fascioloze ljudi u Srbiji. Čovek postaje slučajan domaćin unošenjem infektivnih oblika parazita kontaminiranom vodom ili biljkama. Klinička slika ove bolesti je raznovrsna i zavisi od stadijuma infekcije: akutna ili hepatična, hronična ili bilijarna, obstruktivna, ređe ektopična ili faringealna. Dijagnostika fascioloze ljudi može da bude komplikovana i dugotrajna, naročito u krajevima gde se bolest retko javlja i gde se na nju retko pomišlja, kao i zbog brojnih bolesti slične kliničke manifestacije, koje treba isključiti. Dijagnostika fascioloze ljudi je kompleksna i podrazumeva primenu direktnih i indirektnih dijagnostičkih procedura. Dijagnoza se zasniva na kliničkoj slici, hematološkim i biohemijskim nalazima, parazitološkom nalazu, imunološkoj dijagnostici, tehnikama vizuelizacije patoloških promena i biopsiji jetre. Na Klinici za infektivne i tropske bolesti 2005. godine je dijagnostikovan prvi slučaj fascioloze ljudi u Srbiji. Pacijentkinja iz Beograda razvila je kliničku sliku akutne fascioloze nakon nekoliko meseci boravka u Hercegovini. Ovaj rad predstavlja osvrt na epidemiološki i dijagnostički aspekt fascioloze ljudi.

tick borne encephalitis in serbia a case series

Introduction: In the Europe, the number of tick-borne encephalitis (TBE) has been increased in the last decade, and the number of endemic areas has been also increased and is still growing. In the present case series, we present clinical and socio-epidemiological data of patients with TBE hospitalized in the period of TBE virus epidemic in Serbia. Methodology: A case series was conducted in Serbia in 2017. Patients with confirmed TBE were included in the study. Biochemical and serological analysis of blood and CSF, as well as radiological imaging (CT and MRI) were done. Results: In total, 10 patients with TBE were included in the study. M:F ratio was 1.5:1, while average age was 45.1 years. Half of the patients had severe clinical picture. Endocranial CT scan and MRI did not reveal any abnormality, except in the patient with the most severe CNS infection (meningoencephalomyelitis). Mean value of sedimentation and CRP was slightly elevated (29.6 mm/1hours and 20.1 mg/L, respectively) in 80% of the patients, although elevation was almost negligible. The average number of leucocytes in the cerebrospinal fluid (CSF) was 171×106/L, the mean value of the CSF protein was 1.1g/L. There were no fatal outcomes. Conclusion: Since other CNS infections have similar clinical picture and CSF finding as TBE, serological analysis for TBE should be included in routine diagnostic practice