ISSN: 0377-9777 / e-ISSN: 1308-2523
Turkish Bulletin of Hygiene and Experimental Biology - Turk Hij Den Biyol Derg: 76 (2)
Volume: 76  Issue: 2 - 2019
1. TBHEB 2019-2 Vol 76 Full Printed Journal
Utku Ercömart
Pages 124 - 229
Abstract |Full Text PDF

RESEARCH ARTICLE
2. Brucella Antibody Seropositivity In Children Living Around Yozgat
Seda Sabah Özcan, Ghaniya Daar Ede, Neziha Yilmaz
doi: 10.5505/TurkHijyen.2018.43660  Pages 125 - 130
INTRODUCTION: Objective: Brucellosis is a zoonotic disease in the World. It is associated with a high degree of morbidity and minimal mortality among the public health problem in Turkey
It is very rare in developed countries. Due to its high morbidity and economic loss, it still remains a major public health problem in our country and in the developing countries.
In our country, the vast majority of the cases are individuals living in the regions of Eastern and Southeastern Anatolia where animal husbandry is intensively performed.
Since brucellosis is not a disease with pathognomonic findings, serological and bacteriological tests are necessary to confirm the diagnosis. In the world, 20-30% of the cases of brucellosis, especially in endemic regions, are children. Childhood brucellosis is most often caused by the consumption of non-pasteurized milk and dairy products. Raw milk and milk products are common in Yozgat province. In childhood, the data about the seropositivity of brucella are very limited. In this study, it was aimed to investigate the seropositivity of brusella antibody in children living in and around Yozgat.


METHODS: Methods: The study included 238 healthy children in the 1-15 age group.
Approved informed by parents before being included in the study.
The number of households the children live in and the places they live in (rural and urban area) were questioned. Serum samples were analyzed for the presence of antibodies to Brucella antigens using a direct enzyme-linked immuno sorbent assay (ELISA).

RESULTS: Results: The average age of the 238 children studied was 7.3 ± 4.1 years, of which 48% were girls and 52% were girls. 71 (30%) of the children included in the study were rural and 167 (70%) were living in urban areas. No Brucella IgM antibody was detected in any of the cases when Brucella IgG antibody was detected in 1.6% of the children included in the study.
DISCUSSION AND CONCLUSION: Conclusions: The high seropositivity in our study may be due to the fact that the study population is formed from hospital applications, the use of non-pasteurized milk and dairy products nowadays, and the fact that families sometimes use dairy products from rural areas.
Brucellosis in children can not usually be treated because it is more subacute or asymptomatic. Brucellosis is a public health problem that needs to be investigated especially in endemic areas in children due to chronicity in the untreated cases and consequent sequelae that can develop in later ages.


3. Hepatitis A seronegativity and its relationship with social determinants in Manisa Province, 2014
hilal görgel kahraman, Özgen Alpay Özbek, Mestan Emek, Gonca Atasoylu, Özgur Sekreter, Belgin Unal
doi: 10.5505/TurkHijyen.2018.05826  Pages 131 - 140
INTRODUCTION: The aim of this cross-sectional study is to investigate the relationship between hepatitis A seronegativity and some social determinants in Manisa Province, in the year 2014.
METHODS: The study was carried out using the data and obtained from the study titled 'Determining the Seroprevalence of Some Vaccine-Preventable Diseases in Manisa'. The dependent variable was hepatitis A seronegativity; gender, age group, educational level, occupational class, annual income per capita, perceived income status, household density (number of people per room) and childhood place of residence were the independent variables. Serum samples were analyzed for total anti-HAV positivity with electrochemiluminescence immunoassay method by a Roche-Cobas e 411 (Roche Diagnostics GmbH, Mannheim, Germany) device and compatible kits. The relationship between dependent and independent variables were examined by using chi-square test for categorical variables. The adjusted odds ratios (OR) and 95% confidence intervals (CI) for each variable were calculated by logistic regression method.
RESULTS: In this study, data from1223 person were analyzed. Hepatitis A seronegativity was 24.4%. The age groups with the highest hepatitis A seronegativity were 2-9, 10-19 and 20-29, with the percents of 78.5%, 65.8% and 31.3% respectively. Seronegativity percentages range from 0.0% to 5.5% in groups over 30 years of age. Köprübaşı district (8.30%) had the lowest hepatitis A seronegativity and Kırkağaç (34.6%) had the highest. When we evaluated the association between social determinants and hepatitis A seronegativity; having an equivalent of annual income per capita equal or lower than 3265 TL had a protective effect on hepatitis A seronegativity (OR: 0.61, 95% CI: 0.42-0.90). According to the density of the households, it was found that those who had more than one person had a protective effect on hepatitis A seronegativity (OR: 0.48, 95% CI: 0.32-0.71). There was no significant association between hepatitis A seronegativity and gender, place of childhood, place of residence, educational status, occupational status, perceived income level and toilet location of the dwelling (p> 0.05 for all).
DISCUSSION AND CONCLUSION: Hepatitis A vaccination should be performed because of high contagiousness during childhood and increasing mortality and morbidity with aging. Districts with high hepatitis A seronegativity, families with low-income and households with high density must be prioritised for immunization and health education services



4. Outbreak of Shigella sonnei infection in Terme City, Turkey, September 2012
SELMUR TOPAL, HUSEYIN CELIK, Şenol YILMAZ, Erdinç Özoğlu, Okan Karaoğlanoğlu, Fehminaz Temel, HULYA SIRIN
doi: 10.5505/TurkHijyen.2018.90277  Pages 141 - 148
INTRODUCTION: Waterborne outbreaks occur in Turkey every year; however, few have been thoroughly investigated. On 24 September 2012, an increase in gastroenteritis cases in Terme City, Samsun Province was reported to the Public Health Institution of Turkey. We investigated this outbreak to determine its source and mode of transmission, and to recommend control measures.
METHODS: A matched case control investigation was conducted. A probable case had onset of diarrhoea (≥2/day) and vomiting plus ≥2 of the following symptoms in a Terme City resident: abdominal pain, nausea, perceived fever. In the study, we compared exposures during 15-24 September, of probable cases and 1: 1 matched neighbourhood control-persons. We took stool samples of 33 cases to identify the agent and for bacteriological, viral and parasitological tests.
We inspected the water sources, water distribution system and tanks for possible cause of contamination and collected water samples.


RESULTS: We identified 4050 hospital admissions with gastroenteritis-related ICD codes from acute gastroenteritis surveillance data. The attack rate was 9.2%. ın this outbreak investigation, of 112 probable cases, 65% had drank unboiled tap-water during 15-24 September, compared to 50% of 112 control-persons (ORadj=1.9; 95% CI: 1.1-3.5); conversely, 39% of case-patients and 54% of control-persons had drank bottled water (ORadj=0.51, 95% CI: 0.29-0.90). Of 33 stool specimens collected, 27 were culture-positive for Shigella sonnei; of 52 water samples collected at various distribution points, 18 had total coliform (range: 47-500) and 4 had E. coli (range: 5-20). Environmental investigation revealed a damaged water-pipe nearby the water tank.
DISCUSSION AND CONCLUSION: This large Shigellosis sonnei outbreak was caused by drinking contaminated tap-water. We recommended thorough inspection and repair of water treatment system.

5. Determination of usage frequency of household type water purifiers and effects on drinking water quality in Meram district
YUSUF KENAN BOYRAZ, Lutfi Saltuk Demir, Kübra Eken, Muhammed Fatih TABARA, Reyhan Evci, Yasemin Durduran, Mehmet Uyar, Tahir Kemal ŞAHİN
doi: 10.5505/TurkHijyen.2018.90197  Pages 149 - 156
INTRODUCTION: In this study, it is aimed to determine usage frequency of household type water purifiers in Meram district and their effects on microbiological and chemical quality of water.
METHODS: This cross-sectional study was conducted in Meram district of Konya province between the dates of 1st April - 1st June 2016. As the usage prevalence of household type water purifiers in Meram district was not known, it was assumed as 50% with G-Power 3.1.9.2 software; sample size was calculated as 810 houses with 95% confidence interval (α=0.05), 7% deviance, 80% power and design effect as 2. 810 houses were selected which were sampled from the neighborhoods of Meram district. A questionnaire was applied to the participants who agree to participate, by face to face interview. Water samples were taken from homes which were accesible, for microbiological and chemical analysis from the water network system and the household water purifier. Microbiological analysis was performed by membrane filtration method in Konya public health laboratory. Chemical analyzes (pH, conductivity, free chlorine, ammonium, nitrite, fluoride, calcium, magnesium and total hardness) were carried out by the Hach Lange DR 3900 UV spectrophotometer and the Hach Lange HQ40D pH-conductivity instrument at Meram Medical Faculty Public Health Department.
RESULTS: It is found that water purifiers are being used in 67 out of 810 households (8.3%) that were interviewed. None of the samples taken from tap water before household type water purifiers were shown total coliform bacteria growth. In one sample taken from treated water thorough purifiers, 9 kob/100 mL total coliform growth was observed (2.5%). In analyses of free chlorine, pH, conductivity, fluoride, calcium, magnesium and total hardness, all parameters were confirmed to be significantly lower in treated water compared to municipal water, while in analyses of nitrite and ammonium no significant differences were observed.
DISCUSSION AND CONCLUSION: Household type water purifiers were found not to be a healthy and high quality preference for drinking water, as a result of both hygienic risks and the fact that they significantly decrease water hardness and amounts of salubrious minerals like fluoride, calcium and magnesium in municipal water. Despite regular maintenance when good hygiene can not be provided they may cause the problem of public health in microbiological terms.

6. Normal values of biochemical parameters in serum of New Zealand White Rabbits
Özcan Özkan, Selcuk PEKKAYA
doi: 10.5505/TurkHijyen.2018.53254  Pages 157 - 162
INTRODUCTION: Laboratory animals, which are an organ complex, are used as model for human in biomedical studies. For this reason, information about the normal physiological values of laboratory animals provides important information on their health status. In this study, it is aimed to determine the serum normal biochemical values of New Zealand rabbits.
METHODS: Blood was taken from the ears of the rabbits. Biochemical tests were performed on serum samples. For analyses, commercial diagnostic kits were used for determination of biochemical parameters. Statistically, the difference between the mean values of the variables according to male and female rabbit was analyzed by independent sample t-test.
RESULTS: Albumin, protein, CK and LDH (p <0.05) values were found statistically significant between male and female rabbits. On the other hand, creatinine, cholesterol and Mg values (p <0.05) increased significantly in female rabbits.
DISCUSSION AND CONCLUSION: Biochemical tests should be conducted at regular intervals to assess the health status of animals. Since many variables are linked, the animals used in the research should be based on the values of the control group on the same conditions.

7. Evaluation of the frequency of Human Papillomavirus (HPV) in women admitted to cancer early diagnosis and screening training centers (KETEM) and analysis of HPV genotypes
Özgur Kan, Umit GORKEM, Ahmet Barış, Özgur Kocak, Cihan Togrul, Engin Yıldırım
doi: 10.5505/TurkHijyen.2018.47123  Pages 163 - 168
INTRODUCTION: Cervical cancer is one of the most common gynecologic cancers among women in Turkey. Human papillomavirus genotypes (HPV) are strongly associated with cervical malignancies, and the distribution of HPV genotypes varies regionally. The population-based epidemiological data of HPV prevalance in the general population in most parts of the country remains unknown. The purpose of the study was to assess HPV positivity rates, detect high-risk HPV types and obtain HPV mapping of Çorum, Turkey.
METHODS: A total of 33,649 patients who applied to Cancer Early Diagnosis, Screening and Training Centers (KETEM) between August 2014 and January 2018 were included in this study. Prior to the study, permission was obtained from the ethics committee of the university. Cervical swab samples were collected for HPV-DNA examination and PCR method used to detect HPV DNA. Genotyping was performed in HPV DNA positive samples. In addition, cytologic examination results were also recorded in patients with HPV positive.
RESULTS: HPV DNA positivity was found in 3.29% of the patients. HPV DNA was positive in 1108 cases, The highest risk subtypes for cervical cancer, Type 16 and 18, were 14.69% and 1.17%, respectively. When cytological results of HPV DNA positive women were examined; 66.52% of the patients had no precancerous lesion and infection-related cytology results were observed in 41.34% of these patients. The most frequent cytologic abnormal result was LGSIL with 8.21%.
DISCUSSION AND CONCLUSION: HPV typing studies are increasingly important in cervical cancer screening. Considering the regional differences and the heterogeneity of the studies, the results of the Ministry of Health's screening program in 2019 will guide the assessment of the prevalence. By mapping HPV genotypes and evaluating advanced data across all country, appropriate vaccination and prevention policies can be developed.

8. Evaluation Of Health-Care Associated Candida Infections In An Intensive Care Unit
Serife Cetin, Hafize Sav, İlhami Çelik, Elif Bolat, Fahriye Afsar Cagır, TUĞBA BULUT, Gulden Şengül, Serpil Başlarlı, Özlem Kaya Hassu
doi: 10.5505/TurkHijyen.2018.78785  Pages 169 - 176
INTRODUCTION: Candida is one of the pathogens with difficult to treat and high mortality that cause Healthcare-Associated Infections (HAIs). Candida infection is 0.8-4.5 per 1000 patient days and the mortality between 5.8% and 83.3%. The aim of this study was to investigate the incidence of HAIs Candida infection, and the risk factors of causing infections, Candida species and mortality.
METHODS: A total of 3399 patients who were hospitalized to Internal Medicine Intensive Care Unit between January 1, 2014 and December 31, 2016 were included in the study. Forty-one patients who were diagnosed with clinic of patient's, laboratory based surveillance method and Centers for Disease Control and Prevention diagnostic criteria with Candida infections were retrospectively investigated.
RESULTS: The incidence of HAIs Candida infection is 3.7 per thousand patient days. 53.7% (n=22) of the patients were female and 85.3% (n=35) were over 65 years old. 73.1% of Candida infections were urinary catheter associated urinary tract infection. Non-albicans were isolated in rate 73.2% (n=30). The mortality of patients with Candida infection were 70.7% (n=29). Fifteen of seventeen patients with mechanical ventilation (MV) died (p=0.038). Seventeen of nineteen patients who underwent total parenteral nutrition (TPN) treatment were found to have died (p=0.01). When investigated mortality by type of Candida, one of eleven patients with C. albicans and 19 of 30 patients with non-albicans died (p=0.08). There was no correlation between mortality with risk factors such as sex, age, dialysis treatment, chronic obstructive pulmonary disease, diabetes mellitus, cardiovascular disease, renal disease, urinary catheter and central venous catheter (p> 0.05).
DISCUSSION AND CONCLUSION: We should not be forgotten that long term hospitalization, MV for respiratory support, TPN treatment and Candida of type in the hospital will may affect mortality. Health professionals working in the ICU are recommended to practice hand hygiene, aseptic techniques in invasive procedures, infection control and prevention procedures. In addition, periodic education of health professionals and development of healthcare standards can reduce the incidence and the mortality of HAIs Candida infection.

9. Detection of adenovirüs frequency in cases with gastroenteritis symptoms by shell-vial cell culture
AYSEGUL AKSOY GOKMEN, Candan Cicek, Hale Kalfaoglu, Eylem Ulaş Saz
doi: 10.5505/TurkHijyen.2018.38233  Pages 177 - 182
INTRODUCTION: Gastroenteritis which is caused by viruses are common all over the world. It is a very important health problem and a leading cause of mortality for children in developed and developing countries. Among the viral pathogens, rotavirus (25-65%) and enteric adenovirus (5-15%) are the most common. In this study, stool specimens of patients sent to Ege University Medical Faculty Medical Microbiology Department Virology Laboratory between January 2010 and March 2014 for pre-diagnosis of gastroenteritis were examined. It is aimed to determine the frequency of adenovirus in stool specimens by shell-vial cell culture technique and to investigate its distribution according to age and season.
METHODS: A retrospective study of 264 patients with acute gastroenteritis were included in the study. The shell-vial cell culture method and HEp-2 cell line (German Collection of Microorganisms and Cell Cultures, DSMZ, Germany) were used for adenovirus isolation. All of the operations were done in second level security cabinets. A cell culture tube was prepared for each patient. In the detection of adenovirus, monoclonal antibody (Light Diagnostic, Millipore, USA) labeled with effect specific fluorescein isothiocyanate was used at the end of the two-day incubation period. The fluorescence microscope (Olympus BX50, Japan) was evaluated at 20x magnification and 40x magnification. Specimens that gave at least two or more of the cells a typical apple green fluorescence were considered positive
RESULTS: Of the 264 patients included in the study with acute gastroenteritis pre-diagnosis, 190 (70%) were children (72.0%) and 74 (%) were adults. 13 (4.9%) of the 264 stool samples sent to the virology laboratory had adenovirüs positivity with the shell-vial cell culture technique (Figure 1). All positive samples were under 18 years of age. Of the cases, 111 were female (42%) and 153 were male (58%). There was no significant difference between genders in terms of adenovirus positive rate (p> 0.05). In terms of seasonal frequency, adenovirüs was found to be the lowest in summer (0.4%) and the highest in winter (2.7%) by shell vial cell culture in stool
DISCUSSION AND CONCLUSION: Although we think that enteric adenoviral agent should be investigated routinely in the gastroenteritis cases in our region, the data obtained from our work done with cell culture, which is the gold standart method, contribute to the epidemiological data.

10. Genetic polymorphism of BMP-6 gene (rs267196 and rs267192) in patients with Ankylosing spondylitis
Özlem Öztopuz, Fatma Sılan, Özlem Coşkun, Ayla Akbal
doi: 10.5505/TurkHijyen.2019.91979  Pages 183 - 194
INTRODUCTION: Bone morphogenetic proteins (BMPs) have been documented to be associated with Ankylosing Spondylitis (AS) in several populations. The goal of the present study was to determine the association of the (BMP-6) gene polymorphism (rs267192 and rs267196) with AS.
METHODS: This case-control study was conducted during August and November 2013 at the physical therapy and rehabilitation outpatient clinics of Çanakkale Onsekiz Mart University Hospital. Forty-two AS patients and 58 healthy controls were checked with reverse transcription-polymerase chain reaction (RT-PCR) analysis for BMP-6 (rs267192 and rs267196) polymorphism. We evaluated the relationship between the BMP-6 polymorphism and laboratory findings.
RESULTS: The frequencies of AA, AT, and TT genotypes for BMP-6 rs267196 were 9.5% (n=4), 38.1% (n=16), and 52.4% (n=22) in AS patients, and 15.5% (n=9), 44.8% (n=26), and 39.7% (n=23) in controls respectively. BMP-6 rs267196 A allele carriers (versus T ancient allele) had 1.4-fold higher risk and rs267192 T allele carriers (versus C ancient allele) had 1.08-fold higher risk for AS.
DISCUSSION AND CONCLUSION: Although some studies have suggested BMP-6 polymorphisms as a possible risk factor for AS, BMP-6, rs267196 and rs267192 alleles were not associated with the disease risk in our study groups.

11. Western blot assay of anti-Echinococcus granulosus antibody positive serum samples by indirect haemagglutination method
Ayşe Semra Güreser, Gamze Gizem Duman, Fakhriddin Sarzhanov, Djursun Karasartova, Funda Dogruman Al, Aysegul Taylan Ozkan
doi: 10.5505/TurkHijyen.2019.03779  Pages 195 - 202
INTRODUCTION: Cystic Echinococcosis (CE) is a zoonotic disease mainly caused by the larvae of Echinococcus granulosus is common in rural areas in Turkey. A multidisciplinary approach consisting of clinicians, radiologists and microbiologists is required for the proper diagnosis of the disease. Enzyme-linked immunosorbent assay (ELISA) and indirect hemagglutination (IHA) tests are preferred in the primer diagnosis of cystic echinococcosis (CE), while western blot (WB) is used to confirm the disease. However the use of serologic tests alone in diagnosis and follow-up of the disease is not recommended due to variable sensitivity and specificity rates and multiple serologic tests are required for appropriate diagnosis. In our study, it was aimed to compare the test results of patients sera sent to Gazi University Medical Faculty Microbiology Laboratory, between December 2015 and December 2016, with the preliminary diagnosis of CE, by WB test after those titrated with IHA. It is also aimed to determine the consistency between the two tests.
METHODS: CE suspicious specimens were first tested by the IHA method (Fumouze Laboratoires, France) prepared with E. granulosus antigens. Afterwards 54 samples were tested again with the WB method (Anti-Echinococcus EUROLINE-WBIgG, Germany). The presence and intensity of antigen bands on the WB strips was assessed using commercial EUROLINE Scansoftware.
RESULTS: Of the 54 cases, we found that 44 (81.48%) were positive with IHA test while 46 (85.19%) of them were positive with WB method. Six patients (11.12%) were positive with WB while they were negative by the IHA (< 1/320 titer). Two of them were IHA-negative in the titer 1/80, four in the titer 1/160. Cohen's Kappa analysis showed fair (slight) consistency (κ = 0.26) between the two tests.
DISCUSSION AND CONCLUSION: As a result, using only IHA test can miss out CE patients therefore, the combined use of immunoassay tests increases the sensitivity in diagnosis. In the case of screening with IHA and confirmation with WB, for the more accurate results, the analysis of all sera titrating with IHA from 1/80 is recommended with WB, even if it is negative according to kit procedures.

12. Effects of progesterone treatment in polycystic ovary syndrome on pulmonary functions
Fikriye Karanfil Yaman, Sertaç Arslan
doi: 10.5505/TurkHijyen.2019.46656  Pages 203 - 210
INTRODUCTION: We aimed to evaluate patients with polycystic ovary syndrome in terms of respiratory function tests and to investigate the relationship between progesterone therapy and pulmonary functions.
METHODS: Fifty patients, who were diagnosed polycystic ovary syndrome (PCOS) according to Rotterdam criteria, at gynecology and obstetrics clinic of a research and training hospital included in the study group. Fifty healthy person were included in the control group. Both groups were evaluated with pulmonary function tests (PFT) at pulmonary medicine clinic of a university hospital. Independent from PFT survey, the patient group was treated with two cycles of medroxyprogesterone acetate between 16 and 25 days of the cycle as the standart follow up and treatment at gynecology and obstetrics clinic. Afterwards they were evaluated with PFT again. Statistical analysis of independent measurements were analyzed by Paired Sample t-test. Mann-Whitney U, Wilcoxon test was used to analyze the data without normal distribution. P value <0.05 was considered as significant.
RESULTS: Post-treatment pulmonary function test values were compared with pre-treatment values. Post-treatment FEV1 and FVC values were found increased after the treatment.
DISCUSSION AND CONCLUSION: Although the pulmonary function of PCOS patients were not different from that of the healthy female population, progesterone treatment has been shown to increase FEV1 and FVC values. However, studies should continue to show which mechanisms are effective at these hormones. A better understanding of the effects of sex hormones on respiration may lead to the application of hormone therapies in respiratory problems.


13. Evaluation of The Application of The "White Flag Cooperation Protocol" in The Schools of National Education Directorate of Province of Ankara in 2017-2018 Academic Year
Asiye Çiğdem Şimşek, Zuhal Yıldırım, Seçil Özkan
doi: 10.5505/TurkHijyen.2019.19327  Pages 211 - 220
INTRODUCTION: School age is a period in which children's physical, cognitive and social growth and development accelerate, nutrition and hyggiene habits develop and the foundations of healthy life are laid. Hygiene habits that will be gained during this period are very important for the development of the child to be an individual.
In 2006, White Flag Cooperation Protocol was signed between the Ministry of Health and the Ministry of National Education, in order to encourage education institutions to promote hygiene, to protect and improve public health, to improve the quality of life and to educate healthy generations with adequate training.
In this study, it is aimed to evaluate the practices of "White Flag Cooperation Protocol" implemented in Ankara in 2017-2018 academic year.

METHODS: In this descriptive study, in the framework of the White Flag Cooperation Protocol in Ankara province, the schools that received White Flag Certificate as a result of the audits conducted in 2017-2018 academic year, were evaluated by the Provincial Health Directorate and authorized personnel of the Provincial Directorate of National Education.
RESULTS: Application of the "white flag cooperation protocol" in the schools of national education directorate of province of Ankara in 2017-2018 academic year is evaluated. In 2017-2018 academic year, “White Flag Certificate " and the applicant of" White Flag Certificate " have seen an increase in the number of schools" and number of schools with White Flag Certificate are 1204 (41.9%).
DISCUSSION AND CONCLUSION: In our country, one-fifth of the population is comprised of students. The creation of health awareness at school ages is an important time period for growing healthy generations. Therefore, hygienic equipment and environmental conditions of the school environment is of great importance in the protection of basic health care.
With the increase in the application of the White Flag Certificate in the schools in Ankara province, the hygienic equipment and environmental conditions of the schools were improved. In addition, it is planned to continue the education and research activities in order to increase the number of schools receiving the ın White Flag Certificate in the next academic year and to improve the hygienic equipment and environmental conditions of the schools.



REVIEW
14. Non-Biological Complex Drugs
BÜŞRA CESUR, Devrim Demir Dora
doi: 10.5505/TurkHijyen.2019.95770  Pages 221 - 228
Non-biological complex drugs have emerged as a new drug group in recent years. These complex drugs are medicinal products, not being a biological or chemical medicine, where the active substance is not a homo-molecular structure, but consists of different structures that cannot be isolated and fully characterized by state of the art physicochemical analytical methods, not synthesized chemically, not biological and often complex with nanoparticle systems. Non-biological complex drugs include liposomes, glatiramoids, iron carbohydrate complexes, polymeric micelles and nano-drugs. These drugs differ from biological and chemical medicines in terms of preparation technology. The major problem that arises during the production of non-biological complex drugs is the inability to control the production process and therefore the differences between the series. As biosimilar products, similar products are obtained in every different production series. Physicochemical properties, such as size and size distribution, surface charge and composition of non-biological complex drugs are factors that effects interaction with biological systems and thus their biological activities. Although not derived from living sources, they have immunogenicity and molecular complexity like biological drugs. Minor changes in the production process of these medicinal products can cause adverse immune system responses, safety problems, and reduced therapeutic efficacy. The requirements for the registration of these drugs in national and international legal regulations are not fully established. There are differences between the legal regulations of EMA and FDA about non-biological complex drugs. Therefore, in order for these products to be used effectively and safely, requirements should be set out the with global harmonization and the guidelines should be published to be followed during and after the approval process. Pharmacodynamic, pharmacokinetic and adverse effect studies on these medicinal products are inadequate. In this review, general information about liposomes, glatiramoids, iron carbohydrate complexes and polymeric micelles are presented.

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