Ph. D. Thesis. HIV infection in children: epidemiological and clinical aspects in Constanta County

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1 UNIVERSITY OF MEDICINE AND PHARMACY CRAIOVA FACULTY OF GENERAL MEDICINE Ph. D. Thesis HIV infection in children: epidemiological and clinical aspects in Constanta County Scientific Supervisor, Professor of Pediatrics DUMITRU BULUCEA, Ph.D. Ph. D. Candidate Viviana Cuzic

2 Summary Table of contents State of knowledge 1. Introduction. Short history 2. The epidemiology of HIV 3. The etiology of HIV 4. Pathophysiology of HIV 5. Classification for pediatric HIV infection 6. Category A of organic specific manifestations 7. Category B of organic specific manifestations 8. Category C of organic specific manifestations 9. Others manifestations Personal contribution I. Objectives II. Methods III. Results III.1. General HIV/AIDS statistics in Constanta County III.2. Epidemiological data III.3. Analysis of deaths III.4. Analysis of clinical manifestations 1. Cutaneous manifestations 2. Neurologic and psychiatric manifestations 3. Pulmonary manifestations 4. Cardiac manifestatons 5. Renal manifestations 6. Gastrointestinal manifestations 7. Hepatitis 8. Lypodistrophy and dislipemic disorders 9. Malignity 10. Malnutrition associated with encephalopathy IV. Discussion V. Clinical cases VI. Conclusions VII. Appendix VIII. References Key words: HIV/AIDS infections, children, epidemiology, common illnesses 2

3 Introduction The global AIDS epidemic is one of the greatest challenges facing our generation. AIDS is a new type of global emergency-an unprecedented threat to human development requiring sustained action and commitment over the long time. In many parts of the world, HIV/AIDS is still seen as a death sentence, a disease from with there is no recovery. But with the ever improving availability of antiretroviral therapy, HIV is increasingly recognized as a chronic rather than terminal illness. This transition requires special adjustments especially in the pediatric and adolescent populations. The paper HIV infection in children-epidemiological and clinical aspects in Constanta County consists in 193 pages: 71 pages about the state of knowledge in HIV/AIDS infection and 122 pages of personal contribution. The author want to show that the children with a chronic illness such as HIV/AIDS face unique challenges that make their lives more difficult.it is important to understand the long-term effects theese challenges can have on the children and their caregivers, whether thaťs their parents, extended family, or others in the community. With proper support from their health care providers and their community, the burden of childhood with HIV/AIDS will seem less great. The first part of the thesis is structured in 9 chapters focuses on the state of the art data regarding HIV/AIDS infection: Historical data, Epidemiology, Etiology, Pathophsiology, Classification and Clinical manifestations in HIV infection. The information is presented using 29 tables and 18 figures. The main historical data about HIV infection are systematically displayed, in terms of international and Romanian chronology. The historical aspects are followed by the theoretical part of the thesis describing the main data regarding HIV infection: etiology, epidemiology, classification system and clinical categories of HIV infection. The second part of the paper: the personal contribution represents two thirds of the thesis, containing 94 tables and 60 figures. There are seven chapters: Objectives, Material and Methods, Results, Discussions, Clinical cases, Conclusions, References and finally an appendix. The aim of the study was to describe the demographic and clinical aspects of HIV-infected children in the Pediatric Departament on the County Hospital of Constanta. Material and Methods An observational study on 153 patients diagnosed with HIV infection in the Pediatric Departament of the County Hospital of Constanta from We conducted a complex analysis extending the observation until

4 Discussion and conclusions On the 153 subjects, the majority (144 cases;94,11%) were born between ; most of them were born in 1988 (62,75%). The mode of transmission was primarily through transfusion of unscreened blood and other medical practices via injections with improperly sterilized equipment: 32,67%; 48,36% with nosocomial transmission and 13,07% of patients had received parenteral treatment at home and in the hospital. Perinatal transmission accounted for 5,22% of cases. At the onset: 62,09% of cases were grouped into B category with moderately severe symptoms and 37, 90% developed severe symptoms and were classified as category C. In the early stage of the HIV infection the patients presented in 68,62% of cases lymphadenopathy; moderate unexplained weight loss (60,13%), hepatosplenomegaly: enlarged liver and spleen in 49,01% of cases and one third of children had respiratory infections. At the end of the study, 96 children (62,74%) died with AIDS and there are 57 survivors (37,2%). The age of the survivors ranges between 14 and 22 years with the highest number at the age group of years: 37 cases. The majority of the survivors are in the clinical category C: 55 patients (96,49%) and two patients in the clinical category B. According to the degree of the immunosupression: 25 patients (43,85%) were allocated to severe immune suppression (C3), 24 cases with moderate immunosupression (C2) and 25 cases with mild immunosupression (C1). The cutaneo-mucous manifestations were due either the opportunistic infections either the therapeutical side effects. Oral candidiasis was the most frequent disorder of the mouth: 60 cases (39,2%) followed by stomatitis due by herpes virus (20 cases) and in a few cases lingual papillomatosis and hair leokoplakia of the tongue. Esophageal candidiasis appeared in 5,2 % cases. Viral infections were observed in patients with severe immunosupression. Among bacterial infections, one of the most incriminated bacteria was Staphylococcus aureus followed by Streptococcus. Among fungal infections the most common disorder was candidiasis dermatosis (3,2%). The most common neurologic manifestations of pediatric HIV infection was progressive encephalopathy (60%) from the total cases with nervous system abnormalities. Opportunistic infections accounted in 16 patients and included: toxoplasmosis, cryptococus and cytomegalovirus infection, TB meningitis and multifocal demyelinating leukoencephalopathy (PML). Mycobacterium tuberculosis infection were diagnosed in 60 patients, and extrapulmonary TB (incuding pleuritis, pericarditis, meningitis and disseminated disease) were observed in 23 cases. The cardiac manifestations of HIV infection included cardiomyopathy, wich was the most common manifestation found in ten cases, followed by miocarditis (3 cases), endocarditis (2 cases) and pericardial effusion (2 cases). Renal disorders are encountered at all stages of HIV infection in 39,21% of cases, the most frequent cause was represented by urinary tract infections (47 cases). Nephrotic syndrome was found in 6 cases. Seven children in treatment with indinavir developed renal complications such as renal pains and hematuria. 4

5 Opportunistic intestinal parasitosis occurred in 76,08% of cases, especially in patients with severe immunosupression. Polyparasitosis predominated ( with protozoa). A common co-infection was HIV and hepatitis. There were 84 patients (54,9%) with chronic hepatitis B infection. Lipodistrophy was diagnosed in 20 patients. The drugs implicated in lipodistrophy etiology included PIs (in 15 cases) and associated treatment with PIs and NRTIs (in 5 cases). Lypodistrophy was more frequent in patients at age of years old with severe immunosupression. There were a slight female predominance. lypodistrophy comparing to male lipoatrophy predominated. Kaposi's sarcoma was diagnosed in 3 patients. In 2 cases the lesions affected the skin and the oral mucosa, and in one case the lesions were found only on the skin. All the patients died in a few months after the diagnosis. From the total number of patients who have died (96), 32 presented wasting syndrome associated with encephalopathy in 26 cases. The highest death-rate (69,79%) was found on children born in The death-rate over studied cases revealed a high mortality in institutionalized children. The number of deceases was increased in children who had poor living conditions. Considering the age on HIV finding, the death analyse showed that 90,91% of the patients have died at the age group of o-2 years-old (p=0,0034, with is significantly hight) Considering the age, the death occurred in patients with age between 8 and 16 (66,66%), the medium age was 8,2. The deceases' analysis according on clinical stage of initially HIV infection revealed a significant statistical relation (p< 0,05) between the two clinical categories: death occurred in 60% of patients diagnosed in stage B and in 67,24% of patients diagnosed in stage C. The average period of time (years) from the moment considered infectious(1988) was 6 years for stage B, 8 years for stage C: in patients alive and 4 years for stage B, 8 years for stage C: in dead patients (p<0,0001). There is a tardy AIDS detection on patients in C-stage, equally survivor and dead children. The cases' analyse concerning the period of death from the diagnosis showed that 82,29% of patients died in the first 6 years from the diagnosis. The survival from the moment of the diagnosis was increased in children in stage B (4 years) comparing to the children in stage C (3 years), the statistical relation being extremely significant (p<0,0001, p<0,0002). 5

6 References 1. HIV/AIDS Surveillance in Europe, 11 December 2008, vol 13, Issue Ministerul Sanătaţii, Compartimentul de Evaluare şi Monitorizare a Infecţiei HIV/SIDA Institutul de Boli Infecţioase Prof. Dr. Matei Balş. Date statistice HIV/SIDA în România, iunie Bulucea D, Cupşa A. Sursa de infecţie, în Infecţia cu HIV/SIDA, o criză a sănataţii mondiale, Editura AIUS, Craiova 1995, Garmen EM, Tying SK. The cutaneous manifestations of HIV infection. Dermatol Clin., 2002; 20: Chiriboga CA, Fleishman S, Champion S, Gave-Robinson L-Incidence and prevalence of HIV encephalopathy in children with HIV infection receiving HAART, J. Pediatr., 2005 Mar; 146(3); Hamid MZ, Azis NA, Zulfliki ZS et al. Clinical features and risk factors for encephalopathy in children: Southeast Assian J Trop Med Public Health, 2008 Mar; 39 (2): Apgall S, Rabaud C, Cosagliola D: Clinical Epidemiology Group of the French Hospital.Date base on HIV. Incidence and risk factors for toxoplasmic encephalitis in HIV-infected patients before and during the HAART era. Clin. Infect. Dis 2001 Nov. 15;33 (10): Mahadevan B, Serane VT: Prognosic factors in childhood tuberculous meningitis.j Trop Pediatr 2002; 48: Epker JL, van Biezen P, van Daele PL, et al: Progressive multifocal leukoencephalopathy, a review and an extended report of five patients with different immune compromised states. Eur J Intern Med; 20 (3): Hull MW, Philips P, Montaner JS: Changing global epidemiology of pulmonary manifestations of HIV/AIDS. Chest, 2009 Dec; 34 (6); Powell DA, Hunt WG: Tuberculosis in children: an update. Adv. Pediatr., 2006; 53: Newton SM, Brent AJ, Anderson S: Paediatric tuberculosis, Lancet Infect Dis, 2008 Aug 8 (8): Velasquez EM, Golancy D.L: Cardiovascular disease in patients infected with human immunodeficiency virus. J Med Soc., 2003 Nov-Dec, 155: Sani MU: Miocardial disease in human immunodeficiency infection: a review. Wien Klin Wochenschr, 2008; 120 (3-4): Ahuja T, Abbot K, Pack L, Kuo YF. Childhood AIDS nephropathy, Pediatr. Nephrol; 2003,19: Wyalt CM, Rosentiel PE, Klotman PE. HIV- associated nephropathy, Contrib Nephrol, 2008; 159: Velasco CA, Valencia P, Cortes EP, Manifestations of the digestive system in children with AIDS, Pediatr. Gastrointestinal Nutr 2000; 31 (Suppl 2): S Stoane JM, Haller JO, Orelicher RJ, The gastrointestinal manifestations of pediatric AIDS and the opportunistic infections, J Pediatr 1997; 130: Ruţa SM, Mătuşa RF, Sultana C, Manolescu L, Kozinetz CA, Kline MW, Cernescu C: High prevalence of hepatitis B virus markers in Romanian adolescents with human immunodeficiency virus infection, MedGenMed, 2005 Mar 28; 7 (1):68 6

7 20. Sarni Ro de Souza, Batistini TR, Pitta TS et al: Lipodistrophy in children and adolescents with acquired immunodeficiency syndrome and its relationship with the antiretroviral therapy employed. J Pediatr (Rio J) Jul-Aug; 85(4): Popielska J: Lipodistrophy in HIV infected children, Pol Mekeer Lekarski, 2008 May; 24 (143): Arkin LM, Cox CM, Kovarik CL: Kaposi sarcoma in the pediatric population, Pediatr Infect Dis J., 2009 May; 28(5): Muşat S: Aspecte clinice şi diagnostice particulare ale sarcomului Kaposi asociat infecţiei HIV. Revista Româna de Boli Infecţioase, vol.xi, Nr.4, 2008, pg

8 CURRICULUM VITAE Name: Cuzic Viviana Date of birth: Married, one child Place of birth: Constanta, Romania Address:1, Stejarului street, Constanta, Romania Studies: -High Sanitary School, Constanta , Bucharest Faculty of Pediatrics, Bucharest, Professional activity: -practitioner doctor: Clinical Hospital Giulesti, Municipal Hospital, Grigore Alexandrescu Hospital, Bucharest - resident doctor: Clinical Hospital Budimex Bucuresti and Clinical County Hospital of Constanta -universitary assistant: from March 1994, in Ovidius University Constanta, Faculty of Medicine - primar pediatrician: in Clinical County Hospital Constanta. Place of work: Pediatric Department - Trainer for a doctor degree : HIV infection in children: epidemiological and clinical aspects in Constanta County, Craiova, from 2001, coordinator Professor Dumitru Bulucea 2. Scientific activity: -participations in National Pediatrics Congresses : Onesti 1994, Sibiu 1998, Constanta 2003, Galati 2005, Sibiu 2007, Iasi participations at Romanian-American Symposiums, Mamaia, Poiana-Brasov, Cluj Napoca, Durau -Participation at National Gastroenterology Congress in Mamaia 2004, Poiana Brasov 2005, National Semiology Symposium, Mamaia, practical training in Pediatric Advance Life Support, Iasi, participation at the International School Best practices in the care of HIV infected adolescents and youth, organized by Baylor-Black Sea Foundation in September 2008 I supervised practical lessons in pediatrics and license thesis. Books (co-author): 1. Co-author of the chapter Laboratory diagnosis of HIV infections from Pharmaceutical an Microbiological notions, publishing house Carol Davila 8

9 2009, ISBN, , Ramona Stoicescu, Cristina Mihai, Cuzic Viviana 2. Pediatrics Publishing house Andrei Saguna foundation, 2001, Valeria Stroia, Cristina Fiscuci, Adriana Balasa, Cuzic Viviana, Corina Frecus, Larisia Mihai Number of summarized scientific studies published in the country: 48(co-author) Number of full scientific studies published in the country: 22 Number of scientific studies to the annual sessions of General Medicine Faculty: 9 Member of Romanian Pediatric Association: Romanian Pediatric Society Member of Genetic Society Dr. Cuzic Viviana 9

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