PATHOPHYSIOLOGY, CLINICAL FEATURES, AND MANAGEMENT OF CHILDREN WITH CHRONIC INFECTIOUS DISEASES
Creators: name: Giannattasio, Antonietta
Publisher: name: Università degli Studi di Napoli Federico II
Year: 2009

description: Children with chronic diseases


Chronic viral hepatitis

Among human hepatitis viruses, hepatitis B (HBV) and C (HCV) viruses are able to persist in the host for years and thereby causing chronic hepatitis. Three hundred and seventy and 130 million people is estimated to be infected with HBV and HCV, respectively, worldwide (1). In endemic areas, HBV infection is often acquired perinatally or early in childhood and becomes chronic in a high proportion of cases. Universal vaccination of newborns has been effective in reducing the spread of infection. However, hepatitis B is still a social and health problem in underdeveloped areas where immunisation policies are unavailable, and even in developed countries, where the reservoir of infection is maintained by immigration and adoption. In some endemic areas children with chronic hepatitis B are also at risk for superinfection with the hepatitis delta virus (HDV), which worsens the prognosis of liver disease. 
HCV is not a less important problem. The prevalence of circulating anti-HCV antibodies in the pediatric population averaged 0.3% in Italy in the early 1990s (2), but a national observational study suggest that the number of “new” pediatric infections dropped by approximately 40% in 2000-2004 compared with the previous 5 years (3). The lower prevalence of HCV in children reflects the disappearance of transfusion-related hepatitis and the reduced efficiency of mother-to-child (vertical or perinatal) transmission, although the latter form of transmission is currently responsible for most “new” infections in the developed world and contributes to maintaining the reservoir of infection worldwide (4-7). This favourable epidemiologic trend is balanced, however, by the strong tendency of HCV infection acquired early in life (either perinatally or following blood transfusions) to become chronic (8-14). In the absence of a specific vaccination, HCV infection remains a major global health problem and HCV-related end-stage liver disease is still the most frequent indication for liver transplantation in adult patients. 
Chronic viral hepatitis acquired in childhood is a long-lasting process based on host-virus interaction, which may change over the years. A number of factors related to the virus (genotype, therapy), to the host (hormonal status, immunocompetence, therapy) and to the environment (alcohol, drugs, co-infections) affects the natural history of the disease, especially during adolescence and early adulthood. Strategies to improve the prevention and treatment of HBV and HCV infection, and the related liver disease in children, before the possible development of irreversible complications, should be investigated and implemented. 


HIV infection

Countries most heavily affected, HIV has reduced life expectancy by more than 20 years, hampered economic growth, and deepened household poverty (UNAIDS. Data from: www.unaids.org/en/KnowledgeCentre/HIVData/GlobalReport/2008/2008_Global_report.asp).
Mother-to-child transmission (MTCT) is the main source of pediatric HIV-1 infection. MTCT of HIV-1 mainly occurs around the time of delivery, but breastfeeding is an additional route of viral transmission and accounts for about one-third of pediatric infections in resource-poor Countries (15). In the absence of antiretroviral therapy, about 30% of women transmit the virus to their infants. The estimated number of perinatally acquired AIDS cases in the United States peaked at 945 in 1992 and declined rapidly with expanding prenatal testing and implementation of appropriate preventive interventions (16). At the end of 2007, there were 2 million children living with HIV around the world, an estimated 370,000 children became newly infected with HIV in 2007, and, of the 2 millions people who died of AIDS during 2007, more than one in seven were children. Every hour, around 31 children die as a result of AIDS. 
HIV can affects a child’s life through its effects directly on the child, on that child’s family, and on the community within the child is growing up:
-	Many children are themselves infected with HIV
-	Children live with family members who are infected with HIV
-	Children act as carers for sick parents who have AIDS
-	Many children have lost one or both parents to AIDS, and are orphaned
-	An increasing number of households are headed by children, as AIDS erodes traditional community support systems
-	Children end up being their family’s principal wage earners, as AIDS prevents adults from working, and creates expensive medical bills
-	As AIDS ravages a community, schools lose teachers and children are unable to access education
-	Doctors and nurses die, and children find it difficult to gain care for childhood diseases
-	Children may lose their friends to AIDS
-	Children who have HIV in their family may be stigmatized and affected by discrimination
In the last 10 years, dramatic advances in medical management of HIV infection have followed the results of clinical trials of antiretroviral combination therapies in children. The use of antiretroviral therapy during pregnancy in HIV-infected women has resulted in a dramatic decrease in the transmission rate to infants, which is currently less than 2% in most high-income Countries (17). In parallel, the introduction of highly active antiretroviral therapy (HAART) has changed the natural history of HIV-1 infection and the life expectancy of HIV-1-infected adults (18,19) and children (20-26). Although in developed Countries children living with HIV infection are expected to live a long life, they still need to face major emotional burden, social stigma and global exclusion from the social contest (27). Being a child or an adolescent with HIV implies major problems in terms of management of multiple drugs, adherence to antiretroviral therapy, drug resistance, quality of life, frequency at school and social interactions with peers (28). 


Immunization in at risk children

Vaccinations programs are one of the greatest public health interventions of the last century and have dramatically improved quality of life (29). Benefits of vaccination to the individual include partial or complete protection against infections and symptoms of illness, improved quality of life, and prevention of up to 3 million pediatric deaths per year worldwide (29,30). Benefits of a universal vaccination program to society include creation and maintenance of herd immunity, prevention of disease outbreaks, and reduced health care costs (30). Despite the availability of safe and effective vaccines and substantial progresses in reducing vaccine-preventable diseases, delivery to and acceptance of vaccinations by targeted populations are essential to further reducing and eliminating vaccine-preventable causes of morbidity and mortality (31). Children who are not vaccinated endanger public health representing a risk for other nonimmunized individuals, including subjects who cannot be immunized due to underlying health problems, and the small percentage of individuals in whom vaccination does not confer protection (29). They also contribute to increase health care costs (29).
Access to immunizations, prevalence of vaccine-preventable diseases, and vaccination rates varies by geographic area or country. Throughout the United States and European Countries, immunization rates of children and adults are rising, but coverage levels have not reached established goals (32). As a result of low immunization rates, vaccine-preventable diseases still occur as evidenced by the measles epidemic, the large number of annual cases of varicella, pertussis, and hepatitis B, and the more than 50,000 annual deaths in adults from influenza or pneumococcal infections (33-36).
In an attempt to eliminate the risk of outbreaks of some diseases, governments and other institutions have instituted policies requiring vaccination for all people (compulsory vaccinations). For example, actual vaccination policies in most developed Counties require that children receive common vaccinations before entering school. In addition to compulsory vaccines, certain populations should receive additional vaccinations. Subjects with chronic medical conditions are at increased risk for severe complications related to vaccine-preventable infections, such as influenza and pneumococcal infections (34,37). In Italy, compulsory vaccines are generally administered in vaccination centers and complementary vaccinations are actively offered to children with chronic conditions and are included in the Essential Levels of Care (38). Despite long-standing recommendations to provide recommended vaccinations to children with chronic medical conditions, immunisation rates in these vulnerable populations remain poor (39). Several conditions hamper implementation of these vaccinations, including problems in identifying at risk children, ineffective organizational strategies and lack of awareness of disease severity or poor confidence by parents in specific recommendations (40,41). Often, the presence of a chronic condition is erroneously considered a contraindication rather than an indication to vaccination.
It is important to ensure that patients comply with the vaccination schedule to the extent possible, and to provide education to parents who may have concerns about pediatric vaccinations. 
   

Goals of the thesis 

In this PhD thesis, the organization and management of pediatric infectious diseases, with a perspective of public health, are investigated. 
Specific chronic diseases, as chronic viral hepatitis and HIV infection, have been selected as models to investigate the main aspects of prevention, management and treatment. The goal is to investigate the efficiency of organization and propose interventions with specific reference to treatment of infectious diseases, their direct and indirect results and how these conditions affect quality of life of at risk children and their families.
The final goal of this research is to provide strategies to optimize public health system.