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This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

83rd Canadian Paediatric Society Annual Conference

St. John’s, Newfoundland and Labrador / June 13-17, 2006

Canadian statistics have shown that the burden of illness associated with rotavirus gastroenteritis is considerable. In a population-based survey of the Greater Toronto Area between November 1997 and June 1998, 18 hospitals reported a total of 345 hospitalizations for rotavirus illness, “with a sharp peak occurring between April and May,” as characterized by Dr. Elizabeth Lee Ford-Jones, Division of Infectious Diseases, Professor of Paediatrics, The Hospital for Sick Children, University of Toronto, Ontario.

In this particular survey, 5% of the infections occurred in children under the age of six months, while one-third occurred after the age of 24 months. By the time children reach the age of five years, the Toronto survey suggested that one child out of 106 is hospitalized for rotavirus infection.

In another survey taken between December 1999 and May 2000, seven Quebec hospitals reported that of those children under the age of five years requiring hospitalization for gastroenteritis, over 70% was due to rotavirus infection. Other studies have similarly shown that between 60% and 80% of rotavirus hospitalizations occur between April and May, the infection itself peaking in children between the ages of six months and three years. Indeed, out of 1000 children hospitalized for any reason, 22 of them under the age of one have rotavirus, as do a similar number of one-year-olds. Once hospitalized, children spend approximately three days in hospital, where most require intravenous rehydration therapy. Overall, it is estimated that rotavirus accounts for nearly 40% of all hospitalizations for acute diarrhea, noted Dr. Ford-Jones.

Vaccine Capabilities

Given the magnitude of morbidity, it is clear that a vaccine against rotavirus could dramatically reduce the burden of illness it causes. One such vaccine, the new pentavalent vaccine, has already been recommended by the US Advisory Committee on Immunization Practices (ACIP) and is expected in Canada shortly. The pentavalent vaccine is a bovine-human oral vaccine that contains five rotavirus strains, including the G2 strain, with a reported prevalence (in some parts of North America) of approximately 31%.

Results of a phase III trial evaluating the efficacy of the pentavalent vaccine in over 70,000 infants showed that it prevented 74% of any rotavirus infection and 98% of all severe rotavirus infections. The vaccine also reduced hospitalization and emergency visits by 94% and visits to a physician by 86%. In the second season, the same vaccine also reduced any rotavirus infection by 63% and severe rotavirus infections by 88%. All gastroenteritis-related hospitalizations were also reduced by 59%, again in the second season.

The oral monovalent vaccine against G1P[8] with the potential for protection against other rotavirus serotypes (with the exception of G2) was shown to be 85% effective against both severe rotavirus, reduced hospitalizations by 85% and all gastroenteritis-related hospitalizations by 42%. Neither vaccine has shown any evidence that it causes intussusception and both were well tolerated. As recommended by the US ACIP, children require three doses of the pentavalent vaccine and the doses should be given at two, four and six months. The initial dose should be started at six weeks of age and the vaccine should not be given after 32 weeks of age. An active surveillance program is also recommended to ensure intussusception does not occur following vaccination.

In addition to having infants vaccinated against rotavirus, Dr. Ran Goldman, Associate Professor of Paediatrics, Division of Paediatric Emergency Medicine and Clinical Pharmacology and Toxicology, The Hospital for Sick Children, University of Toronto, reminded delegates that there are many ways to prevent gastroenteritis, starting by washing hands thoroughly after any fecal contact and prior to food preparation and to make sure households contacts are less in contact during an outbreak.

Human Papillomavirus and Sexually Transmitted Infections

Human papillomavirus (HPV) is the most common sexually transmitted disease worldwide. As discussed by Dr. Samuel Ratnam, Associate Clinical Professor of Epidemiology, Memorial University of Newfoundland, St. John’s, the high-risk oncogenic HPV types are 16 and 18, together which account for nearly 70% of worldwide cervical cancers; low-risk HPV types include 6 and 11, both accounting for over 90% of genital warts. Apart from being painful and distressing, “treatments are expensive and often ineffective,” Dr. Ratnam noted. The lifetime risk of developing genital warts ranges from less than 2% to more than 10%, while the lifetime risk of developing HPV is 75%.

Although most HPV infections are cleared within one to two years, infection can become persistent in a small proportion of patients and result in cervical intraepithelial neoplasia (CIN) grades 2/3, a direct precursor to cervical cancer. An effective vaccine that can reduce the burden of HPV infection may therefore have a dramatic impact on sexual health in Canada, provided it is given in a timely fashion.

Study results cited by Dr. Ratnam indicate that several new HPV vaccines are undergoing testing, including a new quadrivalent vaccine producing immunogenicity against HPV 6, 11, 16, 18. Phase III efficacy data showed that it was 100% effective against HPV 16 and 18-related CIN 2/3, which can lead to external vaginal, vulvar and cervical cancers. The quadrivalent vaccine also demonstrated a 95% reduction in the combined incidence of HPV 6, 11, 16 and 18-related persistent infection and cervical dysplasia as well as a 99% rate of efficacy against condyloma acumination, for which 90% of are associated with HPV types 6 and 11.

“We still have cervical cancer despite considerable cervical cancer screening,” Dr. Ratnam reminded delegates. The bigger challenge is to prevent women from developing high-grade lesions in the first place, not find them and treat them “after the fact,” he stated. “Immunization is the single most cost-effective health investment we have. If proven safe and effective, a vaccine targeting pathogenic HPV types will greatly reduce the burden of diseases associated with HPV.”

Dr. Diane Francoeur, Associate Clinical Professor of Medicine, Université de Montréal, Quebec and President, Quebec Association of Obstetricians and Gynecologists, in turn made it clear why adolescent girls should receive the vaccine prior to their sexual debut. “Transmission occurs through skin-to-skin contact, and condoms offer little protection against HPV infection,” she stressed. A recent Canadian survey among adolescents also showed that half a million teens between the ages of 14 and 17 had three sexual partners on average and their knowledge of sexually transmitted infections—including HPV—was very limited. They are also at extreme risk of going from HPV-negative prior to becoming sexually involved to becoming positive within a median of 2.6 years after initiating sexual activity.

In one study of over 2000 girls between the ages of 15 and 19, the risk of becoming HPV-positive three years after their first sexual experience was 44%. Studies have also shown the risk of HPV infection may be as high as 70% in female adolescents, partially because they have a large transformation zone that increases the risk of getting infected. As Dr. Francoeur noted, even when genital warts are treated, rates of recurrence range from 7% to 38%, treatments are painful and unsatisfactory, and they are costly to the health care system. They may also lead to laryngeal papillomas, also known as recurrent respiratory papillomas, now the most common tumour of the larynx in childhood and which are caused by HPV types 6 and 11.

“We need paediatricians to know about these issues in adolescents and we need them to talk to parents about them. Even if you do not feel comfortable talking about these issues or doing the exam, please refer [to a physician]. We need primary prevention before adolescents start sexual activity because once they start, it is too late,” Dr. Francoeur concluded.