Spotlight on AS04-Adjuvanted Human Papillomavirus (HPV) Types 16 and 18 Vaccine (Cervarix®)

The AS04-adjuvanted human papillomavirus (HPV) 16/18 vaccine (Cervarix®) is a noninfectious recombinant vaccine produced using purified virus-like particles (VLPs) that induce a strong immunogenic response eliciting high levels of anti-L1 VLP antibodies that persist at levels markedly greater than those observed with natural infection. The vaccine adjuvant (AS04) is composed of monophosphoryl-lipid A, which enhances cellular and humoral immune response, adsorbed to aluminum hydroxide. The vaccine is indicated for the prevention of premalignant cervical lesions and cervical cancer causally related to certain oncogenic HPV types in females aged ≥10 years. The AS04-adjuvanted HPV 16/18 vaccine, administered via an intramuscular injection in a three-dose schedule over 6 months, elicits a high immunogenic response and is highly protective against cervical intraepithelial neoplasia and infection causally related to high-risk oncogenic HPV types. In well designed clinical trials in young women aged 15–25 years who were HPV 16/18 seronegative and DNA negative to 14 HPV high-risk types, high levels of immunogenicity and protection were sustained for follow-up periods of up to 8.4 years. High and persistent immunogenicity against infection with HPV 16/18 has also been demonstrated in older and younger females (aged 10–55 years) who were seronegative for vaccine HPV types. The AS04-adjuvanted HPV 16/18 vaccine elicited a greater immunogenic response than the quadrivalent HPV vaccine in women aged 18–45 years who were seronegative and DNA negative for HPV 16/18. The AS04-adjuvanted HPV 16/18 vaccine confers cross protection against certain non-vaccine, high-risk HPV types. A rapid and strong anamnestic humoral immune response was elicited following a fourth dose of the vaccine. The AS04-adjuvanted HPV 16/18 vaccine is generally well tolerated, and pharmacoeconomic analyses have demonstrated the potential for public health benefits and cost effectiveness when vaccination programs are run in conjunction with screening programs. Thus, the AS04-adjuvanted HPV 16/18 vaccine prevents cervical disease associated with certain oncogenic HPV types, thereby reducing the burden of premalignant cervical lesions and, very likely, cervical cancer.     

Spotlight on Pentavalent Rotavirus Vaccine (RotaTeq®) in the Prevention of Rotavirus Gastroenteritis in Europe

In Europe, rotavirus gastroenteritis is associated with a significant health, economic, and social burden, as it is responsible for large numbers of hospitalizations and other healthcare encounters among infants and children, as well as numerous days of work lost by parents and caregivers. RotaTeq® is a three-dose, orally administered, live, pentavalent human-bovine reassortant rotavirus vaccine used for the active immunization of infants for prevention of rotavirus gastroenteritis. The protective efficacy of RotaTeq® has been evaluated in terms of its effects on the incidence of rotavirus gastroenteritis and on healthcare resource use. Clinical trial data from REST (a randomized, double-blind, placebo-controlled, multinational study in ≈70 000 healthy infants aged 6–12 weeks) and various subgroup analyses, including a large European cohort, have shown that RotaTeq® may be administered at the same time as various other routine vaccines, has high and sustained efficacy covering the main period of risk for rotavirus gastroenteritis, has early protective efficacy after the first and second doses, reduces rotavirus gastroenteritis-associated hospitalization and emergency department and physician visits, and is generally well tolerated. Moreover, RotaTeq® has demonstrated efficacy against the five most prevalent serotypes of rotavirus in Europe (G1-G4, G9), in terms of reductions in associated healthcare resource use. There is also evidence that the widespread use of RotaTeq® may provide herd immunity, as it appears to have indirect benefits in older, unvaccinated children. Reports on the ‘real world’ effectiveness of RotaTeq® in Europe are just emerging, but data from the US have shown a rapid and marked reduction in rotavirus burden nationwide during the ≈2-year period following the introduction of RotaTeq® and the subsequent availability of official recommendations advocating universal use of the vaccine as part of routine childhood immunization. Postmarketing surveillance ? Adapted and reproduced from Drugs 2010; 70 (9): 1165-1188. The full text article^[1] was reviewed by: H. Antunes, Gastroenterology, Hepatology and Nutrition Unit, Pediatrics Department, Braga Hospital, Braga, Portugal; G. Gabutti, Department of Clinical and Experimental Medicine, Hygiene and Occupational Health Unit, University of Ferrara, Ferrara, Italy; D. Gendrel, Service de Pédiatrie, Hôpital Saint-Vincent-de-Paul, Paris, France; F. Omeñaca, Neonatal Unit, Department of Neonatology, La Paz Hospital, Madrid, Spain. The manufacturer of the agent under review was offered an opportunity to comment on the original article during the peer review process. Changes based on any comments received were made on the basis of scientific and editorial merit. The preparation of the original article and this spotlight was not supported by any external funding. data from the US have not identified any concerns, such as an association with intussusception or Kawasaki disease, related to the safety of RotaTeq®. In conclusion, RotaTeq® is a generally well tolerated vaccine that has efficacy against the five most prevalent serotypes of rotavirus in Europe and provides sustained efficacy over the main risk period for rotavirus gastroenteritis in infants and children, reducing hospitalizations and emergency department visits by decreasing the incidence and severity of illness.     

Comments on “Changing attitudes towards the care of children in hospital: a new assessment of the influence of the work of Bowlby and Robertson in the UK, 1940–1970” by Frank C.P. van der Horst and Rene van der Veer (Attachment & Human Development Vol 11, No 2, March 2009, 119–142)

The importance of James Robertson's work in changing the hospital conditions for young children is widely acknowledged but disputed by van der Horst and van der Veer (2009), although they presented evidence supporting his influence, they also presented considerable evidence showing that others were ignored, including writers in The Lancet and the British Medical Journal. van der Horst and van der Veer presented a muddled picture by failing to understand how the work of James Robertson influenced a wide range of people, opened up the debate and, through the Platt Report, gave parents the authority and confidence to challenge hospitals and stay with their young children. James Robertson's 1952 film “a Two-year-old Goes to Hospital” provided the ‘visual communication to pierce defences as the spoken word cannot do’. This film continues to be widely used today in teaching about young children.     

Comments on the article “Changing attitudes towards the care of children in hospital: a new assessment of the influence of the work of Bowlby and Robertson in the UK, 1940–1970” by Frank C.P. van der Horst and Rene van der Veer (Attachment and Human Development Vol 11, No 2, March 2009, 119–142)

The authors give an impressive list of references, but these do not reflect the situation in the UK; most of those looking after children in hospital did not write about what they did or read about what others did. Children in hospital saw little or nothing of their parents, and once they had ‘settled’ the doctors and nurses were unaware of their distress. John Bowlby's interest in maternal deprivation led him to appoint James Robertson as his research assistant, to observe responses of young children to loss of maternal care on admission to hospital. They formulated the theoretical framework of the three stages through which the children went; protest, despair, and detachment constituting a developmental interference. Robertson was so concerned when nobody would listen that in 1952 he made the film ‘A Two Year Old Goes to Hospital’, which upset children's doctors and nurses. It also probably contributed to the government setting up in 1957 a Committee chaired by Sir Harry Platt to consider the Welfare of Children in Hospital. ‘Going to Hospital with Mother’ was made by Robertson in 1958. With Dermod MacCarthy he showed the films to the Committee, who accepted the suggestions in Robertson's Memorandum which included unrestricted visiting and mothers being admitted with their young children. The Report, known as the Platt Report, was published in 1959. Robertson could then show his films publicy, campaign in the media and encourage the pressure group NAWCH (the National Association for the Welfare of Children in Hospital) who were successful in getting many of the Committee's recommendations implemented, to the benefit of all children in hospital.