Evidence based route of administration of vaccines.

Vaccination is a proven public health initiative, however it is imperative in the context of increasing concerns about vaccine induced adverse reactions and a decreasing incidence of diseases they prevent that the optimal route for their administration is defined. Traditionally all vaccines were given by subcutaneous injection until it was recognized that adjuvanted vaccines given via this route induced an unacceptable rate of injection site reaction. Evidence-based medicine has been championed as a way of improving the quality of patient care. Application of this methodology to the route of administration of vaccines demonstrates that vaccines should be given by intramuscular injection in preference to subcutaneous injection as the intramuscular route is associated with better immune response and a lower rate of injection site reaction. The basis of this superiority is discussed.

Ventrogluteal area--a suitable site for intramuscular vaccination of infants and toddlers.

Buttock vaccination has lower reactogenicity and similar immunogenicity to the two other recommended paediatric vaccination sites (deltoid and anterolateral thigh). Safety concerns about buttock injection derived from injections with neurotoxic agents, like penicillin but not vaccines, have become entrenched. However, the ventrogluteal area is considered safe for intramuscular injection. This study outlines the development of the ventrogluteal area as a suitable site for intramuscular vaccination of infants and toddlers. Measurement was made in 642 children, aged 2-18 months and age-specific templates were prepared. These were used in an untrasonographic study of 57 children aged 2-18 months to determine the tissue composition of the ventrogluteal area compared with the recommended anterolateral thigh vaccination site. The ventrogluteal area was found to be clearly defined by the template and suitable for intramuscular injection. Subsequent vaccination studies with the area showed that it was:

Definition of needle length required for intramuscular deltoid injection in elderly adults: an ultrasonographic study.

An ultrasound study in elderly patients (> or =65 years) showed that body mass index (BMI) was strongly correlated with deltoid subcutaneous layer thickness in males (r = 0.69 dominant arm, 0.71 non-dominant arm) and females (r = 0.79 both arms). Females with the same BMI as males had significantly thicker subcutaneous layers (p = 0.0001) and thinner muscle layers (p = 0.0003). Minimal needle length required for deltoid intramuscular injection where the needle was entered at 90 degrees to the long axis of the humerus was defined by BMI group. In all BMI males and females, BMI <35, intramuscular injection could be achieved with a 25 mm long needle, whilst in females BMI >35, a 32 mm long needle is required. These data will be used in studies to resolve the clinical equipoise regarding the optimal route of administration (intramuscular versus subcutaneous) of vaccines (e.g. influenza and pneumococcal vaccines), which are provided through public health programs for the elderly.

Comparative reactogenicity and parental acceptability of pertussis vaccines administered into the ventrogluteal area and anterolateral thigh in children aged 2, 4, 6 and 18 months.

The importance of site of injection of combined pertussis/diphtheria/tetanus vaccines was investigated in two single blind studies. In the pilot study, in which the research instrument was trialed, 283 children aged 2-18 months received whole cell pertussis vaccine (DTPw) by the intramuscular route either into the anterolateral thigh or the ventrogluteal site. In the larger randomised study, 566 children aged 2-18 months were similarly injected with acellular pertussis vaccine (DTPa). Adverse reactions monitored after 24h showed the same lower rates for both vaccines with ventrogluteal injection compared with anterolateral thigh injection for systemic reactions (irritability (P<0.0001), perceived fever (P<0.0001), persistent crying/screaming (P<0.0001) and local reactions (bruising (P<0.0001) and redness/swelling (P<0.0001)). The Haemophilus influenzae type b vaccine (HibTITER) given concurrently in the contralateral site to the pertussis vaccine showed the same lower rates in both studies for ventrogluteal injection compared with anterolateral thigh injection for local reactions (redness/swelling both studies (P<0.0001) and bruising DTPw study (P<0.0001) and DTPa study (P<0.0004)).Parental acceptability was greater (P<0.0001) in both studies for ventrogluteal injection compared with anterolateral thigh injection.

Comparative immunogenicity of hepatitis B vaccine administered into the ventrogluteal area and anterolateral thigh in infants.

OBJECTIVE: To compare the immunological response of hepatitis B vaccine given by intramuscular injection into the anterolateral thigh and ventrogluteal site of infants up to 10 months old at initiation of vaccination. METHODS: An open, randomized study of 200 healthy infants recruited from a single practice in a small regional town in New South Wales was carried out. Infants were vaccinated with hepatitis B vaccine (Engerix-B 10 microg) using a 0 months, 1 month, 6 months regimen, with venous blood being collected from children 4-6 weeks after the last dose of vaccine for quantitative determination of hepatitis B surface antibody (anti-HBs) titre. Infants with anti-HBs titre > or = 100 m IU/mL were considered to be 'good' responders and were unlikely to acquire clinically significant hepatitis B infection. Infants with anti-HBs titre < 100 m IU/mL were considered to be 'poor' responders and were given a booster dose of Engerix-B 20 micro g; serology was repeated for anti-HBs titre 2-3 months after this injection. RESULTS: Quantitative anti-HBs titre was obtained from 177 infants: 171 4-6 weeks after the last dose of vaccine; 87 at the ventrogluteal site (46 boys, 41 girls); and 84 at the anterolateral thigh site (38 boys, 46 girls). Good antibody response (anti-HBs titre > or = 100 m IU/mL) was not significantly different for the two sites (ventrogluteal 96.6%, anterolateral thigh 93.2%), and antibody geometric mean titres (GMT) for anti-HBs were comparable for the two sites (ventrogluteal 2071.2 +/- 5.8m IU/mL, anterolateral thigh 2073.2 +/- 5.2m IU/mL). CONCLUSION: The ventrogluteal and anterolateral thigh vaccination sites in infants are immunologically comparable for hepatitis B vaccine. Presumably the variance of this study with studies of adults reflected the uniform injection of vaccine antigen into muscle tissue in infants.

Paediatric vaccination practice in a division of general practice.

BACKGROUND: Currently the National Health and Medical Research Council (NH&MRC) recommend the use of a 23 gauge, 25 mm long needle inserted 45-60 degrees into the anterolateral thigh for paediatric vaccination. AIM: To assess the compliance of general practitioners (GPs) in a rural practice division with vaccination practice (site and needle size and gauge) prescribed for infants and toddlers by the NH&MRC. METHOD: In 1999, a questionnaire survey was sent by the divisional office to all 150 GPs in the Hunter Rural Division of General Practice. The questionnaire collected demographic data (age, gender, university of graduation, number of paediatric vaccines administered per week) and elicited responses about the site of vaccination and the size and gauge of needle to be used for children 2-18 months and 18 months and older. RESULTS: Completed questionnaires were available from 112 GPs (74.6% completion rate). There was a high level of compliance with the NH&MRC proscription of buttock vaccination with only 4.3% and 4.1% of responses to the question of vaccination site at 2-18 months and 18 months and older respectively nominating this site. The anterolateral thigh was the favoured site for vaccination in children 2-18 months old (77.5% of responses) with the deltoid being the favoured site in children 18 months and older (59.2% of responses). There was a very low level of compliance with the NH&MRC recommended standard needle (23 gauge, 25 mm long, blue hub needle) (3.5% of responses). The orange hub needle (25 gauge, 16 mm long needle) was most favoured (48.7% of responses) with additional strong support for the 25 gauge, 25 mm long needle (40.2% of responses). CONCLUSION: In the Hunter Rural Division of General Practice there was good compliance with the NH&MRC's recommendations for site of vaccination, but not needle size and gauge to be used in infants and small children. Imprecise wording of these recommendations has created apparent uncertainty about the site of vaccination of children at 18 months of age.

Race-linked differences in serum concentrations of dapsone, monoacetyldapsone and pyrimethamine during malaria prophylaxis.

Serum concentrations of dapsone (DDS), monoacetyldapsone (MADDS), the principal acetylated metabolite of DDS, and pyrimethamine (PYR) were measured in 55 Caucasian adults (31 males, 24 females) and 159 Papua New Guinean adults (140 males, 19 females) following the oral administration of Folaprim (100mg DDS; 12.5mg PYR). Blood samples were collected at mean sampling times of eight hours after medication and 18 hours before the next weekly dose for malaria prophylaxis. Clearance of DDS and MADDS from serum were significantly faster (p less than 0.001) in Caucasians than in Papua New Guineans. Significantly lower (p less than greater 0.001) serum concentrations of PYR were found in Papua New Guineans than in Caucasians at both sampling times, an observation which may reflect differences in the bioavailability of PYR between the two racial groups. The theoretical implications of these results are that Caucasians may be more susceptible to PYR-resistant Plasmodium falciparum malaria than Papua New Guineans whilst Papua New Guineans may be more susceptible to P. vivax; malaria than Caucasians.

Herpes zoster in children following malaria.

Herpes zoster is uncommon in normal children in the 0-9 year age group. However, its incidence is markedly increased in those who are immunosuppressed. Six Papua New Guinean children under 9 years of age developed herpes zoster following an episode of malaria, due to Plasmodium falciparum or Plasmodium vivax which was treated with chloroquine. The reactivation of the varicella-zoster virus in these patients may reflect transient depression of cell-mediated immunity by these malaria parasites, possibly augmented by the chloroquine used in their treatment.

Haematological safety of long-term malarial prophylaxis with dapsone-pyrimethamine.

There are no published haematological data on the long-term (more than one year) use of dapsone-pyrimethamine (Maloprim, Folaprim; one tablet a week) for malarial prophylaxis. In a study of 373 male Papua New Guinean soldiers who had used this combination for five years, we found no haematological abnormalities attributable to dapsone-pyrimethamine. Furthermore, the haematological parameters of these soldiers were not clinically different from those of Papua New Guinean university students who did not ingest antimalarial drugs prophylactically. In a parallel study, 9 of 159 white persons (6 children and 3 adult females) who had used dapsone-pyrimethamine prophylaxis for more than one year had haematological abnormalities attributable to the drug. Additionally, the mean leucocyte count of children aged 1-9 years who took dapsone-pyrimethamine was markedly lower--although within the normal range--than that of similarly aged children who received chloroquine for malarial prophylaxis. The appreciable incidence of haematological abnormalities observed in children during malarial prophylaxis with dapsone-pyrimethamine demonstrates the need to select a dose for this group on a weight rather than an age basis and to use a liquid formulation to facilitate the administration of the appropriate dose of this combination. Haematological monitoring of the long-term use of dapsone-pyrimethamine is recommended and a suitable monitoring regimen is suggested.

Inadequate prophylaxis of malaria with dapsone-pyrimethamine.

The dapsone-pyrimethamine combination (100 mg of dapsone, 12.5 mg of pyrimethamine [Folaprim; Maloprim, one tablet a week) is considered to provide adequate prophylaxis for Plasmodium falciparum malaria, but to be inadequate for the prevention of P. vivax malaria. Field trials and case reports, however, have shown the comparable efficacy of this combination in the suppression of parasitaemias caused by both parasites. In Lae, Papua New Guinea, 12 patients with clinical signs of malaria had serum concentrations of dapsone-pyrimethamine which were consistent with appropriate weekly use of this combination. The fact that 10 of these patients had P. vivax malaria supports the hitherto unsubstantiated view that dapsone-pyrimethamine can be ineffective in suppressing parasitaemias caused by this parasite. In the two patients with P. falciparum malaria, host factors rather than parasite resistance to dapsone-pyrimethamine were implicated in the development of the parasitaemias.

Intracranial complications of sphenoidal sinus inflammation.

A young man who presented with bacterial meningitis and visual disturbance developed a left sixth nerve palsy due to an isolated sphenoidal sinus inflammation caused by Corynebacterium haemolyticum. Sphenoidal sinusitis and intracranial infection by C. haemolyticum are uncommon complications.