Localized lipoatrophy and inadvertent subcutaneous administration of a COVID-19 vaccine.

A 60-year-old woman presented with a depressed lesion at the site of her first COVID-19 (Astra Zeneca) vaccine injection. The lesion was diagnosed as a case of injection related localized lipoatrophy as markers of autoimmune disease were negative and biopsy differentiated it from localized involutional lipoatrophy. This case of localized lipoatrophy was likely due to inadvertent subcutaneous injection of the COVID-19 vaccine with a 16 mm long needle.

Subcutaneous vaccine administration - an outmoded practice.

Subcutaneous vaccine (SC) administration is an outmoded practice which complicates vaccine administration recommendations. Local adverse events following immunization (AEFIs) are a recognized determinant of vaccine hesitancy/refusal which can lead to an increased prevalence of vaccine-preventable disease.This extensive narrative review provides high-grade evidence that intramuscular (IM) administration of all vaccine types [adjuvanted, live virus and non-adjuvanted (inactivated whole cell, split cell and subunit)] significantly reduces the likelihood of local adverse events. This, combined with moderate grade evidence that IM injection generates significantly greater immune response compared with SC injection, allows a strong recommendation to be made for the IM injection of all vaccines except BCG and Rotavirus.This will simplify vaccination practice, minimize the inadvertent misadministration of vaccines and potentially improve public trust in vaccination.

Herpes zoster vaccine (Zostavax®): Cellulitic injection site reaction or bacterial cellulitis?

A 70 y old woman presented with a cellulitic reaction following Zostavax® injection. This reaction could be differentiated from bacterial cellulitis on the basis of the temporal relationship between vaccination and onset of the reaction, its non progression and unresponsiveness to antibiotic therapy. Alerting health care providers to this type of reaction, also seen with pneumococcal and pertussis containing vaccines, should avoid the inappropriate use of antibiotics.

Sepsis, parenteral vaccination and skin disinfection.

ASBSTRACT Disinfection should be required for all skin penetrative procedures including parenteral administration of vaccines. This review analyses medically attended infectious events following parenteral vaccination in terms of their microbiological aetiology and pathogenesis. Like 'clean' surgical site infections, the major pathogens responsible for these events were Staphylococcal species, implicating endogenous con-tamination as a significant source of infection. As 70% isopropyl alcohol swabbing has been shown to effectively disinfect the skin, it would be medico-legally difficult to defend a case of sepsis with the omission of skin disinfection unless the very low risk of this event was adequately explained to the patient and documented prior to vaccination. There was a significant cost-benefit for skin disinfection and cellulitis. Skin disinfection in the context of parenteral vaccination represents a new paradigm of medical practice; the use of a low cost intervention to prevent an event of very low prevalence but of significant cost.

Best vaccination practice and medically attended injection site events following deltoid intramuscular injection.

Analysis of medically attended injection site events data provides a vehicle to appreciate the inadequacies of vaccination practice for deltoid intramuscular injection and to develop best practice procedures. These data can be divided into 3 groups; nerve palsies, musculoskeletal injuries and cutaneous reactions and reflect inappropriate site of injection, needle over or under penetration, local sepsis and vascular complications. The aim of this review is to formulate best vaccination practice procedures for deltoid intramuscular injection of vaccines through the collation and analysis of medically attended injection site events.

Subdeltoid/subacromial bursitis associated with influenza vaccination.

A 76-year-old male presented with subacromial/subdeltoid bursitis following influenza vaccine administration into the left deltoid muscle. This shoulder injury related to vaccine administration (SIRVA) could have been prevented by the use of a safe, evidence based protocol for the intramuscular injection of the deltoid muscle.

An evidence based protocol for the prevention of upper arm injury related to vaccine administration (UAIRVA).

Upper arm injury related to vaccine administration (UAIRVA) is an infrequent but increasingly recognised complication of deltoid muscle vaccination. Vaccine administration reported injury to the subdeltoid/subacromial bursa, anterior branch of the axillary nerve and the radial nerve presumably reflects the lack of awareness of the anatomical position of these structures in and near this muscle and the multiplicity of methods for the selection of the injection site in the muscle. An evidence based protocol for safe vaccine administration into the deltoid muscle is presented. This was developed using anthropometric measurements of the surface anatomical landmarks in adults who regularly receive intramuscular injection of vaccines into the deltoid muscle (adults ≥ 65 years old) and mapping the position of structures potentially injured by injection observed in ultrasonographic and cadaveric studies. The mid point of the muscle (midway between the acromion and the deltoid tuberosity) with the arm abducted to 60° is a safe site for injection. The protocol for vaccine administration in this way involves the vaccinee placing the hand on the ipsilateral hip with the vaccinator then placing their index finger on the acromion and their thumb on the deltoid tuberosity and administering the vaccine at midpoint between these anatomical landmarks.

Sex differences in injection site reactions with human vaccines.

Adverse events following immunization (AEFI) are not uncommon, with injection site reactions (ISRs) being the most common. Predictors of injection site reactions are vaccine factors (antigen characteristics, antigen dose, dose number of antigen, antigen adjuvanting and type of diluent), vaccine administration factors (site and route of administration) and vaccinee factors (age and sex, the latter the subject of this review). 1,074 studies which reported ISRs were retrieved by searching of on line journals and databases. Analysis of these data for sex-difference was only reported in 57 studies, with 54 of these studies reporting a sex-difference (42 in subjects >17 years and 12 in subjects <17 years). In accord with the well documented greater pain sensitivity in females compared with males, in all studies with vaccines which reported pain during and post vaccination [hepatitis A, B, diphtheria/tetanus toxoid, diphtheria/tetanus/pertussis(DTaP and Tdap), anthrax and inactivated influenza], females reported a greater rate of pain than males. The pathophysiology of the sex-difference in local reactions (induration, tenderness, erythema, pruritus) following vaccination is clearly multifactorial with hypersensitivity reaction (type III, Arthus reaction-antigen/antibody immune complex formation), route of administration and hormonal factors being suggested. The data presented in this review demonstrate that studies of AEFI should recruit similar numbers of females and males and that these data should be analyzed for sex-difference. Additionally, unlike as at present, reporting of analysis of AEFI data by sex should become standard practice.

Comparative reactogenicity and immunogenicity of 23 valent pneumococcal vaccine administered by intramuscular or subcutaneous injection in elderly adults.

23 Valent pneumococcal vaccine is provided to the elderly through public health programs in many countries. However there is no clear recommendation regarding its route of administration (subcutaneous or intramuscular). In a randomised, observer blind study of 254 elderly subjects, the immunogenicity of a 23 valent pneumococcal vaccine was not influenced by its route of administration. A low rate of systemic adverse reactions was observed with the vaccine (subcutaneous and intramuscular both 6.3%). Local adverse reaction rates were; intramuscular 7.1% and subcutaneous 18.9% and these were predicted by: * Pre-vaccination antibody titres>1 microg/ml, odds ratio 22.4 (8.06-74.84) compared with pre-vaccination antibody titre<1 microg/ml. * Female gender, odds ratio 5.0 (1.85-14.83) compared with male gender. * Subcutaneous injection route, odds ratio 3.20 (1.13-9.13) compared with intramuscular injection route. * Female gender subcutaneous injection route, odds ratio 2.99 (1.10-8.70) compared with female gender intramuscular injection route. These data support the intramuscular injection of 23 valent pneumococcal vaccine, especially in elderly females.

Reactogenicity and immunogenicity of an inactivated influenza vaccine administered by intramuscular or subcutaneous injection in elderly adults.

In many countries there is no clear recommendation regarding the preferred route of administration of inactivated influenza vaccines. In a randomised, observer blind study of 720 elderly subjects, a split, trivalent influenza vaccine was significantly more immunogenic for both A strains (H3N2 and H1N1, p = 0.0016 and 0.003, respectively) when given intramuscularly compared to subcutaneously. This difference was due entirely to a gender effect, with females in the intramuscular (IM) group having a significantly greater serological response than females in the subcutaneous (SC) group for both of these strains. Similar results were seen with local adverse effects. These data suggest that vaccination practices that ensure intramuscular injection are required for optimal administration of influenza vaccines in the elderly.

Optimal technique for intramuscular injection of infants and toddlers: a randomised trial.

OBJECTIVE: To compare the rates of adverse reactions and parental approval ratings for three different techniques for anterolateral thigh vaccination in children aged 2, 4, 6 and 18 months. DESIGN: Randomised, observer-blind trial. PARTICIPANTS: 375 children who received pertussis-containing vaccines in a regional New South Wales town between 29 May 2001 and 30 June 2002. INTERVENTIONS: Children were randomised to receive intramuscular injection with acellular pertussis-containing and Haemophilus influenzae type b vaccines with one of three recognised injection techniques (Australian, World Health Organization or United States). MAIN OUTCOME MEASURES: Local adverse reactions (bruising and redness/swelling), systemic adverse reactions (irritability, perceived fever, persistent crying/screaming, drowsiness, vomiting/poor feeding) and parental acceptance were assessed 24 hours after injection. RESULTS: 361 children (96%) were evaluated 24 hours after vaccination. The WHO technique resulted in significantly fewer children, than with the other two techniques, with the systemic adverse reaction variable "irritability" (P = 0.0039). There was a significant difference between the technique groups overall for the local adverse reaction "bruising" with acellular pertussis-containing vaccines (P = 0.0418), due to a lower reaction rate in the WHO group compared with the US group (P = 0.0356). CONCLUSION: The WHO technique appears to be the optimal technique for anterolateral thigh injection in children--it ensures that the injection is intramuscular, results in fewer adverse reactions, and is the easiest technique to perform as it does not require angling of the needle to the long axis of the femur.

Needle length required for intramuscular vaccination of infants and toddlers. An ultrasonographic study.

BACKGROUND: To be maximally effective and to induce less adverse reactions, injection with many vaccine antigens must penetrate muscle rather than subcutaneous tissue. AIM: To determine the length of needle needed to penetrate muscle at the anterolateral thigh vaccination site in children aged two, four, six and 18 months. METHOD: Ultrasound measurements were made of the subcutaneous and muscle layer thickness of children aged two, four, six and 18 months at the junction of the upper and middle thirds of the anterolateral thigh with the probe applied parallel to the long axis of the leg and at 45 degrees to the vertical and at 90 degrees to the skin's plane. RESULTS: Subcutaneous tissue (SCT) and muscle layer (ML) thickness were measured in 57 children (2 months, n = 14; 4 months, n = 13; 6 months, n = 18; 18 months, n = 12) with mean SCT thickness of: 8.6 +/- 3.0 mm at 2 months; 9.4 +/- 2.0 mm at 4 months; 10.2 +/- 2.1 mm at 6 months; and 8.1 +/- 1.7 mm at 18 months. Muscle layer thickness in these children was: 10.5 +/- 2.4 mm at 2 months; 12.2 +/- 2.0 mm at 4 months; 14.8 +/- 2.0 mm at 6 months, and 16.5 +/- 4.6 mm at 18 months. CONCLUSION: The optimal needle length to routinely penetrate muscle of the anterolateral thigh in children aged two, four, six and 18 months depends on the technique employed. A 16 mm long needle is suitable with the WHO technique (injecting at 90 degrees to skin's surface) and 25 mm long needle with the NH&MRC and American techniques (injecting at 45 degrees to skin's surface).

Mode of formulation of cholesta-5,7-dien-3beta-ol from Cholest-5-en-3beta-ol by Larvae of Calliphora erythrocephala.

1. The conversion of cholest-5-en-3beta-ol (cholesterol) into cholesta-5,7-dien-3beta-ol by axenic Calliphora erythrocephala larvae was demonstrated. 2. The transformation is probably direct (Delta(5)-->Delta(5,7)) and does not involve a Delta(0) intermediate (Delta(5)-->Delta(0)-->Delta(7)--> Delta(5,7)). 3. Delta(7)-bond formation involves the stereospecific elimination of the 7beta hydrogen atom. 4. The relative amounts of free and esterified sterols were determined in larvae grown on cholesterol as sole sterol source and on 5alpha-cholestan-3beta-ol supplemented with minimal amounts of cholesterol. 5. The significance of the results is assessed in relation to the probable role of cholesta-5,7-dien-3beta-ol as an intermediate in the biosynthesis of ecdysones.