Ann Gardulf

Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs

Immunoglobulins (IgG) as replacement therapy in primary antibody deficiencies can be given as intramuscular injections, or as intravenous or subcutaneous infusions. Our aims were to obtain information on the frequency of adverse systemic reactions during subcutaneous therapy, the occurrence and intensity of tissue reactions at the infusion sites, and serum IgG changes. Furthermore, we compared costs between the different replacement regimes. Our study included 165 patients (69 women, 96 men, aged 13-76 years) with primary hypogammaglobulinaemia or IgG-subclass deficiencies. Data were compiled from questionnaires filled in by the patients and from their medical records. 33,168 subcutaneous infusions (27,030 in home therapy) had been given. 106 (of which 16 were at home) adverse systemic reactions (100 mild, 6 moderate) were recorded in 28 patients (17%). No severe or anaphylactoid reactions occurred. Despite large immunoglobulin volumes given during 434 patient years (28,480 infusions), no signs have been found that indicate the transmission of hepatitis virus. Transient tissue reactions occurred at the infusion sites but were not troublesome to most patients and we found significant increases in mean serum IgG. The use of subcutaneous instead of intravenous infusions at home would reduce the yearly cost per patient for the health-care sector by US

HOME TREATMENT OF HYPOGAMMAGLOBULINAEMIA WITH SUBCUTANEOUS GAMMAGLOBULIN BY RAPID INFUSION

10,100 in Sweden alone. We conclude that subcutaneous administration of IgG is a safe and convenient method of providing immunoglobulins. We were able to reach serum IgG concentrations similar to those by the intravenous therapy and we found that the method could also be used successfully in patients with previous severe or anaphylactoid reactions to intramuscular injections.

Two-year survey of the incidence of lyme borreliosis and tick-borne encephalitis in a high-risk population in Sweden

Intramuscular and intravenous gammaglobulin treatment for hypogammaglobulinaemia is often associated with systemic adverse reactions in some patients. Subcutaneous infusions of gammaglobulin are usually given at a slow rate. To assess the safety of home treatment with subcutaneous gammaglobulin, rapid infusions (34-40 ml/h) given by small portable pumps were used to treat twenty-five patients with hypogammaglobulinaemia. Fifteen patients had previously had adverse reactions to intramuscular or intravenous gammaglobulin treatment. After the patients had been taught how to use the pumps during 6 months of treatment in hospital, in which they initially received 100 mg of an intramuscular gammaglobulin preparation/kg per week, they went on to use the pumps at home or at work. So far, the patients have given themselves 3232 rapid subcutaneous infusions (2308 in home therapy). A median pre-infusion serum IgG concentration of 8.1 g/l resulted after 6 months of treatment. There were only 30 (0.93%) mild systemic adverse reactions; there were fewer reactions with subcutaneous gammaglobulin than with previously given intramuscular injections (n = 21, p less than 0.001) or intravenous infusions (n = 9, p less than 0.001) in this group of patients. Overall, the patients spent 0.2 days a year in hospital due to respiratory tract infections. The findings show that the method for subcutaneous administration is very easy to learn and is appreciated by the patients; moreover, the infusions can be given much faster than previously reported without any pronounced local reaction.

Systemic and Topical Immunoglobulin Treatment in Immunocompromised Patients

A survey was made over a two-year period (September 1987 to August 1989) of a population living in an area endemic for Lyme borreliosis and tick-borne encephalitis in Sweden. For each patient a blood sample was collected and a questionnaire completed annually. All sera were tested for an antibody response toBorrelia burgdorferi in an EIA using sonicated antigen and for an antibody response to the tick-borne encephalitis virus using an EIA and a haemagglutination inhibition test. Antibodies toBorrelia burgdorferi and tick-borne encephalitis virus were detected in 89 (25.7 %) and 40 (11.6 %) respectively of 346 samples collected in August 1987. In the first year of the study 14 of 303 subjects (4.6 %) developed Lyme borreliosis and in the second year 9 of 277 subjects (3.2 %). A significant increase in the antibody titre forBorrelia burgdorferi was seen in 14 of 303 (4.6 %) subjects in the first year and 8 of 277 (2.9 %) subjects in the second year. An earlier episode of Lyme borreliosis or an elevated antibody titre did not seem to protect against reinfection. One case of tick-borne encephalitis was seen each year. Seroconversion for tick-borne encephalitis virus was found in 3 of 258 (1.2 %) subjects in the first year and 5 of 211 (2.4 %) in the second year, excluding subjects who had undergone successful immunisation or had earlier been hospitalised for tick-borne encephalitis. The study thus demonstrated a high yearly incidence of tick-borne infections in a population at risk.

Prevalence of Borrelia burgdorferi sensu lato infection in Ixodes ricinus in Sweden

Different immunoglobulin preparations have been successfully used for the past century as prophylaxis and therapy in various infectious diseases. The antibodies are thought to be effective by binding and neutralization of microbial antigens, blocking of binding of virus and bacteria to target cells and by acting as opsonins, thereby initiating uptake and degradation by phagocytosing cells. Gammaglobulin preparations also contain neutralizing antibodies against superantigens such as Staphylococcal toxins (Takei et al. 1993) which have been implicated in immune dysregulation. More recently, immunoglobulin intended for intravenous use (i.v.Ig) has also been used therapeutically as an immunomodulating agent. This stems from the initial report on the use of i.v.Ig in autoimmune disorders (Imbach et al. 1981), and a vast number of studies have been performed to date, aimed at elucidating the mechanism of action. The ones proposed initially included Fc receptor blockade and Fc receptor modulation (for review see Jungi et al. 1990, Halma et al. 1991, Jungi & Nydegger 1992) by the infused i.v.Ig and idiotypic anti-idiotypic interactions (for review see Nydegger et al. 1991). Recently, additional mechanisms have been suggested including the downregulation of Interleukin production (Andersson et al. 1993), possibly due to the presence of anti-IL antibodies in the i.v.Ig, and an effect on T cells due to the presence of specific antibodies against the T-cell receptor (Marchalonis et al.

Clinical Manifestations and Antibody Prevalence of Lyme Borreliosis and Tick-borne Encephalitis in Sweden: A Study in Five Endemic Areas Close to Stockholm

Between 1988-1991, a total of 3,141 Ixodes ricinus ticks, 2,740 adults and 401 nymphs, was collected from different localities in 23 of the 25 provinces of Sweden. The ticks were identified, dissected and examined for the presence of Borrelia spirochetes. Indirect immunofluorescence was performed, using an antiserum obtained from rabbits, immunized with sonicated, whole Borrelia burgdorferi spirochetes isolated from Swedish Ixodes ricinus ticks. Borrelia-positive I. ricinus were found in all 23 provinces. The prevalence of infection in adults ranged from 3% in Jämtland to 23% in Södermanland. In nymphs, the infection prevalence ranged from 0% in 9 provinces to 15% in Södermanland. A significantly greater proportion of the adult ticks were found to be positive for Borrelia in the southern and central parts of Sweden as compared to the northern part (Norrland). No significant difference in prevalence could be demonstrated between the western and eastern parts of Sweden. On average, 10% of the nymphs and 15% of the adult I. ricinus were positive for Borrelia. Of 41 non-I. ricinus ticks, none was positive for Borrelia. This study shows that Borrelia burgdorferi sensu lato is present throughout the distributional area of I. ricinus in Sweden. This should lead to increased awareness of signs and symptoms compatible with Lyme borreliosis in persons living in or visiting areas where I. ricinus is present.

Antibody Prevalence and Clinical Manifestations of Lyme Borreliosis and Tick-borne Encephalitis in Swedish Orienteers

Five populations, including 903 individuals living in 5 different areas close to Stockholm, were studied with regard to clinical manifestations and antibody prevalence of Lyme borreliosis (LB) and tick-borne encephalitis (TBE). The study areas involved 4 groups of islands in the Baltic Sea and 1 island in Lake Mälaren. Serum samples from each individual were tested for antibody activity to Borrelia burgdorferi using a sonicated whole spirochete antigen in an ELISA, and to TBE-virus (TBEV) by ELISA and haemagglutination inhibition. A history of LB was reported by 1-21% and antibodies to Borrelia burgdorferi were found in 7-29% of the participants from the various areas. An increasing seroprevalence with age was seen. In sera from 3 different control groups, including 502 individuals living in non-endemic areas, antibodies to Borrelia burgdorferi were detected in 1-2% and from 1 control group including 150 individuals living in the city of Stockholm, in 9%. A history of TBE was reported by 0-6% of the individuals and in non-immunized individuals seropositivity was seen in 4-22%, depending on the area investigated. No antibody activity to TBEV could be detected in sera from persons in the 3 control groups living in non-endemic areas, whereas 5% of the controls from Stockholm were found to be positive. The prevalence rates of antibodies to TBEV in persons vaccinated against TBE were 40%, 53% and 79% after 1, 2 and 3 injections, respectively.

The Opinions of Nursing Documentation Held by District Nurses and by Nurses at Primary Health Care Centres

Antibody prevalence and clinical manifestations of Lyme borreliosis (LB) and tick-borne encephalitis (TBE) were studied in 362 orienteers from the county of Stockholm during a large relay race in October 1990. From all participating orienteers, a blood sample was collected and a questionnaire completed. Antibody activity to Borrelia burgdorferi was measured using a sonicated whole spirochete antigen in an ELISA, and to TBE virus (TBEV) by ELISA and haemagglutination inhibition (HI) test. A past history of LB was reported by 6% of the orienteers and antibodies to B. burgdorferi were found in 9%. Antibody reactivity to B. burgdorferi was found in 1-2% of the sera from 3 different control groups comprising 502 persons living in non-endemic areas. The corresponding value was 9% in sera from a fourth control group consisting of 150 persons living in the city of Stockholm. A past history of TBE was reported by 1 orienteer (0.3%) and detectable antibodies to TBEV in non-immunized individuals were found in 1%. No antibody activity to TBEV could be detected in sera from the control individuals living in the 3 non-endemic areas, but in 5% of the controls from Stockholm. In this study, there was no indication that frequent or severe manifestations of LB or TBE are common among orienteers in Sweden.

Subcutaneous Administration of Immunoglobulins

Before a general, nursing documentation model was implemented in one health care region of the Stockholm County Council the opinions which district nurses and nurses at the primary health care centres (PHCCs) had of nursing documentation were investigated. 164 nurses (94%) at all the 22 PHCCs within the region answered a questionnaire in October, 1995. The study showed that the nurses in general were dissatisfied with their own, as well as with their colleagues, nursing documentation. The lack of a common, patient-record model for nursing documentation was concidered the greatest obstacle, followed by lack of time and lack of knowledge. Most of the nurses believed that patient records which clearly included all parts of the nursing process would promote patient care. However, according to the nurses themselves, less than one-fifth of them recorded nursing history and nursing outcomes for all or most of their patients. One-third of the nurses reported that documented planned nursing interventions, about one-fourth nursing status and about half of them implemented nursing interventions for all or most of their patients. The nurses said that nursing diagnoses, goals and epicrises were rarely documented. There was no significant correlation between the nurses ages and their opinions of nursing documentation. Nurses who had completed their education after 1985 were more positive to further education in nursing documentation and to computerised patient records, and confirmed more than others that patient records which included the entire nursing process model would promote patient care. Nurses who worked only at PHCCs care. Nurses who worked only at PHCCs were more satisfied with their own documentation as well as with that at their centres and were more positive to computer support than district nurses. Nurses at PHCCs were less in favour of education in nursing documentation, compared with nurses working in home health care and child care. The nurses who were not satisfied with their own nursing documentation were not satisfied with their colleagues documentation either, but they were positive to further nursing education. More than others, they were of the opinion that better patient care follows from patient records which include the entire nursing process model. The study shows the need for education and continuous support aimed at nurses within the primary health care system regarding nursing documentation.

Predictive markers for humoral influenza vaccine response in patients with common variable immunodeficiency

Immunoglobulin (IgG) therapy has hitherto mainly been given as intramuscular injections or intravenous infusions. However, due to disadvantages using these methods, we have developed a method for rapid subcutaneous infusion of IgG which is well tolerated (no virus transmission and no severe adverse reactions), improves the health-related quality of life, is highly appreciated by patients and leads to reduced costs for the healthcare sector and the patients. Altogether, more than 60 000 subcutaneous IgG infusions have now been given to patients with primary and secondary antibody deficiencies. Our experience suggests that this form of therapy constitutes the current treatment of choice both for the clinician and the patient.