1289

pentamidine in 6 ml water through a modified system 22 nebuliser, with a ’CR60 Compressor’ [Medic-Aid] delivering air at 101/min and terbutaline 2-5 mg in 3 ml saline immediately beforehand).3 Cough during administration occurred in 5 (3 1%) patients. The median duration of prophylaxis was 13 months (range 1-36). Four (25%) pneumothoraces developed overall-two (patients A and B) in 118 patients receiving primary prophylaxis and two (patients C and D) in 44 patients receiving secondary prophylaxis. Patient A had undergone pleurectomy for recurrent spontaneous pneumothoraces 8 years before introduction of pentamidine prophylaxis, and had not had any pneumothoraces in the intervening years. Bronchoalveolar lavage at the time of pneumothorax failed to identify P carinii. Patient B had PCP confirmed at bronchoalveolar lavage. A presumptive diagnosis of PCP was made in patient C who had a pneumothorax in the terminal stages of HIV dementia. In patient D, bronchoalveolar lavage did not reveal P carinii. The frequency of pneumothoraces in our series (2-5%) is much lower than that found in the 13 haemophiliacs (30-8%) reported by Cuthbert et al. This difference may reflect fewer failures of prophylaxis associated with alveolar targeting of our nebuliser system. S. B. SQUIRE E. K. BAGDADES CHRISTINE A. LEE MARGARET A. JOHNSON

Department of Thoracic Medicine and Haemophilia Centre, Royal Free Hospital, London NW3 2QG, UK

GS, Ward DJ, Pierce PF. Spontaneous pneumothorax in patients with acquired immunodeficiency syndrome treated with prophylactic aerosolised pentamidine. Arch Intern Med 1990; 150: 2167-68. 2. Simonds AK, Newman SP, Johnson MA, Talaee N, Lee CA, Clarke SW. Alveolar targeting of aerosol pentamidine. Am Rev Respir Dis 1990; 141: 827-29. 3. Simonds AK, Newman SP, Johnson MA, Talaee N, Lee CA, Clarke SW. Simple nebuliser modification to enhance alveolar deposition of pentamidine. Lancet 1989;

times greater than the responses obtained by oral immunisation with soluble antigen. The second project concerns local vaginal immunisation. Vaginal immunisation with an HIV gp120 peptide in a novel antigen delivery system resulted in the induction of both local and systemic antibody responses. With colleagues I am assessing if the antibodies have neutralising activity against HIV. Subject to the availability of both antigens and suitable animal models, I hope to extend these studies to establish the ability of both oral and vaginal immunisation, or combined immunisation schedules, to induce protection against local genital viral challenge. The development of suitable animal models of HIV sexual transmission is essential if the role of local IgA in protecting against sexual transmission is to be determined. The development of such models should become a research priority. Department of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK

1. Mestecky J, McGhee JR. Immunoglobulin A (IgA): molecular and cellular interactions involved in IgA biosynthesis and immune response. Adv Immunol 1987; 40: 153-255. 2. Besredka A. Local immunization. Baltimore: Williams and Wilkins, 1927. 3. Mestecky J, McGhee JR. Oral immunization: past and present. Curr Top Microbial Immunol 1989; 146: 3-12. 4. Bergman K-C, Waldman RH. Stimulation of secretory antibody following oral administration of antigen. Rev Infect Dis 1988; 10: 939-50. 5. World Health Organisation. Potential use of live viral and bacterial vectors for

1 Newsome

ii: 953.

HIV and mucosal

immunity

SIR,—Iagree with Dr Forrest (April 6, p 835) that "it is time for HIV vaccine research to focus on stimulating protective immunity at the sites of most common exposure". Although the important protective functions of secretory IgA at mucosal sites have been well de6ned/ the potential role of oral immunisation in inducing protective immunity at mucosal sites has remained underappreciated. Oral immunisation was introduced in the early part of the twentieth century to protect against intestinal infections,2 though the history of oral immunisation dates back over several centuries.3Such immunisation with a wide range of bacterial and viral antigens has proved the most effective way to induce secretory immune responses both in the gut and at other mucosal sites 4 Nevertheless, despite the obvious advantages of ease of administration and better patient compliance, oral immunisation has remained unpopular, mainly because of the large amounts of antigens generally required compared with parenteral immunisation.

However, developments in the design and preparation of novel antigen delivery system, both replicating; (live) and non-

replicatingb (dead), have raised exciting possibilities. Through the exploitation of the immunisation may

common

mucosal immune system, oral

prove an acceptable method of inducing responses at all mucosal sites, although findings in

secretory IgA

small animals indicate that locally protective vaginal antiviral IgA responses may be most efficiently elicited by local immunisation.’ Two research projects looking into the role of local antibodies in the prevention of genital infection by HIV are underway in Nottingham. One is concerned with the preparation of biodegradable microparticles as antigen delivery systems for oral

immunisation.

The microparticles stimulate the mucosal immune system because they are taken up across the intestine through

Peyer’s patches.8 Investigations

undertaken with Prof S. J. Guys’ Hospital, London, have confirmed that microparticles can induce secretory IgA responses to an entrapped antigen, at a remote mucosal site, after oral immunisation (unpublished). The mean salivary IgA antibody responses to the microparticle entrapped antigen were, at best, almost two hundred

Challacombe

at

D. T. O’HAGAN

vaccines.

6.

Vaccine 1990; 8: 425-37.

O’Hagan DT. Novel non-replicating antigen delivery systems.

Curr

Opin Infect Dis

1990; 3: 393-401. 7.

McDermott MR, Brais LJ, Evelegh MJ. Mucosal and systemic antiviral antibodies in mice inoculated intravaginally with herpes simplex virus type 2. J Gen Virol 1990;

8.

O’Hagan DT. Intestinal translocation of particulates: implications antigen delivery. Adv Drug Deliv Rev 1990; 5: 265-85.

71: 1497-504. for

drug and

Disposable syringes and needles for Romania SIR,-In The Lancet of Dec 22/29, 1990, we presented data on the spread of bloodbome diseases among orphans in hospital or in three orphanages in the Pascani region of north-eastern Romania. We blamed the "lack of disposable syringes, needles, and medical supplies and a policy of transfusion of untested blood". Dr Mihaescu and Dr Veres, writing from Lasi, Romania (March 9, p 615) warn that the widespread supply of disposable needles and syringes could result in access to large numbers of used, uncleaned needles and syringes, to increased use of parenteral treatment, and to the loss of sterilisation skills. This concern is real enough in Romania, and the supply of disposable syringes and needles might well, if isolated from other assistance, leave our Romanian colleagues "weaving between sadness and despair", which is how your correspondents put it. When we arrived in Pascani last summer we found hardly any disposable needles or syringes. Nearly all the sterilisers in the hospital and clinics were defective and people were trying to sterilise used disposable syringes and needles in rusty boxes with boiling water. This was why we decided to organise a supply of disposables. Aware of the difficulties Mihaescu and Veres mention we delivered safe disposal boxes (Baxter) to Pascani and organised a supply of sterile material in exchange for used syringes and needles. The used ones were taken to Switzerland because correct disposal is not available in Pascani. Another important aspect of preventing the transmission of bloodbome diseases is education, and nurses and doctors from Switzerland have been present in the region ever since our long-term support project began. Romanian doctors and nurses have been given the opportunity to stay in a Swiss hospital. A booklet on the transmission of HIV and preventive strategies, in Romanian, was distributed to health care staff. Enteral treatments are strongly promoted and the formulations needed for this, which were lacking completely when we arrived, are delivered monthly. We realised that people’s behaviour and the desperate social infrastructure are important deficiencies in Romania. It is crucial therefore, that all support be carefully planned and that the supply of materials be combined with the continued presence of experienced personnel and with education. Having been involved in

HIV and mucosal immunity.

1289 pentamidine in 6 ml water through a modified system 22 nebuliser, with a ’CR60 Compressor’ [Medic-Aid] delivering air at 101/min and terbutaline...
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