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Severe Serum Sickness Following Pneumococcal Vaccination in an AIDS Patient

Posted on: Wednesday, 29 March 2006, 09:01 CST

By Hengge, Ulrich R; Scharf, Ruediger E; Kroon, Frank P; Pfeffer, Klaus

Streptococcus pneumoniae is the leading cause of invasive bacterial pneumonia in HIV infection, especially when CD4 cell counts are below 200cells/L. While the clinical efficacy of the available pneumococcal vaccines is undisputed in immunocompetent individuals, their benefit in immunocompromised patients is largely unknown.1 A large phase-III study using the 23-valent pneumococcal vaccine in HIV-1-infected Ugandans has proven ineffective in a six- year follow-up to prevent invasive pneumococcal pneumonia.2 The pneumococcal vaccines have been recommended in the USA on the basis of limited immunogenicity data. However, a recent Cochrane report has not shown efficacy among vaccinated HIV-1-infected adults.1

The currently available 7-valent conjugate and 23-valent pneumococcal vaccines contain purified capsular polysaccharide antigens (25 g of each) of S. pneumoniae representing 85-90% of the serotypes that cause invasive pneumococcal infections in the USA. Generally, pneumococcal vaccination is recommended for immunocompromised individuals with above 200/L CD4-positive lymphocytes, according to the 2002 guidelines of the US Public Health Service and the Infectious Diseases Society of America.2 After vaccination, an antigen-specific antibody response develops within 2-3 weeks in at least 80% of healthy young adults.1 In HIV patients, especially in those with CD4-positive lymphocyte concentrations of less than 500/L, antibody responses to the pneumococcal vaccine are diminished or absent in at least 50%.1

Recently, a post-licensure safety surveillance for the 7-valent pneumococcal conjugate vaccine (Prevnar, Wyeth, PA) has been published.3 This vaccine adverse event reporting system (VAERS) is a national passive surveillance database. Common adverse events among the 4154 reports included injection site reactions, fever, rashes, irritability, drowsiness, restless sleep, decreased appetite, vomiting, and diarrhoea in up to 50% of vaccinated children.3 Serious events were described in 14.6% of reports, including 393 seizures and 117 deaths, which were not considered to be directly related to vaccination.3 The kinetics and avidity of antibodies evoked by the heptavalent vaccine have also recently been studied.3

We report on a 66-year-old AIDS patient (cerebral toxoplasmosis in 1992) with 81/L CD4 cells (CD4/CD8 ratio: 0.1; viral load: 18,400/ mL), who was vaccinated with 0.5 mL of the Pneumovax vaccine (Aventis Pasteur MSD, Leimen, Germany) in the left deltoid muscle. The patient had type II diabetes, cardiac insufficiency and hypertension, which was controlled with ramipril and telmisartan. His antiretroviral therapy (abacavir, didanosin, TMC-114 and ritonavir/lopinavir) had caused severe lipodystrophy and hypertriglyceridaemia. Genotypic resistance testing revealed reduced sensitivity to all currently licensed HIV medications.

Nine days after vaccination, the patient developed septic temperatures up to 40.8C, somnolence, severe general malaise, and lower back muscle pain. On admission, his C-reactive protein (CRP) was 18.3mg/dL; the WBC count was 4.4 1000/L with 25.1% lymphocytes. Two days after admission, the relative lymphocyte count increased to 51.7. The dynamics of the CD4 cell count and viral load are depicted in Figure 1. Importantly, circulating immune complexes were significantly elevated to 141 mg/mL. Other causes of somnolence such as cerebrovascular, metabolic (e.g. hyperglycaemia) or infectious origin were excluded. On day 2 of admission, the patient's lipase increased to 565 U/L and he developed proteinuria and microhaematuria at a creatinine of 1.4mg/dL, being consistent with incipient pancreatitis and glomerulonephritis, respectively. All body fluid cultures were negative for bacteria and fungi. Upon treatment with intravenous phosphate-buffered solution and prednisolone (50 mg for 5 days), his condition improved gradually, with a similar, yet less severe, episode occurring two weeks later. Five weeks following the vaccination, we observed regular antibody titres against pneumococcal polysaccharides 3 (37U/mL), 15 (137U/ mL) and 18C (192U/mL), while no antibody titres against all other strains were induced.

This case report of a severe serum sickness-type immune reaction and insufficient response to the 23-valent pneumococcal polysaccharide vaccine in an advanced AIDS patient showed transient, yet massive immunological and virological activation and severe general symptoms. Serum sickness is a rare but potentially life- threatening adverse event. It is a type-III immune reaction and may present with arthralgias, myalgias and glomerulonephritis from the deposition of immune complexes.

Serum sickness has not been previously reported upon pneumococcal vaccination in advanced HIV patients receiving the 7- or 23-valent pneumococcal vaccine. Neither massive increases in HIV load nor transient augmentation of CD4 lymphocytes have been described during pneumococcal vaccination.

Figure 1 Dynamics of CD4 lymphocyte counts (absolute and relative) and HIV viral load over the course of 21 days

Given the unproven benefit of pneumococcal vaccination in advanced HIV patients (CD4 lymphocytes <500/L and the adverse event profile,3 this report should caution physicians to balance the risk and questionable benefit of pneumococcal vaccination in advanced HIV patients. Given this serious adverse event, we strongly encourage caregivers to counsel patients, prior to vaccination, in contrast to a previous report.4 This report and the lack of efficacy data in the literature support the contention that pneumococcal vaccination guidelines in HIV-infected individuals need to be reassessed. It may be more cost-effective to favour strategies that improve adherence to antiretroviral therapy as this has unequivocally been shown to reduce the incidence of pneumococcal disease.1,5 Additional safety and efficacy studies should address patients with symptomatic HIV disease as they seem to be at higher risk for adverse events to pneumoccoccal vaccinogens.

References

1 Dear K, Holden J, Andrews R, Tatham D. Vaccines for preventing pneumococcal infection in adults. Cochrane Database Syst Rev 2003;4:CD000422

2 Masur H, Kaplan JE, Holmes KK, US Public Health Service; Infectious Diseases Society of America. Guidelines for preventing opportunistic infections among HIV-infected persons - 2002. Recommendations of the US Public Health Service and the Infectious Diseases Society of America. Ann Intern Med 2002;137:435-78

3 Wise RP, Iskander J, Pratt RD, et al. Postlicensure safety surveillance for 7-valent pneumococcal conjugate vaccine. JAMA 2004;292:1702-10

4 Ekstrom N, Ahman H, Verho J, et al. Kinetics and avidity of antibodies evoked by heptavalent pneumococcal conjugate vaccines PncCRM and PncOMPC in the Finnish Otitis Media Vaccine Trial. Infect Immun 2005;73:369-77

5 Watera C, Nakiyingi J, Miiro G, et al. 23-valent pneumococcal polysaccharide vaccine in HIV-infected Ugandan adults: 6-year follow- up of a clinical trial cohort. AIDS 2004;18:1210-13

Ulrich R Hengge1, Ruediger E Scharf2, Frank P Kroon3 and Klaus Pfeffer4

1 Department of Dermatology, University of Duesseldorf, Moorenstrasse 5, D-40225 Duesseldorf; 2 Institute of Hemostasis and Transfusion Medicine, University of Duesseldorf, Germany; 3 Department of Infectious Diseases, Leiden University Medical Center, Netherlands; 4 Institute of Virology, University of Duesseldorf, Germany

Correspondence to: Ulrich R Hengge

Email: ulrich.hengge@uni-duesseldorf.de

Copyright Royal Society of Medicine Press Ltd. Mar 2006

Source: International Journal of STD & AIDS

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