impaginato piccolo - Società Italiana di Parassitologia (SoIPa)
impaginato piccolo - Società Italiana di Parassitologia (SoIPa)
impaginato piccolo - Società Italiana di Parassitologia (SoIPa)
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<strong>Parassitologia</strong> 50: 45-50, 2008<br />
Clinical and Diagnostic Management of Toxoplasmosis in the<br />
Immunocompromised Patient<br />
C. Contini<br />
Section of Infectious Diseases, Department of Clinical and Experimental Me<strong>di</strong>cine, University of Ferrara, via Fossato <strong>di</strong><br />
Mortara 23, 44100 Ferrara, Italy<br />
Abstract. With the advent of the highly active antiretroviral therapy (HAART), the natural course of HIV infection<br />
has markedly changed and opportunistic infections inclu<strong>di</strong>ng toxoplasmosis have declined and mo<strong>di</strong>fied<br />
in presentation, outcome and incidence. However, TE is a major cause of morbi<strong>di</strong>ty and mortality especially<br />
in resource-poor settings but also a common neurological complication in some countries despite the<br />
availability of HAART and effective prophylaxis. In most cases toxoplasmosis occurs in brain and toxoplasmic<br />
encephalitis (TE) is the most common presentation of toxoplasmosis in immunocompromised patients<br />
with or without AIDS. The need of a definitive <strong>di</strong>agnosis is substantial because other brain <strong>di</strong>seases could<br />
share similar fin<strong>di</strong>ngs. Rapid and specific <strong>di</strong>agnosis is thus crucial as early treatment may improve the clinical<br />
outcome. Classical serological <strong>di</strong>agnosis is often inconclusive as immunodeficient in<strong>di</strong>viduals fail to produce<br />
significant titres of specific antibo<strong>di</strong>es. Polymerase chain reaction (PCR) has a high <strong>di</strong>agnostic value<br />
in the acute <strong>di</strong>sease, but like many ‘in-house’ PCR assays, suffers from lack of standar<strong>di</strong>zation and variable<br />
performance accor<strong>di</strong>ng to the laboratory. Molecular <strong>di</strong>agnosis of toxoplasmosis can be improved by performing<br />
real-time PCR protocols. This article summarises the clinical manifestations, <strong>di</strong>agnostic procedures<br />
and management strategies for this con<strong>di</strong>tion.<br />
Key words: toxoplasmosis, immunocompromised patients, AIDS, transplantation<br />
Introduction and background<br />
Toxoplasma gon<strong>di</strong>i infects up to 80% of some<br />
European populations and 20% of people in the United<br />
States (Hall S et al., 2001). Normally, infection is generally<br />
benign as immune system keeps the parasite in<br />
check and parasitaemia is self-limited resulting in an<br />
asymptomatic clinical form in most cases. In developing<br />
foetus and in immunocompromised in<strong>di</strong>viduals<br />
especially those with deficient cellular immunity, it can<br />
cause significant morbi<strong>di</strong>ty and mortality.<br />
The first reports of T. gon<strong>di</strong>i in immunocompromised<br />
patients involved persons with leukaemia and myeloma<br />
and cerebral toxoplasmosis was recognized early as a<br />
particular problem. With the advancements made in<br />
transplantation of <strong>di</strong>fferent organs, especially of the<br />
heart and bone marrow (BMT), allogeneic haematopoietic<br />
stem cell transplants patients (HSCT) and, less<br />
often, after kidney transplants, toxoplasmosis in these<br />
subjects has become a well-recognized and serious clinical<br />
problem (Slavin MA et al., 1994, Martino R et al.,<br />
2005). The frequency of parasitic infections as complications<br />
of organ transplantation is unknown; however,<br />
these are much less prevalent than bacterial and viral<br />
infections. Only 5% of human pathogenic parasites<br />
Correspondence: Prof. Carlo Contini<br />
MD Section of Infectious Diseases, Department of Clinical and<br />
Experimental Me<strong>di</strong>cine, University of Ferrara, via Fossato <strong>di</strong><br />
Mortara, 23, 44100 Ferrara, Italy.<br />
Tel: +39 532 455490; Fax: +39 532 455495<br />
e-mail: cnc@unife.it<br />
have been reported to cause significant illness in heart<br />
transplant recipients (Montoya JG et al., 2001).<br />
With the advent of human immunodeficiency virus<br />
(HIV) pandemic, toxoplasmic encephalitis (TE) has<br />
become one of the most common cerebral opportunistic<br />
infection complicating the course of AIDS, often fatal,<br />
if untreated (Luft JB et al., 1993; Richards F et al., 1995<br />
) and the most frequent cause of focal intracerebral<br />
lesions in this group. TE is also the most common presentation<br />
of toxoplasmosis in immunocompromised<br />
patients other than AIDS (Israelski DM et al., 1993).<br />
Although the epidemiology of the central nervous system<br />
(CNS) opportunistic <strong>di</strong>seases has changed after the<br />
introduction of the highly active antiretroviral therapy<br />
(HAART), TE is still a common neurological complication<br />
in AIDS patients from Brazil, despite the availability<br />
of HAART and effective prophylaxis (Vidal JE et al.,<br />
2005).<br />
The peak incidence of TE is highest among patients<br />
between 25 and 35 years old, whereas the incidence is<br />
<strong>di</strong>rectly proportional to the prevalence of latent<br />
Toxoplasma infection which increases with age<br />
(Holliman RE et al., 1990). Differences in genotypes of<br />
T. gon<strong>di</strong>i specific strain, races and ethnicities and the<br />
mode of transmission seem also to account in influencing<br />
the occurrence of TE (Sarciron ME et al., 2000;<br />
Khan A et al., 2005).<br />
Cellular immunity is one of the main mechanisms of<br />
defence in the control of toxoplasmosis. The variety of<br />
immune system defects found in in<strong>di</strong>viduals with<br />
AIDS, such as CD4 + T lymphocyte deficiency, reduced<br />
activity of cytotoxic T and NK cells, and the low production<br />
of immunoregulatory lymphokines such as