Viêm Màng Não Ái Toan
Viêm Màng Não Ái Toan
Viêm Màng Não Ái Toan
2
0893-8512/09/$08.00⫹0 doi:10.1128/CMR.00044-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
INTRODUCTION .......................................................................................................................................................323
The Eosinophils.......................................................................................................................................................323
ANGIOSTRONGYLIASIS .........................................................................................................................................323
The Parasite.............................................................................................................................................................323
History ......................................................................................................................................................................324
322
VOL. 22, 2009 EOSINOPHILIC MENINGOENCEPHALITIS 323
Treatment.................................................................................................................................................................337
PARAGONIMIASIS....................................................................................................................................................337
The Parasite.............................................................................................................................................................337
History ......................................................................................................................................................................337
Life Cycle and the CNS .........................................................................................................................................337
Epidemiology ...........................................................................................................................................................337
Disease......................................................................................................................................................................337
Diagnosis..................................................................................................................................................................338
Treatment.................................................................................................................................................................338
OTHER INFECTIOUS AGENTS LESS COMMONLY CAUSING EOSINOPHILIC
MENINGOENCEPHALITIS ................................................................................................................................338
Trichinellosis ...........................................................................................................................................................338
Hydatidosis ..............................................................................................................................................................338
Coenurosis ...............................................................................................................................................................339
Strongyloidiasis .......................................................................................................................................................339
Filariasis ..................................................................................................................................................................339
Myiasis .....................................................................................................................................................................339
severe cluster in Beijing of 160 cases (43, 171, 293). The out- ity of patients manifest persisting paresthesias, weakness, and
breaks detected in Thai workers in Kaohsiung, Taiwan, and in cognitive deficits, which may represent rare chronic forms of
U.S. travelers returning from a very brief stay in Jamaica high- the disease (238). Clinicians should consider angiostrongyliasis
light the importance of angiostrongyliasis as a risk for human when evaluating a patient with eosinophilic meningitis, even in
health. In both situations exposure to infection probably took regions outside its traditional geographic boundaries, espe-
place at leisure time, either when individuals ate raw mollusks cially when travelers or suspected imported food are involved
collected in ponds surrounding the factory in the case of the (144, 262).
Thai workers or during a regular meal including a green salad
in the case of the U.S. travelers (262, 281). With the exception Diagnosis
of Taiwan, where most patients are children, A. cantonensis
usually infects men in the third and fourth decades of life (127, Magnetic resonance imaging (MRI) examination of a pa-
230). tient with angiostrongyliasis often reveals multiple micronodu-
The main mode of infection is the consumption of raw snails, lar enhancements in brain tissues and linear enhancement in
reported by 51% in a study in Taiwan (127). Another source of the pia mater. Complete resolution of abnormal MRI findings
infection can be other mollusks, and paratenic hosts, such as typically occurs after 4 to 8 weeks (127, 136, 281). Micronod-
frogs, freshwater prawns, crabs, fish, and planaria. A less com- ules have also been detected in MRI imaging of lung paren-
TABLE 1. Frequency of clinical manifestations and evaluation of blood and CSF eosinophilia in four series of patients with
cerebral angiostrongyliasis
Parameter Result reported in reference:
Mean incubation period (range), in days 13 (6–20) 17 (2–34) 13 (2–45) NRa (2–18)
Eosinophilia
% of patients with CSF prevalence (ⱖ10%) 47 96 62 95
Avg initial no. in CSF (cells/mm3) 100 700 NR NR
% of patients with blood prevalence (criterion) 77 (ⱖ10) 73 (ⱖ10) 84 (ⱖ10) 90 (ⱖ3)
Avg initial no. in blood (cells/mm3) 1,990 3,000 NR NR
a
NR, not reported.
TABLE 2. References and websites with images of histological sections from parasites causing eosinophilic meningoencephalitis
Agent or infection Reference(s) and/or website
A. cantonensis 291
picasaweb.google.com/idintl/ParasitologyVolume2ForWeb02#5195514234701040466
Cysticercus 256
pro.corbis.com/images/42-18708066.jpg?size⫽67&uid⫽%7be46c3c48-e880-4b98-87d2-8fbdace4873d%7d
Toxocara spp. 74
www.dpd.cdc.gov/dpdx/HTML/Toxocariasis.htm
gsbs.utmb.edu/microbook/ch091.htm
Hydatidosis www.dpd.cdc.gov/dpdx/HTML/Echinococcosis.htm
www.pucrs.br/fabio/atlas/parasitologia
Coenurosis 130
www.scielo.br/scielo.php?script⫽sci_arttext&pid⫽S0103–84782008000400021&lng⫽e&nrm⫽iso&tlng⫽e
Filariasis www.dpd.cdc.gov/DPDX/HTML/ImageLibrary/Filariasis_il.htm
www.eyepathologist.com/disease.asp?IDNUM⫽345150
Myiasis www.dpd.cdc.gov/DPDx/html/ImageLibrary/M-R/Myiasis/body_Myiasis_il5.htm
since most of the data come from uncontrolled studies or The following combinations have been implemented: albenda-
clinical reports of a few patients (51, 127, 230, 281, 293). zole and thalidomide (42), mebendazole and interleukin 12
Combinations of anthelmintics with anti-inflammatory agents (85), and albendazole with extract from the Chinese medicinal
have been investigated in animal models with positive results. herb Artemisia capillaris (157). Evidently, the key issue in treat-
Crude L3 antigen ELISA (IgG) Serum (4 cutaneous ⫹ 10 CNS) Overall, 59; CNS, 100 Overall, 84; CNS, NR 273
Crude L3 antigen ELISA (IgG) Serum (46 cutaneous) 100 NR 77
Crude antigen Somatic antigen ELISA Serum 87 96 178
ES antigen ELISA 87 97
Crude antigen G. doloresi ELISA (IgG) Serum (299 cutaneous ⫹ 1 ocular) 93 98 79
24-kDa antigen WB Serum 100 100 206
(pI 8.5)
23- to 25-kDa antigen Two-dimensional PAGE Serum 83 100 301
(pI 8.3–8.5) and WB
Crude L3 antigen ELISA (IgG and isotypes) Serum (cutaneous) IgG1: 98 IgG2: 88 209
21-kDa antigen ELISA (IgG4) Serum (11 cutaneous; 2 ocular; 1 100 100 6
peritoneal)
24-kDa antigen ELISA (IgG4) Serum (11 cutaneous; 2 ocular; 1 93 93 6
peritoneal)
100- to 3-kDa antigen Dot blot Serum (10 cutaneous) 100 100 89
24-kDa antigen WB, isotypes Serum IgG, 91; IgG1, 66; IgG, 97; IgG1, 98; 161
isolated subarachnoid hemorrhage is not the usual presen- were evaluated for detection of antibodies in serum of patients
tation of gnathostomiasis, hemorrhagic lesions are common with cutaneous disease. Detection of antibodies in CSF was
and are a main factor in mortality. evaluated in only a very small number of patients with appar-
ent high sensitivity (273, 284). As the detection of antigen or
Diagnosis immune complexes is considered less reliable, the detection of
antibodies at the class or isotype level is a promising approach
A bloody and xanthochromic CSF is highly suggestive of (6, 195, 284). However, significant cross-reactivity has been
gnathostomiasis and is a particularly helpful criterion for dif- demonstrated in several antibody detection systems testing se-
ferentiating from meningitis caused by A. cantonensis (see rum samples from patients infected with A. cantonensis, hook-
above). Eosinophilia is not always present in peripheral blood worms, Strongyloides stercoralis, Trichuris trichiura, Capillaria
but is very common in the CSF. In two studies from Thailand philippinensis, Wuchereria bancrofti, and Opisthorchis viverrini
with large numbers (24 and 162) of patients (24, 231), CSF (89, 209).
eosinophilia (⬎10%) was detected in 74% and 100% of pa- Antigen detection methods have been used for L3 larva
tients, respectively. In the same studies, CSF eosinophilia
confirmation. A 24-kDa glycoprotein specific to L3 is a prom-
⬎30% was detected in 64% and 65% of patients. Protein levels
ising antigen for diagnosis, with sensitivities ranging from
were elevated in two-thirds of patients, and glucose levels were
100% in ELISA to 75% for immunoglobulin G4 (IgG4) in WB.
unchanged or only slightly reduced (24, 231).
The specificity of this method ranges from 100% in ELISA to
Upon MRI examination of the spine, lesions may appear
as diffuse or segmental enlargement, with or without post- 93 to 94% for IgG4 in ELISA or immunoblotting (6, 161, 206).
gadolinium linear enhancement. Hyperintense micronodu- There is also a 21-kDa antigen with 100% sensitivity and spec-
lar or fuzzy lesions on T2-weighted brain images, with or ificity in an IgG4 ELISA that deserves more extensive evalu-
without enhancement, can suggest intraparenchymatous or ation (6).
intraventricular hemorrhage (38, 237, 250, 251). Although
only a small number of reports with MRI examination are
currently available, the description of focal brain lesions or Treatment
segmental or nodular enlargements in the spine should be
For the treatment of cutaneous gnathostomiasis, both al-
considered an important aspect for differentiation from
bendazole and ivermectin are reported as effective thera-
angiostrongyliasis.
It is unusual to detect L3 larvae in the CSF. These larvae are pies, but no anthelmintic agent or corticosteroids have been
2.8 to 5.2 mm long and 0.3 to 0.8 mm wide, and, like adult formally evaluated for the treatment of CNS disease (150,
worms, their body surface is covered by spines. When biopsy or 151, 204). Alongside these curative therapies, radicular pain
necropsy specimens are examined, the presence of spines or and headache require supplemental symptomatic and sup-
hooks in regular rows, as well as the identification of the portive treatment. Though full recovery can be expected in
cephalic bulb, allows the definitive diagnosis of gnathostomia- most instances, the prognosis for neurological disease
sis (Table 2). caused by G. spinigerum is poor. Mortality with this infection
Serological techniques have evolved from the use of crude is in the range of 12 to 15%, and permanent sequelae, such
antigenic preparations to that of partially purified or single as paraplegia, radicular lesions, cranial nerve lesions, and
antigenic components (Table 4). Historically, most methods hemiparesis, remain in 23 to 46% of patients (231, 253).
330 GRAEFF-TEIXEIRA ET AL. CLIN. MICROBIOL. REV.
Epidemiology
Diagnosis
Although no gender preference has been suggested, the
disease appears to be more severe in women. There is a hy- Live and uncomplicated cysts are spherical lesions measur-
pothesis that female hormones exacerbate the outcome (101). ing approximately 1 cm. By computerized tomography (CT) or
Peak age incidence is found in middle-aged adults (267). MRI, it is possible to identify the presence of a small dot inside
Infection with T. solium and cysticercosis are probably more the cyst that corresponds to the invaginated scolex, or proto-
widespread than what is known from reports in the literature. scolex. When cysts degenerate, they are surrounded by edema
The countries with the largest prevalence of NCC are Mexico and a ring enhancement. Calcification may ensue both around
and India. Infections are also prevalent in other countries of and within the lesion at a final stage. Due to isodensity, intra-
Latin America, Africa, and Asia. ventricular cysts are seen only by MRI scans. CT is still the first
Cysticercosis is acquired by ingestion of eggs released with line of image examination, since it reveals the cysts and calci-
feces, not by ingestion of undercooked pork. A frequent mis- fications, a feature not well demonstrated by MRI. This makes
take in reports of clinical cases is to exclude the possibility of CT a crucial diagnostic tool for NCC.
NCC, due to underreporting of eating raw pork. Good sanita- The CSF of NCC patients shows mononuclear pleocytosis
tion and health education are key measures to ensure elimi- and eosinophilia. Cell counts rarely exceed 300 per mm3. Pro-
VOL. 22, 2009 EOSINOPHILIC MENINGOENCEPHALITIS 333
teins in CSF are elevated within the range of 50 to 300 mg/dl, The use of other recombinant antigens (54, 96) or synthetic
and glucose levels are usually normal (267). peptides (100), examination of isotypes such as IgG4 (55), the
Immunological diagnosis of cysticercosis has mainly been use of tertiary conformational alterations (227) or multie-
made with antibody detection by ELISA and WB. There is a pitope chimeric proteins (245) and other novel strategies may
long list of antigens that have been evaluated, in both crude further improve immunological detection methods.
and purified forms (Tables 5 and 6). WB with purified cystic- Nucleic acid detection by PCR was positive in the CSF of 29
ercus glycoprotein antigens is the current “gold standard” an- out of 30 patients with NCC (5). Identification of Taenia spe-
tibody detection assay, and three to five main components have cies is possible in feces and in tissues by restriction fragment
been evaluated as synthetic or recombinant peptides, with ex- length polymorphism analysis, base excision sequence scan-
ceptional performance in serology (134, 248, 282) (Tables 5 ning, thymine-based analysis, and multiplex PCR (305).
and 6). The use of these peptides to detect antibodies in the In 2000, a panel of experts convened in Peru and proposed
CSF is expected to reproduce what has been well demon- diagnostic criteria for NCC. The following criteria are now
strated in serum. Immunological tests are more successful with considered absolute: histological demonstration of the parasite
CSF samples, but results are dependent upon the activity of the from biopsy of a brain or spinal cord lesion (Table 2), cystic
infection. Inactive cysticerci are usually associated with very lesions showing the scolex on CT or MRI, and direct visual-
low reactivity (162, 192). Immunofluorescence and comple- ization of subretinal parasites by funduscopic examination. The
ment fixation (CFA) tests are much less sensitive and specific isolated presence of one absolute criterion or different combi-
than ELISA and WB, especially with use of purified antigens nations of major, minor, and epidemiologic criteria supports
(30). two degrees of diagnostic certainty: definitive or probable di-
TABLE 6. Antibody detection immunoassays for the diagnosis of cysticercosis in serum samplesa
Target Method Sensitivity (%) Specificity (%) Reference(s)
agnosis. For details, see the report of the consensus meeting caused by migrating larvae of the Toxocara species (15). In
(73). 1951, a larva was found for the first time in the brain of a
patient, and it was subsequently proven to be T. canis (14). In
Treatment 1958, Sprent gave the first detailed description of the life cycle
of T. canis (268).
The therapeutics of NCC varies according to the clinical
situation. Corticoids may be necessary with the inflammatory
Life Cycle and the CNS
clinical forms, such as meningitis and co-occurrence of NCC
with vasculitis. Corticoids are mandatory treatment for large Adult T. canis lives in the lumen of dog intestine and pro-
intraventricular cysts and encephalitis (236); the recommenda- duces eggs, which are eliminated in feces. Eggs are thick-
tion is dexamethasone, 4 to 30 mg/day, or prednisolone, 1 walled and can remain in the environment for a long period of
mg/kg/day, as long as necessary. Adequate seizure control may time before they embryonate and become infective. When the
require antiepileptic drugs. Ventricular shunting is required eggs are ingested by dogs, L2 larvae are liberated and pene-
for persistent hydrocephalus. Surgical removal is necessary to trate the intestinal wall. Larvae travel through the circulatory
relieve life-threatening giant and/or racemose cysts, or cysts system to the liver and lungs. From the lungs, they crawl up the
producing significant compression syndromes. Advances in di- bronchial tree and re-enter the digestive system, where they
TOXOCARIASIS Epidemiology
The Parasite Toxocariasis is a cosmopolitan parasitic infection. Sero-
The superfamily Ascaridoidea includes cylindrical worm prevalence is highly variable, but children are considered the
parasites of vertebrates, whose larvae migrate in host tissues on most likely exposed population, due to outdoor activities and
their way to becoming adults inside the gut lumen. Ascaris frequent contact with dogs and cats (75, 97). Interestingly,
lumbricoides is a well-known enteroparasite of humans. Ascaris there is not a clear association of human toxocariasis with the
and Toxocara species have very similar morphologies, habitats, presence of pets in the house, probably because contaminated
and life cycles. In the genus Toxocara, there are the ascarids of outdoor areas are the main source of infection (45). Infective
dogs (T. canis) and cats (T. cati), which measure between 7.5 Toxocara eggs can remain viable for months or years in the
and 12.5 cm and exhibit characteristic cervical alae. Among environment, which increases the chance for their dissemina-
felids, parasitic larvae of T. cati and Toxascaris leonina do not tion by paratenic hosts or by rain and wind (75). The contam-
have the same migration behavior and preference for nervous ination of drinking water supplies can lead to waterborne out-
tissue shown by T. canis, which may explain the prominence of breaks (16).
T. canis as a cause of CNS infections.
Disease
History
Human toxocariasis manifests as either VLM or ocular larva
Toxocara specimens were initially described by Werner in migrans syndrome. Ocular infection is considered a compart-
1782, but the genus was not established until 1905 by Stiles mentalized infection, and patients may present isolated ocular
(302). Human infection was first documented in the 1950s, larva migrans syndrome.
when Wilder discovered a larval nematode within a retinal CNS infection is rare, and pure meningitis is also rare. Re-
granuloma of a child (298). Around the same time, Beaver and ports of not more than 50 patients with neurotoxocariasis can
colleagues described what today is called “visceral larva mi- be found in the literature, and in many reports the diagnosis
grans” (VLM), a severe multisystem disease with eosinophilia was only presumptive. For example, diagnoses have been made
VOL. 22, 2009 EOSINOPHILIC MENINGOENCEPHALITIS 335
based on the presence of neurological dysfunctions and eosino- tools for toxocariasis. These tests have a high sensitivity and
Mortality occurs primarily in children less than 6 years old (90, a very low number is required to produce infection and disease.
196). Experimental toxocariasis infections in mice have shown Male children are prevalent among reported cases of B. pro-
several alterations in brain lesion biomarkers that suggest pro- cyonis infection, which has been attributed to their more fre-
gression toward chronic neurodegenerative disorders (168). quent engagement in exploratory outdoor activities (266).
This is yet another justification for multicentric studies of treat- However, changes in the behavior of both raccoons and girls
ment evaluation and long-term follow-up of toxocariasis infec- may alter this observed prevalence, so this alternate etiological
tions. pairing should not be ignored. Domestic dogs and puppies
have been found to be infected with B. procyonis. Infected pets
BAYLISASCARIASIS represent a possible great risk of infection, particularly for
children (266).
The Parasite
The superfamily Ascaridoidea includes large cylindrical Disease
worms that live within the lumen of the intestines. These ani-
mals produce thick-walled eggs that spend some time in the Infection with B. procyonis is known as baylisascariasis. The
environment before becoming infective. One of the most prev- systemic erratic migration of B. procyonis larvae may be asymp-
ninges in the first exudative stage, when eosinophils may be cluster for diagnosis is the combination of swelling facial le-
present. Meningitis is secondary to parenchymal lesions, which sions on the lids or the lips, an acute fever, and myalgias.
progress chronically to granulomatous and fibrotic lesions Trichinella infection is most commonly acquired by con-
(211, 212). Eggs may be found in histological sections at the sumption of inadequately cooked pork from domestic pigs.
border of necrotic nodules (141). Undercooked meat from walrus, bear, cougar, and wild boar
can also be a source of trichinellosis (173, 185). The main
Diagnosis diagnostic criterion for trichinellosis is a history of eating un-
dercooked meat, especially pork products, together with the
CNS paragonimiasis can be difficult to detect. CSF eosino- clinical detection of blood eosinophilia. CSF is normal in most
philia is not present in all paragonimiasis patients. Thus, dif- patients (173). Antibodies are detected by serology, with either
ferentiation from tuberculous meningitis is mandatory. Other ELISA or WB (308). The study of trichinellosis in animals has
bacterial etiologies should also be considered, since CSF glu- led to some well-defined and cloned molecules that may im-
cose levels are typically low (212). Cerebral involvement may prove antibody detection methods in humans (29, 200). At the
include chronic silent lesions, detectable with image examina- onset of the clinical course, weak humoral reactivity may lead
tion as multiple conglomerated iso-intensity or low-signal-in- to false-negative results in immunological tests (199). Multi-
tensity round nodules, with peripheral rim enhancement (39, plex PCR can detect Trichinella DNA and differentiate it from
nique (puncture, aspiration of fluid, injection of 15% saline of thiabendazole or other anthelmintic therapeutics is not es-
solution, and reaspiration) and complete surgical resection of tablished, and surgical resection may be necessary (104).
the cyst (285).
Fungal Infections
Coenurosis Coccidioidomycosis is the most prevalent fungal cause of
Coenurosis is infection with larval stages of Taenia multiceps, eosinophilic meningitis. It has a well-defined geographic dis-
a cestode that is parasitic in canids. Cysts are larger than tribution; it is endemic to desert areas in the southwestern
cysticerci (4 to 5 cm in diameter) and have multiple invagi- United States and northwestern Mexico. Besides Coccidioides
nated scolices (Table 2). CNS disease following Taenia multi- immitis, Coccidioides posadasii has been described as a new
ceps infection is very rare and manifests as increased intracra- species causing coccidioidomycosis (98). First, inhalation of
nial pressure. CSF eosinophilia is not the rule (19, 130). conidia causes a systemic mycosis. The first stage of multipli-
cation takes place in the lungs and is followed by dissemina-
tion, which does not necessarily result in disseminated disease.
Strongyloidiasis According to records from areas of endemicity in the United
States, roughly 30% of patients with CNS infections caused by
TABLE 8. Most common causes of eosinophilic meningoencephalitis, with percentages of the helminthiasis cases with CSF eosinophiliaa
Parasite’s usual habitat Maximum % of patients
Helminthiasis Total no. of infected humans Reference(s)
in humans with CSF eosinophilia
Behçet’s disease (115), and neurosarcoidosis (254) are occa- polypeptide), should be included in the diagnostic workup
TABLE 9. Conditions less commonly associated with This concept is unfortunately not clear to many researchers
CSF eosinophilia and physicians, as demonstrated by equivocal statements
Frequency of that a given serological method was “able to specifically
Cause of eosinophilia Reference(s)
association confirm a presumptive diagnosis.” Detection of antibodies
Nematode infections (roundworms) will never be confirmatory, but it may certainly give strong
Trichinellosis Rare 105, 173 support to the etiological hypothesis. An active search for
Strongyloidiasis Exceptionally rare 143
Filariasis Exceptionally rare 80, 288 useful panels of well-defined and purified antigens, prefer-
ably recombinant molecules, is urgently needed. Also urgent
Cestode infections (tapeworms) is the need for standardization of nucleic acid detection
Hydatidosis (surgical Rare 26
complication) methods that can be applied to CSF samples, for better
Coenurosis Exceptionally rare 19, 130 detection of meningoencephalitis. There is an ongoing effort
Arthropod infections to establish a worldwide multicenter laboratory network for
Myiasis Exceptionally rare 104 evaluation and quality control of diagnostic methods for
helminthic causes of eosinophilic meningoencephalitis. Phy-
Fungal infections
Coccidioidomycosis 70% of patients 235 sicians should contact local public health services for up-
Cryptococcosis Exceptionally rare 114 dated information on sources for diagnostic tests.
recognized by IgG antibodies in cerebrospinal fluid and serum paired sam- 38. Chandenier, J., J. Husson, S. Canaple, C. Gondry-Jouet, P. Dekumyoy, M.
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Carlos Graeff-Teixeira (M.D., Ph.D.) grad- Ana Cristina Arámburu da Silva (M.Sc.,
uated at the Medical School, University of Ph.D.) graduated in Clinical Analysis and
Passo Fundo, and was a clinical fellow, In- Biochemistry, at the Pharmacy School, Fed-
ternal Medicine, at Hospital das Clinicas, eral University of Rio Grande do Sul, Porto
Federal University of Rio Grande do Sul, Alegre, Brazil, and got her M.Sc. (1999) and
Brazil (1980 to 1982). He got an M.Sc. de- Ph.D. (2007) in Zoology at the Faculdade
gree on Infectious Diseases at Universidade de Biociencias, PUCRS University, Porto
Federal do Rio de Janeiro (1986) and Ph.D. Alegre, Brazil. She was a postdoctoral re-
in Tropical Medicine at Instituto Oswaldo search fellow at the Division of Parasitic
Cruz, Fiocruz, Rio de Janeiro, Brazil (1991). Diseases, National Center for Zoonotic,
He was also a research fellow at the Na- Vector Borne and Enteric Diseases, Centers
tional Institute for Medical Research, London, United Kingdom for Disease Control and Prevention, Atlanta, GA (2008). She is cur-
(1990), at R. M. E. Parkhouse’s laboratory. As well, he is a past rently Associate Professor of Parasitology, Faculdade de Biociencias,
president of the Brazilian Society for Parasitology (2000 to 2004). and head of the Molecular Diagnosis Laboratory, Instituto de Pesqui-
Since 1992, he has been Professor of Parasitology at the Ecology and sas Biomedicas, PUCRS, Porto Alegre, Brazil. She works with molec-
Diversity Department, Faculdade de Biociencias, Pontifı́ca Univer- ular biology and has made contributions for the development of nu-
sidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. cleic acid detection methods for both A. cantonensis and A.
He is also head of the Molecular Parasitology Laboratory at the In- costaricensis infections.
stituto de Pesquisas Biomedicas at the same university and a scientific
advisor for the Ministry of Health, Brazil. He has been studying the
disease diagnoses and epidemiologies of Angiostrongylus costaricensis Continued next page
since 1978 and A. cantonensis since 2000.
348 GRAEFF-TEIXEIRA ET AL. CLIN. MICROBIOL. REV.