Herpes zoster-associated acute urinary retention in immunocompetent patient

Herpes zoster-associated urinary retention is an uncommon event related to virus infection of the S2-S4 dermatome. The possible major reasons are ipsilateral hemicystitis, neuritis-induced or myelitis-associated virus infection. We report a case of a 65-year-old immunocompetent female patient who presented an acute urinary retention after four days under treatment with valacyclovir for gluteal herpes zoster. The patient had to use a vesical catheter, was treated with antibiotics and corticosteroids and fully recovered after eight weeks.

Clinical and laboratory description of a series of cases of acute viral myositis

Describe the clinical and laboratory profile, follow-up, and outcome of a series of cases of acute viral myositis. A retrospective analysis of suspected cases under observation in the emergency department was performed, including outpatient follow-up with the recording of respiratory infection and musculoskeletal symptoms, measurement of muscle enzymes, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), transaminases (AST and ALT), blood count, C-reactive protein, and erythrocyte sedimentation rate in the acute phase and during follow-up until normalization. Between 2000 and 2009, 42 suspected cases were identified and 35 (27 boys) were included. The median age was 7 years and the diagnosis was reported in 89% in the first emergency visit. The observed respiratory symptoms were cough (31%), rhinorrhea (23%), and fever (63%), with a mean duration of 4.3 days. Musculoskeletal symptoms were localized pain in the calves (80%), limited ambulation (57%), gait abnormality (40%), and muscle weakness in the lower limbs (71%), with a mean duration of 3.6 days. There was significant increase in CPK enzymes (5507±9180U/L), LDH (827±598U/L), and AST (199±245U/L), with a tendency to leukopenia (4590±1420) leukocytes/mm(3). The complete recovery of laboratory parameters was observed in 30 days (median), and laboratory and clinical recurrence was documented in one case after 10 months. Typical symptoms with increased muscle enzymes after diagnosis of influenza and self-limited course of the disease were the clues to the diagnosis. The increase in muscle enzymes indicate transient myotropic activity related to seasonal influenza, which should be considered, regardless of the viral identification, possibly associated with influenza virus or other respiratory viruses.

Experimental infection of suckling mice by subcutaneous inoculation with Oropouche virus

Oropouche virus, of the family Bunyaviridae, genus Orthobunyavirus, serogroup Simbu, is an important causative agent of arboviral febrile illness in Brazil. An estimated 500,000 cases of Oropouche fever have occurred in Brazil in the last 30 years, with recorded cases also in Panama, Peru, Suriname and Trinidad. We have developed an experimental model of Oropouche virus infection in neonatal BALB/c mouse by subcutaneous inoculation. The vast majority of infected animals developed disease on the 5th day post infection, characterized mainly by lethargy and paralysis, progressing to death within 10 days. Viral replication was documented in brain cells by in situ hybridization, immunohistochemistry and virus titration. Multi-step immunohistochemistry indicated neurons as the main target cells of OROV infection. Histopathology revealed glial reaction and astrocyte activation in the brain and spinal cord, with neuronal apoptosis. Spleen hyperplasia and mild meningitis were also found, without viable virus detected in liver and spleen. This is the first report of an experimental mouse model of OROV infection, with severe involvement of the central nervous system, and should become useful in pathogenesis studies, as well as in preclinical testing of therapeutic interventions for this emerging pathogen. (c) 2012 Elsevier B.V. All rights reserved.

Prevalence of hepatitis B virus infection and carriage after nineteen years of vaccination program in the Western Brazilian Amazon

Introduction: Reductions in the prevalence of hepatitis B virus (HBV) infection and carriage, decreases in liver cancer incidence, and changes in patterns of liver dysfunctions are described after hepatitis B vaccination. Methods: We conducted a population-based seroprevalence study aimed at estimating the HBV prevalence and risk of infection in the rural area of Labrea following nineteen years of HBV vaccination. Results: Half of the subjects showed total anti-HBc of 52.1% (95% CI 49.6-54.7). The HBsAg prevalence was 6.2% (95% CI 5.1-7.6). Multivariate analysis showed an inverse association between HBV infection and vaccination (OR 0.62; 95% CI 0.44-0.87). HBsAg remained independently associated with past hepatitis (OR 2.44; 95% CI 1.52-3.89) and inversely to vaccination (OR 0.43; 95% CI 0.27-0.69). The prevalence of HBeAg among HBsAg-positive individuals was 20.4% (95% CI 12.8-30.1), with the positive subjects having a median age of 11 years (1-46) p=0.0003. Conclusions: We demonstrate that HBV infection is still an important public health issue and that HBV vaccination could have had better impact on HBV epidemiology. If we extrapolate these findings to other rural areas in the Brazilian Amazon, we can predict that the sources of chronic infected patients remain a challenge. Future studies are needed regarding clinical aspects, molecular epidemiology, surveillance of acute cases, and risk groups.

Diversity and Adaptation of Human Respiratory Syncytial Virus Genotypes Circulating in Two Distinct Communities: Public Hospital and Day Care Center

HRSV is one of the most important pathogens causing acute respiratory tract diseases as bronchiolitis and pneumonia among infants. HRSV was isolated from two distinct communities, a public day care center and a public hospital in Sao Jose do Rio Preto - SP, Brazil. We obtained partial sequences from G gene that were used on phylogenetic and selection pressure analysis. HRSV accounted for 29% of respiratory infections in hospitalized children and 7.7% in day care center children. On phylogenetic analysis of 60 HRSV strains, 48 (80%) clustered within or adjacent to the GA1 genotype; GA5, NA1, NA2, BA-IV and SAB1 were also observed. SJRP GA1 strains presented variations among deduced amino acids composition and lost the potential O-glycosilation site at amino acid position 295, nevertheless this resulted in an insertion of two potential O-glycosilation sites at positions 296 and 297. Furthermore, a potential O-glycosilation site insertion, at position 293, was only observed for hospital strains. Using SLAC and MEME methods, only amino acid 274 was identified to be under positive selection. This is the first report on HRSV circulation and genotypes classification derived from a day care center community in Brazil.

Neutrophil Paralysis in Plasmodium vivax Malaria

Background: The activation of innate immune responses by Plasmodium vivax results in activation of effector cells and an excessive production of pro-inflammatory cytokines that may culminate in deleterious effects. Here, we examined the activation and function of neutrophils during acute episodes of malaria. Materials and Methods: Blood samples were collected from P. vivax-infected patients at admission (day 0) and 30-45 days after treatment with chloroquine and primaquine. Expression of activation markers and cytokine levels produced by highly purified monocytes and neutrophils were measured by the Cytometric Bead Assay. Phagocytic activity, superoxide production, chemotaxis and the presence of G protein-coupled receptor (GRK2) were also evaluated in neutrophils from malaria patients. Principal Findings: Both monocytes and neutrophils from P. vivax-infected patients were highly activated. While monocytes were found to be the main source of cytokines in response to TLR ligands, neutrophils showed enhanced phagocytic activity and superoxide production. Interestingly, neutrophils from the malaria patients expressed high levels of GRK2, low levels of CXCR2, and displayed impaired chemotaxis towards IL-8 (CXCL8). Conclusion: Activated neutrophils from malaria patients are a poor source of pro-inflammatory cytokines and display reduced chemotactic activity, suggesting a possible mechanism for an enhanced susceptibility to secondary bacterial infection during malaria.

Phylogenetic analysis of rubella virus strains during an outbreak in Sao Paulo, 2007-2008

Rubella virus (RV) is an important human pathogen that causes rubella, an acute contagious disease. It also causes severe birth defects collectively known as congenital rubella syndrome when infection occurs during the first trimester of pregnancy. Here, we present the phylogenetic analysis of RV that circulated in Sao Paulo during the 20072008 outbreak. Samples collected from patients diagnosed with rubella were isolated in cell culture and sequenced. RV RNA was obtained from samples or RV-infected cell cultures and amplified by reverse transcriptase-polymerase chain reaction. Sequences were assigned to genotypes by phylogenetic analysis using RV reference sequences. Seventeen sequences were analyzed, and three genotypes were identified: 1a, 1G, and 2B. Genotypes 1a and 1G, which were isolated in 2007, were responsible for sporadic rubella cases in Sao Paulo. Thereafter, in late 2007, the epidemiological conditions changed, resulting in a large RV outbreak with the clear dominance of genotype 2B. The results of this study provide new approaches for monitoring the progress of elimination of rubella from Sao Paulo, Brazil. J. Med. Virol. 84:16661671, 2012. (c) 2012 Wiley Periodicals, Inc.

Role of Neutralizing Antibodies in Adults With Community-Acquired Pneumonia by Respiratory Syncytial Virus

Background. Respiratory syncytial virus (RSV) has been implicated in the etiology of adult community-acquired pneumonia (CAP). We investigated RSV infection in Chilean adults with CAP using direct viral detection, real-time reverse-transcription polymerase chain reaction (rtRT-PCR), and serology (microneutralization assay). Methods. RSV, other respiratory viruses, and bacteria were studied by conventional and molecular techniques in adults aged >= 18 years presenting with CAP to the healthcare facilities in Santiago, Chile from February 2005 through December 2007. Results. All 356 adults with CAP enrolled had an acute blood sample collected at enrollment, and 184 had a convalescent blood sample. RSV was detected in 48 cases (13.4%). Immunofluorescence assay and viral isolation each detected only 1 infection (0.2%), whereas rtRT-PCR was positive in 32 (8.9%) cases and serology was positive in 20 (10.8%) cases. CAP clinical characteristics were similar in RSV-infected and non-RSV-infected cases. RSV-specific geometric mean serum-neutralizing antibody titer (GMST) was significantly lower at admission in the 48 RSV-infected cases compared with 308 non-RSV-infected adults (GMST in log(2): RSV/A 8.1 vs 8.9, and RSV/B 9.3 vs 10.4; P < .02). Conclusions. RSV infection is frequent in Chilean adults with CAP. Microneutralization assay was as sensitive as rtRT-PCR in detecting RSV infection and is a good adjunct assay for diagnostic research. High RSV-specific serum-neutralizing antibody levels were associated with protection against common and severe infection. The development of a vaccine could prevent RSV-related CAP in adults.

Chronic pain associated with the Chikungunya Fever: long lasting burden of an acute illness

Abstract Background Chikungunya virus (CHIKV) is responsible for major epidemics worldwide. Autochthonous cases were recently reported in several European countries. Acute infection is thought to be monophasic. However reports on chronic pain related to CHIKV infection have been made. In particular, the fact that many of these patients do not respond well to usual analgesics suggests that the nature of chronic pain may be not only nociceptive but also neuropathic. Neuropathic pain syndromes require specific treatment and the identification of neuropathic characteristics (NC) in a pain syndrome is a major step towards pain control. Methods We carried out a cross-sectional study at the end of the major two-wave outbreak lasting 17 months in Réunion Island. We assessed pain in 106 patients seeking general practitioners with confirmed infection with the CHIK virus, and evaluated its impact on quality of life (QoL). Results The mean intensity of pain on the visual-analogical scale (VAS) was 5.8 ± 2.1, and its mean duration was 89 ± 2 days. Fifty-six patients fulfilled the definition of chronic pain. Pain had NC in 18.9% according to the DN4 questionnaire. Conversely, about two thirds (65%) of patients with NC had chronic pain. The average pain intensity was similar between patients with or without NC (6.0 ± 1.7 vs 6.1 ± 2.0). However, the total score of the Short Form-McGill Pain Questionnaire (SF-MPQ)(15.5 ± 5.2 vs 11.6 ± 5.2; p < 0.01) and both the affective (18.8 ± 6.2 vs 13.4 ± 6.7; p < 0.01) and sensory subscores (34.3 ± 10.7 vs 25.0 ± 9.9; p < 0.01) were significantly higher in patients with NC. The mean pain interference in life activities calculated from the Brief Pain Inventory (BPI) was significantly higher in patients with chronic pain than in patients without it (6.8 ± 1.9 vs 5.9 ± 1.9, p < 0.05). This score was also significantly higher in patients with NC than in those without such a feature (7.2 ± 1.5 vs 6.1 ± 1.9, p < 0.05). Conclusions There exists a specific chronic pain condition associated to CHIKV. Pain with NC seems to be associated with more aggressive clinical picture, more intense impact in QoL and more challenging pharmacological treatment.

Prospective surveillance study of acute respiratory infections, influenza-like illness and seasonal influenza vaccine in a cohort of juvenile idiopathic arthritis patients

Background Acute respiratory infections (ARI) are frequent in children and complications can occur in patients with chronic diseases. We evaluated the frequency and impact of ARI and influenza-like illness (ILI) episodes on disease activity, and the immunogenicity and safety of influenza vaccine in a cohort of juvenile idiopathic arthritis (JIA) patients. Methods Surveillance of respiratory viruses was conducted in JIA patients during ARI season (March to August) in two consecutive years: 2007 (61 patients) and 2008 (63 patients). Patients with ARI or ILI had respiratory samples collected for virus detection by real time PCR. In 2008, 44 patients were immunized with influenza vaccine. JIA activity index (ACRPed30) was assessed during both surveillance periods. Influenza hemagglutination inhibition antibody titers were measured before and 30-40 days after vaccination. Results During the study period 105 ARI episodes were reported and 26.6% of them were ILI. Of 33 samples collected, 60% were positive for at least one virus. Influenza and rhinovirus were the most frequently detected, in 30% of the samples. Of the 50 JIA flares observed, 20% were temporally associated to ARI. Influenza seroprotection rates were higher than 70% (91-100%) for all strains, and seroconversion rates exceeded 40% (74-93%). In general, response to influenza vaccine was not influenced by therapy or disease activity, but patients using anti-TNF alpha drugs presented lower seroconversion to H1N1 strain. No significant differences were found in ACRPed30 after vaccination and no patient reported ILI for 6 months after vaccination. Conclusion ARI episodes are relatively frequent in JIA patients and may have a role triggering JIA flares. Trivalent split influenza vaccine seems to be immunogenic and safe in JIA patients.

Untersuchungen über Wechselwirkungen zwischen Proteinen der Leber und dem großen Hüllprotein des Hepatitis-B-Virus

Zusammenfassung:Im Infektionszyklus des Hepatitis-B-Virus spielt das große L-Hüllprotein mit seiner einzigartigen PräS1-Domäne eine zentrale Rolle. Es vermittelt die Bindung und Aufnahme in die Leberzelle, die Verpackung der Nukleokapside in die Virushülle, die Regulation der cccDNA-Amplifikation und eine transkriptionelle Aktivierung in der Wirtszelle. Zur Erfüllung seiner vielfältigen Aufgaben benötigt das L-Protein Unterstützung durch Wirtzellfaktoren, von denen einige im Rahmen dieser Untersuchung durch Verwendung von PräS1-Konstrukten als Fängerproteine im Hefe-Zwei-Hybrid-System identifiziert wurden. Mehrere Klone, die im Hefe-Zwei-Hybrid-Test mit dem C-terminalen PräS1-Fängerprotein (Aminosäure 44-108) isoliert worden waren, enthielten Teile der cDNA von gamma2-Adaptin, einem mutmaßlichen Mitglied der Clathrin-Adaptor-Proteine. Diese sind für intrazelluläre Membrantransportprozesse mittels clathrinumhüllter Vesikel verantwortlich. Unter den interagierenden Klonen, die mit dem N-terminalen Konstrukt des L-Proteins (Aminosäure 1-70) isoliert worden waren, befand sich überproportional häufig eine cDNA, die der schweren Kette H4 der Inter-Alpha-Trypsin-Inhibitor-Familie homolog war. H4 besitzt vermutlich bei der 'Akute-Phase-Reaktion', die Entzündungen folgt, und bei der Stabilisierung der extrazellulären Matrix physiologische Bedeutung. Weitere Klone kodierten für die Serinprotease C1r. Diese ist Bestandteil des C1-Komplex, der ersten Komponente des klassischen Komplementsystems. Die Spezifität der Bindung zwischen den positiven Klonen und der PräS1-Domäne wurde in weiteren biochemischen Interaktionstests bestätigt, sodaß H4, C1r und gamma2-Adaptin als Wirtszellfaktoren in der Physiologie des Hepatitis-B-Virus wahrscheinlich eine Rolle spielen.Abstract:Little is known about host cell factors necessary for hepatitis B virus assembly and infectivity. Central to virogenesis is the large L envelope protein that mediates hepatocyte receptor binding, envelopment of viral capsids, regulation of supercoiled DNA amplification and transcriptional transactivation. To assess its multiple functions and host-protein assistance involved, we here initiated a yeast two-hybrid screen using the L-specific preS1 domain as bait to screen a human liver cDNA library for L-interacting proteins. One of the most prominent cDNAs interacting with aminoacid sequence 44-108 of L-protein encodes for gamma2-adaptin, a novel clathrin adaptor-related protein responsible for protein sorting and trafficking. Among the clones interacting with the N-terminal construct of L-protein (aminoacid sequence 1-70), a frequently isolated cDNA corresponds to the gene for inter-alpha-trypsin family heavy chain H4, likely to be involved in acute inflammatory phase response and stabilization of extracellular matrices. Some other interacting clones were found to carry the cDNA for the serine protease C1r, a subunit of the C1 complex which initiates the classical complement cascade. The specificity of the interaction between the positive clones and the preS1 domain was further confirmed in independent biochemical experiments. Taken together, the results suggest a role for H4, C1r and gamma2-adaptin as host-cell factors in L-mediated process of viral biogenesis and/or pathogenesis.

Epidemiologia e caratterizzazione molecolare di virus emergenti responsabili di Zoonosi: Calcivirus e Virus dell'Epatite E

Il virus dell’Epatite E (HEV) e i calicivirus (norovirus e sapovirus) causano rispettivamente epatite acuta e gastroenterite. Questi virus sono considerati agenti eziologici emergenti rappresentando un problema di sanità pubblica e di sicurezza alimentare. Per HEV, è ormai confermata la trasmissione zoonotica, e il suino è considerato il principale serbatoio asintomatico. Norovirus e sapovirus infettano sia i bambini che gli adulti. Sebbene questi virus siano stati identificati anche negli animali, la possibile trasmissione zoonotica non è stata dimostrata in modo conclusivo. Il lavoro sperimentale condotto durante il Dottorato di Ricerca è stato focalizzato sullo studio degli aspetti biologici ed epidemiologici dell’infezioni causate da HEV e da calicivirus. Per la prima volta in Italia, i risultati ottenuti hanno dimostrato la presenza del virus HEV nei fegati di suini in fase di macellazione ed hanno confermato, attraverso la ricerca di anticorpi, un’elevata esposizione degli animali al virus. Inoltre, mediante la produzione di antigeni e reattivi immunologici, sono stati messi a punto test diagnostici per la ricerca di anticorpi contro HEV nel suino e nei cinghiali. Il lavoro svolto per la ricerca di calicivirus nel suino e nel bovino ha dimostrato la circolazione dei sapovirus in popolazioni di suini asintomatici e la presenza di norovirus nei vitelli affetti da diarrea acuta.Sono stati inoltre sviluppati reattivi immunologici, utilizzando proteine del capside di norovirus umano e bovino espresse con il sistema ricombinante baculovirus. Questi hanno permesso di evidenziare la presenza di anticorpi contro norovirus umano e bovino, in sieri di veterinari professionalmente esposti. Inoltre, sono stati utilizzati per sviluppare metodi per la concentrazione dei virus da matrici a bassa concentrazione.Infine, le VLP sono state utilizzate per valutare l’attivazione del sistema immunitario umano ex vivo. I risultati hanno dimostrato che le VLP di NoV stimolano il sistema immunitario attivando risposte di tipo Th1 e Th2 .

Sorveglianza dell’infezione da virus dell’epatite E (HEV) in Italia: from farm to table

L'epatite E è una malattia umana con caratteristiche di epatite acuta, causata da un ssRNA virus (HEV). Nel 1997, HEV è stato identificato per la prima volta nei suini (SwHEV). In seguito, diverse evidenze, tra cui la vicinanza genetica tra ceppi umani e suini, suggerirono la trasmissione zoonotica del virus. Nella presente tesi, l’identificazione di SwHEV è stata condotta mediante ricerca di porzioni di genoma virale attraverso RT-PCR. Dal 2011 al 2013, sono stati analizzati 343 campioni fecali (da 19 allevamenti) e 70 bili (da 2 macelli) prelevati da altrettanti suini, in diverse Regioni italiane. E’ stato inoltre condotto uno studio retrospettivo su 78 feci (da 3 allevamenti) raccolte nel 2000. Il virus è stato identificato nel 24,5% e 19,2% delle feci raccolte rispettivamente nel 2011-2013 e nel 2000. Nessuna bile è risultata positiva. Mediante sequenziamento del genoma intero di uno dei virus identificati, è stata condotta l’analisi filogenetica per valutarne il grado di correlazione con alti ceppi suini e umani. La presenza di HEV è stata valutata lungo la filiera di produzione suina, dal macello al punto vendita. Trentaquattro campioni di feci, fegato e muscolo sono stati raccolti in un macello da altrettanti suini sani (età:6-7 mesi). Quattordici feci e 2 fegati, sono risultati positivi per HEV. Sono state prelevate 129 salsicce sia allo stabilimento di trasformazione sia alla vendita, ma nessuna è risultata positiva. La presenza di HEV è stata valutata anche nelle salsicce di fegato, fresche e secche, acquistate presso una macelleria. Il genoma virale è stato rilevato nel 22,2% delle salsicce fresche e nel 4,3 % di quelle secche ma la vitalità del virus non è stata dimostrata. In conclusione, lo studio condotto ha confermato l’ampia circolazione di HEV nei suini e la possibile contaminazione dei prodotti carnei derivati, confermando la necessità di una continua sorveglianza.

Genetic and environmental factors associated with cardiovascular diseases and acute myocardial infarction

Acute myocardial infarction (AMI) is a multifactorial disease with a complex pathogenesis where lifestyle, individual genetic background and environmental risk factors are involved. Altered inflammatory responses seems to be implicated in the pathogenesis of atherosclerosis. To understand which genes may predispose to increased risk of cardiovascular disease gene polymorphism of immune regulatory genes, and clinical events from the Offs of parents with an early AMI were investigated. Genetics data from Offs were compared with those obtained from healthy subjects and an independent cohort of patients with clinical sporadic AMI. Rates of clinical events during a 24 years follow up from Offs and from an independent Italian population survey were also evaluated. This study showed that a genetic signature consisting of the concomitant presence of the CC genotype of VEGF, the A allele of IL-10 and the A allele of IFN-γ was indeed present in the Offs population. During the 24-year follow-up, Offs with a positive familiarity in spite of a relatively young age showed an increased prevalence of diabetes, ischemic heart disease and stroke. In these patients with the genetic signature the EBV and HHV-6 herpes virus were also investigated and founded. These findings reinforce the notion that subjects with a familial history of AMI are at risk of an accelerated aging of cardiovascular system resulting in cardiovascular events. These data suggest that selected genes with immune regulatory functions and envoronmental factors are part of the complex genetic background contributing to familiarity for cardiovascular diseases.N

The role of B cells during acute and latent infections with murine cytomegalovirus and Leishmania major

This thesis focuses on the role of B cells in mCMV and Leishmania major infection. B cells are an essential component of the adaptive immune system and play a key role in the humoral immune response. In mCMV infection we analyzed the influence of B cells on the virus-specific CD8 T cell response, in detail the role of B cells as IL-10 secreting cells, as source of immunoglobulin (Ig) and as antigen presenting cells. In Leishmania major infection we investigated the role of Ig in Th1 and Th2 directed disease.rnWe found in mCMV infection that the B cell secreted IL-10 suppresses effectively the acute virus-specific CD8 T cell response, while the IL-10 secreted by dendritic cell has no obvious effect. Ig has no effect in the acute virus-specific CD8 T cell response, but in memory response Ig is essential. If Ig is missing the CD8 T cell population remains high in memory response 135 days post infection. The complete absence of B cells dramatically reduces the acute virus-specific CD8 T cell response, while B cell reconstitution just partially rescues this dramatic reduction. A comparison of this reduction in a B cell free organism to an organism with depleted dendritic cells gave a similar result. To exclude a malfunction of the CD8 T cells in the B cell deficient mice, the decreased virus-specific CD8 T cell population was confirmed in a B cell depletion model. Further, bone marrow chimeras with a B cell compartment deficient for CD40-/- showed a decrease of the virus-specific response and an involvement of CD40 on B cells. Taken together these results suggest a role for B cells in antigen presentation during mCMV infection.rnFurther we took advantage of the altered mCMV specific CD8 T cell memory response in mice without Ig to investigate the memory inflation of CD8 T cells specific for distinct mCMV specifc peptides. Using a SIINFEKL-presenting virus system, we were able to shorten the time until the memory inflation occurs and show that direct presentation stimulates the memory inflation. rnIn Leishmania major infection, Ig of Th2 balanced BALB/c mice has a central role in preventing a systemic infection, although the ear lesions are smaller in IgMi mice without specific Ig. Here the parasite loads of ears and spleen are elevated, and an IMS-reconstitution does not affect the parasite load. In contrast in Th1 balanced C57BL/6 mice, reconstitution of IgMi mice with serum of either untreated or immunized mice decreased the parasite load of spleen and ear, further IMS treatment reduces the size of the spleen and the cytokine-levels of IL-10, IL-4, IL-2 and IFN-γ to a level comparable to wt mice. rn