Mycobacterium tuberculosis: Active disease and latent infection in a renal transplant cohort.

AIM: Our aim was threefold: first, to determine the incidence of active TB in our cohort, second to investigate the risk factors for active TB and third, to understand current screening practices. The ultimate goal was to use our findings to inform development of local and national guidelines. METHODS: The records of all adult patients who underwent renal transplantation at our centre from 2005 to 2014 were retrospectively reviewed to assess current screening practices, the risks for and burden of active TB. RESULTS: A total of 660 individuals underwent renal transplantation during this period, totalling 3647 person years of follow up. Two patients were diagnosed with active TB after renal transplant, resulting in an incidence of 55 per 100 000 person-years. Of 656 transplant recipients, 102 (15.5%) were born in high TB incidence countries and 89 (13.5%) had an interferon gamma release assay (IGRA) at any point. Individuals born in high TB risk countries had a much higher incidence of active TB (353 per 100 000 person-years). Ten individuals had positive IGRA tests, of whom two were treated for active TB, two received chemoprophylaxis and six were not treated. CONCLUSIONS: In the absence of formal guidelines, IGRA-based screening for LTBI was infrequently performed. Our data suggest that screening and treatment of renal transplant recipients born in high incidence countries is an important preventive measure.

Underdiagnosis of Chlamydia trachomatis and Chlamydia psittaci revealed by introduction of respiratory multiplex PCR assay with Chlamydiaceae family primers.

We describe unanticipated detection of respiratory infection with Chlamydia trachomatis and Chlamydia psittaci after introduction of respiratory multiplex polymerase chain reaction assay that includes Chlamydiaceae family primers. We detected cases of pediatric C. trachomatis and of adult C. psittaci infection in patients with previously unrecognized risk factors. Directed testing for C. trachomatis and C. psittaci based on clinical features and risk factors alone is likely to miss the majority of infected cases.

Effects of Midazolam and Midazolam-Butorphanol on Gastrointestinal Transit Time and Motility in Cockatiels (Nymphicus hollandicus).

Positive contrast gastrointestinal (GI) studies are performed frequently in avian medicine to identify GI obstruction, luminal distension, and intracoelomic mass effects. However, repeated manual restraint and radiographic positioning may result in a stress-response and associated morbidity in birds, which can be attenuated by administration of sedative drugs. In mammals, many sedative drugs have been shown to affect GI transit times and motility. In this randomized, blinded, controlled prospective study, the effects of midazolam (M; 6 mg/kg IM) and midazolam-butorphanol (MB; 3 mg/kg each IM) on GI transit times were evaluated in 12 healthy cockatiels (Nymphicus hollandicus). Iohexol (20 mL/kg) was administered by crop gavage 15 minutes after induction of sedation, and fluoroscopic images were obtained at different time points. Both sedation protocols significantly affected GI transit times and motility, and the MB protocol had more pronounced effects. Overall median (range) GI transit times were 60 (30-120), 90 (30-120), and 120 (120-180) minutes for the control, M, and MB groups, respectively. Ventricular contractions were markedly reduced with both sedation protocols, while esophageal boluses were reduced only in the MB group. Visualization of the GI tract after iohexol administration was graded highest in the control group and poorest in the MB group. Our results show that commonly used sedative drugs have significant effects on GI transit time and motility in birds. Therefore, GI transit times obtained in sedated birds should not be compared to available reference transit times obtained from unsedated animals.

Contrast fluoroscopic evaluation of gastrointestinal transit times with and without the use of falconry hoods in red-tailed hawks (Buteo jamaicensis).

OBJECTIVE To evaluate gastrointestinal transit times in red-tailed hawks (Buteo jamaicensis) by use of contrast fluoroscopic imaging and investigate the effect of falconry hooding in these hawks on gastrointestinal transit time. DESIGN Prospective, randomized, blinded, complete crossover study. ANIMALS 9 healthy red-tailed hawks. PROCEDURES Hawks were gavage-fed a 30% weight-by-volume barium suspension (25 mL/kg [11.3 mL/lb]) into the crop. Fluoroscopic images were obtained at multiple time points after barium administration. Time to filling and emptying of various gastrointestinal tract organs and overall transit time were measured. The effect of hooding (hooded vs nonhooded) on these variables was assessed in a randomized complete crossover design. RESULTS In nonhooded birds, overall gastrointestinal transit time ranged from 30 to 180 minutes (mean ± SD, 100 ± 52 min). Time to complete crop emptying ranged from 30 to 180 minutes (83 ± 49 min). Contrast medium was present in the ventriculus in all birds within 5 minutes of administration and in the small intestines within 5 to 15 minutes (median, 5 min). Hooding of red-tailed hawks resulted in a significant delay of complete crop emptying (no hood, 83 ± 49 minutes; hood, 133 ± 48 minutes), but no significant effects of hooding were found on other measured variables. CONCLUSIONS AND CLINICAL RELEVANCE These results indicated that overall gastrointestinal transit times are faster in red-tailed hawks than has been reported for psittacines and that the use of a falconry hood in red-tailed hawks may result in delayed crop emptying. Hooding did not exert significant effects on overall gastrointestinal transit time in this raptorial species.

Determination of Gastrointestinal Transit Times in Barred Owls ( Strix varia ) by Contrast Fluoroscopy.

Contrast imaging studies are routinely performed in avian patients when an underlying abnormality of the gastrointestinal (GI) tract is suspected. Fluoroscopy offers several advantages over traditional radiography and can be performed in conscious animals with minimal stress and restraint. Although birds of prey are commonly encountered as patients, little is known about GI transit times and contrast imaging studies in these species, especially owls. Owls are commonly encountered in zoological, educational, and wildlife settings. In this study, 12 adult barred owls ( Strix varia ) were gavage fed a 30% weight-by-volume barium suspension (25 mL/kg body weight). Fluoroscopic exposures were recorded at 5, 15, 30, 60, 120, 180, 240, and 300 minutes after administration. Overall GI transit time and transit times of various GI organs were recorded. Median (interquartile range [IQR]) overall GI transit time was 60 minutes (IQR: 19-60 minutes) and ranged from 5-120 minutes. Ventricular and small intestinal contrast filling was rapid. Ventricular emptying was complete by a median of 60 minutes (IQR: 30-120 minutes; range: 30-240 minutes), whereas small intestinal emptying was not complete in 9/12 birds by 300 minutes. Median small intestinal contraction rate was 15 per minute (IQR: 13-16 minutes; range: 10-19 minutes). Median overall GI transit time in barred owls is more rapid than mean transit times reported for psittacine birds and red-tailed hawks ( Buteo jamaicensis ). Fluoroscopy is a safe, suitable method for investigating GI motility and transit in this species.

COMPARISON OF FLUOROSCOPY AND COMPUTED TOMOGRAPHY FOR TRACHEAL LUMEN DIAMETER MEASUREMENT AND DETERMINATION OF INTRALUMINAL STENT SIZE IN HEALTHY DOGS.

Tracheal collapse is a progressive airway disease that can ultimately result in complete airway obstruction. Intraluminal tracheal stents are a minimally invasive and viable treatment for tracheal collapse once the disease becomes refractory to medical management. Intraluminal stent size is chosen based on the maximum measured tracheal diameter during maximum inflation. The purpose of this prospective, cross-sectional study was to compare tracheal lumen diameter measurements and subsequent selected stent size using both fluoroscopy and CT and to evaluate inter- and intraobserver variability of the measurements. Seventeen healthy Beagles were anesthetized and imaged with fluoroscopy and CT with positive pressure ventilation to 20 cm H2 O. Fluoroscopic and CT maximum tracheal diameters were measured by three readers. Three individual measurements were made at eight predetermined tracheal sites for dorsoventral (height) and laterolateral (width) dimensions. Tracheal diameters and stent sizes (based on the maximum tracheal diameter + 10%) were analyzed using a linear mixed model. CT tracheal lumen diameters were larger compared to fluoroscopy at all locations (P-value < 0.0001). When comparing modalities, fluoroscopic and CT stent sizes were statistically different. Greater overall variation in tracheal diameter measurement (height or width) existed for fluoroscopy compared to CT, both within and among observers. The greater tracheal diameter measured with CT and lower measurement variability has clinical significance, as this may be the imaging modality of choice for appropriate stent selection to minimize complications in veterinary patients.

Effect of 6-8 weeks of oral ursodeoxycholic acid administration on serum concentrations of fasting and postprandial bile acids and biochemical analytes in healthy dogs.

BACKGROUND: Ursodeoxycholic acid (UDCA) is commonly used for the treatment of hepatobiliary disease. UDCA is a bile acid that can be detected in the bile acid assay. Its effect on biochemical analytes is unknown. OBJECTIVES: The aim of this study was to determine the effect of 6-8 weeks of UDCA administration on fasting and postprandial concentrations of serum bile acids (SBA), cholesterol, triglycerides, bilirubin, and liver enzyme activities in healthy dogs. METHODS: Twenty healthy dogs received UDCA for 6-8 weeks. CBC, biochemistry profile, urinalysis, fasting and postprandial SBA, and hepatobiliary ultrasound examination were performed prior to starting UDCA (timepoint 0) and after 6-8 weeks of therapy, while animals were still receiving UDCA (timepoint 1). Timepoint 0 and timepoint 1 values were compared with a paired t-test. SBA were remeasured 72 hours after UDCA discontinuation. RESULTS: Only mean fasting SBA at timepoint 1 increased significantly (P = .03) from timepoint 0 (2.26 µmol/L at time 0 and 3.81 µmol/L at time 1) but were not elevated above the normal reference interval (0-9 µmol/L). Two dogs had timepoint 1 fasting SBA above the reference interval (10 and 11.7 µmol/L). One dog had timepoint 1 postprandial SBA above the reference interval at 20.1 µmol/L (reference interval 0-17 µmol/L). Repeat SBA 72 hours after UDCA discontinuation were normal. CONCLUSIONS: Long-term administration of UDCA to healthy dogs may increase fasting SBA above pretreatment values (typically within the reference interval). Long-term administration of UDCA to healthy dogs does not alter liver enzyme activities, and bilirubin, cholesterol, or triglyceride concentrations.

Suspected primary hematomyelia in 3 dogs.

Primary hematomyelia refers to hemorrhage occurring within the spinal cord without an identifiable etiology. Clinical signs, magnetic resonance imaging characteristics, and histopathological findings are described. Diagnosis was made through histological analysis and rule-outs for underlying factors. Following removal of the hematoma, neurologic deficits improved, although some residual deficits persisted.

Hématomyélie primaire suspectée chez 3 chiens. L'hématomyélie primaire fait référence à l'hémorragie qui se produit dans la moelle épinière sans une étiologie identifiable. Les signes cliniques, les caractéristiques de l'imagerie par résonance magnétique et les résultats de l'histopathologie sont décrits. Le diagnostic a été posé à l'aide d'une analyse histologique et de l'élimination des facteurs sous-jacents. Après l'enlèvement de l'hématome, le déficit neurologique s'est amélioré, même si des déficits résiduels ont persisté.(Traduit par Isabelle Vallières).

Interobserver variability of radiographic pulmonary nodule diameter measurements in dogs and cats.

The purpose of this study was to determine the interobserver variability of radiographic pulmonary nodule diameter measurements among readers with varying levels of experience. Because interobserver variability may lead to inaccurate estimations of nodule growth on repeat radiographic assessment, an incorrect presumption of malignant etiology or misclassification of tumor response to treatment may result. The maximum diameters of 47 pulmonary nodules from 22 dogs and 7 cats were measured. Measurements were performed using one digital thoracic radiographic projection by eight clinicians. The eight clinicians included two interns, two residents, two board-certified veterinary specialists, and two board-certified veterinary radiologists. A mixed-effect analysis of variance model was used to evaluate the contribution of reader, experience level, patient, nodule, and nodule size to the overall variability in mean pulmonary nodule diameter. The interobserver variability in diameter measurement for any given nodule was 16%, and experience level and nodule size classification did not contribute to measurement variability. Linear measurements of the diameter of a pulmonary nodule can vary significantly among a group of clinicians; however, depending on the criteria used to evaluate nodule growth or tumor response, the 16% interobserver variability reported here is likely not clinically significant.

Adenovirus-5-vectored P. falciparum vaccine expressing CSP and AMA1. Part B: safety, immunogenicity and protective efficacy of the CSP component.

BACKGROUND: A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge. METHODOLOGY/PRINCIPAL FINDINGS: NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one adenovector encoding CSP and one encoding apical membrane antigen-1 (AMA1) that was evaluated for safety and immunogenicity in an earlier study (see companion paper, Sedegah et al). Fourteen Ad5 seropositive or negative adults received two doses of NMRC-MV-Ad-PfC sixteen weeks apart, at 1 x 1010 particle units per dose. The vaccine was safe and well tolerated. All volunteers developed positive ELISpot responses by 28 days after the first immunization (geometric mean 272 spot forming cells/million[sfc/m]) that declined during the following 16 weeks and increased after the second dose to levels that in most cases were less than the initial peak (geometric mean 119 sfc/m). CD8+ predominated over CD4+ responses, as in the first clinical trial. Antibody responses were poor and like ELISpot responses increased after the second immunization but did not exceed the initial peak. Pre-existing neutralizing antibodies (NAb) to Ad5 did not affect the immunogenicity of the first dose, but the fold increase in NAb induced by the first dose was significantly associated with poorer antibody responses after the second dose, while ELISpot responses remained unaffected. When challenged by the bite of P. falciparum-infected mosquitoes, two of 11 volunteers showed a delay in the time to patency compared to infectivity controls, but no volunteers were sterilely protected. SIGNIFICANCE: The NMRC-MV-Ad-PfC vaccine expressing CSP was safe and well tolerated given as two doses, but did not provide sterile protection. TRIAL REGISTRATION: ClinicalTrials.gov NCT00392015.

A human Phase I/IIa malaria challenge trial of a polyprotein malaria vaccine.

We examined the safety, immunogenicity and efficacy of a prime-boost vaccination regime involving two poxvirus malaria subunit vaccines, FP9-PP and MVA-PP, expressing the same polyprotein consisting of six pre-erythrocytic antigens from Plasmodium falciparum. Following safety assessment of single doses, 15 volunteers received a heterologous prime-boost vaccination regime and underwent malaria sporozoite challenge. The vaccines were safe but interferon-γ ELISPOT responses were low compared to other poxvirus vectors, despite targeting multiple antigens. There was no vaccine efficacy as measured by delay in time to parasitaemia. A number of possible explanations are discussed, including the very large insert size of the polyprotein transgene.

Children's executive functions: are they poorer after very early brain insult.

Traditionally early brain insult (EBI) has been considered to have better outcome than later injury, consistent with the notion that the young brain is flexible and able to reorganize. Recent research findings question this view, suggesting that EBI might lead to poorer outcome than brain insult at any other age. Exploring this early vulnerability perspective, we investigated whether skills developing later in childhood, for example, executive functions (EF), would be at greater risk of disruption from EBI. The aim of this study was to investigate EF in children sustaining EBI at different developmental stages. We expected that brain insult during gestation and infancy, before the emergence of EF, would lead to global EF deficits. In contrast, we predicted that brain injury in late childhood would have fewer consequences. Using a cross-sectional, retrospective, group design we compared six groups of children (Total N=164), with a history of brain insult and documented focal brain pathology, aged 10-16 years on a range of measures of EF. Groups were based on age of EBI: (1) Congenital; (2) Peri-natal; (3) Infancy; (4) Preschool; (5) Middle Childhood; and (6) Late Childhood. Children with EBI were at increased risk for impairment across all aspects of EF. Presence of seizures and/or frontal pathology were not predictive of outcome, but age at insult was. Children sustaining EBI before age 3 recorded more global and severe EF deficits, while children with later EBI performed closer to normal expectations. With the exception of attentional control, skills emerging at time of insult were found to be more vulnerable to disruption than those previously established, supporting the 'early vulnerability' model for EBI.

Does early age at brain insult predict worse outcome? Neuropsychological implications.

OBJECTIVE: Traditionally early brain insult (EBI) has been argued to have better outcome than later injury, consistent with the notion that the young brain is flexible and able to reorganize. This view was investigated by comparing neurobehavioral outcomes of children sustaining EBI at different developmental stages (gestation to late childhood). METHODS: One hundred and sixty four children who had sustained focal brain insult (confirmed by MRI) formed six groups, based on age at EBI, (a) Congenital; (b) Peri-natal; (c) Infancy; (d) Preschool; (e) Middle Childhood; (f) Late Childhood, and were compared on a range of standardized neurobehavioral measures. Groups were matched for lesion characteristics and demographics. RESULTS: Children sustaining EBI before age 2 recorded global deficits, while children with later EBI performed closer to average. CONCLUSION: These results question the advantages of early brain plasticity, demonstrating poorer outcome from very early insults, and increasingly better function with lesions later in childhood.

Childhood brain insult: can age at insult help us predict outcome?

Until recently, the impact of early brain insult (EBI) has been considered to be less significant than for later brain injuries, consistent with the notion that the young brain is more flexible and able to reorganize in the context of brain insult. This study aimed to evaluate this notion by comparing cognitive and behavioural outcomes for children sustaining EBI at different times from gestation to late childhood. Children with focal brain insults were categorized according to timing of brain insult, represented by six developmental periods: (i) Congenital (n = 38): EBI: first-second trimester; (ii) Perinatal (n = 33); EBI: third trimester to 1 month post-natal; (iii) Infancy (n = 23): EBI: 2 months-2 years post-birth; (iv) Preschool (n = 19): EBI: 3-6 years; (v) Middle Childhood (n = 31): EBI: 7-9 years; and (vi) Late Childhood (n = 19): EBI: after age 10. Groups were similar with respect to injury and demographic factors. Children were assessed for intelligence, academic ability, everyday executive function and behaviour. Results showed that children with EBI were at increased risk for impairment in all domains assessed. Furthermore, children sustaining EBI before age 2 years recorded global and significant cognitive deficits, while children with later EBI performed closer to normal expectations, suggesting a linear association between age at insult and outcome. In contrast, for behaviour, children with EBI from 7 to 9 years performed worse than those with EBI from 3 to 6 years, and more like those with younger insults, suggesting that not all functions share the same pattern of vulnerability with respect to age at insult.

Phase 2a trial of 0, 1, and 3 month and 0, 7, and 28 day immunization schedules of malaria vaccine RTS,S/AS02 in malaria-naïve adults at the Walter Reed Army Institute of Research.

BACKGROUND: Immunization with RTS,S/AS02 consistently protects some vaccinees against malaria infection in experimental challenges and in field trials. A brief immunization schedule against falciparum malaria would be compatible with the Expanded Programme on Immunization, or in combination with other prevention measures, interrupt epidemic malaria or protect individuals upon sudden travel to an endemic area. METHODS: We conducted an open label, Phase 2a trial of two different full dose schedules of RTS,S/AS02 in 40 healthy malaria-naïve adults. Cohort 1 (n=20) was immunized on a 0, 1, and 3 month schedule and Cohort 2 (n=20) on a 0, 7, and 28 day schedule. Three weeks later, 38 vaccinees and 12 unimmunized infectivity controls underwent malaria challenge. RESULTS: Both regimens had a good safety and tolerability profile. Peak GMCs of antibody to the circumsporozoite protein (CSP) were similar in Cohort 1 (78 microg/mL; 95% CI: 45-134) and Cohort 2 (65 microg/mL; 95% CI: 40-104). Vaccine efficacy for Cohort 1 was 45% (95% CI: 18-62%) and for Cohort 2, 39% (95% CI: 11-56%). Protected volunteers had a higher GMC of anti-CSP antibody (114 microg/mL) than did volunteers with a 2-day delay (70 microg/mL) or no delay (30 microg/mL) in the time to onset of parasitemia (Kruskal-Wallis, p=0.019). A trend was seen for higher CSP-specific IFN-gamma responses in PBMC from protected volunteers only in Cohort 1, but not in Cohort 2, for ex vivo and for cultured ELISPOT assays. CONCLUSION: In malaria-naïve adults, the efficacy of three-dose RTS,S/AS02 regimens on either a 0, 1, and 3 month schedule or an abbreviated 0, 7, and 28 day schedule was not discernibly different from two previously reported trials of two-dose regimens given at 0, 1 month that conferred 47% (95% CI: -19 to 76%) protection and in another trial 42% (95% CI: 5-63%). A strong association of CSP-specific antibody with protection against malaria challenge is observed and confirms similar observations made in other studies. Subsequent trials of adjuvanted RTS,S in African children and infants on a 0, 1, and 2 month schedule have demonstrated a favorable safety and efficacy profile.

Protection of rhesus monkeys by a DNA prime/poxvirus boost malaria vaccine depends on optimal DNA priming and inclusion of blood stage antigens.

BACKGROUND: We have previously described a four antigen malaria vaccine consisting of DNA plasmids boosted by recombinant poxviruses which protects a high percentage of rhesus monkeys against Plasmodium knowlesi (Pk) malaria. This is a multi-stage vaccine that includes two pre-erythrocytic antigens, PkCSP and PkSSP2(TRAP), and two erythrocytic antigens, PkAMA-1 and PkMSP-1(42kD). The present study reports three further experiments where we investigate the effects of DNA dose, timing, and formulation. We also compare vaccines utilizing only the pre-erythrocytic antigens with the four antigen vaccine. METHODOLOGY: In three experiments, rhesus monkeys were immunized with malaria vaccines using DNA plasmid injections followed by boosting with poxvirus vaccine. A variety of parameters were tested, including formulation of DNA on poly-lactic co-glycolide (PLG) particles, varying the number of DNA injections and the amount of DNA, varying the interval between the last DNA injection to the poxvirus boost from 7 to 21 weeks, and using vaccines with from one to four malaria antigens. Monkeys were challenged with Pk sporozoites given i.v. 2 to 4 weeks after the poxvirus injection, and parasitemia was measured by daily Giemsa stained blood films. Immune responses in venous blood samples taken after each vaccine injection were measured by ELIspot production of interferon-gamma, and by ELISA. CONCLUSIONS: 1) the number of DNA injections, the formulation of the DNA plasmids, and the interval between the last DNA injection and the poxvirus injection are critical to vaccine efficacy. However, the total dose used for DNA priming is not as important; 2) the blood stage antigens PkAMA-1 and PkMSP-1 were able to protect against high parasitemias as part of a genetic vaccine where antigen folding is not well defined; 3) immunization with PkSSP2 DNA inhibited immune responses to PkCSP DNA even when vaccinations were given into separate legs; and 4) in a counter-intuitive result, higher interferon-gamma ELIspot responses to the PkCSP antigen correlated with earlier appearance of parasites in the blood, despite the fact that PkCSP vaccines had a protective effect.

Genetically attenuated Plasmodium berghei liver stages induce sterile protracted protection that is mediated by major histocompatibility complex Class I-dependent interferon-gamma-producing CD8+ T cells.

At present, radiation-attenuated plasmodia sporozoites ( gamma -spz) is the only vaccine that induces sterile and lasting protection in malaria-naive humans and laboratory rodents. However, gamma -spz are not without risks. For example, the heterogeneity of the gamma -spz could explain occasional breakthrough infections. To avoid this possibility, we constructed a double-knockout P. berghei parasite by removing 2 genes, UIS3 and UIS4, that are up-regulated in infective spz. We evaluated the double-knockout Pbuis3(-)/4(-) parasites for protective efficacy and the contribution of CD8(+) T cells to protection. Pbuis3(-)/4(-) spz induced sterile and protracted protection in C57BL/6 mice. Protection was linked to CD8(+) T cells, given that mice deficient in beta (2)m were not protected. Pbuis3(-)/4(-) spz-immune CD8(+) T cells consisted of effector/memory phenotypes and produced interferon- gamma . On the basis of these observations, we propose that the development of genetically attenuated P. falciparum parasites is warranted for tests in clinical trials as a pre-erythrocytic stage vaccine candidate.

The immune status of Kupffer cells profoundly influences their responses to infectious Plasmodium berghei sporozoites.

Multi-factorial immune mechanisms underlie protection induced with radiation-attenuated Plasmodia sporozoites (gamma-spz). Spz pass through Kupffer cells (KC) before invading hepatocytes but the involvement of KC in protection is poorly understood. In this study we investigated whether gamma-spz-immune KC respond to infectious spz in a manner that is distinct from the response of naive KC to infectious spz. KC were isolated from (1) naive, (2) spz-infected, (3) gamma-spz-immune, and (4) gamma-spz-immune-challenged C57BL/6 mice and examined for the expression of MHC class I and II, CD40 and CD80/CD86, IL-10 and IL-12 responses and antigen-presenting cell (APC) function. KC from gamma-spz-immune-challenged mice up-regulated class I and costimulatory molecules and produced elevated IL-12p40, relative to naive KC. In contrast, KC from naive mice exposed to infectious spz down-modulated class I and IL-12p40 was undetectable. Accordingly, KC from spz-infected mice had reduced APC function, while KC from gamma-spz-immune-challenged mice exhibited augmented APC activity. The nearly opposite responses are consistent with the fact that spz challenge of gamma-spz-immune mice results in long-lasting sterile protection, while infection of naive mice always results in malaria.