Complement-fixing Antibody Titers Research Articles

Liposome engraftment and antigen combination potentiate the immune response towards conserved epitopes of the malaria vaccine candidate MSP2

Merozoite surface protein 2 (MSP2) is a highly abundant, GPI-anchored surface antigen on merozoites of the malaria parasite Plasmodium falciparum. It consists of highly conserved N- and C-terminal domains, and a central polymorphic region that allows all MSP2 alleles to be categorized into the 3D7 or FC27 family. Previously it has been shown that epitope accessibility differs between lipid-bound and lipid-free MSP2, suggesting that lipid interactions modulate the conformation and antigenicity in a way that may better mimic native MSP2 on the merozoite surface. Therefore, we have immunised mice with MSP2 engrafted onto liposomes using a C-terminal tether that mimics the native GPI anchor. To improve the immunogenicity of the formulated antigen, liposomes were supplemented with Pathogen Associated Molecular Pattern molecules, specifically agonists of the Toll-like receptor 4 (TLR4) or TLR2. Induced antibodies were directed mostly towards conserved epitopes, predominantly in the conserved C-terminal region of MSP2. We also found that immunisation with a combination of 3D7 and FC27 MSP2 enhanced antibody responses to conserved epitopes, and that the overall responses of mice immunised with MSP2-engrafted liposomes were comparable in magnitude to those of mice immunised with MSP2 formulated in Montanide ISA720. The antibodies elicited in mice by immunising with MSP2-engrafted liposomes recognised the native form of parasite MSP2 on western blots and were found to be cross-reactive with isolated 3D7 and FC27 merozoites when investigated by ELISA. The liposome-tethered MSP2 induced higher titres of complement-fixing antibodies to 3D7 and FC27 MSP2 than did MSP2 formulated in Montanide ISA720. Our results indicate that liposomal formulation represents a viable strategy for eliciting a strong immune response that favours conserved epitopes in MSP2 and thus a strain-transcendent immune response.

A quantitative enzyme-linked immunoassay (ELISA) to approximate complement-fixing antibody titers in serum from patients with coccidioidomycosis

Coccidioidomycosis is most frequently diagnosed serologically, and the quantitative test for complement-fixing antibodies is considered prognostically useful. Because complement-fixing antibody testing is complex, labor-intensive, and poorly standardized, an enzyme-linked immunoassay (ELISA) alternative would be attractive. In this report, we restrict the complement-fixing, antibody-binding domain to a 200-amino-acid recombinant peptide of the known antigen. Over-lapping truncations of this peptide do not bind complement-fixing antibodies, suggesting that the responsible epitope(s) are conformational. Further, anchoring the antigenic peptide to the ELISA plate by means of a C-terminal biotin-mimic peptide tag instead of allowing the peptide to randomly adhere to the plastic plate improves sensitivity of antibody detection by 1–2 logs in different sera. The newly developed ELISA shows a significant quantitative correlation with complement-fixing antibody titers. This ELISA shows potential as the basis for a new quantitative assay for coccidioidal antibodies.

DISSEMINATED COCCIDIOMYCOSIS MASQUERADING AS SUBARACHNOID HEMORRHAGE

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Increased attenuation of basal cisterns and subarachnoid space on the computed tomography (CT) scan is the typical finding of subarachnoid hemorrhage (SAH). Several causes have been known to mimic the radiological findings of SAH, including pyogenic meningitis, leptomeningeal carcinomatosis, or recently administered intrathecal or intravenous contrast. We report a case of persistent headache whose CT scan had the typical finding of SAH and hydrocephalus but was diagnosed as disseminated coccidiomycosis. CASE PRESENTATION: A 53-year-old African American male with unknown medical history who live in TX. He is an operator for an oil company and has to travel around the States. He presented with a 1-month history of persistent headaches, night sweat, and weight loss. His boss noticed that he had been having episodes of confusion for the past 2 weeks and requested him to be evaluated. Upon arrival at the ED, he was confused without significant neurological abnormality on the exam. Vital signs were unremarkable. CT head without contrast revealed hydrocephalus, with areas of increased attenuation noted within the bilateral sylvian fissures, mid brain, and cerebral peduncle consistent with SAH. CT angiography did not show cerebral aneurysms. Magnetic Resonance imaging (MRI) revealed diffuse leptomeningeal enhancement, hydrocephalus, and papilledema. Lumbar puncture revealed colorless cerebrospinal fluid (CSF) with remarkable for white cell count of 250 cells/mm3 (59% lymphocytes), protein of 360 mg/dL, glucose of 36 mg/dL, and elevated open pressure of 45 cm of water. Serum and CSF Coccidioides complement fixing antibody titer were elevated, 1:32 and 1:2048 respectively. CSF culture grew Coccidioides immitis/posadasii. CT chest showed ground glass lesions on the right upper lobe. Bronchoalveolar lavage grew Coccidioides sp.. Ventriculoperitoneal shunt was placed and fluconazole was initiated. Neurological status improved and he was discharged a week later. DISCUSSION: Coccidioides spp. typically cause asymptomatic or mild primary infection. Infection can disseminate and involve the central nervous system (CNS), skin, joints, and bones. Meningitis with hydrocephalus is the most common CNS presentation. Our case posed a diagnostic difficulty because of the SAH appearance and hydrocephalus on the initial CT scan. Based on the imaging findings alone, the most likely diagnosis was felt to be SAH with complicated hydrocephalus. However, there was a disparity between the radiologic findings and the symptoms onset. This was reinforced by the MRI and lumbar punctures, which gave the definite diagnosis of disseminated coccidiomycosis with meningitis. CONCLUSIONS: We suggest that CNS infection should be considered if the clinical presentation is atypical or not in keeping with the radiological findings of SAH. Reference #1: Al-Yamany M, et al. Pseudo-subarachnoid hemorrhage: a rare neuroimaging pitfall. Can J Neurol Sci 1999;26: 57–59 Reference #2: Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Geertsma F, Hoover SE, et al. 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clin Infect Dis. 2016;63(6):e112-46. DISCLOSURES: No relevant relationships by Cinthya Carrasco Barcenas, source=Web Response No relevant relationships by John Makram, source=Web Response No relevant relationships by Haneen Mallah, source=Web Response No relevant relationships by David Sotello Aviles, source=Web Response No relevant relationships by Myrian Vinan Vega, source=Web Response No relevant relationships by Wasawat Vutthikraivit, source=Web Response

Immunologic studies of patients with histoplasmosis.

Immunologic responses of patients with active histoplasmosis (Group I) were compared to the responses of healthy persons with positive histoplasmin skin-test reactions (Group II), and to those of healthy persons with negative histoplasmin skin-test reactions (Group III). Cellular immune responses were significantly depressed in patients. Seven (54 per cent) of 13 patients failed to respond to histoplasmin skin testing, and two (15 per cent) failed to respond to skin-test antigens unrelated to Histoplasma capsulatum. Lymphocyte transformation (LT) responses of patients were severely depressed in vitro (p less than 0.001) to Histoplasma antigens when compared to the responses of healthy, histoplasmin-reactive donors. Transformation responses to Candida antigen were not impaired in the patient population. Culturing lymphocytes of patients in serum obtained from healthy donors as opposed to autologous serum resulted in a significant (p less than 0.05) increase in LT responses to H. capsulatum. Responses to Candida antigen and to mitogens were not affected by the serum source. Serum-mediated suppression of LT responses correlated (p less than 0.01) with complement-fixing antibody titers to Histoplasma yeast-phase antigen and suggests that antibody, either alone or complexed with antigen, may suppress T-cell response in vitro in this disease.

Routine CSF Analysis in Coccidioidomycosis Is Not Required

Although routinely done, there has been no evaluation of the utility of performing routine cerebrospinal fluid (CSF) examination in patients with active coccidioidomycosis and high complement fixation (IgG) antibody titers or other risk factors for disseminated infection. In our review 100% of patients diagnosed with coccidioidal meningitis had at least one sign or symptom consistent with infection of the central nervous system, headache was present in 100% of those with meningitis, while no patients without signs/symptoms of CNS infection were found to have coccidioidal meningitis, irrespective of antibody titers or other risk factors. Thus routine lumbar puncture may be unnecessary for patients with coccidioidomycosis who lack suggestive clinical symptoms.

Pediatric Coccidioidomycosis in Central California: A Retrospective Case Series

Coccidioidomycosis, an endemic fungal infection seen throughout the southwestern United States, is not well described in children. We performed a retrospective observational study of all children admitted to Children's Hospital Central California with coccidioidomycosis from 1 January 2010 to 1 September 2011. Thirty-three children, aged 6 months to 17 years, were hospitalized during the study period. These included patients with pneumonia (n = 28), pleural effusion (n = 13), pleural empyema (n = 4), lung abscess (n = 7), pericarditis (n = 2), osteomyelitis (n = 5), meningitis/cerebritis (n = 2), and vocal cord infection (n = 1). Mediastinitis, with radiographic evidence of purulence and necrotic/abscessed lymph nodes in the mediastinum, was present in 7 patients (21%) and tended to occur more often in younger children (median age, 3 years [range, 0.5-11 years] vs 7 years [range, 0.6-17 years] for non-mediastinitis patients; P = .10). Seven patients were admitted to the intensive care unit and 10 required surgical intervention. One patient died of meningitis. Hospitalizations were longer for patients with mediastinitis (median, 130 days [range, 58-200 days] vs 43 days [range, 3-273 days for non-mediastinitis patients]; P < .01) and those with maximum coccidioidal complement fixing antibody titers ≥1:128 (median, 174 days [range, 53-273 days] vs 33 days [range, 3-200 days] for those with maximum titers <1:128; P < .01). Coccidioidomycosis causes a substantial disease burden in the children of central California. Mediastinitis is common and tends to occur in younger children. Patients with mediastinitis or elevated coccidioidal complement fixation titers require longer hospitalizations. Further research is needed on the prevention and treatment of this disease.

Persistent pulmonary infection with an azole-resistantCoccidioidesspecies

We report a case of a life-threatening, recurrent, and azole-resistant pulmonary coccidioidomycosis in a patient receiving long-term fluconazole therapy for a history of coccidioidal meningitis. Since this diagnosis, the patient has received weekly amphotericin B for more than four years and remains in remission with a stable serum Coccidioides complement fixation antibody titer.

Immunomodulatory activity of biopolymeric fraction BOS 2000 from Boswellia serrata

Oral administration of BOS 2000 (1-10 mg/kg) elicited a dose related increase in the delayed hypersensitivity reaction (early 24 h and delayed 48 h) in mice. It also stimulated the IgM and IgG titre expressed in the form of plaques (PFC) and complement fixing antibody titre. The concentration of cytokines (IL-4, IFN-gamma and TNF-alpha) in serum with respect to T cell interactions, i.e. (CD4/CD8) and the proliferation of lymphocytes were significantly increased at 10 mg/kg compared with the control. The results in these studies demonstrated the immunostimulatory effect of BOS 2000 in a dose-dependent manner with respect to the macrophage activation possibly expressing the phagocytosis and nitrite production by the enhancement of TNF-alpha and IFN-gamma production as a mode of action.

Chronic Foot Ulcers in a Patient with Hepatitis C

The warty lesions (figure 1) and ulcers (figure 2) were consistent with a chronic, indolent infectious process. Biopsy of the heel ulcer revealed marked verrucuform hyperplasia and occasional microabscesses in the epidermis. The biopsy showed spherules with mixed inflammatory infiltrates and granulomas characteristic of Coccidioides immitis in the dermis (figure 3). Fungal culture of a deep swab of the calcaneal ulcer grew C. immitis. Routine culture grew mixed gram-negative species, including Pseudomonas aeruginosa. Serologic tests showed a highly elevated Coccidioides complement-fixation antibody titer of 1:256. Results of a total coccidioidal IgG EIA were positive. Findings of a chest radiograph were normal. Plain films of the foot showed no bone destruction, but a bone scan of the affected foot revealed uptake consistent with osteomyelitis. The case we report illustrates disseminated coccidioidomycosis in a patient with classic risk factors. He was of Filipino descent, lived for an extended time in the southwest corner of the United States, and worked outdoors. All of these factors, in addition to his sex, increased the risk for the development of active disease caused by this endemic fungus [1]. Coccidiomycosis has also been reported in patients with end-stage liver disease who live in an area where Coccidioides species are endemic [2]. The stage of this patient's liver disease, which resulted from hepatitis C infection, was not known at the time this report was prepared. Despite the localized presentation of his coccidioidal infection, this patient most likely had an initial pulmonary infection with subsequent dissemination. Disseminated coccidioidal infection is thought to result from hematogenous spread from the lungs after inhalation of arthroconidial spores, which can survive in soil [1, 3]. At least two-thirds of primary pulmonary infections are benign and self-limited [3, 4]. A recent, large

Influenza-Like Illness During Pregnancy: Results from a Study in the Eastern Townships, Province of Quebec

Objectives: (1) To assess the frequency of influenza and influenza-like illness (ILI) during pregnancy; (2) to explore the associated risk of adverse maternal and fetal outcomes.Methods: All women who delivered at the Sherbrooke University Hospital in the province of Quebec during the period of February 15 to April 30, 2002, were invited to complete a questionnaire. Medical records of participating women and of their infants were reviewed. Complement-fixing antibody titres against influenza A were measured in paired sera drawn during antenatal screening and at delivery.Results: The study participation rate was 96. 3%. Nine of 517 women stated that they had received the influenza vaccine during pregnancy, and only 3 of 47 women with a chronic pulmonary disease had been immunized. Overall, 464 ILI episodes were reported by 331 women, and a significant maternal complication occurred in 8 cases. ILI episodes resulted in medical consultations in 55.4% of cases, and in antibiotic prescriptions in 13.8% of cases. There was no indication of an increased frequency of adverse perinatal outcomes associated with ILI during pregnancy. Paired sera were available for 156 participants and seroconversion was observed in 6.6%.Conclusions: ILI during pregnancy was associated with health services utilization but complications were infrequent. More studies are needed to demonstrate the usefulness of routine vaccination of healthy pregnant women against influenza.

Pre-infection frequencies of equine herpesvirus-1 specific, cytotoxic T lymphocytes correlate with protection against abortion following experimental infection of pregnant mares

In general, vaccines containing inactivated equine herpesvirus-1 (EHV-1) fail to prevent abortion in pregnant mares following infection with a virulent strain of EHV-1. We have tested the hypothesis that resistance to EHV-1-induced abortion in pregnant mares is associated with high frequencies of EHV-1 specific, major histocompatibility complex (MHC) class I-restricted, cytotoxic T lymphocytes (CTL) in the circulation. To test this theory, three groups of pregnant mares were assembled with varying backgrounds of infection or vaccination in an attempt to mimick the immune status of the general population. Group 1 mares ( n=9) were untreated controls selected at random. Group 2 mares ( n=5) were vaccinated three times intramuscularly with inactivated EHV-1. Group 3 mares ( n=3) had been infected with EHV-1 on four previous occasions. The frequency of CTL in blood leucocytes was measured by limiting dilution analysis at three time points; at the beginning of pregnancy (approximately 28 weeks before infection) in the Group 2 and Group 3 mares (4–7 weeks of gestation) (Group 1 was unavailable for sampling) and then 2 weeks before (30–40 weeks of gestation) and 3 weeks after experimental infection in all the mares. Serum samples were collected to monitor complement fixing (CF) antibody titres. Mares in all three groups were infected experimentally with EHV-1 strain Ab4/8 by the intranasal route after which they were monitored clinically to determine the outcome of pregnancy and samples were collected to determine the duration of nasopharyngeal shedding and cell-associated viraemia. The untreated control mares showed low pre-infection CTL. After experimental infection, they all seroconverted, aborted and demonstrated expected clinical and virological signs. Some vaccinated mares (3/5) had elevated titres of CF antibody prior to their first vaccination. All the vaccinated mares seroconverted after vaccination and exhibited higher CTL frequencies than controls before infection. Four of the five foaled normally. The multiply infected mares had low CF antibody titres prior to infection and showed neither seroconversion nor clinical or virological signs after infection. All multiply infected mares exhibited high frequencies of CTL before infection and they all foaled normally. The CTL frequencies observed differed significantly from the expected frequencies in the control and multiply infected groups at 2 weeks pre-infection ( P=0.034) and between the foaling and aborting mares at 2 weeks pre-infection ( P=0.005) and 3 weeks post-infection ( P=0.015). The results show a positive correlation between the number of virus-specific CTL in the peripheral blood of pregnant mares and their protection against abortion induced by EHV-1 infection. Therefore, as indicated by this study, rational approaches to the development of new vaccines for EHV-1 should stimulate cytotoxic immune responses and develop virus-specific CTL as pre-requisites for protection against abortion.

Pre-infection frequencies of equine herpesvirus-1 specific, cytotoxic T lymphocytes correlate with protection against abortion following experimental infection of pregnant mares

In general, vaccines containing inactivated equine herpesvirus-1 (EHV-1) fail to prevent abortion in pregnant mares following infection with a virulent strain of EHV-1. We have tested the hypothesis that resistance to EHV-1-induced abortion in pregnant mares is associated with high frequencies of EHV-1 specific, major histocompatibility complex (MHC) class I-restricted, cytotoxic T lymphocytes (CTL) in the circulation. To test this theory, three groups of pregnant mares were assembled with varying backgrounds of infection or vaccination in an attempt to mimick the immune status of the general population. Group 1 mares (n=9) were untreated controls selected at random. Group 2 mares (n=5) were vaccinated three times intramuscularly with inactivated EHV-1. Group 3 mares (n=3) had been infected with EHV-1 on four previous occasions. The frequency of CTL in blood leucocytes was measured by limiting dilution analysis at three time points; at the beginning of pregnancy (approximately 28 weeks before infection) in the Group 2 and Group 3 mares (4–7 weeks of gestation) (Group 1 was unavailable for sampling) and then 2 weeks before (30–40 weeks of gestation) and 3 weeks after experimental infection in all the mares. Serum samples were collected to monitor complement fixing (CF) antibody titres. Mares in all three groups were infected experimentally with EHV-1 strain Ab4/8 by the intranasal route after which they were monitored clinically to determine the outcome of pregnancy and samples were collected to determine the duration of nasopharyngeal shedding and cell-associated viraemia. The untreated control mares showed low pre-infection CTL. After experimental infection, they all seroconverted, aborted and demonstrated expected clinical and virological signs. Some vaccinated mares (3/5) had elevated titres of CF antibody prior to their first vaccination. All the vaccinated mares seroconverted after vaccination and exhibited higher CTL frequencies than controls before infection. Four of the five foaled normally. The multiply infected mares had low CF antibody titres prior to infection and showed neither seroconversion nor clinical or virological signs after infection. All multiply infected mares exhibited high frequencies of CTL before infection and they all foaled normally. The CTL frequencies observed differed significantly from the expected frequencies in the control and multiply infected groups at 2 weeks pre-infection (P=0.034) and between the foaling and aborting mares at 2 weeks pre-infection (P=0.005) and 3 weeks post-infection (P=0.015). The results show a positive correlation between the number of virus-specific CTL in the peripheral blood of pregnant mares and their protection against abortion induced by EHV-1 infection. Therefore, as indicated by this study, rational approaches to the development of new vaccines for EHV-1 should stimulate cytotoxic immune responses and develop virus-specific CTL as pre-requisites for protection against abortion.

A role for nonprotective complement-fixing antibodies with low avidity for measles virus in atypical measles.

In the 1960s, a formalin-inactivated measles vaccine (FIMV) predisposed recipients to atypical measles, an immune complex-mediated disease. To identify characteristics of the immune priming that leads to atypical measles, responses of monkeys to FIMV were compared with responses to live attenuated virus (LAV) and hemagglutinin (H-DNA) vaccines that do not prime for atypical measles. Antibodies induced by FIMV were transient and avidity did not mature. Antibodies induced by LAV and H-DNA vaccines were sustained and avidity matured over time. After challenge with measles virus, FIMV and H-DNA recipients developed high titers of complement-fixing antibodies. In FIMV recipients, the antibodies were of low avidity, whereas in H-DNA vaccine recipients, the antibodies were of high avidity. Neutralizing capacity in B958 cells correlated with avidity. Only FIMV recipients had immune complex deposition. Failure of FIMV to induce affinity maturation results in anamnestic production of nonprotective, complement-fixing antibodies, immune complex deposition and atypical measles.

A cross-protection experiment in pigs vaccinated with Haemophilus parasuis serovars 2 and 5 bacterins, and evaluation of a bivalent vaccine under laboratory and field conditions.

Cross-protection between Haemophilus parasuis serovars 2 and 5 was examined in pigs using a bacterin based vaccine, and subsequently the safety and efficacy of a bivalent vaccine were evaluated. Upon intratracheal challenge of a serovar 2 or 5 strain, pigs immunized with a monovalent vaccine were protected against challenge with a homologous serovar strain, but not with a heterologous serovar strain. Immunization with a bivalent vaccine containing both serovars 2 and 5 bacterins conferred protection in pigs against lethal challenge with each of the serovar strains. A total of 86 pigs from two SPF herds were injected with the bivalent vaccine intramuscularly twice at a four-week interval. No adverse reactions following the vaccination were observed. On day 7 after the second vaccination, vaccinated and non-vaccinated control pigs from herd A were transferred to herd B, where Glasser's disease had broken out. Pigs in the control group developed clinical signs of the disease, and 6 of 8 (75%) pigs died until slaughter, in contrast with only 4 of 46 (9%) pigs in the vaccinated group. In herd C, where there was no outbreak of Glasser's disease, complement fixation antibody titer was raised only in the vaccinated group. A challenge experiment on days 20 and 79 after the second vaccination showed that only the vaccinated pigs were protected. From these findings, the safety and efficacy of the bivalent vaccine were confirmed under laboratory and field conditions.

The therapeutic use of isometamidium chloride against Cryptobia salmositica in rainbow trout Oncorhynchus mykiss.

Rainbow trout Oncorhynchus mykiss injected intramuscularly with isometamidium chloride (0.01 or 0.1 mg kg-1) at 3 wk post-infection and given a booster 2 wk later had significantly lower parasitaemias than infected controls. Packed cell volume increased after treatment and remained higher than in infected controls. The concentration of isometamidium in plasma was highest at 2 wk after injection and then declined. An intramuscular dose of 1.0 mg kg-1 of isometamidium chloride at 1, 2 and 3 wk postinfection (preclinical) significantly reduced the parasitaemia in rainbow trout 2 wk after treatment. A booster at 9 wk postinfection (chronic disease phase) reduced the parasitaemia further in all fish. The packed cell volume in these fish was higher than in infected controls. Treatment at 5, 6, and 7 wk postinfection (acute disease) had no effects and parasitaemias in treated fish were higher than in infected controls; also, anti-Cryptobia salmositica antibodies and titres of complement-fixing antibody were higher in these than in infected controls. Incubation of immune plasma or complement with isometamidium for 3 h did not affect the lytic titres of complement-fixing antibodies nor rainbow trout complement.

Late lesions of experimental contagious caprine pleuropneumonia caused by Mycoplasma capricolum ssp. capripneumoniae.

A clinical, bacteriological, serological and patho-anatomical study was carried out on 12 goats surviving the acute stage of contagious caprine pleuropneumonia (CCPP), experimentally produced with Mycoplasma capricolum ssp. capripneumoniae (M. capripneumoniae), with the major aims of investigating the chronic stage of the disease and elucidating the possibility of a carrier state beyond the acute fulminant phase. The goats were killed 9, 16, 82 or 126 days after the onset of acute clinical signs. On day 9, clinical signs included low grade fever and persistent coughing. Thereafter, only intermittent coughing was recorded. Serum titres of complement-fixing antibodies to M. capripneumoniae were high at the period of fever but dropped thereafter. Post-mortem examination showed acute fibrinous pleuropneumonia on days 9 and 16, and chronic pleuropneumonia on days 82 and 126, including sequester formations in goats killed on day 126. Mycoplasma capripneumoniae was isolated on days 9 and 16 but not on later occasions. The study showed that goats recovered from acute CCPP may have lesions for a long time thereafter but provide no evidence of a carrier state among long-term survivors.

頭振後眼振を示した片側性ベル麻ひ例

A case of idiopathic unilateral peripheral facial palsy showing unique findings and time course of the head shaking nystagmus was reported.A 15 year-old woman complained of right facial paralysis. She was admitted to our hospital for treatment using a drip infusion of steroids. Three days after onset of the paralysis, she complained of vertigo. At that time she showed no spontaneous or positional nystagmus but manifested right beating nystagmus 5 seconds after the cessation of head shaking stimulation. Six days after onset of the vertigo, right beating nystagmus was also observed but it appeared 40 seconds after the cessation of head shaking. It is assumed that she showed only the 2nd phase of head shaking nystagmus without the 1st phase because of the long latency period. She showed a mild increase in complement fixing antibody titer to the varicella-zoster virus.The head shaking test is well known to be quite sensitive in the detection of unilateral vestibular disorders. Since the 1st phase of head shaking nystagmus is due to velocity storage, any process that interferes with velocity storage can alter the pattern of nystagmus. When velocity storage is very poor, the 1st phase of head shaking nystagmus may be brief or absent. Thus, it is assumed that the patient in the present report had a lesion in the central vestibular system, presumably in the velocity storage mechanism due to varicella-zoster virus infection.

Treatment of Atypical Pneumonia with Azithromycin: Comparison of a 5-Day and a 3-Day Course

The efficacy of a 5-day regimen consisting of 500 mg in a single dose on the first day followed by 250 mg once daily for 4 consecutive days was compared with that of a 3-day course of azithromycin given in single daily doses of 500 mg for treatment of atypical pneumonia. Adult patients hospitalized with atypical pneumonia in the years 1990 to 1993 were studied retrospectively. For each patient, the medical history, laboratory data, the results of serological tests, chest radiographs and treatment outcome were reviewed. Out of 148 patients with atypical pneumonia, 40 were treated with azithromycin for 5 days (Group 1) and 41 for 3 days (Group 2). The success rate in Group 1 was 80% (32 patients). Eight patients did not respond to treatment: 5 had significant complement fixing antibody titers to adenovirus and in 3 the etiology was unknown. The success rate in Group 2 was 88% (36 patients). Azithromycin was ineffective in all 3 patients with adenoviral pneumonia, in 1 patient with Q fever, and in 1 patient with no identified pathogen. Azithromycin is equally effective as treatment of atypical pneumonia in adult patients if given for 3 or 5 days at the same total dose.

Prediction of relapse after treatment of coccidioidomycosis.

Relapse after apparently successful treatment of coccidioidomycosis has been a problem with both amphotericin B and the azoles. We conducted a retrospective cohort study of 34 patients who required therapy for coccidioidomycosis between 1973 and 1993; 10 relapsed and 25 (one patient received two courses of therapy) did not relapse during follow-up. The mean time to relapse after completion of therapy was 7.3 months (range, 1-21 months). All 34 patients responded clinically to therapy. A fourfold or greater decrease in titers of antibody, as determined by complement fixation (CF), during therapy was seen in seven (78%) of nine patients who relapsed and 17 (85%) of 20 patients who did not relapse (P = .956). There was no significant difference between relapsers and nonrelapsers in terms of the lowest CF titer during therapy, the CF titer at the end of therapy, or the peak CF titer. The risk of relapse was increased among those with a peak CF titer of > or = 1:256 (relative risk [RR] = 4.7; 95% confidence interval [CI] = 1.4-16.1), as compared with patients who did not mount such a high antibody response. Similarly, the risk of relapse was higher among those with serially negative coccidioidin skin tests (CSTs) than those with serially positive CSTs (RR = 4.8; 95% CI = 1.2-19.5). We conclude that clinical response, lowest CF titer, end-of-therapy CF titer, and decrease in the CF titer of at least fourfold are not predictive of relapse in patients with coccidioidomycosis. Negative serial coccidioidin skin tests and a peak CF antibody titer of > or = 1:256 are independently associated with increased risk of relapse.

Protective Antibodies and Anamnestic Response in Salvelinus fontinalis to Cryptobia salmositica and Innate Resistance of Salvelinus namaycush to the Hemoflagellate

Cryptobia-susceptible Salvelinus fontinalis vaccinated with a live Cryptobia salmositica vaccine were protected against C. salmositica and they were still protected 53 wk after their initial challenge. Parasites were lysed when they were incubated with immune plasma and complement and this confirms that complement-fixing antibody is an important part of the protective mechanism. Immunological memory was demonstrated in both vaccinated-challenged, and infected-recovered S. fontinalis as there were rapid and significant increases in complement-fixing antibody titers after parasite challenge. This indicates that S. fontinalis are capable of an anamnestic response. Most naive Salvelinus namaycush were not susceptible to C. salmositica infection, and their fresh plasma lysed C. salmositica under in vitro conditions. The lytic factor(s) was inactivated by heating the plasma prior to parasite incubation. This indicates that the alternate pathway of complement activation is likely the mechanism of innate resistance in S. namaycush.