The use of an excretory-secretory antigen for an ELISA specific sero-diagnosis of visceral larva migrans

In sera from patients with visceral larva migrans (VLM) syndrome, enzyme-linked immunospecific assay (ELISA) was used to detect IgG and IgE antibody anti-excretory-secretory antigen (ESA) from the second larval stage of Toxocara canis. The technical conditions of the assay were determined. The specificity of IgG ELISA-ESA (with OD values greater than 0.34) allowed the differentiation of VLM syndrome from ascaris or other human parasite infections.     

Hepatic granulomas due to visceral larva migrans in adults: Appearance on US and MRI

Visceral larva migrans is a syndrome characteristically involving children with a history of pica, and usually presents with fever, abdominal pain, tender hepatomegaly, and hypereosinophilia. Hepatic granulomas of visceral larva migrans are rare in adults. We describe three adult patients with hepatic lesions which on histopathology demonstrated characteristic granulomas of visceral larva migrans. All patients had abdominal sonograms and two had additional MR scans of the liver. Both ultrasound and magnetic resonance imaging demonstrated characteristic appearances which have not been described previously (viz., ill-defined central necrotic areas surrounded by concentric thick walls and perifocal edema in the liver parenchyma).     

Hepatic imaging studies on patients with visceral larva migrans due to probable Ascaris suum infection

Visceral larva migrans (VLM) is a disease usually observed in children in which the larvae of animal parasites invade and reside in human tissues for long periods. Although the common causal species of VLM are Toxocara canis and T. cati, we identified three adult patients with VLM, probably due to Ascaris suum, whose diagnosis was made by specific immunoserological tests. The patients complained of respiratory symptoms, and laboratory tests showed pronounced eosinophilia, but neither larvae nor eggs were detected in stool samples. We present the findings of various imaging studies of the patients. Multiple small hypoechoic mass lesions were demonstrated by ultrasound tomography, which disappeared after anti-helminthic therapy. Hepatic mass lesions were detected as low-density areas on computed tomography, as high signal intensities on T2-weighted magnetic resonance images, as space-occupying regions in liver scintigraphy, and as yellow-white nodules in laparoscopy. Although biopsied liver tissue specimens showed marked infiltrations of eosinophiles in the portal tracts and hepatic sinusoids, neither larvae nor eggs could be identified.     

Treatment of cutaneous larva migrans and Toxocara infection

The treatment of cutaneous larva migrans and Toxocara infection relies on antihelminthic agents such as thiabendazole, albendazole and ivermectin. The efficacy of these agents varies according to the helminthic disease.     

Toxocariasis of the liver: visceral larva migrans

Toxocariasis is caused by dog ascarid, Toxocara canis, forming eosinophilic inflammation such as eosinophilic abscess or granuloma in the liver and lungs. The lesions move slowly and thus the disease is called as visceral larva migrans. On CT or MR imaging, hepatic lesions are seen as multiple, ill-defined, oval lesions that measure 1.0–1.5 cm in diameter. Sometimes, the lesion may be angular or trapezoid. The lesions are usually best seen on the portal venous phase in dynamic contrast-enhanced CT and MR imaging; the lesions are either not seen or only faintly seen on arterial and equilibrium phases. Either an enhancing rim or enhancing nodules are sometimes observed. On sonography, the lesions appear as multiple, small, oval hypoechoic lesions in the liver parenchyma. The lesions differ from metastatic nodules is as much as they have fuzzy margins, are uniform in size, non-spherical shape and are best seen on portal venous phase. On follow-up imaging, the lesions may improve, or sometimes a change positions, reflecting migration of larva in the liver, supporting the phenomenon of visceral larva migrans.     

Parasites, pets, and people

It is important for the family physician to understand that patients' relationships with their pets play an important role in helping maintain mental and physical health yet provide the potential for causing illness in the patient. Toxocara canis (dog roundworm) and Toxocara cati (cat roundworm) are the ascarids most commonly responsible for VLM and ocular larva migrans in humans. These roundworms live in their adult stage in the small intestine of the dog and cat where their eggs are passed in the feces. The eggs containing the infective larva are very sticky, thus an infant crawling around on the floor can easily pick these up on fingers that almost invariably end up in the mouth. Infections are usually mild and asymptomatic but with a persistent eosinophilia. Ocular larva migrans is the form usually occurring in older children and adults. Some public health veterinarians recommend that a puppy or kitten should not be obtained as a companion for a child who is not old enough to read, thus bypassing the crawling and toddler stages. Hookworm eggs, shed in the feces of infected dogs or cats, develop into the infective second stage within a week. Humans are usually infected when bare areas of skin such as bare feet or the torso come in contact with soil contaminated with the larvae. The second-stage larvae are able to penetrate the intact skin of humans and the foot pads of dogs and cats. In the United States, the common dog hookworm, A. caninum, is a widespread parasite. Human intestinal ancylostomiasis caused by this species is rare, with only six cases recorded in the literature. Infection in humans or animals by the common tapeworm of dogs and cats (Dipylidium caninum) requires ingestion of the intermediate host, the dog or cat flea containing the larva (cysticercoids) of the agent. Many cases in humans are asymptomatic. Dipylidiasis affects mainly infants and young children who may swallow a flea that hops up while the infant is crawling on the floor or fondling the family pet. Humans appear to be highly resistant to the infection, given the high frequency of flea infestation on dogs and cats and the relative rarity of human disease. Pinworms of animal hosts are not transmissible to humans. Humans become an accidental host of dirofilaria when bitten by an infected mosquito, although the microfilaria will not mature to the adult form in humans. Radio-opaque coin-type lung lesions can be noted on radiographs.(ABSTRACT TRUNCATED AT 400 WORDS)     

COVERT TOXOCARIASIS – A CAUSE OF RECURRENT ABDOMINAL PAIN IN CHILDHOOD

Toxocariasis, usually caused by Toxocara canis, is a zoonosis acquired by ingestion of worms which inhabit the gut of young canines. Domestic pets, such as dogs, become infected from soil in public parks and playgrounds which are often heavily contaminated.¹ Although toxocariasis is often regarded as having two principal, though uncommon, manifestations — visceral larva migrans (VLM) and ocular toxocariasis (OT) — recent studies have suggested otherwise.^2,3 A third, more common, condition, termed ‘covert toxocariasis’, describes patients in whom positive toxocara serology is associated with a number of systemic and localised symptoms and signs (notably abdominal pain) but not VLM or OT. A quarter of patients with covert toxocariasis have no eosinophilia and, although symptoms regress after treatment, they may persist for months or years. We report a 13-year-old girl with recurrent abdominal pain who, despite positive toxocara serology, was extensively investigated for other abdominal pathology.     

Cutaneous larva migrans in northern climates

Cutaneous larva migrans is a distinctive dermatitis caused by the filariform larvae of certain nematode parasites. Most often associated with tropical climates, it has increasingly been noted in nontropical settings. To familiarize northern clinicians with this condition, a case report is presented and its pathophysiology, diagnosis, and treatment are reviewed.     

Electrocardiographic findings in children with erythema migrans

OBJECTIVE: To assess electrocardiographic findings in children with erythema migrans and to compare them with findings obtained in a healthy control group of comparable age and with a similar proportion of boys and girls. METHODS: Electrocardiograms were carried out in 147 children under the age of 15 years before treatment with antibiotics for erythema migrans (solitary 68 patients, multiple 79 patients) and in the control group of 148 healthy children. RESULTS: Abnormal electrocardiographic findings were detected more often in healthy children than in patients (14% versus 5%; P = 0.0303) and among patients more often in boys than in girls (10% versus 0%; P = 0.0107). Electrocardiographic abnormalities characteristic for Lyme borreliosis, such as atrioventricular blocks, were rare: in patients with erythema migrans only one child had first-degree atrioventricular block; in the control group one child had first-degree and another had second-degree atrioventricular block. Patients with erythema migrans had shorter PR and RR intervals and lower R and S wave voltages in V1 than the healthy children. Comparison among patients with solitary and multiple erythema migrans did not reveal significant electrocardiographic differences. The frequency of electrocardiographic abnormalities in patients with erythema migrans was not associated with the presence of systemic symptoms, or with the presence of meningitis or the isolation of Borrelia burgdorferi sensu lato from the blood. CONCLUSIONS: Electrocardiographic abnormalities in children with erythema migrans are mild, nonspecific and rare. The presence of clinical signs and symptoms indicative or suggestive of disseminated Lyme borreliosis is not associated with higher frequency of such abnormalities. Comparison of findings in patients with erythema migrans and healthy children revealed several distinctions, some of which might have been interpreted as a result of altered activity of the autonomic nervous system.     

Clinical appearance of erythema migrans caused by Borrelia afzelii and Borrelia garinii – effect of the patient's sex

AIM: The aim in this survey was to study the clinical characteristics of infections caused by Borrelia genospecies in patients with erythema migrans where borrelial origin was confirmed by polymerase chain reaction. The aim was also to study factors influencing the clinical appearance of erythema migrans. METHODS: The study was conducted in southern Sweden from May 2001 to December 2003 on patients 18 years and older attending with erythema migrans at outpatient clinics. All erythema migrans were verified by polymerase chain reaction, photographed and categorized as "annular" or "non-annular" lesions. A logistic regression model was used to analyze relations between the appearance of the erythema migrans (i.e. annular or non-annular) and factors that influenced its clinical appearance. RESULTS: A total of 118 patients, 54 women (45.8%) and 64 men (54.2%), fulfilled the inclusion criteria. Of these patients, 74% were infected by B. afzelii and 26% by B. garinii (p < 0.001). A total of 45% (38/85) of the erythema migrans were annular, 46% (39/85) were nonannular and 9.4% (8/85) were atypical. For men infected by B. afzelii, the odds ratio of developing non-annular erythema migrans was 0.09 (95% CI: 0.03-0.33) in comparison with women with the same infection. CONCLUSIONS: In this prospective study of a large series of erythema migrans, where infecting genospecies were confirmed by polymerase chain reaction, the sex of patients infected with B. afzelii had a strong influence on the appearance of the rash. Patients infected by B. garinii more often had non-annular erythema migrans and a more virulent infection with more individuals presenting with fever, raised levels of C-reactive protein and seroreactivity in the convalescence sera.     

Toxocara and bronchial hyperreactivity--results of a seroprevalence study

For more than 30 years the ascarid Toxocara canis, a parasite of the dog, has been considered a possible cause of allergic-pulmonal irritations (i.e. asthma bronchial) in man. According to a British study thousands of people are presumably suffering from asthma bronchial as a consequence of Toxocara infestations. The aim of our recent study was the assessment of the Toxocara seroprevalence in patients of varying bronchial reactivity and status of atopy suffering from respiratory disturbances. 191 serum samples from 59 male (mean age: 31.7 years) and 132 female patients (mean age: 36.6 years) with varying atopy status and degree of bronchial reactivity, living in or near Vienna, were examined for specific IgG antibodies against excretory-secretory (E/S) Toxocara canis antigen with enzyme-linked immunosorbent assay (TES-ELISA) and Western blot (TES-WB). In total a Toxocara seroprevalence of 9.4% could be assessed among these patients. 10% of the patients with and 7.8% of the patients without bronchial hyperreactivity were Toxocara-positive. Atopic patients were serologically positive in 7.1% of the cases tested whereas non-atopics showed an antibody prevalence of 14.3%. A comparison of Toxocara seroprevalence assessed within the recent study and in an earlier study among healthy pregnant women in Vienna did not show significant differences. The results of this study carried out in Vienna indicate that patients with bronchial hyper-reactivity or atopy show no higher seroprevalence than the normal population.     

Case studies in international travelers.

Family physicians should be alert for unusual diseases in patients who are returning from foreign travel. Malaria is a potentially fatal disease that can be acquired by travelers to certain areas of the world, primarily developing nations. Transmitted through the bite of the Anopheles mosquito, malaria usually presents with fever and a vague systemic illness. The disease is diagnosed by demonstration of Plasmodium organisms on a specially prepared blood film. Travelers can also acquire amebic infections, which may cause dysentery or, in some instances, liver abscess. Amebiasis is diagnosed by finding Entamoeba histolytica cysts or trophozoites in the stool. Invasive amebic infections are generally treated with metronidazole followed by iodoquinol or paromomycin. Cutaneous larva migrans is acquired by skin contact with hookworm larvae in the soil. The infection is characterized by the development of itchy papules followed by serpiginous or linear streaks. Cutaneous larva migrans is treated with invermectin or albendazole. Case studies are presented.     

Has the presence or absence of Borrelia burgdorferi sensu lato as detected by skin culture any influence on the course of erythema migrans?

The aim of this prospective study was to compare epidemiological and clinical data in patients with a positive Borrelia burgdorferi sensu lato culture and culture-negative erythema migrans skin lesions. Of the 546 adult patients with erythema migrans seen at our institution in 1997 in whom a skin biopsy was performed and the specimen cultured for the presence of B. burgdorferi sensu lato, 235 (43%) had a positive and 311 (57%) a negative skin culture. More women than men were present in both groups and women were also significantly older than men. Tick bites resulting in culture-positive erythema migrans predominated in May (p = 0.012), while in August and September tick bites with subsequent culture-negative skin lesions were more common (p = 0.018 and 0.011, respectively). Similarly, erythema migrans lesions noticed by our patients in May were significantly more often Borrelia culture positive than negative (p = 0.004), while lesions appearing in October were significantly more often culture negative (p = 0.004). In addition to these seasonal differences, the comparison of the large number of Borrelia skin culture-positive and -negative patients with erythema migrans also revealed differences in several clinical parameters including a larger diameter of skin lesions in the culture-positive group (p = 0.007 at presentation, and p = 0.039 at registration, respectively), a lesser number of multiple skin lesions (7/235 versus 27/311, p = 0.006), and a lower frequency of signs/symptoms (p = 0.039) associated with erythema migrans lesions in culture-positive than in culture-negative patients. We have no plausible explanation for the majority of these rather unexpected findings. Of the 59 patients who, prior to biopsy, had received brief courses of antibiotics known to be effective in the treatment of erythema migrans, 12 (20.3%) were culture positive. As anticipated, the ratio of culture positivity in pretreated patients was significantly lower (p < 0.001) than in those without antecedent antibiotic therapy.     

Cerebrospinal fluid findings in adult patients with multiple erythema migrans

This prospective study was performed at the Department of Infectious Diseases, University Medical Centre Ljubljana, Slovenia, in the period from 1991 to 2000. We included all adult patients with multiple erythema migrans who gave consent to lumbar puncture, had routine blood and CSF tests performed, and borrelial antibody titres in CSF and blood determined. In the majority of these patients skin, blood, and CSF specimens were cultured in MKP medium for the presence of Borrelia. Of 332 patients with multiple erythema migrans, 200 (115 females, 85 males, aged 15-80 years) fulfilled inclusion criteria. The median number of skin lesion was three (2-60). Sixty-three (31.5%) patients had no associated symptoms, whereas 137 (68.5%) patients (including two with arthritis, six with radicular pain, a patient with facial palsy, another patient with foot palsy and a patient with transitory diplopia) reported local and/or constitutional symptoms. Routine CSF examination revealed abnormal results in 62/200 (31%) patients: lymphocytic pleocytosis (6-1119 x 10(6)/L leukocytes) was found in 15 (7.5%) patients (six were clinically without systemic symptoms, six had mild systemic symptoms, three reported radicular pains) and elevated CSF protein concentration was present in 52 (26%) patients (nine also had elevated CSF cell counts). Intrathecal borrelial antibody production was demonstrated in eight (4%) patients (only three of them had elevated CSF cell counts) and B. burgdorferi sensu lato was isolated from skin lesions, blood, and CSF in 77/191 (40.3%), 3/154' (1.95%), and 2/200 (1%) patients, respectively. B. afzelii predominated among the isolates. In patients with multiple erythema migrans abnormal CSF findings are not rare and may be present without any clinical sign of central nervous system involvement.     

Comparison of five diagnostic modalities for direct detection of Borrelia burgdorferi in patients with early Lyme disease

Lyme disease, the most commonly reported tick-borne infection in North America, is caused by infection with the spirochete Borrelia burgdorferi. Although an accurate clinical diagnosis can often be made based on the presence of erythema migrans, in research studies microbiologic or molecular microbiologic confirmation of the diagnosis may be required. In this study, we evaluated the sensitivity of 5 direct diagnostic methods (culture and nested polymerase chain reaction [PCR] of a 2-mm skin biopsy specimen, nested PCR and quantitative PCR (qPCR) performed on the same 1-mL aliquot of plasma and a novel qPCR-blood culture method) in 66 untreated adult patients with erythema migrans. Results of one or more of these tests were positive in 93.9% of the patients. Culture was more sensitive than PCR for both skin and blood, but the difference was only statistically significant for blood samples (P<0.005). Blood culture was significantly more likely to be positive in patients with multiple erythema migrans skin lesions compared to those with a single lesion (P=0.001). Positive test results among the 48 patients for whom all 5 assays were performed invariably included either a positive blood or a skin culture. The results of this study demonstrate that direct detection methods such as PCR and culture are highly sensitive in untreated adult patients with erythema migrans. This enabled microbiologic or molecular microbiologic confirmation of the diagnosis of B. burgdorferi infection in all but 4 (6.1%) of the 66 patients evaluated.     

Rates of Severe Outcomes After Bamlanivimab-Etesevimab and Casirivimab-Imdevimab Treatment of High-Risk Patients With Mild to Moderate Coronavirus Disease 2019

Bamlanivimab-etesevimab and casirivimab-imdevimab are authorized by the US Food and Drug Administration for emergency treatment of mild to moderate coronavirus disease 2019 (COVID-19) in high-risk persons. There has been no study comparing their clinical efficacy. In this retrospective study of 681 patients with mild to moderate COVID-19 during a period dominated by severe acute respiratory syndrome coronavirus 2 wild-type and alpha variants, 25 patients (3.7%) had progression to a severe outcome requiring hospitalization and oxygen supplementation within 30 days after monoclonal antibody infusion. Severe outcome was significantly higher among the 181 patients who were treated with casirivimab-imdevimab when compared with the 500 patients who received bamlanivimab-etesevimab (21 [6.6%] vs 13 [2.6%]; P=.01). Patients treated with casirivimab-imdevimab had higher odds of severe outcomes compared with those who received bamlanivimab-etesevimab (odds ratio, 2.67; 95% CI, 1.17 to 6.06). The demographic and clinical characteristics, and the time to monoclonal antibody infusion, of the 2 treatment cohorts were not significantly different. The reason behind this significant difference in the clinical outcomes is unclear, but our observations emphasize potential efficacy differences among antispike monoclonal antibodies against COVID-19. Further clinical studies using larger cohorts of patients are needed to confirm or refute these observations.     

寄生虫感染致外周血嗜酸性粒细胞增多的临床特点

  目的  总结寄生虫感染患者外周血嗜酸性粒细胞的临床变化特点。  方法  北京协和医院2010年1月至2014年12月收治并明确诊断为寄生虫感染的患者87例, 收集其临床资料, 回顾性分析患者外周血嗜酸性粒细胞与感染寄生虫种类及临床受累系统的相关情况。  结果  87例寄生虫感染患者中, 33.3%(29/87)的患者外周血嗜酸性粒细胞绝对计数升高, 14.9%(13/87)的患者绝对计数明显升高(> 1.5×10⁹/L)。卫氏并殖吸虫(100%)、血吸虫(83.3%)及华支睾吸虫(57.1%)是引起外周血嗜酸性粒细胞比例升高的最常见三种寄生虫。呼吸系统和消化系统受累后出现外周血嗜酸性粒细胞比例升高最为常见, 出现嗜酸性粒细胞比例升高的患者分别占85.7%及50.0%, 出现嗜酸性粒细胞绝对计数明显升高的患者分别占28.6%及33.3%。  结论  寄生虫感染患者中, 出现外周血嗜酸性粒细胞升高的患者比例随感染寄生虫种类或主要受累脏器部位不同而有所不同。当遇到高嗜酸细胞血症患者时, 应注意寄生虫感染的鉴别诊断。     

Worms: transmission from animals to man.

It is useful to know that household pets are not involved in the life cycles of some worms, for example, pinworms. Some worms require a household pet in their cycles: the dog and cat roundworms, heartworms, and the dog and cat hookworms, the larvae of which are responsible for cutaneous larva migrans. Strongyloides (threadworm) infestation is sometimes difficult to diagnose and may be traced directly to the family dog.     

Evaluation of immunofluorescence test (IFT) and immuno (western) blot (WB) test in patients with erythema migrans

The diagnosis of Lyme borreliosis is based on the recognition of typical clinical signs and is assisted by laboratory confirmation of borrelial infection. The aim of the present study was to assess the value of an immunofluorescence test (IFT) and an immuno (western) blot (WB) test for the detection of Borrelia burgdorferi sensu lato antibodies in patients with erythema migrans residing in Slovenia. We determined specific IgM and IgG antibodies in 117 patients with erythema migrans and 96 healthy persons using an IFT (in-house test) and a commercial WB test. Skin biopsies of erythema migrans lesions were cultured, and isolated strains were identified with PFGE. There were 66/117 (56.4%) culture-positive and 51/117 (43.6%) culture-negative patients. B. afzelii was found in 52/62 (84%) and B. garinii in 10/62 (16%) biopsies. IFT-IgM antibodies were established in 2/117 (1.7%) erythema migrans patients and in none of the control group, while WB-IgM antibodies were present in 56/117 (48%) patients with erythema migrans and 21/96 (22%) members of the control group (p = 0.002). IFT-IgG antibodies were demonstrated in 3/117 (2.2%) erythema migrans patients and 2/96 (4%) persons of the control group, while corresponding values for WB-IgG were 36/117 (31%) and 26/96 (27%), respectively (non-significant differences). IgM antibodies directed against p41 and OspC, and IgG antibodies directed against p41, p18 and OspC were frequently found in both erythema migrans patients and the control group. The only significant difference between erythema migrans patients and the control group in the WB test was in the reaction of IgM antibodies with OspC antigen, which was found in 54/117 (46%) erythema migrans patients and 18/96 (18.8%) healthy persons (p < 0.0001). The immune response in patients with erythema migrans was very similar to that of the control group determined with either the IFT or WB test.     

Solitary erythema migrans in children: comparison of treatment with azithromycin and phenoxymethylpenicillin

OBJECTIVE: To compare clinical effectiveness and side effects of treatment with azithromycin or phenoxymethylpenicillin in children with solitary erythema migrans. METHODS: Consecutive patients younger than 15 years, referred to our institution in 1998 and 1999 with previously untreated typical solitary erythema migrans, were included in this prospective study. Basic demographic features and clinical data were collected by means of a questionnaire. The efficiency of treatment of acute disease, development of later major and/or minor manifestations of Lyme borreliosis and side effects of treatment were surveyed by follow-up visits during the first year. RESULTS: Forty-two patients received azithromycin 20 mg/kg/day for the first day followed by 10 mg/kg/day for a further four days and phenoxymethylpenicillin 100,000 IU/kg/day for 14 days. No differences in demographic and clinical pre-treatment characteristics were present in the two groups, with the exception of the duration of erythema migrans before treatment (3 days in the azithromycin group versus 4 days in the phenoxymethylpenicillin group; p = 0.0320). The clinical course during the post-treatment period revealed no significant differences between the two groups in the duration of EM (3 days versus 4 days; p = 0.2471), the appearance of minor manifestations of Lyme borreliosis (17.5% in the azithromycin group versus 24.4% in the phenoxymethyl-penicillin group; p = 0.6252), or in the emergence of major manifestations of Lyme borreliosis (one patient in each treatment group). One year after antibiotic treatment all patients were asymptomatic. Side effects of treatment were observed in 5.3% of patients treated with azithromycin and in 6% treated with phenoxymethylpenicillin. The appearance of "Herxheimer's reaction" at the beginning of treatment was recorded in 7 out of 42 patients (6%) in each treatment group. CONCLUSIONS: Azithromycin and phenoxymethylpenicillin are equally effective in treatment of children with solitary erythema migrans and have comparable side effects.