Innate and Adaptive Immune Genes Associated with MERS-CoV Infection in Dromedaries.

The recent SARS-CoV-2 pandemic has refocused attention to the betacoronaviruses, only eight years after the emergence of another zoonotic betacoronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV). While the wild source of SARS-CoV-2 may be disputed, for MERS-CoV, dromedaries are considered as source of zoonotic human infections. Testing 100 immune-response genes in 121 dromedaries from United Arab Emirates (UAE) for potential association with present MERS-CoV infection, we identified candidate genes with important functions in the adaptive, MHC-class I (HLA-A-24-like) and II (HLA-DPB1-like), and innate immune response (PTPN4, MAGOHB), and in cilia coating the respiratory tract (DNAH7). Some of these genes previously have been associated with viral replication in SARS-CoV-1/-2 in humans, others have an important role in the movement of bronchial cilia. These results suggest similar host genetic pathways associated with these betacoronaviruses, although further work is required to better understand the MERS-CoV disease dynamics in both dromedaries and humans.

Gabapentin in horses: validation of an analytical method for gabapentin quantitation.

Gabapentin [1-(aminomethyl)cyclohexaneacetic acid, Neurontin], is a new anticonvulsant used as adjunctive therapy in the treatment of partial seizures in humans not controlled with standard antiseizure drugs, and it has also been used in veterinary medicine. In performance horses, gabapentin is listed as a class 3 performance-enhancing substance by the Association of Racing Commissioners International, and thus is considered to have the potential to influence the outcome of races. Therefore, we developed and validated a sensitive gas chromatographic-mass spectrometric (GC-MS) method for gabapentin detection. Gamma-aminobutyric acid-d(2) (GABA-d(2)) was used as an internal standard during solid-phase extraction; lacking the cyclohexyl ring of gabapentin, GABA-d(2) formed a lactam structure to only a minor extent. Gabapentin, on the other hand, readily formed a lactam on thermal exposure during trimethylsilyl-derivatization and/or GC analysis; electrospray-ionization MS was employed to verify that the original compound was present as the expected 171 m.w. compound. Extraction efficiency for the assay was about 60%, and a curvilinear standard curve ranging from 50 ng/mL to 3000 ng/mL provided excellent within-run and between-run coefficients of variation and accuracies over a range of low, medium, and high values. The limit of detection, defined as the concentration calculated from the mean response at zero concentration plus two times the standard deviation, was calculated at 7.6 ng/mL; the limit of quantitation, defined as the concentration calculated from the mean of the zero responses plus five times the standard deviation, was calculated at 17 ng/mL. This method will enable accurate quantification of gabapentin in equine biological fluids for use in both pharmacokinetic and forensic studies.

Morbidity associated with Schistosoma mansoni infection as determined by ultrasound: a study in Gezira, Sudan.

Previous studies demonstrated the usefulness of ultrasonography in diagnosing Symmers' periportal fibrosis. The prevalence and grade of Symmers' fibrosis was determined using ultrasonography in two villages in the Gezira region of Sudan and compared to standard clinical criteria. In El Dar 18% and Abu Jin 13% of the population had Symmers' fibrosis by ultrasonography. In contrast, only 6.3% in El Dar and 5.2% in Abu Jin with Symmers' fibrosis had splenomegaly, thus most of the population with Symmers' fibrosis would not have been diagnosed clinically. The degree of involvement was estimated by a set of previously defined criteria which ranged from mild (grade 1) to severe (grade 3). Involvement was greatest between 20-30 years and followed the age peak egg excretion rate by 5 years. The prevalence and degree of splenomegaly as well as the portal and splenic vein diameters increased with grade. The presence of hepatomegaly did not correlate with increasing grade. Ultrasonography is a much more sensitive technique than clinical evaluation in estimating the degree of Symmers' fibrosis in this population. A more accurate assessment of involvement will allow a more rational approach to the study of the pathophysiology of this complication and its eventual control.

Diagnosis of pathologically confirmed Symmers' periportal fibrosis by ultrasonography: a prospective blinded study.

Symmers' periportal fibrosis of the liver is the major cause of morbidity and mortality in Schistosoma mansoni infection. The diagnosis is best established definitively by a wedge biopsy of the liver. The ability of abdominal ultrasonography to diagnose this condition was prospectively compared with two independent pathological examinations of wedge biopsies of the liver. Both pathologists and the ultrasonographer were unaware of the clinical diagnosis and each other's findings. Twenty-eight of 41 patients had Symmers' fibrosis by pathological examination and all were diagnosed correctly by ultrasonography prior to surgery. Symmers' fibrosis was not diagnosed by ultrasound in any of 10 patients without Symmers' fibrosis on biopsy. In 3 patients the diagnosis of Symmers' fibrosis was uncertain because the pathologists disagreed as to its presence. These results confirm the findings of previous studies and establish that ultrasonography is at least as sensitive as wedge biopsy in diagnosing Symmers' fibrosis.

Mixed Schistosoma haematobium and S. mansoni infection: effect of different treatments on the serum level of circulating anodic antigen (CAA).

In this study, levels of circulating anodic antigen (CAA) in serum were investigated after differential treatment of 160 Sudanese patients with mixed Schistosoma haematobium and S. mansoni infections. The patients were randomly divided into four groups, which were treated with metrifonate (two doses of 10 mg/kg bodyweight), oxamniquine (60 mg/kg), praziquantel (40 mg/kg), or a multivitamin preparation, respectively. Serum, stool and urine samples were taken prior to treatment as well as one month and five months after chemotherapy. Before chemotherapy CAA levels were similar in the four groups. Antigenemia remained unchanged in the control group. In patients treated with praziquantel or oxamniquine the concentration of CAA decreased to a similar extent. However, whereas in the praziquantel group absence of CAA was already observed one month after treatment, clearing of CAA from the circulation seemed to take longer in patients treated with oxamniquine. Treatment with metrifonate did not result in a reduction of the CAA titres.

A study of the urban malaria transmission problem in Khartoum.

A study of malaria prevalence and transmission was carried out in Khartoum, the capital of Sudan. The sentinel sites were El manshia, an urban area on the Blue Nile and Ed dekheinat, a lower-income peri-urban area bordering the White Nile. Anopheles arabiensis, the only malaria vector encountered, was present throughout the year although vector density varied seasonally. Plasmodium falciparum was the only species found in El manshia. In Ed dekheinat P. falciparum, Plasmodium ovale and Plasmodium vivax constituted 84.9, 8.2 and 6.9% of the cases, respectively. Plasmodium ovale appears to have recently spread into Khartoum since it has not previously been reported there. We conclude that focal transmission of malaria in the districts bordering both Niles has become established and that the reservoir of human infections has increased in recent years leading to increased risk of malaria epidemics, particularly in the aftermath of seasonal flooding.

Anatomical relationship between the collecting system and the intrarenal arteries in the rabbit: contribution for an experimental model.

Intrarenal anatomy was studied in detail to evaluate how useful rabbits could be as a urologic model. Only one renal artery was observed, which was divided into dorsal and ventral branches in all cases. Three segmental arteries (cranial, mesorenal and caudal) was the most frequent branching pattern found in both the dorsal and ventral division. There was an important artery related to the ureteropelvic junction in both dorsal and ventral surfaces in all specimens. The cranial pole was supplied by both dorsal and ventral divisions of the renal artery in 23 of 41 casts (56%). Although the cranial pole of the rabbit kidney could be useful as a model because of the resemblances with human kidney, the different relationship between the intrarenal arteries and the kidney collecting system in other regions of the kidney must be taken into consideration by the urologists, when using rabbit kidney in urological research.

Fetal immune response following maternal diphtheria during early pregnancy.

A pregnant Sudanese woman contracted pharyngeal diphtheria during the first trimester of gestation. She had a severe diphtheritic toxaemia and paralysis of all four limbs but made a full recovery from these manifestations. Pregnancy, apart from vaginal bleeding, was not interrupted. At term she was delivered of a female baby who was physically normal but had a very high level of IgA in cord blood. Diphtheria in adults is a rare disease and the occurrence of diphtheria in a pregnant woman has not, as yet, been reported. Accordingly it is not known how fetal growth and development progress in the presence of diphtheria toxin in the maternal circulation. Similarly the effects on fetal immune responses of an acute maternal infection like diphtheria occurring in early pregnancy are not known.

Intermittent chemotherapy with trichlorfon (metrifonate) reverses proteinuria, hematuria, and leukocyturia in urinary schistosomiasis: results of a three-year field study.

Trichlorfon (metrifonate) was given intermittently to 37 schoolboys with urinary schistosomiasis living in a hyperendemic area of the Sudan. Patients were followed up for three years. Initially, 10 mg of trichlorfon/kg of body weight was administered; this dosage was repeated 14 days and 16 months later. Patients still excreting eggs after 24 months received a fourth dose. At month 24, 61% and at month 36, 56% of the patients had no detectable egg excretion; the others showed severe reduction of egg output. The number of ova excreted was always paralleled by a combined scale of hematuria, leukocyturia , and proteinuria, as assessed by urine analysis reagent strips. Quantitative urine analysis at month 36 revealed pathological findings in only eight individuals. Thus, trichlorfon given three or four times in a dose of 10 mg/kg of body weight spaced over a period of two years was highly effective in reducing parasite load and disease in children living under hyperendemic conditions.

Detection and quantification of circulating antigen in schistosomiasis by monoclonal antibody. II. The quantification of circulating antigens in human schistosomiasis mansoni and haematobium: relationship to intensity of infection and disease status.

Circulating cathodic and circulating anodic antigens were quantified in sera of patients infected with S. mansoni, S. haematobium or both parasites. A monoclonal antibody and a polyclonal antiserum were applied in precipitation and solid phase immunosorbent techniques using radio- and enzyme-labelled antibody as a tracer to detect the cathodic and anodic antigen respectively. The results show that circulating cathodic antigen can frequently be detected in an immunoprecipitation or an immunoradiometric assay in serum of infected patients. The serum concentration of this antigen was found to be significantly correlated to the number of S. mansoni worms and to be higher in patients with the hepatosplenic form of the disease than in those without such complications. Examining paired serum samples before and after specific treatment the determination of this antigen by monoclonal antibody reliably indicated efficacy of chemotherapy in patients having received different forms of treatment.