Carbohydrate fatty acid monosulphate ester is a potent adjuvant for low-dose seasonal influenza vaccines.

There is still a need for a better and affordable seasonal influenza vaccine and the use of an adjuvant could solve both issues. Therefore, immunogenicity of a combination of low dose of 1/5TH (3 µg of HA) a licensed seasonal flu vaccine with the novel carbohydrate fatty acid monosulfate ester (CMS)-based adjuvant was investigated in ferrets and safety in rabbits. Without CMS, hemagglutination inhibition (HI) antibody titers ranged from ≤5 to 26 three weeks post immunization 1 (PV-1) and from 7 to 134 post-immunization 2 (PV-2) in ferrets. Virus neutralizing (VN) antibody titers ranged from 20 to 37 PV-1 and from 21 to 148 PV-2. CMS caused 10 to 111- fold increase in HI titers and 3 to 58- fold increase in VN titers PV-1 and PV-2, depending on influenza strain and dose of adjuvant. Eight mg of CMS generated significantly higher antibody titers than 1 or 4 mg, while 1 and 4 mg induced similar responses. Three µg of HA plus 4 mg of CMS was considered the highest human dose and safety of two-fold this dose was determined in acute and repeated-dose toxicity studies in rabbits conducted according to OECD GLP guidelines. The test item did not elicit any clinical signs, local reactions, effect on body weight, effect on urine parameters, effect on blood biochemistry, or gross pathological changes. In blood, increased numbers of neutrophils, lymphocytes and/or monocytes were noted and in iliac lymph nodes, increased cellularity of macrophages of minimal to mild degree were observed. In both ferrets and rabbits, body temperature increased with increasing dose of CMS to a maximum of 1 ˚C during the first day post-immunization, which returned to normal values during the second day. In the local tolerance study, histopathology of the site of injection at 7 days PV-1 revealed minimal, mild or moderate inflammation in 5, 8 and 5 animals, respectively. In the repeated-dose study and 21 days PV-3, minimal, mild or moderate inflammation was observed in 15, 18 and 3 animals, respectively. We concluded that the data show CMS is a potent and safe adjuvant ready for further clinical development of a seasonal influenza vaccine and combines high immunogenicity with possible antigen-sparing capacity.

Antischistosomal effects of praziquantel, its alkaline hydrolysis and sun decomposed products on experimentally S. mansoni infected albino mice. (A) Efficacy assessment based on clinicopathological findings.

The antischistosomal activity of praziquantel (PZQ), its alkaline hydrolysis product (HP) and its sun-decomposed (SD) products was investigated in S. mansoni experimentally infected mice. The evaluation was made depending on the degree of clinico-pathological changes. The results obtained revealed that, PZQ, HP and the SD have induced partial suppression of worm fecundity as judged by the significant reduction in eggs per gram of faeces in comparison with the infected untreated control. The effect on tissue egg deposition in the treated groups was comparable to the infection of untrea ted control. Worm recovery showed large reduction in the number of worms for SD (47.6%) and HP (28.6%) compared to PZQ (16.6%) treated groups. So, the former two compounds have the superior antischistosomal activities. Glutamate pyruvate transominase (GPT) and glutamate oxaloacetate transaminase (GOT) concentrations were measured. The GOT values for all treated groups were significantly higher than those for the healthy control group (p=0.01). The SD group enzyme concentration was even higher than the infected untreated control. The GPT values of all groups were greater than the uninfected control and the difference was significant for the infected untreated, PZQ and the SD treated groups (p=0.05).

Effect of castration on acetyl salicylic acid metabolism in rabbits.

OBJECTIVES: The biotransformation of acetyl salicylic acid (ASA) differs within species, and gender differences have been documented and attributed to the effect of sex hormones. Castration remains a standard therapy for men with advanced prostate cancer. We studied the effect of castration on the metabolism of ASA in rabbits to find out whether the metabolism of ASA is adversely affected after castration. METHODS: ASA in doses of 12.5, 25, and 50 mg/kg body weight was given intravenously to male and female prepubertal and adult rabbits, castrated adult male rabbits, and castrated male rabbits given testosterone (3 animals per group). Blood samples were collected at 0, 10, 30, 60, 120, and 180 minutes. The high-performance liquid chromatography method was used for the quantitation of salicylic acid (SA) in serum. The percentage of SA not metabolized was determined by comparing the serum level at 10 and 180 minutes for each group. RESULTS: At a dose of 50 mg/kg in the adult rabbits, the mean +/- SD of SA in serum at 10 and 180 minutes was 146.54 +/- 29.54 microg/mL and 19.12 +/- 5.93 microg/mL for males, 158.25 +/- 6.70 microg/mL and 33.24 +/- 2.78 microg/mL for females, 229.72 +/- 47.85 microg/mL and 44.33 +/- 5.64 microg/mL for castrated male rabbits, and 170.88 +/- 12.03 microg/mL and 68.1 +/- 37.54 microg/mL for castrated male rabbits given testosterone, respectively. Also, at 180 minutes, the percentage of SA not metabolized in adult male rabbits was 12.82% +/- 1.65% compared with 21.04% +/- 2.14% (P <0.01) in adult females, 19.53% +/- 1.73% (P <0.01) in castrated adult male rabbits, and 38.95% +/- 19.48% (P <0.001) in castrated male rabbits given testosterone. At all doses of ASA, the serum SA concentration in male and female prepubertal rabbits was not significantly different for each time point. CONCLUSIONS: These results indicate that male rabbits are able to metabolize ASA faster than are females. After castration, this ability is significantly decreased. If these experimental results are confirmed in humans, men who are undergoing hormonal manipulation for advanced prostate cancer and who require high-dose ASA, such as in the treatment of stroke or rheumatoid arthritis or as an antioxidant, may need lower doses to reduce the possible toxic effects of ASA.

Some aspects in the control of schistosomosis and soil-transmitted helminthosis in Yemeni children.

OBJECTIVE: Prevalence, intensity and incidence of schistosomosis and soil-transmitted helminthosis among school children in an ignored area in Yemen were determined. The study aimed to investigate the impact of single doses of Praziquantel or Albenedazole or both, relating to sanitary, socioeconomic and behavioral practices on the prevalence and intensity of infections. METHODS: Out of a total number of 897 pupils, 453 were randomly selected from AlMahweet town and 444 from rural surrounding areas. Millipore filtration, modified Kato and precipitation techniques were applied for urine and stool analysis. RESULTS: Prevalence rates were 27% for schistosomosis, 61% for ascariosis, 21% for trichuriosis, 2% for fascilosis, 0.3% for entrobiosis, 0.7% for hook worm infection and 0.2% for strongloydiosis. Factors found confounding the relationship between schistosomosis and residence, under logistic regression analysis, were sex and frequency of water contact. Probability of infection by Bilharzia for boys who reside in rural AlMahweet and visit the water source is 0.52, compared to 0.30 for their mates who reside in AlMahweet town. Odds ratio estimates accounted for via residence was 2.5, via water contact 1.7 and via boys 3.2. With regards to other helminthic infections, availability of latrines remained the only significant factor under ANOVA. CONCLUSION: In conclusion, annual campaigns for treatment as a single control measure can reduce the infection rate of S. mansoni by 62.5%, T. trichura by 48% and A. lumbricoides by 24%. Whereas for S. hematobium the appropriate time interval for intervention should be shortened according to the findings of a properly designed intervention study before used as a single control measure. Since 77% of the children were infected by other helminthes, therefore mass treatment should be extended to cover all children. For those boys in rural AlMahweet who visited the water source during the week before the interview, mass treatment for schistosomosis is recommended since the prediction of infection rate reached 52%.

Nutritional status of Yemeni schoolchildren in Al-Mahweet Governorate.

The nutritional status of 948 children selected randomly from Al-Mahweet Governorate schools was investigated. Age range was 5-18 years with a mean of 10.6 +/- 2.8 years. Among the children, 3.4% had depleted iron and 43.4% had below average skin-fold thickness. Approximately half of the children were either stunted or chronically underweight and 1 child in 20 was underfed. Depleted fat stores affected two-fifths of the children and approximately one-fifth were anaemic. Urban residents scored significantly higher on nutritional parameters than rural children. Serum ferritin levels were significantly greater among males than females whereas mean height-for-age, weight-for-age and skin-fold thickness were lower.

Nutritional status of Yemeni schoolchildren in Al-Mahweet Governorate

The nutritional status of 948 children selected randomly from Al-Mahweet Governorate schools was investigated. Age range was 5-18 years with a mean of 10.6 +/- 2.8 years. Among the children, 3.4% had depleted iron and 43.4% had below average skin-fold thickness. Approximately half of the children were either stunted or chronically underweight and 1 child in 20 was underfed. Depleted fat stores affected two-fifths of the children and approximately one-fifth were anaemic. Urban residents scored significantly higher on nutritional parameters than rural children. Serum ferritin levels were significantly greater among males than females whereas mean height-for-age, weight-for-age and skin-fold thickness were lower

The Marrara syndrome: a hypersensitivity reaction of the upper respiratory tract and buccopharyngeal mucosa to nymphs of Linguatula serrata.

The Marrara syndrome, like Halazoun in Lebanon, is a hypersensitivity reaction of the upper respiratory tract and buccopharyngeal mucosa to nymphs of Linguatula serrata. The condition follows the consumption of Marrara which consists of raw liver, lungs, trachea and rumen of goats and sheep infected with larvae of L. serrata. The adult worm is found in the nasal passages of dogs. Sheep and goats are infected by eggs from infected dogs. A survey that included 240 adult individuals in a village of endemic L. serrata infection in the Sudan showed that 20% experienced symptoms of allergic nasopharyngitis (Marrara syndrome) following the consumption of raw viscera of goats or sheep at least once in their life. In a prospective study of 24 patients who reported to hospital with the Marrara syndrome, the clinical features included itching in the throat and nose, unilateral conductive deafness, tinnitus and facial palsy. Secondary bacterial infection caused suppurative otitis media. Adult L. serrata parasites were found in the nasal passages of 56 and 47% of male and female dogs in the endemic area. Nymphs were recovered from the mesenteric lymph nodes, lungs and livers of goats in the area.

Specific immunoglobulin measurements related to exposure and resistance to Schistosoma mansoni infection in Sudanese canal cleaners.

The present work comprises a longitudinal study of Schistosoma mansoni infection in occupationally hyper-exposed canal cleaners in the Sudan and the influence of chemotherapy on humoral immune parameters. The study groups included chronically infected canal cleaners (n = 19), newly recruited canal cleaners (n = 17), normally exposed adults (n = 31), school children (n = 46) and Sudanese negative controls (n = 48). Previous studies of the same canal cleaners have demonstrated that chronically infected canal cleaners were more resistant to reinfection than newly recruited canal cleaners. ELISA was used to detect specific IgE and IgG subclasses in response to whole worm antigen (WWH) and soluble egg antigen (SEA) before and 3 months after praziquantel treatment in the groups of canal cleaners and before and 1 year after treatment in normally exposed adults. When intensity of infection was correlated with IgE antibody response, the resistant group of canal cleaners (those who stopped passing ova after treatment) showed a significant positive correlation between intensity of infection and specific IgE to WWH (Spearman's correlation coefficient = 0.49, P < 0.05) compared with a highly significant negative correlation in the susceptible group (acquired new infection after treatment, Spearman's correlation coefficient = -0.94, P < 0.01). Normally exposed adults and school children had significantly less specific IgE to WWH than canal cleaners, while chronically infected canal cleaners had significantly higher levels of specific IgG1 to WWH than newly recruited canal cleaners and school children, and significantly higher levels of specific IgG4 to WWH than school children. There was a significant increase in specific IgG1 and IgG4 to WWH, 3 months after treatment, in newly recruited canal cleaners and a significant decrease, 1 year after treatment, in normally exposed adults. None of the groups studied after treatment showed a significant change in their specific IgE to WWH. Normally exposed adults had significantly lower levels of specific IgE to SEA than newly recruited canal cleaners, and significantly lower levels of specific IgG1 to SEA than other infected groups. Both newly recruited canal cleaners and school children had significantly higher levels of specific IgG2 to SEA than persons in other groups. Only small differences between groups were observed with regard to specific IgG3 and IgM to SEA. Specific IgG4 to WWH and SEA showed different patterns after treatment between the resistant and susceptible groups of canal cleaners. The resistant group maintained the same level of IgG4 to WWH after treatment compared with a significant increase in the susceptible group. On the other hand, levels of specific IgG4 to SEA showed a highly significant decrease after treatment in the resistant group. In contrast, the same antibody subclass increased after treatment in the susceptible group. Generally, results show an association between IgE and IgG1 responses to WWH and resistance to reinfection. In contrast, an association was observed between IgG2 and IgM responses to SEA and susceptibility to reinfection.

Clinical, parasitological and immunological features of canal cleaners hyper-exposed to Schistosoma mansoni in the Sudan.

The present work was a longitudinal study on Schistosoma mansoni infection in occupationally hyperexposed canal cleaners in the Sudan and the influence of therapy on the parasitological and humoral immune parameters. Chronically infected canal cleaners (n = 28) were more resistant to reinfection (Fisher's exact test, P < 0.05) than newly recruited canal cleaners (n=17). Chronically infected canal cleaners had a significantly higher degree of Symmers' fibrosis (chi2 = 19.1, P < 0.0001), significantly larger portal vein diameter (P < 0.05) and enlarged spleen (chi2 = 4.2, P < 0.05) than recently infected, newly recruited canal cleaners. ELISA was used to detect IgG, IgA and IgM in response to whole worm homogenate (WWH) and cercarial homogenate (CH). Chronically infected canal cleaners had significantly higher IgG to WWH antigen than newly recruited canal cleaners and normally exposed individuals (P < 0.05), while both chronically infected and newly recruited canal cleaners had higher IgG levels to CH antigen than normally exposed individuals (P < 0.05). The newly recruited canal cleaners had a significantly higher IgM level to CH antigen than chronically infected canal cleaners (P < 0.05). The IgG level to WWH antigen increased significantly after treatment in newly recruited canal cleaners and normally exposed individuals (P < 0.05). The IgA level to CH antigen increased significantly after treatment in the chronically infected group (P < 0.05). Comparison of the serological parameters between the different study groups with regards to infection and treatment is discussed.

Infection with Schistosoma mansoni in two different endemic areas: a comparative population-based study in Elziedab and Gezira-Managil irrigation schemes, Sudan.

A cross-sectional survey of schistosomiasis was carried out in five villages around the Elziedab irrigation scheme, in the north, and three villages in the Gezira-Managil area in central Sudan. Stools and urine from 53% (2832 individuals) and 72% (3684 individuals) of the population of these villages, respectively, were examined using the modified Kato thick smear for stools and sedimentation for urine. Clinical history and examination were done on 2832 subjects (53%) in Elziedab and on 893 (18%) randomly selected samples in Gezira-Managil. Prevalence of Schistosoma mansoni was 36% in Elziedab and the mean egg count was 150 eggs per gram of faeces (e.p.g.). Prevalence of bloody diarrhoea was 6%, hepatomegaly 6% and splenomegaly 10%. There was a significant association between these parameters and infection in the age group 10-24 years. Prevalence and intensity in Gezira-Managil area were significantly higher than in Elziedab, 52% and 234 e.p.g. Prevalences of bloody stool 29%, hepatomegaly 17% and splenomegaly 15% were also significantly higher than in Elziedab. These parameters were unrelated to the presence of eggs in the stool. Advanced hepatosplenic schistosomiasis is less than 1% in both areas. While S. haematobium was not found in Elziedab, its prevalence varied from 10 to 15% in Gezira-Managil area. In conclusion, S. mansoni is much less prevalent in Elziedab than Gezira, signs and symptoms are much less prominent in Elziedab, and most of the symptoms are unrelated to the presence of eggs in the stool.

Schistosoma mansoni diagnostic antigens (Sm 31/12): a sero-epidemiological study in the Sudan.

A cross-sectional study was performed in a Sudanese village endemic for intestinal schistosomiasis and not located in a control area. Immunological and parasitological diagnosis were compared in 156 individuals. Sera were tested with defined diagnostic Schistosoma mansoni antigens (Sm 31/32, i.e. hemoglobinase and cathepsin), and repeated stool examinations were performed. In immunoblots, 98% of the egg excretors were correctly identified. On the other hand, 75% of the parasitologically negative individuals had anti-Sm 31/32 antibodies. Cross-reactivity of these antigens with other parasites was excluded earlier, and the patients had not received previous chemotherapy. It is concluded that the sensitivity of these defined antigens to detect immunologically infections with S. mansoni compares favourably with stool examinations.

Efficacy of a new Hoffmann-La Roche compound (Ro 15-5458) against Schistosoma mansoni (Gezira strain, Sudan) in vervet monkeys (Cercopithecus aethiops).

Some compounds of the class 9-acridanone-hydrazones have recently been developed by Hoffmann-La Roche (Basel-Switzerland) and were shown to have antischistosomal effects. One of these compounds (RO 15-5458/000) was administered at two dose levels (25 mg and 15 mg/kg body-weight) to S. mansoni (Gezira strain-Sudan) infected vervet monkeys. The faecal egg-output was terminated, worm-burden killed and tissue egg-counts were greatly reduced as compared with the untreated control monkey. Severe necrotic changes were seen around dead worms in sections from treated animals' livers. The efficacy of this compound as an antischistosomal is encouraging and deserves further studying.

Long-term infection with Schistosoma mansoni (Gezira strain--Sudan) in the Nile rat (Arvicanthis niloticus).

The long-term infection with Schistosoma mansoni (Gezira strain--Sudan) was studied in the Nile rat (Arvicanthis niloticus) to investigate the 'self cure' phenomenon. The results indicated that while a considerable number of worms and eggs were still recovered by week 28 post-infection, elimination of some of the worms occurred by week 20.

Efficacy and tolerance of praziquantel in patients with Schistosoma mansoni infection and Symmers' fibrosis: a field study in the Sudan.

Ultrasonography was used in a village in the Gezira-Managil scheme in the Sudan to identify patients with Symmers' fibrosis. In a random sample from patients with active Schistosoma mansoni infection, 238 patients were found to have no liver involvement while 59 had Symmers' periportal fibrosis. Patients were treated with a single dose of 40 mg/kg body weight of praziquantel. Six months after dosing, 51% and 58% were cured of the infection with 81% and 84% reduction in egg burden in the Symmers' and non-Symmers' patients, respectively. The drug was equally well tolerated by the two groups. It is concluded that patients with Symmers' fibrosis respond to praziquantel and tolerate the drug in a similar manner to patients without Symmers'.