A multimodality therapeutic application on Toxoplasma gondii encephalitis utilizing Spiramycin and 'de novo' Ferula asafetida in immunodeficient mice.

This study investigated a 'de Novo' medicinal herb, Ferula asafetida (FA), against toxoplasma encephalitis either alone or combined with spiramycin (SP). Female Swiss-Webster mice (n = 72) were divided into three batches. Batch-I received no DMS to serve as an immunocompetent control, batch-II was immune-suppressed with the DMS (0.25 mg/g/day) for 14 days pre-infection, whilst batch-III was immune-suppressed with the DMS on the same day of infection. All experimental mice were inoculated with Toxoplasma gondii ME49 cysts (n = 75). Each batch was split into four subgroups: Mono-SP, mono-FA, combined drug (SP + FA), or neither. Therapies were administered on day zero of infection in batches (I and II) and 35 days post-infection in batch (III). Treatments lasted for 14 days, and mice were sacrificed 60 days post-infection. Histopathological changes, cysts load, and CD4 and CD8 T-cells were counted in brain tissues. The cyst-load count in mice receiving SP + FA was significantly (p < .0001) the least compared to the mono treatments in all protocols. Interestingly, the combined therapy demolished the T-cell subsets to zero in immunocompetent and immunocompromised infected mice. In conclusion, F. asafetida might be a powerfully natural, safe vehicle of SP in the digestive system and/or across the brain-blood barrier to control toxoplasmosis even through immunodeficient conditions.

Adjunctive bradyzoite-directed therapy for reducing complications of congenital toxoplasmosis.

Congenital toxoplasmosis is caused by in utero infection of the fetus with the intracellular parasite Toxoplasma gondii. Upon infection, the parasite forms life-long cysts in fetal brain and eyes which are resistant to the currently accepted therapy of pyrimethamine and sulfadiazine. These cysts commonly reactivate later in life causing chorioretinitis and visual impairment, and rarely cause neurological complications. I hypothesize that adjunctive, bradyzoite-directed therapies have the potential to alleviate a significant burden of disease by reducing cyst burden in neonatal brain and eyes. Atovaquone is perhaps the most promising drug for further evaluation given its low side-effect profile, established safety, and efficacy in animal models reducing cyst burden. Very limited observational data in humans suggests atovaquone may prevent Toxoplasma-associated chorioretinitis recurrence. Clinical trials are needed to evaluate it and other potential drugs as adjunctive treatment in congenital toxoplasmosis.

Antiparasitic effects of oxymatrine and matrine against Toxoplasma gondii in vitro and in vivo.

Toxoplasma gondii (T. gondii) is an important pathogen which can causes serious public health problems. Since the current therapeutic drugs for toxoplasmosis present serious host toxicity, research on effective and new substances of relatively low toxicity is urgently needed. This study was carried out to evaluate the anti-parasitic effect of oxymatrine (OM) and matrine (ME) against T. gondii in vitro and in vivo. In our study, the anti-T. gondii activities of ME and OM were evaluated in vitro using cell counting kit-8 assay, morphological observation and trypan blue exclusion assay. In vivo, mice were sacrificed four days post-infection and ascites were drawn out to determine the extent of tachyzoite proliferation. Viscera indexes and liver biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione (GSH) and malondialdehyde (MDA), were examined to evaluate the toxicity of compounds to mice. As a result, OM and ME showed anti-T. gondii activity but low selectivity toxicity to HeLa cells. Both compounds also significantly decreased the number of tachyzoites in peritoneal cavity and recovered the levels of ALT, AST, GSH and MDA in liver. Moreover, the mice treated with OM or ME achieved better results in viscera index and survival rate than that of spiramycin. These results suggest that OM and ME are likely the sources of new drugs for toxoplasmosis, and further studies will be necessary to compare the efficacy of drug combination, as well as identify its action of mechanism.

A Systematic Review and Meta-Analysis of the Efficacy of Anti-Toxoplasma gondii Medicines in Humans.

No effective drug and definitive "gold standard" treatment for Toxoplasma gondii (T. gondii) infection has been available so far, though some medicines have been commonly used in the treatment of T. gondii infection, such as spiramycin, azithromycin, traditional Chinese medicine (TCM), pyrimethamine- sulfadiazine (P-S), trimethoprim-sulfamethoxazole (TMP-SMX), and pyrimethamine-clindamycin (P-C). A systematic review and meta-analysis were performed to compare the efficacies of these conventional medicines in the treatment. Cohort studies for the treatment of acute T. gondii infection were searched from PubMed, Google Scholar, ect. All the cases number for different group extracted from each included literature were input to meta-analysis 3.13 software to calculate the pooled negative conversion rate (NCR), cure rate (CR) or vertical transmission rate based on their sample size and weight. The pooled NCR with 95% confidence intervals (CI) was used to evaluate the overall rate of a diagnosis positive result conversion to a negative result after treatment, which of spiramycin, azithromycin and TCM were 83.4% (95%CI, 72.1%-90.8%), 82.5% (95%CI, 75.9%-87.6%), and 85.5% (95%CI, 71.3%-93.3%) respectively, with no statistical difference between them. The pooled CR with 95% CI was used to evaluate the overall rate of complete disappearance of clinical symptoms for toxoplasmic encephalitis after therapy, which of P-S, TMP-SMX, and P-C were 49.8% (95%CI, 38. 8% -60.8%), 59.9% (95%CI, 48.9%-70.0%), and 47.6% (95%CI, 24.8%-71.4%) respectively, with no statistical difference between them. Primary T. gondii infection in pregnancy was treated mainly with spiramycin alone or combined with other drugs, and the pooled rate of vertical transmission was about 9.9% (95%CI, 5.9%-16.2%) after therapy. Toxoplasmic encephalitis in AIDS patients was usually treated with sulfonamides combined with other drugs and the pooled CR was 49.4% (95%CI, 37.9%-60.9%).

Azithromycin inhibits vertical transmission of Toxoplasma gondii in Calomys callosus (Rodentia: Cricetidae).

Toxoplasma gondii infection during pregnancy may cause severe consequences to the embryo. Current toxoplasmosis treatment for pregnant women is based on the administration of spiramycin or a drug combination as sulphadiazine-pyrimethamine-folinic acid (SPFA) in cases of confirmed fetal infection. However, these drugs are few tolerated and present many disadvantages due to their toxic effects to the host. The aim of this study was to evaluate the effectiveness of different treatments on the vertical transmission of T. gondii, including azithromycin, Artemisia annua infusion, spiramycin and SPFA in Calomys callosus as model of congenital toxoplasmosis. C. callosus females were perorally infected with 20 cysts of T. gondii ME49 strain at the day that a vaginal plug was observed (1st day of pregnancy - dop). Treatment with azithromycin, A. annua infusion, and spiramycin started at the 4th dop, while the treatment with SPFA started at the 14th dop. Placenta and embryonic tissues were collected for morphological and immunohistochemical analyses, mouse bioassay and PCR from the 15th to 20th dop. No morphological changes were seen in the placenta and embryonic tissues from females treated with azithromycin, spiramycin and SPFA, but embryonic atrophy was observed in animals treated with A. annua infusion. Parasites were found in the placenta and fetal (brain and liver) tissues of animals treated with SPFA, A. annua infusion and spiramycin, although the number of parasites was lower than in non-treated animals. Parasites were also observed in the placenta of animals treated with azithromycin, but not in their embryos. Bioassay and PCR results confirmed the immunohistochemical data. Also, bradyzoite immunostaining was observed only in placental and fetal tissues of animals treated with SPFA. In conclusion, the treatment with azithromycin showed to be more effective, since it was capable to inhibit the vertical transmission of T. gondii in this model of congenital toxoplasmosis.

Toxoplasmosis congénita: revisión / Congenital toxoplasmosis: a review

La forma congénita de infección por Toxoplasma gondii se produce a partir de una primo infección gestacional con consecuencias en distintos órganos del feto, especialmente oculares (coriorretinitis), SNC (hidrocefalia, convulsiones) y sistémicos(hepatoesplenomegalia), aunque entre el 80 y 90% son formas subclínicas. El diagnóstico se realiza mediante estudio serológico materno, dependiendo el riesgo de infección fetal del trimestre en que se produzca la seroconversión. Debido a la ausencia de estudios sobre la eficacia del tratamiento prenatal, se administrará a la madre con primoinfección tratamiento con espiramicina hasta conocer los resultados delos estudios complementarios. Ante infección en el recién nacido, se instaurará tratamiento con pirimetamina, sulfadiazina y ácido fólico, siendo el objetivo la disminución del riesgo de secuelas a largo plazo. El cribado gestacional es uno de los puntos de controversia, ya que tanto el gasto sanitario como el nivel de falsos + es elevado. Los programas de educación sanitaria han logrado disminuir en algunos países la tasa de infección al 50%

The congenital form of Toxoplasmga ondii infection is caused by primary maternal infection, with consequences in different fetal systems, especially the ocular system (chorioretinitis) and central nervous system (hydrocephalu, seizures), as well as systemic involvement(hepatosplenomegaly), although between 80% and 90% of the resulting disorders are subclinical. The diagnosis involves maternal serology, as the risk of fetal infection depends on the trimester in which seroconversion occurs. Given the lack of studies on the efficacy of prenatal treatment, spiramycin should be administered to pregnant women with primary infection until the results of complementary studies are known. Should the new born be infected, treatment with pyrimethamine, sulfadiazine and folic acid should be begunin the attempt to reduce the risk of long-term sequelae. Prenatal screening is a controversial issue since both the health care costs and rate of false positives are high. In some countries, health education programs have resulted in a decrease in the rate of infection of 50%

[Efficacy variation of erythromycin and spiramycin on periopathogens in aggressive periodontitis. An in vitro comparative study]. / Variabilité de l'efficacité de l'érythromycine et de la spiramycine sur les pathogènes parodontaux dans les parodontites agressives. Etude in vitro comparative.

AIMS: Erythromycin (ERY) and spiramycin (SPI) are the most frequently prescribed macrolides by dentists. However, the emergence of resistant anaerobic subgingival bacteria imposes an increased vigilance. This study aims to compare these macrolides efficacy on principal periopathogens. MATERIALS AND METHODS: Twenty adult patients with aggressive periodontitis were selected and a total of 60 samples were taken from subgingival flora. Bacterial strains of Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, Fusobacterium nucleatum, Peptostreptococcus micros and Actinobacillus actinomycetemcomitans were isolated according to J. Slots's rapid identification method. The susceptibilities to ERY and SPI were studied using disk diffusion susceptibility test and minimum inhibitory concentration test (MIC test). RESULTS: The efficiency variability of ERY and SPI on the 50 isolated anaerobic periopathogens was present either interindividually (between different patients) and intra-individually (within the same patient). While 68% of the tested anaerobic bacteria were sensitive to SPI (22% resistant), only 54% were sensitive to ERY (34% resistant). Although moderate, the efficacy of SPI seemed more regular in general than ERY: it's variation coefficient (40%) is lower than the ERY one (53%). The 7 A. actinomycetemcomitans tested showed all a high resistance. CONCLUSION: In a general way, the spectre of activity of SPI is stacked in that of ERY. However, this study shows a better and regular activity of SPI on the main tested periopathogens. These results are in favour of the use of SPI in periodontology when penicillins and doxycycline are not useful because specific problems are identified (allergy, pregnancy...).

A blind parallel comparative study of the efficacy and safety of rovamycin versus augmentin in the treatment of acute otitis media.

A single blind randontised controlled parallel clinical trial of Rovamycin was conducted in which (Rovamycin Rhone-Poulenc Rorer) was compared with Augmentin in patients with acute otitis media. Forty patients were randomised to treatment with either Rovamycin or Augmentin and the drugs were evaluated for efficacy and safety. The efficacy parameters used were fever clearance, symptom clearance and cure rate after 8 days of treatment Our study showed that fever regressed in 19 (95%) of the 20 patients in both groups; otalgia in 19 (95) patients for the Augmentin and 18 (90%) for Rovamycin after 8 days of application of the trial drugs in these parameters. There was also no significant difference between them in their safety and tolerability profiles. These results showed that Rovamycin is a useful addition to our armamentarium in the fight against bacterial otitis media. Operationally, Rovamycin has an advantage over Augmentin for the reason that is given only twice a day as against thrice-daily dosage f orAugmentin. Compliance and consequently effectiveness in practices should therefore be better for Rovamycin.

[Recurrent parotitis in children and HIV infection. Apropos of 4 cases]. / Parotidites récidivantes de l'enfant et infection HIV. A propos de 4 observations.

We report four cases of recurrent infectious parotiditis in children and recall the clinical radiographic and pathogenic features. Particular attention was paid to the possible relationship between sialadenitis and HIV infection in two cases. This would open a large etiological field when HIV contamination is suspected. Treatment if all four cases (spiramycine, diclofenac, soframycin washing, lipiodol instillation and local bucco-dental treatment) was successful leading to longer intervals between relapses.

Control of proliferative enteropathy in growing/fattening pigs using growth promoters.

The aim of this study was to evaluate the effect of different antibiotics used as growth promoters on the control of porcine intestinal adenomatosis when administered in weaning, growing and fattening pig diets, according to Annex I of the European Union directive (70/524/EEC and its subsequent amendments to date) for the use of feed additives. On a farm with a previous history of proliferative enteropathy outbreaks, 648 weaned piglets (23 days old) were divided into nine experimental groups according to bodyweight and sex ratio, each group comprising four pens with 18 pigs in each pen. One group served the trial as a negative (unmedicated) control: another (the positive control) received monensin via feed at 100 p.p.m. up to the end of the growing phase (107 days old) and 50 p.p.m. up to slaughter age (156 days old). The remaining seven groups were offered feed with the addition of the following antibiotics: virginia-mycin (50-20 p.p.m.), avilamycin (40-20 p.p.m.), spiramycin (50-20 p.p.m.), zinc bacitracin (50-10 p.p.m.), avoparcin (40-20 p.p.m.), tylosin (40-20 p.p.m.) and salinomycin (60-30 p.p.m.), respectively. The performance of the pigs in the positive control group was very satisfying and among the highest in the trial, verifying earlier field studies. As a general conclusion it seems that all tested growth promoters had a beneficial effect compared with the untreated control, indicated by the decrease of mortality rate, the elimination of diarrhoeal incidence and the enhancement of growth performance, although the proliferative enteropathy control achieved by each substance was not always satisfactory. More specifically, the antibiotic growth promoters tested can be scaled according to their total efficacy as follows: 1. Salinomycin, tylosin, spiramycin; 2. Virginiamycin, zinc bacitracin, avilamycin; and 3. Avoparcin. Finally, it is considered that part of the growth promotion efficacy of the tested substances is due to their potential capacity to control porcine intestinal adenomatosis; thus, in future growth performance trials, the disease background of the trial farms must be examined, especially for porcine enteropathy challenges.

Efficacy of parenteral administration of three antimicrobial agents in treatment of clinical mastitis in lactating cows: 487 cases (1989-1995).

OBJECTIVE: To evaluate the efficacy of parenteral administration of procaine penicillin G, spiramycin, or enrofloxacin in the treatment of clinical mastitis in lactating cows. DESIGN: Noncontrolled, clinical retrospective study. ANIMALS: 487 cows with mastitis involving 543 quarters. PROCEDURE: Clinical signs, histories, and results of bacteriologic examination, somatic cell count, and N-acetyl-beta-D-glucosaminidase activity of milk samples taken before and 3 to 4 weeks after treatment were retrieved from hospital records. Cows treated parenterally with procaine penicillin G, spiramycin, or enrofloxacin for 3 to 5 days were included. Supportive treatment alone was given to 35 cows infected with Escherichia coli. Factors possibly affecting outcome were analyzed, using ANOVA, correlation analyses, and the Mann-Whitney test. chi 2 Test was used to compare bacteriologic cure rates. RESULTS: Bacteriologic cure rates for mastitis caused by Staphylococcus aureus, coagulase-negative staphylococci, and streptococci were 34, 76, and 65%, respectively. Cure rates in cows in their first lactation and infected with S aureus and coagulase-negative staphylococci were significantly higher than those for older cows. In cows with mastitis caused by E coli, the cure rate was 74% for those treated with penicillin G and 71% for those not treated with antimicrobials. High N-acetyl-beta-D-glucosaminidase activity in milk samples obtained at initial examination indicated a poor outcome in S aureus and streptococcal mastitis. Cows infected in the early lactation period had more severe inflammatory responses and clinical signs if infected with coagulase-negative staphylococci and coliforms. CLINICAL IMPLICATIONS: 3 to 5 days of treatment with parenterally administered penicillin G for clinical mastitis caused by penicillin-susceptible S aureus strains is efficacious in young cows. Parenteral administration of spiramycin or enrofloxacin does not give satisfactory results in mastitis caused by penicillin-resistant S aureus. Use of antimicrobials in the treatment of mastitis caused by coliform bacteria is questionable.

[Therapeutic approaches to cryptosporidiosis. A review of the literature]. / Los abordajes terapéuticos de la criptosporidiosis. Revisión de la literatura.

Cryptosporidiosis is a coccidian infection that usually occurs in children an immunocompromised patients. With the AIDS (Acquired Immunodeficiency Syndrome) epidemic there have been an increased number of clinical cases and still we don't have an optimal therapeutic regimen to eradicate the infection. Since 1907 when the organism was first described, a large amount of anti-infective agents have been used without success. We present herein a review of the new therapeutic approaches, although none of them is satisfactory and new studies are required for the development of an optimal treatment. Symptomatic and nutritional support are the unique treatment we have so far.

[Combined gu chi wan and spiramycin in the treatment of periodontal disease].

The purpose of the present study is to evaluate clinical effect of the integrated traditional Chinese and western medicine in the treatment of periodontal disease. 90 patients suffered from mild to advanced periodontitis were divided into two groups. The gu chi wan (tooth firming pills) group was administered tooth firming pills 4 mg twice daily for 3-6 months combined with spiramycin 0.2 four times daily for 5 days and routine periodontal treatment. The spiramycin group, as control, was administered spiramycin 0.2 four times daily for 5 days combined with routine periodontal treatment. The clinical parameters: GI, PLI, PDI and serial radiographs were checked on the beginning of study and through 3, 6, 12, 24 months follow up study. The results showed that the GI and PDI of the gu chi wan group decreased significantly than the control group (P less than 0.001). The inflammatory recurrence rate was 33% in the control group and 12% in gu chi wan group and the serial radiographs demonstrated that a higher incidence of bone fill occurred in gu chi wan group than in the control group (P less than 0.01).

In vivo activity of the macrolide antibiotics azithromycin, roxithromycin and spiramycin against Toxoplasma gondii.

The macrolide antibiotics azithromycin, roxithromycin and spiramycin were examined in parallel for in vivo activity against Toxoplasma gondii. Azithromycin was considerably more active in protecting mice against death due to acute toxoplasmosis even when the other two antibiotics were used at twice its dose. The higher activity of azithromycin prompted a further examination of its activity against five different strains of Toxoplasma gondii, including two isolated from patients with AIDS. Although variable degrees of protection against death were noted, treatment with 200 mg/kg/day for ten days was sufficient to promote survival of 100% of mice infected with inocula as high as 1 x 10(5) tachyzoites of Toxoplasma gondii. 90% of mice inoculated with 1 x 10(5) tachyzoites of strain MO, isolated from an AIDS patient, and treated orally with 200 mg/kg/day for ten days survived the infection whereas only 40% of mice infected with the same inoculum of the SOU strain, also isolated from an AIDS patient, survived. Tissue concentrations of azithromycin were examined in treated infected and non-infected mice. In both groups of mice azithromycin attained high concentrations in liver, spleen and heart, which exceeded concurrent serum levels by 25- to 200-fold. The concentrations in the brain were almost tenfold higher than the concentrations in serum after treatment with 200 mg/kg/day for ten days. Moreover, the concentrations in brains of infected mice were approximately two-fold higher than in brains of non-infected mice.