Graciela Tapia

Symptomatic human neurocysticercosis: Age, sex and exposure factors relating with disease heterogeneity

Abstract.Objective:To evaluate the relevance of exposure and host biological factors in the heterogeneity of the clinical, radiological and inflammatory picture of neurocysticercosis (NCC).Methods:105 Mexican symptomatic NCC patients confirmed by imaging were studied before they received any specific treatment. The relationships studied were those between a) the patients’ characteristics (gender, age and level of exposure), b) the type of clinical picture and c) the radiological and inflammatory characteristics of the disease (number, aspect, localization of the parasites, and CSF leukocytecounts).Results:Results Seizures were the most frequent symptom and multiple subarachnoid cysticerci the most frequent localization. Symptomatology related to the developmental stage, number and localization of the parasites as well as the CSF leukocyte-counts. The total number of cysticercal lesions and of vesicular cysticerci increased with age,whereas the number of colloidal cysticerci decreased. CSF leukocyte-counts were higher in women than in men. Levels of exposure did not correlate with the clinical and radiological pictures.Conclusions:The variability found in the number, stage, localization and inflammation in the parasite lesions is strongly associated with the heterogeneity of NCC symptoms. The increased number of vesicular cysticerci and the decreased number of degenerating cysticerci with aging, as well as the prominence of inflammation in women suggest that immuno-endocrinological factors may play a role in susceptibility and pathogenesis. The data also show that with increasing age and exposure there is no increment in severity, a suggestion that there might be ways of regulating pathogenicity.

TH2 profile in asymptomatic Taenia solium human neurocysticercosis

Neurocysticercosis (NC), a parasitic disease caused by Taenia solium, may be either asymptomatic or have mild to severe symptoms due to several factors. In this study, the immunological factors that underlie NC pleomorphism were studied. Ten of the 132 inhabitants of a rural community in Mexico (Tepez) had a computerized tomography (CT) scan compatible with calcified NC, and all were asymptomatic. Their immunological profiles were compared with those of 122 CT scan negative (non-NC) subjects from the same village. NC was associated with a TH2 response (IgG4, IL-4, IL-5, IL-13). Subjects from Tepez had higher levels of specific antibodies (IgG1, IgG2, IgG4, IgE) and specific cell proliferation than subjects from an area with low exposure (Ensenada). This suggests that non-NC subjects from Tepez had been exposed to T. solium and resisted infection in the brain. Distinct immunological profiles in equally exposed individuals differing in outcome of infection support the hypothesis of host-related factors in resistance to and pathogenesis of NC. This is the first study reporting the immunological profile associated with the asymptomatic form of NC.

Plasma concentrations resulting from florfenicol preparations given to pigs in their drinking water1

Florfenicol administered through the drinking water has been recommended as a metaphylactic antibacterial drug to control outbreaks of respiratory diseases in pigs caused by strains of Actinobacillus pleuropneumoniae and Pasteurella multocida, yet it is difficult to pinpoint in practice when the drug is given metaphylactically or therapeutically. Further, pigs are likely to reject florfenicol-medicated water, and plasma concentrations of the drug are likely to be marginal for diseases caused by Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. The reported minimal inhibitory concentration (MIC) values for these organisms show a breakpoint of 2 to 3 μg/mL. An experiment was conducted during September and October 2009. One hundred twenty healthy crossbred pigs (Landrace-Yorkshire), weighing 23 ± 6.2 kg, were used in this trial. They were randomly assigned to 5 groups, with 3 replicates of 8 animals/group. Two commercial preparations of florfenicol were administered through the drinking water at 2 concentrations (0.01 and 0.015%). Water intake was measured before and after medication, and plasma concentrations of florfenicol were determined by HPLC. Considerable rejection of florfenicol-medicated water was observed. However, plasma florfenicol concentrations were of a range sufficient for a methaphylaxis approach to preventing disease by bacteria, with MIC breakpoints of ≤ 0.25 μg/mL. Decreased efficacy as a metaphylactic medication should be expected for bacteria with MIC >0.25 μg/mL, considering the reported existence of bacteria resistant to florfenicol and the natural resistance of Streptococcus suis or E. coli to this drug.

Efficacy of a New Recrystallized Enrofloxacin Hydrochloride-Dihydrate against Leptospirosis in a Hamster Model.

ABSTRACT A trial on Syrian hamsters (Mesocricetus auratus) infected with Leptospira interrogans serovar Canicola was established to compare treatment efficacies of daily intramuscular (i.m.) injections of either 10 mg/kg of 5% enrofloxacin (Baytril [BE]; Bayer Animal Health, Mexico) or the same dose of enrofloxacin hydrochloride-dihydrate (enro-C). Hamsters were experimentally infected via the oral submucosa with 400 microorganisms/animal, in a sequential time schedule aligned to the initial treatment day, and were treated in groups as follows: a group treated with 5% enrofloxacin daily for 7 days after 24 h of infection (group BE24); a group treated as described for group BE24 but with enro-C (enro-C24); a group also treated with 5% enrofloxacin but starting at 72 h after infection (BE74); a group treated as described for group BE74 but with injection of enro-C (enro-C74). An untreated-uninfected control group (group CG−) and an infected-untreated control group (group CG+) were assembled (n = 18 in all groups). Weights and temperatures of the hamsters were monitored daily for 28 days. After hamsters were euthanatized or following death, necropsy, histopathology, macroscopic agglutination tests (MAT), bacterial culture, and PCR were performed. The mortality rates were 38.8% in group BE24 and 100% in group BE74. No mortality was observed in group enro-C24, and 11.1% mortality was recorded in group enro-C74. The mortality rates in groups CG+ and CG− were 100% and zero, respectively. Combined necropsy and histopathologic findings revealed signs of septicemia and organ damage in groups BE24, BE72, and CG+. Groups enro-C24 and CG− showed no lesions. Moderated lesions were registered in 3 hamsters in group enro-C72. MAT results were positive in 83.3% of BE24 hamsters (83.3%) and 100% of BE72 and CG+ hamsters; MAT results were positive in 16.7% in group Enro-C24 and 38.9% in group enro-C72. Only 4/18 were PCR positive in group enro-C72 and only 1 in group enro-C24 (P < 0.05). It can be concluded that enro-C may be a viable option to treat leptospirosis in hamsters and that this may be the case in other species.

Efficacy of a pharmaceutical preparation based on glycyrrhizic acid in a challenge study of white spot syndrome in white shrimp (Litopenaeus vannamei)

Abstract There is a lack of preventive and therapeutic drug-based treatments for the shrimp viral disease known as white spot syndrome (WSSV). Thus a challenge study inducing WSSV in juvenile white shrimp (Litopenaeus vannamei) was established, setting 4 groups: challenged — not treated and unchallenged, untreated control groups and two experimental ones (E1 and E2) both treated with diammonium glycyrrhizic acid, extracted from licorice with added vitamins and oligoelements, and as in-feed medication. Group E1 received diammonium glycyrrhizic acid included in their daily feed, starting 17days before challenge with WSSV and maintaining the treatment for further 5days after the end of the trial, which was set on day 18. Group E2 received this medication as group E1 throughout the trial, but starting 1day before the challenge with WSSV. The group with highest surviving median values was E1, amounting two times the survival median in comparison with the control groups (P=0.007). Also a statistical difference was found in terms of survival means in favor of group E1 as compared to group E2. Macroscopic and histopathological findings revealed lesions compatible with WSSV and similar mortality in the challenged untreated group. These findings were highly reduced or inexistent in mortality analyzed from groups E1 as well as in the unchallenged — untreated control group and greatly reduced in group E2. Considering the apparent high efficacy observed and that glycyrrhizic acid and mineral and vitamin components added as treatment, and taking as an advantage that this preparation has been regarded as nutraceuticals, it is here proposed that large scale trials should be conducted to evaluate the effects here observed in commercial and larger scale shrimp farms.

Antibacterial activity of amoxicillin in vitro and its oral bioavailability in broiler chickens under the influence of 3 water sanitizers

ABSTRACT The interaction of 3 water sanitizers (sodium hypochlorite, iodine‐polyvinylpyrrolidone, and citrate) utilized in poultry production on antibacterial activity and bioavailability of amoxicillin trihydrate (AMX) were studied. Sanitizers were mixed with AMX in prepared water, the resulting substances were regarded as amoxicillin‐sanitizer products (ASP). First, the in vitro antibacterial activity of each ASP was compared to that of AMX. Then, pharmacokinetics (PK) of ASP and AMX diluted in prepared water, were carried out in broiler‐chickens. Amoxicillin or ASP (20 mg/kg) from different concentrations of sanitizers was directly placed into the chickens crop and blood samples were taken. Basic PK parameters were obtained. Serum activity/concentrations of AMX were assessed by agar diffusion and corroborated with high performance liquid chromatography. Results show that ASP of AMX/sodium hypochlorite decrease both, the antimicrobial activity of in vitro AMX and its relative bioavailability (Fr) assessed with the maximum serum concentration (Cmax), the area under the concentration‐time curve, and the mean residence time (MRT) (3.80 &mgr;g/mL, 2.70 &mgr;g/mL·h, and 0.59 h, respectively), compared to the AMX administered alone (12.54 &mgr;g/mL, 44.02 &mgr;g/mL·h, and MRT 2.78 h). ASP from amoxicillin/ionophore, reduced the Cmax (10.62 &mgr;g/mL), Fr (94.67%), and MRT (2.07 h), at the highest tested concentrations. In contrast, the 2 highest concentrations of the citrate sanitizer increased the Cmax (15.07 and 15.47 &mgr;g/mL), Fr (119 and 132%), and MRT (3.32 and 4.06 h) and their in vitro antimicrobial activity. Interactions between the tested water sanitizers and AMX modify the Cmax, Fr, MRT of the latter, altering the PK/pharmacodymanic ratios for a time‐dependent antibiotic. Results also reveal that the use of amoxicillin trihydrate administered through the drinking water does not meet the required PK/pharmacodymanic ratios. Thus, it is here postulated that this antibiotic should be administered at least twice a day and that its interaction with water sanitizers should be considered.

Pharmacokinetics of enrofloxacin HCl-2H2O (Enro-C) in dogs and pharmacokinetic/pharmacodynamic Monte Carlo simulations against Leptospira spp.

Pharmacokinetic/pharmacodynamic (PK/PD) ratios of reference enrofloxacin (Enro-R) and enrofloxacin as HCl-2H2O (Enro-C), as well as Monte Carlo simulations based on composite MIC50 and MIC90 (MIC, minimum inhibitory concentration) vs. Leptospira spp., were carried out in dogs after their intramuscular (IM) or oral administration (10 mg/kg). Plasma determination of enrofloxacin was achieved by means of high-performance liquid chromatography. Maximum plasma concentration values after oral administration were 1.47 ± 0.19 µg/mL and 5.3 ± 0.84 µg/mL for Enro-R and Enro-C, respectively, and 1.6 ± 0.12 µg/mL and 7.6 ± 0.93 µg/mL, respectively, after IM administration. Areas under the plasma vs. time concentration curve in 24 h (AUC0–24) were 8.02 µg/mL/h and 36.2 µg/mL/h for Enro-Roral and Enro-Coral, respectively, and 8.55 ± 0.85 µg/mL/h and 56.4 ± 6.21 µg/mL/h after IM administration of Enro-R and Enro-C, respectively. The PK/PD ratios and Monte Carlo simulations obtained with Enro-C, not Enro-R, indicated that its IM administration to dogs will result in therapeutic concentrations appropriate for treating leptospirosis. This is the first time enrofloxacin has been recommended to treat this disease in dogs.

Influence of chlorine, iodine, and citrate-based water sanitizers on the oral bioavailability of enrofloxacin in broiler chickens

Abstract This experiment was conducted to determine if the 3 most commonly used water sanitizers in commercial broiler chicken production affected the stability of enrofloxacin (ENR), when each was administered concurrently with ENR to broiler chickens via the drinking water. To that effect, the in vitro antibacterial activity of the solution of each ENR‐sanitizer product (ESP) was compared to that of ENR alone. Also, bioavailability (F) studies of ESP were carried out in chickens and compared to the corresponding values of ENR in drinking water without sanitizer. Water sanitizers tested were iodine (as iodine‐polyvinylpyrrolidone), chlorine (as sodium hypochlorite), and a citrate‐based sanitizer from grapefruit extract. They were mixed with ENR in sterile de‐ionized water, and the resulting substances were regarded as ESP. Then, the referred studies of ESP were carried out. Results showed that ESP of ENR/sodium hypochlorite decreased both the antimicrobial activity, as well as maximum serum concentration (Cmax) and F of ENR in chickens. ESP of ENR/citrate‐based sanitizer increased both the in vitro antimicrobial activity and Cmax and F values of ENR at the 2 highest concentrations tested. ESP of ENR/iodine reduced both in vitro antimicrobial activity and Cmax values of ENR at the highest concentrations tested. This study demonstrated that interactions between water sanitizers and ENR must be considered when medicating chickens via the drinking water to meet pharmacokinetics/pharmacodynamics ratios. The use of a citrate‐based sanitizer is recommended, as relative F was increased.

Development of an Aqueous Ophthalmic Solution with an Enhanced-Solubility Enrofloxacin Crystal, and its Clinical Evaluation in Dogs

BACKGROUND The concern about the frequent use of ciprofloxacin in veterinary medicine is linked to increased antimicrobial resistance. The corresponding fluoroquinolone for veterinary use is enrofloxacin. A new solvate form of enrofloxacin, as dihydrate-hydrochloride (enro-C) with higher water solubility than the parent compound, was formulated as an ophthalmic solution (pH 5). A multicentre, longitudinal, non-inferiority clinical study in a non-hospital environment was designed to treat 36 dogs affected by tobramycin-unresponsive conjunctivitis with either the experimental 0.5% enro-C ophthalmic preparation (enro-CG) or a commercial preparation of ciprofloxacin (cipro-G). Other causes of conjunctivitis were ruled out. Pathogens were isolated and minimum inhibitory concentration (MIC) studies of tobramycin were carried out. Three blocks of bacterial resistance were set up, beginning at the established breakpoint i.e., 4 µg/mL; 8 µg/mL and 16 µg/mL. Eighteen dogs were randomly assigned to each block. The enro-CG group was treated with two drops of the referred preparation (10 mg/eye) twice a day for 7 days, and the cipro-G group was treated with four drops of a 0.3% commercially available ciprofloxacin eye-drop preparation (9 mg/eye) twice a day, also for 7 days. Clinical and bacteriological cure rates were evaluated. RESULTS Enro-C-treated dogs achieved a clinical cure one day earlier than ciprofloxacin-treated dogs, and unlike this latter group, enro-CG achieved bacteriological cure in all cases. No side effects were observed in either group, but dogs treated with enro-C showed no discomfort, allowing easier treatment-compliance. CONCLUSION This is the first study reported on the successful formulation of enrofloxacin as an ophthalmic solution. Clinical assessment reveals outstanding clinical efficacy. It is necessary to conduct further research on clinical efficacy and toxicity, with the chronic use of this preparation under different clinical challenges.

In vivo anticoccidial activity of quinfamide in broilers: a preliminary report

Abstract The aim of this trial was to evaluate the anticoccidial efficacy of quinfamide in broilers. Three different treatments were implemented over a 49-day period as follows: quinfamide; quinfamide plus carbopol and decoquinate, all prepared as small pellets and mixed with feed at a final dose of either active principle of 30 ppm. Parameters measured were: weight gain, number of oocysts shedding per gram of litter and degree of gross lesions caused by coccidia. Body weight gain was statistically greater for quinfamide and quinfamide-carbopol groups in comparison to other groups. However, only the quinfamide-carbopol group showed similar efficacy in the occyst counts as compared to the decoquinate group. Statistically significant differences were observed when intestinal lesions score were compared and the less affected group was quinfamide-carbopol. Based on these results, it is concluded that quinfamide possesses a low anticoccidial efficacy. However, this is noticeably improved when it is prepared as pellets with carbopol. The adhesion of carbopol to intestinal mucosa may influence residence time of quinfamide in the gastrointestinal tract, thus enhancing efficacy.