Attempted chemoprophylaxis of cryptosporidiosis in chickens, using diclazuril, toltrazuril, or garlic extract

Three battery tests were conducted to study the anticryptosporidial efficacy of the 2 commercially available anticoccidial triazinone derivates, diclazuril and toltrazuril, and a garlic extract. At the recommended level, diclazuril reduced the oocyst output of birds by 14.6%. The efficacy of toltrazuril was 52.1% at the recommended level, which could be moderately increased using 5 or 10 times the recommended dose. However, these doses resulted in significant weight gain reduction. The efficacy of garlic extract was 24.4%. It is concluded that none of the drugs can be recommended for chemoprophylaxis or therapy of cryptosporidiosis in chickens.     

Pilot study on the efficacy of paromomycin as a histomonostatic feed additive in turkey poults experimentally infected with Histomonas meleagridis

Paromomycin is an aminoglycoside antibiotic with activity against protozoa. Currently, paromomycin is registered for food producing animal species. In a pilot study we evaluated the efficacy of different doses of paromomycin in the feed against Histomonas meleagridis in experimentally challenged turkey poults. Groups consisting of 30 birds each were given feed with 100, 200 and 400 ppm paromomycin, respectively, starting on day 1 through to day 42. One group of 30 birds was left untreated. On day 21 all birds were infected intracloacally with H. meleagridis. Additionally, 10 birds were kept as a non-infected and non-treated control group. Before the challenge there was no significant difference between untreated and treated groups with regards to feed consumption and feed conversion rate. After the challenge, mortality was 80% in the infected non-treated birds. In the treated groups the mortality rate was 73.3%, 43.3% and 20%, respectively. No histomonal DNA was found in caeca and livers of the surviving birds. In addition, higher doses of paromomycin (200 and 400 ppm) led to reduced counts of Clostridium perfringens in the droppings. In conclusion, a prophylactic application of paromomycin as a feed additive was effective against the challenge with H. meleagridis under experimental conditions.     

Campylobacter susceptibility to ciprofloxacin and corresponding fluoroquinolone concentrations within the gastrointestinal tracts of chickens

AIMS: This study evaluated the relationship between Campylobacter susceptibility and enteric fluoroquinolone concentrations in chickens treated with different doses of enrofloxacin. METHODS AND RESULTS: All chickens were challenged with seven fluoroquinolone sensitive Campylobacter jejuni (6.6 x 10(6) CFU per bird) at 2 weeks posthatch. At 26 days of age chickens were treated with 0 (n = 29 birds), 25 mg ml(-1) enrofloxacin (Baytril, Bayer Corp., Shawnee Mission, KS, USA) for 3 days (n = 45 birds) or 50 mg ml(-1) enrofloxacin for 7 days (n = 65 birds) in the drinking water. The crop, upper ileum, lower ileum, ceca and colon contents were collected from both enrofloxacin treatment groups (n = 5 birds per day per treatment group) and nonmedicated controls. The minimum inhibitory concentration (MIC) of ciprofloxacin for Campylobacter increased for isolates from both treatment groups within the first day of dosing and the daily average ranged from 1.4 to 6.5 microg ml(-1) throughout the study. Although enteric fluoroquinolone concentrations were higher (P < 0.05) in birds dosed with 50 mg ml(-1)vs 25 mg ml(-1) enrofloxacin, there were no differences between the isolates collected from these groups for MIC values. CONCLUSION: These data indicate, for the doses used, differences in gut fluoroquinolone concentrations do not produce isolates of Campylobacter with differing susceptibility to ciprofloxacin. SIGNIFICANCE AND IMPACT OF THE STUDY: Using the manufacturers lowest, shortest duration dose vs the highest, longest duration dose of enrofloxacin did not change Campylobacter susceptibility to ciprofloxacin. However, ciprofloxacin MIC values for Campylobacter determined in this study were lower than previously reported.     

Drug treatment and novel drug target against Cryptosporidium

Cryptosporidiosis emergence triggered the screening of many compounds for potential anti-cryptosporidial activity in which the majority were ineffective. The outbreak of cryptosporidiosis which occurred in Milwaukee in 1993 was not only the first significant emergence of Cryptosporidium spp. as a major human pathogen but also a huge waterborne outbreak thickening thousands of people from a major city in North America. Since then, outbreaks of cryptosporidiosis are regularly occurring throughout the world. New drugs against this parasite became consequently urgently needed. Among the most commonly used treatments against cryptosporidiosis are paromomycin, and azithromycin, which are partially effective. Nitazoxanide (NTZ)'s effectiveness was demonstrated in vitro, and in vivo using several animal models and finally in clinical trials. It significantly shortened the duration of diarrhea and decreased mortality in adults and in malnourished children. NTZ is not effective without an appropriate immune response. In AIDS patients, combination therapy restoring immunity along with antimicrobial treatment of Cryptosporidium infection is necessary. Recent investigations focused on the potential of molecular-based immunotherapy against this parasite. Others tested the effects of probiotic bacteria, but were unable to demonstrate eradication of C. parvum. New synthetic isoflavone derivatives demonstrated excellent activity against C. parvum in vitro and in a gerbil model of infection. Newly synthesized nitro- or non nitro- thiazolide compounds, derived from NTZ, have been recently shown to be at least as effective as NTZ against C. parvum in vitro development and are promising new therapeutic agents.     

兽药恩诺沙星(enrofloxacin)的水解特性

研究了恩诺沙星在不同pH、不同光照及不同微生物条件下的水解,为其生态风险评价提供依据.结果表明,恩诺沙星的水解产物中没有环丙沙星;50 ℃时,避光5 d后恩诺沙星在pH 1～10缓冲液中的水解都小于10%,表明恩诺沙星在恒温避光下的水解半衰期将超过1年,同时溶液pH值的变化对恩诺沙星的水解速率无显著影响;恩诺沙星在天然水中的降解与光照有关,在室外自然光照条件下恩诺沙星降解很快,3 d后水中已经检测不出恩诺沙星.在室内自然光下,恩诺沙星降解较慢,在初始浓度分别为0.05、0.2、1.0 mg·L^-1条件下,31 d试验期内分别降解了48%、72%和65%;在避光条件下,恩诺沙星非常稳定,不易降解.在不同初始浓度下,微生物对恩诺沙星的水解无显著影响.由于恩诺沙星在室外自然光照条件下会迅速降解,因此不会对水环境构成直接的危害,但不能忽视其潜在的生态风险.     

Dientamoeba fragilis in the North-East of Italy: Prevalence study and treatment

Dientamoeba fragilis is an intestinal protozoan, an inhabitant of the human gastrointestinal tract, with a worldwide distribution. The reported prevalence of D. fragilis varies worldwide in different populations between 0.3% and 82.9%, and its role as a pathogen is still unclear. The parasite has been identified in the faeces of asymptomatic patients and with different acute and chronic symptoms, like abdominal pain, diarrhoea, flatulence, nausea and vomiting.The aims of this study were to evaluate the prevalence of D. fragilis in the North-East of Italy, and the clinical improvement of symptoms after recommended treatment with paromomycin or metronidazole. Furthermore, a literature review of D. fragilis prevalence studies in Italy was carried out to show the Italian situation.Of 575 enrolled people, 85 (14.8%) were positive for D. fragilis. The most prevalent symptoms were abdominal pain 28.2%, anal itching 27.1%, watery diarrhoea 18.8%, meteorism 16.5% and nausea/lack of appetite 14.1%. The high rate of anal itching was unexpected, because it wasn't a common symptom. 32 patients were co-infected with B. hominis (37.7%) and three with G. lamblia (3.5%).Our study showed paromomycin had a high efficacy for treatment of D. fragilis infections 100.0% (45/45), while caution must be used when using metronidazole 53.3% (24/40). We recommend paromomycin for empirical treatment, given its great effectiveness in our population.     

Use of enrofloxacin in the treatment of canine brucellosis in a dog kennel (clinical trial)

To date, no totally effective antibiotic for the eradication of canine brucellosis has been found. The purpose of this study was to evaluate the efficacy of enrofloxacin in a kennel infected with Brucella canis. Twelve dogs, 2 males and 10 females (including 1 in estrus, 3 pregnant, and 6 in anestrus) infected with B. canis were given 5 mg/kg of enrofloxacin orally every 12 h for 30 days. Females received additional courses of enrofloxacin during the estral and luteal phases of the subsequent cycles (0-2 cycles). They were repeatedly mated by infected males. A serological follow-up was carried out for 38 months. The clinical, serological and bacteriological findings were recorded. In a trial carried out 14 months after the beginning of this study, all dogs were negative on the Rapid Slide Agglutination Test (RSAT). No abortions were observed. All mated female dogs conceived and gave birth to healthy puppies. Cultures of postpartum vaginal discharges (lochia) were negative for B. canis. Similar to other treatments, although enrofloxacin was not completely efficacious in treating canine brucellosis, it maintained fertility and avoided the recurrence of abortions, transmission of the disease to the puppies and dissemination of microorganisms during parturition. We inferred that enrofloxacin could be used as an alternative drug for the treatment of canine brucellosis.     

Diagnosis and treatment of conjunctivitis in house finches associated with mycoplasmosis in Minnesota

An ongoing outbreak of Mycoplasma gallisepticum-associated conjunctivitis in house finches (Carpodacus mexicanus) that began in 1994 in the eastern United States has been spreading westward. House finches presenting with the clinical signs of M. gallisepticum-associated conjunctivitis were first seen at the Wildlife Rehabilitation Center of Minnesota (Minnesota, USA) in July of 1996, and 42 cases were admitted from 26 December 1996 to 10 August 1997. A nested PCR was designed for sensitive and specific detection of the presence of the organism. Twelve birds were treated with oral enrofloxacin (15 mg/kg, twice daily for 21 days) and ophthalmic gentamicin (twice daily for 21 days). All treated birds showed resolution of clinical signs. Following treatment, finches were held for up to 6 mo and tested for the presence of M. gallisepticum by culture and nested polymerase chain reaction (PCR). Eight of twelve finches (67%) were positive for M. gallisepticum by nested-PCR and four (33%) were positive by culture. The results suggest that oral enrofloxacin and opthalmic gentamicin are not an effective treatment for the eradication of M. gallisepticum in house finches. Further, the results show that nested PCR is an effective method for detection of M. gallisepticum in house finches and was more sensitive than culture.     

In vivo activity of orally administered antibiotics and chemotherapeutics against acute septicaemic pasteurellosis in rabbits

Different antibiotics and chemotherapeutics were tested for therapeutic efficacy in rabbits, in an experimental model using a Pasteurella multocida strain which causes hyperacute septicaemia in this animal species. Only enrofloxacin, administered in the drinking water at a concentration of 50-100 mg/l cured the rabbits, provided that a daily intake of 5 mg/kg body weight was achieved. The other drugs tested (tetracycline, spiramycin, erythromycin and a combination of sulfamerazine with trimethoprim), at doses recommended for rabbits, showed little or no activity at all, with the exception of chloramphenicol, which was only partially effective.     

Efficacy and safety of paromomycin for treating amebiasis in Japan

The clinical management of amebiasis is a growing concern, particularly among human immunodeficiency virus (HIV)-infected individuals who are predisposed to severe illness. Treatment with a luminal amebicide is strongly recommended following acute-stage treatment with a nitroimidazole. In 2004, the Japanese Research Group on Chemotherapy of Tropical Diseases introduced paromomycin, which was not nationally licensed, and offered it to a number of patients. From 2004 to 2011, 143 case records of amebiasis (123 with amebic colitis, 16 with amebic liver abscess, and 4 with both) in which patients were treated with paromomycin, mainly 1500 mg/day for 9 or 10 days following metronidazole treatment, were submitted. Among 123 evaluable cases, 23 (18.7%) experienced possible adverse effects, the most common being diarrhea (17/123, 13.8%) and other gastrointestinal problems that were resolved after the completion or discontinuation of treatment. In addition, single cases of bloody stools associated with Clostridium difficile colitis, skin rash, and the elevation of liver enzymes were also reported, although the causal relationship was not clear. HIV infection did not appear to increase the incidence of adverse drug effects. Each of the 11 asymptomatic or mildly symptomatic amebic colitis cases became negative for stool cysts after paromomycin treatment. Paromomycin was shown to be safe and well tolerated, as well as effective in a special subset of amebic colitis cases.     

不同氮磷浓度下周丛生物对水体中磺胺和恩诺沙星的去除

周丛生物膜是一种对水体污染物净化的新兴生物技术。有关水体不同氮磷营养水平下周丛生物对水体抗生素类污染物去除作用的研究还未见报道。本研究设置4个氮磷营养盐浓度水平[N-P (mg·L^-1):2-0.2、5-0.5、8-0.8、11-1.1],用塑料筐装置在室外培养周丛生物膜,对其生长、光合活力、物种组成以及对磺胺和恩诺沙星去除作用进行中型模拟试验。结果表明: 各处理组中周丛生物的生物量随培养时间的增加而升高,光合色素含量和光合活力则呈现先降低后上升的“单峰”模式,表明生物膜中的藻类会受到抗生素的胁迫,但可快速适应并恢复活力。除此之外,不同氮磷浓度处理造成各组生物群落组成差异,随营养盐浓度的升高,周丛藻类物种丰富度逐渐下降,但各处理胶网藻和小球藻都具有较高的相对丰度;16S rRNA高通量测序发现,根瘤菌科、放线菌门和莫拉氏菌科菌群在(N-P)2-0.2组显著富集,而几丁质嗜菌科在4个处理中的相对丰度都处在最高水平。所有处理的磺胺去除率均高于50%,而恩诺沙星去除率均达到90%以上,其中,(N-P)2-0.2 mg·L^-1组对磺胺的去除率(65.8%)显著高于其他各组,但各处理对恩诺沙星的去除率差异不显著,表明周丛生物在较宽的N-P营养水平范围内对磺胺和恩诺沙星均具有良好的去除能力。各处理组对水体可溶性氮的去除效果不明显,但对可溶性磷的去除效果显著。本研究为水体磺胺和恩诺沙星的生态去除提供了基础数据,为研发水体抗生素类新型污染物生态去除技术提供了新思路。     

Lethal and sub‐lethal impacts of respiratory cryptosporidiosis on Red Grouse,a wild gamebird of economic importance

Respiratory cryptosporidiosis was first diagnosed in Red Grouse Lagopus lagopus scotica, the UK subspecies of Willow Ptarmigan, in 2010. In the next 3 years, respiratory infection by Cryptosporidium baileyi had manifested itself in Grouse on half the moors in northern England and 80% of moors in the North Pennine Hills. In this first account of the impact of respiratory cryptosporidiosis on the population dynamics of a wild bird we fitted 111 diseased and 67 healthy Grouse with radio‐transmitters at two North Pennine moors where disease prevalence averaged 8.1% and monitored their survival and fecundity between autumn 2013 and autumn 2015. Six‐month natural survival rates (excluding shooting) were 0.70 in healthy Grouse, but only 0.44 in diseased females, and 0.22 in diseased males. Some 39% of diseased birds died from their infection, whereas 28% of healthy birds were shot. A similar proportion of each group were killed by predators, either by Stoat Mustela erminea or raptors. Diseased females bred 8 days later than healthy females, but clutch size, egg volume and nesting success did not differ in relation to disease status. Productivity was 43% lower among pairs with a diseased member than in healthy pairs, but appeared impaired only if the female was diseased, not the male. Differences in productivity were related to chick survival rather than the proportion of pairs that reared broods, with chick survival being lower in the 10 days after hatching and again when chicks were 20–50 days old. This latter period was when respiratory infection among chicks was first noticed and the onset of infection may have been a contributing factor to higher mortality during this period. Described levels of respiratory infection reduced the number of birds available to shoot in August by 6%, which represented a mean annual loss of £0.9 million in revenue across managed grouse moors. Likely reductions in shoot economics could escalate should prevalence increase. This disease is a welfare concern and potentially a conservation concern, too, should infection cross to other bird species occupying the same moors.     

Pharmacokinetic interactions of flunixin meglumine and enrofloxacin in ICR mice.

We examined the pharmacokinetic interactions of enrofloxacin and flunixin in male ICR mice that were subcutaneously (SC) administered with both or either one of the drugs. The experiments were performed on the following three groups: flunixin alone (2 mg/kg, SC), combination of flunixin (2 mg/kg, SC) and enrofloxacin (10 mg/kg, SC), and enrofloxacin alone (10 mg/kg, SC). Blood samples were collected at 5, 15 and 30 min, and 1, 2, 3, 4, 5 and 6 h after the drug administration, and the pharmacokinetic parameters of flunixin and enrofloxacin were evaluated from the plasma drug concentrations. Significant changes were detected in the pharmacokinetics of flunixin following its coadministration with enrofloxacin. Coadministration of flunixin and enrofloxacin resulted in a 41% increase of the area under the curve (AUC) and a 53% extension of the terminal half-life of flunixin; moreover, flunixin attained the maximum plasma drug concentration 2.75 times faster than when administered alone. The terminal rate constant and the maximum plasma drug concentration showed significant decreases of 34% and 33%, respectively, following the coadministration of enrofloxacin and flunixin as compared to those following the administration of flunixin alone. In contrast, no significant difference in the pharmacokinetics of enrofloxacin was detected following its coadministration with flunixin, as compared to those following the administration of enrofloxacin alone. Following the administration of enrofloxacin alone or its coadministration with flunixin, the plasma level of ciprofloxacin, the metabolite of enrofloxacin, was very low or undetectable. In conclusion, the pharmacokinetics of flunixin in ICR mice are altered by the coadministration of flunixin and enrofloxacin.     

Leishmania major: histopathological responses before and after topical treatment in experimental animals

The cellular response in the cutaneous leishmaniasis lesion (CL), of BALB/c mice treated topically with an ointment composed of 15% paromomycin and 12% methylbenzethonium chloride (PR-ointment) was studied. In the infected, untreated control group, the lesion showed progressive necrosis with an increase in the number of parasites, macrophages, lymphocytes, and polymorphonuclear cells over a period of 18 weeks. In the PR ointment-treated group, complete healing of the lesion was observed 4 weeks after termination of treatment, but total elimination of the parasites from the lesion was observed only 2 weeks later. A marked reduction in the number of macrophages and polymorphonuclear cells was observed during the healing process. A similar phenomenon was observed with mice inoculated intraperitoneally with paromomycin alone, although total elimination of the parasites from the lesions of these mice was not demonstrated over a period of 18 weeks. Neither L3T4 helper T cells nor Ly2 cytotoxic suppressor T cells were detected in the CL lesion, either before or after treatment.     

Selecting for development of fluoroquinolone resistance in a Campylobacter jejuni strain 81116 in chickens using various enrofloxacin treatment protocols

Aims: To determine the effect of various enrofloxacin dose regimes on the colonization and selection of resistance in Campylobacter jejuni strain 81116P in experimentally colonized chickens. Methods and Results: Two experiments were undertaken, in which 14‐day‐old chickens were colonized with 1 × 10⁷–1 × 10⁹ CFU g^?1Camp. jejuni strain 81116P and then treated with enrofloxacin at 12–500 ppm in drinking water for various times. Caecal colonization levels were determined at various time‐points after start‐of‐treatment, and the susceptibility of recovered isolates to ciprofloxacin was monitored. Resistance was indicated by growth on agar containing 4 μg ml^?1 ciprofloxacin, MICs of 16 μg ml^?1 and the Thr86Ile mutation in gyrA. Enrofloxacin at doses of 12–250 ppm reduced Camp. jejuni colonization over the first 48–72 h after start‐of‐treatment. The degree of reduction in colonization was dose, but not treatment time, dependent. In all cases, maximal colonization was re‐established within 4–6 days. Fluoroquinolone‐resistant organisms were recoverable within 48 h of start‐of‐treatment; after a further 24 h all recovered isolates were resistant. In contrast, a dose of 500 ppm enrofloxacin reduced colonization to undetectable levels within 48 h, and the treated birds remained Campylobacter negative throughout the remaining experimental period. By high pressure liquid chromatography, for all doses, the maximum concentrations of enrofloxacin and ciprofloxacin in the caecal contents were detected at the point of treatment completion. Thereafter, levels declined to undetectable by 7 days post‐treatment withdrawal. Conclusions: In a model using chickens maximally colonized with Camp. jejuni 81116P, treatment with enrofloxacin, at doses of 12–250 ppm in drinking water, enables the selection, and clonal expansion, of fluoroquinolone‐resistant organisms. However, this is preventable by treatment with 500 ppm of enrofloxacin. Significance and impact of the study: Treatment of chickens with enrofloxacin selects for resistance in Camp. jejuni in highly pre‐colonized birds. However, a dose of 500 ppm enrofloxacin prevented the selection of resistant campylobacters.     

Subcellular responses of p53 and Id2 in fast and slow skeletal muscle in response to stretch-induced overload.

Tumor suppressor p53 and inhibitor of DNA-binding/differentiation Id2 were examined after 7 or 21 days of wing weighting in fast patagialis (PAT) and slow anterior latissimus dorsi (ALD) wing muscles of young adult and old Japanese quails. The contralateral wing served as the intra-animal control. Seven days of loading increased PAT and ALD muscle weight by 28 and 96%, respectively, in young birds. PAT and ALD muscle weight was 49 and 179% greater, respectively, than control muscles after 21 days of loading in young birds. In aged birds, no PAT or ALD hypertrophy was found after 7 days of loading; however, PAT and ALD muscle weight increased by 29 and 102%, respectively, after 21 days of loading. Id2 protein in the nuclear muscle fraction increased in both PAT and ALD muscles from young adult and old birds that were loaded for 7 days and in ALD muscles after 21 days of loading relative to contralateral control muscles. Nuclear p53 protein was greater in 7- or 21-day loaded PAT and ALD muscles relative to control muscles in both age groups. Cytosolic Id2 and p53 protein contents were not changed in loaded PAT or ALD muscles relative to control muscles at any time point. These data suggest that nuclear, but not cytosolic, Id2 and p53 are responsive to stretch-induced muscle overload. Moreover, the attenuated ability of the aged skeletal muscle to achieve hypertrophy does not appear to be explained by the subcellular changes in Id2 and p53 content with overload.     

Successful topical treatment of murine cutaneous leishmaniasis with a combination of paromomycin (Aminosidine) and gentamicin

Cutaneous leishmaniasis is presently treated with 20 days of parenteral therapy with a frequently toxic drug (antimony). Topical formulations of paromomycin (15%) plus methylbenzethonium chloride (MBCL, 12%) or plus urea (10%) in soft white paraffin have been tested for Old and New World disease in humans. We compared the efficacy of a new topical formulation, WR 279,396 (paromomycin [15%] plus gentamicin [0.5%]) to the clinical formulations in the treatment of cutaneous disease in BALB/c mice. Sixty-day-old lesions were treated twice a day for 10 days, and the response to therapy was determined over a further 70 days. For ulcers due to Leishmania major or to Leishmania mexicana, 100% of lesions in the WR 279,396 group healed by day 20 after therapy and did not relapse by day 70; 83% of lesions healed without relapse in the paromomycin-MBCL group. In the paromomycin-urea group, 100% of L. major lesions healed by day 30 but 30% relapsed. For ulcers due to Leishmania panamensis or Leishmania amazonensis, all lesions treated with WR 279,396 healed and did not relapse; < 50% of lesions treated with paromomycin-MBCL healed by day 30, and all lesions relapsed by day 70. In addition to being active, WR 279,396 was not toxic in this model and appears to have a cosmetic effect (promoting hair growth, healing, and limiting the size of the scar).     

Proportion of insoluble fibre in the diet affects behaviour and hunger in broiler breeders growing at similar rates

With a view to alleviate the feeling of hunger in broiler breeders, different types of fibre sources were used in high-fibre diets to increase feed quantity while limiting growth to industry recommended levels. Using scatter feeding, three diets (C1: commercial control diet, 1 × fibre content, 80% insoluble fibre (ISF); H2: 2 × fibre content, 89% ISF; and L2: 2 × fibre content, 71% ISF) were each fed to 10 groups of 16 broiler breeder chickens. Similar growth rates were obtained on different quantities of food with all birds reaching commercial target weight at 15 weeks of age. In a hunger test, birds fed C1 ate significantly faster and showed a higher compensatory feed intake than birds on diets H2 and L2, indicating that the two high-fibre diets did reduce the level of hunger experienced by the birds. Behavioural observations carried out at 14 weeks of age showed high levels of tail pecking in birds fed C1 and almost none in birds fed L2, whereas birds fed H2 were intermediate. Stereotypic pecking at fixtures was seen twice as frequently in birds fed C1. Birds on diet L2 displayed behavioural signs indicative of discomfort, and the high water usage on this diet created problems with litter quality. Birds on diet H2 continued to show foraging behaviour throughout the day, and were more frequently engaged in dust bathing and other comfort behaviour. This experiment indicates that high-fibre diets can alleviate the feeling of hunger currently experienced by broiler breeders, and a high ratio of ISF may improve the well-being of the birds.     

Immunomodulatory effect of picroliv on the efficacy of paromomycin and miltefosine in combination in experimental visceral leishmaniasis

Combination therapy for the treatment of visceral leishmaniasis has increasingly been advocated as a way to increase treatment efficacy and tolerance, to reduce treatment duration and cost, and to limit the emergence of drug resistance. In the present work, we have adopted a rational approach, which can modulate the immune response to overcome the negative control systems and to boost the positive killing responses. This study was designed to investigate the immunomodulatory effect of picroliv (standardized fraction from the alcoholic extract of root and rhizome of Picrorhiza kurroa) on a combination of paromomycin and miltefosine using Leishmania donovani/hamster model. Picroliv has significantly enhanced antileishmanial efficacy and lymphocyte proliferation when given in combination with paromomycin and miltefosine. Increased toxic oxygen metabolite generation and phagocytosis were also witnessed. Present study thus establishes the possible use of picroliv as adjunct to antileishmanial chemotherapy.