BackgroundStrains of Dirofilaria immitis suspected of lack of efficacy (LOE) to macrocyclic lactone (ML) preventive drugs have been increasingly reported in dogs by practicing veterinarians since 2005 in the Lower Mississippi Delta region. If proven, and not controlled in the early stages, the emergence of ML drug resistance threatens to become a widespread problem in the US that may limit the effectiveness of current preventive drug treatment methods.MethodsTo validate practice reports, a statewide survey of Louisiana veterinarians was done to define the extent of the problem and identify focal ‘hotspots’ of reported ML LOEs using Geographic Information Systems (GIS) methods. The present study then utilized microfilariae (Mf) from two canine field cases from different state locations that fit criteria for a high index of suspicion of LOE against heartworms by ML drugs. Blood containing Mf from the canine field cases was used to infect and produce L3 in Aedes aegypti for experimental infection of two groups of dogs, each of which contained two laboratory dogs, one treated with prophylactic ivermectin (12 μg/kg) monthly for 6 months at twice the label dose (6 μg/kg), and one untreated control.ResultsBoth treated and untreated dogs from Group I and Group II developed patent D. immitis infections by 218 DPI and 189 DPI, respectively, as evidenced by a positive occult heartworm antigen test and microfilaremia by the Knott’s test. Mf counts gradually increased post-patency in test and control dogs. Infective larvae raised from microfilariae from the treated Group I dog were used to successfully establish a second generation isolate, confirming heritability of resistance in the face of a monthly ivermectin challenge dose of 24 μg/kg, given monthly for 3 months.ConclusionsThese experimental infection studies provide in vivo evidence of the existence of ML drug resistance in dogs infected by D. immitis L3 from suspect field LOE cases in the Lower Mississippi Delta. Results encourage further work on mechanisms underlying the emergence of ML resistance in D. immitis and development of evidence-based resistance management strategies for heartworm preventives in order to extend the useful life of current drugs.
Background: Strains of Dirofilaria immitis suspected of lack of efficacy (LOE) to macrocyclic lactone (ML) preventive drugs have been increasingly reported in dogs by practicing veterinarians since 2005 in the Lower Mississippi Delta region. If proven, and not controlled in the early stages, the emergence of ML drug resistance threatens to become a widespread problem in the US that may limit the effectiveness of current preventive drug treatment methods.
Vaccination of Mongolian gerbils with Brugia malayi cysteine protease inhibitor-2 in which the amino acid Asn66 was mutated to Lys66 (Bm-CPI-2M) resulted in reduced parasite numbers of 48.6% and 48.0 % at 42 and 90 days p.i. with B. malayi L3s. Fertility of female worms was also affected at 90 days p.i. In vitro killing of L3s observed in the presence of gerbil peritoneal exudate cells and anti-Bm-CPI-2M sera suggests antibody-dependent cell-mediated cytotoxicity as a putative protective mechanism. These observations suggest that Bm-CPI-2M is a promising prophylactic and anti-fecundity vaccine candidate.
BackgroundCysteine protease inhibitors of Brugia malayi have been ascribed to be involved in parasite development as well as to immunomodulate the host’s immune response. In Onchocerca volvulus, Onchocystatin has been shown to induce partial protection in the mouse diffusion chamber vaccination model. In the present study we investigated the impact of vaccination with recombinant Bm-CPI-1 and Bm-CPI-2 proteins on protection against a subcutaneous challenge of B. malayi third stage larvae in gerbils.FindingsVaccination with E. coli derived recombinant B. malayi cysteine protease inhibitors (Bm-CPI-1 or -2) did not confer protection against B. malayi L3 challenge infection in gerbils but altered the homing of a significant number of adult worms from the lymphatics to the heart and lungs.ConclusionBm-CPI vaccination-induced alteration in worm migration is consistent with our previous observations in gerbils vaccinated with B. pahangi excretory-secretory (ES) proteins, which resulted in delayed migration of the L3s and altered the final location of adult worms. Similar observations have also been made in dogs vaccinated with Ancylostoma caninum proteins; an increased number of worms were recovered in the colon and not the expected small intestine. A change in the final niche was also reported in immune versus non-immune hosts of two other gut dwelling nematodes. Vaccination induced alteration of the parasite’s final homing might be a rare or a common phenomenon, which unfortunately is rarely recorded. The reason for the alteration in the final niche selection by adult nematode worms following vaccination is unknown and necessitates further investigation.
Introduction and importance
During gestation, laparoscopic procedures, if needed, are generally considered most ideal within the second trimester. There are less reports of successful laparoscopic procedures in the third trimester of pregnancy due to performance hesitancy with concerns of preterm labor and/or other complications. While it is rare for laparoscopic cholecystectomy to be performed within the third trimester, it should not be delayed if needed, and excellent outcomes can be achieved with proper port placement and procedure.
Case presentation
We present the case of a 22-year-old female thirty-two weeks and six days into gestation who underwent a laparoscopic cholecystectomy with intraoperative cholangiogram after presenting with acute-on-chronic cholecystitis. The procedure was without complications, and both the patient and fetus remained stable following surgery, and were discharged on postoperative day 2.
Clinical discussion
The long-established belief is laparoscopic procedures should ideally be attempted in the second trimester to decrease the risk of preterm labor or spontaneous abortion in obstetric patients. Per SAGES guidelines, when clearly indicated, laparoscopic cholecystectomy should not be avoided in any trimester.
Conclusion
This case highlights the relative safety of a laparoscopic cholecystectomy in the third trimester of pregnancy with emphasis on standard technique and proper port placement based on uterus size.
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