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Topic:Prophylaxis

Prophylaxis in horses refers to the preventive measures and strategies implemented to protect equine health by reducing the risk of disease occurrence. These measures can include vaccinations, parasite control, nutrition management, and biosecurity practices. Vaccinations help to stimulate the horse's immune system to protect against specific infectious diseases. Parasite control programs aim to minimize the impact of internal and external parasites through strategic deworming and environmental management. Nutrition management ensures that horses receive balanced diets that support their overall health and immune function. Biosecurity practices involve procedures to prevent the introduction and spread of infectious agents within equine populations. This page gathers peer-reviewed research studies and scholarly articles that explore various prophylactic approaches, their implementation, and their effectiveness in maintaining equine health.
Control of lice infestation in horses using a 10 mg/mL deltamethrin topical application.
Irish veterinary journal    June 19, 2017   Volume 70 22 doi: 10.1186/s13620-017-0100-2
Castilla-Castaño E, Vischi A, Navarro C, Lecru LA, Ribeiro C, Pradier S, Cadiergues MC.Two open-controlled studies evaluated the tolerance and the efficacy of a 10 mg/mL deltamethrin-based pour-on solution (Deltanil®; Virbac, France) in treating (study 1) and preventing (study 2) natural Damalinia equi infestations in horses. In study 1, seven adult horses received 10 mL of the solution from mane to tail head on day 0 (D0). Four adult horses, living separately, served as non-treated controls. All were naturally infected. Lice burden was recorded by counting the number of live parasites, bilaterally, over seven anatomic regions. Lesional score was based on alopecia, crusts, papu...
Papillomavirus infection and squamous cell carcinoma in horses.
Veterinary journal (London, England : 1997)    May 31, 2017   Volume 223 48-54 doi: 10.1016/j.tvjl.2017.05.007
Sykora S, Brandt S.Squamous cell carcinoma (SCC) is a common disease that seriously impairs the health and welfare of affected horses and other equids. In humans, almost all cervical carcinomas, a high percentage of anogenital SCCs and a subset of SCCs of the head and neck are caused by high-risk human papillomavirus (hrHPV) infection. Since hrHPV-induced human cancers and equine SCC have similar cytological and histopathological features, it has been hypothesised that equine SCCs could also be induced by papillomaviruses. This review provides an overview of the current evidence for an aetiological association b...
Antigen-specific immunoglobulin variable region sequencing measures humoral immune response to vaccination in the equine neonate.
PloS one    May 16, 2017   Volume 12, Issue 5 e0177831 doi: 10.1371/journal.pone.0177831
Tallmadge RL, Miller SC, Parry SA, Felippe MJB.The value of prophylactic neonatal vaccination is challenged by the interference of passively transferred maternal antibodies and immune competence at birth. Taken our previous studies on equine B cell ontogeny, we hypothesized that the equine neonate generates a diverse immunoglobulin repertoire in response to vaccination, independently of circulating maternal antibodies. In this study, equine neonates were vaccinated with 3 doses of keyhole limpet hemocyanin (KLH) or equine influenza vaccine, and humoral immune responses were assessed using antigen-specific serum antibodies and B cell Ig var...
Antimicrobial Pharmacology for the Neonatal Foal.
The Veterinary clinics of North America. Equine practice    March 23, 2017   Volume 33, Issue 1 47-65 doi: 10.1016/j.cveq.2016.12.004
Magdesian KG.Neonatal foals are at high risk of developing sepsis, which can be life-threatening. Early antimicrobial use is a critical component of the treatment of sepsis. Because the neonatal foal has unique pharmacologic physiology, antimicrobial choice and dosing are often different than in adult horses. Broad-spectrum, bactericidal, and intravenous antimicrobials should be considered first-line therapy for septic foals. A combination of aminoglycoside and beta-lactam antimicrobial or third-generation cephalosporin is an excellent empirical first choice for treating septic foals, until culture and sus...
Potential of a BPV1 L1 VLP vaccine to prevent BPV1- or BPV2-induced pseudo-sarcoid formation and safety and immunogenicity of EcPV2 L1 VLPs in horse.
The Journal of general virology    March 13, 2017   Volume 98, Issue 2 230-241 doi: 10.1099/jgv.0.000673
Hainisch EK, Abel-Reichwald H, Shafti-Keramat S, Pratscher B, Corteggio A, Borzacchiello G, Wetzig M, Jindra C, Tichy A, Kirnbauer R, Brandt S.We have previously shown that immunization of horses with bovine papillomavirus type 1 (BPV1) L1 virus-like particles (VLPs) is safe and highly immunogenic and that BPV1 and bovine papillomavirus type 2 (BPV2) are closely related serotypes. Here we evaluated the protective potential of a BPV1 L1 VLP vaccine against experimental BPV1 and BPV2 challenge and studied the safety and immunogenicity of a bivalent equine papillomavirus type 2 (EcPV2)/BPV1 L1 VLP vaccine. Fourteen healthy horses were immunized with BPV1 L1 VLPs (100 µg per injection) plus adjuvant on days 0 and 28, while seven remai...
Immune protection against reinfection with nonprimate hepacivirus.
Proceedings of the National Academy of Sciences of the United States of America    March 8, 2017   Volume 114, Issue 12 E2430-E2439 doi: 10.1073/pnas.1619380114
Pfaender S, Walter S, Grabski E, Todt D, Bruening J, Romero-Brey I, Gather T, Brown RJ, Hahn K, Puff C, Pfankuche VM, Hansmann F, Postel A, Becher P....Hepatitis C virus (HCV) displays a restricted host species tropism and only humans and chimpanzees are susceptible to infection. A robust immunocompetent animal model is still lacking, hampering mechanistic analysis of virus pathogenesis, immune control, and prophylactic vaccine development. The closest homolog of HCV is the equine nonprimate hepacivirus (NPHV), which shares similar features with HCV and thus represents an animal model to study hepacivirus infections in their natural hosts. We aimed to dissect equine immune responses after experimental NPHV infection and conducted challenge ex...
Therapeutics for Equine Protozoal Myeloencephalitis.
The Veterinary clinics of North America. Equine practice    February 1, 2017   Volume 33, Issue 1 87-97 doi: 10.1016/j.cveq.2016.12.001
Pusterla N, Tobin T.Equine protozoal myeloencephalitis is an infectious disease of the central nervous system caused by Sarcocystis neurona or Neospora hughesi. Affected horses routinely present with progressive and asymmetrical neurologic deficits. The diagnosis relies on the presence of neurologic signs, ruling out other neurologic disorders, and the detection of intrathecally derived antibodies to either S neurona and/or N hughesi. Recommended treatment is use of an FDA-approved anticoccidial drug formulation. Medical and supportive treatment is provided based on the severity of neurologic deficits and complic...
Effects of pre-shipping enrofloxacin administration on fever and blood properties in adult Thoroughbred racehorses transported a long distance.
The Journal of veterinary medical science    January 22, 2017   Volume 79, Issue 3 464-466 doi: 10.1292/jvms.16-0465
Endo Y, Ishikawa Y, Arima D, Mae N, Iwamoto Y, Korosue K, Tsuzuki N, Hobo S.To evaluate the effects of single-dose enrofloxacin (ERFX) on fever and blood properties in 68 Thoroughbred racehorses after long-distance transportation, horses were assigned to receive ERFX (5 mg/kg, IV; ERFX group; n=52) or saline (0.9% NaCl) solution (50 ml, IV; control group; n=16) ≤1 hr before transportation. Horses were transported 1,122 km using commercial vans over the course of approximately 21 hr. Clinical examinations and hematologic analyses were performed before and after transportation. Rectal temperatures, white blood cell counts and serum amyloid A concentration of ERFX grou...
Neonatal Immunization with a Single IL-4/Antigen Dose Induces Increased Antibody Responses after Challenge Infection with Equine Herpesvirus Type 1 (EHV-1) at Weanling Age.
PloS one    January 3, 2017   Volume 12, Issue 1 e0169072 doi: 10.1371/journal.pone.0169072
Wagner B, Perkins G, Babasyan S, Freer H, Keggan A, Goodman LB, Glaser A, Torsteinsdóttir S, Svansson V, Björnsdóttir S.Neonatal foals respond poorly to conventional vaccines. These vaccines typically target T-helper (Th) cell dependent B-cell activation. However, Th2-cell immunity is impaired in foals during the first three months of life. In contrast, neonatal basophils are potent interleukin-4 (IL-4) producers. The purpose of this study was to develop a novel vaccine triggering the natural capacity of neonatal basophils to secrete IL-4 and to evaluate if vaccination resulted in B-cell activation and antibody production against EHV-1 glycoprotein C (gC). Neonatal vaccination was performed by oral biotinylated...
Equine Immunoglobulin and Equine Neutralizing F(ab’)₂ Protect Mice from West Nile Virus Infection.
Viruses    December 18, 2016   Volume 8, Issue 12 332 doi: 10.3390/v8120332
Cui J, Zhao Y, Wang H, Qiu B, Cao Z, Li Q, Zhang Y, Yan F, Jin H, Wang T, Sun W, Feng N, Gao Y, Sun J, Wang Y, Perlman S, Zhao J, Yang S, Xia X.West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab')₂ fragments from horses immunized with the WNV virus-like particles (VLP) expressing the WNV M and E proteins. Immune equine F(ab')₂ fragments and immune horse sera efficiently neutralized WNV infec...
Selection of a candidate probiotic strain of Pediococcus pentosaceus from the faecal microbiota of horses by in vitro testing and health claims in a mouse model of Salmonella infection.
Journal of applied microbiology    December 14, 2016   Volume 122, Issue 1 225-238 doi: 10.1111/jam.13339
Silva BC, Sandes SH, Alvim LB, Bomfim MR, Nicoli JR, Neumann E, Nunes AC.The aim of this study was to verify the suitable use of candidate 'probiotics' selected by in vitro tests and the importance of in vivo assays to nominate micro-organisms as probiotics and alternative prophylactic treatments for Salmonella Typhimurium infection. Results: Thirty-three lactic acid bacteria (LAB) isolated from foal's faeces were assessed based on the main desirable functional in vitro criteria. Based on these results, Pediococcus pentosaceus strain 40 was chosen to evaluate its putative probiotic features in a mouse model of Salmonella infection. Daily intragastric doses of Pe...
Antimicrobial stewardship in the treatment of equine bacterial infections.
Veterinary journal (London, England : 1997)    November 21, 2016   Volume 219 4-5 doi: 10.1016/j.tvjl.2016.11.009
Johns I.No abstract available
The preventive effects of two nutraceuticals on experimentally induced acute synovitis.
Equine veterinary journal    October 13, 2016   Volume 49, Issue 4 532-538 doi: 10.1111/evj.12629
van de Water E, Oosterlinck M, Dumoulin M, Korthagen NM, van Weeren PR, van den Broek J, Everts H, Pille F, van Doorn DA.Nutraceuticals are often used in the management of equine osteoarthritis, but scientific evidence of their efficacy is lacking. Objective: To study the preventive effects of two new nutraceuticals after the experimental induction of synovitis in comparison with positive and negative control treatments. Methods: Blinded, controlled, randomised experiment. Methods: Twenty-four healthy Standardbred horses were randomly allocated to supplement AT (multi-ingredient, 28 days), supplement HP (collagen hydrolysate, 60 days), meloxicam (4 days) or placebo (60 days). Synovitis was induced in the right i...
Evaluation of an oral direct factor Xa inhibitor anticoagulant in healthy adult horses.
Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001)    October 6, 2016   Volume 27, Issue 1 82-88 doi: 10.1111/vec.12540
Rodríguez-Pozo ML, Armengou L, Monreal L, Viu J, Cesarini C, Jose-Cunilleras E.To assess whether an oral direct factor Xa inhibitor (DiXaI) anticoagulant drug used at the low end of the recommended dose in people achieves presumed prophylactic plasma concentrations and does not induce bleeding in horses. Methods: Experimental study. Methods: Field study. Methods: Ten healthy adult horses. Methods: A DiXaI was administered at a dose of 0.125 mg/kg every 24 h orally for 4 days. Following a wash-out period of 2 weeks, 8 of 10 horses received daily subcutaneous doses of a low molecular weight heparin (dalteparin) for 4 consecutive days at 50 IU/kg. In both trials, antifactor...
Efficacy of intravenous administration of hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses.
American journal of veterinary research    September 27, 2016   Volume 77, Issue 10 1064-1070 doi: 10.2460/ajvr.77.10.1064
Frisbie DD, McIlwraith CW, Kawcak CE, Werpy NM.OBJECTIVE To evaluate the efficacy of IV administration of a product containing hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses. ANIMALS 32 healthy 2- to 5-year-old horses. PROCEDURES The study involved 2 portions. To evaluate prophylactic efficacy of the test product, horses received 5 mL of the product (n = 8) or saline (0.9% NaCl) solution (8; placebo) IV every fifth day, starting on day 0 (when osteoarthritis was induced in the middle carpal joint of 1 forelimb) and ending on day 70. To evaluate treatment efficacy, ...
Prevention of equine herpesvirus myeloencephalopathy – Is heparin a novel option? A case report.
Tierarztliche Praxis. Ausgabe G, Grosstiere/Nutztiere    September 21, 2016   Volume 44, Issue 5 313-317 doi: 10.15653/TPG-150451
Walter J, Seeh C, Fey K, Bleul U, Osterrieder N.Equine herpesvirus myeloencephalopathy (EHM) is a severe manifestation of equine herpesvirus 1 (EHV-1) infection. Prevention and treatment of EHM during EHV-1 outbreaks is critical, but no reliable and tested specific medication is available. Due to the thromboischemic nature of EHM and due to the fact that EHV-1 entry in cells is blocked by heparin, it was hypothesized that this compound may be useful in reduction of EHM incidence and severity. Therefore, during an acute EHV-1 outbreak with the neuropathogenic G/D Pol variant, metaphylactic treatment with heparin to prevent EHM was initiated....
Therapeutic and prophylactic uses of invertebrates in contemporary Spanish ethnoveterinary medicine.
Journal of ethnobiology and ethnomedicine    September 5, 2016   Volume 12, Issue 1 36 doi: 10.1186/s13002-016-0111-1
González JA, Amich F, Postigo-Mota S, Vallejo JR.Zootherapeutic practices in ethnoveterinary medicine are important in many socio-cultural environments around the world, particularly in developing countries, and they have recently started to be inventoried and studied in Europe. In light of this, the purpose of this review is to describe the local knowledge and folk remedies based on the use of invertebrates and their derivative products in contemporary Spanish ethnoveterinary medicine. An overview in the fields of ethnozoology, ethnoveterinary medicine and folklore was made. Automated searches in the most important databases were performed....
Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis.
Applied and environmental microbiology    August 15, 2016   Volume 82, Issue 17 5332-5339 doi: 10.1128/AEM.01166-16
Furusawa T, Iwano H, Hiyashimizu Y, Matsubara K, Higuchi H, Nagahata H, Niwa H, Katayama Y, Kinoshita Y, Hagiwara K, Iwasaki T, Tanji Y, Yokota H....Bacterial keratitis of the horse is mainly caused by staphylococci, streptococci, and pseudomonads. Of these bacteria, Pseudomonas aeruginosa sometimes causes rapid corneal corruption and, in some cases, blindness. Antimicrobial resistance can make treatment very difficult. Therefore, new strategies to control bacterial infection are required. A bacteriophage (phage) is a virus that specifically infects and kills bacteria. Since phage often can lyse antibiotic-resistant bacteria because the killing mechanism is different, we examined the use of phage to treat horse bacterial keratitis. We isol...
Duration of serum antibody response to rabies vaccination in horses.
Journal of the American Veterinary Medical Association    August 2, 2016   Volume 249, Issue 4 411-418 doi: 10.2460/javma.249.4.411
Harvey AM, Watson JL, Brault SA, Edman JM, Moore SM, Kass PH, Wilson WD.OBJECTIVE To investigate the impact of age and inferred prior vaccination history on the persistence of vaccine-induced antibody against rabies in horses. DESIGN Serologic response evaluation. ANIMALS 48 horses with an undocumented vaccination history. PROCEDURES Horses were vaccinated against rabies once. Blood samples were collected prior to vaccination, 3 to 7 weeks after vaccination, and at 6-month intervals for 2 to 3 years. Serum rabies virus-neutralizing antibody (RVNA) values were measured. An RVNA value of ≥ 0.5 U/mL was used to define a predicted protective immune response on the b...
Protection from Hendra virus infection with Canarypox recombinant vaccine.
NPJ vaccines    July 28, 2016   Volume 1 16003 doi: 10.1038/npjvaccines.2016.3
Guillaume-Vasselin V, Lemaitre L, Dhondt KP, Tedeschi L, Poulard A, Charreyre C, Horvat B.Hendra virus (HeV) is an emerging zoonotic pathogen, which causes severe respiratory illness and encephalitis in humans and horses. Since its first appearance in 1994, spillovers of HeV from its natural reservoir fruit bats occur on almost an annual basis. The high mortality rate in both humans and horses and the wide-ranging reservoir distribution are making HeV a serious public health problem, especially for people exposed to sick horses. This study has aimed to develop an efficient low-cost HeV vaccine for horses based on Canarypox recombinant vector expressing HeV glycoproteins, attachment...
Protection of horse ears against Simulid parasitism: Efficacy of a mammal semiochemical solution over 10hours.
Veterinary parasitology    July 9, 2016   Volume 227 15-19 doi: 10.1016/j.vetpar.2016.07.007
Creton B, Pageat P, Robejean M, Lafont-Lecuelle C, Cozzi A.Hematophagous insects can be vectors of pathogens and cause significant economic loss in zootechnical production. Among biting insects, many dipteran species feed on horse blood. The black fly (Diptera: Simuliidae) group, is responsible for several disorders in horses and inflicts painful bites that lead to undesirable behaviours in horses, particularly when bites occur in sensitive areas such as the inner ear. A field study was conducted in a French equestrian center during which a semiochemical was applied on horses' ears to assess repellent efficacy against simulid infestation. During the f...
Engineered Mesenchymal Cells Improve Passive Immune Protection Against Lethal Venezuelan Equine Encephalitis Virus Exposure.
Stem cells translational medicine    June 22, 2016   Volume 5, Issue 8 1026-1035 doi: 10.5966/sctm.2015-0341
Braid LR, Hu WG, Davies JE, Nagata LP.: Mesenchymal stromal cells (MSCs) are being exploited as gene delivery vectors for various disease and injury therapies. We provide proof-of-concept that engineered MSCs can provide a useful, effective platform for protection against infectious disease. Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne pathogen affecting humans and equines and can be used in bio-warfare. No licensed vaccine or antiviral agent currently exists to combat VEEV infection in humans. Direct antibody administration (passive immunity) is an effective, but short-lived, method of providing immediate prote...
Immune Dysfunction in Aged Horses.
The Veterinary clinics of North America. Equine practice    June 18, 2016   Volume 32, Issue 2 333-341 doi: 10.1016/j.cveq.2016.04.009
McFarlane D.The aging process in people is associated with changes in adaptive and innate immune responses. Similar changes occur in aged horses. Age-related progressive impairment in the ability to respond to pathogen challenge and an increased inflammatory reactivity may predispose geriatric horses to many diseases of old age. Specific recommendations for immune modification of older horses, including an age-appropriate vaccination schedule, are not currently available. In addition, the effect of old age on risk of infectious disease is poorly documented. More work is needed to better understand the int...
A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation.
Vaccine    May 17, 2016   Volume 34, Issue 31 3607-3612 doi: 10.1016/j.vaccine.2016.04.077
Hannaman D, Dupuy LC, Ellefsen B, Schmaljohn CS.Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid™ Delivery System. Subjects in IM-EP gro...
Designing a field trial of an equine grass sickness vaccine: A questionnaire-based feasibility study.
Veterinary journal (London, England : 1997)    May 4, 2016   Volume 213 64-71 doi: 10.1016/j.tvjl.2016.05.001
Ireland JL, McGorum BC, Proudman CJ, Newton JR.Without an experimental model of equine grass sickness (EGS), a randomised controlled field trial (RCT) represents the only method of evaluating the efficacy of Clostridium botulinum type C vaccination in preventing naturally occurring disease. Clinical trial feasibility is an important aspect of preliminary work undertaken prior to initiating RCTs, estimating parameters that are important for study design. This cross-sectional study aimed to assess the feasibility of conducting a nationwide RCT of a candidate vaccine for EGS based on responses from a sample of British equine veterinary practi...
The appropriate antiparasitic treatment: Coping with emerging threats from old adversaries.
Equine veterinary journal    April 12, 2016   Volume 48, Issue 3 374-375 doi: 10.1111/evj.12550
Nielsen MK, von Samson-Himmelstjerna G, Pfister K, Reinemeyer CR, Molento MB, Peregrine AS, Hodgkinson JE, Jacobsen S, Kaplan RM, Matthews JB.No abstract available
A preventive immunization approach against insect bite hypersensitivity: Intralymphatic injection with recombinant allergens in Alum or Alum and monophosphoryl lipid A.
Veterinary immunology and immunopathology    March 2, 2016   Volume 172 14-20 doi: 10.1016/j.vetimm.2016.02.017
Jonsdottir S, Svansson V, Stefansdottir SB, Schüpbach G, Rhyner C, Marti E, Torsteinsdottir S.Insect bite hypersensitivity (IBH) is an IgE-mediated dermatitis of horses caused by bites of Culicoides insects, not indigenous to Iceland. Horses born in Iceland and exported to Culicoides-rich areas are frequently affected with IBH. The aims of the study were to compare immunization with recombinant allergens using the adjuvant aluminum hydroxide (Alum) alone or combined with monophosphoryl lipid A (MPLA) for development of a preventive immunization against IBH. Twelve healthy Icelandic horses were vaccinated intralymphatically three times with 10 μg each of four recombinant Culicoides nub...
Preventing haemorrhage in equine guttural pouch mycosis.
The Veterinary record    January 9, 2016   Volume 178, Issue 2 42-43 doi: 10.1136/vr.i37
Dixon PM.No abstract available
Optimizing selection of large animals for antibody production by screening immune response to standard vaccines.
Journal of immunological methods    January 9, 2016   Volume 430 56-60 doi: 10.1016/j.jim.2016.01.006
Thompson MK, Fridy PC, Keegan S, Chait BT, Fenyö D, Rout MP.Antibodies made in large animals are integral to many biomedical research endeavors. Domesticated herd animals like goats, sheep, donkeys, horses and camelids all offer distinct advantages in antibody production. However, their cost of use is often prohibitive, especially where poor antigen response is commonplace; choosing a non-responsive animal can set a research program back or even prevent experiments from moving forward entirely. Over the course of production of antibodies from llamas, we found that some animals consistently produced a higher humoral antibody response than others, even t...
[Evaluation of an immunochromatographic dipstick test for the assessment of tetanus immunity in horses].
Berliner und Munchener tierarztliche Wochenschrift    November 26, 2015   Volume 128, Issue 9-10 376-383 
Recknagel S, Snyder A, Blanke A, Uhlig A, Brüser B, Schusser GF.Knowledge of tetanus immunity in equine patients is crucial in cases of injuries, elective surgeries, or when effective vaccination protocols are to be designed. The Fassisi® TetaCheck is a stall-side rapid test which was developed to address these issues. The purpose of the present study was to evaluate its performance parameters. To this end, the qualitative test results obtained by two blinded observers were compared to tetanus toxoid antibody levels from 99 serum samples, measured with a double antigen ELISA. Additionally the colour intensities of the test window were quantified using a c...
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