By Dr Balkar Bains
Coccidiosis control in commercial poultry has been heavily reliant upon the application of anticoccidial drugs via feed. The development of coccidia resistance to anticoccidial drugs was a common occurrence and problematic because coccidia were resistant to all chemical drugs within the same family.
Coccidiosis outbreaks frequently require treatment to minimize morbidity and mortality. Affected flocks experience poor growth rates and feed conversion efficacy, resulting in adverse economic consequences. There were concerted efforts in recent times to identify and implement better alternatives to the currently range of chemical anticoccidial drugs.
Types of anticoccidial combinations
Chemical and chemical anticoccidials
The concept of combinations of different drugs first commenced with chemical anticoccidials, to prolong the use of chemical compounds and overcome coccidia resistance. Combining two chemicals in practice proved to be effective in extending the efficacy period of several anticoccidials. However, chemical anticoccidials in combination were not completely effective in preventing resistance. The combination concept was based upon the principles of synergy or additive effects with some complementary mechanism of action of both compounds.
Initial success led to the development of several combination products made available to the poultry industry including Amprolium plus, Pancoxin, Rofenaid, Toltro and Lerbek (table 1). These products must be carefully managed to avoid the emergence of coccidia resistance.
Chemical and ionophore anticoccidials
In subsequent years, the concept of ionophore and chemical anticoccidial combinations was adopted most effectively to improve the efficacy of ionophore anticoccidials. This new concept was based upon the use of both ionophore and chemical anticoccidials at a lower dosage levels while maintaining the desired anticoccidial efficacy. The efficacy of these combinations does decline over time following continuous use under commercial conditions.
The most widely used commercially available products of this combination include Maduramicin + Nicarbazin and Narasin + Nicarbazin. The chemical compound Nicarbazin is used at a reduced dosage level and thus prone to the loss of efficacy particularly in the control of E. tenella. In addition, all limitations for the use of Nicarbazin in combination still apply.
Ionophore and ionophore anticoccidials
The combination concept appears to be more suited to ionophore anticoccidials. Ionophore combinations have greater potential for limiting coccidia resistance development compared with individual ionophore anticoccidials used at present. Ionophores belong to the same family of compounds and their mechanism of action against coccidia is similar. The loss of efficacy of ionophores under commercial conditions is gradual and often different with each coccidian strain.
These observations can be interpreted as being strengths or weakness of an individual ionophore. The identification of strengths offers a greater advantage in selecting ionophores for a specific application or known coccidia resistance problem in commercial flocks. The mechanism of action is coccidiocidal, yet it permits enough coccidia challenge to generate sufficient immune response that may enable the withdrawal of the anticoccidial from broiler feed after 35 days. The efficacy of ionophore combinations has been the subject of research in the past, which is reviewed here to evaluate the use of combinations under commercial conditions.
Efficacy of ionophore combinations
- In a controlled series of battery trials (Untewale & Schildknecht 1985) the efficacy of Monensin and Lasalocid was compared with uninfected unmedicated controls (UUC), infected unmedicated controls (IUC) and three combinations (normal inclusion rate of each ionophore is 100ppm):
- Lasalocid 75 ppm + Monensin 25 ppm
- Lasalocid 50 ppm + Monensin 50 ppm
- Lasalocid 25ppm + Monensin 75 ppm
Field isolates of coccidia in the challenge included E. acervulina, E. tenella and E. maxima. Results of the trial in table 2 (below), following E. tenella and E. acervulina challenge, show that the weight gain of chickens increased linearly as the proportion of Lasalocid increased in each treatment.
Similarly, the feed conversion also showed linear improvement. Results of E. maxima challenge in table 3 (below) shows that the combination improved both weight gain and FCR as the Lasalocid content of the combination increased.
- Anticoccidial efficacy of Salinomycin combination with other Ionophore anticoccidials at different ratios was evaluated (Wolfgang Raether and G. Dost 1985) in battery trials. For the challenge in this trial, strains of field isolated E. tenella 48%, E. brunetti 20% and E. acervulina 32% of unknown drug sensitivity. The significant findings of the trials were that Salinomycin and Lasalocid combination have an additive effect against coccidia as compared to other Ionophore combinations with Salinomycin. The authors concluded that the limited effect of some mixtures of Salinomycin and related ionophores might have resulted from reduced anticoccidial sensitivity due to prior use under commercial conditions. The results of the trials are summarized in table 4 below.
- Another trial (Research report) evaluated different dosage levels of combinations of Lasalocid plus Salinomycin (table 5, below), Lasalocid plus Maduramicin, and Maduramicin plus Salinomycin (table 6) against the challenge of mixed infection of E. tenella, E. acervulina and E. maxima from field isolates. Efficacy criteria included weight gain and FCR as percentage of uninfected unmedicated controls. The combination of Lasalocid and Salinomycin showed the best results when both compounds are used at 50% of the dosage currently used under commercial conditions.
- For the Maduramicin and Lasalocid combination the best results (table 6 below) were at the higher dosage of Lasalocid (67 ppm) inclusion, which were reflected in both weight gain % and FCR. Results for the Maduramicin and Salinomycin combination at 50% dosage inclusion level were comparable with other combinations.
Learnings on anticoccidial combinations
- It is generally agreed that continuous use of ionophore anticoccidials invariably results in some loss of efficacy as determined by commercial parameters. The rotation and shuttle programs are often used to recover loss of efficacy, which primarily is the FCR.
- The combination of two ionophore anticoccidials at dosage levels of 50% each offers an alternative that minimizes loss of efficacy.
- Combinations also provide the opportunity to use those ionophores that, when used in alone, are less effective against some coccidia strains.
- Combinations of those ionophores that experienced some loss of efficacy when used alone are likely to be less efficacious and may lead to a loss of efficacy after a short duration of use under commercial conditions.
- The low dosage of each ionophore in combination does offer less chance of tissue residues yet effectively controls coccidiosis.
- Caution must be observed in regards to toxicity and known side effects even if the levels are used in combinations are lower than used by single ionophores.
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Kwa Dr. Balkar Bains Udhibiti wa Coccidiosis katika kuku wa kibiashara umekuwa ukitegemea sana matumizi ya dawa za anticoccidial kupitia chakula. Uvumilivu wa coccidia kwa dawa za anti-coccidial ni tatizo la kawaida kwa sababu coccidia ni sugu kwa dawa zote za kemikali ndani ya familia moja. Mara nyingi milipuko ya coccidiosis huhitaji kutibiwa ili kupunguza ugonjwa na vifo. Makundi yaliyoathiriwa hupata viwango vya chini vya ukuaji na ufanisi wa kubadilisha chakula, na kusababisha matokeo mabaya ya kiuchumi. Katika miaka ya hivi karibuni, jitihada nyingi zimefanywa ili kutambua na kutumia dawa mbadala bora za dawa za kemikali zinazopinga ugonjwa wa kibofu. Aina ya mchanganyiko wa anticoccidial: Anticoccidial kemikali na kemikali, pamoja na dawa za kulevya, ni pamoja na dawa za kulevya, kwa sababu ya kuimarisha uwezo wa kukabiliana na coccidia. Kuchanganya kemikali mbili katika mazoezi ilithibitika kuwa na ufanisi katika kupanua kipindi cha ufanisi wa anticoccidials kadhaa. Hata hivyo, dawa za kemikali za kuzuia kuambukizwa kwa wadudu hazikuwa na matokeo kabisa katika kuzuia upinzani. Dhana ya mchanganyiko ilitegemea kanuni za ushirikiano au athari za ziada na baadhi ya utaratibu wa ziada wa hatua ya misombo yote miwili. Mafanikio ya awali yalisababisha maendeleo ya bidhaa kadhaa za mchanganyiko zilizotolewa kwa sekta ya kuku ikiwa ni pamoja na Amprolium plus, Pancoxin, Rofenaid, Tolter, na Leberk. Bidhaa hizi lazima zisimamiwe kwa uangalifu ili kuepuka kuibuka kwa upinzani wa coccidia. Katika miaka ya baadaye, dhana ya ionophore na kemikali anticoccidial mchanganyiko ilipitishwa kwa ufanisi zaidi ili kuboresha ufanisi wa ionophore anticoccidials. Dhana hii mpya ilitegemea matumizi ya ionophore na kemikali anticoccidials katika viwango vya chini dosage wakati kudumisha ufanisi anticoccidial taka. Ufanisi wa mchanganyiko huu hupungua kwa muda baada ya matumizi ya kuendelea chini ya hali za kibiashara. Bidhaa zinazopatikana kibiashara zinazotumiwa sana za mchanganyiko huu ni pamoja na Maduramicin + Nicarbazin na Narasin + Nicarbazin. Nikarbazine ni kemikali ya kawaida ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa ya dawa. Kwa kuongezea, mapungufu yote kwa matumizi ya Nicarbazin katika mchanganyiko bado yanatumika. Ionofor na ionophore anticoccidials dhana ya mchanganyiko inaonekana kuwa yanafaa zaidi kwa ionophore anticoccidials. Mchanganyiko wa ionophore una uwezo mkubwa wa kupunguza maendeleo ya upinzani wa coccidia ikilinganishwa na anti-coccidials ya ionophore ya mtu binafsi inayotumiwa kwa sasa. Ionophores ni mali ya familia moja ya misombo na utaratibu wao wa hatua dhidi ya coccidia ni sawa. Kupoteza ufanisi wa ionophores chini ya hali ya kibiashara ni hatua kwa hatua na mara nyingi tofauti na kila coccidian strain. Uchunguzi huu unaweza kutafsiriwa kama kuwa nguvu au udhaifu wa ionophore ya mtu binafsi. Utambulisho wa nguvu inatoa faida kubwa katika kuchagua ionophores kwa ajili ya maombi maalum au inayojulikana coccidia upinzani tatizo katika makundi ya kibiashara. Mchakato wa hatua ni coccidioside, lakini inaruhusu changamoto ya coccidia ya kutosha ili kuzalisha majibu ya kinga ya kutosha ambayo yanaweza kuwezesha uondoaji wa anticoccidial kutoka kwa chakula cha kuku baada ya siku 35. Ufanisi wa mchanganyiko wa ionophore umekuwa suala la utafiti katika siku za nyuma, ambayo ni kukaguliwa hapa kutathmini matumizi ya mchanganyiko chini ya hali ya kibiashara. Katika mfululizo wa majaribio ya betri (Untweil na Schildknecht, 1985), ufanisi wa Monensin na Lasalocid ulilinganishwa na udhibiti wa uninfected unmedicated (UIC), udhibiti wa uninfected unmedicated (IUC) na mchanganyiko wa tatu (kiwango cha kawaida cha ujumuishaji wa kila ionophore ni 100 ppm) - Lasalocid + Monensin + 50 ppm - Lasalocid + Monensin + 75 ppm. Matokeo ya majaribio katika meza 2 (chini) kufuatia E. tenella na E. acervulina changamoto, kuonyesha kwamba uzito wa kuku kuongezeka linearly kama uwiano wa lasalocid kuongezeka katika kila matibabu. Vivyo hivyo, kubadilisha kulisha pia ilionyesha uboreshaji linear. Matokeo ya E. maxima challenge katika meza 3 (chini) yanaonyesha kwamba mchanganyiko huo uliboresha kuongeza uzito na FCR wakati maudhui ya Lasalocid ya mchanganyiko huo yalipokuwa yakiongezeka. Salinomycin na ionophores nyingine anti-coccidial katika uwiano tofauti ilikuwa tathmini (Wolfgang Raether na G. Dost 1985) katika majaribio ya betri. Kwa mfano, katika majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio ya majaribio. Matokeo ya utafiti huo ni kwamba salinomicini na lasalocidi pamoja na salinomicini ina athari ya kuongeza dhidi ya coccidia ikilinganishwa na ionophore nyingine pamoja na salinomicini. Kwa hivyo, matokeo ya matokeo ya mchanganyiko wa salinomycin na ionophores zinazohusiana na hiyo inaweza kuwa matokeo ya kupunguza unyeti wa anticoccidial kutokana na matumizi ya awali chini ya hali za kibiashara. Matokeo ya majaribio hayo yameorodheshwa katika Jedwali la 4 hapa chini. Utafiti mwingine (Research Report) ulichunguza viwango tofauti vya kipimo cha Lasalocid na Salicylic Acid (Table 5, chini), Lasalocid na Maduramicine, na Maduramicine na Salicylic Acid (Table 6) dhidi ya changamoto ya maambukizi ya mchanganyiko ya E. tenera, E. acervulina na E. maxima kutoka kwa maeneo ya mashamba. Kiwango cha ufanisi kilijumuisha kuongezeka kwa uzito na FCR kama asilimia ya udhibiti usioambukizwa usio na dawa. Mchanganyiko wa lasalocid na salinomycin ulionyesha matokeo bora wakati misombo yote miwili ilitumiwa kwa 50% ya kipimo kinachotumiwa kwa sasa chini ya hali za kibiashara. Kwa maduramicine na lasalocid, matokeo bora (tabula 6 hapa chini) yalikuwa katika kipimo cha juu cha Lasalocid (67 ppm), ambayo ilionyeshwa katika asilimia ya kuongezeka kwa uzito na FCR. Matokeo ya maduramicini na salinomicini kwa kiwango cha ujumuishaji wa kipimo cha 50% yalikuwa sawa na mchanganyiko mwingine. Mafunzo juu ya mchanganyiko wa anticoccidial - Ni kwa ujumla kukubaliana kwamba matumizi ya kuendelea ya ionophore anticoccidials daima husababisha baadhi ya hasara ya ufanisi kama ilivyoamuliwa na vigezo kibiashara. Programu za mzunguko na shuttle hutumiwa mara nyingi kurudisha hasara ya ufanisi, ambayo ni hasa FCR. Mchanganyiko wa ionophore anti-coccidial katika viwango vya kipimo cha 50% kila mmoja hutoa mbadala ambayo hupunguza hasara ya ufanisi. - Mchanganyiko pia kutoa fursa ya kutumia wale ionophores kwamba, wakati kutumika katika peke yake, ni chini ya ufanisi dhidi ya baadhi ya coccidia strains. Mchanganyiko wa ionophores ambayo ilipata kupoteza ufanisi wakati kutumika peke yake ni uwezekano wa kuwa chini ya ufanisi na inaweza kusababisha kupoteza ufanisi baada ya muda mfupi wa matumizi chini ya hali ya kibiashara. - kipimo cha chini cha kila ionophore katika mchanganyiko haina kutoa nafasi kidogo ya mabaki ya tishu bado ufanisi kudhibiti coccidiosis. - Tahadhari lazima ifuatwe kuhusiana na sumu na athari za upande zinazojulikana hata kama viwango vinavyotumiwa katika mchanganyiko ni vya chini kuliko vinavyotumiwa na ionophores moja. Zamira ni kampuni ya afya ya wanyama ya Australia na lengo lake ni kuboresha afya, ustawi na uzalishaji wa wanyama duniani kote. Soma zaidi kuhusu sisi hapa.