Effect of different doses of ivermectin on the survival and fecundity of Glossina palpalis gambiensis Vanderplank 1949 fed on treated cattle

Effect of different doses of ivermectin on the survival and fecundity of Glossina palpalis gambiensis Vanderplank 1949 fed on treated cattle | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of different doses of ivermectin on the survival and fecundity of Glossina palpalis gambiensis Vanderplank 1949 fed on treated cattle Sié Hermann Pooda, Soumaïla Pagabeleguem, Ange Irénée Toé, Adrien Marie Gaston Belem, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7605011/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Feb, 2026 Read the published version in Parasites & Vectors → Version 1 posted 10 You are reading this latest preprint version Abstract Background Tsetse flies, (Glossina spp), are the main vectors of trypanosome parasites responsible for the the Human African Trypanosomiasis (HAT) and the African Animal Trypanosomosis (AAT), both of which remain significant obstacles to the socio-economic development of affected regions in sub-Saharan Africa. Several control strategies have been developed, among which, vector control plays a central role. To achieve the elimination of HAT and AAT, additional and integrated complementary control strategies, such as the ivermectin treatments of animals, need to be explored. Methods To assess the systemic insecticidal efficacy of ivermectin on the survival and fecundity of Glossina palpalis gambiensis , batches of tsetse flies were fed on 6 calves that were treated with three different doses of the drug: therapeutic dose (TD) of 0.2 mg/kg, two-fold TD, and four-fold TD. Two untreated calves were used as the control group. Results The TD and 2TD induced significant mortality of the tsetse flies up to 1 days post injection (DPI), with mortality rates varying from 59.82% to 90.43%. The 4TD caused a significant decrease of 55.09% of the survival of the tsetse flies up to 15 DPI (Z = -4.37; P < 0.001 ). The cattle treatments with ivermectin also resulted in a decrease of the number of pupae produced by tsetse flies, of 43.57% with the TD, and 92.47% with the 4TD. A delay from 9 to 13 days has also been observed in the deposit of the first larva, with the doses 2TD and 4TD at 1DPI and to 10 days with the dose 4TD at 8DPI. Conclusions The ivermectin treatments to animals against the common parasitosis have an additional effect against insect vectors like tsetse flies. Thus, mass treatments of farmed animals with ivermectin, may be considered in order to improve both human and animal health. Ivermectin Cattle Glossina palpalis gambiensis vector control Integrated control Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Livestock production has an important place in the economies of developing countries, which roughly represents 10 to 20% of Gross Domestic Product [ 1 ]. Cattle are particularly valuable for their multifaced contributions including meat and milk production, draft power, and manure for use as fertilizer. Parasitic infections represent a major constraint in livestock production, contributing to reduced productivity, increased mortality, and elevated management costs [ 2 , 3 ]. African Animal Trypanosomosis (AAT), or Nagana are major parasitosis that seriously impede the development of the livestock production [ 4 , 5 ]. They are due to blood parasites, the Trypanosoma sp . transmitted to animals mainly by tsetse flies (Diptera: Glossinidae). Tsetse flies are present exclusively in Africa and also transmit trypanosomes responsible for Human African Trypanosomiasis (HAT) or sleeping sickness. HAT and AAT generate significant health problem and social and economic losses for Africa [ 6 ]. To control sleeping sickness, the health services primarily rely on medical screening and treatment of confirmed cases, alongside tsetse fly control. Chemotherapy remains the main approach to control Nagana, despite the development of chemo-resistance [ 7 , 8 ]. However, vector control is still a preferential choice method, in addition to chemotherapy, particularly in the absence of a vaccine to prevent these diseases [ 9 ]. Vector control interventions have significantly reduced tsetse flies populations, and, consequently, the transmission of both HAT and AAT [ 4 , 10 , 11 ]. The principal methods of tsetse control include the use of toxic attractants (such as insecticide-impregnated traps and targets), the topical application of insecticides to cattle serving as live bait, the ground and aerial spraying of insecticide, and the implementation of the Sterile Insect Technique (SIT) [ 12 ]. Despite considerable efforts, tsetse flies and the transmission of trypanosomosis continue to pose significant adverse public health and economic challenges in the affected regions. It is therefore necessary to pursue researches into complementary or alternative tools for the control of both AAT and HAT, particularly in the context of diseases elimination goal. One such promising tool is ivermectin, a broad-spectrum endectocide widely used in both human and veterinary medicine, which has demonstrated systemic insecticidal effects against arthropods including various tsetse species. Ivermectin belongs to the avermectin family of macrocyclic lactones discovered in 1973 [ 13 ]. These compounds, termed endectocides, are effective against both internal parasites (endo-parasitic) and external parasites (ecto-parasitic) organism [ 13 , 14 ]. Ivermectin is active against a broad range of parasites including gastrointestinal nematodes (roundworms), extra-intestinal nematodes such as Dictyocaulis viviparus and Parafilaria bovicola , microfilariae of Onchocerca spp , and various arthropods (insects and mites) [ 14 , 15 ]. The standard therapeutic dose for field treatment in cattle is 0.2 mg/kg body weight [ 16 ]. Once administrated, ivermectin circulates systemically and can adversely affect blood-feeding insects including tsetse flies, by disrupting key history traits. The systemic insecticidal effect of ivermectin on adult flies of Glossina palpalis palpalis was first reported by Distelmans and al. [ 17 ], who observed mortality in tsetse flies fed on goats treated with a high dose of 10 mg/kg (50 fold the therapeutic dose), and on guinea pigs treated with 2 mg/kg (10 fold the therapeutic dose) was reported [ 17 ]. Insects typically died 4 to 8 days after repeated feeding. These authors, noted the onset of ivermectin’effects on G. p. palpalis begins at doses between 1 and 2 mg/kg of body weight. Subsequent studies confirmed similar systemic effects on G. morsitans [ 18 ], G. tachinoides [ 19 ], and notably on G. p. gambiensis , a vector of both HAT and AAT in West Africa [ 20 ]. In the later study, ivermectin administrated at the therapeutic dose of of 0.2 mg/kg exhibited only a short-term insecticidal effect on G. p. gambiensis , lasting less than one week post-treatment [ 20 ]. These findings highlighted the need to investigate adjusted dosing regimens capable of sustaining systemic insecticidal activity over longer periods. The present study therefore aimed at comparing effects of therapeutic and increased doses of ivermectin on the life history traits of G. p. gambiensis , to identify an optimized dose that can maintain prolonged insecticidal efficacy against this specie. Methods Tsetse flies specie and rearing conditions We used the reference colony of G. p. gambiensis from the Centre International de Recherche-Développement sur l’Elevage en zone Subhumide (CIRDES) . The CIRDES colony was established in 1972 using specimens collected in the Guinguette, a locality near from Bobo-Dioulasso, Burkina Faso [ 21 – 23 ]. It has been maintained on cattle blood given through silicone membranes and in the Center dedicated insectary (25 ± 1° C and 70 ± 5% relative humidity). Freshly emerged flies were separated by sex and put into Roubaud cages (13.5 × 8 × 4.5 cm), 20 females or 20 males per cage, and kept into holding room (25 ± 1° C and 70 ± 5% relative humidity) during 2 days, the necessary time for flies to become sexually mature [ 24 ]. Three days old males and females of G. p. gambiensis were then fed on treated or control animals. Females were subsequently mated with 6 days-old virgin males at the ratio of 1:3 [ 25 ] to examine treatment’ effects on fecundity and fertility of the flies. Feeding hosts, acre Eight calves (cross-breed between the local “Baoulé” and the Fulani Zebu strains) were purchased from surrounding farms near Bobo-Dioulasso to be used as the tsetse flies feeding host. The calves were in average 3 years old and weighted 120.75 (± 16.44) kg. Before starting the experiment, animals were washed using soapy water to remove any residues of topical dewormers potentially administered of origin. They also dewormed with Albendazol at the recommended dosage and treated with a curative trypanocide (Berenil®) to address potential infection of African animal trypanosomosis which is endemic in this region. Their diet consisted of rice straw, cotton cake and water given ad libitum. They were maintained in the CIRDES stable protected by mesh against another insects biting. The animal were monitored daily by a trained veterinarian technician to ensure their well-being, and an antibiotic treatment was provided when needed. Ivermectin drug and cattle treatment The injectable veterinary ivermectin formulation IVOMEC-D® (Boehringer Ingelheim, Lyon, France) was used for animal’s treatments. This formulation contains 1% ivermectin and 10% Clorsulon as active ingredients. Ivermectin targets mainly gastrointestinal nematodes, strongyles, lungworms, and external parasites in cattle and sheep while Clorsulon targets liver flukes. Three different doses of the drug were injected subcutaneously at the neck of the different animals (TD = therapeutic dose of 0.2 mg/kg, 2TD = 0.4 mg/kg and 4TD = 0.8 mg/kg) (Table 1 ). Control calves did not receive ivermectin injection but were kept under the same conditions as the treated ones. Table 1 Description of the experimental design Value Number of cattle by dose 2 Ivermectin doses tested (mg/kg) 0, 0.2, 0.4 and 0.8 Days Post injection of ivermectin 1, 8, 15, 22, 29 and 36 Number of blood meal taken 1 Parameters evaluated Daily mortality, pupal production, time to first pupae, and emergence rate Survival follow up To evaluate the systemic insecticidal effects of ivermectin on tsetse survival, two cages containing each, males or females flies were placed on the flanks of each animal during 15 minutes. These cages were secured using rubber band and covered with black cloth to create darkness, thereby facilitating effective blood feeding. Following feeding on cattle, engorged flies were monitored daily over 30 days period to assess mortality. These step were repeated at different times post-injection with the fresh batches of tsetse flies (Table 1 ). Since tsetse flies are obligate hematophagous insects, subsequent blood meals were provided every two days using a silicone membrane feeding system, as previously described [ 26 , 27 ]. For membranes feeding, bovine or pig blood collected at the Bobo-Dioulasso slaughterhouse, defibrinated and sterilized prior to use. Systemic effects of ivermectin on the fecundity of tsetse females Mating cages were placed in individual larviposition cups and then, the pupae were collected daily and sorted into normal and aborted L3. Normal pupae were transferred to an incubation room for adult emergence. Pupal production was recorded daily for each treatment group and each cage. To evaluation the systemic effects of ivermectin on tsetse fecundity, several reproductive parameters were measured for each treatment: (i) the average number of pupae produced per initially blood fed females over 30-days period following the first blood meal; (ii) the average time of the first larva production (i.e. the interval time between female emergence and the production of the first pupae), (iii) and the average adult emergence rate from the pupae. 2.7. Data analysis Statistical analysis and data visualization were performed using R software [ 28 ]. Fly survival was analyzed using Kaplan and Meier survival analysis, and the survival curve were compared using the Cox proportional hazard model (Coxph) [ 29 ]. In this model, treatment, time post injection, and fly sex were included as explanatory variables, with survival rate as the response variable. Multiple comparisons between survival outcomes across treatment groups were conducted using the "glht" function from Multcomp package [ 30 ]. Cumulative mortalities over follow up period were also calculated and analysed to facilitate survival comparison between treatments. Difference in hhe mean number of pupae produced and the adult emergence rate between treatments were analysed using a general linear model with quasi-Poisson distribution [ 31 ]. The timing fof first pupae production were compared between treatments groups using Kruskall Wallis test [ 31 ]. Results Effects of ivermectin on the survival of tsetse Overall, the effects of the different doses of ivermectin on the survival of G. palpalis gambiensis varied according to the treatment, the time post injection at which tsetse were fed, and the sex of the flies (Fig. 1 ). Overall, the data showed a significant effect of ivermectin treatment ( \(\:{X}_{3}^{2}\) = 353.63, P < 0.001), the time post injection ( \(\:{X}_{2}^{2}\) = 450.90, P < 0.001), and the tsetse fly sex ( \(\:{X}_{2}^{2}\) = 278.21, P < 0.001) on the survival rate. Among the three doses of ivermectin tested, the TD and the 2TD treatment induced a significant decrease of the survival of G. palpalis gambiensis only at 1 day post injection of the drug to cattle. For TD, the tsetse mortality rate at this time point and was 59.82% (48.57% for females and 70.18% for males), compared to 29.90% for the control (11.88% for females and 35.58% for males) (Z = 7.36; P < 0.001) (Fig. 2 ). The effect of the TD was significant on both the mortality of female (Z = 5.47; P < 0.001) and males (Z = 5.12; P < 0.001). The ivermectin dose of 0.4 mg /kg (2TD) also decreased significantly the survival at 1 DPI (Z = -14.68; P < 0.001), with mortality’ rates of 90.43% for treated flies (87.29% for the females and 93.75% for the males) against 23.90% for the control flies (11.88% for the females and 35.58% for the males). The four-fold therapeutic dose (4TD) of ivermectin significantly decreased tsetse survival at the 1 DPI (Z = -16.96; P < 0.001), 8 DPI (Z = -11.99; P < 0.001) and 15 DPI (Z = -4.37; P < 0.001). The mortality rate of tsetse due to the 4TD of ivermectin at different DPI were 94.55%, 86.41% and 55.09%, respectively at 1, 8 and 15 DPI. At 22 DPI to 29 DPI and 36 DPI, no significant survival difference in survival was observed between tsetse flies fed on treated and control cattle ( P > 0.05). Systemic effects of ivermectin on fecundity Average number of pupae produced by female The fecundity of female of G. p. gambiensis (i.e. the average number of pupae produced per female) varied according to the treatments and the DPI (Fig. 3 ). Females fed on cattle treated with the TD at 1 DPI produced 0.43 pupae per female compared to 0.99 pupae per female in the control group, representing a significant reduction of 56.56% (Estimate = -0.83, Z value =-5.77, P < 0.0001 ). Females fed on cattle treated with 2TD of ivermectin at 1 DPI showed an even greater reduction in fecundity, producing 0.09 pupae/female against 0.99 for control, a 90.09% decrease (Estimate = -2.41, Z value =-5.75, P < 0.0001 ). At 8 DPI, the 4TD significantly reduced significantly the average number of pupae produced by 92.47%, with 0.02 pupae per female in the treated group versus 0.78 in the controls (Estimate = -3.92, Z value =-3.38, P = 0.003 ). For the other DPI and ivermectin doses where pupae were produced, there was no significant effect of the treatment on the average number of pupae produced. First larval period The first larval period varied from 14.5 days to 30 days according to the treatment (Table 2 ). Table 2 Average date of first larval period DPI Average days of first larval period according to the treatment (SE) Control TD 2 TD 4 TD 1 17,00 (1.05) a 20,71 (0.36) a 26,67 (1.67) b 30,00 (0.00) b 8 19,13 (0.55) a 20,42 (0.95) a 19,75 (0.63) ab 29,40 (0.60) b 15 17,50 (0.50) ab 17,75 (0.25) b 19,75 (1.55) ab 19,75 (0.86) a 22 17,25 (0.41) a 16,88 (0.23) a 17,38 (0.26) a 18,25 (0.37) a 29 17,00 (0.31) a 17,25 (0.25) a 17,50 (0.71) a 17,63 (0.42) a 36 18,00 (0.00) a 18,00 (0.00) a 18,13 (0.13) a 17,13 (1.03) a DPI : Days Post Injection of ivermectin; TD : Therapeutic Dose of ivermectin; 2TD: 2 fold therapeutic dose; 4TD: 4 fold therapeutic dose of ivermectin. The data in the same row with the different letter are significantly different at P < 0.05; SE: Standard error. No significant effect of the therapeutic dose of ivermectin was observed on the average time to first larvisposition. However, the 2TD of ivermectin induced a significantly delay of 9 days in the average day of first larval period at 1 DPI ( P = 0.01 ). Females of G. p. gambiensis fed on cattle treated with the 4TD of ivermectin, exhibited a delay of 13 days at 13 days at 1 DPI ( P = 0.0001 ) and 10 days at 8 DPI ( P = 0.0017 ) in the timing of first larviposition. Adult emergence The emergence rates of pupae produced by females of G. palpalis gambiensis are presented in the Fig. 4 . No significant difference was found in the hatching rates between control and treated flies for all doses and all DPI (Treatment effect: Deviance = 0.80, P = 0.98 ). Discussion This study demonstrated that the ivermectin treatment of cattle significantly reduces the survival of G. P. gambiensis that feed on them. The insecticidal effect of ivermectin at the therapeutic dose persisted up to 1 day post injection, while the four-fold therapeutic dose (0.8 mg/kg) extended this effect to maximum of 15 days. Doubling the therapeutic dose did not further prolong the insecticidal effect on G. p. gambiensis . These finding differ from our previous study, in which the therapeutic dose exhibited an insecticidal effect lasting up to 8 days post-treatment in same specie [ 20 ]. As ivermectin is progressively eliminated from the blood of treated cattle, variability in tsetse fly survival was observed, notably between sexes, with females generally exhibiting longer lifespans than males, which may reflect sex-related differences in susceptibility to ivermectin. A sex-based difference in longevity has also been reported in previous studies on the same species under varying temperature conditions [ 32 ] and different feeding regimes [ 33 ]. Interestingly, the pronounced systemic insecticidal effect on male suggests that ivermectin could serve as a valuable complementary tool in tsetse eradication efforts, particularly when integrated with the Sterile Insect Technique (SIT,[ 34 ]). The increased mortality of male flies following ivermectin treatment may reduce the population of wild males, thereby decreasing competition with released sterile males and enhancing of effectiveness of SIT in the field. However, careful consideration must be given to dose selection to minimize unintended impacts on female tsetse flies, especially their reproductive capacity. Sub-lethal exposure that affects fecundity without achieving full mortality may pose a risk for the development of resistance over time [ 35 ]. The mean elimination half-life of ivermectin following subcutaneous injection of the conventional formulation at the therapeutic dose in cattle is approximately 8 days [ 36 – 38 ]. The present study shows that a yet low, safe dose (4TD), can reduce tsetse flies survival for up to 15 days post-treatment. This finding contrasts with earlier observations by Distelmans et. al. [ 17 ], who reported a shorter duration of effect despite using a higher dose of 2mg/kg However, in their study, the blood meal hosts were guinea pigs and goats rather than cattle, which likely influenced the pharmacokinetics of ivermectin and thus the extent of its systemic insecticidal action [ 39 ]. Similarly, Van Den Abbeele et al. found no significant impact on the survival of G. palpalis palpalis fed on guinea-pigs with 0,5 mg/kg [ 40 ] and Van Den Bossche and Geerts reported no effect on G. tachinoides fed on pigs treated with 1 mg/kg [ 19 ]. These discrepancies our findings may be due not only to the interspecies differences in ivermectin pharmacokinetics between the different host animals (guinea pig, goat and pig vs. cattle) but also to differences in tsetse species, which may vary in their susceptibility to ivermectin, like shown for Anopheles [ 41 ]. As with survival, discrepancies in the effects of ivermectin on tsetse fly fecundity across studies can likely be attributed to differences in tsetse species, the animal host used for blood feeding, ivermectin pharmacokinetics, and experimental design. In the present study, the therapeutic dose of the ivermectin formulation used resulted in a 56.56% reduction in fecundity at 1 DPI. In contrast, Van Den Abbeele et al. [ 42 ] found no effect of the therapeutic dose of ivermectin on fecundity in G. p. palpalis fed on rabbits. In our study, increasing the ivermectin dose to 0.4 mg/kg did not extend the duration of its effect on fecundity in G. p. gambiensis . Van Den Abbeele et al. [ 40 ] found also that ivermectin at a dose of 0.5 mg/kg decreased fecundity (measured by both the number of pupae and pupal mass) of G. palpalis palpalis fed one day post treatment. In addition to reducing the number of pupae per female, our study also showed a delay in the onset of the first larval deposition occurring at 29 days post feeding in treated females versus 19 days in the control group at 8 DPI and with 4TD. No significant effect on adult emergence rates was observed in the present study, consistent with previous findings [ 18 ]. However, a previous study on G. morsitans reported that a single blood meal taken from cattle 7 days after treatment with a therapeutic dose of ivermectin ( 0.2 mg/kg) induced a 44% decrease in fertility during the second ovarian cycle [ 18 ]. Thereafter, fertility gradually evolved towards normal. According to Van Den Abbeele et al. [ 42 ], the effect of ivermectin on tsetse fecundity is likely due to a combination of delayed ovulation, increased gestation duration, and disruption of pupation. Overall, the results of present study on G. p. gambiensis are consistent with findings from other tsetse species, supporting the general conclusion that ivermectin, even if its effect are transient using commercial formulation, can negatively impact tsetse longevity and reproduction. The biological impacts could play a meaningful role in the control of trypanosomosis, given the relatively slow reproductive cycle of tsetse and the duration of trypanosome development within the fly. Specifically, Trypanosoma vivax typically requires around 10 days to complete development in the fly, T. congolense requires 12–14 days and T. brucei 20–30 days [ 43 , 44 ]. Therefore, any reduction in tsetse survival caused by ivermectin during the early days post-treatment would interrupt the transmission cycle of all three major trypanosome species, with the strongest impact expected for T. brucei , both in terms of intensity and duration. While the effects of ivermectin on tsetse are largely indirect (by reducing vector survival and, consequently, parasite development), it would be worth investigating whether ivermectin might also exert direct effects on trypanosome development within the vector, as it does for other pathogens [ 45 , 46 ]. Although promising in terms of disease management, mass treatment of livestock with ivermectin have potential ecological consequences that should not be overlooked. Adverse effects on non-target dung fauna and other wildlife have been documented [ 47 – 49 ], highlighting the need for responsible and targeted use of endectocides [ 50 ]. Additionally, although the low reproductive rate of tsetse limits the rapid development of insecticide resistance, the relatively weak systemic insecticidal effect of ivermectin on this species warrants further investigation. Proactive resistance mitigation strategies should also be considered to preserve the efficacy of ivermectin within integrated vector control programs. The low reproductive rate of tsetse reduces the development of insecticide resistance, but the weakness of the systemic insecticidal effects of ivermectin on this specie deserves special attention. The demonstration of glutamate-dependent chloride channels not sensitive to ivermectin could explain this weak effect of the molecule on tsetse flies [ 51 ] compared to mosquitoes [ 52 ]. Conclusions The results of this study demonstrate that ivermectin administered to cattle affects the longevity and fertility of Glossina palpalis gambiensis . These findings confirm the systemic insecticidal properties of ivermectin against hematophagous insects, as previously reported in the literature, and reinforce earlier observations made on this tsetse species. Notably, this study highlights the effects of a therapeutic dose of ivermectin on the species G. p. gambiensis feeding directly on treated cattle under in vivo conditions. The insecticidal impact persisted for up to 15 days post- treatment when cattle received a dose four times the standard therapeutic level. These findings lead to two important considerations. First, the widespread use of ivermectin in the field for both human and animal health could have a more substantial impact on tsetse populations and trypanosomiasis transmission than previously recognized. This potential has likely been underestimated and warrants further investigations through studies linking ivermectin use to key epidemiological indicators of trypanosomiasis. The second consideration is that avermectins in general, and ivermectin in particular, may represent valuable complementary tools in the integrated control of trypanosomoses, especially in areas where the vectors feed primarily or occasionally on domestic animals such as cattle. In such settings, periodic and synchronized ivermectin treatments of men and/or livestock could significantly reduce vector longevity and fecundity, and consequently, disease transmission. Additional effects on vector fertility, as well as possible direct impacts on parasite development within the vector, should also be further explored. Moreover, given that trypanosomiasis and malaria are often co-endemic in sub-Saharan Africa, the use of ivermectin offers a unique opportunity to develop integrated vector control strategies targeting both diseases. Ivermectin has been shown to reduce the survival of Anopheles mosquitoes, the vectors of malaria, and is being evaluated in large-scale clinical trials. Notably, Phase 3 trials investigating the impact of ivermectin on malaria epidemiology have yielded contrasting results, likely due to differences in trial design, vector species, treatment regimens, and local epidemiological contexts. Nevertheless, this area of research remains highly dynamic, and continued investigation may help define the optimal conditions under which ivermectin can serve as a dual-action intervention against both malaria and trypanosomiasis. However, there are important limitations to consider before ivermectin can be widely promoted for vector control purposes. These include potential adverse effects on non-target organisms, the presence of drug residues in milk when dairy cattle are treated, and the risk of resistance development due to extensive use. These concerns underscore the need for a cautious and evidence-based approach when considering the integration of ivermectin into broader vector control strategies. Declarations Ethics approval and consent to participate The study has received an approval of the ethical committee of the “Centre International de Recherche Développement sur l’Elevage en zones Sub-humides” (CIRDES). Competing interests Authors declare no competing interests. Funding This study was funded mainly by, the “Laboratoire Mixte International sur les maladies à vecteurs (LAMIVECT)”. It received also the financial resource of the International Foundation of Sciences (IFS). Author Contribution All authors participated to the project’s elaboration and the design of the study. They all amended the present paper. M.K., S.H.P., A.M.G.B. and S.P. conceived the study. M.K., S.H.P., and A.I.T. elaborated the protocols. S.H.P., S.P., and A.I.T. did the survival and reproduction experiments . S.H.P. and M.K. performed the statistical analysis and drafted the paper. All authors read and approved the final version of the manuscript. 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Administration of ivermectin to peridomestic cattle: a promising approach to target the residual transmission of human malaria. Malar J. 2015;14. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 06 Feb, 2026 Read the published version in Parasites & Vectors → Version 1 posted Editorial decision: Revision requested 02 Oct, 2025 Reviews received at journal 01 Oct, 2025 Reviews received at journal 22 Sep, 2025 Reviewers agreed at journal 22 Sep, 2025 Reviewers agreed at journal 19 Sep, 2025 Reviewers agreed at journal 18 Sep, 2025 Reviewers invited by journal 16 Sep, 2025 Editor assigned by journal 16 Sep, 2025 Submission checks completed at journal 16 Sep, 2025 First submitted to journal 13 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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female.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7605011/v1/6cbb25499664ba2046342c78.png"},{"id":92182688,"identity":"6f398dee-2224-4730-906b-814a4da441ed","added_by":"auto","created_at":"2025-09-25 13:52:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":27964,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative mortality of G. p. gambiensis fed on treated and control cattle at different days post injection (DPI)\u003c/p\u003e\n\u003cp\u003eTD = Therapeutic dose (0.2 mg/kg); 2TD = two-fold therapeutic dose; 4TD = four-fold therapeutic dose.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7605011/v1/238f9a0b2839d702d23e1971.png"},{"id":92184132,"identity":"d14344fa-64af-4c8c-bc75-c1bce3ff28ea","added_by":"auto","created_at":"2025-09-25 14:00:32","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":36752,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAverage number of pupae produced by female of \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eG. p. gambiensis\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTD = Therapeutic dose (0.2 mg/kg); \u003c/em\u003e\u003cem\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/em\u003e\u003cem\u003eTD = \u003c/em\u003e\u003cem\u003e\u003cstrong\u003etwo-\u003c/strong\u003e\u003c/em\u003e\u003cem\u003efold therapeutic dose;\u003c/em\u003e\u003cem\u003e\u003cstrong\u003e 4\u003c/strong\u003e\u003c/em\u003e\u003cem\u003eTD = \u003c/em\u003e\u003cem\u003e\u003cstrong\u003efour-\u003c/strong\u003e\u003c/em\u003e\u003cem\u003efold therapeutic dose DPI: Days post injection of ivermectin\u003c/em\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7605011/v1/85bc1d1eb618d968467d2b15.png"},{"id":92184131,"identity":"93147cf6-fc38-497f-8c40-5a1ff0de409b","added_by":"auto","created_at":"2025-09-25 14:00:31","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":37464,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAverage emergence rate of pupae produced by female of \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eG. p. gambiensis \u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003efemale\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTD, Therapeutic dose (0.2 mg/kg); \u003c/em\u003e\u003cem\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/em\u003e\u003cem\u003eTD, two\u003c/em\u003e\u003cem\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/em\u003e\u003cem\u003efold therapeutic dose;\u003c/em\u003e\u003cem\u003e\u003cstrong\u003e 4\u003c/strong\u003e\u003c/em\u003e\u003cem\u003eTD, four-fold therapeutic dose DPI: Days post injection of ivermectin\u003c/em\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7605011/v1/7310985272374474a651b311.png"},{"id":102234437,"identity":"bdd2c9ac-9c31-4044-b3b6-65cea6e9b4ff","added_by":"auto","created_at":"2026-02-09 16:11:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1039027,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7605011/v1/1a046dff-3005-4450-9c65-c5beaad08ab5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eEffect of different doses of ivermectin on the survival and fecundity of \u003cem\u003eGlossina palpalis gambiensis\u003c/em\u003e Vanderplank 1949 fed on treated cattle\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eLivestock production has an important place in the economies of developing countries, which roughly represents 10 to 20% of Gross Domestic Product [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Cattle are particularly valuable for their multifaced contributions including meat and milk production, draft power, and manure for use as fertilizer. Parasitic infections represent a major constraint in livestock production, contributing to reduced productivity, increased mortality, and elevated management costs [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. African Animal Trypanosomosis (AAT), or Nagana are major parasitosis that seriously impede the development of the livestock production [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. They are due to blood parasites, the \u003cem\u003eTrypanosoma sp\u003c/em\u003e. transmitted to animals mainly by tsetse flies (Diptera: Glossinidae). Tsetse flies are present exclusively in Africa and also transmit trypanosomes responsible for Human African Trypanosomiasis (HAT) or sleeping sickness. HAT and AAT generate significant health problem and social and economic losses for Africa [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. To control sleeping sickness, the health services primarily rely on medical screening and treatment of confirmed cases, alongside tsetse fly control. Chemotherapy remains the main approach to control Nagana, despite the development of chemo-resistance [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, vector control is still a preferential choice method, in addition to chemotherapy, particularly in the absence of a vaccine to prevent these diseases [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Vector control interventions have significantly reduced tsetse flies populations, and, consequently, the transmission of both HAT and AAT [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The principal methods of tsetse control include the use of toxic attractants (such as insecticide-impregnated traps and targets), the topical application of insecticides to cattle serving as live bait, the ground and aerial spraying of insecticide, and the implementation of the Sterile Insect Technique (SIT) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDespite considerable efforts, tsetse flies and the transmission of trypanosomosis continue to pose significant adverse public health and economic challenges in the affected regions. It is therefore necessary to pursue researches into complementary or alternative tools for the control of both AAT and HAT, particularly in the context of diseases elimination goal. One such promising tool is ivermectin, a broad-spectrum endectocide widely used in both human and veterinary medicine, which has demonstrated systemic insecticidal effects against arthropods including various tsetse species.\u003c/p\u003e\u003cp\u003eIvermectin belongs to the avermectin family of macrocyclic lactones discovered in 1973 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. These compounds, termed endectocides, are effective against both internal parasites (endo-parasitic) and external parasites (ecto-parasitic) organism [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Ivermectin is active against a broad range of parasites including gastrointestinal nematodes (roundworms), extra-intestinal nematodes such as \u003cem\u003eDictyocaulis viviparus\u003c/em\u003e and \u003cem\u003eParafilaria bovicola\u003c/em\u003e, microfilariae of \u003cem\u003eOnchocerca spp\u003c/em\u003e, and various arthropods (insects and mites) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The standard therapeutic dose for field treatment in cattle is 0.2 mg/kg body weight [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Once administrated, ivermectin circulates systemically and can adversely affect blood-feeding insects including tsetse flies, by disrupting key history traits.\u003c/p\u003e\u003cp\u003eThe systemic insecticidal effect of ivermectin on adult flies of \u003cem\u003eGlossina palpalis palpalis\u003c/em\u003e was first reported by Distelmans and al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], who observed mortality in tsetse flies fed on goats treated with a high dose of 10 mg/kg (50 fold the therapeutic dose), and on guinea pigs treated with 2 mg/kg (10 fold the therapeutic dose) was reported [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Insects typically died 4 to 8 days after repeated feeding. These authors, noted the onset of ivermectin\u0026rsquo;effects on \u003cem\u003eG. p. palpalis\u003c/em\u003e begins at doses between 1 and 2 mg/kg of body weight. Subsequent studies confirmed similar systemic effects on \u003cem\u003eG. morsitans\u003c/em\u003e [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], \u003cem\u003eG. tachinoides\u003c/em\u003e [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and notably on \u003cem\u003eG. p. gambiensis\u003c/em\u003e, a vector of both HAT and AAT in West Africa [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the later study, ivermectin administrated at the therapeutic dose of of 0.2 mg/kg exhibited only a short-term insecticidal effect on \u003cem\u003eG. p. gambiensis\u003c/em\u003e, lasting less than one week post-treatment [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. These findings highlighted the need to investigate adjusted dosing regimens capable of sustaining systemic insecticidal activity over longer periods. The present study therefore aimed at comparing effects of therapeutic and increased doses of ivermectin on the life history traits of \u003cem\u003eG. p. gambiensis\u003c/em\u003e, to identify an optimized dose that can maintain prolonged insecticidal efficacy against this specie.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eTsetse flies specie and rearing conditions\u003c/h2\u003e\u003cp\u003eWe used the reference colony of \u003cem\u003eG. p. gambiensis\u003c/em\u003e from the \u003cem\u003eCentre International de Recherche-D\u0026eacute;veloppement sur l\u0026rsquo;Elevage en zone Subhumide (CIRDES)\u003c/em\u003e.\u003c/p\u003e\u003cp\u003eThe CIRDES colony was established in 1972 using specimens collected in the Guinguette, a locality near from Bobo-Dioulasso, Burkina Faso [\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. It has been maintained on cattle blood given through silicone membranes and in the Center dedicated insectary (25\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u0026deg; C and 70\u0026thinsp;\u0026plusmn;\u0026thinsp;5% relative humidity).\u003c/p\u003e\u003cp\u003eFreshly emerged flies were separated by sex and put into Roubaud cages (13.5 \u0026times; 8 \u0026times; 4.5 cm), 20 females or 20 males per cage, and kept into holding room (25\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u0026deg; C and 70\u0026thinsp;\u0026plusmn;\u0026thinsp;5% relative humidity) during 2 days, the necessary time for flies to become sexually mature [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Three days old males and females of \u003cem\u003eG. p. gambiensis\u003c/em\u003e were then fed on treated or control animals. Females were subsequently mated with 6 days-old virgin males at the ratio of 1:3 [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] to examine treatment\u0026rsquo; effects on fecundity and fertility of the flies.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eFeeding hosts, acre\u003c/h3\u003e\n\u003cp\u003eEight calves (cross-breed between the local \u0026ldquo;Baoul\u0026eacute;\u0026rdquo; and the Fulani Zebu strains) were purchased from surrounding farms near Bobo-Dioulasso to be used as the tsetse flies feeding host. The calves were in average 3 years old and weighted 120.75 (\u0026plusmn;\u0026thinsp;16.44) kg. Before starting the experiment, animals were washed using soapy water to remove any residues of topical dewormers potentially administered of origin. They also dewormed with Albendazol at the recommended dosage and treated with a curative trypanocide (Berenil\u0026reg;) to address potential infection of African animal trypanosomosis which is endemic in this region. Their diet consisted of rice straw, cotton cake and water given \u003cem\u003ead libitum.\u003c/em\u003e They were maintained in the CIRDES stable protected by mesh against another insects biting. The animal were monitored daily by a trained veterinarian technician to ensure their well-being, and an antibiotic treatment was provided when needed.\u003c/p\u003e\n\u003ch3\u003eIvermectin drug and cattle treatment\u003c/h3\u003e\n\u003cp\u003eThe injectable veterinary ivermectin formulation IVOMEC-D\u0026reg; (Boehringer Ingelheim, Lyon, France) was used for animal\u0026rsquo;s treatments. This formulation contains 1% ivermectin and 10% Clorsulon as active ingredients. Ivermectin targets mainly gastrointestinal nematodes, strongyles, lungworms, and external parasites in cattle and sheep while Clorsulon targets liver flukes. Three different doses of the drug were injected subcutaneously at the neck of the different animals (TD\u0026thinsp;=\u0026thinsp;therapeutic dose of 0.2 mg/kg, 2TD\u0026thinsp;=\u0026thinsp;0.4 mg/kg and 4TD\u0026thinsp;=\u0026thinsp;0.8 mg/kg) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Control calves did not receive ivermectin injection but were kept under the same conditions as the treated ones.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDescription of the experimental design\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eValue\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of cattle by dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIvermectin doses tested (mg/kg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0, 0.2, 0.4 and 0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDays Post injection of ivermectin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1, 8, 15, 22, 29 and 36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of blood meal taken\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameters evaluated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eDaily mortality, pupal production, time to first pupae, and emergence rate\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003eSurvival follow up\u003c/h3\u003e\n\u003cp\u003eTo evaluate the systemic insecticidal effects of ivermectin on tsetse survival, two cages containing each, males or females flies were placed on the flanks of each animal during 15 minutes. These cages were secured using rubber band and covered with black cloth to create darkness, thereby facilitating effective blood feeding. Following feeding on cattle, engorged flies were monitored daily over 30 days period to assess mortality. These step were repeated at different times post-injection with the fresh batches of tsetse flies (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eSince tsetse flies are obligate hematophagous insects, subsequent blood meals were provided every two days using a silicone membrane feeding system, as previously described [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. For membranes feeding, bovine or pig blood collected at the Bobo-Dioulasso slaughterhouse, defibrinated and sterilized prior to use.\u003c/p\u003e\n\u003ch3\u003eSystemic effects of ivermectin on the fecundity of tsetse females\u003c/h3\u003e\n\u003cp\u003eMating cages were placed in individual larviposition cups and then, the pupae were collected daily and sorted into normal and aborted L3. Normal pupae were transferred to an incubation room for adult emergence. Pupal production was recorded daily for each treatment group and each cage.\u003c/p\u003e\u003cp\u003eTo evaluation the systemic effects of ivermectin on tsetse fecundity, several reproductive parameters were measured for each treatment: (i) the average number of pupae produced per initially blood fed females over 30-days period following the first blood meal; (ii) the average time of the first larva production (i.e. the interval time between female emergence and the production of the first pupae), (iii) and the average adult emergence rate from the pupae.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u003cb\u003e2.7. Data analysis\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eStatistical analysis and data visualization were performed using R software [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Fly survival was analyzed using Kaplan and Meier survival analysis, and the survival curve were compared using the Cox proportional hazard model (Coxph) [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In this model, treatment, time post injection, and fly sex were included as explanatory variables, with survival rate as the response variable. Multiple comparisons between survival outcomes across treatment groups were conducted using the \"glht\" function from Multcomp package [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Cumulative mortalities over follow up period were also calculated and analysed to facilitate survival comparison between treatments.\u003c/p\u003e\u003cp\u003eDifference in hhe mean number of pupae produced and the adult emergence rate between treatments were analysed using a general linear model with quasi-Poisson distribution [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The timing fof first pupae production were compared between treatments groups using Kruskall Wallis test [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003eEffects of ivermectin on the survival of tsetse\u003c/h2\u003e\n\u003cp\u003eOverall, the effects of the different doses of ivermectin on the survival of \u003cem\u003eG. palpalis gambiensis\u003c/em\u003e varied according to the treatment, the time post injection at which tsetse were fed, and the sex of the flies (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eOverall, the data showed a significant effect of ivermectin treatment (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{X}_{3}^{2}\\)\u003c/span\u003e\u003c/span\u003e = 353.63, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), the time post injection (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{X}_{2}^{2}\\)\u003c/span\u003e\u003c/span\u003e = 450.90, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and the tsetse fly sex (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{X}_{2}^{2}\\)\u003c/span\u003e\u003c/span\u003e = 278.21, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) on the survival rate.\u003c/p\u003e\n\u003cp\u003eAmong the three doses of ivermectin tested, the TD and the 2TD treatment induced a significant decrease of the survival of \u003cem\u003eG. palpalis gambiensis\u003c/em\u003e only at 1 day post injection of the drug to cattle. For TD, the tsetse mortality rate at this time point and was 59.82% (48.57% for females and 70.18% for males), compared to 29.90% for the control (11.88% for females and 35.58% for males) (Z\u0026thinsp;=\u0026thinsp;7.36; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The effect of the TD was significant on both the mortality of female (Z\u0026thinsp;=\u0026thinsp;5.47; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and males (Z\u0026thinsp;=\u0026thinsp;5.12; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The ivermectin dose of 0.4 mg /kg (2TD) also decreased significantly the survival at 1 DPI (Z = -14.68; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with mortality\u0026rsquo; rates of 90.43% for treated flies (87.29% for the females and 93.75% for the males) against 23.90% for the control flies (11.88% for the females and 35.58% for the males).\u003c/p\u003e\n\u003cp\u003eThe four-fold therapeutic dose (4TD) of ivermectin significantly decreased tsetse survival at the 1 DPI (Z = -16.96; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), 8 DPI (Z = -11.99; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 15 DPI (Z = -4.37; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mortality rate of tsetse due to the 4TD of ivermectin at different DPI were 94.55%, 86.41% and 55.09%, respectively at 1, 8 and 15 DPI. At 22 DPI to 29 DPI and 36 DPI, no significant survival difference in survival was observed between tsetse flies fed on treated and control cattle (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eSystemic effects of ivermectin on fecundity\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003eAverage number of pupae produced by female\u003c/h2\u003e\n\u003cp\u003eThe fecundity of female of \u003cem\u003eG. p. gambiensis\u003c/em\u003e (i.e. the average number of pupae produced per female) varied according to the treatments and the DPI (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eFemales fed on cattle treated with the TD at 1 DPI produced 0.43 pupae per female compared to 0.99 pupae per female in the control group, representing a significant reduction of 56.56% (Estimate = -0.83, Z value =-5.77, \u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e). Females fed on cattle treated with 2TD of ivermectin at 1 DPI showed an even greater reduction in fecundity, producing 0.09 pupae/female against 0.99 for control, a 90.09% decrease (Estimate = -2.41, Z value =-5.75, \u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e). At 8 DPI, the 4TD significantly reduced significantly the average number of pupae produced by 92.47%, with 0.02 pupae per female in the treated group versus 0.78 in the controls (Estimate = -3.92, Z value =-3.38, \u003cem\u003eP\u0026thinsp;=\u0026thinsp;0.003\u003c/em\u003e). For the other DPI and ivermectin doses where pupae were produced, there was no significant effect of the treatment on the average number of pupae produced.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003ch2\u003eFirst larval period\u003c/h2\u003e\n\u003cp\u003eThe first larval period varied from 14.5 days to 30 days according to the treatment (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eAverage date of first larval period\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eDPI\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eAverage days of first larval period according to the treatment (SE)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eControl\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTD\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e2 TD\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e4 TD\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17,00 (1.05) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20,71 (0.36) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26,67 (1.67) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30,00 (0.00) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19,13 (0.55) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20,42 (0.95) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19,75 (0.63) \u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29,40 (0.60) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17,50 (0.50) \u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17,75 (0.25) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19,75 (1.55) \u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19,75 (0.86) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17,25 (0.41) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16,88 (0.23) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17,38 (0.26) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18,25 (0.37) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17,00 (0.31) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17,25 (0.25) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17,50 (0.71) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17,63 (0.42) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18,00 (0.00) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18,00 (0.00) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18,13 (0.13) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17,13 (1.03) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cem\u003eDPI : Days Post Injection of ivermectin; TD : Therapeutic Dose of ivermectin; 2TD: 2 fold therapeutic dose; 4TD: 4 fold therapeutic dose of ivermectin. The data in the same row with the different letter are significantly different at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05; SE: Standard error.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNo significant effect of the therapeutic dose of ivermectin was observed on the average time to first larvisposition. However, the 2TD of ivermectin induced a significantly delay of 9 days in the average day of first larval period at 1 DPI (\u003cem\u003eP\u0026thinsp;=\u0026thinsp;0.01\u003c/em\u003e). Females of \u003cem\u003eG. p. gambiensis\u003c/em\u003e fed on cattle treated with the 4TD of ivermectin, exhibited a delay of 13 days at 13 days at 1 DPI (\u003cem\u003eP\u0026thinsp;=\u0026thinsp;0.0001\u003c/em\u003e) and 10 days at 8 DPI (\u003cem\u003eP\u0026thinsp;=\u0026thinsp;0.0017\u003c/em\u003e) in the timing of first larviposition.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n\u003ch2\u003eAdult emergence\u003c/h2\u003e\n\u003cp\u003eThe emergence rates of pupae produced by females of \u003cem\u003eG. palpalis gambiensis\u003c/em\u003e are presented in the Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. No significant difference was found in the hatching rates between control and treated flies for all doses and all DPI (Treatment effect: Deviance\u0026thinsp;=\u0026thinsp;0.80, \u003cem\u003eP\u0026thinsp;=\u0026thinsp;0.98\u003c/em\u003e).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated that the ivermectin treatment of cattle significantly reduces the survival of \u003cem\u003eG. P. gambiensis\u003c/em\u003e that feed on them. The insecticidal effect of ivermectin at the therapeutic dose persisted up to 1 day post injection, while the four-fold therapeutic dose (0.8 mg/kg) extended this effect to maximum of 15 days. Doubling the therapeutic dose did not further prolong the insecticidal effect on \u003cem\u003eG. p. gambiensis\u003c/em\u003e. These finding differ from our previous study, in which the therapeutic dose exhibited an insecticidal effect lasting up to 8 days post-treatment in same specie [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAs ivermectin is progressively eliminated from the blood of treated cattle, variability in tsetse fly survival was observed, notably between sexes, with females generally exhibiting longer lifespans than males, which may reflect sex-related differences in susceptibility to ivermectin. A sex-based difference in longevity has also been reported in previous studies on the same species under varying temperature conditions [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] and different feeding regimes [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Interestingly, the pronounced systemic insecticidal effect on male suggests that ivermectin could serve as a valuable complementary tool in tsetse eradication efforts, particularly when integrated with the Sterile Insect Technique (SIT,[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]). The increased mortality of male flies following ivermectin treatment may reduce the population of wild males, thereby decreasing competition with released sterile males and enhancing of effectiveness of SIT in the field. However, careful consideration must be given to dose selection to minimize unintended impacts on female tsetse flies, especially their reproductive capacity. Sub-lethal exposure that affects fecundity without achieving full mortality may pose a risk for the development of resistance over time [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe mean elimination half-life of ivermectin following subcutaneous injection of the conventional formulation at the therapeutic dose in cattle is approximately 8 days [\u003cspan additionalcitationids=\"CR37\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. The present study shows that a yet low, safe dose (4TD), can reduce tsetse flies survival for up to 15 days post-treatment.\u003c/p\u003e\u003cp\u003eThis finding contrasts with earlier observations by Distelmans et. al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], who reported a shorter duration of effect despite using a higher dose of 2mg/kg However, in their study, the blood meal hosts were guinea pigs and goats rather than cattle, which likely influenced the pharmacokinetics of ivermectin and thus the extent of its systemic insecticidal action [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Similarly, Van Den Abbeele et al. found no significant impact on the survival of \u003cem\u003eG. palpalis palpalis\u003c/em\u003e fed on guinea-pigs with 0,5 mg/kg [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e] and Van Den Bossche and Geerts reported no effect on \u003cem\u003eG. tachinoides\u003c/em\u003e fed on pigs treated with 1 mg/kg [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. These discrepancies our findings may be due not only to the interspecies differences in ivermectin pharmacokinetics between the different host animals (guinea pig, goat and pig vs. cattle) but also to differences in tsetse species, which may vary in their susceptibility to ivermectin, like shown for Anopheles [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAs with survival, discrepancies in the effects of ivermectin on tsetse fly fecundity across studies can likely be attributed to differences in tsetse species, the animal host used for blood feeding, ivermectin pharmacokinetics, and experimental design. In the present study, the therapeutic dose of the ivermectin formulation used resulted in a 56.56% reduction in fecundity at 1 DPI. In contrast, Van Den Abbeele et al. [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e] found no effect of the therapeutic dose of ivermectin on fecundity in \u003cem\u003eG. p. palpalis\u003c/em\u003e fed on rabbits. In our study, increasing the ivermectin dose to 0.4 mg/kg did not extend the duration of its effect on fecundity in \u003cem\u003eG. p. gambiensis\u003c/em\u003e.\u003c/p\u003e\u003cp\u003eVan Den Abbeele et al. [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e] found also that ivermectin at a dose of 0.5 mg/kg decreased fecundity (measured by both the number of pupae and pupal mass) of \u003cem\u003eG. palpalis palpalis\u003c/em\u003e fed one day post treatment. In addition to reducing the number of pupae per female, our study also showed a delay in the onset of the first larval deposition occurring at 29 days post feeding in treated females versus 19 days in the control group at 8 DPI and with 4TD.\u003c/p\u003e\u003cp\u003eNo significant effect on adult emergence rates was observed in the present study, consistent with previous findings [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, a previous study on \u003cem\u003eG. morsitans\u003c/em\u003e reported that a single blood meal taken from cattle 7 days after treatment with a therapeutic dose of ivermectin ( 0.2 mg/kg) induced a 44% decrease in fertility during the second ovarian cycle [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Thereafter, fertility gradually evolved towards normal. According to Van Den Abbeele et al. [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e], the effect of ivermectin on tsetse fecundity is likely due to a combination of delayed ovulation, increased gestation duration, and disruption of pupation.\u003c/p\u003e\u003cp\u003eOverall, the results of present study on \u003cem\u003eG. p. gambiensis\u003c/em\u003e are consistent with findings from other tsetse species, supporting the general conclusion that ivermectin, even if its effect are transient using commercial formulation, can negatively impact tsetse longevity and reproduction. The biological impacts could play a meaningful role in the control of trypanosomosis, given the relatively slow reproductive cycle of tsetse and the duration of trypanosome development within the fly. Specifically, \u003cem\u003eTrypanosoma vivax\u003c/em\u003e typically requires around 10 days to complete development in the fly, \u003cem\u003eT. congolense\u003c/em\u003e requires 12\u0026ndash;14 days and \u003cem\u003eT. brucei\u003c/em\u003e 20\u0026ndash;30 days [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Therefore, any reduction in tsetse survival caused by ivermectin during the early days post-treatment would interrupt the transmission cycle of all three major trypanosome species, with the strongest impact expected for \u003cem\u003eT. brucei\u003c/em\u003e, both in terms of intensity and duration. While the effects of ivermectin on tsetse are largely indirect (by reducing vector survival and, consequently, parasite development), it would be worth investigating whether ivermectin might also exert direct effects on trypanosome development within the vector, as it does for other pathogens [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough promising in terms of disease management, mass treatment of livestock with ivermectin have potential ecological consequences that should not be overlooked. Adverse effects on non-target dung fauna and other wildlife have been documented [\u003cspan additionalcitationids=\"CR48\" citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e], highlighting the need for responsible and targeted use of endectocides [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Additionally, although the low reproductive rate of tsetse limits the rapid development of insecticide resistance, the relatively weak systemic insecticidal effect of ivermectin on this species warrants further investigation. Proactive resistance mitigation strategies should also be considered to preserve the efficacy of ivermectin within integrated vector control programs. The low reproductive rate of tsetse reduces the development of insecticide resistance, but the weakness of the systemic insecticidal effects of ivermectin on this specie deserves special attention. The demonstration of glutamate-dependent chloride channels not sensitive to ivermectin could explain this weak effect of the molecule on tsetse flies [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e] compared to mosquitoes [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe results of this study demonstrate that ivermectin administered to cattle affects the longevity and fertility of \u003cem\u003eGlossina palpalis gambiensis\u003c/em\u003e. These findings confirm the systemic insecticidal properties of ivermectin against hematophagous insects, as previously reported in the literature, and reinforce earlier observations made on this tsetse species. Notably, this study highlights the effects of a therapeutic dose of ivermectin on the species \u003cem\u003eG. p. gambiensis\u003c/em\u003e feeding directly on treated cattle under \u003cem\u003ein vivo\u003c/em\u003e conditions. The insecticidal impact persisted for up to 15 days post- treatment when cattle received a dose four times the standard therapeutic level.\u003c/p\u003e\u003cp\u003eThese findings lead to two important considerations. First, the widespread use of ivermectin in the field for both human and animal health could have a more substantial impact on tsetse populations and trypanosomiasis transmission than previously recognized. This potential has likely been underestimated and warrants further investigations through studies linking ivermectin use to key epidemiological indicators of trypanosomiasis. The second consideration is that avermectins in general, and ivermectin in particular, may represent valuable complementary tools in the integrated control of trypanosomoses, especially in areas where the vectors feed primarily or occasionally on domestic animals such as cattle. In such settings, periodic and synchronized ivermectin treatments of men and/or livestock could significantly reduce vector longevity and fecundity, and consequently, disease transmission. Additional effects on vector fertility, as well as possible direct impacts on parasite development within the vector, should also be further explored.\u003c/p\u003e\u003cp\u003eMoreover, given that trypanosomiasis and malaria are often co-endemic in sub-Saharan Africa, the use of ivermectin offers a unique opportunity to develop integrated vector control strategies targeting both diseases. Ivermectin has been shown to reduce the survival of \u003cem\u003eAnopheles\u003c/em\u003e mosquitoes, the vectors of malaria, and is being evaluated in large-scale clinical trials. Notably, Phase 3 trials investigating the impact of ivermectin on malaria epidemiology have yielded contrasting results, likely due to differences in trial design, vector species, treatment regimens, and local epidemiological contexts. Nevertheless, this area of research remains highly dynamic, and continued investigation may help define the optimal conditions under which ivermectin can serve as a dual-action intervention against both malaria and trypanosomiasis.\u003c/p\u003e\u003cp\u003eHowever, there are important limitations to consider before ivermectin can be widely promoted for vector control purposes. These include potential adverse effects on non-target organisms, the presence of drug residues in milk when dairy cattle are treated, and the risk of resistance development due to extensive use. These concerns underscore the need for a cautious and evidence-based approach when considering the integration of ivermectin into broader vector control strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cp\u003e The study has received an approval of the ethical committee of the \u0026ldquo;Centre International de Recherche D\u0026eacute;veloppement sur l\u0026rsquo;Elevage en zones Sub-humides\u0026rdquo; (CIRDES).\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eCompeting interests\u003c/h2\u003e\u003cp\u003eAuthors declare no competing interests.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis study was funded mainly by, the \u0026ldquo;Laboratoire Mixte International sur les maladies \u0026agrave; vecteurs (LAMIVECT)\u0026rdquo;. It received also the financial resource of the International Foundation of Sciences (IFS).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors participated to the project\u0026rsquo;s elaboration and the design of the study. They all amended the present paper. M.K., S.H.P., A.M.G.B. and S.P. conceived the study. M.K., S.H.P., and A.I.T. elaborated the protocols. S.H.P., S.P., and A.I.T. did the survival and reproduction experiments . S.H.P. and M.K. performed the statistical analysis and drafted the paper. All authors read and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe are grateful for technicians from CIRDES whom contribute in this study. We are also memory of are senior colleagues, Issa Sidib\u0026eacute; and Jean-Baptiste Rayaiss\u0026eacute;, passed away, rested in peace.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data generated in the study are presented in the paper.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFaye B, Alary V. Les enjeux des productions animales dans les pays du Sud. INRA Prod Anim. 2001;14:3\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBelem AMG, Ou\u0026eacute;draogo OP, Bessin R. Gastro-intestinal nematodes and cestodes of cattle in Burkina Faso. Biotechnol Agron Soc Environ. 2001;5:17\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLe Gall F, Leboucq N. 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Characterization of the target of ivermectin, the glutamate-gated chloride channel, from \u003cem\u003eAnopheles gambiae\u003c/em\u003e. J Exp Biol. 2015;218:1478\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePooda HS, Rayaiss\u0026eacute; J-B, Fran\u0026ccedil;ois D, Hien DS, Lef\u0026egrave;vre T, Yerbanga SR, et al. Administration of ivermectin to peridomestic cattle: a promising approach to target the residual transmission of human malaria. Malar J. 2015;14.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"parasites-and-vectors","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"parv","sideBox":"Learn more about [Parasites \u0026 Vectors](http://parasitesandvectors.biomedcentral.com/)","snPcode":"13071","submissionUrl":"https://submission.nature.com/new-submission/13071/3","title":"Parasites \u0026 Vectors","twitterHandle":"@bugbittentweets","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Ivermectin, Cattle, Glossina palpalis gambiensis, vector control, Integrated control","lastPublishedDoi":"10.21203/rs.3.rs-7605011/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7605011/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eTsetse flies, (Glossina spp), are the main vectors of trypanosome parasites responsible for the the Human African Trypanosomiasis (HAT) and the African Animal Trypanosomosis (AAT), both of which remain significant obstacles to the socio-economic development of affected regions in sub-Saharan Africa. Several control strategies have been developed, among which, vector control plays a central role. To achieve the elimination of HAT and AAT, additional and integrated complementary control strategies, such as the ivermectin treatments of animals, need to be explored.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eTo assess the systemic insecticidal efficacy of ivermectin on the survival and fecundity of \u003cem\u003eGlossina palpalis gambiensis\u003c/em\u003e, batches of tsetse flies were fed on 6 calves that were treated with three different doses of the drug: therapeutic dose (TD) of 0.2 mg/kg, two-fold TD, and four-fold TD. Two untreated calves were used as the control group.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe TD and 2TD induced significant mortality of the tsetse flies up to 1 days post injection (DPI), with mortality rates varying from 59.82% to 90.43%. The 4TD caused a significant decrease of 55.09% of the survival of the tsetse flies up to 15 DPI (Z = -4.37; \u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e). The cattle treatments with ivermectin also resulted in a decrease of the number of pupae produced by tsetse flies, of 43.57% with the TD, and 92.47% with the 4TD. A delay from 9 to 13 days has also been observed in the deposit of the first larva, with the doses 2TD and 4TD at 1DPI and to 10 days with the dose 4TD at 8DPI.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe ivermectin treatments to animals against the common parasitosis have an additional effect against insect vectors like tsetse flies. Thus, mass treatments of farmed animals with ivermectin, may be considered in order to improve both human and animal health.\u003c/p\u003e","manuscriptTitle":"Effect of different doses of ivermectin on the survival and fecundity of Glossina palpalis gambiensis Vanderplank 1949 fed on treated cattle","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-25 13:52:27","doi":"10.21203/rs.3.rs-7605011/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-02T20:53:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-01T14:07:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-22T20:51:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"118418433942199562885589093048162085151","date":"2025-09-22T10:56:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"19917904332725023168961434304149056496","date":"2025-09-19T09:56:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"251810069817384162308327138297398629953","date":"2025-09-18T14:05:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-17T00:08:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-16T16:14:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-16T09:03:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"Parasites \u0026 Vectors","date":"2025-09-13T06:09:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"parasites-and-vectors","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"parv","sideBox":"Learn more about [Parasites \u0026 Vectors](http://parasitesandvectors.biomedcentral.com/)","snPcode":"13071","submissionUrl":"https://submission.nature.com/new-submission/13071/3","title":"Parasites \u0026 Vectors","twitterHandle":"@bugbittentweets","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"37d80279-5127-4612-9c6d-c01a44f7b192","owner":[],"postedDate":"September 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-09T16:07:22+00:00","versionOfRecord":{"articleIdentity":"rs-7605011","link":"https://doi.org/10.1186/s13071-026-07277-5","journal":{"identity":"parasites-and-vectors","isVorOnly":false,"title":"Parasites \u0026 Vectors"},"publishedOn":"2026-02-06 15:57:47","publishedOnDateReadable":"February 6th, 2026"},"versionCreatedAt":"2025-09-25 13:52:27","video":"","vorDoi":"10.1186/s13071-026-07277-5","vorDoiUrl":"https://doi.org/10.1186/s13071-026-07277-5","workflowStages":[]},"version":"v1","identity":"rs-7605011","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7605011","identity":"rs-7605011","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}