http://orcid.org/0000-0002-3375-2212
Figures
Abstract
Background
Dogs are important reservoirs of rabies, a zoonotic viral encephalitis that kills thousands of people in Asia and Africa annually. Mass dog vaccination is recommended for the prevention of rabies in both humans and dogs. Mass vaccinations should be conducted annually but more frequent campaigns may be required in areas with high dog turnover rates. Consequently, a good understanding of dog demography is essential for the control of the disease. The aim of this study was to explore the effect of dog demography on rabies vaccination coverage following a mass vaccination campaign with at least 70% vaccination coverage.
Methodology/Principal findings
A dog population model was constructed to explore the effect of dog demography on rabies vaccination coverage decline. Important model parameters were identified through a comprehensive literature search on dog demography in Africa. A system dynamics approach was adopted to build a dog population model to simulate the effects of demographic processes on rabies vaccination coverage. Vensim PLE Plus software was used to construct the model. Multivariate sensitivity simulations using data from 22 studies and 12 African countries were performed to investigate the effect of dog turnover rates on vaccination coverage decline. In addition, an adjusted vaccination coverage to estimate the proportion of vaccinated dogs with adequate immunity at 12 months post-vaccination was calculated. The results demonstrated that the vaccination coverage and adjusted vaccination coverage remained over 30% and 20% respectively at 12 months if annual mass vaccinations achieved at least 70% coverage.
Citation: Chidumayo NN (2018) System dynamics modelling approach to explore the effect of dog demography on rabies vaccination coverage in Africa. PLoS ONE 13(10): e0205884. https://doi.org/10.1371/journal.pone.0205884
Editor: Charles E. Rupprecht, Wistar Institute, UNITED STATES
Received: February 13, 2018; Accepted: October 3, 2018; Published: October 25, 2018
Copyright: © 2018 Nozyechi Ngulube Chidumayo. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: The author received no specific funding for this work.
Competing interests: The author has declared that no competing interests exist.
Introduction
Rabies is a viral encephalitis transmitted through the saliva of an infected animal [1]. The reservoirs of rabies include domestic dogs, bats and wild carnivores [2–4]. Rabies accounts for up to 55, 000 human deaths annually and the most affected areas are Asia and Africa [5]. The World Health Organisation (WHO) recommends a vaccination coverage of at least 70% to interrupt the transmission cycle [6]. However, the level of vaccination coverage is thought to vary depending on the demographic characteristics of the population [6,7]. Hampson et al. reported that vaccination coverage levels of 20‒45% could interrupt rabies transmission in free-roaming dogs in rural Tanzania [7]. Rabies vaccination provides adequate immunity if dogs develop at least 0.5 IU/ml neutralising antibody titres [6]. Immunity should be maintained for one to three years depending on the vaccine manufacturer and local regulations [8,9]. Antibody titres of vaccinated dogs in Africa vary with some animals failing to seroconvert 30 days after vaccination [10,11]. In addition, some animals develop antibodies 30‒35 days post-vaccination that decline 60‒180 days after vaccination [12,11]. Vaccine efficacy may be compromised as a result of low potency vaccines [13] and immunosuppression due to disease [14,11]
Dog ownership is common in Africa, with 7.7%‒94% dog-owning households [15–23] and an estimated human: dog ratio of 3.7:1‒121:1 [24,22,25,23,20,21,26–28,19,29,30,17,16]. There is generally a male bias [21,29,19,15,31,26,17,20,32,24,30,33,16] that has been attributed to owners preferring male dogs which are considered better at guarding and hunting [25,18]. Dog turnover rates are high and the life expectancy has been reported at 1.7 years [17], 2.9 years [29] and 1.1 years [20]. Most of the dogs in Africa are owned and are therefore available for vaccination [34,35,11,15]. The proportion of ownerless free-roaming dogs has been estimated at <1%‒10.6% [32,17,15,36,37]. The low proportion of ownerless dogs has been attributed to limited food sources to support large populations [17,15]
Demography is the study of populations and is concerned with the size, the age and sex composition of the population, and how the population changes over time [38]. Demographic processes, namely births, deaths and migration, affect how populations change over time [38]. Dog demographic processes have an effect on rabies control because they affect vaccination coverage decline. Removal of vaccinated dogs from the population through deaths and emigration can cause a rapid decline in the vaccination coverage [15,18]. This decline may be compounded by the addition of susceptible animals through births and immigration [15,18]. The rate at which the vaccination coverage declines influences how often mass vaccination campaigns should be conducted in an area [15,39]. The WHO recommends annual mass vaccinations with at least 70% vaccination coverage [6]. However, more frequent campaigns may be required for dog populations with high turnover rates [6]. The aim of this study was to assess if annual mass vaccination campaigns with at least 70% vaccination coverage are sufficient to maintain a herd immunity of 20‒45% between campaigns, in dog populations with high turnover rates. Simulation modelling was used to explore the effect of dog demographic processes and vaccine immune response on rabies vaccination coverage decline in dogs in Africa. The influence of demographic processes was assessed using a system dynamics approach. System dynamics is a modelling method that has been used to understand complex environmental [40] and public health [41–44] issues. System dynamics models consist of stock (level) and flow (rate) variables which represent ordinary differential equations [40]. Stocks represent the major accumulations in the system [45]. In a population model, stocks can include the total population or specific subpopulations such as males, females, adults and young. Flows control the rate of change in the stock variables [45]. Inflows and outflows add and deduct from the stocks respectively. In population models, flows can include births, deaths and migrations. Fig 1 shows a population stock and flow diagram with stocks and flows represented by rectangles and circles respectively. The model variables are connected by arrows and mathematical equations are formulated based on the relationships between the variables [45]. For example in Fig 1 the model equations are:
- Births = Adults × Birth rate
- Young to adult = Young ÷ Maturation time
- Young deaths = Young × Young death rate
- Adult deaths = Adults × Adult death rate
- Total population = Young + Adults
Methods
Identification of parameters and model development
Literature on dog demography in Africa was reviewed to identify significant model parameters and parameter values. The following data were extracted where possible: the proportion of male dogs; the proportion of female dogs; the proportion of young dogs; the proportion of adult dogs; age-specific mortality rates; mean litter size; the proportion of spayed females and the annual female reproduction probability. For simplicity, dogs aged ≤ 12 months were characterised as young while dogs aged > 12 months were characterised as adults. Age data was further grouped into subpopulations namely: puppies (0–3 months); juveniles (>3 months -12 months); adults 1 (>12 ≤ 24 months); adults 2 (> 24 ≤ 36 months); adults 3 (> 36 ≤ 48 months); adults 4 (> 48 ≤ 60 months); and adult 5 (> 60 months). Table 1 shows the identified model parameters and parameter values.
A stock and flow diagram was constructed based on the parameters identified in Table 1. Vensim PLE Plus (Ventana Systems, 2015) was used to construct the system dynamics model. The model divides the population into susceptible (unvaccinated) and vaccinated dogs. The puppies, juveniles and adults (adults 1‒5) add up to the total population (S1 Dataset: Equation 64) while the puppies and juveniles add up to young dogs. Each compartment has a mortality rate and deaths from each compartment affect the flow of dogs out of the population. The equations for the age-specific deaths are shown in S1 Dataset (Equation 41, 43, 45, 47, 49, 50, 54, 68, 70, 72, 74, 76, 77, 81). Adults are considered to be fertile and therefore contribute to the births that affect the inflow of dogs into the population. Puppies and juveniles are considered to be infertile and therefore do not contribute to the births. The birth rate is the product of the reproduction probability, litter size and the population of reproductive (adult intact) females (S1 Dataset: Equation 14). The model assumes that dogs are born susceptible. The survival rates denote the rate at which dogs in one age group flow into the successive age group (S1 Dataset: Equation 51, 55, 56, 57, 58, 59, 78, 82, 83, 84, 85, 86). The maturation time is the average time for individuals to move from one age class to the next. The puppy, juvenile and adult maturation times are three months, nine months and 12 months respectively. The parts of the model and their relationships are shown in Fig 2. The vaccination coverage is the number of vaccinated dogs divided by the total population (S1 Dataset: Equation 87). The model assumes 100% vaccination of initial juveniles and adults.
Model validation
Model validation is used to reveal any mathematical and logical flows in the model. Model validation was performed using the boundary adequacy test, structure verification test, parameter verification test, extreme condition test and dimensional consistency test [50–52]. The dimensional consistency of the model was assessed using the Vensim units check function. The model behaviour was evaluated using data from Machakos District, Kenya [29]. This study was selected for model validation because it provided the most information on the model parameter values. The variables used in the model are shown in Table 2. Parameters that affected the births and deaths were selected for model validation (Table 3). To perform the model validation, each selected parameter value was changed while the other parameters remained as shown in Table 2. The model behaviour was then assessed for each scenario and compared to the baseline. The initial population of 5117 dogs was based on the total dog population of Machakos District, Kenya [29].
Sensitivity simulations
Multivariate sensitivity simulations were performed to investigate how sex, age, reproductive probability, neutering, mortality rates and litter size interact and affect vaccination coverage decline. Values for the sensitivity simulations were based on the data extracted from the articles identified in the literature review shown in Table 1. The minimum, median and maximum values were obtained for parameters where data could be extracted from at least five articles. The calculated minimum, median and maximum values were used to generate random numbers for the simulations based on triangular distributions. For parameters where data could be extracted from three or four articles, the minimum and maximum values were used as boundaries for uniform distributions. Parameters where data was reported in less than three articles were excluded from the analysis. Multivariate sensitivity simulations were performed using the Vensim Monte Carlo function. To perform the multivariate sensitivity simulations, parameter values were sampled from within the bounds of the random distributions and the resulting values were used in the simulations. A total of 1000 simulations were performed. The variables used in the simulations are shown in Table 4. The results of the simulations were represented as sensitivity histograms and sensitivity graphs. The sensitivity histogram displayed the number of simulations for which the vaccination coverage was in a given range at 12 months post-vaccination. The sensitivity graph showed the confidence bounds of the vaccination coverage at 12 months post-vaccination.
Univariate sensitivity analysis was performed to assess which parameter had the most impact on vaccination coverage decline. To perform univariate simulations, each selected parameter was changed independently, while the other parameters were held as shown in Table 2.
To estimate the proportion of vaccinated dogs with adequate immunity, the vaccination coverage at 12 months was multiplied by the immune proportion. The immune proportion is the proportion of vaccinated dogs with neutralising antibody titres of ≥ 0.5 IU/ml at 12 months post-vaccination. A uniform distribution with minimum and maximum values of 60.6% and 80% was used for the simulations [11,53,54]. The adjusted vaccination coverage is the number of vaccinated dogs that maintained antibody titres at 12 months divided by the total population (S1 Dataset: Equation 1 and S1 Fig).
Results
Model validation
Model validation did not reveal any mathematical and logical flows in the model. Fig 3 shows the vaccination coverage output for five scenarios: baseline; an initial adult proportion of 0% (extreme adults); a female proportion of 0% (extreme females); a female proportion of 26.1% (low females); an initial adult proportion of 39.4% (low adults); a female proportion of 61.2% (high females); and an initial adult proportion of 79.3% (high adults). All other variables are as described in Table 2. The vaccination of all juveniles and adults resulted in an initial vaccination coverage of 74% that declined to 44% at 12 months for the baseline. The initial vaccination coverage was lower for the extreme adults and low adults scenarios compared to the baseline while the high adults scenario had a higher initial vaccination coverage compared to the baseline. The vaccination coverage at 12 months was lower for the high females scenario compared to the baseline despite having the same initial vaccination coverage. Conversely, the vaccination coverage at 12 months for the extreme females and low females scenarios was higher than the baseline despite having the same initial vaccination coverage.
Simulation results for five scenarios: baseline; an initial adult proportion of 0% (extreme adults); a female proportion of 0% (extreme females); a female proportion of 26.1% (low females); an initial adult proportion of 39.4% (low adults); a female proportion of 61.2% (high females); and an initial adult proportion of 79.3% (high adults).
Sensitivity simulations
To assess how the interaction of various model parameter values affect vaccination coverage 1000 simulations using ten parameters (Table 4) were performed. Data from 22 studies and 12 countries were included in the analysis. Fig 4A and 4B depict the sensitivity histogram and sensitivity graph results of 1000 simulations at 12 months post-vaccination. Vaccination of all juveniles and adults resulted in an initial vaccination coverage of 68.6‒89.3% and the vaccination coverage remained above 30% at 12 months post-vaccination. Univariate sensitivity simulations showed that the female proportion and mean litter size had the highest impact on vaccination coverage (Fig 5 and S2 Fig).
(a) Sensitivity histogram and (b) Sensitivity graph.
To estimate the proportion of vaccinated dogs with adequate immunity, an adjusted vaccination coverage was calculated. Fig 6 depicts the sensitivity histogram results of 1000 simulations at 12 months post-vaccination. The results showed that the adjusted vaccination coverage remained within 20‒45% at 12 months post-vaccination.
Discussion
Policy decisions on rabies vaccination campaigns require an understanding of dog demography and how demographic processes interact. This study presents a system dynamics model that explores the effect of dog demographic processes on rabies vaccination coverage decline. A case study of Machakos District demonstrated that an initial mass vaccination coverage of 74% declined to 44% at 12 months post-vaccination. In model validation, the model behaviour for various scenarios was compared with the baseline. Realistically, scenarios with high proportions of unvaccinated puppies due to: high reproduction probabilities; large litter sizes; high proportions of intact adult females; or low puppy mortality are expected to have higher rates of vaccination coverage decline compared to the baseline. Conversely, scenarios with low proportions of unvaccinated puppies due to: low reproduction probabilities; low litter sizes; low proportions of intact adult females; or high puppy mortality would have lower rates of vaccination coverage decline. In the extreme conditions test, the model is expected to generate plausible results outside realistic parameter values. For example, the births should be zero when the female proportion or litter size or reproduction probability is zero as seen in the extreme females scenario. The model behaved in a realistic manner under the various scenarios and the model validation did not reveal mathematical or logical flaws to the model.
Multivariate sensitivity simulations were performed to assess how the interaction of various parameter values would affect the vaccination coverage 12 months after a mass vaccination campaign. The results showed that an initial vaccination of 68.6‒89.3% remained above 30% at 12 months post-vaccination. Moreover, the adjusted vaccination coverage remained within the 20‒45% threshold assuming a seroconversion rate of 60.6‒80%. The results of the model demonstrated that annual mass vaccination campaigns are sufficient to maintain a herd immunity of 20‒45% between vaccination campaigns in dog populations with high turnover rates.
The model assumed that dogs were vaccinated with Rabisin [9] which has been shown to have good seroconversion rates [11,53–56]. The proportion of Rabisin vaccinated dogs with adequate neutralising antibody titres at 12 months post-vaccination has been reported at 60.6%‒80% in Africa [11,53,54], 97% in Peru [56] and 78.4% in Indonesia [11]. Seghaier et al. reported that 36% of dogs vaccinated with a locally produced vaccine had adequate antibody titres 12 months post-vaccination [10]. The model estimated that the adjusted vaccination coverage at 12 months is likely to fall below 20% when the immune proportion is 36% (S3 Fig). It is essential that mass vaccination campaigns use potent vaccines to maintain the desired herd immunity between campaigns. Vaccinations with low potency vaccines result in poor seroconversion rates and/or inadequate persistence of immunity. The use of low potency vaccines would result in a rapid decline in vaccination coverage following a mass vaccination campaign. It is therefore important to conduct studies on the efficacy of locally produced vaccines.
The model did not consider vaccination of puppies since vaccine manufacturers recommend vaccination of dogs at three months of age [9]. However, rabies has been reported in puppies [57–59] and the low vaccination coverage in this age group poses a public health risk given that puppies may represent up to a third of the total population [17,19]. Dogs less than 3 months are usually not vaccinated because they may possess maternal rabies neutralising antibodies that might interfere with the immune response to the vaccine [60]. However, rabies vaccinated puppies in Tanzania and South Africa, demonstrated adequate seroconversion [61]. The WHO recommends that all dogs presented at mass vaccination campaigns should be immunised regardless of age [6]. Vaccination of puppies would, therefore, increase the vaccination coverage in populations with a high proportion of puppies, which is a critical but overlooked variable.
This model has several limitations; firstly, the model does not account for population variations due to the movement of dogs into and out of the population but only considers the population dynamics of the initial population. A high inflow of unvaccinated dogs would increase the rate of vaccination coverage decline. Secondly, the assumption that only dogs over 12 months are fertile is a simplification of the reproductive process. A small proportion of dogs reach fertility at six [32] and ten months [17], however, the vast majority of reproductive dogs are at least 12 months of age [29,17,16]. The exclusion of reproductive dogs under 12 months would underestimate the birth rate and vaccination coverage decline. Another simplification of the model is the assumption that vaccinated and unvaccinated dogs have similar mortality. It has been reported that unvaccinated dogs have a higher mortality rate compared to vaccinated dogs [62]. The assumption that unvaccinated and vaccinated dogs have the same mortality rate may overestimate the rate of vaccination coverage decline. The model only considered owned dogs since the majority of dogs in Africa are owned and therefore available for vaccination [34,35,11,15]. The low proportion of ownerless dogs implies that at least 70% vaccination coverage is attainable by vaccination of owned dogs only. Assuming an ownerless free-roaming dog population of 10%, immunisation of approximately 78% of the owned dog population would achieve at least 70% vaccination coverage. However, baseline data on the owned dog population size is required for adequate human resource mobilisation and procurement of vaccine stocks [63,64]. Unfortunately owned dog populations may be much larger than those reported by officials records [17] and an underestimation of the population could result in a low vaccination coverage. It is important to evaluate the success of vaccination campaigns by conducting post-vaccination studies to estimate the vaccination coverage [64,37,36] and to monitor the occurrence of rabies in dogs and humans [63,65]. Understanding rabies epidemiology in a locality could facilitate targeted vaccination of dogs in areas with the highest rabies transmission rates [63,65]. In addition, targeted vaccination of high risk populations could reduce rabies transmission to adjust areas through incursions of rabid dogs [65].
Conclusion
This paper employs a system dynamics method to provide an insight on the effect of dog demographic processes on rabies vaccination coverage decline. The results demonstrated that annual vaccination campaigns with at least 70% vaccination coverage would maintain a herd immunity of 20‒45% despite high turnover rates.
Supporting information
S1 Fig. Conceptual model to estimate adjusted vaccination coverage.
https://doi.org/10.1371/journal.pone.0205884.s002
(TIF)
S2 Fig. Univariate sensitivity histograms of the vaccination coverage at 12 months post-vaccination.
https://doi.org/10.1371/journal.pone.0205884.s003
(TIF)
S3 Fig. Multivariate sensitivity histogram of the adjusted vaccination coverage at 12 months post-vaccination.
https://doi.org/10.1371/journal.pone.0205884.s004
(TIF)
References
- 1. Rupprecht CE, Hanlon CA, Hemachudha T. Rabies re-examined. Lancet Infect Dis. 2002; 2(6): 327–343. pmid:12144896
- 2. Rupprecht CE, Smith JS, Krebs J, Niezgoda M, Childs JE. Current issues in rabies prevention in the United States health dilemmas. Public coffers, private interests. Public Health Rep. 1996; 111(5): 400–407. pmid:8837628
- 3. Rupprecht CE, Smith JS, Fekadu M, Childs JE. The ascension of wildlife rabies: a cause for public health concern or intervention? Emerg Infect Dis. 1995; 1(4): 107–114. pmid:8903179
- 4. Nel LH, Rupprecht CE. Emergence of lyssaviruses in the Old World: the case of Africa. Curr Top Microbiol Immunol. 2007; 315: 161–193. pmid:17848065
- 5. Knobel DL, Cleaveland S, Coleman PG, Fèvre EM, Meltzer MI, Miranda MEG, et al. Re-evaluating the burden of rabies in Africa and Asia. Bull World Health Organ. 2005; 83(5): 360–368. pmid:15976877
- 6.
World Health Organisation. WHO Expert Consultation on Rabies 2004: First report. WHO technical report series. 2005 pp. 47–56.
- 7. Hampson K, Dushoff J, Cleaveland S, Haydon DT, Kaare M, Packer C, et al. Transmission dynamics and prospects for the elimination of canine rabies. PLoS biol. 2009; 7(3): e1000053.
- 8.
MSD Animal Health. NOBIVAC rabies. Summary of product characteristics. http://www.emergence-msd-animal-health.com/Resources/Rabies/Nobivac-Rabies-SPC.pdf Accessed 6 May 2018.
- 9.
Merial Animal Health. Rabisin data sheet. Merial South Africa (Pty) Ltd. South Africa 2015.
- 10. Seghaier C, Cliquet F, Hammami S, Aouina T, Tlatli A, Aubert M. Rabies mass vaccination campaigns in Tunisia: are vaccinated dogs correctly immunized? AJTMH. 1999; 61(6): 879–884.
- 11. Morters MK, McKinley TJ, Horton DL, Cleaveland S, Schoeman JP, Restif O, et al. Achieving population-level immunity to rabies in free-roaming dogs in Africa and Asia. PLoS Negl Trop Dis. 2014; 8(11): e3160. doi: 3110.1371/journal.pntd.0003160. pmid:25393023
- 12. Darkaoui S, Fassi Fihri O, Schereffer JL, Aboulfidaa N, Wasniewski M, Zouine K, et al. Immunogenicity and efficacy of Rabivac vaccine for animal rabies control in Morocco. Clin Exp Vaccine Res. 2016; 5(1): 60–69. pmid:26866025
- 13. Hu R, Fooks A, Zhang S, Liu Y, Zhang F. Inferior rabies vaccine quality and low immunization coverage in dogs (Canis familiaris) in China. Epidemiol Infect. 2008; 136(11): 1556–1563. pmid:18177524
- 14. Mojžišová J, Süli J, Goldová M, Bajová V, Švrček Š. The effect of endoparasitism on the immune response to antirabies vaccination in puppies. Acta Parasitologica. 2007; 52(2): 176–180.
- 15. Morters MK, McKinley TJ, Restif O, Conlan AJ, Cleaveland S, Hampson K, et al. The demography of free-roaming dog populations and applications to disease and population control. J Appl Ecol. 2014; 51(4): 1096–1106. pmid:25657481
- 16. Mauti S, Traoré A, Sery A, Bryssinckx W, Hattendorf J, Zinsstag J. First study on domestic dog ecology, demographic structure and dynamics in Bamako, Mali. Prev Vet Med. 2017; 146: 44–51. pmid:28992927
- 17. Gsell AS, Knobel DL, Kazwala RR, Vounatsou P, Zinsstag J. Domestic dog demographic structure and dynamics relevant to rabies control planning in urban areas in Africa: the case of Iringa, Tanzania. BMC Vet Res. 2012; 8: 236. pmid:23217194
- 18. Conan A, Akerele O, Simpson G, Reininghaus B, van Rooyen J, Knobel D. Population dynamics of owned, free-roaming dogs: Implications for rabies control. PLoS Negl Trop Dis. 2015; 9(11): e0004177. pmid:26545242
- 19. De Balogh K, Wandeler AI, Meslin F-X. A dog ecology study in an urban and a semi-rural area of Zambia. 1993: 437–443. pmid:7777333
- 20. Butler J, Bingham J. Demography and dog-human relationships of the dog population in Zimbabwean communal lands. Vet Rec. 2000; 147(16): 442–446. pmid:11079440
- 21. Tschopp R, Bekele S, Aseffa A. Dog demography, animal bite management and rabies knowledge-attitude and practices in the Awash Basin, Eastern Ethiopia. PLoS Negl Trop Dis. 2016; 10(2): e0004471. pmid:26900855
- 22. Omudu E, Otache E, Adelusi S. Studies on dog population in Makurdi, Nigeria (I): demography and survey of pet owners' beliefs and attitudes. JRFWE. 2010; 2(1): 85–93.
- 23.
Dlamini RX Dog ecology survey questionnaire with reference to improving rabies awareness and control in rural suburban and urban areas of Swaziland. Southern and Eastern African Rabies Group/World Health Organization. 1999 pp. 129–133.
- 24. Mshelbwala P, Akinwolemiwa D, Maikai B, Otolorin R, Maurice N, Weese J. Dog ecology and its implications for rabies control in Gwagwalada, Federal Capital Territory, Abuja, Nigeria. Zoonoses and Public Health. 2017; 65(1): 168–176. pmid:28782905
- 25. Atuman Y, Ogunkoya A, Adawa D, Nok A, Biallah M. Dog ecology, dog bites and rabies vaccination rates in Bauchi State, Nigeria. IJVSM. 2014; 2(1): 41–45.
- 26. Ratsitorahina M, Rasambainarivo JH, Raharimanana S, Rakotonandrasana H, Andriamiarisoa MP, Rakalomanana FA, et al. Dog ecology and demography in Antananarivo, 2007. BMC Vet Res. 2009; 5: 21. pmid:19486516
- 27. Garba A, Dzikwi A, Kazeem H, Makanju O, Hambagba F, Abduazeez N, et al. Dog Ecology and Management in Niger State, Nigeria: A Basic Tool for Rabies Control. JAERI. 2017; 12(1): 1–9.
- 28.
Ahmed G Dog ecology, dog bite cases and molecular characterization of rabies virus in slaughtered dogs in Niger State, Nigeria. NVRI SEMINAR SERIES 2014. 2009 pp. 74–85.
- 29. Kitala P, McDermott J, Kyule M, Gathuma J, Perry B, Wandeler A. Dog ecology and demography information to support the planning of rabies control in Machakos District, Kenya. Acta Trop. 2001; 78(3): 217–230. pmid:11311185
- 30. Otolorin GR, Umoh JU, Dzikwi AA. Demographic and ecological survey of dog population in Aba, Abia State, Nigeria. ISRN Vet Sci. 2014:
- 31. Hyeroba D, Friant S, Acon J, Okwee-Acai J, Goldberg TL. Demography and health of “village dogs” in rural Western Uganda. Prev Vet Med. 2017; 137: 24–27. pmid:28107877
- 32. Czupryna AM, Brown JS, Bigambo MA, Whelan CJ, Mehta SD, Santymire RM, et al. Ecology and demography of free-roaming domestic dogs in rural villages near Serengeti National Park in Tanzania. PLoS One. 2016; 11(11): e0167092. pmid:27893866
- 33. van Sittert SJ, Raath J, Akol GW, Miyen JM, Mlahlwa B, Sabeta CT. Rabies in the Eastern Cape Province of South Africa—where are we going wrong? J S Afr Vet Assoc. 2010; 81(4): 207–215. pmid:21526734
- 34. Lembo T, Hampson K, Kaare MT, Ernest E, Knobel D, Kazwala RR, et al. The feasibility of canine rabies elimination in Africa: dispelling doubts with data. PLoS Negl Trop Dis. 2010; 4(2): e626 doi: 610.1371/journal.pntd.0000626. pmid:20186330
- 35. Jibat T, Hogeveen H, Mourits MC. Review on dog rabies vaccination coverage in Africa: A question of dog accessibility or cost recovery? PLoS Negl Trop Dis. 2015; 9(2): e0003447. doi: 0003410.0001371/journal.pntd.0003447. pmid:25646774
- 36. Muthiani Y, Traoré A, Mauti S, Zinsstag J, Hattendorf J. Low coverage of central point vaccination against dog rabies in Bamako, Mali. Preventive veterinary medicine. 2015; 120(2): 203–209. pmid:25953653
- 37. Kayali U, Mindekem R, Yemadji N, Vounatsou P, Kaninga Y, Ndoutamia A, et al. Coverage of pilot parenteral vaccination campaign against canine rabies in N'Djamena, Chad. Bulletin of the World Health Organization. 2003; 81: 739–744. pmid:14758434
- 38.
Poston DL Jr, Bouvier LF ''We are all population actors'': An introduction to demography. Population and society: An introduction to demography. New York, USA: Cambridge University Press. 2010 pp. 3–14.
- 39. Davlin SL, VonVille HM. Canine rabies vaccination and domestic dog population characteristics in the developing world: a systematic review. Vaccine. 2012; 30(24): 3492–3502. pmid:22480924
- 40. Chaves R, López D, Macías F, Casares J, Monterroso C. Application of System Dynamics technique to simulate the fate of persistent organic pollutants in soils. Chemosphere. 2013; 90(9): 2428–2434. pmid:23177003
- 41. Sharareh N, Sabounchi NS, Sayama H, MacDonald R. The Ebola Crisis and the Corresponding Public Behavior: A System Dynamics Approach. PLoS Curr. 2016; 8:
- 42. Ritchie-Dunham JL, Galvan JFM. Evaluating epidemic intervention policies with systems thinking: a case study of dengue fever in Mexico. Syst Dyn Rev. 1999; 15(2): 119.
- 43. Homer JB, Hirsch GB. System dynamics modeling for public health: background and opportunities. Am J Public Health. 2006; 96(3): 452–458. pmid:16449591
- 44. Semwanga AR, Nakubulwa S, Adam T. Applying a system dynamics modelling approach to explore policy options for improving neonatal health in Uganda. Health Res Policy Syst. 2016; 14(1): 35. pmid:27146327
- 45. Ciplak N, Barton JR. A system dynamics approach for healthcare waste management: a case study in Istanbul Metropolitan City, Turkey. Waste Manag Res. 2012; 30(6): 576–586. pmid:22517528
- 46. Laurenson K, Esterhuysen J, Stander P, Van Heerden J. Aspects of rabies epidemiology in Tsumkwe District, Namibia. Onderstepoort J Vet Res. 1997; 64(1): 39–45. pmid:9204502
- 47. Hambolu SE, Dzikwi AA, Kwaga JK, Kazeem HM, Umoh JU, Hambolu DA. Dog ecology and population studies in Lagos State, Nigeria. Glob J Health Sci. 2014; 6(2): 209–220. pmid:24576383
- 48. Aiyedun JO, Olugasa BO. Use of aerial photograph to enhance dog population census in Ilorin, Nigeria. SJVS. 2012; 10(1): 22–27.
- 49. Kitala P, McDermott J, Kyule M, Cathuma J. Features of dog ecology relevant to rabies spread in Machakos District, Kenya. Onderstepoort J Vet Res. 1993; 60(4): 445–449. pmid:7777334
- 50.
Qudrat-Ullah H Structural validation of system dynamics and agent-based simulation models. 19th European Conference on Modelling and Simulation, Riga, Latvia, 2005 Accessed 15 October 2017.
- 51. Martis MS. Validation of simulation based models: a theoretical outlook. EJBRM. 2006; 4(1): 39–46.
- 52. Ding Z, Yi G, Tam VW, Huang T. A system dynamics-based environmental performance simulation of construction waste reduction management in China. Waste Manag. 2016; 51: 130–141. pmid:26969286
- 53. Bahloul C, Taieb D, Diouani MF, Ahmed SBH, Chtourou Y, B’chir BI, et al. Field trials of a very potent rabies DNA vaccine which induced long lasting virus neutralizing antibodies and protection in dogs in experimental conditions. Vaccine. 2006; 24(8): 1063–1072. pmid:16213633
- 54.
Hikufe EH Rabies sero-survey in vaccinated domestic dogs and knowledge assessment of rabies among dog owners, Ohangwena region, Namibia (MSc Thesis): University of Namibia. 2016.
- 55. Mantik-Astawa I, Putra A. The humoral immunity response of dog vaccinated with oral SAG2 and parenteral Rabisin and Rabivet Supra92. Indones J Biomed Sci. 2012; 6: 26–29.
- 56. Chomel B, Chappuis G, Bullon F, Cardenas E, de Beublain TD, Lombard M, et al. Mass vaccination campaign against rabies: are dogs correctly protected? The Peruvian experience. Rev Infect Dis. 1988; 10(Supplement_4): S697–S702.
- 57. Okolo M. A case of dumb rabies and trypanosomiasis in an eight‐week‐old puppy. JSAP. 1986; 27(7): 471–475.
- 58. Van Rijckevorsel G, Swaan C, Van Den Bergh J, Goorhuis A, Baayen D, Isken L, et al. Rabid puppy-dog imported into the Netherlands from Morocco via Spain, February 2012. Euro Surveill. 2012; 17(10): pii: 20112. pmid:22433596
- 59. White J, Taylor SM, Wolfram KL, O’Conner BP. Rabies in a 10-week-old puppy. The Canadian Veterinary Journal. 2007; 48(9): 931. pmid:17966334
- 60. Aghomo H, Oduye O, Rupprecht C. The serological response of young dogs to the Flury LEP strain of rabies virus vaccine. Vet Res Commun 1990; 14(5): 415–425. pmid:2247948
- 61. Morters MK, McNabb S, Horton DL, Fooks AR, Schoeman JP, Whay HR, et al. Effective vaccination against rabies in puppies in rabies endemic regions. Vet Rec. 2015; 177(6): 150. pmid:26109286
- 62. Knobel DL, Arega S, Reininghaus B, Simpson GJ, Gessner BD, Stryhn H, et al. Rabies vaccine is associated with decreased all-cause mortality in dogs. Vaccine. 2017; 35(1): 3844–3849. doi: 3810.1016/j.vaccine.2017.3805.3095.
- 63. LeRoux K, Stewart D, Perrett K, Nel LH, Kessels J, Abela-Ridder B. Rabies control in KwaZulu-Natal, South Africa. Bull World Health Organ. 2018; 96(5): 360. pmid:29875521
- 64. Gibson AD, Handel IG, Shervell K, Roux T, Mayer D, Muyila S, et al. The vaccination of 35,000 dogs in 20 working days using combined static point and door-to-door methods in Blantyre, Malawi. PLoS neglected tropical diseases. 2016; 10(7): e0004824. pmid:27414810
- 65. Laager M, Mbilo C, Madaye EA, Naminou A, Léchenne M, Tschopp A, et al. The importance of dog population contact network structures in rabies transmission. PLoS neglected tropical diseases. 2018; 12(8): e0006680. pmid:30067733