Cattle protected from onchocerciasis by ivermectin are highly susceptible to infection after drug withdrawal

Ivermectin administration is now the major tool in the control of human onchocerciasis (caused by Onchocerca volvulus) based on its suppression of microfilariae and hence the prevention of disease. However, in Africa, transmission is not eliminated and treated populations continue to be exposed to infective larval (L(3)) challenge, albeit at reduced levels. We have investigated whether protective immunity might develop under such conditions using the analogous host-parasite system Onchocerca ochengi in cattle, based on our previous findings in cattle exposed to challenge, that in vivo ivermectin attenuates the development of adult infections and that irradiation-attenuated L(3) induce significant protection. In a two-phase prospective study over 4 years, groups of cattle were exposed to severe natural challenge. In the first phase, 38/40 animals treated either with ivermectin or with moxidectin at either monthly or 3-monthly intervals had not developed detectable infections after 22 months of exposure whereas, in a non-treated control group (n = 14) nodule prevalence was 78.6% and the geometric mean (range) nodule load was 4.8 (0-33). In the second phase, all drug treatments were withdrawn, a new control group (n = 8) introduced, and exposure continued at the same site. After 24 months, all groups had developed patent infections, with geometric mean (range) nodule loads of 17.4 (4-99), 38.4 (10-111), 50.7 (26-86), 14.3 (0-69) and 14.7 (0-55) for the control, monthly-ivermectin, 3-monthly ivermectin, monthly moxidectin and 3-monthly moxidectin groups, respectively. There was no evidence of protection-indeed the 3-monthly ivermectin group was significantly (P < 0.05) hyper-susceptible. In addition, microfilarial densities and the rate of increase in microfilarial load were significantly higher (P < 0.05) in the ivermectin-treated groups than in control animals. These results have important implications for ivermectin-based control of human onchocerciasis and suggest that humans exposed to ongoing transmission in endemic areas whilst receiving ivermectin are unlikely to develop immunity and will be highly susceptible should drug distribution cease.     

On treatment of tuberculosis in heterogeneous populations

Global eradication of tuberculosis (TB) is an international agenda. Thus understanding effects of treatment of TB in different settings is crucial. In previous work, we introduced the framework for a mathematical model of epidemic TB in demographically distinct, heterogeneous populations. Simulations showed the importance of genetic susceptibility in determining endemic prevalence levels. In the work presented here, we include treatment and investigate different strategies for treatment of latent and active TB disease in heterogeneous populations. We illustrate how the presence of a genetically susceptible subpopulation dramatically alters effects of treatment in the same way a core population does in the setting of sexually transmitted diseases. In addition, we evaluate treatment strategies that focus specifically on this subpopulation, and our results indicate that genetically susceptible subpopulations should be accounted for when designing treatment strategies to achieve the greatest reduction in disease prevalence.     

Bovine babesiosis and anaplasmosis: Control by premunition and chemoprophylaxis

Experiments were carried out to evaluate two systems: (1) premunition and (2) chemoprophylaxis for the control of bovine babesiosis and anaplasmosis in the Cauca River Valley, Colombia. Control of these diseases was achieved by inoculating cattle with virulent Babesia bigemina, Babesia argentina, and Anaplasma marginale and subsequent treatment with Imidocarb and Gloxazone to moderate the postpremunition reactions. Chemoprophylactic treatment with Imidocarb and Gloxazone was administered to cattle before and during field exposure. Premunized cattle were highly resistant to tick-borne (Boophilus microplus) challenge. Imidocarb had therapeutic and chemoprophylactic properties against babesiosis, but appeared toxic. Gloxazone moderated the A. marginale postpremunition reaction, but failed to prevent clinical anaplasmosis under the conditions of this investigation.     

Tuberculosis Transmission Model with Chemoprophylaxis and Treatment

A tuberculosis model which incorporates treatment of infectives and chemoprophylaxis is presented. The model assumes that latently infected individuals develop active disease as a result of endogenous re-activation, exogenous re-infection and disease relapse, though a small fraction is assumed to develop active disease soon after infection. We start by formulating and analyzing a TB model without any intervention strategy that we extend to incorporate chemoprophylaxis and treatment of infectives. The epidemic thresholds known as reproduction numbers and equilibria for the models are determined, and stabilities analyzed. The reproduction numbers for the models are compared to assess the possible community benefits achieved by treatment of infectives, chemoprophylaxis and a holistic approach of these intervention strategies. The study shows that treatment of infectives is more effective in the first years of implementation (≈ 10 years) as treatment results in clearing active TB immediately and there after chemoprophylaxis will do better in controlling the number of infectives due to reduced progression to active TB.     

A Mathematical Model of Schistosoma mansoni in Biomphalaria glabrata with Control Strategies

We describe and analyze a mathematical model for schistosomiasis in which infected snails are distinguished from susceptible through increased mortality and no reproduction. We based the model on the same derivation as Anderson and May (J. Anim. Ecol. 47:219–247, 1978), Feng and Milner (A New Mathematical Model of Schistosomiasis, Mathematical Models in Medical and Health Science, Nashville, TN, 1997. Innov. Appl. Math., Vanderbilt Univ. Press, Nashville, pp. 117–128, 1998), and May and Anderson (J. Anim. Ecol. 47:249–267, 1978), but used logistic growth both in human and snail hosts. We introduce a parameter r, the effective coverage of medical treatment/prevention to control the infection. We determine a reproductive number for the disease directly related to its persistence and extinction. Finally, we obtain a critical value for r that indicates the minimum treatment effort needed in order to clear out the disease from the population.