Background: Some vaccine preventable diseases still remain a public health burden in many African countries. The occurrence of vaccine preventable diseases in all age groups has led to the realization of the need to extend routine immunisation services to school age children and adolescents. Supplemental immunisation activities (SIAs) and school based vaccination (SBV) are two common strategies used to complement the EPI in vaccine delivery. Therefore, this review aimed to assess the effectiveness of SIAs compared to SBV in the administration of vaccines to 5-19 year olds in Africa. Methods and findings: Systematic review methods (protocol number CRD42017057475) were used to address our study aim. Electronic databases were searched up to March 30, 2017 for primary studies investigating the delivery of vaccines via SIAs or SBV to 5-19 year olds. To be included in the review, studies must have reported any of the following outcomes: vaccination coverage, cost of the vaccination strategy or effect of the strategy on routine immunisation. During the search, no restriction was placed on language or the study period. The search was complemented by browsing reference lists of potential studies. Out of the 4938 studies identified, 31 studies met our inclusion criteria. Both SIAs and SBV showed high vaccination coverage. This result should be interpreted with caution due to the high heterogeneity observed across the included studies. The SIAs reported a higher coverage of 91% (95% CI: 84%, 98%) than SBV which had a coverage of 75% (95% CI: 67%, 83%). In most settings, SBV was reported to be more expensive than SIAs. The SIAs were found to negatively affect routine immunisation services. Conclusions: Both SIAs and SBV are routinely used to complement the EPI in the delivery of vaccines in Africa. In settings where school enrolment is suboptimal as is the case in many African countries, our results show SIAs may be more effective in reaching school age children and adolescents than SBV. The SBV has only been tested in the delivery of two or three dose HPV vaccine to adolescent girls, whereas SIAs have been tested in the delivery of different types of vaccines. Our results re-iterate the importance of systematic evidence to best inform African authorities on the optimal delivery strategies of vaccines targeting school age children and adolescents into their immunisation programme.

<p>The main body of this thesis deals with three related concepts pertaining to vaccination strategies for childhood infectious disease. Chapter 2 deals with the implications of reversion in the Oral Polio Vaccine on global polio eradication programs. Chapter 3 explores the phenomenon of contact or secondary vaccination in the use of live-attenuated virus vaccines. Chapter 4 explores the importance of demographic stochasticity in pulse vaccination campaigns. largely focusing on measles dynamics. Abstracts for each chapter are given below.</p><p>Poliomyelitis vaccination via live Oral Polio Vaccine (OPV) suffers from the inherent problem of reversion: the vaccine may, upon replication in the human gut, mutate back to virulence and transmissibility resulting in circulating vaccine derived polio viruses (cVDPVs). We formulate a general mathematical model to assess the impact of cVDPVs on prospects for polio eradication. We find that for OPV coverage levels below a certain threshold, cVDPVs have a small impact in comparison to the expected endemic level of the disease in the absence of reversion. Above this threshold, the model predicts a small but significant endemic level of the disease, even where standard models predict eradication. In light of this, we consider and analyze three alternative eradication strategies involving a transition from continuous OPV vaccination to either continuous Inactivated Polio Vaccine (IPV), pulsed OPV vaccination, or a one-time IPV pulse vaccination. Stochastic modeling shows continuous IPV vaccination is effective at achieving eradication for moderate coverage levels, while pulsed OPV is effective if higher coverage levels are maintained. The one-time pulse IPV method may also be a viable strategy, especially in terms of the number of vaccinations required and time to eradication, provided that a sufficiently large pulse is practically feasible. More investigation is needed rq?;arding the frequency of revertant virus infection resulting directly from vaccination, the ability of IPV to induce gut immunity, and the potential role of spatial transmission dynamics in eradication efforts.</p> <p>Viruses contained in live-attenuated vims vaccines (LAVV) can be transmitted between individuals, resulting in secondary or contact vaccinations. This fact has been exploited successfully in the use of the Oral Polio Vaccine (OPV) to better control wild polio viruses. In this work we analyze general LAVV vaccination models for infections that confer lifelong immunity. We consider both standard (continuous) vaccination strategies and pulse vaccination programs (where mass vaccination is carried out at regular intervals). For continuous vaccination, we provide a complete global analysis of a very general compartmental ordinary differential equation LAVV model. We find that the threshold vaccination level required for eradication of wild virus depends on the basic reproduction numbers of both the wild and vaccine viruses, but is otherwise independent of the distributions of the durations in each of the sequence of stages of disease progression (e.g., latent, infectious, etc.). Furthermore, even for vaccine viruses with reproduction numbers below one. which would naturally fade from the population upon cessation of vaccination, there can be a significant reduction in the threshold vaccination level. The dependence of the threshold vaccination level on the virus reproduction numbers largely generalizes to the pulse vaccination model. For shorter pulsing periods there is negligible difference in threshold vaccination level as compared to continuous vaccination campaigns. Thus, we conclude that current policy in many countries to employ annual pulsed OPV vaccination does not significantly diminish the benefits of contact vaccination.</p><p> In the last two decades, many countries have implemented pulse vaccination for infectious diseases (mass vaccination campaigns repeated annually or at other regular intervals). Based on deterministic mathematical models, previous work has shown that the total expected cost of control or eradication (measured by the number of vaccine doses required) is identical for pulse vaccination (with any pulse interval) and for traditional, continuous vaccination. We reconsider this problem using stochastic epidemic models (both by direct simulation and by employing a moment closure approximation). We focus on measles and show that demographic stochasticity has a large impact on the relative success of pulse and continuous vaccination programs, even for well-mixed populations as large as 10 million.</p> / Thesis / Doctor of Philosophy (PhD)

[ES] Desde tiempos inmemorables en la historia de la humanidad las enfermedades de transmisión sexual (ETSs) han sido una gran amenaza para la salud pública. Las preocupaciones comienzan en la edad moderna con pandemias tales como la sífilis, cuya propagación ocurre en Europa a comienzos del siglo XVI. El virus de papiloma humano (VPH) es la causa directa de más de medio millón de casos nuevos de cáncer de cuello de útero, el segundo más maligno entre mujeres y una de las principales causas de muerte por cáncer en todo el mundo. Además causa verrugas anogenitales y otras enfermedades relacionadas. En este trabajo estudiamos el contagio del VPH en una red de contactos sexuales. Para predecir la evolución de este tipo de enfermedades, necesitamos un modelo fiable de la red social subyacente sobre el que la infección prolifera. Hemos construido una red de parejas sexuales durante toda la vida basada en datos demográficos y encuestas sobre hábitos sexuales. La mayoría de los enfoques para modelizar ETSs por lo general y del VPH en particular, se hacen usando modelos clásicos donde la hipótesis de mezcla homogénea (todo el mundo puede transmitir a todo el mundo) es asumida de manera implícita. Sin embargo, la mezcla homogénea no es una hipótesis razonable y las consecuencias de estas suposiciones se ven de hecho, en que los efectos de los calendarios de vacunación contra el VPH se detectan en Australia mucho antes de lo que los modelos clásicos predijeron. Hay un debate sobre la conveniencia de la vacunación de los niños. Elbasha et al. encontraron evidencias de que la vacunación en niños podría llegar a ser coste-efectiva. En nuestro modelo consideramos poblaciones tanto de hombres que solo tienen relaciones con mujeres y que las tienen entre ellos, permitiéndonos sacar conclusiones al respecto. Con nuestro modelo simulamos y llevamos a cabo campañas de vacunación de modo que podemos sacar conclusiones atendiendo a las mejores estrategias. Estos resultados pueden ayudar a los responsables de Salud Pública a tomar decisiones apropiadas con respecto al VPH. / [CAT] Des de temps inmemorables en la història de la humanitat les malalties de transmissió sexual (MTSs) han sigut una gran amenaça per a la salut pública. Les preocupacions comencen en l'edat moderna amb pandèmies com ara la sífilis, la propagació de la qual ocorre a Europa al començament del segle XVI. El virus de papilloma humà (VPH) és el causant directe de més de mig milió de casos nous de càncer de coll d'úter, el segon mes maligne entre dones i una de les principals causes de mort per càncer en tot el món. A més causa berrugues anogenitales i altres malalties relacionades. En este treball estudiem la dinàmica de transmissió del VPH en una xarxa de contactes sexuals. Per a predir l'evolució d'este tipus de malalties, necessitem un model fiable de la xarxa social subjacent sobre la qual la infecció prolifera. Hem construït un xarxa de parelles sexuals durant tota la vida basada en dades demogràfiques i enquestes sobre hàbits sexuals. La majoria dels enfocaments per a modelizar MTSs generalment i del VPH en particular, es fan usant models clàssics on la hipótesi de mescla homogènia (tot el món pot transmetre a tot el món) és assumida de manera implícita. No obstant això la mescla homogènia no és una hipòtesi raonable i les conseqüències d'estes suposicions es veuen de fet, en que els efectes dels calendaris de vacunació contra el VPH es detecten a Austràlia molt abans del que els models clàssics van predir. / [EN] Sexually transmitted diseases (STDs) have been a major public health threat for a long time in human history. Modern concerns about STD began with the pandemic of syphilis which spread over Europe in the early sixteenth century. The human papillomavirus (HPV) is the direct cause of more than half million new cases of cervical cancer, the second most common malignancy among women and a leading cause of cancer death worldwide. It also causes anogenital warts and other related diseases. In this work we have studied the transmission dynamics of HPV over a sexual contacts network. In order to predict the evolution of these kind of diseases, we need a reliable model of the underlying social network in which the infection spreads. We have built a lifetime sexual partners (LSP) network based on demographic data and surveys about sexual habits. Most of the modeling approaches to STD in general and HPV in particular, are done using classical models where the hypothesis of homogeneous mixing (everybody can transmit a disease to everybody) is assumed. However, homogeneous mixing is not a reasonable hypothesis and consequences of this assumption can be seen, for instance, in that the effects of vaccination schedules against HPV have been detected in Australia much sooner than what the classical models predicted. There is a debate concerning the vaccination of young men. Elbasha et al. found some evidences that the vaccination of boys could also be cost-effective. In our model we consider both heterosexual men, and men who have sex with men (MSM) populations and the connections among them letting us to study this matter. With our model simulate and carry out vaccination campaigns in order to figure out the best strategies. All these results can be useful for policy makers in Public Health to make appropriate decisions respect to HPV. / Sánchez Alonso, V. (2019). Building networks of sexual partners. Application for the study of the transmission dynamics of Human Papillomavirus (HPV) [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/124344 / TESIS