Antibody response and risk factors for seropositivity in backyard poultry following mass vaccination against highly pathogenic avian influenza and Newcastle disease in Indonesia.

A large-scale mass vaccination campaign was carried out in Java, Indonesia in an attempt to control outbreaks of highly pathogenic avian influenza (HPAI) in backyard flocks and commercial smallholder poultry. Sero-monitoring was conducted in mass vaccination and control areas to assess the proportion of the target population with antibodies against HPAI and Newcastle disease (ND). There were four rounds of vaccination, and samples were collected after each round resulting in a total of 27 293 samples. Sampling was performed irrespective of vaccination status. In the mass vaccination areas, 20-45% of poultry sampled had a positive titre to H5 after each round of vaccination, compared to 2-3% in the control group. In the HPAI + ND vaccination group, 12-25% of the population had positive ND titres, compared to 5-13% in the areas without ND vaccination. The level of seropositivity varied by district, age of the bird, and species (ducks vs. chickens).

The effectiveness of preventative mass vaccination regimes against the incidence of highly pathogenic avian influenza on Java Island, Indonesia.

We conducted an operational research study involving backyard and semicommercial farms on Java Island, Indonesia, between April 2008 and September 2009 to evaluate the effectiveness of two preventive mass vaccination strategies against highly pathogenic avian influenza (HPAI). One regimen used Legok 2003 H5N1 vaccine, while the other used both Legok 2003 H5N1 and HB1 Newcastle disease (ND) vaccine. A total of 16 districts were involved in the study. The sample size was estimated using a formal power calculation technique that assumed a detectable effect of treatment as a 50% reduction in the baseline number of HPAI-compatible outbreaks. Within each district, candidate treatment blocks with village poultry populations ranging from 80 000 to 120 000 were created along subdistrict boundary lines. Subsequently, four of these blocks were randomly selected and assigned one treatment from a list that comprised control, vaccination against HPAI, vaccination against HPAI + ND. Four rounds of vaccination were administered at quarterly intervals beginning in July 2008. A vaccination campaign involved vaccinating 100 000 birds in a treatment block, followed by another 100 000 vaccinations 3 weeks later as a booster dose. Data on disease incidence and vaccination coverage were also collected at quarterly intervals using participatory epidemiological techniques. Compared with the unvaccinated (control) group, the incidence of HPAI-compatible events declined by 32% (P = 0.24) in the HPAI-vaccinated group and by 73% (P = 0.00) in the HPAI- and ND-vaccinated group. The effect of treatment did not vary with time or district. Similarly, an analysis of secondary data from the participatory disease and response (PDSR) database revealed that the incidence of HPAI declined by 12% in the HPAI-vaccinated group and by 24% in the HPAI + ND-vaccinated group. The results suggest that the HPAI + ND vaccination significantly reduced the incidence of HPAI-compatible events in mixed populations of semicommercial and backyard poultry.

Estimating the transmissibility of H5N1 and the effect of vaccination in Indonesia.

The spread of H5N1 avian influenza continues to pose an economic burden and a public health risk worldwide. Despite this, estimates of the transmissibility of infection exist in only a handful of settings and vary considerably. Using final size methods and flock-level infection data from a field trial of mass vaccination, we obtained the first estimates of the transmissibility of infection between and within flocks in Indonesia. We also found that outbreaks in areas designated as vaccination zones were less transmissible than in non-vaccination zones. However, this reduction is only comparable with a limited degree of protective vaccination coverage. Quantifying the overall effect of vaccination in these zones remains challenging. However, this result would appear to imply that, although the interventions applied in vaccination zones were not sufficient to completely prevent transmission in all areas, when outbreaks occur, they are less transmissible than those in areas where vaccination was not applied. This could be either a direct or an indirect effect of vaccination. Given the dynamism of small-scale poultry production in Indonesia, more regular vaccination may be required to ensure that infection is fully controlled in vaccination zones.

Institutions: stronger veterinary services for better governance.

Veterinary Services (VS) as defined by the World Organisation for Animal Health (OIE) are institutions that can have varied structures, from the centralised to the completely decentralised, with ranges in between these two extremes. The VS include a broad range of public and civil society organisations and actors whose shared purpose is to deliver animal health services, and the interactions of these actors are governed by a range of formal and informal rules. The range of essential services to be carried out by the VS is laid out in the OIE Terrestrial Animal Health Code, which also provides certain key definitions. To provide these services, there must be strong institutions, as these are key elements of good governance. This, in turn, enhances the efficient provision of global public goods and services to the citizens. Therefore, the VS must be properly resourced and structured to carry out all their tasks. This paper highlights some important factors that can help achieve this goal and discusses possible VS administrative structures, human and financial resources, and national systems for the early detection and notification of disease events as well as those for disease prevention. These are essential elements of the public good functions of VS and they warrant prioritisation by OIE Member Countries.

The 2006-2007 Rift Valley fever outbreak in Kenya: sources of early warning messages and response measures implemented by the Department of Veterinary Services.

The authors characterised sources of early warning messages about occurrences of Rift Valley fever (RVF) and examined the response measures that were used by the Department of Veterinary Services (DVS) to manage the 2006-2007 RVF outbreaks in Kenya. The study was conducted between November 2009 and March 2010 and it included national, provincial and district veterinary officers who were involved in the management of the outbreak. Structured questionnaires were used to collect the data. Although the majority of the respondents reported having limited capacity to implement response measures, they perceived that the measures implemented were effective. Vaccination, movement control and market closures were the main response measures implemented, particularly in districts that had cases in both livestock and humans. Vaccination, however, was implemented too late and the coverage achieved was too low to be effective. The authors suggest ways to improve the capacity of the DVS to respond to similar outbreaks in the future.

Integration of participatory approaches into surveillance systems.

Animal health surveillance is essential for protecting public health, enhancing access to international markets for animals and their products, and improving animal health, production and welfare. It is of vital importance for protecting and improving the livelihoods of diverse groups of livestock keepers and stakeholders in livestock value chains. Surveillance systems consist of sets of complementary components which generate information to inform risk assessment, decision-making and policy formulation for both national programmes and international trade. Participatory approaches have the potential to add value to surveillance systems by enhancing their performance, especially their sensitivity and timeliness, and encouraging the inclusion of marginalised groups. This paper summarises key considerations in the assessment and design of animal health surveillance and discusses how participatory approaches can be integrated into comprehensive surveillance systems, leading to a more effective overall outcome for both domestic and international purposes.

More appropriate disease control policies for the developing world.

Investment in disease control should be targeted to critical points that provide the greatest benefit to the livelihoods of livestock-dependent stakeholders. Risk-based targeting should balance the impacts of diseases against the feasibility of their control. This requires sensitive and specific surveillance systems that provide representative overviews of the animal health situation for accurate assessment of disease impact and transmission patterns. Assessment of impact should include household and market effects. The key in surveillance is involving livestock owners using active methods that ensure their disease priorities are addressed. Epidemiological targeting of interventions to critical points in disease transmission cycles should be done to obtain maximal disease reduction. Interventions should be delivered in full partnership with both private and community-based stakeholders to assure high uptake and sustainability. In developing countries, approaches such as participatory disease surveillance and community-based animal health programs have been effective and comply with international animal health standards.

Using participatory epidemiological techniques to estimate the relative incidence and impact on livelihoods of livestock diseases amongst nomadic pastoralists in Turkana South District, Kenya.

A participatory epidemiological (PE) study was carried out with Turkana pastoralists in Turkana South District, Kenya, to determine the relative incidence of livestock diseases and their impact on livelihoods. A sub-location was used as the sampling unit. A sub-location is the smallest administrative unit and is occupied by clusters of families (called adakars) that share common grazing patterns. A total of 32 sub-locations were randomly selected for the study. At least one focus group discussion involving more than 10 people was held with each adakar. In addition, key informant interviews involving local leaders and animal health service providers were conducted before or after the group sessions. PE techniques that were used with the stock owners include participatory mapping, relative incidence scoring, proportional piling, disease impact matrix scoring, seasonal calendars and probing. The methods used were pre-tested in four sub-locations that were excluded from further study. The study revealed that goats, with median score of 33 (10th and 90th percentiles of 25, 44, respectively) and sheep, median score of 20.5 (15, 26) were perceived to be the most abundant livestock species while goats (median score of 32 [21, 56]) and camels (median score of 22.5 [11, 33]) contributed the most to the livelihoods of the pastoralists. For goats, the overall relative incidence scores of peste des petits ruminants (PPR), contagious caprine pleuropneumonia (CCPP) and mange were 23.5% (15, 34), 25% (21, 45) and 20% (19, 28), respectively. The respective median scores for case fatality rates were 66% (45, 76.5), 62.5% (25, 100) and 73.2% (21.4, 85.7). Disease impact matrix scores indicated that mange was the most important disease of goats. Mange (range: 28-32%) and pox (range: 16-38%) were perceived to be the most prevalent diseases in camels. Livestock movements, limited access to veterinary services and stock theft were identified as key factors that contributed to the high prevalence and persistence of these diseases. This paper discusses strategies that could be used to control these diseases given the challenges associated with nomadic pastoralism and insecurity.

A simple model for simulating immunity rate dynamics in a tropical free-range poultry population after avian influenza vaccination.

In developing countries, vaccination against highly pathogenic avian influenza subtype H5N1 (HPAI) in free-range poultry flocks is usually implemented as periodic campaigns and newborn chicks are generally not vaccinated by farmers between vaccination passes. The demographic population turnover leads to a continuous decrease in the population immunity rate (PIR) over time. We present a simple Leslie matrix model for estimating population turnover and PIR dynamics in a hypothetical small-size vaccinated free-range poultry population. Four different vaccination scenarios were identified assuming necessary procedures to achieve immunity. The results indicate that high levels of population immunity are difficult to sustain. Assuming an animal immunity response of 80% after vaccination and a constant population size, PIR 4 months after vaccination was 30% in all the scenarios. Predictions averaged over time showed mean PIR between 36% and 48%, which is below the population immunity thresholds for eradication approximated from R0 estimates.

The epidemiology of peste des petits ruminants in Pakistan and possible control policies.

Peste des petits ruminants made its first clinical appearance in Pakistan during an epidemic in Punjab Province in 1991, but its level of activity in subsequent years was never systematically recorded. In 2003, 2004 and 2005 teams trained in participatory disease surveillance methods visited a large number of villages throughout Pakistan to record the prevalence and impact of key livestock diseases. Peste des petits ruminants has emerged from their study as a common and economically damaging disease of small ruminants within the country, appearing to be endemic in the north of Punjab and epidemic in Azad Jammu and Kashmir, and Sindh during the study period. It should be possible to reduce the incidence level using a combination of zoosanitary measures and the intensive use of vaccine.

Participatory epidemiology in disease surveillance and research.

Participatory epidemiology is the application of participatory methods to epidemiological research and disease surveillance. It is a proven technique which overcomes many of the limitations of conventional epidemiological methods, and has been used to solve a number of animal health surveillance and research problems. The approach was developed in small-scale, community animal health programmes, and then applied to major international disease control efforts. The Global Rinderpest Eradication Program adopted participatory epidemiology as a surveillance tool for controlling rinderpest. This approach was subsequently used in both rural and urban settings in Africa and Asia, for foot and mouth disease, peste des petits ruminants and highly pathogenic avian influenza. Participatory disease surveillance has made an important contribution towards controlling both rare and common diseases. This paper reviews the principal applications of participatory epidemiology and highlights the lessons learned from field applications. In addition, the authors examine future challenges and consider new areas for research.

A model of contagious bovine pleuropneumonia transmission dynamics in East Africa.

The dynamics of contagious bovine pleuropneumonia (CBPP) transmission vary widely between livestock production systems. This paper describes the development of a homogeneous, stochastic, compartmental model for CBPP transmission in pastoral herds of East Africa. The model was built using parameter estimates based on data published in the literature and on observations of livestock owners obtained through participatory research. The basic reproduction number for CBPP in southern Sudan was estimated to range from 3.2 to 4.6. The homogeneous model indicates that the critical community size for the persistence of CBPP falls within the typical herd sizes for pastoral communities in East Africa suggesting that individual isolated herds are capable of maintaining infection indefinitely. Vaccination alone with currently available vaccines was unlikely to eradicate the disease.

A heterogeneous population model for contagious bovine pleuropneumonia transmission and control in pastoral communities of East Africa.

Pastoral cattle live in highly structured communities characterized by complex contact patterns. The present paper describes a spatially heterogeneous model for the transmission of contagious bovine pleuropneumonia (CBPP) developed specifically for pastoral communities of East Africa. The model is validated against serological data on the prevalence of CBPP infection in several communities of southern Sudan and against livestock owner information on community structure, livestock contact and cattle exchange. The model is used to assess the impact of alternative control strategies including mass and elective vaccination programmes, potential treatment regimes and the combination of vaccination and treatment in a single unified strategy. The results indicate that the eradication of CBPP using mass vaccination with currently available vaccines is unlikely to succeed. On the other hand, elective control programmes based on herd level vaccination, treatment of clinical cases or a combination of both vaccination and treatment enabled individual livestock owners to capture a large benefit in terms of reduced animal-level prevalence and mortality experience. The most promising intervention scenario was a programme which combined the vaccination of healthy animals with treatment of clinical cases.

A model of lineage-1 and lineage-2 rinderpest virus transmission in pastoral areas of East Africa.

The development of a stochastic, state-transition model of rinderpest transmission dynamics is described using parameter estimates obtained from both laboratory and participatory research. Using serological data, the basic reproduction numbers for lineage-1 rinderpest virus in southern Sudan and for lineage-2 rinderpest virus in Somali livestock were estimated as 4.4 and between 1.2 and 1.9, respectively. The model predictions for the inter-epidemic period in Sudan and Somalia (1.2 and 4.2 years, respectively) were in agreement with analysis of livestock-owner reports (1-2 years and 5 years, respectively).

Para-veterinary professionals and the development of quality, self-sustaining community-based services.

Livestock are a major asset for rural households throughout the developing world and are increasingly regarded as a means of reducing poverty. However, many rural areas are characterised by limited or no accessibility to veterinary services. Economic theory indicates that primary level services can be provided by para-veterinary professionals working as private operators and as an outreach component of veterinary clinics and pharmacies in small urban centres. Experience from the development of community-based animal health worker (CAHW) systems indicates that these workers can have a substantial impact on livestock morbidity and mortality through the treatment or prevention of a limited range of animal health problems. Factors for success include community involvement in the design and implementation of these systems, and involvement of the private sector to supply and supervise CAHWs. Examples of privatised and veterinary supervised CAHW networks are cited to show the considerable potential of this simple model to improve primary animal health services in marginalised areas. An analysis of constraints indicates that inappropriate policies and legislation are a major concern. By referring to the section on the evaluation of Veterinary Services in the OIE (World organisation for animal health) Terrestrial Animal Health Code, the paper proposes guidelines to assist governments in improving the regulation, quality, and co-ordination of privatised, veterinary supervised CAHW systems.

Ex-ante economic analysis of animal disease surveillance.

This paper provides an ex-ante economic analysis comparing four alternative intervention strategies for the control and eradication of rinderpest against a scenario of no intervention in a cattle population similar in size to that of Ethiopia. The interventions were three different coverage levels of mass vaccination and one surveillance-based programme where vaccination targeted infected sub-populations. For each scenario, the disease impact was estimated using an open-population, state-transition SEIR ('susceptible', 'exposed', 'infectious', 'recovered') disease transmission model with parameter estimates developed for lineage 1 rinderpest virus. Projected economic surplus gains and costs estimated from the rinderpest eradication programme in Ethiopia were analysed using benefit-cost methods. Social net present values (NPVs) and benefit-cost ratios (BCRs) were calculated. Although the economic model found that BCRs were greater than one for all interventions examined, the scenarios of intensive mass vaccination (75% vaccination coverage) and surveillance with targeted vaccination were economically preferable. The BCRs for these strategies were 5.08 and 3.68, respectively. Sensitivity analysis revealed that an increase in market prices for beef and milk increased the value of economic loss, the economic surplus and returns to investments in terms of NPVs and BCRs. An increase in demand and supply elasticities for beef and milk decreased the value of economic losses. This also had a negative effect on economic surplus and NPVs. The effect of an increase in the discount rate reduced returns to investments, with lower NPVs and BCRs. The authors note that 75% mass vaccination coverage was attempted in Ethiopia in the early 1990s, but failed to eradicate rinderpest because the approach was logistically too difficult to implement in practice. Subsequently, an effective surveillance and epidemiologically targeted vaccination programme was developed and has apparently resulted in the eradication of rinderpest from Ethiopia (the last case was recorded in 1996). The authors conclude that epidemio-surveillance with targeted vaccination is both an economically viable and realistic strategy and offers benefits that extend beyond rinderpest eradication.

Use of participatory epidemiology in studies of the persistence of lineage 2 rinderpest virus in East Africa.

In 1994, rinderpest virus of African lineage 2 was detected in East Africa after an apparent absence of more than 30 years. In 1996, a disease search, based on participatory epidemiological techniques supplemented by serological and virological analyses, was undertaken in southern Somalia and north-eastern Kenya to collate past and current epidemiological information about rinderpest-compatible disease events, and to test the hypothesis that African lineage 2 rinderpest virus persists in populations of transhumant cattle in the Somali ethnic areas. The findings in Afmadu in Lower Juba led the search for rinderpest to the communities in the Bardera area and then on to the Kenya/Somalia border areas between Mandera and El Wak. The herders had a specific knowledge of the clinical signs of rinderpest and provided detailed and accurate descriptions of cases. They differentiated between classical acute rinderpest and a milder syndrome characterised by an ocular discharge and diarrhoea, few oral lesions, corneal opacity and occasional mortality. The studies provided evidence for the endemic occurrence of rinderpest back to at least 1981, with a periodicity of five years in the incidence of the disease. After a period of high mortality in 1992 to 1993, around Afmadu, herders reported a mild disease, with occasional increases in mortality, from other areas of Lower Juba and the Gedo Region. Reports by herders of a rinderpest-compatible disease in the El Wak area were pursued until active cases were located and rinderpest was confirmed.

Rinderpest surveillance performance monitoring using quantifiable indicators.

This paper describes an objective system of monitoring the performance of disease surveillance. The system was developed through dialogue with a number of countries in Africa and adopted as part of the Global Rinderpest Eradication Programme of the Food and Agriculture Organization of the United Nations. The performance monitoring system uses a clinical stomatitis-enteritis case definition, an outbreak investigation classification scheme, and a series of eight performance indicators to measure the sensitivity, specificity and timeliness of the surveillance system. Field-testing indicates that the approach is successful when good record-keeping is practiced and highlights the importance of dialogue in helping to ensure that the system is simple and acceptable. The system provides a quantitative measure of the efficacy of national disease surveillance programmes and of the quality of data derived from such programmes for use in international disease control, animal health information exchange and trade risk analysis.

Human T cell lymphotropic virus type I Tax activates IL-15R alpha gene expression through an NF-kappa B site.

IL-15 mRNA levels are increased in diseases caused by human T cell lymphotropic virus type I (HTLV-I). In this study, we demonstrated that IL-15Ralpha, the IL-15-specific binding receptor, mRNA and protein levels were also elevated in HTLV-I-infected cells. We showed that transient HTLV-I Tax expression lead to increased IL-15Ralpha mRNA levels. In addition, by using a reporter construct that bears the human IL-15Ralpha promoter, we demonstrated that Tax expression increased promoter activity by at least 4-fold. Furthermore, using promoter deletion constructs and gel shift analysis, we defined a functional NF-kappaB-binding motif in the human IL-15Ralpha promoter, suggesting that Tax activation of IL-15Ralpha is due, in part, to the induction of NF-kappaB. These data indicate that IL-15Ralpha is transcriptionally regulated by the HTLV-I Tax protein through the action of NF-kappaB. These findings suggest a role for IL-15Ralpha in aberrant T cell proliferation observed in HTLV-I-associated diseases.

How does interleukin 15 contribute to the pathogenesis of HTLV type 1-associated myelopathy/tropical spastic paraparesis?

HTLV-1 is the etiological agent of a neurological disease named HAM/TSP that has clinical characteristics similar to those of multiple sclerosis (MS). The PBMC obtained from HAM/TSP patients undergo spontaneous proliferation in the absence of addition of any exogenous cytokines in an ex vivo culture. This spontaneous proliferation has been thought to be due to the proliferation of T cells. It was demonstrated that this proliferation is, in part, due to the production of IL-2 and its receptor (IL-2Ralpha) by HTLV-1-infected T cells. In this review, we demonstrate that IL-15 production also contributes to the spontaneous proliferation of T cells obtained from HAM/TSP PBMC. We provide data indicating that IL-15 expression is elevated in HAM/TSP PBMC when compared to that of the normal donors. Furthermore, we demonstrate that IL-15 overexpression by HTLV-1 is due to Tax trans-activation of its promoter and induction of NF-kappaB transcription factors. On the basis of these studies, we propose a model in which HTLV-1 infection of T cells results in the production of both IL-2 and IL-15 cytokines, growth factors that support the proliferation of T cells.