Search

A team of interdisciplinary researchers undertook a mixed methods, participatory epidemiology (PE) based study as part of a pilot project for localized control of Peste des petits ruminants (PPR), a small ruminant disease of high socio-economic impact. Mixed methods research combines qualitative and quantitative methods, allowing iterative comparison of results to arrive at a more comprehensive and informed outcome. In this study, the use of PE and a household survey (HHS) resulted in contradictory results. However, the mixed methods approach also facilitated the detection and the explanation of bias in the HHS, which may have gone undetected and unexplored had only one method been used. Results show that logistical constraints leading to a failure to apply key aspects of the sampling strategy led to problematic gender/ethnic composition of the HHS sample population. Additionally, while PE findings on local disease and terminology were integrated during HHS development and training, there is apparent measurement error related to enumerator bias in HHS results, possibly due to insufficient respondent understanding or a lack of analytic clarity. The extensive nature of the PE, surveillance methodologies used in the initial site assessment, and formative research for the HHS allowed for a critical analysis and interpretation of HHS results as well as reflection on the research process. The findings of this paper underscore the (1) flexibility and utility of participatory methods, (2) the importance of mixed methods research in designing health interventions, and (3) the necessity of tight integration of study design with team planning for implementation of research in environments such as Karamoja, Uganda. If all three are to be achieved not only researchers but funders must provide these space and structure beginning in the study design phase. These findings are relevant in many places, but have particular importance for international, interdisciplinary teams working from various on-and-off-site locations with traditional or indigenous knowledge systems., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Growing evidence suggests that multiple wildlife species can be infected with peste des petits ruminants virus (PPRV), with important consequences for the potential maintenance of PPRV in communities of susceptible hosts, and the threat that PPRV may pose to the conservation of wildlife populations and resilience of ecosystems. Significant knowledge gaps in the epidemiology of PPRV across the ruminant community (wildlife and domestic), and the understanding of infection in wildlife and other atypical host species groups (e.g., camelidae, suidae, and bovinae) hinder our ability to apply necessary integrated disease control and management interventions at the wildlife-livestock interface. Similarly, knowledge gaps limit the inclusion of wildlife in the FAO/OIE Global Strategy for the Control and Eradication of PPR, and the framework of activities in the PPR Global Eradication Programme that lays the foundation for eradicating PPR through national and regional efforts. This article reports on the first international meeting on, "Controlling PPR at the livestock-wildlife interface," held in Rome, Italy, March 27-29, 2019. A large group representing national and international institutions discussed recent advances in our understanding of PPRV in wildlife, identified knowledge gaps and research priorities, and formulated recommendations. The need for a better understanding of PPRV epidemiology at the wildlife-livestock interface to support the integration of wildlife into PPR eradication efforts was highlighted by meeting participants along with the reminder that PPR eradication and wildlife conservation need not be viewed as competing priorities, but instead constitute two requisites of healthy socio-ecological systems., (Copyright © 2020 Fine, Pruvot, Benfield, Caron, Cattoli, Chardonnet, Dioli, Dulu, Gilbert, Kock, Lubroth, Mariner, Ostrowski, Parida, Fereidouni, Shiilegdamba, Sleeman, Schulz, Soula, Van der Stede, Tekola, Walzer, Zuther, Njeumi and Meeting Participants.)

This paper describes an assessment of the patterns of peste des petits ruminants virus circulation in the Karamoja subregion of Uganda conducted to identify the communities that maintain the virus and inform the development of a targeted vaccination strategy. Participatory epidemiological methods were used to develop an operational hypothesis for the patterns of PPR in Karamoja that was subsequently validated through outbreak investigation and genomics. The participatory epidemiological assessment included risk mapping with livestock owners, community animal health workers and veterinarians and indicated there were two critical foci of virus transmission on the Uganda-Kenya border. One was located in two adjacent subcounties of Kotido and Kaabong Districts in northern Karamoja and the other in Loroo subcounty of Amudat District in southern Karamoja. Participants reported that these were locations where outbreaks were usually first observed in Karamoja and subsequently spread to other areas. Following the participatory assessment, surveillance activities were implemented across the Karamoja subregion in 2018. Three outbreak were detected, investigated and sampled. Two outbreaks were located in the northern and one on the southern focus of transmission. No Outbreaks were diagnosed in Karamoja outside of these foci during 2018. Genomics indicated different clusters of viruses were associated with the northern and southern foci that were more closely related to other East African isolates than to each other. This indicates these are two separate systems of virus circulation which should be explicitly addressed in eradication as separate cross-border systems that require integrated cross-border interventions.

The research objective was to develop a thermostable vaccine against peste des petits ruminants (PPR), a morbilliviral disease of small ruminants targeted for eradication that is a major constraint on the livelihoods of the rural poor throughout much of Africa and Asia. Although existing PPR vaccines provide life-long immunity, they require continuous refrigeration. This limits their utility in developing countries. Methods for the lyophilization of a related morbillivirus, rinderpest (RP), resulted in vaccine that could be used in the field for up to 30days without refrigeration which was a major contribution to the global eradication of RP completed in 2011. The present research applied the rinderpest lyophilization method to the attenuated Nigeria 75/1 PPR vaccine strain, and measured thermostability in accelerated stability tests (AST) at 37°C. The shelf-life of the vaccine was determined as the time a vial retained the minimum dose required as a 25-dose presentation at the specified temperature. A lactalbumin hydrolysate and sucrose (LS) stabilizer was compared to stabilizers based on trehalose. PPR vaccine produced using the Xerovac drying method was compared to vaccine produced using the rinderpest lyophilization method in AST. LS vaccine was evaluated in AST at 37, 45 and 56°C and an Arrhenius plot was constructed for estimation of stability at temperatures not tested. Vaccines produced using LS and the rinderpest method of lyophilization were the most stable. The shelf-life of the Xerovac preparation was 22.2days at 37°C. The three LS vaccine batches had shelf-lives at 37°C of 177.6, 105.0 and 148.9days, respectively, at 37°C. At 56°C, the shelf-life was 13.7days. The projected half-life at 25°C was 1.3years. This is sufficient thermostability for use without a cold chain for up to 30days which will greatly facilitate the delivery of vaccination in the global eradication of PPR., (Copyright © 2017. Published by Elsevier Ltd.)

Peste des petits ruminants (PPR) is a highly infectious disease of sheep and goats that is caused by PPR virus, a member of the genus Morbillivirus that includes the viruses that cause rinderpest (RP) in cattle. RP was the first animal disease to be globally eradicated in 2011 and is only the second disease, after smallpox, to have ever been eradicated. PPR is one of the principal constraints to small ruminant production in Africa, Asia, and the Middle East. The epidemiology of PPR and RP as well as the technologies available for their diagnosis and control are similar. The conditions that favored the eradication of RP are also largely present for PPR. In this work, we outline the evolving strategy for eradication in light of current opportunities and challenges, as well as the lessons from other eradication programs in animal and human health. The global PPR situation and technology for its control are summarized. A strategy based on the lessons from previous eradication efforts that integrate epidemiology, social science, and economics as tools to target and motivate vaccination is summarized. Major aspects of the cost and benefit-cost analysis of the indicated program are presented. The overall undiscounted cost of eradication was estimated as $3.1 billion, and the benefit-cost ratio for the most likely scenario was estimated at 33.8. We close with a discussion of the possible next steps., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Peste des petits ruminants (PPR) is an important cause of mortality and production loss among sheep and goats in the developing world. Despite control efforts in a number of countries, it has continued to spread across Africa and Asia, placing an increasing burden on the livelihoods of livestock keepers and on veterinary resources in affected countries. Given the similarities between PPR and rinderpest, and the lessons learned from the successful global eradication of rinderpest, the eradication of PPR seems appealing, both eliminating an important disease and improving the livelihoods of the poor in developing countries. We conducted a benefit-cost analysis to examine the economic returns from a proposed programme for the global eradication of PPR. Based on our knowledge and experience, we developed the eradication strategy and estimated its costs. The benefits of the programme were determined from (i) the averted mortality costs, based on an analysis of the literature, (ii) the downstream impact of reduced mortality using a social accounting matrix, and (iii) the avoided control costs based on current levels of vaccination. The results of the benefit-cost analysis suggest strong economic returns from PPR eradication. Based on a 15-year programme with total discounted costs of US$2.26 billion, we estimate discounted benefits of US$76.5 billion, yielding a net benefit of US$74.2 billion. This suggests a benefit cost ratio of 33.8, and an internal rate of return (IRR) of 199%. As PPR mortality rates are highly variable in different populations, we conducted a sensitivity analysis based on lower and higher mortality scenarios. All the scenarios examined indicate that investment in PPR eradication would be highly beneficial economically. Furthermore, removing one of the major constraints to small ruminant production would be of considerable benefit to many of the most vulnerable communities in Africa and Asia.

Contagious bovine pleuropneumonia (CBPP) is a cattle disease that has hampered the development of the livestock sector in sub-Saharan Africa. Currently, vaccination with a live vaccine strain is its recommended control measure although unofficial antimicrobial use is widely practiced. Here, modelling techniques are used to assess the potential impact of early elimination of infected cattle via accurate diagnosis on CBPP dynamics. A herd-level stochastic epidemiological model explicitly incorporating test sensitivity and specificity is developed. Interventions by annual vaccination, annual testing and elimination and a combination of both are implemented in a stepwise manner and their effectiveness compared by running 1000 simulations per intervention over ten years. The model predicts that among the simulated interventions, the ones likely to eliminate the disease from an isolated herd all involved annual vaccination of more than 75% of the animals with a vaccine that protects for at least 18 months combined with annual testing (and elimination of positive reactors) of 75% of the animals every six months after vaccination. The highest probability of disease elimination was 97.5% and this could occur within a median of 2.3 years. Generally, our model predicts that regular testing and elimination of positive reactors using improved tests will play a significant role in minimizing CBPP burden especially in the current situation where improved vaccines are yet to be developed.

Participatory surveillance (PS) is the application of participatory rural appraisal methods to the collection of epidemiological information to inform decision-making and action. It was applied in Africa and Asia as part of emergency programs to address the H5N1 highly pathogenic avian influenza (HPAI) pandemic. The approach resulted in markedly increased case detection in countries experiencing HPAI, and a better understanding of the epidemiological situation. Where HPAI was absent and PS was implemented, the method did not result in false positives and contributed to the overall epidemiological assessment that the country was free of disease. It was noted that clarity of surveillance objectives and resulting data needs at the outset was essential to optimize the balance of surveillance methods, size of the program and costs. The quality of training programs and adherence to international guidelines on good PS training practice were important for assuring the competence of PS practitioners. Orientation of senior decision-makers was an important step in assuring effective program management and appropriate use of results. As a problem-solving methodology, PS is best used to rapidly assess situations and inform strategy. Several countries continued PS after the end of projects and went on to apply PS to other health challenges.

Contagious bovine pleuropneumonia (CBPP) caused by Mycoplasma mycoides subsp. mycoides (Mmm) is an economically very important cattle disease in sub-Saharan Africa. CBPP impacts animal health and poverty of livestock-dependent people through decreased animal productivity, reduced food supply, and the cost of control measures. CBPP is a barrier to trade in many African countries and this reduces the value of livestock and the income of many value chain stakeholders. The presence of CBPP also poses a constant threat to CBPP-free countries and creates costs in terms of the measures necessary to ensure the exclusion of disease. This opinion focuses on the biomedical research needed to foster the development of better control measures for CBPP. We suggest that different vaccine development approaches are followed in parallel. Basic immunology studies and systematic OMICs studies will be necessary in order to identify the protective arms of immunity and to shed more light on the pathogenicity mechanisms in CBPP. Moreover a robust challenge model and a close collaboration with African research units will be crucial to foster and implement a new vaccine for the progressive control of this cattle plague.

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., (© World Organisation for Animal Health (OIE), 2012)

Rinderpest is only the second infectious disease to have been globally eradicated. In the final stages of eradication, the virus was entrenched in pastoral areas of the Greater Horn of Africa, a region with weak governance, poor security, and little infrastructure that presented profound challenges to conventional control methods. Although the eradication process was a development activity rather than scientific research, its success owed much to several seminal research efforts in vaccine development and epidemiology and showed what scientific decision-making and management could accomplish with limited resources. The keys to success were the development of a thermostable vaccine and the application of participatory epidemiological techniques that allowed veterinary personnel to interact at a grassroots level with cattle herders to more effectively target control measures.

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.

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.

To capture lessons from the 2007 Rift Valley fever (RVF) outbreak, epidemiological studies were carried out in Kenya and Tanzania. Somali pastoralists proved to be adept at recognizing symptoms of RVF and risk factors such as heavy rainfall and mosquito swarms. Sandik, which means "bloody nose," was used by Somalis to denote disease consistent with RVF. Somalis reported that sandik was previously seen in 1997/98, the period of the last RVF epidemic. Pastoralists communicated valuable epidemiological information for surveillance and early warning systems that was observed before international warnings. The results indicate that an all or none approach to decision making contributed to the delay in response. In the future, a phased approach balancing actions against increasing risk of an outbreak would be more effective. Given the time required to mobilize large vaccine stocks, emergency vaccination did not contribute to the mitigation of explosive outbreaks of RVF.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

Samples of eyelid, tongue, soft palate and palatine tonsil were collected from calves infected experimentally with rinderpest virus. The tissues were fixed in 10 per cent neutral buffered formalin immediately, 24 or 48 hours post mortem. Then, after three days, 10 days, 28 days or three months in formalin, they were processed into paraffin blocks and examined immunohistochemically for rinderpest viral antigen. The tonsil was the best of the four tissues in providing a consistently positive immunohistochemical signal for the presence of virus, despite autolytic changes and/or prolonged fixation.

Rinderpest (RP), a lethal disease of cattle, was almost eradicated from the African continent under Joint Project 15 (JP15), using an excellent modified live virus vaccine. Due to marked instability of the vaccine, a cold chain was required to ensure that the vaccine was potent at the time of application. Rinderpest re-emerged in the early 1980s. The Pan African Rinderpest Campaign (PARC) was developed to combat the new epidemic. For PARC to be efficacious and affordable, there was a clear need to have a vaccine that was thermostable. The need for a stable vaccine was underscored in politically unstable areas such as the Sudan, where the veterinary infrastructure has diminished and vaccination has been left in the hands of personnel who must act expeditiously. This paper reviews studies on various stabilizers and a modified lyophilization cycle that resulted in a highly thermostable RP vaccine. The useful shelf life of the vaccine, under African field conditions, was increased from less than one week to at least 100 days. For practical reasons, PARC recommends that the vaccine be used within 30 days of leaving refrigeration (the cold chain).

A repository of domestic animal sera collected in Niger between 1984 and 1988 was assayed for antibody against two zoonotic hemorrhagic fever viruses known to be present in the West African Sahel. A total of 2,540 serum samples from 2,324 cattle, sheep, goats, and camels were tested by an IgG-specific enzyme-linked immunosorbent assay (ELISA) and the 80% plaque reduction neutralization test (PRNT80) for Rift Valley fever (RVF) virus antibody. Of the 2,540 sera tested for RVF-specific IgG antibody, 1,676 sera from cattle, sheep, and goats were examined for RVF-specific IgM antibody by ELISA. A subset of 2,263 sera were examined for evidence of Crimean-Congo hemorrhagic fever (CCHF) virus antibody by an IgG-specific ELISA. Antibody against CCHF virus was found to be most prevalent in adult cattle (422 of 732 or 57.7% positive) sampled at nine locations in the Niamey area. The highest prevalence for RVF neutralizing antibodies was found in camels from the Agadez Department with 67 (47.5%) of 141 positive. The results indicate that both CCHF and RVF viruses are circulating in Niger and are potential zoonotic health risks.

The thermostable Vero cell-adapted rinderpest vaccine was evaluated in terms of immunogenicity as a heterologous vaccine against peste des petits ruminants. A titration to establish the minimum immunising dose was performed in American mixed breed goats by vaccinating test subjects with dilutions of Vero cell-adapted rinderpest vaccine and then challenging 26 days later with virulent peste des petits ruminants virus. All animals were followed for virus neutralising antibodies against both rinderpest and peste des petits ruminants virus after vaccination and challenge. The antibody response to vaccination was primarily against rinderpest virus with very low levels of cross-reactivity to peste des petits ruminants virus. Following challenge, animals which possessed anti-rinderpest neutralising antibodies remained clinically normal but mounted strong anti-peste des petits ruminants virus neutralising antibody responses indicating that replication of challenge virus took place without the induction of illness. The 50 per cent minimum goat immunising dose was 3 tissue culture infectious doses 50 per cent (TCID50) as established by serological response and protection against challenge. The thermostable Vero cell-adapted rinderpest vaccine is a suitable immunogen for the protection of goats against peste des petits ruminants.

Ten goats were inoculated with peste des petits ruminants virus, a paramyxovirus closely related to rinderpest virus. All goats developed severe clinical disease, 8/10 having coughing or dyspnea as prominent clinical signs. In addition, all of the goats had stomatitis and diarrhea. Histopathologic and immunohistochemical studies were done only on the respiratory tracts. Pathologic changes ranged from mild multifocal bronchiolitis and bronchitis to severe bronchointerstitial pneumonia. Lesions were more severe in anteroventral than caudal lobes. The histologic nature of the viral process in the goat lungs had many features in common with the processes of pneumonia in dogs, due to canine distemper, or pneumonia in human beings, due to measles virus. Immunohistochemical staining of formalin-fixed, paraffin-embedded respiratory tract tissue was performed using an indirect system with rabbit anti-rinderpest virus serum, biotinylated anti-rabbit antibody, streptavidin-alkaline phosphatase, and nitroblue tetrazolium chromogen. Staining was sensitive, highlighting the presence of viral antigen in both lung and trachea of all goats. Viral antigen was found in both cytoplasm and nucleus of tracheal, bronchial, and bronchiolar epithelial cells, type II pneumocytes, syncytial cells, and alveolar macrophages. In general, the amount of staining correlated directly with the severity of the inflammatory process.

A lyophilized thermostable Vero cell-adapted ringerpest vaccine, stabilized with lactalbumin hydrolysate and sucrose, was tested for safety, serological response and suitability for use with an abbreviated cold chain under field conditions in Niger. A total of 480 cattle, 90 goats and 55 sheep of unknown serological status were vaccinated on government ranches and observed for at least 22 days. No untoward effects of the vaccine were detected. The serological response to the vaccine stored at environmental temperatures for 30 to 34 days was determined in 144 previously unvaccinated yearling calves. Seroconversion was demonstrated in 98% of the yearling calves using seroneutralization. The un-refrigerated vaccine retained a titer of 3.69 log10 TCID50 per dose through day 34.

The thermostability of a rinderpest vaccine produced on Vero cells was evaluated using a variety of chemical stabilizers and lyophilization protocols. Three stabilizer preparations and three lyophilization schedules were examined using accelerated stability testing at 37 degrees C. The vaccine preparation exhibiting the greatest stability at 37 degrees C was tested at three additional temperatures, 42, 45 and 56 degrees C, and an Arrhenius plot was constructed from the data. The stability of the reconstituted vaccine produced with the two most efficacious stabilizers was examined using three different diluent preparations. The stabilization method and high Vero cell virus batch titers resulted in a lyophilized vaccine which maintained the minimum required dose of log10 2.5 TCID50 tissue culture infectious dose for more than 20 weeks at 37 degrees C.

The effect of large-dose heparin therapy on erythrocyte mass depletion in ponies was investigated to determine whether stimulation of reticuloendothelial cell activity and catabolic function would be evidenced by enhanced catabolism of heme to bilirubin. Ponies with chronic external biliary fistula were used to examine biliary excretion of bilirubin both before and after heparin loading (107 U/kg, IV, plus 320 U/kg, subcutaneously) and at maintenance dosages of 320 U/kg given (subcutaneously) at 12 and 24 hours after initial loading with heparin. Results indicated that by 48 hours after ponies were first treated with heparin, catabolism of heme increased, resulting in a 35% increase in plasma bilirubin concentration and a 65% enhancement in biliary bilirubin excretion. During this period, both hematocrit and blood hemoglobin concentrations decreased by 35%. After the last heparin treatment at 24 hours after initial heparin loading, all measured variables returned toward base line within 48 hours. These studies indicated that heparin augments phagocytosis of erythrocytes, resulting in enhanced plasma bilirubin concentration and biliary bilirubin excretion.