Differences between coverage of yellow fever vaccine and the first dose of measles-containing vaccine: A desk review of global data sources.

INTRODUCTION: The strategy to Eliminate Yellow Fever Epidemics (EYE) is a global initiative that includes all countries with risk of yellow fever (YF) virus transmission. Of these, 40 countries (27 in Africa and 13 in the Americas) are considered high-risk and targeted for interventions to increase coverage of YF vaccine. Even though the World Health Organization (WHO) recommends that YF vaccine be given concurrently with the first dose of measles-containing vaccine (MCV1) in YF-endemic settings, estimated coverage for MCV1 and YF vaccine have varied widely. The objective of this study was to review global data sources to assess discrepancies in YF vaccine and MCV1 coverage and identify plausible reasons for these discrepancies. METHODS: We conducted a desk review of data from 34 countries (22 in Africa, 12 in Latin America), from 2006 to 2016, with national introduction of YF vaccine and listed as high-risk by the EYE strategy. Data reviewed included procured and administered doses, immunization schedules, routine coverage estimates and reported vaccine stock-outs. In the 30 countries included in the comparitive analysis, differences greater than 3 percentage points between YF vaccine and MCV1 coverage were considered meaningful. RESULTS: In America, there were meaningful differences (7-45%) in coverage of the two vaccines in 6 (67%) of the 9 countries. In Africa, there were meaningful differences (4-27%) in coverage of the two vaccines in 9 (43%) of the 21 countries. Nine countries (26%) reported MVC1 stock-outs while sixteen countries (47%) reported YF vaccine stock-outs for three or more years during 2006-2016. CONCLUSION: In countries reporting significant differences in coverage of the two vaccines, differences may be driven by different target populations and vaccine availability. However,these were not sufficient to completely explain observed differences. Further follow-up is needed to identify possible reasons for differences in coverage rates in several countries where these could not fully be explained.

The Public Health Benefits and Economic Value of Routine Yellow Fever Vaccination in Colombia.

OBJECTIVES: To evaluate the public health benefits and economic value of live-attenuated yellow fever (YF) 17D vaccine in Colombia. METHODS: A decision tree model was used to assess the theoretical impact of routine YF vaccination of 1-year-olds (no "catch-up") during the interepidemic period from 1980 to 2002, avoiding capturing the impact of YF vaccine introduction in 2003. The vaccine was assumed to be 99% effective, to provide lifetime protection, and to cover 85% of the target population. Costs per disability-adjusted life-year (DALY) averted were computed from payer and societal perspectives. Univariate sensitivity analyses were performed. RESULTS: During the interepidemic period, routine YF vaccination would have averted 2223 nonfatal cases of YF and 65 deaths, leading to an overall reduction of 1365 DALYs. The net cost of this vaccination would have been $25 964 813 (payer's perspective) and $16 535 465 (societal perspective). Cost per DALY averted was $19 022 and $12 114 from payer and societal perspectives, respectively (all costs in 2015 US dollars). Vaccination was considered cost-effective from both perspectives (ie, between 1- and 3-fold the gross domestic product per capita, $7158) and remains so if price per dose was $2.75 or less and $4.66 from payer and societal perspectives, respectively. Underreporting had the largest impact on the results. CONCLUSIONS: Routine toddler YF vaccination in Colombia would have been considered cost-effective in the prevaccination era. This study provides insights on the value of vaccination in an upper middle-income country.

Evaluating scenarios of locations and capacities for vaccine storage in Nigeria.

Many developing countries still face the prevalence of preventable childhood diseases because their vaccine supply chain systems are inadequate by design or structure to meet the needs of their populations. Currently, Nigeria is evaluating options in the redesign of the country's vaccine supply chain. Using Nigeria as a case study, the objective is to evaluate different regional supply chain scenarios to identify the cost minimizing optimal hub locations and storage capacities for doses of different vaccines to achieve a 100% fill rate. First, we employ a shortest-path optimization routine to determine hub locations. Second, we develop a total cost minimizing routine based on stochastic optimization to determine the optimal capacities at the hubs. This model uses vaccine supply data between 2011 and 2014 provided by Nigeria's National Primary Health Care Development Agency (NPHCDA) on Tuberculosis, Polio, Yellow Fever, Tetanus Toxoid, and Hepatitis B. We find that a two-regional system with no central hub (NC2) cut costs by 23% to achieve a 100% fill rate when compared to optimizing the existing chain of six regions with a central hub (EC6). While the government's leading redesign alternative - no central three-hub system (Gov NC3) - reduces costs by 21% compared with the current EC6, it is more expensive than our NC2 system by 3%. In terms of capacity increases, optimizing the current system requires 42% more capacity than our NC2 system. Although the proposed Gov NC3 system requires the least increase in storage capacity, it requires the most distance to achieve a 100% coverage and about 15% more than our NC2. Overall, we find that improving the current system with a central hub and all its variants, even with optimal regional hub locations, require more storage capacities and are costlier than systems without a central hub. While this analysis prescribes the no central hub with two regions (NC2) as the least cost scenario, it is imperative to note that other configurations have benefits and comparative tradeoffs. Our approach and results offer some guidance for future vaccine supply chain redesigns in countries with similar layouts to Nigeria's.

Is the absence or intermittent YF vaccination the major contributor to its persistent outbreaks in eastern Africa?

Despite the availability of a safe and efficacious yellow fever vaccine since 1937, yellow fever remains a public health threat as a re-emerging disease in Africa and South America. We reviewed the trend of reported yellow fever outbreaks in eastern African countries, identified the risk epidemiological factors associated with the outbreaks and assessed the current situation of Yellow Fever vaccination in Africa. Surveillance and case finding for yellow fever in Africa are insufficient primarily due to lack of appropriate diagnostic capabilities, poor health infrastructure resulting in under-recognition, underreporting and underestimation of the disease. Despite these challenges, Ethiopia reported 302,614 cases (30,505 deaths) in 1943-2015, Kenya had 207 cases (38 deaths) in 1992-2016, Sudan experienced 31,750 suspected cases (1855 deaths) from 1940 to 2012 and Uganda had 452 cases (65 deaths) in 1941-2016. Major risk factors associated with past yellow fever outbreaks include climate, human practices and virus genetics. Comparisons between isolates from different outbreaks after 45 years have revealed the genetic stability of the structural proteins of YFV which are the primary targets of the host immune cells. This probably explains why yellow fever 17D vaccine is considered as outstandingly efficacious and safe after being used for 75 years. However, the 14 amino-acid changes among these isolates may have a greater impact on the changing disease epidemiology, virulence and transmission rate. Low population immunity against YF influences outbreak frequency especially in countries where the incorporation of YF vaccination is not combined with mass vaccination campaigns or vaccination is limited to international travellers. Understanding Yellow fever virus epidemiology as determined by its evolution underscores appropriate disease mitigation strategies and immunization policies. Mobilizing scarce resources to enhance population immunity through sufficient vaccination, promoting environmental sanitation/hygienic practices, driving behavioral change and community-based vector control are significant to preventing future epidemics.

[Microeconomic evaluation of a mass preventive immunisation campaign against meningococcal meningitis and yellow fever in Senegal in 1997]. / Evaluation des coûts opérationnels d'une campagne de masse préventive contre la méningite à méningocoque et la fièvre jaune au Sénégal, en 1997.

Large epidemics of group A meningococcal meningitis occurred in 1995 and 1996 in several countries of the Sub-Saharan Africa zone known as the "meningitis belt", and more particularly in West Africa. Most of these countries affected by the epidemics met difficulties to set up the strategy recommended by the World Health Organization and which includes: Epidemiological surveillance and epidemic incidence threshold calculation to detect early meningitis epidemics and emergency vaccination campaigns with meningococcal A + C polysaccharide vaccine, if possible within the 4-to-6 weeks following the moment the threshold is reached. In this context of epidemics, notably in Mali, and in front of the risk of resurgence of yellow fever, the Ministry of Health of Senegal decided to conduct mass preventive immunization campaigns in 1997 against meningo- coccal meningitis and yellow fever in the districts located in the eastern part of the country and where emergency vaccination would have been difficult in case of epidemic because these area are difficult to reach. A short-term microeconomic evaluation of additional costs that are necessary to organize one of these mass preventive immunization campaigns was conducted in 1997 in the Matam District, in the Northeast part of Senegal. The method rested on value attribution and accounting procedure. The cost was defined as the monetary value of all mobilized resources to product the campaign corresponding to a plurality of charges and representing all of the effective expenses and donations. During this campaign, 85,925 people were vaccinated and a total number of 163,981 doses of both polysaccharide A + C meningococcal and yellow fever vaccines were administered within 3 weeks. Four intervention strategies were involved: Three for vaccination (mobile, fixed and outreach strategy) and one for coordination, information and training. The total cost of the campaign was 55,322.75 euros. Vaccines and solvents represented 60% of the total cost of the campaign, materiel for injection and safety of injection 26%, vaccination staff 7%, and logistics 7%. The mean cost was 0.34 euro per administered dose and 0.64 euro per vaccinee. The mean cost per administered dose of meningococcal vaccine was 0.44 euro. The mean cost of preventive meningococcal immunization was not higher than the mean cost of meningococcal vaccination during mass emergency immunization campaigns in other countries. The addition of yellow fever antigen brought down the campaign mean cost by 0.11 euro and it allowed economies of scales. Direct unit costs per administered dose were higher when people were vaccinated through the outreach strategy (0.35 euro) than when fixed and mobile strategies were used (0.318 and 0.323 euro, respectively). Costs related to transportation and staff were proportionally higher for the outreach strategy. Direct unit costs per administered dose were higher when vaccinations were done in rural areas (0.32 euro) than when done in urban areas (0.31 euro). Direct unit costs increased when the size of target communities decreased (in communities with less than 100 people to vaccinate versus 0.38 euro in communities with more than 2,000 people to vaccinate). This study allowed us to set up a method to measure, describe and analyze the costs of a mass preventive campaign. It demonstrated the economic impact of using multiple antigens during a single preventive campaign.

Impact of yellow fever on the developing world.

Yellow fever (YF) has remained a disease of public health importance since it was first described in the fifteenth century. At different periods in human history, YF has caused untold hardship and indescribable misery among populations in the Americas, Europe, and Africa. It brought economic disaster in its wake, constituting a stumbling block to development. Yellow fever is an arboviral infection with three epidemiological transmission cycles between monkeys, mosquitoes, and humans. It is an acute infectious disease characterized by sudden onset, with two phases of development separated by a short period of remission. The clinical spectrum of YF varies from a very mild, nonspecific, febrile illness to a fulminating, sometimes fatal disease with pathognomonic features. In severe cases, jaundice and bleeding diathesis with hepatorenal involvement are common. The fatality rate of severe YF is 50% or higher. Despite landmark achievements in the understanding of the epidemiology of YF and the availability of a safe, efficacious vaccine, YF remains a major public health problem in both Africa and South America, where annually the disease affects an estimated 200,000 persons, causing an estimated 30,000 deaths. Since the 1980s epidemics of YF in Africa have affected predominantly children under the age of 15 years. The failure to control YF arises from a misapplication of public health strategies and insufficient political commitment by governments in YF endemic areas, especially in Africa, to control the disease.

A febre amarela na regiäo de Ribeiräo Preto durante a virada do século XIX: importancia científica e repercussöes econômicas / Yellow fever in the region of Ribeiräo Preto at the end of the Nineteenth Century: scientific importance and economic repercussions

Yellow fever in the Region of Ribeirao Preto at the turn of XIX century: scientific importance and economic repercussion. This historical review describes the bad situation of public health in Brazil during the XIX Century caused by multiple yellow fever outbreaks. The knowledge regarding to yellow fever at that time is also described. A short history is presented of the development of the Region of Ribeirao Preto, located in the Northeast of Sao Paulo State, Brazil, emphasising the actuation of immigrants and pioneer coffee farmers like Luiz Pereira Barreto. Yellow fever outbreaks occurred in the City of Sao Simao in 1896, 1898, and 1902 are described as well as an outbreak in the City of Ribeirao Preto occurring in 1903. It is shown that yellow fever outbreaks were stopped in the 2 cities by Emilio Ribas who led the fight against the transmitting mosquito Aedes aegypti. Emilio Ribas, helped by Adolpho, Lutz and Luiz Pereira Barreto, promoted scientific experiments in order to confirm the vectorial transmission of yellow fever and to annul the supposed importance of other kinds of contagion. The yellow fever outbreaks caused damage to the development of Sao Simao and influenced the transference of the economic pole of the region to the City of Ribeirao Preto. The vector control work done during yellow fever outbreak and the scientific experiments on the transmission of yellow fever were important for the development of medical science and fpublic health in Brazil.

[Yellow fever in the Ribeirão Preto region at the turn of the 19th century: its scientific importance and economic repercussions]. / A febre amarela na região de Ribeirão Preto durante a virada do século XIX: importancia científica e repercussões econômicas.

Yellow fever in the Region of Ribeirao Preto at the turn of XIX century: scientific importance and economic repercussion. This historical review describes the bad situation of public health in Brazil during the XIX Century caused by multiple yellow fever outbreaks. The knowledge regarding to yellow fever at that time is also described. A short history is presented of the development of the Region of Ribeirao Preto, located in the Northeast of Sao Paulo State, Brazil, emphasising the actuation of immigrants and pioneer coffee farmers like Luiz Pereira Barreto. Yellow fever outbreaks occurred in the City of Sao Simao in 1896, 1898, and 1902 are described as well as an outbreak in the City of Ribeirao Preto occurring in 1903. It is shown that yellow fever outbreaks were stopped in the 2 cities by Emilio Ribas who led the fight against the transmitting mosquito Aedes aegypti. Emilio Ribas, helped by Adolpho, Lutz and Luiz Pereira Barreto, promoted scientific experiments in order to confirm the vectorial transmission of yellow fever and to annul the supposed importance of other kinds of contagion. The yellow fever outbreaks caused damage to the development of Sao Simao and influenced the transference of the economic pole of the region to the City of Ribeirao Preto. The vector control work done during yellow fever outbreak and the scientific experiments on the transmission of yellow fever were important for the development of medical science and fpublic health in Brazil.