Yellow Fever in Africa: Estimating the Burden of Disease and Impact of Mass Vaccination from Outbreak and Serological Data

Background

Yellow fever is a vector-borne disease affecting humans and non-human primates in tropical areas of Africa and South America. While eradication is not feasible due to the wildlife reservoir, large scale vaccination activities in Africa during the 1940s to 1960s reduced yellow fever incidence for several decades. However, after a period of low vaccination coverage, yellow fever has resurged in the continent. Since 2006 there has been substantial funding for large preventive mass vaccination campaigns in the most affected countries in Africa to curb the rising burden of disease and control future outbreaks. Contemporary estimates of the yellow fever disease burden are lacking, and the present study aimed to update the previous estimates on the basis of more recent yellow fever occurrence data and improved estimation methods.

Methods and Findings

Generalised linear regression models were fitted to a dataset of the locations of yellow fever outbreaks within the last 25 years to estimate the probability of outbreak reports across the endemic zone. Environmental variables and indicators for the surveillance quality in the affected countries were used as covariates. By comparing probabilities of outbreak reports estimated in the regression with the force of infection estimated for a limited set of locations for which serological surveys were available, the detection probability per case and the force of infection were estimated across the endemic zone.The yellow fever burden in Africa was estimated for the year 2013 as 130,000 (95% CI 51,000–380,000) cases with fever and jaundice or haemorrhage including 78,000 (95% CI 19,000–180,000) deaths, taking into account the current level of vaccination coverage. The impact of the recent mass vaccination campaigns was assessed by evaluating the difference between the estimates obtained for the current vaccination coverage and for a hypothetical scenario excluding these vaccination campaigns. Vaccination campaigns were estimated to have reduced the number of cases and deaths by 27% (95% CI 22%–31%) across the region, achieving up to an 82% reduction in countries targeted by these campaigns. A limitation of our study is the high level of uncertainty in our estimates arising from the sparseness of data available from both surveillance and serological surveys.

Conclusions

With the estimation method presented here, spatial estimates of transmission intensity can be combined with vaccination coverage levels to evaluate the impact of past or proposed vaccination campaigns, thereby helping to allocate resources efficiently for yellow fever control. This method has been used by the Global Alliance for Vaccines and Immunization (GAVI Alliance) to estimate the potential impact of future vaccination campaigns. Please see later in the article for the Editors'' Summary     

Assessing the impact of preventive mass vaccination campaigns on yellow fever outbreaks in Africa: A population-level self-controlled case series study

BackgroundThe Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, to what extent PMVCs are associated with a decreased risk of outbreak has not yet been quantified.Methods and findingsWe used the self-controlled case series (SCCS) method to assess the association between the occurrence of yellow fever outbreaks and the implementation of PMVCs at the province level in the African endemic region. As all time-invariant confounders are implicitly controlled for in the SCCS method, this method is an alternative to classical cohort or case–control study designs when the risk of residual confounding is high, in particular confounding by indication. The locations and dates of outbreaks were identified from international epidemiological records, and information on PMVCs was provided by coordinators of vaccination activities and international funders. The study sample consisted of provinces that were both affected by an outbreak and targeted for a PMVC between 2005 and 2018. We compared the incidence of outbreaks before and after the implementation of a PMVC. The sensitivity of our estimates to a range of assumptions was explored, and the results of the SCCS method were compared to those obtained through a retrospective cohort study design. We further derived the number of yellow fever outbreaks that have been prevented by PMVCs. The study sample consisted of 33 provinces from 11 African countries. Among these, the first outbreak occurred during the pre-PMVC period in 26 (79%) provinces, and during the post-PMVC period in 7 (21%) provinces. At the province level, the post-PMVC period was associated with an 86% reduction (95% CI 66% to 94%, p < 0.001) in the risk of outbreak as compared to the pre-PMVC period. This negative association between exposure to PMVCs and outbreak was robustly observed across a range of sensitivity analyses, especially when using quantitative estimates of vaccination coverage as an alternative exposure measure, or when varying the observation period. In contrast, the results of the cohort-style analyses were highly sensitive to the choice of covariates included in the model. Based on the SCCS results, we estimated that PMVCs were associated with a 34% (95% CI 22% to 45%) reduction in the number of outbreaks in Africa from 2005 to 2018. A limitation of our study is the fact that it does not account for potential time-varying confounders, such as changing environmental drivers of yellow fever and possibly improved disease surveillance.ConclusionsIn this study, we provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. This study illustrates that the SCCS method can be advantageously applied at the population level in order to evaluate a public health intervention.

In this cohort study, Kévin Jean and colleagues correlate lower risk of disease outbreaks with mass vaccination against yellow fever.     

Yellow Fever Outbreaks in Unvaccinated Populations,Brazil, 2008–2009

Due to the risk of severe vaccine-associated adverse events, yellow fever vaccination in Brazil is only recommended in areas considered at risk for disease. From September 2008 through June 2009, two outbreaks of yellow fever in previously unvaccinated populations resulted in 21 confirmed cases with 9 deaths (case-fatality, 43%) in the southern state of Rio Grande do Sul and 28 cases with 11 deaths (39%) in Sao Paulo state. Epizootic deaths of non-human primates were reported before and during the outbreak. Over 5.5 million doses of yellow fever vaccine were administered in the two most affected states. Vaccine-associated adverse events were associated with six deaths due to acute viscerotropic disease (0.8 deaths per million doses administered) and 45 cases of acute neurotropic disease (5.6 per million doses administered). Yellow fever vaccine recommendations were revised to include areas in Brazil previously not considered at risk for yellow fever.     

Yellow fever and dengue—the interactions of virus,vector and host in the re-emergence of epidemic disease

The incidence of the mosquito-borne flavivirus diseases, yellow fever, dengue and dengue hemorrhagic fever has increased dramatically in recent years. Both diseases are characterized by the emergence of explosive epidemics. Yellow fever outbreaks appear to have a periodicity dependent upon fluctuations in sylvatic (enzootic) transmission cycles and the ecological factors that influence these cycles. Spread of the virus from the sylvatic cycle to human settlements, ultimately with interhuman transmission by domestic Aedes aegypti is a repeating event in Africa, and presents a renewed threat in the Americas, where effective Ae. aegypti control collapsed in the 1970s. The incidence of dengue has also increased dramatically in recent years, with up to 80 million persons living in tropical regions of the world now affected annually—an attack rate of 4%. The severe form, dengue hemorrhagic fever (DHF) has become a leading health problem throughout Asia in the last 20 years and is emerging as an epidemic disease in the Americas. Unlike yellow fever, sylvatic dengue transmission cycles are not responsible for disease emergence. The major factors underlying dengue epidemics are changes in human ecology, increasing contact with Ae. aegypti, the co-circulation of multiple dengue serotypes, and a rising prevalence of immunity and immunopathological events that underlie the pathogenesis of DHF. In this review, the complex interplay of virus, host, vector, environment and weather in the ecology of yellow fever and dengue are explored.     

Emerging and reemerging infections in africa: the need for improved laboratory services and disease surveillance

Emerging and reemerging infections pose a serious public health threat to most countries of tropical Africa. In the past decade, epidemics of diseases including cholera, dysentery, meningitis, yellow fever and Ebola virus have resulted in significant morbidity and mortality. Improved laboratory services and disease surveillance systems are essential to monitor disease trends and to initiate public health action. The present situation of emerging and reemerging infections in Africa is described in this review, and strategies for improved disease surveillance and monitoring are discussed.     

Evaluation of Whatman FTA cards for the preservation of yellow fever virus RNA for use in molecular diagnostics

Yellow fever virus (YFV) is a flavivirus that frequently causes outbreaks of hemorrhagic fever in Africa and South America and is considered a reemerging public health threat. Accurate diagnosis of yellow fever (YF) disease is critical as one confirmed case constitutes an outbreak and may trigger a mass vaccination campaign. Highly sensitive and specific molecular diagnostics have been developed; however, these assays require maintenance of cold-chain during transport of specimens to prevent the degradation of viral RNA prior to testing. Such cold-chain requirements are difficult to meet in some regions. In this study, we investigated Whatman FTA cards as an alternative stabilization method of YFV RNA for use in molecular diagnosis. Using contrived specimens, linear regression analysis showed that RNA detection from a single 6mm FTA card punch was significantly less sensitive than traditional RNA extraction; however, pooling RNA extracted from two FTA punches significantly lowered the limit of detection to be equal to that of the traditional RNA extraction gold standard. In experiments addressing the ability of FTA card methodology to stabilize YFV RNA at variable temperature, RNA could be detected for more than two weeks following storage at 25°C. Even more promising, YFV RNA was detectable on cards held at 37°C from two days to over two weeks depending on viral input. FTA cards were also shown to stabilize YFV RNA at high humidity if cards were desiccated prior to inoculation. These results support that FTA cards could be cost effective and easy to use in molecular diagnosis of YF, preserving viral RNA to allow for positive diagnoses in situations where maintaining cold-chain is not feasible.     

Epidemiology of yellow fever virus in humans,arthropods, and non-human primates in sub-Saharan Africa: A systematic review and meta-analysis

Yellow fever (YF) has re-emerged in the last two decades causing several outbreaks in endemic countries and spreading to new receptive regions. This changing epidemiology of YF creates new challenges for global public health efforts. Yellow fever is caused by the yellow fever virus (YFV) that circulates between humans, the mosquito vector, and non-human primates (NHP). In this systematic review and meta-analysis, we review and analyse data on the case fatality rate (CFR) and prevalence of YFV in humans, and on the prevalence of YFV in arthropods, and NHP in sub-Saharan Africa (SSA). We performed a comprehensive literature search in PubMed, Web of Science, African Journal Online, and African Index Medicus databases. We included studies reporting data on the CFR and/or prevalence of YFV. Extracted data was verified and analysed using the random effect meta-analysis. We conducted subgroup, sensitivity analysis, and publication bias analyses using the random effect meta-analysis while I² statistic was employed to determine heterogeneity. This review was registered with PROSPERO under the identification CRD42021242444. The final meta-analysis included 55 studies. The overall case fatality rate due to YFV was 31.1% (18.3–45.4) in humans and pooled prevalence of YFV infection was 9.4% (6.9–12.2) in humans. Only five studies in West and East Africa detected the YFV in mosquito species of the genus Aedes and in Anopheles funestus. In NHP, YFV antibodies were found only in members of the Cercopithecidae family. Our analysis provides evidence on the ongoing circulation of the YFV in humans, Aedes mosquitoes and NHP in SSA. These observations highlight the ongoing transmission of the YFV and its potential to cause large outbreaks in SSA. As such, strategies such as those proposed by the WHO’s Eliminate Yellow Fever Epidemics (EYE) initiative are urgently needed to control and prevent yellow fever outbreaks in SSA.     

The epidemiology of yellow fever in Africa

Yellow fever (YF) is still a major public heath problem, particularly in Africa, despite the availability of a very efficacious vaccine. The World Health Organization estimates that there are 200,000 cases of YF annually, including 30,000 deaths, of which over 90% occur in Africa. In the past 15 years, the number of YF cases has increased tremendously, with most of the YF activity in West Africa. This increase in YF activity is in part due to a breakdown in YF vaccination and mosquito control programs. Five genotypes of YF virus have been found in Africa, and each genotype circulates in a distinct geographical region. West Africa genotype I, found in Nigeria and surrounding areas, is associated with frequent epidemics, whereas the three genotypes in East and Central Africa are in regions where YF outbreaks are rare. Other factors, including genetic and behavioral variation among vector species, are also thought to play a role in the epidemiology of YF in Africa.     

What Factors Might Have Led to the Emergence of Ebola in West Africa?

An Ebola outbreak of unprecedented scope emerged in West Africa in December 2013 and presently continues unabated in the countries of Guinea, Sierra Leone, and Liberia. Ebola is not new to Africa, and outbreaks have been confirmed as far back as 1976. The current West African Ebola outbreak is the largest ever recorded and differs dramatically from prior outbreaks in its duration, number of people affected, and geographic extent. The emergence of this deadly disease in West Africa invites many questions, foremost among these: why now, and why in West Africa? Here, we review the sociological, ecological, and environmental drivers that might have influenced the emergence of Ebola in this region of Africa and its spread throughout the region. Containment of the West African Ebola outbreak is the most pressing, immediate need. A comprehensive assessment of the drivers of Ebola emergence and sustained human-to-human transmission is also needed in order to prepare other countries for importation or emergence of this disease. Such assessment includes identification of country-level protocols and interagency policies for outbreak detection and rapid response, increased understanding of cultural and traditional risk factors within and between nations, delivery of culturally embedded public health education, and regional coordination and collaboration, particularly with governments and health ministries throughout Africa. Public health education is also urgently needed in countries outside of Africa in order to ensure that risk is properly understood and public concerns do not escalate unnecessarily. To prevent future outbreaks, coordinated, multiscale, early warning systems should be developed that make full use of these integrated assessments, partner with local communities in high-risk areas, and provide clearly defined response recommendations specific to the needs of each community.     

SimFection: a digital resource for vaccination education

Vaccination coverage in the United Kingdom is below the level recommended by the World Health Organisation, and when vaccination coverage is not sufficient, outbreaks of infectious diseases can occur. In 2015, coverage of the first dose of the Measles-Mumps-Rubella vaccine declined in the United Kingdom for the first time since 2008, indicating a need to raise public awareness and understanding of the importance of vaccination to public health. Identifying 16 – 18-year olds as a target audience, being future parents who would make decisions regarding vaccination of their children, a digital educational resource (‘SimFection’) was developed to deliver key messages about the spread and control of vaccine-preventable infectious diseases (identified via school curricula). The process of development utilised an iterative approach, involving a cyclic process of prototyping, testing, analysis and refinement with a range of audiences including students, schoolchildren, and trainee teachers. The completed resource is now available online for free download.     

Mass Vaccination with a New,Less Expensive Oral Cholera Vaccine Using Public Health Infrastructure in India: The Odisha Model

Introduction

The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model.

Methods

All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel.

Results

The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25% between the two doses. Higher coverage was observed among females and among 6–17 year-olds. Vaccine cost at market price (about US$1.85/dose) was the costliest item. The vaccine delivery cost was $0.49 per dose or $1.13 per fully vaccinated person.

Discussion

This is the first undertaken project to collect empirical evidence on the use of Shanchol within a mass vaccination campaign using existing public health program resources. Our findings suggest that mass vaccination is feasible but requires detailed micro-planning. The vaccine and delivery cost is affordable for resource poor countries. Given that the vaccine is now WHO pre-qualified, evidence from this study should encourage oral cholera vaccine use in countries where cholera remains a public health problem.     

Considerations for community engagement when conducting clinical trials during infectious disease emergencies in West Africa

Community engagement in research, including public health related research, is acknowledged as an ethical imperative. While medical care and public health action take priority over research during infectious disease outbreaks, research is still required in order to learn from epidemic responses. The World Health Organisation developed a guide for community engagement during infectious disease epidemics called the Good Participatory Practice for Trials of Emerging (and Re‐emerging) Pathogens that are Likely to Cause Severe Outbreaks in the Near Future and for which Few or No Medical Counter‐Measures Exist (GPP‐EP). This paper identified priorities for community engagement for research conducted during infectious disease outbreaks drawing on discussions held with a purposive sample of bioethicists, social scientists, researchers, policy makers and laypersons who work with ethics committees in West Africa. These perspectives were considered in the light of the GPP‐EP, which adds further depth and dimension to discussions on community engagement frameworks. It concludes that there is no presumptive justification for the exclusion of communities in the design, implementation and monitoring of clinical trials conducted during an infectious disease outbreak. Engagement that facilitates collaboration rather than partnership between researchers and the community during epidemics is acceptable.     

A comparative approach to the French medical missions in Brazil and in sub-Saharan Africa before the Second World War

Franco-Brazilian cooperation in the field of microbiology and tropical diseases dates back to the onset of those disciplines. Physicians were sent over by France, namely Marchoux, Simond and Salimbeni from 1901 to 1905 to study yellow fever, and Emile Brumpt from 1913 to 1914 to teach parasitology. These missions brought in some important results. After confirming that the yellow fever agent was a filterable virus and that Stegomya (Aedes) its only vector, Simond and Marchoux clarified the biology of the mosquito and showed that sexual transmission of the virus could occur. They also set up different measures for the control of yellow fever outbreaks which Oswaldo Cruz was inspired by for his campaign against yellow fever. Emile Brumpt implemented the teaching of parasitology at the Faculty of Medicine in S?o Paulo and contributed to human American trypanosomiasis by defining the transmission of the disease and the cycle of the parasite responsible for it. He also developed the technique known as xenodiagnosis. Simond and Marchoux's works on yellow fever found an immediate application in French colonies, particularly in sub-Saharan Africa. However, the fight against large African endemics such as sleeping sickness, the other human trypanosomiases, could not have been carried out successfully without the contribution of mobile teams following Eugène Jamot's initiative in addition to the permanent centres which characterized the French colonial system.     

黄热病现状及其疫苗的研究与应用

黄热病(yellow fever,YF)是一种经由伊蚊叮咬传播的急性出血性传染病,流行区主要集中在非洲西部、南美洲等热带地区,临床症状包括高热、恶心、呕吐、黄疸、出血等。黄热病的病原体为黄热病毒(yellow fever virus, YFV),是黄病毒科黄病毒属的单股正链RNA病毒。目前,YF治疗尚无特效药物,以对症治疗和支持治疗为主,接种YF-17D减毒活疫苗是最有效的预防方法。尽管YF-17D已被全球认可,但是疫苗接种所致的不良反应时有报道。本文对近年黄热病的流行情况、疫苗研究进展和应用进行综述。     

The co-circulation of two infectious diseases and the impact of vaccination against one of them

An epidemiological model based on probabilistic cellular automaton is proposed to investigate the dynamics of two co-circulating infections. In the model, one of these two diseases compromises the immune response to future infections; however, there is vaccine against this immunosuppressive disease. The goal is to evaluate the impact of the vaccination coverage on the prevalence and on the cumulative deaths associated with both contagious diseases. The performed numerical simulations highlight the importance of vaccination on decreasing morbidity and mortality. The results are discussed from a public health standpoint, by taking into account outbreaks of measles and COVID-19.     

Rapid Molecular Assays for the Detection of Yellow Fever Virus in Low-Resource Settings

Background

Yellow fever (YF) is an acute viral hemorrhagic disease transmitted by Aedes mosquitoes. The causative agent, the yellow fever virus (YFV), is found in tropical and subtropical areas of South America and Africa. Although a vaccine is available since the 1930s, YF still causes thousands of deaths and several outbreaks have recently occurred in Africa. Therefore, rapid and reliable diagnostic methods easy to perform in low-resources settings could have a major impact on early detection of outbreaks and implementation of appropriate response strategies such as vaccination and/or vector control.

Methodology

The aim of this study was to develop a YFV nucleic acid detection method applicable in outbreak investigations and surveillance studies in low-resource and field settings. The method should be simple, robust, rapid and reliable. Therefore, we adopted an isothermal approach and developed a recombinase polymerase amplification (RPA) assay which can be performed with a small portable instrument and easy-to-use lyophilized reagents. The assay was developed in three different formats (real-time with or without microfluidic semi-automated system and lateral-flow assay) to evaluate their application for different purposes. Analytical specificity and sensitivity were evaluated with a wide panel of viruses and serial dilutions of YFV RNA. Mosquito pools and spiked human plasma samples were also tested for assay validation. Finally, real-time RPA in portable format was tested under field conditions in Senegal.

Conclusion/Significance

The assay was able to detect 20 different YFV strains and demonstrated no cross-reactions with closely related viruses. The RPA assay proved to be a robust, portable method with a low detection limit (<21 genome equivalent copies per reaction) and rapid processing time (<20 min). Results from real-time RPA field testing were comparable to results obtained in the laboratory, thus confirming our method is suitable for YFV detection in low-resource settings.     

Methodology for definition of yellow fever priority areas, based on environmental variables and multiple correspondence analyses

Yellow fever (YF) is endemic in much of Brazil, where cases of the disease are reported every year. Since 2008, outbreaks of the disease have occurred in regions of the country where no reports had been registered for decades, which has obligated public health authorities to redefine risk areas for the disease. The aim of the present study was to propose a methodology of environmental risk analysis for defining priority municipalities for YF vaccination, using as example, the State of São Paulo, Brazil. The municipalities were divided into two groups (affected and unaffected by YF) and compared based on environmental parameters related to the disease''s eco-epidemiology. Bivariate analysis was used to identify statistically significant associations between the variables and virus circulation. Multiple correspondence analysis (MCA) was used to evaluate the relationship among the variables and their contribution to the dynamics of YF in Sao Paulo. The MCA generated a factor that was able to differentiate between affected and unaffected municipalities and was used to determine risk levels. This methodology can be replicated in other regions, standardized, and adapted to each context.     

A Bayesian Approach to Quantifying the Effects of Mass Poultry Vaccination upon the Spatial and Temporal Dynamics of H5N1 in Northern Vietnam

Outbreaks of H5N1 in poultry in Vietnam continue to threaten the livelihoods of those reliant on poultry production whilst simultaneously posing a severe public health risk given the high mortality associated with human infection. Authorities have invested significant resources in order to control these outbreaks. Of particular interest is the decision, following a second wave of outbreaks, to move from a “stamping out” approach to the implementation of a nationwide mass vaccination campaign. Outbreaks which occurred around this shift in policy provide a unique opportunity to evaluate the relative effectiveness of these approaches and to help other countries make informed judgements when developing control strategies. Here we use Bayesian Markov Chain Monte Carlo (MCMC) data augmentation techniques to derive the first quantitative estimates of the impact of the vaccination campaign on the spread of outbreaks of H5N1 in northern Vietnam. We find a substantial decrease in the transmissibility of infection between communes following vaccination. This was coupled with a significant increase in the time from infection to detection of the outbreak. Using a cladistic approach we estimated that, according to the posterior mean effect of pruning the reconstructed epidemic tree, two thirds of the outbreaks in 2007 could be attributed to this decrease in the rate of reporting. The net impact of these two effects was a less intense but longer-lasting wave and, whilst not sufficient to prevent the sustained spread of outbreaks, an overall reduction in the likelihood of the transmission of infection between communes. These findings highlight the need for more effectively targeted surveillance in order to help ensure that the effective coverage achieved by mass vaccination is converted into a reduction in the likelihood of outbreaks occurring which is sufficient to control the spread of H5N1 in Vietnam.     

Climate teleconnections and recent patterns of human and animal disease outbreaks

Background

Recent clusters of outbreaks of mosquito-borne diseases (Rift Valley fever and chikungunya) in Africa and parts of the Indian Ocean islands illustrate how interannual climate variability influences the changing risk patterns of disease outbreaks. Although Rift Valley fever outbreaks have been known to follow periods of above-normal rainfall, the timing of the outbreak events has largely been unknown. Similarly, there is inadequate knowledge on climate drivers of chikungunya outbreaks. We analyze a variety of climate and satellite-derived vegetation measurements to explain the coupling between patterns of climate variability and disease outbreaks of Rift Valley fever and chikungunya.

Methods and Findings

We derived a teleconnections map by correlating long-term monthly global precipitation data with the NINO3.4 sea surface temperature (SST) anomaly index. This map identifies regional hot-spots where rainfall variability may have an influence on the ecology of vector borne disease. Among the regions are Eastern and Southern Africa where outbreaks of chikungunya and Rift Valley fever occurred 2004–2009. Chikungunya and Rift Valley fever case locations were mapped to corresponding climate data anomalies to understand associations between specific anomaly patterns in ecological and climate variables and disease outbreak patterns through space and time. From these maps we explored associations among Rift Valley fever disease occurrence locations and cumulative rainfall and vegetation index anomalies. We illustrated the time lag between the driving climate conditions and the timing of the first case of Rift Valley fever. Results showed that reported outbreaks of Rift Valley fever occurred after ∼3–4 months of sustained above-normal rainfall and associated green-up in vegetation, conditions ideal for Rift Valley fever mosquito vectors. For chikungunya we explored associations among surface air temperature, precipitation anomalies, and chikungunya outbreak locations. We found that chikungunya outbreaks occurred under conditions of anomalously high temperatures and drought over Eastern Africa. However, in Southeast Asia, chikungunya outbreaks were negatively correlated (p<0.05) with drought conditions, but positively correlated with warmer-than-normal temperatures and rainfall.

Conclusions/Significance

Extremes in climate conditions forced by the El Niño/Southern Oscillation (ENSO) lead to severe droughts or floods, ideal ecological conditions for disease vectors to emerge, and may result in epizootics and epidemics of Rift Valley fever and chikungunya. However, the immune status of livestock (Rift Valley fever) and human (chikungunya) populations is a factor that is largely unknown but very likely plays a role in the spatial-temporal patterns of these disease outbreaks. As the frequency and severity of extremes in climate increase, the potential for globalization of vectors and disease is likely to accelerate. Understanding the underlying patterns of global and regional climate variability and their impacts on ecological drivers of vector-borne diseases is critical in long-range planning of appropriate disease and disease-vector response, control, and mitigation strategies.     

Lewis W. Hackett and the early years of the International Health Board's Yellow Fever Program in Brazil, 1917-1924

Lewis W. Hackett joined the staff of the International Health Board (IHB) in 1914. He was sent to Brazil in 1916, where his original responsibility was hookworm control, but he was gradually and inevitably drawn into combating other diseases. Hackett had a strong influence on public health in Brazil. In 1922 he instituted grass-roots (local) health units and programs. The next year, he negotiated with the federal government a cooperative yellow fever control program, which was described in the IHB's 1923 annual report as the "new and final campaign against yellow fever" in Brazil. Eleven offices were established in northern Brazil, where it was expected that yellow fever would quickly be eradicated. Just as the new program got underway Hackett was reassigned to Italy, where he remained until the beginning of World War II. Nonetheless, Hackett had done a classic job of developing the IHB program in Brazil, moving carefully but authoritatively from the initial focus on hookworm, to the development of a more comprehensive public health program, and then to the strategic thrust toward yellow fever.