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Yellow fever vaccine supply: a possible solution

Sunday, 15th of May 2016 Print

The Lancet, Volume 387, No. 10028, p1599–1600, 16 April 2016

Yellow fever vaccine supply: a possible solution

Thomas P Monath

NewLink Genetics Corp, Devens, MA, USA,

Jack P Woodall

Affiliations

ProMED, International Society for Infectious Diseases, Brookline, MA, USA,

Duane J Gubler

Affiliations

Department of Tropical Medicine, Duke-NUS Graduate Medical School, Singapore,

Thomas M Yuill

Affiliations

Pathobiological Science, Forest and Wildlife Ecology, University of Wisconsin-Madison, Madison, WI, USA,

John S Mackenzie

Affiliations

Tropical Infectious Diseases, Curtin University, Perth, WA, Australia,

Reinaldo M Martins

Affiliations

Bio-Manguinhos/Fiocruz, Rio de Janeiro, RJ, Brazil,

Paul Reiter

Affiliations

Institut Pasteur, Paris, France,

David L Heymann

Affiliations

Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK

DOI: http://dx.doi.org/10.1016/S0140-6736(16)30195-7

Article Info

© 2016 Elsevier Ltd. All rights reserved.

Summary

Related Articles

The global threat of the emerging epidemic of yellow fever in Angola1x1The Lancet. Yellow fever: a global reckoning. Lancet. 2016; 387: 1348

See all References1 is underscored by the recent spread of similar Aedes aegypti mosquito-borne viruses including dengue, chikungunya, and now Zika. Since their emergence in the 1950s, dengue virus infection has been reported from more than 128 countries, the chikungunya virus has been reported from over 60 countries,2x2WHO. Dengue and severe dengue. http://www.who.int/mediacentre/factsheets/fs117/en/; March, 2016. ((accessed April 11, 2016).)

See all References, 3x3WHO. Dengue control: chikungunya. http://www.who.int/denguecontrol/arbo-viral/other_arboviral_chikungunya/en/; 2016. ((accessed April 11, 2016).)

See all References while yellow fever, first identified as a viral infection in 1900, has been reported from more than 57 countries and is on the move once again.4x4Monath, TP, Gershman, M, Staples, JE et al. Yellow fever. in: S Plotkin, W Orenstein, P Offit (Eds.) Vaccines. 6th edn. Saunders Elsevier, Philadelphia; 2013: 870–968

See all References4 Although outbreaks of chikungunya and dengue seem to have case fatality rates of less than 1%, yellow fever outbreaks have case fatality rates as high as 75% in hospitalised cases.5x5De Cock, KM, Monath, TP, Nasidi, A et al. Epidemic yellow fever in eastern Nigeria, 1986. Lancet. 1988; 1: 630–633

Summary | PubMed | Scopus (25)See all References, 6x6Nasidi, A, Monath, TP, De Cock, K et al. Urban yellow fever epidemic in western Nigeria, 1987. Trans R Soc Trop Med Hyg. 1989; 83: 401–406

PubMed | Scopus (43)See all References

There has been an effective yellow fever vaccine since the late 1930s, but in 1987 Nigeria had an urban outbreak among an unvaccinated population that caused an estimated 120 000 infections with a case fatality rate of 20% despite a mass vaccination campaign.6x6Nasidi, A, Monath, TP, De Cock, K et al. Urban yellow fever epidemic in western Nigeria, 1987. Trans R Soc Trop Med Hyg. 1989; 83: 401–406

PubMed | Scopus (43)See all References6 Presently, according to WHO,7x7WHO. Emergencies preparedness, response yellow fever. http://www.who.int/csr/don/archive/disease/yellow_fever/en/; 2016. ((accessed April 11, 2016).)

See all References7 outbreaks of yellow fever are occurring in more than six of Angolas 18 provinces, and unvaccinated travellers from Angola have arrived in neighbouring Democratic Republic of the Congo, and as far away as Kenya, Mauritania, and China. Yellow fever has heretofore never been recorded in Asia. China, India, and southeast Asian countries are considered at great risk of introduction and spread of urban yellow fever because the Aedes vector is present and the population is unvaccinated.8x8WHO. Disease outbreak news 6 April 2016 yellow fever—China. http://www.who.int/csr/don/6-april-2016-yellow-fever-china/en/. ((accessed April 8, 2016).)

See all References8

Should yellow fever outbreaks occur elsewhere in Africa, in Latin America, or in Asia, current global supplies of yellow fever vaccine will be inadequate. A blueprint for national yellow fever contingency plans in southeast Asia had been developed in 2011 at a WHO meeting in India.9x9WHO Regional Office for South-East Asia. Informal expert consultation on yellow fever threat to India and other SEA region countries. Report of the Consultation, Goa, India, March 23–25, 2011. World Health Organization, New Delhi; 2012: 39

See all References9

In 2000, when there was a global shortage of yellow fever vaccines for outbreak response, an International Coordinating Group (ICG)10x10WHO. Yellow fever vaccine: a global partnership. http://www.who.int/csr/disease/yellowfev/global_partnership/en/#icg. ((accessed April 11, 2016).)

See all References10—a partnership of WHO, UNICEF, Médecins Sans Frontières, and the International Federation of Red Cross and Crescent Societies—began procurement and stockpiling of yellow fever vaccine that is released to countries reporting yellow fever outbreaks based on agreed criteria for yellow fever vaccine release during outbreaks. The current global stockpile of yellow fever vaccine, however, may demand more attention. To date WHO, through the ICG, has provided 7·3 million doses of yellow fever vaccine to Angola (population about 23 million) and routine immunisation of children in those African countries that have included yellow fever vaccine in their routine childhood immunisation programmes has in some instances been suspended because of diversion of global stocks to Angola.

The global supply of immediately available yellow fever vaccine from all six of the worlds manufacturers is about 5 million doses currently. The annual production is about 80 million doses per year, while the one manufacturer in China produces only 0·3 million doses per year, and the ability of all manufacturers to ramp up production is limited. Overall, supply falls short of demand nearly every year and this is accentuated during emergencies such as that in Angola. The Director-General of WHO recently visited Angola and promised 3 million more doses, but it could be that millions of additional doses will be needed as vaccine demand increases in Angola and in neighbouring countries. If outbreaks were to occur in densely populated areas of Asia, there could be a requirement for very large amounts of vaccine.

The yellow fever vaccine is a live, attenuated vaccine that replicates within the body and produces long-duration (probably lifelong) immunity. We suggest that the most expedient approach to increase yellow fever vaccine supply would be to use a lower dose of vaccine to immunise those at risk. Clinical trials have shown that a one-tenth dose of the vaccine is as effective as full dose vaccine in rapidly stimulating immunity.11x11Hickling, J and Jones, R. Yellow fever vaccination: the potential of dose-sparing to increase vaccine supply and availability. PATH, Seattle, WA; 2013: 118

See all References, 12x12Martins, RM, Maia M de, L, Farias, RH et al. 17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study. Hum Vaccin Immunother. 2013; 9: 879–888

CrossRef | PubMed | Scopus (7)See all References Consideration should therefore be given to using the existing formulation by subcutaneous injection of a dose reduced from 0·5 mL to 0·1 mL, expanding the supply by five-fold. The 0·1 mL volume can be accurately given with a 1 mL syringe13x13Campi-Azevedo, AC, de Almeida Estevam, P, Coelho-dos-Reis, JG et al. Subdoses of 17DD yellow fever vaccine elicit equivalent virological/immunological kinetics timeline. BMC Infect Dis. 2014; 14: 391

CrossRef | PubMed | Scopus (3)See all References13 and this strategy would increase the current vaccine stockpiles held globally and in Angola.

There is not, however, regulatory acceptance of a dosage change. One important issue is stability and expiration dating, which is determined by virus titre in each of the vaccine manufacturers formulations. Another is whether long-term duration of immunity would be affected by the lower dose, although this is not an impediment to emergency use. A third issue is efficacy of the lower dose in children, which has not been determined by clinical testing. In some studies, yellow fever vaccine has been shown somewhat less effective in children than in adults.14x14Gotuzzo, E, Yactayo, S, and Cordova, E. Efficacy and duration of immunity after yellow fever vaccination: systematic review on the need for a booster every 10 years. Am J Trop Med Hyg. 2013; 89: 434–444

CrossRef | PubMed | Scopus (21)See all References14

Even so, WHO could consider recommending the use of 0·1 mL of vaccine using the Emergency Use Assessment and Listing (EUAL) procedure,15x15WHO. WHO Emergency use assessment and listing procedures for medical products during public health emergencies. http://www.who.int/medicines/news/public_consult_med_prods/en/. ((accessed April 11, 2016).)

See all References15 which was invoked to allow use of unlicensed products against Ebola during the recent crisis. At the same time, WHO should continue encouraging countries to enhance surveillance and intensify control activities against mosquito-borne viral infections in general.

Invoking the EUAL now, rather than waiting for a major yellow fever vaccine shortage to occur, and stronger surveillance and vector control, could potentially avoid the need to declare a Public Health Emergency of International Concern (PHEIC), and better ensure our global health security.

This online publication has been corrected. The corrected version first appeared at thelancet.com on April 15, 2016

We declare no competing interests.

References

1The Lancet. Yellow fever: a global reckoning. Lancet. 2016; 387: 1348

 

2WHO. Dengue and severe dengue. http://www.who.int/mediacentre/factsheets/fs117/en/; March, 2016. ((accessed April 11, 2016).)

 

3WHO. Dengue control: chikungunya. http://www.who.int/denguecontrol/arbo-viral/other_arboviral_chikungunya/en/; 2016. ((accessed April 11, 2016).)

 

4Monath, TP, Gershman, M, Staples, JE et al. Yellow fever. in: S Plotkin, W Orenstein, P Offit (Eds.) Vaccines. 6th edn. Saunders Elsevier, Philadelphia; 2013: 870–968

 

5De Cock, KM, Monath, TP, Nasidi, A et al. Epidemic yellow fever in eastern Nigeria, 1986. Lancet. 1988; 1: 630–633

 

| Summary

| PubMed

| Scopus (25)

6Nasidi, A, Monath, TP, De Cock, K et al. Urban yellow fever epidemic in western Nigeria, 1987. Trans R Soc Trop Med Hyg. 1989; 83: 401–406

 

| PubMed

| Scopus (43)

7WHO. Emergencies preparedness, response yellow fever. http://www.who.int/csr/don/archive/disease/yellow_fever/en/; 2016. ((accessed April 11, 2016).)

 

8WHO. Disease outbreak news 6 April 2016 yellow fever—China. http://www.who.int/csr/don/6-april-2016-yellow-fever-china/en/. ((accessed April 8, 2016).)

 

9WHO Regional Office for South-East Asia. Informal expert consultation on yellow fever threat to India and other SEA region countries. Report of the Consultation, Goa, India, March 23–25, 2011. World Health Organization, New Delhi; 2012: 39

 

10WHO. Yellow fever vaccine: a global partnership. http://www.who.int/csr/disease/yellowfev/global_partnership/en/#icg. ((accessed April 11, 2016).)

 

11Hickling, J and Jones, R. Yellow fever vaccination: the potential of dose-sparing to increase vaccine supply and availability. PATH, Seattle, WA; 2013: 118

 

12Martins, RM, Maia M de, L, Farias, RH et al. 17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study. Hum Vaccin Immunother. 2013; 9: 879–888

 

| CrossRef

| PubMed

| Scopus (7)

13Campi-Azevedo, AC, de Almeida Estevam, P, Coelho-dos-Reis, JG et al. Subdoses of 17DD yellow fever vaccine elicit equivalent virological/immunological kinetics timeline. BMC Infect Dis. 2014; 14: 391

 

| CrossRef

| PubMed

| Scopus (3)

14Gotuzzo, E, Yactayo, S, and Cordova, E. Efficacy and duration of immunity after yellow fever vaccination: systematic review on the need for a booster every 10 years. Am J Trop Med Hyg. 2013; 89: 434–444

 

| CrossRef

| PubMed

| Scopus (21)

15WHO. WHO Emergency use assessment and listing procedures for medical products during public health emergencies. http://www.who.int/medicines/news/public_consult_med_prods/en/. ((accessed April 11, 2016).)

 

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