Vaccinating against monkeypox in the Democratic Republic of the Congo

Brett W Petersen, Joelle Kabamba, Andrea M McCollum, Robert Shongo Lushima, Emile Okitolonda Wemakoy, Jean-Jacques Muyembe Tamfum, Beatrice Nguete, Christine M Hughes, Benjamin P Monroe, Mary G Reynolds, Brett W Petersen, Joelle Kabamba, Andrea M McCollum, Robert Shongo Lushima, Emile Okitolonda Wemakoy, Jean-Jacques Muyembe Tamfum, Beatrice Nguete, Christine M Hughes, Benjamin P Monroe, Mary G Reynolds

Abstract

Healthcare-associated transmission of monkeypox has been observed on multiple occasions in areas where the disease is endemic. Data collected by the US Centers for Disease Control and Prevention (CDC) from an ongoing CDC-supported program of enhanced surveillance in the Tshuapa Province of the Democratic Republic of the Congo, where the annual incidence of human monkeypox is estimated to be 3.5-5/10,000, suggests that there is approximately one healthcare worker infection for every 100 confirmed monkeypox cases. Herein, we describe a study that commenced in February 2017, the intent of which is to evaluate the effectiveness, immunogenicity, and safety of a third-generation smallpox vaccine, IMVAMUNE®, in healthcare personnel at risk of monkeypox virus (MPXV) infection. We describe procedures for documenting exposures to monkeypox virus infection in study participants, and outline lessons learned that may be of relevance for studies of other investigational medical countermeasures in hard to reach, under-resourced populations.

Keywords: Clinical trial; Democratic Republic of the Congo; IMVAMUNE; Monkeypox; Smallpox vaccine.

Copyright © 2018. Published by Elsevier B.V.

Figures

Fig. 1
Fig. 1
(A) Suspect monkeypox case notifications and deaths in the DRC from 1996 to 2016. Cases are often not followed to outcome; thus, this does not represent a fatality rate. (B) Distribution of monkeypox cases and deaths in the DRC from 1996 to 2015 (Nakazawa et al., 2013).
Fig. 2
Fig. 2
Countries that have reported cases of human MPX, including those that have sent samples to the INRB Laboratory in Kinshasa for diagnostic testing from 2007 to 2017.
Fig. 3
Fig. 3
IMVAMUNE vaccine study. (A) Prospective participant reviewing study consent documents with local study coordinator. (B) Serum collection prior to vaccination. (C) Vaccination of the first participant in the study.

References

    1. Bass J., Tack D.M., McCollum A.M., Kabamba J., Pakuta E., Malekani J., Nguete B., Monroe B.P., Doty J.B., Karhemere S., Damon I.K., Balilo M., Okitolonda E., Shongo R.L., Reynolds M.G. Enhancing healthcare worker ability to detect and care for patients with monkeypox in the Democratic Republic of the Congo. Int. Health. 2013;5:237–243.
    1. Bray M., Wright M.E. Progressive vaccinia. Clin. Infect. Dis. 2003;36:766–774.
    1. Burns D.L. Licensure of vaccines using the animal rule. Curr. Opin. Virol. 2012;2:353–356.
    1. Durski K.N., McCollum A.M., Nakazawa Y., Petersen B.W., Reynolds M.G., Briand S., Djingarey M.H., Olson V., Damon I.K., Khalakdina A. Emergence of monkeypox - West and Central Africa, 1970-2017. MMWR Morb. Mortal. Wkly. Rep. 2018;67:306–310.
    1. Earl J.L., Americo P.L., Wyatt L.S., et al. Rapid protection in a monkeypox model by a single injection of a replication-deficient vaccinia virus. Proc. Natl. Acad. Sci. U. S. A. 2008;105:10889–10894.
    1. Frey S.E., Newman F.K., Kennedy J.S., Sobek V., Ennis F.A., Hill H., Yan L.K., Chaplin P., Vollmar J., Chaitman B.R., Belshe R.B. Clinical and immunologic responses to multiple doses of IMVAMUNE (Modified Vaccinia Ankara) followed by Dryvax challenge. Vaccine. 2007;25:8562–8573.
    1. Frey S.E., Winokur P.L., Salata R.A., El-Kamary S.S., Turley C.B., Walter E.B., Jr., Hay C.M., Newman F.K., Hill H.R., Zhang Y., Chaplin P., Tary-Lehmann M., Belshe R.B. Safety and immunogenicity of IMVAMUNE(R) smallpox vaccine using different strategies for a post event scenario. Vaccine. 2013;31:3025–3033.
    1. Frey S.E., Wald A., Edupuganti S., Jackson L.A., Stapleton J.T., El S.H., El-Kamary S.S., Edwards K., Keyserling H., Winokur P., Keitel W., Hill H., Goll J.B., Anderson E.L., Graham I.L., Johnston C., Mulligan M., Rouphael N., Atmar R., Patel S., Chen W., Kotloff K., Creech C.B., Chaplin P., Belshe R.B. Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naive subjects. Vaccine. 2015;33:5225–5234.
    1. Greenberg R.N., Overton E.T., Haas D.W., Frank I., Goldman M., von K.A., Virgin G., Badeker N., Vollmar J., Chaplin P. Safety, immunogenicity, and surrogate markers of clinical efficacy for modified vaccinia Ankara as a smallpox vaccine in HIV-infected subjects. J. Infect. Dis. 2013;207:749–758.
    1. Hoff N.A., Morier D.S., Kisalu N.K., Johnston S.C., Doshi R.H., Hensley L.E., Okitolonda-Wemakoy E., Muyembe-Tamfum J.J., Lloyd-Smith J.O., Rimoin A.W. Varicella coinfection in patients with active monkeypox in the democratic Republic of the Congo. EcoHealth. 2017 Sep;14(3):564–574.
    1. Jezek Z., Grab B., Szczeniowski M.V., Paluku K.M., Mutombo M. Human monkeypox: secondary attack rates. Bull. World Health Organ. 1988;66:465–470.
    1. Keckler M.S., Carroll D.S., Gallardo-Romero N.F., et al. Establishment of the black-tailed prairie dog (Cynomys ludovicianus) as a novel animal model for comparing smallpox vaccines administered preexposure in both high- and low-dose monkeypox virus challenges. J. Virol. 2011;85:7683–7698.
    1. Ladnyj I.D., Ziegler P., Kima E. A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo. Bull. World Health Organ. 1972;46:593–597.
    1. Lane J.M., et al. Complications of smallpox vaccination, 1968: results of ten statewide surveys. J. Infect. Dis. 1970;122(4):303–309.
    1. Lane J.M., et al. Complications of smallpox vaccination, 1968. N. Engl. J. Med. 1969;281(22):1201–1208.
    1. McCollum A.M., Damon I.K. Human monkeypox. Clin. Infect. Dis. 2014;58:260–267.
    1. Mora L.F., Khan A.H., Sperling L.S. Cardiac complications after smallpox vaccination. South Med. J. 2009;102(6):615–619.
    1. Morgan J., et al. Myocarditis, pericarditis, and dilated cardiomyopathy after smallpox vaccination among civilians in the United States, January-October 2003. Clin. Infect. Dis. 2008;46(Suppl 3):S242–S250.
    1. Nakazawa Y., Lash R.R., Carroll D.S., Damon I.K., Karem K.L., Reynolds M.G., Osorio J.E., Rocke T.E., Malekani J.M., Muyembe J.J., Formenty P., Peterson A.T. Mapping monkeypox transmission risk through time and space in the Congo Basin. PloS One. 2013;8
    1. Norheim O.F., Jha P., Admasu K., Godal T., Hum R.J., Kruk M.E., Gomez-Dantes O., Mathers C.D., Pan H., Sepulveda J., Suraweera W., Verguet S., Woldemariam A.T., Yamey G., Jamison D.T., Peto R. Avoiding 40% of the premature deaths in each country, 2010-30: review of national mortality trends to help quantify the UN sustainable development goal for health. Lancet. 2015;385:239–252.
    1. Petersen B.W., Damon I.K., Pertowski C.A., Meaney-Delman D., Guarnizo J.T., Beigi R.H., Edwards K.M., Fisher M.C., Frey S.E., Lynfield R., Willoughby R.E. Clinical guidance for smallpox vaccine use in a postevent vaccination program. MMWR Recomm. Rep. 2015;64:1–26.
    1. Petersen B.W., Harms T.J., Reynolds M.G., Harrison L.H. Use of vaccinia virus smallpox vaccine in laboratory and healthcare personnel at risk for occupational exposure to orthopoxviruses - recommendations of the advisory committee on immunization practices (ACIP) MMWR Morb. Mortal. Wkly. Rep. 2016. 2015;65:257–262.
    1. Reed K.D., Melski J.W., Graham M.B., Regnery R.L., Sotir M.J., Wegner M.V., Kazmierczak J.J., Stratman E.J., Li Y., Fairley J.A., Swain G.R., Olson V.A., Sargent E.K., Kehl S.C., Frace M.A., Kline R., Foldy S.L., Davis J.P., Damon I.K. The detection of monkeypox in humans in the Western Hemisphere. N. Engl. J. Med. 2004;350:342–350.
    1. Reed J.L., Scott D.E., Bray M. Eczema vaccinatum. Clin. Infect. Dis. 2012;54:832–840.
    1. Rimoin A.W., Graham B.S. Whither monkeypox vaccination. Vaccine. 2011;29(Suppl. 4):D60–D64.
    1. Rimoin A.W., Mulembakani P.M., Johnston S.C., Lloyd Smith J.O., Kisalu N.K., Kinkela T.L., Blumberg S., Thomassen H.A., Pike B.L., Fair J.N., Wolfe N.D., Shongo R.L., Graham B.S., Formenty P., Okitolonda E., Hensley L.E., Meyer H., Wright L.L., Muyembe J.J. Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo. Proc. Natl. Acad. Sci. U. S. A. 2010;107:16262–16267.
    1. Ryan M.A., Seward J.F., T. Smallpox Vaccine in Pregnancy Registry, Pregnancy, birth, and infant health outcomes from the National Smallpox Vaccine in Pregnancy Registry, 2003-2006. Clin. Infect. Dis. 2008;46(Suppl 3):S221–S226.
    1. Shiferaw M.L., Doty J.B., Maghlakelidze G., Morgan J., Khmaladze E., Parkadze O., Donduashvili M., Wemakoy E.O., Muyembe J.J., Mulumba L., Malekani J., Kabamba J., Kanter T., Boulanger L.L., Haile A., Bekele A., Bekele M., Tafese K., McCollum A.A., Reynolds M.G. Frameworks for preventing, detecting, and Controlling zoonotic diseases. Emerg. Infect. Dis. 2017;23
    1. Stittelaar K.J., van Amerongen G., Kondova I., Kuiken T., van Lavieren R.F., Pistoor F.H., Niesters H.G., van Doornum G., van der Zeijst B.A., Mateo L., Chaplin P.J., Osterhaus A.D. Modified vaccinia virus Ankara protects macaques against respiratory challenge with monkeypox virus. J. Virol. 2005 Jun;79(12):7845–7851.
    1. Vollmar J., Arndtz N., Eckl K.M., Thomsen T., Petzold B., Mateo L., Schlereth B., Handley A., King L., Hulsemann V., Tzatzaris M., Merkl K., Wulff N., Chaplin P. Safety and immunogenicity of IMVAMUNE, a promising candidate as a third generation smallpox vaccine. Vaccine. 2006;24:2065–2070.
    1. von K.A., Vollmar J., Pokorny R., Rapp P., Wulff N., Petzold B., Handley A., Mateo L., Siersbol H., Kollaritsch H., Chaplin P. A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE. Vaccine. 2010;28:1209–1216.
    1. Walsh S.R., Wilck M.B., Dominguez D.J., Zablowsky E., Bajimaya S., Gagne L.S., Verrill K.A., Kleinjan J.A., Patel A., Zhang Y., Hill H., Acharyya A., Fisher D.C., Antin J.H., Seaman M.S., Dolin R., Baden L.R. Safety and immunogenicity of modified vaccinia Ankara in hematopoietic stem cell transplant recipients: a randomized, controlled trial. J. Infect. Dis. 2013;207:1888–1897.

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