Ebola vaccines, malaria vaccines and certain travel-related vaccines

Ebola vaccines, malaria vaccines and certain travel-related vaccines
Lynne Webber Consultant pathologist and clinical virologist

The History of Medicine
2000 BC: Here take this root and eat it! 1800 AD: Try this snake oil 1900 AD: That snake oil is heathen, say a prayer 1920 AD: That prayer is useless, try this lotion 1940 AD: Stop that lotion, here swallow this pill 1980 AD: Stop swallowing that pill, here use these antibiotics 2000 AD: The antibiotics don’t work anymore. Here take this root and eat it!

Laboratory safety: Laboratory biosafety level criteria
4/14/2018 Laboratory safety: Laboratory biosafety level criteria

It’s a Friday afternoon, about 15h30 and you are starting to look forward to the weekend when one of your staff brings a sample to you. In the diagnosis field it says “?VHF”. The sample is not packaged in any special way and there are no details of the doctor who sent the sample. If you have not prepared for such an event, you are not going to have a weekend you will have a nightmare.

Differential Diagnosis

Septicaemia Infections such as: malaria, typhoid, Tick-bite fever. Viral infections – various Non-infective: neoplasia, drug sensitivity, OD, snake bite, poisoning, tribal medicines

Containment levels for biocontainment laboratories
BSL-4 BSL-3 BSL-2 BSL-1 BSL = biosafety level

1 2 3 4 BSL LAB TYPE LAB PRACTICES SAFETY EQUIPMENT
RISK GROUP BSL LAB TYPE LAB PRACTICES SAFETY EQUIPMENT 1 Basic – Biosafety level 1 Basic teaching Research GMT None: Open bench work 2 Basic – Biosafety level 2 Primary health services Diagnostic services GMT + protective clothing Biohazard sign Open bench + BSC for potential aerosols 3 Containment – Biosafety level 3 Special diagnostic services research As level 2 + special clothing, controlled access, directional airflow BSC and/or other primary devices for ALL activities 4 Maximum containment – Biosafety level 4 Dangerous pathogen units As level 3 + airlock entry, shower exit, special waste disposal Class III BSC or positive pressure suits in conjunction with Class II BSCs, double autoclave (through wall), filtered air BSC=biological safety cabinet; GMT=good microbiological techniques

Biosafety level 1 (BSL-1)
4/14/2018 Biosafety level 1 (BSL-1) Well characterized agents Not known to consistently cause disease in healthy adult humans Minimal potential hazard to lab personnel & the environment Appropriate for Undergraduate and secondary educational training and teaching labs Biosafety Level 1 practices, safety equipment, and facility design and construction are appropriate for undergraduate and secondary educational training and teaching laboratories, and for other laboratories in which work is done with defined and characterized strains of viable microorganisms not known to consistently cause disease in healthy adult humans. Bacillus subtilis, Naegleria gruberi, infectious canine hepatitis virus, and exempt organisms under the NIH Recombinant DNA Guidelines are representative of microorganisms meeting these criteria. Many agents not ordinarily associated with disease processes in humans are, however, opportunistic pathogens and may cause infection in the young, the aged, and immunodeficient or immunosuppressed individuals. Vaccine strains that have undergone multiple in vivo passages should not be considered avirulent simply because they are vaccine strains. .

BSL-2 Procedures likely to produce aerosols are performed in a BSC
4/14/2018 Procedures likely to produce aerosols are performed in a BSC Doors kept closed Hazard signs Potentially contaminated wastes separated from the general waste system BSL-2 Biosafety Level 2 practices, equipment, and facility design and construction are applicable to clinical, diagnostic, teaching, and other laboratories in which work is done with the broad spectrum of indigenous moderate-risk agents that are present in the community and associated with human disease of varying severity. With good microbiological techniques, these agents can be used safely in activities conducted on the open bench, provided the potential for producing splashes or aerosols is low. Hepatitis B virus, HIV, the salmonellae, and Toxoplasma spp. are representative of microorganisms assigned to this containment level. Biosafety Level 2 is appropriate when work is done with any human-derived blood, body fluids, tissues, or primary human cell lines where the presence of an infectious agent may be unknown. Primary hazards to personnel working with these agents relate to accidental percutaneous or mucous membrane exposures, or ingestion of infectious materials. Extreme caution should be taken with contaminated needles or sharp instruments. Even though organisms routinely manipulated at Biosafety Level 2 are not known to be transmissible by the aerosol route, procedures with aerosol or high splash potential that may increase the risk of such personnel exposure must be conducted in primary containment equipment, or in devices such as a BSC or safety centrifuge cups. Other primary barriers should be used as appropriate, such as splash shields, face protection, gowns, and gloves. Secondary barriers such as handwashing sinks and waste decontamination facilities must be available to reduce potential environmental contamination.

4/14/2018 Biosafety level 3 (BSL-3) Indigenous or exotic agents with a potential for respiratory transmission May cause serious and potentially lethal infection Primary hazards to personnel relate to autoinoculation, ingestion and exposure to infectious aerosols More emphasis on primary and secondary barriers e.g. All manipulations should be performed in a BSC or other enclosed equipment Secondary barriers for this level include Controlled access to the lab Specialized ventilation requirements that minimize the release of infectious aerosols from the laboratory E.g. MTB, SLE, Coxiella Burnetti Biosafety Level 3 practices, safety equipment, and facility design and construction are applicable to clinical, diagnostic, teaching, research, or production facilities in which work is done with indigenous or exotic agents with a potential for respiratory transmission, and which may cause serious and potentially lethal infection. Mycobacterium tuberculosis, St. Louis encephalitis virus, and Coxiella burnetii are representative of the microorganisms assigned to this level. Primary hazards to personnel working with these agents relate to autoinoculation, ingestion, and exposure to infectious aerosols. At Biosafety Level 3, more emphasis is placed on primary and secondary barriers to protect personnel in contiguous areas, the community, and the environment from exposure to potentially infectious aerosols. For example, all laboratory manipulations should be performed in a BSC or other enclosed equipment, such as a gas-tight aerosol generation chamber. Secondary barriers for this level include controlled access to the laboratory and ventilation requirements that minimize the release of infectious aerosols from the laboratory

Arbo- & certain other viruses assigned to BSL-3 (CDC)
4/14/2018 Arbo- & certain other viruses assigned to BSL-3 (CDC) Aino Akabane Banna Bhanja Central Eurupe TBE Chikungunya* Cocal Dhori Dobrava-Belgrade Dugbe Everglades Flexal Germiston Getah Hantaan Israel Turkey meningitis Japanese encephalitis* Junin Kairi Kimberley Koutango Louping ill* Mayaro Middelburg Mobala Mopeia Mucambo Murray Valley encephalitis Nairobi sheep disease Ndumu Negishi Oropouche Orungo Peaton Piry* Powassa Puumala Rift Valley fever* Rocio Sagiyama Sal Vieja San Perlita Semliki Forest Seoul Sin Nombre Spondweni St. Louis encephalitis Thogoto Turuna Venezuelan equine encephalitis* Vesicular stomatitis Wesselsbron* West Nile* Yellow fever* Zinga Lab or lab animal-associated infections have been reported with the following BSL-3 agents: Venezuelan equine encephalomyelitis* " 150 (1 death) Rift Valley fever* " 47 (1 death) Chikungunya* 39 Yellow fever* 38 (8 deaths) Japanese encephalitis* 22 Louping ill " 22 West Nile 18 Lymphocytic choriomeningitis* 15 Orungo 13 Piry 13 Wesselsbron " 13 Mucambo 10 Oropouche 7 Germiston 6 Bhanja 6 Hantaan* 6 Mayaro 5 Spondweni 4 Murray Valley encephalitis 3 Semliki Forest 3 (1 death) Powassan 2 Dugbe 2 Issyk-kul 1 Koutango 1

All infectious material handled in BSCs Located away from doors, from room supply louvers, and from heavily-traveled lab areas PPE e.g. solid-front or wrap-around gowns, scrub suits or coveralls are worn by workers when in the lab Not worn outside the lab Reusable clothing is decontaminated before being laundered Clothing is changed when overtly contaminated

4/14/2018 Biosafety level 3 (BSL-3) Laboratory Facilities (Secondary Barriers) Lab separated from areas that are open to unrestricted traffic flow within the building Access to the lab is restricted Passage through a series of two self-closing doors is the basic requirement for entry into the laboratory from access corridors Laboratory Facilities (Secondary Barriers) 1. The laboratory is separated from areas that are open to unrestricted traffic flow within the building, and access to the laboratory is restricted. Passage through a series of two self-closing doors is the basic requirement for entry into the laboratory from access corridors. Doors are lockable (see Appendix F). A clothes change room may be included in the passageway. 2. Each laboratory room contains a sink for handwashing. The sink is hands-free or automatically operated and is located near the room exit door. 3. The interior surfaces of walls, floors, and ceilings of areas where BSL-3 agents are handled are constructed for easy cleaning and decontamination. Seams, if present, must be sealed. Walls, ceilings, and floors should be smooth, impermeable to liquids and resistant to the chemicals and disinfectants normally used in the laboratory. Floors should be monolithic and slip-resistant. Consideration should be given to the use of coved floor coverings. Penetrations in floors, walls, and ceiling surfaces are sealed or capable of being sealed to facilitate decontamination. Openings such as around ducts and the spaces between doors and frames are capable of being sealed to facilitate decontamination. 4. Bench tops are impervious to water and are resistant to moderate heat and the organic solvents, acids, alkalis, and those chemicals used to decontaminate the work surfaces and equipment. 5. Laboratory furniture is capable of supporting anticipated loading and uses. Spaces between benches, cabinets, and equipment are accessible for cleaning. Chairs and other furniture used in laboratory work should be covered with a non-fabric material that can be easily decontaminated. 6. All windows in the laboratory are closed and sealed. 7. A method for decontaminating all laboratory wastes is available in the facility and utilized, preferably within the laboratory (i.e., autoclave, chemical disinfection, incineration, or other approved decontamination method). Consideration should be given to means of decontaminating equipment. If waste is transported out of the laboratory, it should be properly sealed and not transported in public corridors. 8. Biological safety cabinets are required and are located away from doors, from room supply louvers, and from heavily-traveled laboratory areas. 9. A ducted exhaust air ventilation system is provided. This system creates directional airflow which draws air into the laboratory from "clean" areas and toward "contaminated" areas. The exhaust air is not recirculated to any other area of the building. Filtration and other treatments of the exhaust air are not required, but may be considered based on site requirements, and specific agent manipulations and use conditions. The outside exhaust must be dispersed away from occupied areas and air intakes, or the exhaust must be HEPA-filtered. Laboratory personnel must verify that the direction of the airflow (into the laboratory) is proper. It is recommended that a visual monitoring device that indicates and confirms directional inward airflow be provided at the laboratory entry. Consideration should be given to installing an HVAC control system to prevent sustained positive pressurization of the laboratory. Audible alarms should be considered to notify personnel of HVAC system failure. 10. HEPA-filtered exhaust air from a Class II biological safety cabinet can be recirculated into the laboratory if the cabinet is tested and certified at least annually. When exhaust air from Class II safety cabinets is to be discharged to the outside through the building exhaust air system, the cabinets must be connected in a manner that avoids any interference with the air balance of the cabinets or the building exhaust system (e.g., an air gap between the cabinet exhaust and the exhaust duct). When Class III biological safety cabinets are used they should be directly connected to the exhaust system. If the Class III cabinets are connected to the supply system, it is done in a manner that prevents positive pressurization of the cabinets (see Appendix A). 11. Continuous flow centrifuges or other equipment that may produce aerosols are contained in devices that exhaust air through HEPA filters before discharge into the laboratory. These HEPA systems are tested at least annually. Alternatively, the exhaust from such equipment may be vented to the outside if it is dispersed away from occupied areas and air intakes. 12. Vacuum lines are protected with liquid disinfectant traps and HEPA filters, or their equivalent. Filters must be replaced as needed. An alternative is to use portable vacuum pumps (also properly protected with traps and filters). 13. An eyewash station is readily available inside the laboratory. 14. Illumination is adequate for all activities, avoiding reflections and glare that could impede vision. 15. The Biosafety Level 3 facility design and operational procedures must be documented. The facility must be tested for verification that the design and operational parameters have been met prior to operation. Facilities should be re-verified, at least annually, against these procedures as modified by operational experience. 16. Additional environmental protection (e.g., personnel showers, HEPA filtration of exhaust air, containment of other piped services and the provision of effluent decontamination) should be considered if recommended by the agent summary statement, as determined by risk assessment, the site conditions, or other applicable federal, state, or local regulations.

4/14/2018 Biosafety level 3 (BSL-3) A ducted exhaust air ventilation system which creates directional airflow which draws air into the laboratory from "clean" areas and toward "contaminated" areas Exhaust air is not recirculated to any other area of the building Outside exhaust must be dispersed away from occupied areas and air intakes or the exhaust must be HEPA-filtered A ducted exhaust air ventilation system Creates directional airflow which draws air into the laboratory from "clean" areas and toward "contaminated" areas Exhaust air is not recirculated to any other area of the building Filtration and other treatments of the exhaust air are not required, but may be considered based on site requirements, and specific agent manipulations and use conditions The outside exhaust must be dispersed away from occupied areas and air intakes or the exhaust must be HEPA-filtered Laboratory personnel must verify that the direction of the airflow (into the laboratory) is proper It is recommended that a visual monitoring device that indicates and confirms directional inward airflow be provided at the laboratory entry. Consideration should be given to installing an HVAC control system to prevent sustained positive pressurization of the laboratory Audible alarms should be considered to notify personnel of HVAC system failure.

4/14/2018 Biosafety level 4 (BSL-4) Applicable for work with dangerous & exotic agents High individual risk of life-threatening disease May be transmitted via the aerosol route No available vaccine or therapy E.g. Marburg or Crim-Congo haemorrhagic fever The primary hazards to personnel are Respiratory exposure to infectious aerosols Mucous membrane or broken skin exposure to infectious droplets Autoinoculation Biosafety Level 4 is required for work with dangerous and exotic agents that pose a high individual risk of aerosol-transmitted laboratory infections and life-threatening disease. Agents with a close or identical antigenic relationship to Biosafety Level 4 agents are handled at this level until sufficient data are obtained either to confirm continued work at this level, or to work with them at a lower level. Members of the laboratory staff have specific and thorough training in handling extremely hazardous infectious agents and they understand the primary and secondary containment functions of the standard and special practices, the containment equipment, and the laboratory design characteristics. They are supervised by competent scientists who are trained and experienced in working with these agents. Access to the laboratory is strictly controlled by the laboratory director. The facility is either in a separate building or in a controlled area within a building, which is completely isolated from all other areas of the building. A specific facility operations manual is prepared or adopted. Within work areas of the facility, all activities are confined to Class III biological safety cabinets, or Class II biological safety cabinets used with one-piece positive pressure personnel suits ventilated by a life support system. The Biosafety Level 4 laboratory has special engineering and design features to prevent microorganisms from being disseminated into the environment. The following standard and special safety practices equipment, and facilities apply to agents assigned to Biosafety Level 4:

Arbo-, Arena- & Filoviruses Assigned to BSL- 4 (CDC)
4/14/2018 Arbo-, Arena- & Filoviruses Assigned to BSL- 4 (CDC) Crimean-Congo haemorrhagic fever Ebola & Marburg viruses Tick-borne encephalitis viruses Omsk haemorrhagic fever Russian Spring-Summer encephalitis Guanarito, Machupo, Junin & Sabia viruses Kyasanur Forest disease Lassa Transfer of agents: For a permit to import these agents, contact CDC. Contact the Department o f Commerce for a permit to export these agents. Laboratory registration with CD C is required before sending or receiving these select agents.

4/14/2018 Biosafety level 4 (BSL-4) The lab worker's complete isolation from aerosolized infectious materials is accomplished primarily by working in Class III BSC (Cabinet laboratory) or Full-body, air-supplied positive-pressure personnel suit (Suit laboratory) BSL-4 labs may be based on either model or a combination of both models in the same facility Safety Equipment (Primary Barriers) All procedures within the facility are conducted in the Class III biological safety cabinet or in Class II biological safety cabinets used in conjunction with one-piece positive pressure personnel suits ventilated by a life support system. Laboratory Facility (Secondary Barriers) There are two models for Biosafety Level 4 laboratories: (A) the Cabinet Laboratory where all handling of the agent is performed in a Class III Biological Safety Cabinet, and (B) the Suit Laboratory where personnel wear a protective suit. Biosafety Level-4 laboratories may be based on either model or a combination of both models in the same facility. If a combination is used, each type must meet all the requirements identified for that type.

4/14/2018 Biosafety level 4 (BSL-4) Personnel wears one-piece positive pressure suit that is ventilated by a life-support system protected by HEPA filtration Personnel who enter this area wear a one-piece positive pressure suit that is ventilated by a life-support system protected by HEPA filtration. The life support system includes redundant breathing air compressors, alarms and emergency backup breathing air tanks.

4/14/2018 Biosafety level 4 (BSL-4) Appropriate communication systems are provided between the lab and the outside e.g. voice, fax, computer Cabinet Laboratory 1. The Biosafety Level 4 facility consists of either a separate building or a clearly demarcated and isolated zone within a building. The rooms in the facility are arranged to ensure passage through a minimum of two doors prior to entering the room(s) containing the Class III biological safety cabinet (cabinet room). Outer and inner change rooms separated by a shower are provided for personnel entering and leaving the cabinet room. A double-door autoclave, dunk tank, fumigation chamber, or ventilated anteroom for decontamination is provided at the containment barrier for passage of those materials, supplies, or equipment that are not brought into the cabinet room through the change room. 2. Daily inspections of all containment parameters (e.g., directional airflow) and life support systems are completed before laboratory work is initiated to ensure that the laboratory is operating according to its operating parameters. 3. Walls, floors, and ceilings of the cabinet room and inner change room are constructed to form a sealed internal shell which facilitates fumigation and is resistant to entry and exit of animals and insects. Floors are integrally sealed and coved. The internal surfaces of this shell are resistant to liquids and chemicals to facilitate cleaning and decontamination of the area. All penetrations in these structures and surfaces are sealed. Openings around doors into the cabinet room and inner change room are minimized and are capable of being sealed to facilitate decontamination. Any drains in the cabinet room floor are connected directly to the liquid waste decontamination system. Sewer vents and other service lines contain HEPA filters and protection against vermin. 4. Bench tops have seamless or sealed surfaces which are impervious to water and are resistant to moderate heat and the organic solvents, acids, alkalis, and chemicals used to decontaminate the work surfaces and equipment. 5. Laboratory furniture is of simple open construction, capable of supporting anticipated loading and uses. Spaces between benches, cabinets, and equipment are accessible for cleaning and decontamination. Chairs and other furniture used in laboratory work should be covered with a non-fabric material that can be easily decontaminated. 6. A hands-free or automatically operated handwashing sink is provided near the door of the cabinet room(s) and the outer and inner change rooms. 7. If there is a central vacuum system, it does not serve areas outside the cabinet room. In-line HEPA filters are placed as near as practicable to each use point or service cock. Filters are installed to permit in-place decontamination and replacement. Other liquid and gas services to the cabinet room are protected by devices that prevent backflow. 8. If water fountains are provided, they are automatically or foot-operated and are located in the facility corridors outside the laboratory. The water service to the fountain is isolated from the distribution system supplying water to the laboratory areas and is equipped with a backflow preventer. 9. Access doors to the laboratory are self-closing and lockable. 10. Any windows are breakage-resistant and sealed. 11. Double-door autoclaves are provided for decontaminating materials passing out of both the Class III biological safety cabinet(s) and the cabinet room(s). Autoclaves that open outside of the containment barrier must be sealed to the wall of the containment barrier. The autoclave doors are automatically controlled so that the outside door can only be opened after the autoclave "sterilization" cycle has been completed. 12. Pass-through dunk tanks, fumigation chambers, or equivalent decontamination methods are provided so that materials and equipment that cannot be decontaminated in the autoclave can be safely removed from both the Class III biological safety cabinet(s) and the cabinet room(s). 13. Liquid effluents from the dirty-side inner change room (including toilets) and cabinet room sinks, floor drains (if used), autoclave chambers, and other sources within the cabinet room are decontaminated by a proven method, preferably heat treatment, before being discharged to the sanitary sewer. Effluents from showers and clean-side toilets may be discharged to the sanitary sewer without treatment. The process used for decontamination of liquid wastes must be validated physically and biologically. 14. A dedicated non-recirculating ventilation system is provided. The supply and exhaust components of the system are balanced to ensure directional airflow from the area of least hazard to the area(s) of greatest potential hazard. The differential pressure/directional airflow between adjacent areas is monitored and alarmed to indicate any system malfunction. An appropriate visual pressure monitoring device that indicates and confirms the pressure differential of the cabinet room is provided and located at the entry to the clean change room. The airflow in the supply and exhaust components is monitored and the HVAC control system is designed to prevent sustained positive pressurization of the laboratory. The Class III cabinet should be directly connected to the exhaust system. If the Class III cabinet is connected to the supply system, it is done in a manner that prevents positive pressurization of the cabinet. 15. The supply air to and exhaust air from the cabinet room, inner change room, and anteroom pass through HEPA filter(s). The air is discharged away from occupied spaces and air intakes. The HEPA filter(s) are located as near as practicable to the source in order to minimize the length of potentially contaminated ductwork. All HEPA filters need to be tested and certified annually. The HEPA filter housings are designed to allow for in situ decontamination of the filter prior to removal, or removal of the filter in a sealed, gas-tight primary container for subsequent decontamination and/or destruction by incineration. The design of the HEPA filter housing should facilitate validation of the filter installation. The use of pre-certified HEPA filters can be an advantage. The service life of the exhaust HEPA filters can be extended through adequate prefiltration of the supply air. 16. The Biosafety Level 4 facility design and operational procedures must be documented. The facility must be tested for verification that the design and operational parameters have been met prior to operation. Facilities should be re-verified annually against these procedures as modified by operational experience. 17. Appropriate communication systems are provided between the laboratory and the outside (e.g., voice, fax, computer).

Are There New Threats With New Species of Ebola virus?
A US physician working in Bundibugyo district remembers the day that her Ugandan colleague, Jonah Kule, went to investigate rumours of a mysterious epidemic in Kikyo “We had not heard of any bleeding, just vomiting and diarrhoea…we wondered if it was a cholera outbreak…When he came back he guessed typhoid fever, due to the prominent abdominal pain.” Kule died of Ebola on 4th December 20007

A recent Ebola outbreak occurred in Bundibugyo, Uganda from August 2007 – January 2008

Ebola Virus Order: Mononegavirales Family: Filoviridae
Genus: Ebola virus Species: Zaire ebolavirus (ZEBOV) Sudan ebolavirus (SEBOV) Ivory Coast ebolavirus (ICEBOV) Reston ebolavirus (REBOV) ?? Uganda ebolavirus

New Ebola virus species
Bundibugyov New Ebola virus species

Ebola Virus Single stranded negative sense RNA genome in a helical nucleocapsid

Ebola outbreak - online
“Ebola vaccine trials in Africa and Europe” “rVSV Ebola vaccine (recombinant vesicular stomatis virus induced Ebola – specific immune responses) “Chimpanzee adenovirus Ebola vaccine – preliminary report” (Ebola glycoproteins) “panic, paranoia and public health” “Ebola vaccine – an urgent international priority”

Ebola vaccines under development
cAd – EBO Z VSV – EBOV Advac/MVA – BN EBOV-GP Nasal vaccine – still in monkey trials Vaxart tablet – temperature stable tablet Novel recombinant adenovirus type-5 vector-based Ebola vaccine Whole virus vaccine – EBOV – delta – VP30

CCTV monitoring of inside & perimeter of BSL3

‘In Heaven you won’t hear the mosquito”
Finnish proverb

Malaria vaccine Considerations: Parasite diversity
Address the symptom or the source such as anti-parasitic immunity and anti-toxic immunity potential targets include the parasitic stage and the actual target – malaria life cycle Mix of antigenic components Vaccine delivery system

Protozoan parasites of genus Plasmodium
P.falciparum – responsible for the majority of malaria deaths and is the most prevalent sp in sub-Saharan Africa P.vivax – second most significant species, prevalent in South-East Asia and Latin America; P.ovale – dormant liver stage complication, leads to clinical symptoms; P. malariae– small percentage of infections; P.knowlesi – infects primates, can cause human malaria, mode of transmission unclear

Parasite diversity P.falciparum - evolutionary changes, drug-resistance P.falciparum has a very high rate of replication

Symptom or the source – antibody response and cell-mediated (T-cell) immune responses Antiparasitic immunity – antibody response and a cell-mediated (T-cell) immune response Anti-toxic immunity – suppression of the immune response factors or anti-toxic by-products production. Example tumour necrosis factor could reduce severe malaria symptoms (therapeutic vaccines!)

Potential vaccine targets
Sporozoite – hepatocyte invasion, direct anti-sporozite Hepatozoite – direct anti-hepatozoite Asexual erythrocyte – anti-host erythrocyte, blocking antibodies, anti-soluble toxin Gametocytes – anti-gametocyte, egress blocking antibodies Ad infinitum

Vaccine delivery systems
May require delivery to different areas and by different means Adjuvants – hepatitis B virus in the RTS,S vaccine, key components, high doses may elicit an auto-immune response Two vaccines – one generating a blood response, the other a liver-stage response

RTS,S vaccine/Mosquirix
Most recently developed recombinant vaccine It consists of the P.falciparum circumsporozoite protein (CSP antigen/protein from the pre-erythrocytic stage) HBV plus a chemical adjuvant boosts the immune response by inducing high antibodies that block the parasite from entering the liver 24 July 2014 EMA recommended to vaccinate children aged 6 weeks to 17 months

Mosquirix for national immunisation programmes in sub-Saharan Africa
2015 WHO policy Mosquirix for national immunisation programmes in sub-Saharan Africa

Yellow fever

Zambia – yellow fever vaccine zone

Rift Valley Fever Countries with endemic disease and substantial outbreaks of RVF: Gambia, Senegal, Mauritania, Namibia, South Africa, Mozambique, Zimbabwe, Zambia, Kenya, Sudan, Egypt, Madagascar, Saudi Arabia, Yemen Countries known to have some cases, periodic isolation of virus, or serologic evidence of RVF: Botswana, Angola, Democratic Republic of the Congo, Congo, Gabon, Cameroon, Nigeria, Central African Republic, Chad, Niger, Burkina Faso, Mali, Guinea, Tanzania, Malawi, Uganda, Ethiopia, Somalia

Viruses borne by mosquitoes
Many and many Relevant for Africa: West Nile virus Yellow Fever Rift Valley Fever Sindbis Wesselsbron Middelburg Chikungunya

Bunyaviruses: Shuni virus
Ortobunyavirus identified in brain of fatal neurological case in horse 2009 Subsequent screening of 104 neurological diseased horses ; identified Shuni virus in 6% Two unpublished reports of Shunivirus in horses with neurological disease, 1 from Zimbabwe and 1 from SA in 1970’s ? Importance in SA Shuni Virus as Cause of Neurologic Disease in Horses Charmaine van Eeden, June H. Williams, Truuske G.H. Gerdes, Erna van Wilpe, Adrianne Viljoen, Robert Swanepoel and Marietjie Venter

West Nile virus (WNV) WNV a mosquito-borne member of the Flaviviridae family (Flavivirus) Belongs to the JE-serogroup, includes JEV (Asia), Kunjin and MVE (Australia) Isolated in 1937 from the blood of a 37y.o febrile woman participating in a malaria study in the West Nile district of Northern Uganda

Transmission Maintains enzootic life cycle between viremic birds and mosquitoes (primarly Culex species) Commonly infects humans and horses (dead end hosts) Large host range 225 spp birds 29 spp mammals 49 spp ticks/mosquitoes Limited transmission Survives winter in hibernating females

Distribution 2002

Short- and long-term outcomes
WN Fever Younger individuals Few physical/neurological sequelae Older individuals high mortality Exacerbation of underlying conditions Extreme fatigue is common  lasting up to 36 days post-illness Self-assessed somatic complaints – Fatigue, weakness, concentration problems

Prevention Active arboviral surveillance &
mosquito vector control in affected areas Mapping of breeding sites Surveillance and vector control implemented early to disrupt springtime viral activity Chemical spraying to control adult vectors as emergency measure after detecting WN activity Public outreach Avoid or decrease risk of mosquito bite- repellent Avoid areas where mosquitoes are common Limit outdoor activity in peak biting periods

Vaccines Inactivated vaccines * Subunit vaccines
Cross-reactive vaccines DNA vaccines Live-attenuated vaccines *

Conclusion Thank you! Touched the tip of the iceberg
Indian Cherokee saying – don’t let yesterday use up too much of today

Ebola vaccines, malaria vaccines and certain travel-related vaccines

Similar presentations

Presentation on theme: "Ebola vaccines, malaria vaccines and certain travel-related vaccines"— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Ebola vaccines, malaria vaccines and certain travel-related vaccines

Similar presentations

Presentation on theme: "Ebola vaccines, malaria vaccines and certain travel-related vaccines"— Presentation transcript:

Similar presentations

About project

Feedback