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VACCINE PREVENTABLE DISEASES – WAY FORWARD IN NIGERIA Prof G. C. Onyemelukwe FWACP, (MON ) 19 TH JULY 2013

VACCINE PREVENTABLE DISEASES – WAY FORWARD IN NIGERIA Prof G. C. Onyemelukwe FWACP, (MON ) 19 TH JULY 2013. VACCINATION POLICY IN NIGERIA SINCE EDWARD JENNER – COW POX.

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VACCINE PREVENTABLE DISEASES – WAY FORWARD IN NIGERIA Prof G. C. Onyemelukwe FWACP, (MON ) 19 TH JULY 2013

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  1. VACCINE PREVENTABLE DISEASES – WAY FORWARD IN NIGERIA Prof G. C. Onyemelukwe FWACP, (MON) 19TH JULY 2013

  2. VACCINATION POLICY IN NIGERIA SINCE EDWARD JENNER – COW POX Mandatory for childhood, social mobilization and health education are very necessary. Child Rights Act vaccination is a right. Niger state Assembly passed a bill in 2010/2011 for compulsory polio vaccination of children. Federal government from 2012purchases all vaccines with donor support of GAVI, WHO, UNICEF, DFID, BILL GATES FOUNDATION, CLINTON HEALTH ACCESS INITIATIVE and other partners. Private sector participation in vaccination. GERIATRIC ACT BY NIGERIA NATIONAL ASSEMBLY PASSED 2009. Abuja Declaration of Africa Union on Tb, HIV and malaria in Africa.

  3. UNIVERSAL HEALTH COVERAGE Access for all to appropriate health services at an affordable cost, with highly cost effective prevention activities and therapies accessible to all citizens; Health care financing system mitigate risk of households falling into poverty or suffering large financial losses because of costly health system . Vaccine security involving all stakeholders is a sine qua non

  4. ACCESSIBLITY AND AFFORDABILITY • (a). A wide range of health services, including highly cost- • effective prevention activities and therapies, should be • accessible to all citizens of a give a Countryand • (b). The system of financing healthcareshould mitigate, as • much as possible, the risk that householdswould fall into • poverty or suffer large financial losses as a result of a • costly health problem. The Joint Learning Network for Universal Health Coverage chronicles the challenges and successes of specific reforms within countries, providing a learning platform for senior policy-makers and practitioners in more than a dozen countries.

  5. GOALS OF VACCINATION • Immunity and herd immunity: Herd Immunity is based on the idea that the pathogen will not spread when a significant part of the population has immunity against it. Primary prevention of cancer of cervix and liver possible. Mass immunization. • Eradication of disease: World Health Organization coordinated the global effort to eradicate smallpox globally. Endemic measles, mumps and rubella in Finland eradicated. Polio has been eradicated in most countries except Pakistan, Afghanistan, and Nigeria as at 2013. • Individual, group, selected vaccination of at risk groups: E.g rabies vaccination for veterinary workers. • Therapeutic vaccines or vaccination – anti-IgE vaccines in asthma, anti-cancer therapeutic vaccines e.g. for prostate cancer. Passive delivery of monoclonal antibodies (MoAb) against cancers.

  6. FASTER PROGRESS WITH VACCINES TO MDGs(2000-2015) MDG1: END POVERTY AND HUNGER – Vaccines protect from death, disability, free family finances MDG2: Achieve universal primary education – Healthy to immunized to attend school MDG3: Promote gender equality- Healthy children free women MDG4: Reduce Child mortality- Vaccines prevent 2.5 million child deaths per year, 79% in developing countries, Pneumonia Diarrhea Rota virus) kill 3 million. MDG5: Improve maternal health- Material neonatal tetanus vaccines MDG 6: Combat HIV/AIDS, malaria other disease- Vaccinate HIV positives, Pneumonia, Diarrhea reduce transmission. MDG7: Ensure environmental sustainability – Rota virus vaccination reenergizes safe drinking water. MDG8: Develop global partnership for development • - WHO, UNICEF, GAVI, Bill and Melinda Gates, IVAC, CLINTON HEALTH ACCESS • INITIATIVE • - Parliamentary Advocacy and financing for immunization in Nigeria (PAFFIN) • HERFON - Women Advocates for vaccine Access (WAVA) - Nigeria National Vaccine Summit,PAN 2012 • - World Pneumonia Day 2011, 2012. GAVI initiative from 2000 – Save children • lives, access to Immunization.

  7. GUAGING COUNTRY LEVEL MDGs ACHIEVEMENT(MIDTERM)

  8. VACCINE LANDSCAPE 2000 TO 2020

  9. IMMUNOLOGICAL SPECTRUM PRE NATAL TO OLD AGE

  10. MATERNAL ANTIBODIES IN BREAST MILK PROTECT THE CHILD FROM ENTEROVIRUS INFECTIONS. Sadeharju K, Knip M, Virtanen SM, Savilahti E, Tauriainen S, Koskela P, Akerblom HK, Hyöty H; Finnish TRIGR Study Group. Pediatrics. 2007 May;119(5):941-6. Protective high maternal antibiotics in serum and breast milk better in breast fed > 2 weeks . SecretoryIgA for mucosal defence of baby . Anti-tetanus transplacental antibodies after maternal immuinization.

  11. BREAST MILK ADVANTAGES • SIMPLE OLIGOSACCHRIDES – Binding sites to intercept bacteria entry into intestinal cell. • 2. MUCINS – Adhere to bacteria, viruses to eliminate them • 3. LACTOFERRIN – Bind iron, unavailable to organisms • 4. B12 BINDING PROTEIN – deprive organisms of Vit B12 • 5. BIFIDUS FACTOR – promotes beneficial Lactobaccilusbifidus growth • 6. INTERFERON – In colostrum, antiviral activity • 7. FIBRONECTIN – In Colostrum, repair of tissues, minimize • inflammation, make phagocytes more aggressive. • 8. INDUCER FACTORS – Induce infants immune system • 9. ENHANCER EFFECT – higher levels of antibodies, cortisol, epidermal • growth factor, nerve growth factor Insulin – like growth factor, • somatomedin C, to close leaky mucosal lining of newborn. • 10. FREE FATTY ACIDS – damage membranes of enveloped viruses e.g. • chicken pox virus • 11. SECRETORY IgA IN URINARY TRACT - Lactoferrin, lysozyme found • in large amounts in urinary tract of breast fed. • 12. Induces increased local production of Lactoferrin

  12. CELLULAR DEFENCES IN BREAST MILK • Immune cells abundant in breast milk – white blood cells, leukocytes 40% are macrophages, manufacture lysozyme that destroy bacteria. • Lymphocyte 10%. • B Lymphocytes produce antibodies. Milk lymphocytes proliferate in presence of Escherichia coli. Produce gamma – interferon, monocytechemotactic factor.

  13. INNATE SYSTEM WORKS WITH ADAPTIVE IMMUNE SYSTEM Cell mediated

  14. HELMINTH- AND BACILLUS CALMETTE-GUÉRIN-INDUCED IMMUNITY IN CHILDREN SENSITIZED IN UTERO TO FILARIASIS AND SCHISTOSOMIASIS Indu Malhotra, Peter Mungai, Alex Wamachi, John Kioko, John H. Ouma, James W. Kazura and Christopher L. King J. Immunol. 1999 Jun 1; 162 (11): 6843 – 8. FOETAL IMMUNOLOGICAL PROGRAMMING • Prenatal sensitization to filarial and schistosomiasis in • mother induces immunology memory that persists in • infancy in 50% of newborns, which leads to reduction • of induction of type I T cell immunity induced by BCG for • at least 2 – 10 years. Avoid parasite infection in pregnant • women. • 2. Malnutrition in under 5 poor immunization antibody

  15. MEMORY B CELLS AND MEMORY TH CELLS ARE GENERATED BY IMMUNIZATION AND HERD IMMUNITY INCREASED • Each case infects 10 A. Each case infects 10 other • other individuals in individuals in a population • a susceptible population. With 80% immunity.

  16. ANTI - IgE VACCINES FOR ASTHMA AND ALLERGY

  17. ASTHMA ALLERGENS IN NIGERIA • Dermatophagoides pteronnysinus • Dermatophagoides farinae Onyemelukwe et al • Egg yolk, egg white Rast specific IgE in Nigerian • Okro, frying oil, pepper asthmatic patients. Ann.Allergy • 1986;56(2) 167-70 • Pollens Onyemelukwe G.Rast specific IgE to egg • Airborne fungi etc. and milk in Nigerian asthmatic patients • African J Med. Med Sci 2011;40(7) 51-7 • A. Severe Acute: Chimeric IgE Vaccines • DNA of Allergenic substances (Derf1) • Dermatophagoides farinae • ANTISERA to spider bites, jellyfish stings and other • allergies. • D. CYTO – 003 wing Q beta derived virus like • particles VLP

  18. PARASITES • MALARIA VACCINE • Phase 3 trials of RTS, S/ASOI Malaria vaccine in Africa Infants (6573 infants). New Engl. J. Med 2012, 367, 2184-2296 RTS, S CLINICAL TRIALS PARTNERSHIP • REDUCE EPISODES OF BOTH CLINICAL AND SEVERE MALARIA IN CHILDREN 5 – 17 months by about 50%. One month after 3doses all was positive for anticircumsporozoite antibodies. • OTHER PARASITE VACCINE APPROACH • 1. PARASITE ANNEXINS (found in Nematodes, Trematodes,Protozoa) Annexins • bind phospholipids. used T. Soliumvaccination of pigs, Giardiaduodenalis • – trophozoitevaccine of cats, dogs. • 2. PARAMYOSIN in muscles of invertebrates, found in Schistosomiasis (SM97) • filariasis, TaeniaSolium, Echinococcusgranulosaproduce TH1 response • J.Vazquez– Talavera et al; America Society Microbiology Infection and • Immunology 2001. • 3. WuchereriaBancrofti GST vaccination for lymphatic filariasis. VeerapathranA et • al PLOS Neglected Tropical Diseases 2009.GST (Glutathione – S- Transferase). • rWbGSTas a potential vaccine candidate against Lymphatic filariasis. • 4. HOOKWORM VACCINES – (a) HHVI (Human Hookworm Vaccine Initiative) Na- • ASP2tried in Brazil. Peptide-Based Subunit Vaccine against Hookworm Infection • (PLOS ONE 2012 /article/info%3Adoi%2F10.1371%2Fjournal.pone.0046870. • M. Skwarczynski et al.

  19. ADVANCES IN TOXOPLASMOSIS VACCINES

  20. CANCERS CANCER PREVENTIVE VACCINES • 1.HPV ( 17 SEROTYPES) – 16 and 18 70%, other cervical cancer, vaginal, vulva, penile, oropharyngealcancer GARDASIL – 16, 18, 6, 11 (Quadruvalent) GARDASIL MERCK and COMPANY Age 6 - 26 6, 11 cause 90% genital wart. Made of virus – like particles (VLPS) And correspond to HPV types 6, 11, 16, 18 • 2. CERVARIX (bivalent) GSK 16, 18. Age 9 – 25 • 3. HBV Vaccine – children vaccinated at birth CANCER THERAPEUTIC VACCINES • 1. SIPULEUCIL – T (PROVENGE BY DENDREON) Use of Dendritic cells. Metastatic prostate cancer – Immune response to prostatic acid phosphate (PAP) Customized to each patient. Leukapharesis of antigen presenting cells (APCs) Dendritic cell cultured with protein PAP – GM – CSF. 3 treatments 2 weeks apart. Antologous vaccine • 2. RUSSIA: VITESPAN (2008) Heat shock protein HSPgp96 coupled to Dendritic cell – kidney cancer HEAT SHOCK PROTEINS NEW TECHNOLOGY FOR CELLULAR IMMUNIT. Response to Leprosy, tuberculosis and cancer. 3. Vaccine against MUC-1 Cancer protein ImMUCIN VAXIL BIOTHERAPEUTICS ONGOING RESEARCH ON OTHER CANCER CAUSING ORGANISMS • 1. Hepatitis C – PLCC • 2. EBV – Burkitt’s lymphoma, NHL • 3. KHSV – Kaposi sarcoma • 4. HTLVI - Adult Tcellleukaemia • 5. Helicobacter pylori – Gastric cancer • 6. Schistoma – bladder cancer • haematodium.

  21. VACCINE ACCEPTANCE(BUY IN) IN NIGERIA CERVICAL CANCER RISK PERCEPTION AND PREDICTORS OF HUMAN PAPILLOMA VIRUS VACCINE ACCEPTANCE AMONG FEMALE UNIVERSITY STUDENTS IN NORTHERN NIGERIA. • Iliyasu Z, Abubakar IS, Aliyu MH, Galadanci HS .J Obstet Gynaecol. 2010;30(8):857-62. • doi: 10.3109/01443615.2010.511724. Of 375 females, 35.5% heard of HPV, 53.9% heard of cervical cancer, 74.0% willing to accept

  22. HUMAN PAPILLOMA VIRUS VACCINE: KNOWLEDGE, ATTITUDE AND PERCEPTION OF PARENTS IN SOUTHWEST, NIGERIA Kola M. Owonikoko, Adeola F. Afolabi, Lawrence A. Adebusoye, Oluseyi O. Atanda. Ref. Medical Sciences and Public Health 1(1)2013; 13 – 19 Interviewed parent and guardians – 51.3% ignorant of vaccines, 89.4% agreed to vaccinate their children.

  23. MONOCLONAL ANTIBODIES IN CANCER THERAPY: 25 YEARS OF PROGRESS MONOCLONAL ANTIBODY PRODUCTS • Abbreviations: NHL, non-Hodgkin's lymphoma; VEGF, vascular endothelial growth factor; CLL, chronic lymphocytic leukemia; EGFR, epidermal growth factor receptor.

  24. FDA APPROVED MONOCLONAL THERAPEUTIC ANTIBODIES

  25. FDA APPROVED MONOCLONAL THERAPEUTIC ANTIBODIES

  26. NIGERIA HEALTH WATCH – YELLOW FEVER SOUTH AFRICA DIPLOMACY On yellow fever, yellow cards, Nigeria and South Africa Paper protection?? Faking?? Saudi Pilgrims – POLIO IMMUNIZATION, MENINGITIS, CHOLERA, REQUIREMENTS

  27. "MEDICINE IS A SOCIAL SCIENCE, AND POLITICS IS NOTHING ELSE BUT MEDICINE ON A LARGE SCALE“ RUDOLF VIRCHOW Nigeria: Vaccine suspicion aggravates measles outbreak in Kano and elsewhere and interrupts polio eradication

  28. . SOURCE: ADAPTED FROM US INSTITUTE OF MEDICINE, 1997

  29. LASSA ENDEMIC STATES BAUCHI PLATEAU TARABA NASARAWA BENUE ENUGU EBONYI ONDO 9. EDO

  30. RABIES ENDEMIC IN NIGERIA Detection of rabies virus antibodies in fruit bats (Eidolon helvum) from Nigeria. Aghomo HO, Ako-Nai AK, Oduye OO, Tomori O, Rupprecht CE. J. Wild Dis. 1990. Five viruses related to rabies occurs in Africa related to rabies occurs in Africa Obodhang – Sudan Kotoukan – Nigeria Mokola – Nigeria (Shrews) Lagos Bat – Nigeria (fruit bats) Duvenlage – South Africa (man bitten by bat) Epizootic in Zimbabwe 1981 in dogs, cats. Africa is ancestral origin Rabid dogs in Nigeria lack of immunization for dogs. Human diploid vaccine available but in short supply in Nigeria as well as anti – serum. PS STAPH INFECTIONS Engineered genetically StaphVAX (NIH)USA

  31. OVER 100M NIGERIANS AT RISK OF YELLOW FEVER OUTBREAK • A. As many as 101 million Nigerians are at risk of a possible outbreak of yellow fever, if a mass vaccination campaign is not carried out,the National Primary Health Care Development Agency has warned. Some 377 local government areas in 25 states have been marked out as high risk areas, indicate an assessment survey of the country. • Oyewale Tomori NOTE EBOLA OUTBREAK IN UGANDA Ebola Outbreak in Uganda 2012. Fruit bats reservoir. Effects to other African countries including Nigeria. Surveillance and preparedness?? Occurs in Remote villages in Central and West Africa from wild animals.

  32. WHO ESTIMATES 20M NIGERIANS HAVE HEPATITIS B VIRUS –SOGHIN (SOCIETY FOR GASTRO ENTEROLOGY AND HEPATOLOGY IN NIGERIA) Sept. 2007 Port Harcourt

  33. HIV, HEPATITIS B AND C VIRUSES’ COINFECTION AMONG PATIENTS IN A NIGERIAN TERTIARY HOSPITAL Taiwo Modupe Balogun,, Samuel Emmanuel1, Emmanuel Folorunso Ojerinde Pan African Medical Journal 2012:12:100 HbsAg + Anti-HIV (4%) HbsAg + HIV (28%) HCV + HIV (14.7%) • Industrialized countries: HCV 20% acute hepatitis 70% chronic hepatitis, 40% cirrhosis, 60% hepatocellular carcinoma, 30% liver transplants. • 15 – 60% normal African positive for one more markers of HBV

  34. EPIDEMIC HISTORY AND EVOLUTIONARY DYNAMICS OF HEPATITIS B VIRUS INFECTION IN TWO REMOTE COMMUNITIES IN RURAL NIGERIA Joseph C. Forbi*, Gilberto Vaughan, Michael A. Purdy, David S. Campo, Guo-liang Xia, Lilia M.Ganova-Raeva, SumathiRamachandran, Hong Thai, Yury E. Khudyakov. PLOS ONE July 2010 | Volume 5 | Issue 7 | e11615. HBV hyperdemic (seropravalence 10 – 40%) in Nigeria. As part of West Africa/ Central Africa crescent from Senegal to Namibia. 11% HBV DNA positive. 37 distinct HBV variants belonging predominantly to genotype E(96.4%) Note HBV genotypes are 8- A,B,C,D,E,F,G,H HBV vaccine in program but became available in 2004 5.6% consists of genotype D and G in 5 individuals. 6. HbVA3 probably from Cameroon.

  35. TECHNOLOGICAL CONJUGATION OF MULTIPLE ANTIGENS IMMUNOGENICITY AND SAFETY OF A DTaP – IPV//PRP~T COMBINATION VACCINE GIVEN WITH HEPATITIS B VACCINE: A randomized open-label trial Maria Rosario Capedinga, Josefina Cadorna-Carlos b, May Book- Montellanoc, Esteban Ortiz Bulletin of the World Health Organization. All antigens were adequately immunogenic without interfering with each other for the era of combined vaccines - pentavalent, hexavalent, heptavalent. RCDCs for anti-hepatitis B surface antigen titres in sera obtained at 6 and 18 weeks of age from infants in Groups A and B

  36. OTHER VIRUSES ROTAVIRUS ENDEMIC IN NIGERIA causing diarrhoea especially in childhood. • 2. ZIKA VIRUS INFECTIONS IN NIGERIA: VIROLOGICAL • AND SEROEPIDEMIOLOGICAL INVESTIGATIONS IN • OYO STATE.J Hyg (Lond). 1979 Oct; 83(2):213- • 9.Fagbami AH. • 3. RIFT VALLEY FEVER VIRUS (BUNYAVIRIDAE: • PHLEBOVIRUS): AN UPDATE ON PATHOGENESIS, • MOLECULAR EPIDEMIOLOGY, VECTORS, DIAGNOSTICS • AND PREVENTION • Michel Pepin, MichèleBouloy, Brian H. Bird, Alan Kemp • and JanuszPaweska. INRAEDP Sciences 2010 • Epidemic in Kenya 1930, Egypt 1977, West Africa including Nigeria 1988, Arabian Peninsula 2000

  37. INFLUENZA SURVEILLANCE JAN – JUN 2013 BY NCDC

  38. RECOMBINANT VACCINE TO PREVENT H5N1 NOT YET AVAILABLE

  39. BACTERIA - PNEUMOCOCCI PRE-VACCINATION NASOPHARYNGEAL PNEUMOCOCCAL CARRIAGE IN A NIGERIAN POPULATION: EPIDEMIOLOGY AND POPULATION BIOLOGY Ifedayo M. O. Adetifa mail, Martin Antonio, Christy A. N. Okoromah, Chinelo Ebruke, Victor Inem, David Nsekpong, Abdoulie Bojang, Richard A. Adegbola. Plus one 2012, 7 (1) e30548 • Pneumococcal carriage 52.5% higher in children (67.4%) than adults 26%, highest in infants < 9 months. • 2. 42 serotypes seen: 19F, 6A, 6B, 23F, 11, 15B, 3, 18C, 9V, 14, 15B, • 20, 21,7F, 4, 11, 13, 17, 7C, 19A, 21, 4, 12, Nontypables. • 3. PCV7 Serotypes – 4, 6B, 9V, 14, 18C, 19F, 23F. PCV10, Serotypes • PCV7 +1,5,7F.PCV13, Serotypes PCV10 + 3,6A, 19A • 4. H influenza H1b meningitis eliminated 90% by H1b vaccine. • 5. Near elimination of meningococcal C in industrial countries by • vaccination

  40. PNEUMOCOCCAL SEROTYPES IN ZARIA, NORTHERN NIGERIA • Onyemelukwe G.C and Greenwood B.M. Journal of Infection 1982 • KEY: • ST= SEROTYPES • Mn= MENINGITIS • Pn=PNEUMONIA • Bc= BACTEREMIA/ANTIGENEMIA • T=TOTAL

  41. VACCINES STRATEGIES 1. Vaccination – pneumococcal conjugate vaccines. (PCV7,PCV10, PCV13 - serotypes 4,6B, 9V, 14, 18C, 19F, 23F, 1, 5, 7F, 3, 6A, 19A) - Pneumococcal polysaccharide protein D-conjugate vaccine (Synflorix; PHiDCV). 2. Vaccination-Pentavalent vaccine.e.g.DTPw-HepB-Hib (Quinvaxem) - Hexavalent vaccine e.g. DTPa-HBV-IPV-Hib (Infanrixhexa) - These vaccines are compatible with measles vaccine and induce adequate immunological memory and persistent antibody production against Hib

  42. ADEQUATE ANTIBODY RESPONSES OF COMPONENT ANTIGENS

  43. PNEUMONIA BURDEN IN NIGERIA Pneumonia reduction is part of MDG 4 targets1. Childhood deaths 200,000 under 5 years per year2.Vulnerable –elderly -Sickle Cell disease -diabetes patients -chronic liver disease patients - Nephrotic syndrome patients - Measles patients - HIV patients 3. Multiple resistance to antibiotics.4. Killer organisms. -Streptococcus pneumonia -Haemophilus influenza -Pneumocystiscarinae

  44. TUBERCULOSIS: NATIONAL TUBERCULOSIS CONTROL TREND 2002 - 2011

  45. TREND OF TB/HIV KEY INDICATORS (2007 – 2011)

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