flu paper

Winnifred Brefo-kesse

Hlth 626

March 31, 2019

Professor Hughes

Part I: THE SITUATION ASSESSMENT

In February and March 2013, a novel influenza A (H7N9) virus emerged in China, causing an acute respiratory distress syndrome and occasionally multiple organ failure with high fatality rates in humans (Li et al., 2014). A total of 681 laboratory-confirmed cases and 275 deaths have been reported as of November 13th, 2015, with a fatality rate of 40% (http://www.who.int/influenza/human_animal_interface/HAI_Risk_Assessment/en/). H7N9 has been evolving and established amongst chickens in China over the past two years with occasional human infections (Lam et al., 2015; Su et al., 2015), thus posing a threat to public health. In the absence of an annually-updated effective vaccine, antiviral drugs constitute the first line of defense against H7N9 infections. H7N9 viruses already possess natural resistance to M2-ion channel blockers (amantadine and rimantadine) when it first emerged in 2013 (Gao et al., 2013). Therefore, neuraminidase inhibitors (NAIs), which include oseltamivir (TamifluH), zanamivir (RelenzaH) and peramivir constitute the main antiviral drugs against H7N9 infections (Hu et al., 2013; Wu et al., 2013). However, treatment with NAIs against H7N9 infections has resulted in the emergence of drug-resistant mutant viruses, as soon as 1~9 days after administration (Gao et al., 2013; Hu et al., 2013). Moreover, the first H7N9 isolate (A/Shanghai/1/2013(H7N9), SH-H7N9) was resistant to oseltamivir (Gao et al., 2013). Avian influenza A H7 viruses are a group of viruses that is mostly found amongst birds. The H7N9 virus is a subgroup of the H7 viruses and was recently discovered in China. There were three cases discovered in March of 2013 which ultimately increased in May by 132 cases. Of those cases, the 39 infected, died because of the virus (Peipei Song1, 2013). The clinical features described in the three patients with H7N9 virus infection, included fulminant pneumonia, respiratory failure, acute respiratory distress syndrome (ARDS), septic shock, multi-organ failure, rhabdomyolysis, and encephalopathy, are very troubling (Timothy M. Uyeki, 2013). As of now, this virus has reached stage two of three which is poultry passing the virus to humans. There is one more stage left which is human to human transmission which the Chinese health officials have confirmed it is not yet occurring. Creating an anti-virus takes a lot of time and until then public health officials should create new tactics in battling this epidemic.

Since there isn’t an anti-virus for the H7N9 virus, different health policies must be put in place to control the outbreak as well as preventative strategies from escalating. This virus was most found amongst poultry, so the Chinese health officials started the management of live poultry markets in urban areas, and free ranged poultry in rural areas. The Chinese health officials concluded that people could be infected through contact with virus-carrying birds or exposure to contaminated environments (Peipei Song1, 2013). China created public health responses to close down all affected markets, stopped the sale of birds, through disinfection, poultry culling, and prohibiting the entry of exotic live poultry that could benefit in preventing more people becoming infected with H7N9 virus (Peipei Song1, 2013). Ultimately closing all the markets permanently will be difficult and changing purchasing habits of live poultry will be challenging and might take a long time. Instead China has decided to enhance regulation of their poultry markets. Regulation includes in establishing quarantine areas at production sites, establish fixed locations for slaughtering and quarantine, implement regular spot checks, implement bio-safety level disinfection, and establish better traceability of frozen poultry (Peipei Song1, 2013).

Not only is there an exposure in urban areas, but there is a significant amount of exposure in rural areas as well. In urban areas people are exposed to the virus in live poultry markets, especially the poultry handlers. In rural areas most people raise their own poultry causing an environmental health concern. The Chinese conducted a study of 1,379 participants, half had contact with wild birds ("often" and "occasionally"); nearly 50% have a semi-closed or open yard that poultry could pass through, 51% kept poultry in their homes(Peipei Song1, 2013). Only a few residents had special poultry coops to maintain their poultry in a proper and feasible manner, and many others did not. People who did not have this luxury were forced to raise their poultry inside their homes for example, common rooms, and extra room or even a restroom (Peipei Song1, 2013). Researchers also found that since poultry was raised inside homes, poultry feces were discovered in the yards, the living rooms, restrooms, and worse, in the kitchens (Peipei Song1, 2013). This is a great environmental concern because family members including children, whom are more susceptible to the disease, are openly exposed to the H7N9 virus. Rx for survival did a piece on the H7N9 virus and stated the Chinese health officials noticed a trend of the virus occurring in young 6-7-year-old boys. This was because young boys were given the job to pluck the feathers off the dead poultry, thus openly exposing them to infected specimens.

Even though there isn’t an anti-virus Chinese health officials have stalked up millions of doses of Tamiflu and a new anti-influenza drug (peramivir sodium chloride injection) that has proven effective in fighting the H7N9 virus (Lin Mei, 2013). This anti-virus is only used to help cure patients who are already infected, not for the prevention of obtaining the virus. A statement about vaccine response had been made by WHO on May 2, 2013(Lin Mei, 2013). USCDC and European center for disease prevention and control (ECDC) also issued guidelines of using antivirals. However, since the outbreak of H7N9 has been in a relatively short period of time, the existing policies about drugstockpiling and vaccine development to treat influenza A (H7N9) are still limited(Lin Mei, 2013). The U.S. Department of Agriculture (USDA) has set up a Situational Awareness Coordination Unit with a core team of subject matter experts and other USDA representatives, including the Animal and Plant Health Inspection Service (APHIS), the Agricultural Research Service (ARS), the Food Safety and Inspection Service, and the Foreign Agricultural Service (Emergence of Avian Influenza A(H7N9) Virus Causing Severe Human Illness , 2013).

The spectre of introduction of avian influenza in Zambia through migratory birds raises concerns for both human and animal health. Although avian influenza virus (AIV) surveillance has been on-going in wild waterfowl in Lochinvar national park (LNP) since 2006, little is known about the ecological drivers of AIV perpetuation in wild birds in Zambia. While several AIV subtypes have been isolated and characterized in Zambia, H10 viruses have not been studied. During routine AIV surveillance conducted in November 2014, of the 287 faecal samples collected from ducks, spur-winged geese and pelicans, four H10N1 viruses were isolated from ducks using embryonated eggs. In this study, the haemagglutinin (HA) and the neuraminidase (NA) genes of one of the isolates (designated A/duck/Zambia/36/2014 H10N1 (Dk-Zb14)) were amplified in a one-step reverse transcriptase polymerase chain reaction. Full length sequencing, phylogenetic and amino acid sequence analyses of the HA and NA genes was performed. The HA and NA gene phylogeny revealed that Dk-Zb14 belonged to the Eurasian-Avian lineage. The HA gene was closely related to that of A/Pekin duck/South Africa/AI1642/09 H10N7. In contrast, the NA gene was closely related to that of A/pelican/Zambia/13/09 H9N1 isolated in LNP. Dk-Zb14 had fewer glycosylation sites (3) than those reported for most AIVs. A glutamine to isoleucine substitution at the receptor biding site (position 226) was observed in the HA gene. The HA gene cleavage site had PEIMQGR?GLF amino acid motif, which is like previously described H10 isolates. Dk-Zb14 and Pel-Zb09 had ten amino acid differences within the NA gene. Additionally, the NA gene of Dk-Zb14 had a lysine at position 432 which formed a second neuraminic acid binding site. Surface glycoprotein phylogeny suggests interspecies transmission and maintenance of AIVs among wild and possibly domestic ducks within the Southern Africa ecosystem. These findings highlight the need for continued monitoring of AIVs in wild and domestic birds in the region. (Chambaro 2006)

The Journal of Thoracic Disease created a guideline on prevention and control of the H7N9 virus. Prevention measures include that health care providers should provide relevant training for the medical staff, and to improve their awareness and capacity in identifying, reporting, and managing the hospital acquired H7N9 infection and enable the early detection, early diagnosis, early isolation, and early report (Team, 2013). The health care providers should enhance their monitoring for hospital acquired infections by dealing with any suspects or cases with human H7N9 virus infection to be immediately reported as required and the patient should be properly managed(Team, 2013). The health care providers must standardize their disinfection, isolation and protection policies to provide sufficient, necessary and qualified disinfection and protection equipment to the medical staff, so as to ensure that all the disinfection, isolation, and personal protection measures are sufficiently and efficiently implemented (Team, 2013). The health care providers must properly clean and disinfect the medical equipment, contaminated items, item surface, and ground in accordance with the Technical Specifications for Implementing Disinfection in Hospitals(Team, 2013).

The bible verse that I will add to this research Paper is Mathew 7:7-11which states that ‘7 “Ask and it will be given to you; seek and you will find; knock and the door will be opened to you. 8 For everyone who asks receives; the one who seeks finds; and to the one who knocks, the door will be opened.

9  “Which of you, if your son asks for bread, will give him a stone? 10 Or if he asks for a fish, will give him a snake? 11 If you, then, though you are evil, know how to give good gifts to your children, how much more will your Father in heaven give good gifts to those who ask him

References

Ribavirin is effective against drug-resistant H7N9 influenza virus infections

1. Ribavirin is effective against drug-resistant H7N9 influenza virus infections. Yuhai Bi, Gary Wong, Yingxia Liu, Lei Liu, George F. Gao, Yi Shi

Protein Cell. 2016 Aug; 7(8): 611–614. Published online 2016 Jul 18. doi: 10.1007/s13238-016-0287-0

2. Peipei Song1, 2. J. (2013). Measures to combat H7N9 virus infection in China: Live poultry purchasing habits, poultry handling, and living conditions increase the risk of exposure to contaminated enviornments. BioScience Trends, 168-171.

3. Timothy M. Uyeki, M. M. (2013). Global Concerns Regarding Novel Influenza A (H7N9) Virus Infections. The New England Journal of Medicine, 1862-1864.

4. Lin Mei, Q. T. (2013). Changes in and shortcomings of drug stockpiling, vaccine development and related policies during outbreaks of avian influenza A H5N1, H1N1, and H7N9 among humans. Drug Discoveries & Therapeutics, 95-100.

5. Editorial Team. Guideline on prevention and control of H7N9 avian influenza human infection. J Thorac Dis 2013;5(S2): S168-S172. doi: 10.3978/j.issn.2072-1439.2013.05.17

6. Chambaro, Herman MosesCharacterisation of influenza A H10N1 virus isolated from ducks in Lochinvar National Park Zambia

7. NIV Bible

PART II: VACCINE DEVELOPMENT PROGRESS RESPORT

Influenza H7N9 virus is a potentially pandemic subtype to which most people are immunologically naïve. To be better prepared for the potential occurrence of an H7N9 pandemic, in 2017 the World Health Organization recommended developing candidate vaccine viruses from two new H7N9 viruses, A/Guangdong/17SF003/2016 (A/GD) and A/Hong Kong/125/2017 (A/HK). This report describes the development of live attenuated influenza vaccine (LAIV) candidates against A/GD and A/HK viruses and study of their safety and immunogenicity in the ferret model in order to choose the most promising one for a phase I clinical trial. The A/HK-based vaccine candidate (A/17/HK) was developed by classical reassortment in eggs. The A/GD-based vaccine candidate (A/17/GD) was generated by reverse genetics. Ferrets were vaccinated with two doses of LAIV or phosphate-buffered saline. Both H7N9 LAIVs tested were safe for ferrets, as shown by absence of clinical signs, and by virologic and histological data; they were immunogenic after a single vaccination. These results provide a compelling argument for further testing of these vaccines in volunteers. Since the A/HK virus represents the cluster that has caused most human cases, and because the A/HK-based LAIV candidate was developed by classical reassortment, this is the preferred candidate for a phase I clinical trial. (1) Live attenuated influenza vaccines (LAIVs) are being developed to protect humans against future epidemics and pandemics. This study describes the results of a double–blinded randomized placebo–controlled phase I clinical trial of cold–adapted and temperature sensitive H7N3 live attenuated influenza vaccine candidate in healthy seronegative adults. IAVs are classified into subtypes based on different combinations of 16 hemagglutinin (HA: H1 – H16) and 9 neuraminidase (NA: N1 – N9) surface antigens, and two pathotypes (low and high pathogenicity) based on lethality for chicken. All highly pathogenic avian IAVs known to date belong to the H5 or H7 subtype. The H7N9 viruses, a subgroup of H7 viruses that normally spread among birds have currently been found to cause human infections in China, prompting intensive research to address the challenge of a potential epidemic/pandemic. Although H7N9 family clusters have been reported in Shanghai and Shandong Province, no evidence of human-to-human H7N9 virus transmission has been found to date. Presently, there is a general lack of information about H7N9 infections, e.g., the transmission mechanism and the number of mild infections in China are unknown. Unlike H5N1, which could wipe out a flock of poultry within days, H7N9 infections in poultry are usually asymptomatic or mild. Nonetheless, based on what has been learned from the H5N1 avian flu virus which has killed 371 people in 15 countries since 2003 and proved extremely difficult to control, the risk of an H7N9 epidemic/pandemic should not be underestimated, especially in China where poultries are reared with diverse methods without strict biosecurity measures . Studies on H7N9 transmission mechanisms and clinical features/outcomes are critical to prevent and control potential H7N9 epidemic/pandemic. (4)Two doses of H7N3 LAIV or placebo were administered to 40 randomly divided subjects (30 received vaccine and 10 placebo). The presence of influenza A virus RNA in nasal swabs was detected in 60.0% and 51.7% of subjects after the first and second vaccination, respectively. In addition, vaccine virus was not detected among placebo recipients demonstrating the absence of person–to–person transmission. The H7N3 live attenuated influenza vaccine demonstrated a good safety profile and was well tolerated. The two–dose immunization resulted in measurable serum and local antibody production and in generation of antigen–specific CD4+ and CD8+memory T cells. Composite analysis of the immune response which included hemagglutinin inhibition assay, microneutralization tests, and measures of IgG and IgA and virus–specific T cells showed that the majority (86.2%) of vaccine recipients developed serum and/or local antibodies responses and generated CD4+ and CD8+ memory T cells. (2)

Another Live attenuated H7N9 influenza vaccine viruses that possess the hemagglutinin (HA) and neuraminidase (NA) gene segments from the newly emerged wild-type A/Anhui/1/2013 (H7N9) and six internal protein gene segments from the cold-adapted influenza virus A/Ann Arbor/6/60 (AA ca) were generated by reverse genetics. The reassortant virus containing the original A/Anhui/1/2013 HA and NA sequences replicated poorly in eggs. Multiple variants with amino acid substitutions in the HA head domain that improved viral growth were identified by viral passage in eggs and MDCK cells. The selected vaccine virus containing two amino acid changes (N133D/G198E) in the HA improved viral titer by more than 10-fold (reached a titer of 10(8.6) fluorescent focus units/ml) without affecting viral antigenicity. Introduction of these amino acid changes into an H7N9 PR8 reassortant virus also significantly improved viral titers and HA protein yield in eggs. The H7N9 ca vaccine virus was immunogenic in ferrets. A single dose of vaccine conferred complete protection of ferrets from homologous A/Anhui/1/2013 (H7N9) and nearly complete protection from heterologous A/Netherlands/219/2003 (H7N7) challenge infection. Therefore, this H7N9 live attenuated influenza vaccine (LAIV) candidate has been selected for vaccine manufacture and clinical evaluation to protect humans from H7N9 virus infection(3) Overall, few cases of H7 virus transmission to mammals have ever been reported in Asia and N9 virus infections in human have never been documented anywhere in the world except H7N9 . The H7N9 variants currently in circulation most likely evolved through a combination of genes from viruses in Beijing bramblings, Zhejiang ducks, and Korean wild birds according to report by Chinese scientists. Human infections with highly pathogenic H7 viruses generally resulted in conjunctivitis or uncomplicated influenza. By April 30, 2013, confirmed cases of H7N9 infections had been reported in 11 provinces across the Yangtze Delta region of Eastern, Northern, and Southeast China. A total of 126 patients have been diagnosed with H7N9 infection and 24 patients have died since the first confirmed case was reported on April 24, 2013 in Taiwan. Among the 33 patients diagnosed in Shanghai, 21 have recovered while 12 died from complications caused by the infection, as confirmed by the Shanghai Municipal Health and Family Planning Commission. The clinical features, treatment, outcomes, and other factors associated with H7N9 infection have not been reported. From April 6 to April 20, 2013, 18 H7N9-infected patients were admitted into our hospital, which is one of the designated treatment centers for H7N9 infection in Shanghai. In the present article, we reported our observations of clinical features and clinical progress in H7N9-infected patients and interpreted factors related to treatment outcomes. The information provided herein could help early screening, diagnosis, and treatment of H7N9 infection and facilitate development of strategies to prevent death. (4) In china progress were made when it came to the treatment of the virus. there. All participating patients were treated by twice daily oral administration of 75 mg oseltamivir. Patients were also given antibiotics based on blood and/or throat-swab specimens/sputum tests for bacterial infections. If no specific bacterial pathogens were detected from the specimens, advanced treatment was considered. Antibiotics given to H7N9-infected patients if applicable included moxifloxacin, sulbactam and cefoperazone, levofloxacin, meropenem, piperacillin, imipenem, and cilastatin. Some patients also received glucocorticoid therapy, intravenous immunoglobulin therapy, and TCM therapy. Only Chinese herbs prescribed according to specific syndromes were considered TCM in this study. Proprietary Chinese medicines and injections of Chinese medicines were excluded because they could contain certain western drug ingredients. These herbal TCMs were prescribed following group discussions of TCM experts from Longhua Hospital, Shanghai University of TCM, Department of TCM of Zhongshan Hospital, Fudan University, and XR Chen in our hospital. Based on syndrome differentiation criteria from Wei-Qi-Ying-Xue and clinic programs of influenza A H7N9 implemented by the National Health and Family Planning Commission of P. R. China, Yinqiao Powder and Hoisting Powder were prescribed for patients with mild syndromes and Qingwen-Baidu-Decoction was prescribed for critically ill patients. TCMs were taken orally twice daily at 150 ml decoction per dose. The purchase, decoction, and administration of Chinese herbs were supervised by Pharmacy Department of TCM in Shanghai Public Health Clinical Center. (4) Influenza virus infections pose a significant threat to public health due to annual seasonal epidemics and occasional pandemics. Influenza is also associated with significant economic losses in animal production. The most effective way to prevent influenza infections is through vaccination. Current vaccine programs rely heavily on the vaccine's ability to stimulate neutralizing antibody responses to the hemagglutinin (HA) protein. One of the biggest challenges to an effective vaccination program lies on the fact that influenza viruses are ever-changing, leading to antigenic drift that results in escape from earlier immune responses. Efforts toward overcoming these challenges aim at improving the strength and/or breadth of the immune response. Novel vaccine technologies, the so-called universal vaccines, focus on stimulating better cross-protection against many or all influenza strains. However, vaccine platforms or manufacturing technologies being tested to improve vaccine efficacy are heterogeneous between different species and/or either tailored for epidemic or pandemic influenza. (5)Vaccination remains the most efficient and cost-effective means to prevent and control influenza in human and animal populations. Vaccines rely on the effective stimulation of the immune response against the virus, mostly against the surface glycoprotein hemagglutinin (HA), the primary immunogen of influenza viruses. Influenza vaccines were a high priority for the U.S. military since the Spanish influenza pandemic of 1918–1919 when 1 in every 67 soldiers died from influenza-related infections. However, it was not until 1946 that influenza vaccines became available for the general population. Despite many advances in terms of vaccine manufacturing and production, the technology available for influenza vaccines differs little from its origins and continue to face significant shortcomings about availability and/or efficacy. (5). As you can see from this research, they have been a lot of progress that has been done when it comes to the H7N9 Influenza Viruses. Vaccines have been created and they are working on preventing the spread of the disease. Hopefully one day this virus with be a thing of the past.

References

1. Rudenko L, Kiseleva I, Krutikova E, et al. Two Live Attenuated Vaccines against Recent Low⁻and Highly Pathogenic H7N9 Influenza Viruses Are Safe and Immunogenic in Ferrets. Vaccines (Basel). 2018;6(4):74. Published 2018 Nov 1. doi:10.3390/vaccines6040074

2. Rudenko L, Kiseleva I, Naykhin AN, et al. Assessment of human immune responses to H7 avian influenza virus of pandemic potential: results from a placebo-controlled, randomized double-blind phase I study of live attenuated H7N3 influenza vaccine. PLoS One. 2014;9(2): e87962. Published 2014 Feb 12. doi: 10.1371/journal.pone.0087962

3. Chen Z, Baz M, Lu J, et al. Development of a high-yield live attenuated H7N9 influenza virus vaccine that provides protection against homologous and heterologous H7 wild-type viruses in ferrets. J Virol. 2014;88(12):7016–7023. doi:10.1128/JVI.00100-14

4. Chen X, Yang Z, Lu Y, Xu Q, Wang Q, Chen L (2013) Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study. PLoS ONE 8(9): e73362. https://doi.org/10.1371/journal.pone.007336

5. Rajão DS, Pérez DR. Universal Vaccines and Vaccine Platforms to Protect against Influenza Viruses in Humans and Agriculture. Front Microbiol. 2018; 9:123. Published 2018 Feb 6. doi:10.3389/fmicb.2018.00123

PART III: DESIGNING A MASS VACCINATION CAMPAIGN

The promotional activities for the vaccine were initiated two months before the immunization process was carried out. The promotional methods included meeting with the leaders of the community as well as advertisement campaign such as the local television, posters and also loud speakers. The mass vaccination was done in four main stages which are: stage 1 which was known as the pilot phase which involved vaccinating a few clusters so as to test as well as fine tune the systems and also to provide final training for the other teams. The second stage was large scale vaccination at post of vaccination which are predefined I every cluster according to schedule that has been pre-set.the third stage is the initial mop-up where the vaccination post at the cluster for the first day are visited by the vaccination team. The final stage was the final centralized vaccination centre after the population used in the study was invited again to go for the vaccination.

The trained personnel coordinated as well as launched the mass vaccination campaign. Training in good clinical practices (GCPs) was given to the members of the vaccination teams as well as their supervisors a month before the campaign kicked on. These vaccinations were given in a way that would stimulate the conditions of public health programs. In every cluster, a site was selected which could have been a healthy facility, a school, locations such as intersections and squares as well as factories. These sites would then be the vaccination posts.

The table below indicates the types of personnel that was involved, their responsibilities as well as the numbers that were needed during the campaign:

Personnel	Function	Number
Vaccine team (30 teams)*
Leaders (physicians)	Overall responsible for cluster vaccination; daily collection of vaccines and supplies; treat SAE	30
Nurses	Vaccinator	43
Other health workers	Recorder	24
Non-health workers	Recorder	9
Community helpers	Facilitated immunization process; liaison between community and Zambian Center for Disease Control	78
Other
Storage room	Maintained cold chain	4
Data management	Data entry of vaccine records	6
Field health workers	SAE 3-day home visit	3
Drivers		3
Supervisors	Assured adherence to standard operating procedures	7

Every team was supposed to vaccinate a maximum of 200 persons daily and also to cover three to three to four clusters in 20 days. The identification which are the same as the local expanded program of immunization were distributed to every household a month before the vaccination was done. The information on these cards include the identification information as well as the study number which is the same as the date of the household and also the time the vaccination was carried out. To ensure that no errors occurred during the allocation of the vaccination, every vaccine team gave only one vaccination. Those who had been registered in the project census were vaccinated and later recorded. However, those who had not been registered in the census of the project were given the vaccine by the end of the campaign.

Every team that was involved in the vaccination was given one or two cold boxes, emergency kits, injecting materials, a safety disposal box as well as stationary. The eligible participants were all listed in a vaccination book of record that was available at the post used for vaccination. The people who came for vaccination and came for informed consent were also assessed for eligibility the team involved in vaccination as well as the status of the vaccination regardless of whether it was received or it was not received. It was recorded in the vaccination record book which was after entered into the vaccination book of record and then into a database. The vaccination coverage would then be calculated from this database.

Every aspect for safety for each study vaccines were emphasized and then the vaccination teams received thorough training. Two main aspects were greatly monitored these are the safe injection practices as well as the adverse events. Proper administration of the vaccines, aseptic technique of injection as well as practices of injection safety which include disposing of used needles into a safety box. These practices were closely monitored by the supervisors and also by the externl observers. The team members were supposed to report to the supervisors in case of any accidents of either sharp objects or needles. The full incineration of used safety boxes was monitored by the vaccination supervisors.

The safety of the vaccines was systematically monitored. All those who had been vaccinated were requested to stay at the vaccination posts for at least 15 minutes after the vaccination so that they can be monitored for any immediate adverse serious event (SAE) by the physician of the vaccination team. 500 vaccines that had been chosen randomly were then visited for three consecutive days after the vaccination. The visits were done by the project personnel for solicited adverse event monitoring. Unsolicited (passive) adverse event monitoring was then done for on month having following vaccinations by having all the healthcare facilities in the study areas so that signs and the symptoms of the patients who have the history of receiving the vaccines of any hospitalization cases of those who had been vaccinated. The physicians who were visiting the patients were requested to fill in a form for all the cases with all the casualties being specified. Inadvertent vaccination of women who were pregnant was also to be passively reported during the vaccination campaign. These cases would then be followed keenly until the woman delivered. The deaths of the study participants are also being ascertained through establishing a mortality surveillance which collects information from death certificates as well as cremation and also the records from the hospital for the two years period of follow up. The project personnel then took a review of all the informed forms so that they can determine the causalities and incase it was not clear, a clinical officer in trail would assist them to review the forms.

The vaccines were stored under a temperature of 2-8 degrees Celsius. All the other supplies sucj as the vaccines were all stored at a logistic hub in one of the health centre in Zambia which is a room that was equipped with 8 refrigerators and one freezer. The total number of the vaccine vials as well as all the supplies which were distributed to every was recorded daily so that the vaccine usage and wastage can be calculated. Maintaining the old chain was highly monitored from the time the vaccine left the manufacturer to the time that it reached to posts used for vaccination. Both maximum and minimum thermometers as well as the battery automated temperatures were used to monitor the temperatures of the vaccines during the transportation as well as the storage. Regular thermometers stored in the cold boxes were used at the posts of vaccines. The temperatures were then documented daily in a temperature chart twice for the vaccines which were stored and 3 times for the cold boxes.

The vaccination campaign took 30 days during which the 53 clusters received the live attenuated influenza vaccine (LAIVs). The thirty teams gave immunizations on an average of 23 days and this covered a target population of 118,500 in the 105 clusters. The results of the mass vaccination campaign revealed that the results of the vaccination were safe as well as feasible. An important rate of coverage was achieved with no main disruptions to the normal EPI or any other heath activities.

Notably, there are three major concerns when launching a population large scale vaccine campaigns which are safety, cost as well as resources. Especially in the countries that are developing such as Zambia, there is the need to identify the resources that are outside the well established local vaccines system of delivery which is the EPI program. The Zambia cvampaign is a indication that a healthcare system that is already existing can have vaccines delivered to large populations in a short period of time. The community members also have a role to play to enhance the success of the promotional campaign and the delivery of vaccines when the whole city is the target.

Mass immunization can be considered to be the most logical strategy that is outside the EPI program in settings which have high incidences of disease or in the populations which are exposed to outbreaks that can be predicted. Besides the school based immunization programs, mass immunization are also an important public health strategy to prevent the influenza H7N9 virus in high risk population in Zambia.

References

Morbidity and Mortality Weekly Report: MMWR. (2008).

Poland, G. (2018). Vaccinations. St. Louis, MO: Elsevier Health Sciences.

Roche, B., Broutin, H., & Simard, É. (2018). Ecology and Evolution of Infectious Disease: Pathogen Control and Public Health Management in Low-Income Countries. New York, NY: Oxford University Press.

T'ai-Pei Public Health Teaching and Demonstration Center. (1964). Report.

United Nations. General Assembly. Committee on Information from Non-Self-Governing Territories. (1957). Non-self-governing Territories: Summaries and Analyses of Information Transmitted to the Secretary-General.

United States. Congress. House. Committee on Appropriations. Subcommittee on the Departments of Labor; Health and Human Services; Education; and Related Agencies. (2015). Departments of Labor, Health and Human Services, Education, and Related Agencies Appropriations for 2016: Hearings Before a Subcommittee of the Committee on Appropriations, House of Representatives, One Hundred Fourteenth Congress, First Session.

PART IV: IMPLEMENTATION

After developing the vaccine and campaigning for the mass immunization of the vaccine, the next step will be the implementation process. this section will discuss the barriers to accessing the vaccine. These are the factors that are derived from health are production which interact to produce healthcare services. the factors include but are not limited to availability of the vaccines, staff that are qualified and their attitude towards their job, materials, appropriate technologies, health priorities, capital equipment as well as the issues in the health system. Individual and the household factors that can affect the implementation of live attenuated influenza vaccines (LAIVs) are income, sex, age, education as well as the knowledge about the illness as well as the need for medical treatment. The community factors that will affect the implementation are religious and cultural influences as well as other social factors which affect the individual preferences (Great Britain: Parliament: House of Commons: International Development Committee, 2014).

Other factors that hindered effective immunization are in Zambia is the lack of communication and immunization transfer between the health providers as well as caretakers and this deterred accessing of the services. The notification of the community between the community members and the service providers was not effective. Thus, efforts are required in Zambia to make sure that the communication strategies as well as the messages used enable increased flow of information and also the resultant service accessibility. Additionally, long distance to the health facilities has been recognized in many studies as a barrier to health care in the rural areas and Zambia is not an exception. The people who were close to where the immunization of the vaccine was being carried out benefited from the services and also utilized the services than those who lived far from where the immunization was being carried out. The approach that can be used to deal with the issue of distance is strengthening of the outreach of the existing programmes as well as strengthening and extending the services being offered by the community health workers to make sure that they the targeted delivery of services is closer to the households. The outreach programs are going to be strengthened by making sure that transport services is always there for the programmes. This can also be done by increasing the number of the outreach posts in areas that are both necessary as well as feasible as it was suggested by the participants. Communication channels to transfer the health relate information, education as well as communication require strengthening to reach to the targeted community members. Various communication channels such as public lectures, dances as well as role plays have shown so much effectiveness in the rural areas (Medical Journal of Zambia, 2003).

Physical barriers are another challenge or the implementation of the vaccine. Zambia being a developing country, there are few health facilities and thus the people are forced to walk for long distances to access the health service. The road network is bad and also most of the roads in the country are in a bas state. The problem occurs during the rainy season where by reaching to the health facility becomes a challenge even with a bicycle or an ox-cart (Milimo, Shilito, & Brock, 2000). The poor roads will make it hard for the people to reach to the health facility even when they have an emergency. The effect of the long distances combined with the absence of transportation as well as the poor roads will increase the challenge that is faced while accessing the health facility.

Economic barriers are another challenge. As mentioned early, Zambia is a developing country and thus most of its citizens are not economically stable. This means that it is very difficult for most of them to raise the money needed for healthcare services or even for transportation to the healthcare facilities. It will be difficult for the people to raise the money required for transport to go and get the free vaccination against influenza virus. They are not only required to budget for transport but also for food since when they leave their homes in the morning, they expect to get back in the evening due to the long distance. It is also hard for them to raise money incase they are referred to the next level of care. Most of the patients who are forced to seek extensive care end up selling their property so that they can have the money. The longer it would take for the patients to get the money, the more the patient was delayed to receive the required care. Although the government of Zambia has introduced the free medical care, there are still direct and indirect costs that are incurred while accessing the health services at the health centers. This is going to hinder many people for accessing care since they are not in a position to meet the cost. This problem is even made worse by the high levels of poverty in most of the areas in Zambia. The costs in the health care centers has risen as a result of insufficient funds from the government where the people will be required to buy their own medical supplies.

Another barrier to the implementation of the vaccine is the cultural barrier and lack of communication. Cultural barrier is one very common in Zambia and can hinder the implementation of the vaccine. This also includes their values as well as their beliefs. Most people in Zambia belief that they consult their family members as well as the elderly before they seek clinical assistance. This means that if the elderly people are against the vaccination, then most people will not go for it. This is due to the fact that the elderly people are said to be most knowledgeable and thus their knowledge cannot be underestimated. The people in the communities are also believed to related different diseases to certain beliefs. In case a person falls ill from a disease that is not known, they are not first of all taken to the clinic as they are believed to have been bewitched (Reaching the Marginalized, 2010). Such patients will only be taken to the clinic when the traditional healers fail in curing the disease. Another common belief of the Zambians is that a baby is not supposed to be taken in the public even in the clinic. This is because most of them believe that if a baby is taken to such a place, they are bound to contract diseases. Due to such beliefs, the mothers do not take their kids to the clinic for either monitoring or for immunization to prevent the kid from falling sick.

Religious beliefs are also a barrier since some religions forbids their believers form seeking conventional medicines and immunization services. As a result, the believers will end up using the traditional medicines over the modern medicine. This turns out to be great immunization barrier in Zambia. Another barrier is the lack of information about the health issues, discrimination, myths as well as misconceptions about certain diseases. The people need to be more educated as well as awareness raised in the communities regarding illnesses as well as the health services. Lack of information about the healthcare services will lead to the community members delaying to seek care on time. This will also be hard for them to the signs of illnesses that require care as well as attention (Seshamani, 2016).

From the above discussion it is evident that there are barriers that hamper the access of care by the people of Zambia among which include physical, cultural and social factors. The distance to the heath facilities as well as the poor roads is also a big barrier. Although the government came up with free medical policy, the citizens in the country are still forced to pay for the services due to the poor funding by the government.

References

Becher, H. (2005). Health Research in Developing Countries: A Collaboration Between Burkina Faso and Germany. Berlin, Germany: Springer Science & Business Media.

Great Britain: Parliament: House of Commons: International Development Committee. (2014). HC 246 - Strengthening Health Systems in Developing Countries. London, England: The Stationery Office.

Medical Journal of Zambia. (2003).

Milimo, J. T., Shilito, T., & Brock, K. (2000). The Poor of Zambia Speak: Who Would Ever Listen to the Poor?

Reaching the Marginalized. (2010). Paris, France: UNESCO.

Seshamani, V. (2016). Overcoming Barriers to Zambia's Development: Dismantling the Tripod of Deprivation, Debt and Disease.