Bartholomew D Akanmori1*, Tieble Traore1, M Balakrishnan2, C Maure2, P Zuber2, R Mihigo2

1Immunization and Vaccines Development Programme, Family & Reproductive Health Cluster, WHO Regional Office for Africa, Djoué, Brazzaville, Congo

2Safety and Vigilance, Essential Medicines and Health Products Department, Health Systems and Innovations Cluster, World Health Organization, 1211 Geneva 27, Switzerland

Introduction: The number of subjects in clinical trials, is often limited and inadequate for detection of all adverse events which may be associated with vaccines, especially very rare ones. In addition, there is a surge in introduction of new vaccines into national immunization programmes in the WHO African Region, some of which have been used in a limited number of people, highlighting the need for functional national for pharmacovigilance systems for adverse events following immunization (AEFIs). Recognizing this, WHO and partners are supporting countries to develop national plans, providing training and investments in vaccine safety and pharmacovigilance. Despite these efforts, surveillance for vaccine safety in many countries remain weak. This paper reviews cases of AEFI reported by countries countries in the WHO/UNICEF Joint Reporting Form of WHO/AFRO between 2010 and 2015, discusses some of the causes of the low reporting while exploring how countries can rely on new opportunities and systems to improve their reporting and vaccine safety in general.

Methodology: The implementation status of multi-stakeholder national plans developed by national immunization programmes, Pharmacovigilance Centres (PVCs) and the National Regulatory Authorities (NRAs) of 28 countries was reviewed. Using data from the WHO/UNICEF Joint Reporting Form and the introduction of new vaccines by countries in the WHO African, the impact of these plans on reporting of AEFIs was assessed for the countries.

Results: The analysis of performance revealed that only five countries have fully implemented plans for vaccine safety monitoring and pharmacovigilance in accordance with the Global Vaccine Safety Initiative (GVSI) blueprint. Implementation of the plans in the remaining 23 countries is slow. From 2010 - 2015, just 28 countries reported AEFIs as part of the WHO /UNICEF JRF. Yet 83% of countries introduced at least one new vaccine, with an average of 2 to 3 new vaccines being introduced per country over the period. Many countries have not fulfilled the responsibility of establishing expert committees on AEFI, developed guidelines, trained their staff on vaccine safety and put in place effective vaccine safety communication.

Discussion: The low AEFI reporting and weak pharmacovigilance demands special emphasis on capacity building, tailored to country needs to improve the reporting to meet the GVAP goals and UMC ADR guidelines. More sustainable support in ways that strengthen pharmacovigilance in general for all medical products and AEFI surveillance in particular in countries is needed. Opportunities are presented by the GVAP, the GVSI, networks such as the African Vaccine Regulatory Forum (AVAREF), Developing Countries Vaccine Regulatory Network (DCVRN), Developing Countries Vaccine Manufacturers Network (DCVM) and the International Federation of Pharmaceutical Manufacturers (IFPMA) as well the African Medicines Regulatory Harmonization (AMRH). African countries should exploit these opportunities to further strengthen their AEFI monitoring and pharmacovigilance.

DOI: 10.29245/2578-3009/2018/si.1112 View / Download Pdf

Amos Petu*

Immunization Financing Sustainability (EPI), Intercountry Support Team East and Southern Africa, World Health Organization, Harare, Zimbabwe

Immunization programme has contributed to saving many lives from avoidable deaths and bring many other benefits, including healthier children, increased school attendance, and increased productivity. In the past 10 years, immunization as a public health intervention has expanded in target as well as number of vaccines to be delivered to a broader range of people and new vaccines. Immunization is also exceptionally of good value, returning many dollars in economic benefits for every dollar invested in immunization services. Healthy individuals are more productive, earn more, save more, invest more, consume more, and work longer: which all impact to increase a nation’s GDP. Immunization is one of the most effective, and cost-effective, public health tools that contribute to this situation. Fully immunized children have better educational outcomes and, over time, make for a more productive workforce. Consequently immunization, which must be sustained indefinitely, as a long-term investment require stable, long-term financing. A start point is a plan which is translated into funding for the programme. In sustainability a detailed planning process that assures a review of the situation leading to detailed programming in terms of response to challenges and finally culminating in costing so that funding requirements are determined and mobilised cannot be overemphasized. The experience has been varied in Africa region. While governments have made significant strides to increase funding for immunization programs over the last five years, further commitment is needed to achieve full financing and national ownership of immunization programs.

Most countries have adopted the Comprehensive Multi-year Planning framework for planning and are thus able to put together their resource needs for immunization programmes. To continue to have the necessary benefits of high coverage and cover the increased investment requirements governments will need to do more to assure robust funding in a sustainable and predictable manner. The paper tells the story of importance of planning using the cMYP processes to immunization financing sustainability as a necessary condition in the trajectory towards sustainability. This article presents the experience of countries from planning to funding, drawing on the interconnectedness of adequate planning, ability to mobilise resources and thus better move towards sustainable funding. As governments pursue high level order of planning, they are in a better position to stem overdependence on Gavi and other external support for future sustainability.

DOI: 10.29245/2578-3009/2018/si.1113 View / Download Pdf

Isaiah Chebrot1,2, Annet Kisakye3, Brendan Kwesiga4, Daniel Okello5, Diana Kiiza6, Eva Kabwongera7, Robert Basaza1*

1International Health Sciences University, Uganda

2Kawempe Division Health Office, Kampala City, Uganda

3World Health Organization, Uganda Country Office, Uganda

4USAID/Management Science for Health, Kampala, Uganda

5Directorate of Public Health and Environment, Kampala City, Uganda

6Health Economist, Elma philanthropies EA, Kampala, Uganda

7United Nations Child Fund, Uganda Country Office, Uganda

Background: Reducing infant and under-five mortality by use of cost-effective strategies like immunization continues to be a challenge, particularly in resource limited settings. Strategic planning for immunization requires credible costing information to estimate available funding, allocate funds within the program and avoid funding shortfalls. This study assessed the total and unit costs of providing routine immunization in health facilities in Kampala.

Methods: This was a retrospective descriptive cost analysis study that applied a bottom-up, ingredients-based costing methodology which identified costs from the perspective of the health service providers. The cost of providing immunization services in health facilities in Kawempe Division in the financial year 2015/2016 was determined using relevant data which was collected using an Excel questionnaire adapted from the CostIt software of the World Health Organization. The analysis was also based on the same CostIt software.

Results: The average total facility immunization costs were USD 14,415.1 with a range of 8,205.3 at private for profit to USD 47,094.9 at public health facilities. Vaccines and supplies were the main cost driver accounting for 63.6% followed by personnel costs at 24.0%. Routine facility based immunization had the highest cost with an average of 47.9% followed by outreach services at 32.3%. The average cost per dose administered was USD 1.4 with a range of USD 1.0 in larger health centres (HCIV) to 1.5 in HCIII (medium-sized HC or dispensary). The average cost per DPT3 immunized child was USD 20.0 with a range of USD 12.6 in HCIV to 22.0 in HCIII. The findings show a great variance between facility ownership and levels.

Conclusions: The study found that the recurrent costs were significantly higher than capital costs and this was across all facilities. Vaccines and personnel costs were the two main cost drivers. Routine facility based immunization was the costliest activity followed by outreaches with social mobilization being the least. The cost per dose administered and DPT3 immunized child were dependent on outputs with high output health facilities having less unit costs compared to facilities with less out outputs. Private health facilities had higher unit costs compared to publicly owned health facility.

PNFP- Private Not for Profit; PFP- Private for Profit; HC-Health Center; KCCA- Kampala Capital City Authority; MOH- Ministry of Health; cMYP- comprehensive Multi-Year Plan; USD- United States Dollars.

DOI: 10.29245/2578-3009/2018/si.1114 View / Download Pdf

Ali Mehdizadeh1, Vahid Shaygannejad2*, Meysam Amidfar3, Seyed Javad Hasheminia4, Mohamad Mousaei Ghasroldasht5

1School of medicine, Isfahan University of medical sciences, Isfahan, Iran.

2Isfahan neuroscience research center, alzahra research institute, Isfahan University of medical sciences, Isfahan, Iran.

3Tehran University of medical sciences, Tehran, Iran

4Department of immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

5Biology department, shahid ashrafi Isfahan University, clinical laboratory, alzahra hospital, Isfahan, Iran.

Background: interleukin-23 (IL-23) is a member of the IL-12 cytokine family that has shown through enhancement of T helper type 17 (Th17) cells expansion could play an important role in the inflammatory autoimmune responses in multiple sclerosis (MS).

Methods: The objective of the present study is to measure the relative expression of IL-23 mRNA in the peripheral blood of 15 MS patients in comparison with 15 healthy control subjects.

Results: the relative gene expression level of IL-23 in the peripheral blood cells from MS Patients was significantly increased compared to healthy controls (p < 0.001).

Conclusions: Our findings revealed upregulated gene expression pattern of IL-23 in the peripheral blood of MS patients that may be a peripheral marker for diagnosis of MS and might be a novel and promising therapeutic target for MS.

DOI: 10.29245/2578-3009/2018/4.1147 View / Download Pdf

Joseph Okeibunor, Richard Mihigo, Blanche Anya*, Felicitas Zawaira

WHO Regional Office for Africa, Brazzaville, Congo

The 5th edition of the African Vaccination Week (AVW) kicked off in Lusaka, Zambia, on 23 April 2016, the same day as did the 4th World Immunization Week (WIW), and vaccination week in other WHO regions. The theme was “Save lives, prevent disabilities, vaccinate!”. The aim was to draw attention to the need to attain universal immunization coverage in the African Region by closing the immunization gap, while also celebrating the important polio eradication milestone reached in the African Region.

Twenty-eight (59.6%) of the 47 countries in the African Region celebrated the AVW within the regionally set dates of 24th to 30th April 2015. However, given its flexibility, the celebration continued until September in 15 other countries in the Region. Three countries, namely Comoros, Gabon, and Cape Verde did not join the celebration for the 2015 edition of the AVW.

Countries used the opportunity to introduce new vaccines into their routine immunization. Populations, hitherto unreached with basic health services were reached with needed services, such as vitamin A supplementation, deworming, and catch up immunization services. The programmes promoted awareness of the benefits of vaccines and the rights of communities to demand vaccines and immunization services to save lives and prevent disabilities. The number of participating countries rose steadily from 40 in 2011 to 43 and 46 countries in 2013 and 2014 respectively. The number ranged from one intervention integrated with AVW in 17 countries to 5 interventions integrated with the AVW in three countries. In 2015, 67.4% of the participating countries integrated other interventions with AVW activities.

DOI: 10.29245/2578-3009/2018/si.1101 View / Download Pdf

Sedera Aurélien Mioramalala1,2*, Rado Malalatiana Ramasy Razafindratovo1, Ando Rakotozanany4, Raharizo Miarimbola1, Goitom Weldegebriel5, Jason M Mwenda6, Annick Lalaina Robinson3,4

1Public Health Department, Faculty of Médicine, Antananarivo, Madagascar

2National Malaria Country Program, Public Health Ministry, Antananarivo, Madagascar

3Mother and Child Department, Faculty of Medicine, Antananarivo, Madagascar

4Center Hospital Academic Mother Child, Public Health Ministry, Centre Hospitalier Universitaire Mère Enfant Tsaralalàna (CHU MET), Antananarivo, Madagascar

5WHO Inter-Country Support Team: East and Southern Africa (WHO IST/ESA)

6WHO Regional Office for Africa (WHO/AFRO), Brazzaville, Congo

Background: Bacterial meningitis (BM) remains a global public health problem and most cases and deaths occur in Sub-Saharan Africa and especially in children less than five years old, due to a variety of factors. This study was conducted to determine the principal factors associated with death and survival of children due to BM in a typical African tertiary health facility.

Methods: A retrospective case-control study of children hospitalized for BM was conducted in the University Hospital of Tsaralalàna (CHUMET). All children aged 3 to 59 months hospitalized for bacterial meningitis and confirmed by bacteriology were included. The cases were children who died from BM, and the controls were the survivors. Data was analyzed using Stata 13.

Results: The factors associated with death were the number of siblings over 3 (14,48 [2,53 - 82,95]), overcrowding (9,31 [1,39 - 62,29]), time before hospitalization of more than five days (9,26 [1,36 – 62,92]), impaired consciousness (47,74 [6,24 - 364,96]), and meningococcal meningitis (36,68 [1,90 – 704,97]).

Conclusion: These factors are mainly indicators of low socioeconomic status, clinical severity of signs and particularly virulent organisms. The early detection of patients at risk allows clinicians to give them appropriate care right from admission. Further studies are necessary especially, the evaluation of the emergency care provided.

DOI: 10.29245/2578-3009/2018/si.1102 View / Download Pdf

Nicksy Gumede1*, Joseph Okeibunor1, Ousmane Diop2, Maryceline Baba1, Jacob Barnor1, Salla Mbaye1, Johnson Ticha1, Goitom Weldegebriel1, Humayun Asghar1, Pascal Mkanda1

1WHO Regional Office for Africa, Brazzaville, Republic of Congo

2WHO Head Quarters, Geneva, Switzerland

3Intercountry support teams (ISTs) in East and Southern Africa, Harare, Zimbabwe

4WHO Regional Office for East and Mediterrian, Cairo, Egypt

Objective: This article summarises the progress made since the introduction of environmental surveillance in the African Region.

Method: Country selection was based on the poor AFP performance indicators i.e. Non polio AFP rate and stool adequacy. It was recommended that any country not meeting the required indicators should consider environmental surveillance activity as an additional tool to support AFP surveillance. The sites selection considered proximity to the target population, the size of the population to be sampled and the sensitivity of the sampling site.

Results: One hundred and fifty three sites have been established in Africa since 2011. In 2011, Nigeria was first country to introduce environmental surveillance and currently with of 59 validated sites, followed by Kenya in 2013 validating and sampling 9 sites and Angola 4 active sites in 2014. In 2014, Cameroon introduced ES and 31 sites followed by Niger with 9 sites and Madagascar with 23 sites. Later in the same year, Chad introduced ES activity and 4 active sites were selected. In 2015 Senegal introduced 3 sites, Guinea and Burkina Faso introduced 4 sites each. , and. In 2016, a total of 179 Sabins, 36 Sabin 2s, 196 non polio enteroviruses (NPEV) and 1 vaccine-derived polioviruses (VDPV) were reported in Nigeria. Cameroon and Chad isolated 14 and 4 Sabins and 72 and 40 NPEV respectively. In Madagascar a total of 39 Sabins, 11 Sabin 2s and 277 NPEV were isolated. In other countries a majority of NPEV were isolated (data not shown).

Conclusion: This report describes the progress and expansion of environmental surveillance that contributed to the identification of polioviruses from the environment and the interruption of wild poliovirus transmission in the African Region.

DOI: 10.29245/2578-3009/2018/si.1103 View / Download Pdf

Edna Moturi1, Carole Tevi-Benissan1*, José E. Hagan2, Stephanie Shendale3, David Mayenga1, Daniel Murokora1, Minal Patel2, Karen Hennessey3, Richard Mihigo1

1World Health Organization Regional Office for Africa, Brazzaville, Republic of Congo

2Global Immunization Division, Centers for Disease Control and Prevention, Atlanta, GA, USA

3World Health Organization, Expanded Programme on Immunization, Geneva, Switzerland

Introduction: Few African countries have introduced a birth dose of hepatitis B vaccine (HepB-BD) despite a World Health Organization (WHO) recommendation. HepB-BD given within 24 hours of birth, followed by at least two subsequent doses, is 90% effective in preventing perinatal transmission of hepatitis B virus. This article describes findings from assessments conducted to document the knowledge, attitudes, and practices surrounding HepB-BD implementation among healthcare workers in five African countries.

Methods: Between August 2015 and November 2016, a series of knowledge, attitude and practices assessments were conducted in a convenience sample of public and private health facilities in Botswana, the Gambia, Namibia, Nigeria, and São Tomé and Príncipe (STP). Data were collected from immunization and maternity staff through interviewer-administered questionnaires focusing on HepB-BD vaccination knowledge, practices and barriers, including those related to home births. HepB-BD coverage was calculated for each visited facility.

Results: A total of 78 health facilities were visited: STP 5 (6%), Nigeria 23 (29%), Gambia 9 (12%), Botswana 16 (21%), and Namibia 25 (32%). Facilities in the Gambia attained high total coverage of 84% (range: 60–100%) but low timely estimates 7% (16–28%) with the median days to receiving HepB-BD of 11 days (IQR: 6–16 days). Nigeria had low total (23% [range: 12–40%]), and timely (13% [range: 2–21%]) HepB-BD estimates. Facilities in Botswana had high total (94% [range: 80—100%]), and timely (74% [range: 57—88%]) HepB-BD coverage. Coverage rates were not calculated for STP because the maternal Hepatitis B virus (HBV) status was not recorded in the delivery registers. The study in Namibia did not include a coverage assessment component. Barriers to timely HepB-BD included absence of standard operating procedures delineating staff responsible for HepB-BD, not integrating HepB-BD into essential newborn packages, administering HepB-BD at the point of maternal discharge from facilities, lack of daily vaccination services, sub-optimal staff knowledge about HepB-BD contraindications and age-limits, lack of outreach programs to reach babies born outside facilities, and reporting tools that did not allow for recording the timeliness of HepB-BD doses.

Discussion: These assessments demonstrate how staff perceptions and lack of outreach programs to reach babies born outside health facilities with essential services are barriers for implementing timely delivery of HepB-BD vaccine. Addressing these challenges may accelerate HepB-BD implementation in Africa.

DOI: 10.29245/2578-3009/2018/si.1104 View / Download Pdf

Richard Mihigo1*, Joseph Okeibunor2, Balcha Masresha1, Pascal Mkanda2, Felicitas Zawaira1, Joseph Cabore3

1Family and Reproductive Health Cluster, WHO Regional Office for Africa

2Polio Eradication Programme, WHO Regional Office for Africa

3Office of the Regional Director, WHO Regional Office for Africa

Objective: This paper gives a brief update on the status of the immunization and vaccine development in the WHO African Region. It also highlights the progress on the control, elimination or eradication of vaccine preventable diseases in the African Region.

Method: The paper reviews national immunization programme data as well as WHO-UNICEF Estimates for Immunization Coverage (WUENIC) in the African Region from 2012-2016.

Results: It revealed that there has been considerable success with the development and introduction of new vaccines in the Region. However, uptake of these vaccines has not matched the level of success in new vaccine introduction. This has made the goal of reaching high and equitable immunization coverage a mirage in the Region. Multiple barriers have been blamed for this, chief among which inadequate commitment of national governments and weak community engagement to immunization service delivery in the Region. Steps are taken to address these issues, including sensitization of government of the African Region to prioritize Universal Access to Immunization as a Cornerstone for Health and Development in Africa. This is because it is argued that development efforts are link to the human beings for whom progress is targeted and/or agents that bring about development.

Conclusion: Saving human lives therefore is critical to the realization of development goals. It is important that immunization coverage is universal to achieve the control/elimination of vaccine preventable diseases.

DOI: 10.29245/2578-3009/2018/si.1105 View / Download Pdf

Amadou Fall1, André Fouda Bita1, Clement Lingani1, Mamoudou Djingarey1, Carole Tevi-Benissan2, Marie-Pierre Preziosi3, Olivier Ronveaux4, R. Mihigo2, J. Okeibunor5, Bartholomew Dicky Akanmori2*

1IST West Africa, WHO Regional Office for Africa, Ougadougou, Burkina Faso

2IVD/FRH, WHO Regional Office for Africa, Brazzaville, Congo

3IVR/IVB WHO HQ, Geneva, Switzerland

4World Health Organization. Department: Control of Epidemic Diseases. City: Geneva

5Polio Eradication Programme, WHO Regional Office for Africa, Brazzaville, Congo

Background: Epidemics of meningococcal disease constitute a major public health challenge in Africa, affecting mostly the 24 countries of the meningitis belt. These epidemics led to a call for a call for a safe, effective and affordable conjugate vaccine against the major serogroup responsible for recent epidemics by leaders of the region.

Objective: This paper documents experiences with efforts at eliminating epidemic meningitis in the African Region.

Method: The meningoccocal serogroup A conjugate vaccine was developed, licensed and offered to more than 235 million people through mass vaccination campaigns in 16 countries since 2010. Future plans include providing the vaccine to the remaining countries in the African Meningitis Belt and, to implement the vaccine into routine national infant immunization programme and to organise catch-up immunization campaigns every 5 years for unvaccinated <5 year-olds who had missed their routine vaccinations.

Results: The success of the project is evidenced by the the large declines in cases of group A meningococcal disease since 2010, with no cases reported in vaccinated persons across the 16 countries, reflecting the highly effective nature of the vaccine. The successful control of serogroup A meningococcal disease has highlighted the need to tackle other meningococcal serogroups through development of polyvalent conjugate vaccines with the aim of eliminating epidemics of meningococcal meningitis in the African region.

DOI: 10.29245/2578-3009/2018/si.1106 View / Download Pdf

Joseph C. Okeibunor1*, Ikechukwu Ogbuanu2, Anya Blanche1, Kwame Chiwaya3, Geoffrey Chirwa4, Zorodzai Machekanyanga5, Richard Mihigo1, Felicitas Zawaira1

1WHO/AFRO, Brazzaville, Congo

2WHO/HQ, Geneva, Switzerland

3WHO, Lilongwe, Malawi

4Ministry of Health, Malawi

5WHO/IST East & Southern Africa

Background: Missed opportunities for vaccination (MOVs), estimated to be about 32-47% of child healthcare clinic visits in various settings globally, contribute to unfulfilled childhood vaccination coverage targets in the African region.

Objective: We assessed the extent of MOVs, identify local drivers and test interventions to reduce MOVs in Malawi.

Method: We conducted in-depth and key informant interviews with administrators of district hospitals and officers in charge of community health facilities. Focus group discussions were held with health workers and caregivers of children under 24 months of age who received services from study health facilities in Malawi. Coverage rates were collected from the health facility récords.

Results: Vaccination is appreciated in the communities, but coverage is generally below targets. In some facilities, reported coverage was less than 50%. Opportunities to provide up-to-date vaccination for children were missed due to lack of awareness and knowledge of health workers and caregivers, attitude and priority of health workers, long waiting time, poor coordination and referral of eligible children by clinicians and nurses and overall lack of a team approach to vaccination perceived as a responsibility of health surveillance assistants. Other notable issues included limited time of caregivers labouring on estate farms, unavailability of vaccines resulting from poorly functioning of cold chain equipment and limited transport and failure to appreciate the impact of MOV on poor immunization coverage.

Conclusion: Simple, low-cost, pragmatic and community-driven interventions that may reduce MOVs and improve vaccine coverage.

DOI: 10.29245/2578-3009/2018/si.1107 View / Download Pdf

Blanche Anya*, Joseph Okeibunor, Richard Mihigo, Alain Poy, Felicitas Zawaira

WHO Regional Office for Africa, Brazzaville, Congo

Background: Some progress has been made in expanding immunization in the African Region over the last four decades. However, an estimated 22% of the eligible children in the African Region, located in four countries of the African Region (Democratic Republic of the Congo, Ethiopia, Nigeria and South Africa), continue to miss vaccination services for various reasons. This paper documents the status of routine immunization in the African Region.

Methods: Programme records, reports and statistics were reviewed for this paper.

Results: Challenges remain in reaching an estimated 20–30% of children across the Region. In addition to the traditional vaccines (DTP, measles, polio and tuberculosis) newer ones, such as for Pneumococcal conjugate vaccine (PCV) and rotavirus, are being rolled out in the Region but uptake and coverage are slow and patchy both within and between countries.

Conclusion: The new regional strategic plan for immunization 2014–2020 is intended to provide policy and programmatic guidance to Member States, in line with the 2011–2020 Global Vaccine Action Plan (GVAP), in order to optimize immunization services and assist countries to further strengthen their immunization programmes.

DOI: 10.29245/2578-3009/2018/si.1108 View / Download Pdf

Godfrey S. Getz1* and Catherine A. Reardon2

1Department of Pathology, The University of Chicago, Chicago, IL 60637, USA

2Ben May Institute for Cancer Research, The University of Chicago, Chicago, IL 60637, USA

Atherosclerosis is the underlying basis for most cardiovascular diseases. It is a chronic inflammation affecting the arterial intima and is promoted by hypercholesterolemia. Cells of both the innate and adaptive immune systems contribute to this inflammation with macrophages and T cells being the most abundant immune cells in the atherosclerotic plaques. In this review, we discuss the studies that examined the role of T cells and T cell subsets in Apoe-/- and Ldlr-/- murine models of atherosclerosis. While there is a general consensus that Th1 cells are pro-atherogenic and regulatory T cells are atheroprotective, the role of other subsets is more ambiguous. In addition, the results in the two models of atherosclerosis do not always yield similar results. Additional studies in the two murine models using cell specific gene manipulations are needed.

DOI: 10.29245/2578-3009/2018/3.1144 View / Download Pdf

Jheng-Yu Wu1, 2, Niko Moses1,2, Wenlong Bai3, Xiaohong Mary Zhang1,2*

1Department of Oncology, Molecular Therapeutics Program, Karmanos Cancer Institute, Detroit, Michigan 48201

2Wayne State University School of Medicine, Detroit, Michigan 48201

3Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612

The oncogene HDAC6 controls numerous cell processes that are related to tumorigenesis and metastasis, and has recently arisen as a target to treat malignancies. The ERK cascade is a classic pathway driving oncogenesis, and the components of this pathway are either highly mutated in cancers or are vital in cancer’s pathological activity. The interactions between these important components of tumor proliferation have been examined, and our research has demonstrated that they regulate each other as evidenced by different posttranslational modifications. Preclinical evidence also supports clinical trials cotargeting these two pathways, which may provide better efficacy than single treatment. Furthermore, HDAC6 and ERK both participate in the regulation of T cell maturation and may have implications on the functions of immune cells. This leads to the possibility of connecting HDAC6 and ERK to immunotherapy. In this review, we summarize the published studies about the interaction of HDAC6 and ERK cascade and their relationship to cancers. We also include the association of HDAC6 and ERK to immune system and discuss the plausibility of linking these to immunotherapy.

DOI: 10.29245/2578-3009/2018/3.1143 View / Download Pdf

Ana Cirac1,2,3, Uta Behrends1,2,3, and Josef Mautner1,2,3*

1Children’s Hospital, Technische Universität München, Munich, Germany

2Research Unit Gene Vectors, Helmholtz Zentrum München, Munich, Germany

2German Centre for Infection Research (DZIF), partner site Munich, Germany

The Epstein-Barr virus (EBV), a ubiquitous γ-herpesvirus, has been implicated in the etiology of several acute and chronic inflammatory, autoimmune, and malignant diseases. Although considered a genetically stable virus, recent sequence information obtained from a large number of viral isolates from around the world revealed that numerous viral variants exist. Whether these different strains differ in pathogenicity and immunogenicity and thereby contribute to the varying incidence rates of several EBV-associated diseases in different geographical regions is now studied intensively. The recent identification of amino acid sequence polymorphisms in a high percentage of all known virus-specific CD4+ and CD8+ T-cell epitopes, and of holes in the individual T-cell repertoire against epitopes derived from strain variants, may suggest that antiviral immunity is incompletely cross-protective against diverse EBV strains. These findings may have implications for immunological approaches seeking to prevent, monitor, or treat EBV-associated diseases.

DOI: 10.29245/2578-3009/2018/3.1145 View / Download Pdf

Wilma Carvalho Neves Forte1*, Tainá Mosca1

1Immunology Discipline, Santa Casa de Sao Paulo School of Medical Sciences, São Paulo, SP, Brazil

DOI: 10.29245/2578-3009/2018/3.1140 View / Download Pdf

Kazuhiko Hashimoto1*, Yutaka Oda1, Kotaro Yamagishi1, Ichiro Tsukamoto1, Masao Akagi1

1Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka 589-8511, Japan

Background: Some reports have shown that metabolic syndrome, including hypertension, hyperlipidemia, and diabetes mellitus, contributes to osteoarthritis (OA) development. Further, lectin-like oxidized low-density lipoprotein (ox-LDL) and ox-LDL receptor-1 (LOX-1), which contributes to atherosclerosis, have also been considered factors contributing to OA development. Several studies have suggested that the LOX-1/ox-LDL system is involved in OA development in vitro. We have suggested the same and conducted in vitro and in vivo studies to validate this concept. However, the role of the LOX-1/ox-LDL system in OA development has not been clarified. This study aimed to identify the mechanism of the LOX-1/ox-LDL system to clarify OA development.

Methods: A zymosan-induced arthritis model was used to identify the mechanism of the LOX-1/ox-LDL system using LOX-1-knockout (KO) mice. Zymosan was administered via the intra-articular route to induce arthritis.

Results: From our experiment, we found that the LOX-1/ox-LDL system contributes to OA development through matrix metalloproteinase-3.

Conclusion: Our findings suggest that the treatment of abnormal lipid metabolism may contribute to the prevention and suppression of arthritis.

DOI: 10.29245/2578-3009/2018/3.1139 View / Download Pdf

Mahmoud M. Bakr1, Simon Guan2, Norman Firth3, Robert M. Love1*

1School of Dentistry and Oral Health, Griffith University, Australia

2School of Dentistry, University of Otago, New Zealand

3University of Queensland, Brisbane, Australia

There is increasing evidence suggesting that cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors (CDIs) either are themselves targets for genetic change in cancer or are disrupted secondarily by other oncogenic events. Cyclin D1 and p27KIP1 are two important regulators at the G1/S checkpoint. Cyclin D1 is an oncogene of cell cycle regulation with positive effect. Normally, cyclin D1 at G1 is constant or at a very low level and its excessive expression may be associated with the disordered proliferation of cells leading to malignant change. On the other hand, p27KIP1 is an anti-oncogene for cell cycle regulation, which functions as a negative regulator. Under the regulation of TGF-β, p27KIP1 inhibits the activity of oncogenes and controls the transition of the G1/S phase mainly by the interaction with CDK and CDK-Cyclin in order to inhibit cell proliferation and give cells opportunities to repair DNA. In addition, p27KIP1 not only acts as CDK inhibitor, but also promotes cell differentiation and induces the apoptosis of cells. In this article we review studies that have explored the effects of cyclin D1 and P27KIP1 on cancer progression and dysplasia with a specific focus on oral dysplasia and oral squamous cell carcinoma (OSCC). We also aim to shed some light on the different means of evaluating the interaction between Cyclin D1 and P27KIP1 as well as the immunohistochemical reactions associated with different forms of cyclin D1.

DOI: 10.29245/2578-3009/2018/3.1142 View / Download Pdf

María Virginia Croce1*, Martín E. Rabassa1, Amada Segal-Eiras1

1Centre of Basic and Applied Immunological Research (CINIBA), Faculty of Medical Sciences, National University of La Plata, Argentina.

DOI: 10.29245/2578-3009/2018/3.1141 View / Download Pdf

Antonio Voza1*

1Emergency Department, Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy

The term post-cardiac injury syndrome (PCIS) defines a group of inflammatory diseases involving predominantly the pericardium. The syndrome results from a cardiac injury and refers mainly to post-myocardial infarction pericarditis, post-pericardiotomy syndrome and post-traumatic pericarditis (including iatrogenic conditions appearing after percutaneous interventions).

Signs and symptoms are similar to those seen in acute pericarditis and pericardial effusion in other clinical settings. The diagnosis is clinical and could be challenging in the Emergency Department (ED). PCIS should be considered as an alternative diagnosis to acute pericarditis in case of unilateral right-sided, massive, or transudative pleural effusion.

Although typically a benign condition, PCIS may result in significant morbidity and potential mortality; tamponade and constrictive pericarditis represent the leading complications. Therefore, early detection is clinically relevant. Currently, a combination of nonsteroidal anti-inflammatory drugs and colchicine is the mainstay treatment for this condition. Colchicine has also appeared to be effective in primary prevention of PCIS after cardiac surgery.

The purpose of this article is to review the principle clinical characteristics of PCIS in order to achieve an early diagnosis.

DOI: 10.29245/2578-3009/2018/3.1127 View / Download Pdf

Emmanuel E. Ekanem1*, Joanan M. Ikobah1, Henry C. Okpara2

1DEPARTMENT OF PAEDIATRICS, UNIVERSITY OF CALABAR AND UNIVERSITY OF CALABAR TEACHING HOSPITAL, CALABAR, NIGERIA.

2DEPARTMENT OF CHEMICAL PATHOLOGY, UNIVERSITY OF CALABAR AND UNIVERSITY OF CALABAR TEACHING HOSPITAL, NIGERIA.

The faeco-orally transmitted hepatotropic viruses – hepatitis A and hepatitis E viruses- are endemic in Africa. While transmission has reduced remarkbly in Europe and North America in the past decades, it has remained unchanged in Africa with hepatitis A prevalence remaining at above 50% and hepatitis E more than 7%. Much of this transmission occurs during childhood with the important drivers/predictors being poor water supply, poor sewage disposal facilities, low socioeconomic class, crowding, and poor social conditions arising from conflict. Initial clinical features in children are difficult to distinguish from malaria which is also endemic in the region. Commercially available ELISA kits present the best option for laboratory diagnosis of both viruses in Africa. While effective vaccines suitable for the African situation have been developed recently, improved water supply and sanitation are sine qua non for the prevention of transmission of both viruses among African children. Interventional studies are needed in the region.

DOI: 10.29245/2578-3009/2018/3.1138 View / Download Pdf

Wee Kiat Tan1, Johan CK Tay2, Jieming Zeng3, Min Zheng4, Shu Wang2,3*

1Tessa Therapeutics, Pte Ltd., Singapore 239351

2Department of Biological Sciences, National University of Singapore, Singapore 117543

3Institute of Bioengineering and Nanotechnology, Singapore 138669

4Department of Dermatology, Second Affiliated Hospital, Zhejiang University, School of Medicine, China 310009

DOI: 10.29245/2578-3009/2018/3.1133 View / Download Pdf

Ulrich Julius1*

1Lipidology and Center for Extracorporeal Treatment, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Germany Fetscherstr. 74, 01307 Dresden (Germany)

DOI: 10.29245/2578-3009/2018/3.1136 View / Download Pdf

Shiyu Dai1, Hualin Wang1, Fei Deng1*

1State Key laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China

Virus-like particles (VLPs) are highly organized particles that self-assemble from viral structural proteins. Like parental viruses, VLPs can be either non-enveloped or enveloped and can be produced in different expression systems depending on their complexity. Over the last three decades, VLPs have developed as a high-priority alternative to traditional vaccines against infectious pathogens due to their safety, simplicity and favorable immunological characteristics to induce both humoral and cellular immune responses. Most of emerging and re-emerging viruses that pose a continuous threat to human health are enveloped, but few vaccines are currently available. Advances in expression technology for complex, enveloped VLPs provide new possibilities to develop potent vaccines against pathogenic enveloped viruses. This review describes major progress and challenges in the production of enveloped VLPs, with respect to the main principles in the assembly and budding process, factors that need to be taken into account for the design strategies and choice of relevant production platforms.

DOI: 10.29245/2578-3009/2018/2.1118 View / Download Pdf

Danielson H1*, Ylinen P1, Yrjönen T1, Lassila R2

1Orton Orthopaedic Hospital, Invalid Foundation, Helsinki, Finland

2Helsinki University and Coagulation Disorders unit, Department of Haematology and Comprehensive Cancer Centre, Helsinki University Hospital, Helsinki, Finland

DOI: 10.29245/2578-3009/2018/2.1129 View / Download Pdf