All Articles

José Perdomo

Haematology Research Unit, St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia

Gulhadiye Avcu¹, Deniz Yilmaz Karapinar^2*

¹Ege University Faculty of Medicine, Children’s Hospital, Department of Pediatric Infectious Disease, 35040 Bornova Izmir, Turkey

²Ege University Faculty of Medicine, Children’s Hospital, Pediatric Hematology, 35040 Bornova Izmir, Turkey

Invasive fungal infections, including invasive aspergillosis are associated with a high morbidity and mortality especially in immunocompromised patients. Diagnosis is often difficult due to several factors such as delay in clinical suspicion and the lack of spesific clinical findings. Galactomannan is a polysaccharide cell wall component of Aspergillus and galactomannan antigen detection has become widely used for diagnosis of invasive aspergillosis. Here, we tried to discuss the diagnostic value of the galactomannan test in the context of literature review.

Astrid Obermayer¹*, Walter Stoiber¹, Fikreta Grabcanovic-Musija², Michael Studnicka²

¹Department of Biosciences, Biomedical Ultrastructure Research, University of Salzburg, Salzburg, Austria

²University Clinic of Pneumology, Paracelsus Medical University, Salzburg, Austria

Since their discovery about fifteen years ago, neutrophil extracellular traps (NETs) have been recognized as an intrinsic part of vertebrate innate immunity and inflammatory response. Consisting of entangled strands of extracellular DNA decorated with histones, elastase, myeloperoxidase and other proteins, NETs entrap and kill pathogens, but are increasingly also found to contribute to acute and chronic inflammatory disease due to their toxicity to host cell and autoimmunity induction. Chronic obstructive pulmonary disease (COPD) turned out to be among the major disorders involving overshooting formation of NETs and associated adverse effect. In the present review, we summarize the progress in knowledge on the role of NETs in COPD pathology made since our first reports on this subject. We highlight recent substantial advances and discuss possible cause-and-effect relationships, connections with common comorbidities and interactions with drugs, also to illustrate the importance of NETs as a future diagnostic tool and target for new medication strategies.

Fani L. Moreira Neto^1,2,3*

¹Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal

²IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal

³Departamento de Biomedicina – Unidade de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Alameda Prof Hernâni Monteiro, 4200-319 Porto, Portugal

Heat shock protein 90 (HSP90) belongs to a highly conserved family of molecular chaperones and is responsible for regulating the protein folding quality control of specific client proteins. In a recent study published in Molecular Neurobiology, HSP90mRNA levels were found significantly decreased after knock-down in vitro of activating transcription factor 3 (ATF3), indicating that this stress-inducible gene that mediates pro-apoptosis or cytoprotection might act as positive regulator of HSP90 expression. In the rodent model of Monoarthritis, characterized by being accompanied by chronic joint inflammatory pain, the mRNA and protein levels for HSP90 were significantly increased in dorsal root ganglia (DRG). Additionally, a reversal in the HSP90 mRNA upregulation and in the 70kDa protein isoform levels following intrathecal delivery of a HSP90 inhibitor, along with an attenuation of movement-induced mechanical allodynia, and reduced neuronal sensitization and satellite glial cells (SGC) activation in ipsilateral DRG of the arthritic animals were also observed. This suggests a putative role of HSP90 in chronic inflammatory pain pathophysiology at sensory ganglia level that is still unexplored. To date only a few studies demonstrated a link between pain and HSP90 modulation, but there are several evidences that HSP90 is involved in inflammation, tumorigenesis and neurodegeneration. Here, we discuss the status of the studies demonstrating a role for HSP90 in inflammation and comment on their possible involvement in neuronal/glial driven pain mechanisms.

Hideto Tamura¹*, Mariko Ishibashi², Mika Sunakawa¹, Hidemi Takahashi², Koiti Inokuchi¹

¹Department of Hematology, Nippon Medical School, Tokyo, Japan

²Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan

Programmed death ligand 1 (PD-L1) expression on myeloma cells is induced by JAK2, STAT3, and MEK1/2-mediated interleukin-6 signaling, a strong inducer of PD-L1 interferon-γ produced by T and natural killer cells, and APRIL produced by osteoclasts in the tumor microenvironment. The soluble form of PD-L1, derived from extracellular domains of PD-L1 molecules expressed in the tumor environment, may also contribute to tumor immune evasion. PD-L1-expressing myeloma cells not only have the ability to escape from the attack of tumor-specific T cells but also high proliferation potential. Furthermore, PD-L1 on myeloma cells delivers a reverse signal to tumor cells through PD-1 binding, resulting in the phosphorylation of Akt accompanied by the acquisition of resistance to anti-myeloma agents. Based on the function of PD-L1 in myeloma, the blockade of the PD-1–PD-L1 pathway is a reasonable treatment in refractory patients. Phase I/II clinical trials of anti-PD-1 antibody combined with immunomodulatory drugs demonstrated excellent effects in heavily pretreated multiple myeloma patients with acceptable tolerability. The timing and combination drug of anti-PD-1/PD-L1 antibodies should be considered to improve clinical effects with low mortality in refractory myeloma patients.

Yasemin Yuyucu Karabulut*

Mersin University Medical School, Department of Pathology, Mersin, Turkey

Intranodal palisaded myofibroblastoma, also known as “intranodal hemorrhagic spindle cell tumor with amianthoid fibers,” is a benign mesenchymal tumor of the lymph node originating from smooth muscle cells and myofibroblasts often with the presence of amianthoid fibers. Ninety-three cases of intranodal palisaded myofibroblastoma have been reported in the literatüre since its first description and most of them have the same clinical history “painless firm nodüle”. It is mostly seen in inguinal region there are few cases have been described in other locations. It’s large and important differential diagnostic spectrum makes this tumor special.

Sabahat Abdullah, Sajjad Ur Rahman, Ahsan Naveed*, Qamar Majeed

Institute of Microbiology, University of Agriculture Faisalabad, 3840, Pakistan

Mosquito-borne diseases can be reduced drastically with the aid of vaccines which provoke mosquitocidal or mosquito-killing effect. The midgut of mosquito performs a fundamental role in the development and the transmission of ailment. Anti-midgut antibodies show the extensive variety of activity, blockading the development of pathogen in various species of mosquitoes. In addition to reducing the egg-laying ability of mosquitoes and survivorship also block the transmission activity of pathogen. Mitsuhashi and Maramorosch media was used to culture the mosquito midgut cells. The cells were formalin inactivated and injected into the rabbits in plain and adjuvanted form to raise hyperimmune serum. The serum was processed for IHA and serum showing high titre were selected for blood feeding assay. The blood from the rabbits was fed to the mosquitos to observe the mosquitocidal effect of the antigen. In blood feeding assay killing of mosquitoes was also observed after regular interval of time. The overall results proved that mosquito midgut contains antigenic peptides that may be able to induce the antibody response. These antigenic peptides somehow irritate digestive mucosa of the mosquitoes on blood feeding and have the potential to kill or reduce the mosquito population.

A Vossenkamper¹, G Warnes^2*

¹Centre for Immunobiology, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary London University, 4 Newark Street, London E1 2AT, UK

²Flow Cytometry Core Facility, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary London University, 4 Newark Street, London E1 2AT, UK

The use of the Western Blot technique has been the gold standard to determine protein expression and to semi-quantitate this expression in cell lysates. The recent publication of a flow cytometric immunophenotyping method employing fluorescently labelled antibodies to the intracellular labelling of antigens involved in Regulated Cell Death (RCD) processes has allowed the detection of three of these processes simultaneously which gave clarity to the interpretation of the relationship between apoptosis, RIP1 dependent apoptosis and necroptosis. Flow cytometry can now immunophenotype necroptosis by virtue of the up-regulation of RIP3 with simultaneous estimations of the degree of classic apoptosis (Caspase-3^+ve/RIP3^-ve) and of RIP1-dependent apoptosis (Caspase-3^+ve/RIP3^+ve) in live and dead cell populations. This approach for detecting multiple forms of cell death has been confirmed by the use of apoptosis and necroptosis blocking agents, zVAD and necrostatin-1 after treatment with etoposide or shikonin which induced apoptosis and necroptosis. The addition of anti-PARP and H2AX antibodies for the detection of parthanatos and DNA damage showed that double negative Caspase-3^-ve/RIP3^-ve cells detected in a previous study have undergone parthanatos or still display a negative phenotype for any cell death process.

Yusuke Masuishi*, Shota Endo, Hideaki Kasuga, Tomoo Hidaka, Takeyasu Kakamu, Tetsuhito Fukushima

Department of Hygiene and Preventive Medicine, Fukushima Medical University School of Medicine, 1Hikariga-oka, Fukushima City 960-1295, Japan

Unique and complex post-translational modifications are present in the outer leaflet of the plasma membrane. Glycosylphosphatidylinositol (GPI) anchoring is essential for the expression of several outer membrane proteins on the cell surface. A common GPI anchor structure is constituted by glycan moiety, lipid moiety, phosphate and ethanolamine. GPI-anchored proteins (GPI-APs) are observed among eukaryotic species. Abnormal GPI anchoring of proteins is thought to cause various diseases such as paroxysmal nocturnal hemoglobinuria. Recently, many inherited GPI deficiencies (IGDs) have been reported to cause epilepsy, mental retardation, coarse facial features, and multiple organ anomalies. Diseases caused by abnormal GPI anchoring will probably continue to increase, because it is still unknown how many causative genes of IGDs are present. Therefore, in order to study these diseases, the analytical methods of GPI-APs will become important in the future. To date, many methods have been developed for analysis of GPI- APs. In this review, we attempt to summarize the present knowledge about comprehensive analytical methods of GPI-APs and introduce briefly some GPI anchor-related diseases.

Atsushi Anzai*, Motoaki Sano

Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

In-hospital outcomes are generally acceptable with the conservative treatment of uncomplicated type B aortic dissection, but some patients present with undesirable complications, such as aortic expansion and rupture. Beyond mechanical and shear forces of blood flow affecting the weakened aortic wall, excessive inflammatory response has been shown to be associated with aortic expansion and adverse clinical outcomes. We have previously demonstrated the underlying mechanisms of catastrophic complications after acute aortic dissection (AAD) in mice. We propose that aortic dissection induces expression of the neutrophil chemoattractants CXCL1 and granulocyte-colony stimulating factor in the aortic tunica adventitia. These local environmental changes recruit neutrophils in combination with alteration of bone marrow milieu where reduced CXCL12 expression enhances neutrophil egress. Interleukin (IL)-6 production in the inflammatory adventitial neutrophils causes vascular inflammation, leading to vascular wall fragility. Targeting CXCR2 or IL-6 mitigates aortic expansion and prevents mice from aortic rupture. Collectively, adventitial neutrophil-mediated inflammation may be a potential therapeutic target to limit lethal complications after AAD.

Hillary W. Bedell^1,2 and Jeffrey R. Capadona^1,2*

¹Department of Biomedical Engineering, Case Western Reserve University, School of Engineering, 2071 MLK Jr. Drive, Wickenden Bldg, Cleveland OH 44106, USA

²Advanced Platform Technology Center, L. Stokes Cleveland VA Medical Center, Rehab. R&D, 10701 East Blvd. Mail Stop 151 AW/APT, Cleveland OH 44106, USA

Intracortical microelectrodes are used both in basic research to increase our understanding of the nervous system and for rehabilitation purposes through brain-computer interfaces. Yet, challenges exist preventing the widespread clinical use of this technology. A prime challenge is with the neuroinflammatory response to intracortical microelectrodes. This mini-review details immunomodulatory strategies employed to decrease the inflammatory response to these devices. Over time, broad-spectrum anti-inflammatory approaches, such as dexamethasone and minocycline, evolved into more targeted treatments since the underlying biology of the neuroinflammation was elucidated. This review also presents studies which examine novel prospective targets for future immunomodulatory targeting.

Eshetu Shibeshi Messeret^1*, Balcha Masresha², Ahmadu Yakubu³, Fussum Daniel¹, Mihigo R², Deo Nshimirimana⁴, Joseph Okeibunor⁵, Batholomew Akanmori²

¹Inter-country Support Team of East and Southern Africa, WHO African Region, Harare, Zimbabwe

²Immunization and Vaccines Development Programme, Family & Reproductive Health Cluster, WHO African Region, Brazzaville, Congo

³Immunization Vaccines and Biologicals Department, WHO Headquarters, Geneva, Switzerland

⁴WHO Country Office, Dakar, Senegal

⁵Polio Eradication Programme, WHO African Region, Brazzaville, Congo

Tetanus is a vaccine-preventable disease of significant public health importance especially in developing countries. The WHO strategy for the elimination of maternal and neonatal tetanus recommends the promotion of clean delivery practices, systematic immunization of pregnant women and those in the reproductive age (15-49 years) and surveillance for neonatal tetanus. Implementation of the recommended strategy with the support of WHO, UNICEF and other partners has led to significant decline in number of cases and deaths due to NT over the last decades. The coverage with the second or more dose of tetanus toxoid-containing vaccines (TT2+) a proxy for Protection at Birth (PAB) for the WHO African region has risen from 62% in 2000 to 77% by 2015 Reported cases of NT declined from 5175 in 2000 to 1289 in 2015.

The goal of eliminating maternal and neonatal tetanus by 2015 was missed, but some progress has been made. By the end of 2016, 37 out of 47 (79%) of the WHO AFR member states achieved elimination. The 10 member states remaining need additional support by all partners to achieve and maintain the goal of MNTE. Innovative ways of implementing the recommendations need to be urgently considered.

Richard Luce¹, Balcha G Masresha^2*, Regis Katsande², Amadou Fall³, Messeret Eshetu Shibeshi⁴

¹WHO Inter-country Support Team for Central Africa, Libreville, Gabon

²WHO Regional Office for Africa, Brazzaville, Congo

³WHO Inter-country Support Team for Western Africa, Ouagadougou, Burkina Faso

⁴WHO Inter-country Support Team for East and Southern Africa, Harare, Zimbabwe

The World Health Organization (WHO) recommends that countries introduce rubella containing vaccines (RCVs) to reduce rubella circulation and the occurrence of congenital rubella syndrome (CRS). As of June 2017, a total of 18 countries have already introduced or are in the process of introducing RCV in routine child vaccination programs. RCV introduction during 2013 - 2014 in five countries in the Region resulted in a reduction of rubella incidence of 48% to 96% in the post-introduction period as compared to the average incidence in the years before introduction. These results suggest that initial mass vaccination campaigns and introduction of RCVs in routine immunization programs result in significant reduction in rubella incidence and a reduced potential for the occurrence of CRS.

Balcha G Masresha^1*, Richard Luce², Joseph Okeibunor¹, Messeret Eshetu Shibeshi³, Raoul Kamadjeu⁴, Amadou Fall⁵

¹WHO Regional Office for Africa. Brazzaville, Congo

²WHO Inter-country Support Team for Central Africa. Libreville, Gabon

³WHO Inter-country Support Team for East and Southern Africa. Harare, Zimbabwe

⁴UNICEF regional office for Eastern and Southern Africa. Nairobi, Kenya

⁵WHO Inter-country Support Team for Western Africa. Ouagadougou, Burkina Faso

Background: WHO recommends all countries to include a second routine dose of measles containing vaccine (MCV2) in their national routine vaccination schedules regardless of the level of coverage with the first routine dose of measles containing vaccine (MCV1). As of Dec 2016, 26 countries in the African Region have introduced MCV2.

Methods: We reviewed the WHO UNICEF coverage estimates for MCV1 and MCV2 in these countries, and the reports of the post introduction evaluation of MCV2 from 11 countries.

Results: Twenty three countries have WHO/UNICEF estimates of MCV2 coverage available in 2015. Of these, 2 countries have coverage of ≥ 95% for both MCV1 and MCV2 while 5 countries have coverage of > 80% for both doses. Dropout rates of >20% MCV1 – MCV2 exist in 12 countries. Post-MCV2 introduction evaluations done in 11 countries from 2012 to 2015 showed that inadequate health worker training, insufficient sensitization and awareness generation among parents and suboptimal dose recording practices were common programmatic weaknesses that contributed to the low MCV2 coverage in these countries.

Conclusion: MCV2 coverage remains low as reflected in large drop-out rates in most countries. Higher MCV2 coverage is necessary to sustainably achieve the regional measles elimination goal. National immunization programs must improve implementation of MCV2 using the standard introduction and evaluation guidelines available for EPI program planning.

Balcha Masresha^1*, Reggis Katsande¹, Richard Luce², Amadou Fall³, Messeret Shibeshi⁴, Goitom Weldegebriel⁴, Richard Mihigo¹

¹WHO Regional Office for Africa, Brazzaville, Congo

²WHO Inter-country Support Team for Central Africa, Libreville, Gabon

³WHO Inter-country Support Team for Western Africa, Ouagadougou, Burkina Faso

⁴WHO Inter-country Support Team for East and Southern Africa, Harare, Zimbabwe

Case based surveillance for measles is implemented in the African Region integrated with Acute Flaccid Paralysis (AFP) surveillance. In 2011, the Region adopted a measles elimination goal to be achieved by 2020, which included coverage, incidence and surveillance performance targets. We reviewed measles case-based surveillance data and surveillance performance from countries in the African Region for the years 2012 - 2016. During this period, a total of 359,019 cases of suspected measles were reported from the 44 of 47 (94%) countries using the case based surveillance system. Of these, 202,126 (56%) had specimens collected for laboratory testing. A total of 39,806 measles cases and 25,679 rubella cases were confirmed by IgM serology. Twelve countries met the two principal surveillance performance indicators for each year during the period and four countries met neither indicator over the period. At the Regional level, both surveillance targets were met in 3 of the 5 years in the period of study; however performance varies widely by country. Surveillance performance did not improve across the Region during the 5 years period. High quality surveillance performance is critical to support the achievement of the regional measles elimination goal. Better integrating implementation with AFP surveillance, securing predictable long-term funding sources, and conducting detailed evaluations at country level to identify and address the root cause of performance gaps is recommended.

Teklay K Desta^1*, Ephrem T. Lemango¹, Jimma D Wayess², Balcha G Masresha³

¹Maternal and Child Health Directorate, FMOH Ethiopia, P.O. Box 1234, Addis Ababa, Ethiopia

²Ethiopian Public Health Institute, FMOH. P.O. Box 1242, Addis Ababa, Ethiopia

³World Health Organization, Regional Office for Africa, Brazzaville, Congo

Background: Ethiopia endorsed the African Regional measles elimination goal and has been implementing the recommended strategies. Measles immunization coverage has been increasing but is still below the target, and measles incidence has remained high.

Objective: To describe the measles epidemiology in Ethiopia, identify predictors of high measles incidence in Ethiopia and recommend strategies to achieve the elimination goal.

Methods: Measles surveillance 2006-2016 data, routine immunization and post measles campaign coverage data was analyzed. We analysed the epidemiology and incidence of measles cases by age, vaccination status, year of occurrence, and geographic area.

Result: There were 66,719 confirmed cases, out of the 94,104 suspected measles cases reported between January 2006 and December 2016. Measles incidence increased from 20 cases per million total population in 2006 to 194 cases per million in 2015 and declined to 49 per million in 2016. On multiple logistic regression analysis, the median age of measles cases, the 2013 measles Supplemental Immunisation Activity (SIAs) coverage, the 2012 routine immunization coverage, and the proportion of reported under-five measles cases were predictors of very high measles incidence (>240 cases per million in the under-five years age population) in the three-year period following the 2013 measles SIAs implementation (p<0.01).

Conclusion: Ethiopia is not on track to achieve the measles elimination goal of less than 1 case per million population by 2020 with the current pace of elimination efforts. Accumulation of susceptible children due to suboptimal routine measles immunization combined with suboptimal and narrow age–group (9-59 months) measles SIAs resulted in continued measles outbreaks.

Recommendation: Ethiopia should scale up the quality and implementation of all the measles elimination strategies, including the introduction of measles second dose and conducting high quality measles SIAs targeting the appropriate age groups as per the measles epidemiology in various parts of the country to accelerate and achieve the 2020 measles elimination goal.

Balcha Masresha^1*, Fiona Braka², Nneka Ukachi Onwu³, Joseph Oteri³, Tesfaye Erbeto², Saliu Oladele², Kyandindi Sumaili⁴, Abimbola Aman-Oloniyo⁴, Regis Katsande¹, Sisay Gashu Tegegn², Amadou Fall⁵

¹World Health Organisation- Regional office for Africa. Brazzaville, Congo

²World Health organisation – Country office for Nigeria. Abuja, Nigeria

³National Primary Health Care Development Agency, Nigeria

⁴United Nations Children’s Fund (UNICEF) - Country Office for Nigeria. Abuja, Nigeria

⁵World Health Organisation- Inter-country support team for West Africa. Ouagadougou, Burkina Faso

Introduction: Nigeria has adopted the African Regional measles elimination targets and is implementing the recommended strategies. Nigeria provides routine measles vaccination for children aged 9 months. In addition, since 2006, Nigeria has been conducting nationwide measles supplemental Immunisation activities (SIAs) or mass vaccination campaigns every 2 years, and has established measles case-based surveillance.

Methods: We reviewed routine and supplemental measles immunization coverage data, as well as measles case-based surveillance data from Nigeria for the years 2012 – 2016, in an attempt to determine the country’s progress towards these elimination targets.

Results: The first dose measles vaccination coverage in Nigeria ranged from 42% and 54% between 2012 and 2015, according to the WHO UNICEF national coverage estimates. Nigeria achieved 84.5% coverage by survey following the 2015 nationwide measles supplemental immunisation activities (SIAs). During this period, the incidence of confirmed measles ranged from 25 - 300 confirmed cases per million population per year, with the Northern States having significantly higher incidence as compared to the Southern States. At the same time, the pattern of confirmed cases indicated a consistent shift in epidemiological susceptibility including older age children.

Conclusions: In order to accelerate its progress towards the measles elimination targets, Nigeria should build population immunity on a sustainable basis by addressing systemic issues in order to scale up routine immunisation coverage, especially in the Northern half of the country; tailoring the target age for measles SIAs so as to sharply reduce measles incidence in age groups heavily affected by the disease; effectively mobilising resources and improving the quality of planning and coverage outcome of SIAs.

Balcha Masresha^1*, Richard Luce², Messeret Shibeshi³, Reggis Katsande¹, Amadou Fall⁴, Joseph Okeibunor¹, Goitom Weldegebriel³, Richard Mihigo¹

¹WHO Regional Office for Africa, Brazzaville, Congo

²WHO Inter-country Support Team for Central Africa, Libreville, Gabon

³WHO Inter-country Support Team for East and Southern Africa, Harare, Zimbabwe

⁴WHO Inter-country Support Team for Western Africa, Ouagadougou, Burkina Faso

Background: Measles elimination is defined as the absence of endemic measles virus transmission in a defined geographic area for at least 12 months in the presence of a well-performing surveillance system. The WHO framework for verification of measles elimination indicates that the achievement of measles and/or rubella elimination should be verified for individual countries.

Objective: We identified 11 high performing countries based on their first dose measles vaccination coverage and looked at their performance across the various programmatic parameters, to see if they are ready to undertake the verification of measles elimination.

Methods: We identified 11 countries with >90% measles first dose coverage for the most recent 5 years according to the WHO UNICEF estimates of national immunisation coverage. We analysed vaccination coverage and surveillance performance in these countries.

Results: Algeria, Botswana, Gambia, Mauritius, Rwanda, Seychelles have maintained measles first dose (MCV1) coverage of 95% or more since 2011. In 2015, only Algeria, Cape Verde and Seychelles had coverage of 95% or more for the second dose of measles vaccine (MCV2). Of the 22 supplemental immunisation activities (SIAs) among the 11 countries, only 6 had administrative coverage of less than 95%. Only Rwanda and Lesotho attained the case-based surveillance performance targets in all the five years.

Conclusion: Despite their high routine first dose measles immunisation coverage, all of the 11 countries have some program gaps indicating that they do not meet all the criteria to undergo verification of elimination at this point. It is recommended for these countries to set up national verification committees as per the WHO framework for verification of measles elimination, in order to initiate the documentation and monitoring of progress, and to address programmatic gaps in the coming years.

Balcha Masresha^1*, Messeret Shibeshi², Reinhard Kaiser⁴, Richard Luce³, Regis Katsande¹, Richard Mihigo¹

¹WHO Regional Office for Africa. Brazzaville, Congo

²WHO Inter-country Support Team for East and Southern Africa. Harare, Zimbabwe

³WHO Inter-country Support Team for Central Africa. Libreville, Gabon

⁴WHO Inter-country Support Team for East and Southern Africa. Harare, Zimbabwe

Introduction: Rubella is a mild febrile rash illness caused by the rubella virus. The most serious consequence of rubella is congenital rubella syndrome (CRS), which occurs if the primary rubella infection occurs during early pregnancy, with subsequent infection of the placenta and the developing fetus.

Methods: WHO supported countries to set up sentinel surveillance for CRS using standard case definitions, protocols, and case classification scheme. This descriptive analysis summarises the data from 5 countries which have been regularly reporting.

Results: A total of 383 suspected cases of CRS were notified from the 5 countries as of December 2016, of which 52 cases were laboratory confirmed and 67 were confirmed on clinical grounds.

The majority (43%) of confirmed CRS cases were in the age group 6 – 11 months. The most common major clinical manifestation (Group A) among the confirmed cases is congenital heart disease (72%) followed by cataracts (32%) and glaucoma (10%).

Discussion and conclusions: The number of years of reporting from these sentinel sites is too short to describe trends in CRS occurrence across the years. However, the limited surveillance data has yielded comparable information with other developing countries prior to introduction of rubella vaccine. As more countries introduce rubella vaccine into their immunisation programs, there is a need to ensure that all rubella outbreaks are thoroughly investigated and documented, to expand sentinel surveillance for CRS in more countries in the Region, and to complement this with retrospective record reviews for CRS cases in selected countries.

Nasim Rahmani Kukia¹, Payam Zandi², Ardeshir Abbasi^3*

¹Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

²Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University Tehran, Iran

³Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Mesenchymal stromal cells(MSCs) have been exploited for their immunomodulatory properties in treating various immune-related disorders. MSCs can modulate the immune system through interactions with a variety of immune cells. Regardless of the researchers focused on understanding how MSCs connect to individual immune system cell subsets, the mechanisms for inducing restorative effect still stay mainly undiscovered. Through this mini-review we address what is known about the associations and effects of educated MSCs with cells of the innate immune system (macrophages and neutrophils) and our knowledge of these interactions will be essential in increasing and expanding new medical protocols for MSC based cell therapy in the foreseeable future.

Hassan Sibomana¹, Muhoza Jered², Celse Rugambawa³, Jethro M. Chakauya⁴, Messeret E Shibeshi^4*, Joseph Okeibunor⁵, Richard Mihigo⁵, Rajesh Bhaskar⁶

¹Ministry of Health, Rwanda Biomedical Center, Rwanda

²MOH Rwanda

³World Health Organization Country Office, Rwanda

⁴World Health Organization Inter-Country Support Team, Harare, Zimbabwe

⁵WHO AFRO

⁶WHO Consultant, WHO Rwanda

Objective: This paper assesses and describes the estimated coverage of the Measles Rubella (MR) campaign in each district; the national estimate of coverage for Human Papilloma Virus (HPV) vaccination campaign and Vitamin A supplementation simultaneously implemented in 2013.

Methods: We applied descriptive statistics and epidemiological tools to the outcomes of the campaigns to assess the coverage achieved on the different child and maternal health interventions. We also assessed the Adverse Events following Immunization (AEFI) where the evaluation was used at the same time to assess the routine immunization performance coverage for children 12-24 months for all childhood antigens, Tetanus Toxoid coverage among mothers of infants, combined with routine immunization performance evaluation, skilled delivery and bed nets use in Rwanda.

Results: Results indicated that among the eligible targets, 97.5% received MR vaccine, 91% received HPV doses, and 83% got Vitamin A. The integrated vaccination of MR with HPV did not result in any serious AEFI. Coverage for antigens and doses given early in life was above 95% with card retention of 80%. BCG to measles dropout by card was 8.5%. Main reasons for non-vaccination indicated need for more specific immunization education. About 96.8% of mothers delivered in health institutions and 95% of the mothers slept under bed nets the night before the survey.

Conclusion: Rwanda successfully implemented an integrated coverage evaluation survey of the integrated vaccination campaign and routine immunization with statistically valid estimates. We drew lessons that information on routine immunization can be collected during post campaign survey evaluations. The district estimates should guide the programme performance improvement.

Oluwasegun Joel Adegoke^1*, Marina Takane², Oladayo Biya⁴, Martin Ota⁵, Bolatito Murele³, Frank Mahoney⁴, Patrick Nguku¹, Hiromasa Okayasu²

¹African Field Epidemiology Network, Nigeria Country Office, Abuja, Nigeria

²World Health Organization, Geneva, Switzerland

³WHO Country Office, Abuja, Nigeria

⁴Centers for Disease Control and Prevention, Atlanta, USA

⁵World Health Organization-Regional Office for Africa, Brazzaville, Republic of Congo

Eradication of poliomyelitis remains a public health priority due to the paralytic effects of the virus on children and impact on global health system. However, existing gaps in surveillance can hinder eradication. Improved timeliness of identification and reporting of acute flaccid paralysis (AFP) cases with further confirmation of Wild Poliovirus (WPV) in stool samples, can help Nigeria achieve the performance indicators of non-polio AFP rate of ≥ 2/100,000 population aged < 15 years and ≥80% stool sample collection adequacy.

To ascertain the awareness of AFP case definition and detection by health care workers and to evaluate the impact of SMS-based reporting on the AFP surveillance system the study was conducted from November 2013 to July 2014.

In Sokoto state, 112 health facilities (focal sites) were operational and participated in this study. All AFP focal points for the 112 facilities were included in the study. In addition to AFP focal points, two clinicians per facility where possible, were included in the study. The study focused exclusively on reports from focal sites. The methodology was a one group pretest-posttest design conducted in 3 phases. 1) Pre-intervention Knowledge, Attitude and Practices (KAP) survey, 2) SMS implementation and 3) Post-intervention KAP. Results were analysed using the independent sample t-test to assess the increase in knowledge, attitudes, or practice scores pre- and post- training.

The study showed improved knowledge gap of health care workers on AFP surveillance between pre and post intervention. It shows that this approach of improved surveillance will be effective in countries in hard to reach, access compromised or countries/place without sufficient surveillance staff.

Bartholomew Dicky Akanmori^1*, David Mukanga², Ahmed Bellah², Tieble Traore¹, Michael Ward², Richard Mihigo¹

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

²Regulatory Systems Strengthening, Essential Medicines and Health Products, WHO Headquarters

In emergency situations, clinical trials of new vaccines and therapies in resource-constrained settings place an additional burden on the limited resources of low and middle-income countries. The clinical trials of vaccines against Ebola Virus Disease (EVD) in Africa presented challenges on how to ensure there was enough capacity for ethics and regulatory reviews and oversight while still allowing for accelerating the clinical evaluations. Using the African Vaccine Regulatory Forum (AVAREF) platform WHO supported African countries to provide ethics and regulatory reviews and oversight, ensuring that these trials were completed in unprecedented shorter timelines than normal, that is, months instead of years. Pathways were defined, external expertise provided and appropriate review models implemented in the countries which hosted these critical studies.

This paper discusses the work around the clinical trials, the models of reviews and timelines for clinical trials and highlights the important lessons revealed. More investments are required to monitor safety during clinical trials, strengthen systems for licensure of new products and implement robust post-marketing surveillance, among other components for effective clinical trials before the next pandemic surfaces.

Bartholomew D Akanmori^1*, 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.

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.