All Articles

Mamadou Diallo¹*, Alimou Traore², Myk Mwanza Nzioki¹, Ayangma Richelot¹, Kouryana Stephane³, Joseph Okeibunor¹, Mkanda Pascal¹, Samuel Okiror⁴, Johnson Ticha¹

¹WHO Regional Office for Africa (WHO AFRO), Brazzaville, Congo

²WHO Headquarters, Geneva

³WHO Chad

⁴WHO Horn of Africa Coordination Office (HOA), Nairobi KENYA

Marcellin Mengouo Nimpa¹, Noëline Ravelomanana Razafiarivao², Annick Robinson³, Mamy Randriatsarafara Fidiniaina⁴, Richter Razafindratsimandresy⁵, Yolande Vuo Masembe¹, Christiane Ramonjisoa Bodohanta⁶, Isidore Koffi Kouadio¹, Issa Kana kode Nyazy¹, Moussa Simpore¹, Charlotte Faty Ndiaye¹, Joseph Chukwudi Okeibunor^1.

¹World Health Organization Regional Office for Africa, Congo

²Faculté de Médécine d’Anatanarivo, Madagascar

³Centre Hospitalier Universitaire Mère Enfant Tsaralalana (CHUMET) -Antananarivo

⁴Direction Centrale du Service Militaire d’Antanarivo

⁵Institut Pasteur de Madagascar

⁶Expanded Programme of Immunization, Madagascar

Background: In 1988, the World Health Assembly launched the Global Polio Eradication Initiative. WHO AFRO is close to achieve this goal with the last wild poliovirus detected in 2014 in Borno States in Nigeria. The certification of the WHO African Region requires that all the 47 member states meet the critical indicators for a polio free status. Madagascar started implementing polio eradication activities in 1996 and was declared polio free in June 2018 in Abuja. This study describes the progress achieved towards polio eradication activities in Madagascar from 1977- 2017 and highlights the remaining challenges to be addressed.

Methods: Data were collected from the national routine immunization services, Country Acute Flaccid surveillance databases and national reports of SIAS and Mop Up campaign. Country complete polio and immunization related documentation provided detailed historical information’s.

Results: From 1997 to 2017, Madagascar reported one wild poliovirus (WPV) outbreak and four circulating Vaccine Derived Polio Virus (cVDPV) oubreaks with a total of 21 polioviruses (1 WPV and 21 cVDPV). The last WPV and cVDPV were notified in 1997 in Antananarivo and 2015 in Sakaraha health districts respectively. Madagascar met the main polio surveillance indicators over the last ten years and made significant progress following the last cVDPV2 outbreak in 2014 -2015. In addition, the country successfully implemented the switch from trivalent Oral Polio Vaccine (tOPV) to bivalent Oral Polio vaccine (bOPV) and containment activities. Environmental Surveillance established since 2015 did not reveal any poliovirus. The administrative coverage of the 3rd dose of oral polio vaccine (OPV3) varied across the years from 55% in 1991 to a maximum of 95% in 2007 before a progressive decrease to 86% in 2017. The percentage of AFP cases with more than 3 doses of oral polio vaccines increased from 56% in 2014 to 88% in 2017. A total of 19 supplementary immunization activities (SIA) were conducted in Madagascar from 1997 to 2017, among which 3 were subnational immunization days (sNID) and 16 were national immunization days (NIDs). Poor routine coverage contributed to the occurrence of cVDPC outbreaks in the country; addressing this should remain a key priority for the country to maintain the polio free status.

From 2015 to June 2017, Madagascar achieved the required criteria leading to the acceptance of the country’s polio-free documentation in June 2018 by ARCC. However, continuous efforts will be needed to maintain a highly sensitive polio surveillance system with emphasis on security compromised areas. Finally strengthening the health system and governance at all levels will be necessary if these achievements are to be sustained.

Conclusions: High national political commitment and support of the Global Polio Eradication Partnership were critical for Madagascar to achieve polio free status. Socio-political instability, weakness of the health system, sub-optimal routine immunization performance, insufficient SIA quality and existing security compromised areas remain critical program challenges to address in order to maintaining the polio free status. Continuous high-level advocacy should be kept in order to ensure that new government authorities maintain polio eradication among the top priorities of the country.

Abubakar Sadiq Umar¹*, Isah Mohammed Bello², Joseph Chukwudi Okeibunor ¹, Pascal Mkanda¹, Godwin Ubong Akpan¹, Daudi Manyanya², Shibeshi Messeret Eshetu², Masvikeni Brine², Matapo Belem², Masumbu Penelope², Daniel Fussum² 

¹WHO Regional Office for Africa (WHO AFRO)

²WHO East & Southern Africa Support Team (WHO ESA IST)

The use of online Integrated Supportive Supervision (ISS) is aimed to improve the quality of services provided by front line health workers. This work is aimed to document the effects of ISS on the performance of health workers in Zambia using selected key surveillance and immunization process indicators. ISS data on WHO ODK server of all Integrated Supportive Supervisory (ISS) visits that were conducted in Zambia between 1^st January 2018 to 30^th September 2018 were analysed to determine the Percentage point difference between the first and the most recent ISS visits in order to determine whether an observed gap during first ISS visit had persisted during the most recent ISS visit. Our study demonstrated that ISS has remarkable percentage point increase between the first and the most recent ISS visits on availability of an updated monitoring chart, health workers knowledge of AFP case definition and AFP case files. However, there exist variations in the frequency of ISS visits across the provinces of the country. Future research effort should consider assessing the quality of the ISS data through periodic data validation missions.

Abdi H. Ahmed¹*, Gedi Mohamed¹, Joseph Okeibunor², Iheoma Onuekwusi¹, Pascal Mkanda², Samuel Okiror³

¹WHO, Nairobi Kenya

²WHO Regional Office for Africa (WHO AFRO), Brazzaville, Congo

³WHO Horn of Africa Coordination Office (HOA), Nairobi KENYA

Background:

Poliomyelitis, often called polio is a viral paralytic disease caused by Polioviruses. Although all susceptible individuals are at risk of getting infected, only about 1% become paralyzed. During the 2013 Polio Outbreak in Garissa County in Kenya, 50% of the confirmed cases were from the nomadic population although it comprises of only less than 20% of the total population in the county. Following concerns from the Horn of Africa Polio Technical Advisory Group (TAG) regarding inadequate vaccine coverage of nomadic population, several strategies were put in place to improve coverage and Acute Flaccid Paralysis case reporting among nomads in the rest of the planned 2014 polio vaccination campaigns. We describe strategies initiated from April 2014 by the Ministry of Health and partners to reach children in nomadic settlements in the two sub-counties of Dadaab and Fafi of Garissa County.

Methods:

The strategies involved improving the mapping and tracking of the nomadic population by establishing lists of nomadic settlements obtained from local clan leaders and government administrators, their <5-year-old populations and focal persons. Focal persons were used to mobilise residents in their respective settlements and guide vaccination teams during campaigns. Settlement leaders were sensitised to report cases of Acute Flaccid Paralysis. In remote hamlets, trained community health volunteers were used as vaccinators. In such places drugs for common illness were also provided during the campaigns. A tracking tool to monitor nomadic population movement and special tally sheets to capture data were created. Training of vaccination personnel and intense social mobilisation activities was done.

Results and conclusion

About 2,000 additional children, from both nomadic and non-nomadic areas were reached when the new initiatives were started. For the first time, an actual number of nomadic children accessed was documented. Suspected AFP cases continued to be reported from nomadic settlements, and the number of zero dose children among the nonpolio AFP cases dropped. With modification and improvement, these strategies may be used to take health services such as routine immunisation to nomadic communities and reduce their vulnerability to vaccine preventable disease outbreaks.

Samuel Okiror¹*, Brigitte Toure², Bob Davis³, Rustum Hydarov², Bal Ram⁴, Joseph Okeibunor⁵, Chidiadi Nwogu¹

¹WHO Horn of Africa Coordination Office (HOA), Nairobi KENYA

²UNICEF, Nairobi Kenya

³American Red Cross, Nairobi Kenya

⁴CORE Group Regional Office Nairobi

⁵WHO Regional Office for Africa (WHO AFRO), Brazzaville, Congo

Following the outbreak of poliovirus in the countries in the Horn of Africa, Somalia, Kenya and Ethiopia, in two WHO regions, an outbreak response involving the WHO Africa and WHO East and Mediterranean Regions and partner agencies like the UNICEF in East and Southern African was developed. This paper documents response to polio virus outbreak in the Horn of Africa and the lessons learnt for the interregional and inter-agency collaboration on the response. This collaboration led to speedy interruption of the outbreak and within a period of one year the total virus load of 217 in 2013 was brought down to mere six. This resulted from collaborative planning and implementation of activities to boost the hitherto low immunity in the countries andimprove surveillance among others. A number of lesson were generated from the process. Some of the lessons is critical role such collaboration plays in ensuring simultaneous immunity boosting, information and resources sharing, among other. Some challenges were equally encountered, chiefly in the appropriation of authorities. In conclusion, however, one is safe to note that the collaboration was very fruitful given the timely interruption of transmission.

Rustam Hydarav¹, Obianuju Igweonu²*, Saumya Anand¹, Mwakisha Jemimah³, Almaz Merdekios¹, Leila Abrar¹, Joseph Okeibunor⁴, Sam Okiror⁵

¹UNICEF, Nairobi Kenya

²University of Nigeria, Nsukka

³WHO, Nairobi, Kenya

⁴WHO AFRO, Brazzaville, Congo

⁵WHO Horn of Africa Coordination Office (HOA), Nairobi KENYA

Background: Between 2013 and 2014, the Horn of Africa countries experienced a severe and prolonged outbreak of polio viruses. It started in one district in Somalia but quickly became a national and even international disaster, crossing international boundaries into Kenya and Ethiopia. This paper documents experiences in the establishment and contributions of the Polio Communication Network (PCN) to the polio outbreak response in the outbreak countries of Somalia, Kenya and Ethiopia from 2013 to 2015. Process: The establishment of the PCN network of partnerships and technical assistance was designed to implement a strategic communication response. Various strategies were used to establish the PCN. Some of these strategies included partnerships with faith-based organizations; involvement of local leaders in microplanning; social mobilization committees and research, monitoring, evaluation and documentation structures. Major Outcomes: PCN contributions through sustained high levels of community awareness of polio rounds were demonstrated. The contributions of the context-sensitive approaches included significant gains in reaching traditionally missed, hard-to-reach, pastoral communities with polio information, improved communication capacity, and successful closure of the outbreak within the expected timeline. This PCN experience provides important communication lessons relevant to polio eradication and other public health programmes. The focus on building capacity in areas such as monitoring, and data collection generated social data that led to the communication approaches making a significant impact. PCN contributed to a better understanding of the behavioral and environmental factors affecting the demand for, and uptake of, health services in the HoA which can be extended to most of the countries in the HoA with the same demographic and epidemiological realities. Conclusion: The use of the PCN helped bring the 2013-2014 polio outbreak under control and illustrates how the PCN can help drive progress towards the realization of the agenda of the universal health coverage and vision 2030 agenda in the African Region and elsewhere.

Ajiri Atagbaza¹*, Joseph Okeibunor¹, Felix Amadou², Souley Kalilou³, Aime Matela Esanga³, Adama Nanko Bagayoko³, Philbert Bohoussou³, Obianuju Igweonu⁴, Mahamat Mbodou Seid³, Ahmad Jibril Aliyu³, Elizabeth Benoit Ntezayabo⁵, Mohamed Alimou Traore⁶, Mwanza Nzioki¹, Adebola Olaleye³, Adele Daleke Lisi Aluma⁷, Djibrine Abakar Sedick³, Adam Mahamat Seid³, Mahamat Saleh Tahir³, Narcisse de Medeiros⁸, Bakoly Rabenarivo⁹, Fabien Diomande¹⁰, Pascal Mkanda¹

¹WHO Regional Office for African (WHO AFRO), Brazzaville, Congo

²WHO Consultant Lake Chad

³Ministry of Health, Chad

⁴University of Nigeria, Nsukka

⁵WHO, Chad

⁶WHO Headquarters, Geneva

⁷Independent Consultant

⁸UNICEF Dakar

⁹UNICEF, Cameroon

¹⁰CDC Atlanta

Introduction: Chad is a country within the Lake Chad sub region, currently at risk for poliovirus infection. The Lake Chad Task Team on polio eradication in this sub region made significant efforts to reduce the risk of polio transmission in Chad by tacking immunization teams in the Island Settlement using a Geographic Information System (GIS) technology. This article demonstrates the application of GIS technology to track vaccination teams to monitor immunization coverage in the Island settlements, reduce the number of missed settlements, to provide evidence for vaccination implementation and accountability and improve team performance.

Methods: In each district where tracking was conducted, global positioning system–enabled Android phones were given to each team on a daily basis and were used to record team tracks. These tracks were uploaded to a dashboard to show the level of coverage and identify areas missed by the teams.

Results: In 2018, tracking covered 30 immunization days, in six rounds. Approximately average of 1173 Island settlements were tracked and covered in each of the six rounds. A total of 806,999 persons aged 0-10 years were immunized, out of which 4273 were zero dose cases at the point of their immunization. Tracking activities were conducted. There was an improvement in the geographic coverage of settlements and an overall reduction in the number of missed settlements.

Conclusions: The tracking of vaccination teams and Island settlements ensured useful information for planning and implementation of polio campaigns and enabled supervisors to evaluate performance of vaccination teams

Atagbaza Ajiri¹*, Joseph Okeibunor¹, Samuel Aiyeoribe², Benoit Ntezayabo³, Melinda Mailhot⁴, Mwanza Nzioki¹, Alimou Traore⁴, Abdelrahim Khalid², Mamadou Diallo¹, Michel Ilboudo³, Bekele Mengistu Mikeyas¹, Dhoud Samba⁵, Twite Mulunda⁶, Narcisse De Medeiros⁷, Bakoly Rabenarivo⁸, Fabien Diomande⁵, Sam Okiror⁹

¹WHO Regional Office for African (WHO AFRO), Brazzaville, Congo

²EHealth Africa

³WHO, Chad

⁴WHO, Headquarters, Geneva

⁵CDC, Atlanta

⁶Mcking Consulting Corporation

⁷UNICEF, Dakar

⁸UNICEF, Cameroon

⁹WHO Horn of Africa Coordination Office (HOA), Nairobi KENYA

The geographic information system (GIS) mapping was used to improve the efficiency of vaccination teams. This paper documents the process in the deployment of geographical information system in response to polio eradication in Chad. It started with a careful review of government official documents as well as review of literature and online resources on Chad, which confirmed that official boundaries existed at two levels, namely Regions and Districts. All settlement locations in the target Districts were identified by manual feature extraction of high-resolution, recent satellite imagery, and map layers created for the following categories: hamlets, hamlet areas, small settlements, and built-up areas (BUAs). This clearly improved microplanning and provided valuable feedback in identifying missed settlements, leading to increased coverage and fewer missed children.

Samuel Okiror¹*, Abraham Mulugeta², Iheoma Onuekwusi³, Fiona Braka⁴, Sylvesta Malengemi⁵, John Burton⁶, Rustam Hydarav⁷, Brigitte Toure⁷, Bob Davis⁸, Carolyn Gathenji¹, Chidiadi Nwogu¹, Joseph Okeibunor⁹

¹WHO Horn of Africa Coordination Office (HOA), Nairobi KENYA

²WHO, EMRO Amman

³WHO, Nairobi Kenya

⁴WHO Country Office, Nigeria

⁵WHO, Juba South Sudan

⁶UNHCR, Nairobi Kenya

⁷UNICEF, Nairobi Kenya

⁸American Red Cross, Nairobi Kenya

⁹WHO Regional Office for Africa (WHO AFRO)

Background:

There has been civil strife, spanning more than two decades in some countries and recurrent natural disasters in the Horn of Africa (HoA). This has consistently maintained these countries in chronic humanitarian conditions. More important however is the fact that these crises have also denied populations of these countries access to access to lifesaving health services. Children in the difficult terrains and security compromised areas are not given the required immunization services to build their immunity against infectious diseases like the poliovirus. This was the situation in 2013 when the large outbreaks of poliovirus occurred in the HoA. This article reviews the epidemiology, risk, and programme response to what is now famed as the 2013-204 poliovirus outbreaks in the HoA and highlights the challenges that the programme faced in interrupting poliovirus transmission here.

Methods:

A case of acute flaccid paralysis (AFP) was defined as a child <15 years of age with sudden onset of fever and paralysis. Polio cases were defined as AFP cases with stool specimens positive for WPV.

Results:

Between 2013 and 2016, when transmission was interrupted 20,266 polio viruses were in the Horn of Africa region. In response to the outbreak, several supplementary immunization activities were conducted with oral polio vaccine (OPV) The trivalent OPV was used initially, followed subsequently by bivalent OPV, and targeting various age groups, including children aged <5 years, children aged <10 years, and individuals of any age. Other response activities were undertaken to supplement the immunization in controlling the outbreak. Some of these activities included the use of various communication strategies to create awareness, sensitize and mobilize the populations against poliovirus transmission.

Conclusions:

The outbreaks were attributed to the existence of clusters of unvaccinated children due to inaccessibility to them by the health system, caused by poor geographical terrain and conflicts. The key lesson therefore is that the existence of populations with low immunity to infections will necessary constitutes breeding grounds for disease outbreak and of course reservoirs to the vectors. Though brought under reasonable control, the outbreaks indicate that the threat of large polio outbreaks resulting from poliovirus importation will remain constant unless polio transmission is interrupted in the remaining polio-endemic countries of the world.

Samuel Okiror¹*, Chidiadi Nwogu¹, Obianuju Igweonu², Rustam Hydarov³, Djiboui Karim⁴, Farkhard Imambakiev⁵, John Ogange⁶, Annet Kisakye⁷, Joseph Okeibunor⁸, Hemant Shukla⁹

¹WHO Horn of Africa Coordination Office (HOA), Nairobi KENYA

²University of Nigeria, Nsukka

³UNICEF, Nairobi

⁴WHO headquarters, Geneva

⁵UNICEF New York

⁶World Health Organization, Kenya Country Office

⁷WHO, Uganda

⁸WHO Regional Office for Africa (WHO AFRO) Brazzaville, Congo

⁹WHO Headquarters, Geneva

Background:

Poliovirus importations and related outbreaks occurred in the Horn of Africa (HoA) following an initial outbreak, which started in Somalia, spread into Kenya within ten days and later into Ethiopia and gradually to other countries in the region. National preparedness plans for responding to poliovirus introduction were insufficient in many countries of the Region. We describe a series of polio outbreak simulation exercises that were implemented to formally test polio outbreak preparedness plans in the HoA countries, as a step to interrupting further transmission.

Methods:

The Polio Outbreak Simulation Exercises (POSEs) were designed and implemented. The results were evaluated and recommendations made. The roles of outbreak simulation exercises in maintaining regional polio-free status were assessed. In addition, we performed a comprehensive review of the national plans of all for seven countries in the HoA Region.

Results:

Seven simulation exercises, delivered between 2016 and 2017 revealed that participating countries were generally prepared for poliovirus introduction, but the level of preparedness needed improvement. The areas in particular need of strengthening were national preparedness plans, initial response, plans for securing vaccine supply, and communications.

Conclusions:

Polio outbreak simulation exercises can be valuable tools to help maintain polio-free status and should be extended to other high-risk countries and subnational areas in the HoA Region and elsewhere. There is also need to standardize the process and methods for conducting POSE for comparability.

Chidiadi Nwogu¹*, Johnny Musyoka², Carolyne Gathenji ¹, Rosemary Nzunza⁴, Iheoma Onuekwusi³, Joseph Okeibunor⁵, Pascal Mkanda⁵, Hemant Shukla¹, Shaikh Humayun Kabir¹, Sam O Okiror¹

¹¹WHO Horn of Africa Coordination Office (HOA), Nairobi, Kenya

²Ministry of Health (MoH), Nairobi, Kenya

³WHO, Nairobi, Kenya

⁴Kenya Medical Research Institute (KEMRI), Nairobi, Kenya

⁵WHO Regional Office for Africa, Brazzaville, Congo

Background:

Globally, tremendous improvement has been made in Polio eradication since its inception in 1988. For the third time in a decade, Kenya has experienced a Polio outbreak along the border with Somalia. The affected areas were in Garissa County, replete with previous occurrences in 2006 and 2012. This article, give an account of series of events and activities that were used to stop the transmission within 13 weeks, an interval between the first and the last case of the 2013 outbreak.

Methods:

In an attempt to stop further transmission and time bound closure of the outbreak, many activities were brought to fore: the known traditional methods, innovative approaches, improved finances and surge capacity. These assisted in case detection, implementation, and coordination of activities. The external outbreak assessments and the six-monthly technical advisory group recommendations were also employed.

Result:

There were increased case detections of >=2/100,000, stool adequacy >=80%, due to enhanced surveillance, timely feedbacks from laboratory investigation and diagnosis. Sustained coverage in supplemental immunisation of > 90%, ensured that immune profile of >=3 polio vaccine doses was quickly attained to protect the targeted population, prevent further polio infection and eventual reduction of cases coming up with paralysis.

Conclusion:

Overall, the outbreak was stopped within the 120 days of the first case using 14 rounds of supplemental immunisation activities.

Vijairam Selvaraj^1,2*, Anneliese Beaubrun^1,2, Shenjun Zhu^1,2, Kwame Dapaah-Afriyie^1,2

¹Division of Hospital Medicine, The Miriam Hospital, Providence, Rhode Island.

²Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Wolters ECh¹, de Hoo K², Kramer BW³, de Munter JPJM^2,4

¹Department of Neurology, UniversitatsSpital Zurich, Zurich, Switzerland

²Neuroplast BV, Urmond, The Netherlands

³Department of Paediatrics, Maastricht University Medical Centre, Maastricht, The Netherlands

⁴School for Mental Health and NeuroScience, Maastricht University, Maastricht, The Netherlands 

A cytokine release syndrome (CRS), associated with elevated circulating levels of several cytokines including interleukin (IL)-6 and interferon (IFN)-γ, might be seen in some infectious insults, for instance in severe acute respiratory syndrome (SARS) induced by Coronavirus (Cov)-2, as well as following administration of natural and bispecific antibodies and, more recently, following adoptive T-cell therapies for cancer. Normally, inflammatory conditions activate the innate and adaptive immune systems, which results in the release of cytokines, responsible for the phagocytosis of apoptotic vesicles and resolution of inflammation. Pro-inflammatory cytokines such as IL-1β, tumor necrosis factor alpha (TNFα) and, especially in chronic inflammatory diseases, autoimmune diseases, cancer and cytokine storms, IL-6 play crucial roles in inflammation. In some instances, however, this release gets out of hand, and features of overzealous immune responses (macrophage activation syndromes) might occur, leading to cytokine release syndromes (CRS) with inflammatory signs such as fever, fatigue, nausea, and sometimes secondary organ dysfunction or multi-organ failure. Apart from specific vaccines and maybe the anti-viral remdesivir and/or dexamethasone for treatment of CRS, there are no convincing disease-modifying interventions. So far, though, non-antiviral and immune-targeted interventions, also affecting non-target cells, were found associated with many side effects. A more targeted or focused approach is thus needed. Pending the site of the CRS-inducing insult, CRSs may occur systemic or compartmental. Recently, preclinical research yielded a beneficial anti-inflammatory effect of fresh naive bone marrow-derived stem cells (bm-SCs) in the treatment of various compartmental CRSs in the immune-privileged central nervous system (CNS). Therefore, it is argued that bm-SCs might also play a disease-modifying role in the systemic CRS. Bm-SCs have the advantage of targeting only the cells of interest as they are very selective in their actions. In addition, they actively move to the sight of inflammation.

Priyanka Ray¹, Noor Haideri², Inamul Haque², Omar Mohammed², Saborni Chakraborty², Snigdha Banerjee^2,3#, Mohiuddin Quadir^1#, Amanda E. Brinker ^4,5, and Sushanta K. Banerjee^2,3*

¹Department of Coatings and Polymeric Materials, North Dakota State University, Fargo, ND

²Cancer Research Unit, VA Medical Center, Kansas City, MO

³Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS

⁴Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS

⁵Institute for Advancing Medical Innovation, University of Kansas Cancer Center, Kansas City, KS

Since the early days marking the first use of nanomedicine in the early 80s, there has been a meaningful change in the scientific field involving the Fabrication, characterization, and application of nanomaterials to treat many diseases, including cancers and genetic disorders. As unique and attractive properties of this novel class of materials unraveled, significant advances and discoveries were made over time. Addressing several challenges posed by conventional therapy, which were the only available treatment option for ailing patients, nanomedicine provided enhanced benefits, including reduced dosing, improved pharmacokinetics, and superior targeting efficiency. Several such formulations have successfully made their way to clinics and have shown promise in prolonging terminally ill patient populations' survival rates. However, the complex immune system and its various components, including various proteins and surface receptors, have made nanomaterials' journey from benchtop to the bedside a treacherous one. The innate and adaptive immune system interactions with nanomaterials are still under investigation and full of mysteries. This review highlights the various aspects of therapeutic nanocarriers and their current understanding of their immune systems' interactions.

Lisa M. James^1,2,3, Rachel A. Johnson¹, Scott M. Lewis^1,4, Adam F. Carpenter^1,4, Brian E. Engdahl^1,2,5, Hollis E. Krug^6,7, Apostolos P. Georgopoulos^1,2,3,4*

¹Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, 55417, USA

²Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA

³Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA

⁴Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA

⁵Department of Psychology, University of Minnesota Medical School, Minneapolis, MN 55455, USA

⁶Department of Rheumatology, Department of Veterans Affairs Health Care System, Minneapolis, MN, 55417, USA

⁷Department of Rheumatology, University of Minnesota Medical School, Minneapolis, MN 55455, USA

Mounting evidence suggests that autoimmune mechanisms may underlie the chronic symptoms characteristic of Gulf War Illness (GWI). The presence of antiphospholipid antibodies including Lupus Anticoagulant (LA) are often associated with autoimmune disorders. Here we evaluated and compared blood samples from veterans with GWI and veterans with other autoimmune conditions including relapsing remitting multiple sclerosis, rheumatoid arthritis, Sjögren’s syndrome, and lupus for the presence of LA using Silica Clotting Time and dilute Russell’s Viper Venom Time assays. Positive LA was identified in one-quarter of veterans with GWI; this proportion was not statistically different from the proportion of positive LA identified in patients diagnosed with the other autoimmune conditions. The present findings add to the literature implicating autoimmune mechanisms in GWI and point to the presence of prothrombotic antiphospholipid antibodies as a common contributing factor in GWI and other autoimmune disorders. Furthermore, activation of the coagulation system suggests new potential avenues for treatment for LA-positive Gulf War veterans.

Christian B. Auclair^* & Annette Ives^#

AC BioScience SA, Biopôle, Route de la Corniche 4 – Lysine, 1066 Epalinges, Switzerland

Brandon C. Smith^1,2 & Jessica L. Williams^1*

¹Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

²Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, OH, USA

Despite an increase in approved therapies for treating the inflammatory and neurodegenerative disease multiple sclerosis (MS), many of which have efficacy in the early, acute phases, there are no reliable treatments for the chronic, progressive stages of the disease. A deeper understanding of the biological underpinnings that govern differences between acute and chronic stages of MS and an animal model of MS, experimental autoimmune encephalomyelitis, will inform therapeutic development and personalized treatment strategies. It is well-known that the effects of inflammation are complex and the implications vary between stages. Complimentary to our recent publication, we will discuss here the pleiotropic effects of the cytokine interferonγ across disease states, along with the implications of downstream mechanisms of action.

Shinya Tanaka^1*, Wataru Ise², Yoshihiro Baba¹, Tomohiro Kurosaki^2,3#

¹Division of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, 812-0054, Japan

²Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Suita, 565-0871,Japan

³Laboratory of Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan

Gene expression must be strictly controlled during cell differentiation and function in mammalian systems. DNA methylation plays an important role in this process, and its pattern is shaped by balancing the activity of methyltransferases and demethylases. Ten-eleven translocation (TET) was identified as a demethylase that catalyzes the oxidation reaction of the methyl group of 5-methylcytosine (5mC), converting it to 5-hydroxymethylcytosine (5hmC). Recently, indispensable roles of TET proteins in the regulation of immune cells have been identified. Here, we review recent studies on the biological consequences of dysregulation of TET proteins in the immune system, with a particular focus on B cell biology. Finally, we discuss future perspectives in this research field.

Giovanna L. Gallo^1*, Julieta S. Roldán², Laura R. Delgui^3,4

¹Centro de Virología Animal (CEVAN)-CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas).

²Instituto de Investigaciones Biotecnológicas "Dr. Rodolfo A. Ugalde" (IIBIO), Universidad Nacional de San Martín (UNSAM) - CONICET, San Martín, Buenos Aires, Argentina.

³Instituto de Histología y Embriología de Mendoza (IHEM-CONICET). Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina.

⁴Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Mendoza, Argentina.

Mammarenavirus genus groups viruses causing human haemorrhagic diseases, including the New World (NW) Junín virus (JUNV), and the Old World (OW) viruses Lassa (LASV), among others. The high mortality and morbidity rates associated to pathogenic mammarenaviruses, the absence of vaccines and the constant threat of new emerging species, make these viruses a public health concern in endemic areas. Autophagy is a widely-known intracellular metabolic pathway involved in maintaining the cellular homeostasis in response to several stress conditions.

R. Christina Smith, MD¹, Meera N. Patel², Richard Sigmon, MD³, Niraj C. Patel, MD, MS¹

¹Division of Pediatrics, Division of Pediatric Infectious Disease and Immunology, Atrium Health, Charlotte, NC, USA

²North Carolina School of Science and Math

³Department of Internal Medicine, Division of Gastroenterology, Atrium Health, Charlotte, NC, USA

The licensed rotavirus vaccines are live attenuated and are a component of the routine U.S. childhood immunization schedule. Live vaccines administered to infants of mothers who received biologic response modifiers (BRM) during pregnancy can potentially cause serious vaccine-associated disease. The Advisory Committee on Immunization Practices (ACIP) recommends infants born to women who received BRM during pregnancy avoid live viral vaccines during the first year of life. There is a paucity of information regarding adverse events following inadvertent administration of live viral vaccines in these infants. We report three infants, born to mothers receiving infliximab during pregnancy, who tolerated multiple doses of rotavirus vaccine. Live viral vaccines may be safe in infants who were exposed to BRM in utero. Further studies are needed to support this observation, as this could affect current ACIP recommendations.

Anurag Singh¹, Lakshya Gupta², Vandana Gupta¹*

¹Department of Microbiology, Ram Lal Anand College, University of Delhi, Benito Juarez Road, New Delhi 110021, India

²Department of Computer Science and Engineering, Indian Institute of Technology, Varanasi, Uttar Pradesh 221005, India

The coronavirus disease (COVID-19) emerged in China in December 2019 and has since spread to over 188 countries affecting millions of individuals. Several reports in favour or against the heterologous protection conferred by the BCG vaccine against COVID-19 came up in the initial days of the pandemic and continue to do so. In this study, we compared the three worst-affected nations: The USA, India, and Brazil, their current pandemic scenario, and their respective national BCG immunization policies. USA recommends BCG vaccine only to a specific group of people and never had a national immunization scheme in place. Meanwhile, India introduced a nationwide scheme as early as 1948 and continues to endorse BCG immunization at birth. Brazil used the oral route to administer the BCG vaccine till 1976, and then shifted to intradermal injection. The correlation coefficient for the total number of cases, cases per million, the total number of deaths, deaths per million and case fatality rate ranges between 0.81-0.98. This indicates a very strong positive correlation in the various epidemiological parameters between countries with no national immunization scheme (USA) and countries with stringent national policies on BCG vaccination. The strongest correlation exists between the USA and Brazil followed by Brazil and India which is very closely followed by the USA and India. We found no consistent evidence to infer in favour of the hypothesis that BCG provides any non-specific protection against COVID-19.

Abbreviations

BCG: Bacillus Calmette-Guérin

COVID-19: Coronavirus Disease 2019

DPT: Diphtheria, Pertussis, and Tetanus

HPV: Human Papillomavirus

HSV: Herpes Simplex Virus

ICTV: International Committee on Taxonomy of Viruses

OPV: Oral Poliovirus Vaccine

RSV: Respiratory Syncytial Virus

SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2

TB: Tuberculosis

WHO: World Health Organization

Sara B. Intner¹, Michelle Altrich², Niraj C. Patel¹

¹Department of Pediatrics, Levine Children’s Hospital, Atrium Health, Charlotte, NC, USA

²Viracor Eurofins, Lee’s Summit, MO, USA

Measurement of pneumococcal antibody concentration is a frequently used parameter for functional antibody response to vaccination. Antibody concentration in response to vaccination and strength of antigen-antibody (avidity) interaction are both important measurements of functional antibody response. Both antibody concentration and avidity contribute to immunity against invasive pneumococcal disease. Higher avidity is correlated with increasing bactericidal activity and opsonophagocytosis. On the other hand, patients with lower pneumococcal avidity may be more likely to develop clinically significant pneumococcal sinopulmonary infections. Nine patients with recurrent bacterial respiratory infections were identified by retrospective chart review as having adequate pneumococcal antibody concentrations, but with low avidity for multiple serotypes following immunization with pneumococcal vaccine polyvalent (PPSV23). We assessed response with IgG replacement therapy in these patients. The mean number of serotypes with a normal antibody response (>1.3 𝛍g/ml) among 9 children following immunization with pneumococcal vaccine polyvalent was 19.1 (range 12-22) of 23 serotypes while the mean number of serotypes with a normal avidity response (≥1.0) was 4.7 (range 2-7) of 23 serotypes. Flow cytometry was performed for 8 of the 9 patients prior to starting SCIG replacement therapy. 100% of the cohort experienced a significant decrease in yearly infection rate after starting immunoglobulin replacement. This is the first study to assess the clinical response to immune globulin replacement in patients with normal pneumococcal antibody response but poor pneumococcal avidity, and suggests that patients with poor pneumococcal avidity but apparent normal response by pneumococcal antibody following PPSV23 may benefit from IgG replacement therapy.

Lisa M. James^1,2,3,4, Effie-Photini C. Tsilibary^1,2, Spyros Charonis^1,2, Apostolos P. Georgopoulos^1,2,3,4*

¹ Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, USA

² Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA

³ Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA

⁴ Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, USA

Spyros S. Charonis ^1,2, Effie-Photini Tsilibary ^1,2, Apostolos P. Georgopoulos ^1,2*

¹Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 55417, USA

²Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA

SARS-CoV-2 causes COVID-19, urgently requiring the development of effective vaccine(s). Much of current efforts focus on the SARS-CoV-2 spike-glycoprotein by identifying highly antigenic epitopes as good vaccine candidates. However, high antigenicity is not sufficient, since the activation of relevant T cells depends on the presence of the complex of the antigen with a suitably matching Human Leukocyte Antigen (HLA) Class II molecule, not the antigen alone: in the absence of such a match, even a highly antigenic epitope in vitro will not elicit antibody formation in vivo. Here we assessed systematically in silico the binding affinity of epitopes of the spike-glycoprotein to 66 common HLA-Class-II alleles (frequency ≥ 0.01). We used a sliding epitope window of 22-amino-acid-width to scan the entire protein and determined the binding affinity of each subsequence to each HLA allele. DPB1 had highest binding affinities, followed by DRB1 and DQB1. Higher binding affinities were concentrated in the initial part of the glycoprotein (S1-S460), with a peak at S223-S238. This region would be well suited for effective vaccine development by ensuring high probability for successful matching of the vaccine antigen from that region to a HLA Class II molecule for CD4⁺ T cell activation by the antigen-HLA molecule complex.

Ioanna Zerva, Vasileia Pateraki, Irene Athanassakis*

Department of Biology, University of Crete, Vassilika Vouton, Heraklion 70013, Crete, Greece

Effective and side-effect-free vaccines are still difficult tasks to achieve for a great majority of antigenic stimuli. Pathogen manipulation to abort infectivity and antigen delivery to ensure immune responsiveness are the major components vaccine technology tries to resolve. However, the development of an immune response is still a complicated matter, lies on hundreds of parameters and any effort towards activation can easily lead to adverse effects, making immunotherapy very difficult to control. The present review attempts to highlight the major parameters affecting immune responsiveness and show that vaccine technology, except from pathogen manipulation and the development of antigen delivery systems, requires attention to additional check-points. Analyzing the recently described personalized implantable vaccine technology, it becomes obvious that the nature of each antigenic stimulus dictates different responsiveness to the organism, which discourages the use of universal adjuvant and antigen-delivery systems. On the contrary, the ex vivo tuning of the immune response proposed by the implantable vaccine technology, allows controllable amendment of the response. The development of personalized technologies is expected to provide valuable tools for the management of human pathology.