Vol 3-1 Review Article

A Review of Exosomes and their Role in The Tumor Microenvironment and Host-Tumor "Macroenvironment"

Kaity H. Tung, Marc S. Ernstoff, Cheryl Allen, Shin La Shu*

Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

Tumor-derived exosomes (TEX) are important intercellular messengers that contribute to tumorigenesis and metastasis through a variety of mechanisms such as immunosuppression and metabolic reprogramming that generate a pre-metastatic niche favorable to tumor progression. Our lab has contributed further to the understanding of the miRNA payloads in TEX by demonstrating that human melanoma-derived exosome (HMEX) associated miRNAs contribute to the metabolic reprogramming of normal stroma. This mini-review highlights the role of TEX in the tumor microenvironment (TME) and the hypothesis that exosomes may also generate a host-tumor “macroenvironment” beyond the TME through their miRNA and protein payloads, so to speak “fertilizing the soil for cancer seeding.”

View / Download Pdf View Full Text

Special Issue: Immunization in the African Region


Special Issue

IMMUNIZATION AND VACCINE DEVELOPMENT: Progress towards High and Equitable Immunization Coverage in the Africa Region from 2012 to 2016

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.

View / Download Pdf View Full Text
Special Issue

Five-year Experience of African Vaccination Week Implemented by the WHO Regional Office

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.

View / Download Pdf View Full Text
Special Issue

Analysis of Death and Survival Factors Associated with Childhood Bacterial Meningitis at a Reference Pediatric Hospital in Antananarivo, Madagascar

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.

View / Download Pdf View Full Text
Special Issue

Progress on the implementation of environmental surveillance in the African Region, 2011-2016

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.

View / Download Pdf View Full Text
Special Issue

Implementing a Birth Dose of Hepatitis B Vaccine in Africa: Findings from Assessments in 5 Countries

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.

View / Download Pdf View Full Text
Special Issue

Elimination of Epidemic Meningitis in the African Region: Progress and Challenges:2010-2016

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.

View / Download Pdf View Full Text
Special Issue

Towards a Strategy for Reducing Missed Opportunities for Vaccination in Malawi: Implications of a Qualitative Health Facility Assessment

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.

View / Download Pdf View Full Text
Special Issue

Efforts to Reach More Children with Effective Vaccines Through Routine Immunization in The WHO African Region: 2013-2015

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.

View / Download Pdf View Full Text
Special Issue

Delivery of Multiple Child and Maternal Health Interventions during Supplementary Immunization Campaign in Rwanda, 2013: Lessons Learnt

Hassan Sibomana1, Muhoza Jered2, Celse Rugambawa3, Jethro M. Chakauya4, Messeret E Shibeshi4*, 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.

View / Download Pdf View Full Text
Special Issue

Strengthening the Acute Flaccid Paralysis (AFP) Surveillance Component of the Polio Eradication Initiative through Short Message Service (SMS) Reminders; Experience from Sokoto State, Nigeria 2014

Oluwasegun Joel Adegoke1*, 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.

View / Download Pdf View Full Text
Special Issue

The Role of The African Vaccine Regulatory Forum (AVAREF) in The Accelerated Clinical Evaluation of Ebola Vaccine Candidates During the Large West Africa Epidemic

Bartholomew Dicky Akanmori1*, 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.

View / Download Pdf View Full Text
Special Issue

Vaccine Safety and Pharmacovigilance in the African Region: Recent updates

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.

View / Download Pdf View Full Text
Special Issue

Towards Immunization Financing Sustainability in Africa

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.

View / Download Pdf View Full Text
Special Issue

The Cost of Routine Immunization Services in A Poor Urban Setting in Kampala, Uganda: Findings of a Facility-Based Costing Study

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.

View / Download Pdf View Full Text
Special Issue

Maternal and Neonatal Tetanus Elimination (MNTE) in The WHO African Region

Eshetu Shibeshi Messeret1*, 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.

View / Download Pdf View Full Text
Special Issue

The Impact of Recent Rubella Vaccine Introduction in 5 Countries in The African Region

Richard Luce1, Balcha G Masresha2*, 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.

View / Download Pdf View Full Text
Special Issue

Introduction of The Second Dose of Measles Containing Vaccine in The Childhood Vaccination Programs Within The WHO Africa Region -Lessons Learnt

Balcha G Masresha1*, 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.

View / Download Pdf View Full Text
Special Issue

Measles Epidemiology in Ethiopia from 2006 - 2016: Predictors of High Measles Incidence from Surveillance Data Analysis

Teklay K Desta1*, 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.

View / Download Pdf View Full Text
Special Issue

Performance of National Measles Case-Based Surveillance Systems in The WHO African Region. 2012 - 2016

Balcha Masresha1*, 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.

View / Download Pdf View Full Text
Special Issue

Progress Towards Measles Elimination in Nigeria: 2012 - 2016

Balcha Masresha1*, 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.

View / Download Pdf View Full Text
Special Issue

Status of Measles Elimination in Eleven Countries with High Routine Immunisation Coverage in The WHO African Region

Balcha Masresha1*, 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.

View / Download Pdf View Full Text
Special Issue

Congenital Rubella Syndrome in The African Region - Data from Sentinel Surveillance

Balcha Masresha1*, 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.

View / Download Pdf View Full Text