Vaccines and Global Health: The Week in Review :: 28 July 2018

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David R. Curry, MS
Executive Director
Center for Vaccine Ethics and Policy

To Our Readers: Vaccines and Global Health: The Week in Review will resume publication on 18 August 2018 following the Editor’s annual leave.

Ebola outbreak in DRC ends: WHO calls for international efforts to stop other deadly outbreaks in the country

Milestones :: Perspectives

Ebola – DRC

Ebola outbreak in DRC ends: WHO calls for international efforts to stop other deadly outbreaks in the country
24 July 2018
Today marks the end of the ninth outbreak of Ebola in the Democratic Republic of the Congo (DRC). The World Health Organization (WHO) congratulates the country and all those involved in ending the outbreak, while urging them to extend this success to combatting other diseases in DRC.

WHO Director-General, Dr Tedros Adhanom Ghebreyesus, and Regional Director for Africa, Dr Matshidiso Moeti, joined Minister of Health Dr Oly Ilunga for the announcement in Kinshasa.
“The outbreak was contained due to the tireless efforts of local teams, the support of partners, the generosity of donors, and the effective leadership of the Ministry of Health. That kind of leadership, allied with strong collaboration between partners, saves lives,” said Dr Tedros.

Unlike previous Ebola outbreaks in the country, this one involved four separate locations, including an urban centre with river connections to the capital and to neighbouring countries, as well as remote rainforest villages. There were initial concerns that the disease could spread to other parts of DRC, and to neighbouring countries.

Within hours of the outbreak being declared on 8 May, WHO released US$2 million from its Contingency Fund for Emergencies, deployed a team to augment capacity in the field, and activated an emergency incident management system.

“WHO moved quickly and efficiently,” said Dr Moeti, “We also demonstrated the tremendous capacity of the African region. More than three-quarters of the 360 people deployed to respond came from within the region. Dozens of experts from Guinea spent weeks leading Ebola vaccination efforts here, transferring expertise which will enable the DRC to mount an effective response both within its borders and beyond.”

Dr Tedros urged the DRC Government and the international community to build on the positive momentum generated by the quick containment of the Ebola outbreak.

“This effective response to Ebola should make the Government and partners confident that other major outbreaks affecting the country such as cholera and polio can also be tackled,” said Dr Tedros. “We must continue to work together, investing in strengthened preparedness and access to healthcare for the most vulnerable.”

:: WHO’s rapid response and scale up of operations in the DRC was funded by a total of US$4 million disbursement from the WHO Contingency Fund for Emergencies (CFE).
:: WHO and partners appealed for US$57 million to stop the spread of Ebola. The total funds received by all partners, as tracked by OCHA, amount to US$63 million.
:: Funding towards WHO’s contribution to the Ebola response was provided from: Italy (€ 300 000), UN CERF (US$ 800 000), Gavi (US$ 1 million), USAID (US$ 5.3 million), Wellcome Trust and UK-DFID (US$ 4.1 million), UK-DFID (£5 million), Germany (€5 million), Norway (NOK 8 million), Canada (CAD$1 million), World Bank PEF (US$ 6.8 million), Japan (US$1.3 million), EU ECHO (€ 1.5 million) and from the Ebola MPTF (US$ 428,000) bringing the total to approximately US$ 36 million.
:: Germany’s contribution is in recognition of the critical role the WHO CFE has played in responding to the Ebola virus disease outbreak in the Democratic Republic of the Congo and will go to replenish the CFE, which provided initial funds for the response efforts.
:: In-kind contributions for medical evacuation were received from Norway. EU ECHO support was provided for flights between Kinshasa and Mbandaka. Technical expertise was provided by Guinea, the UK, USA and Germany through the Global Outbreak Alert and Response Network (GOARN). Merck provided the vaccines that were used to protect over 3300 people.

WHO partners in the DRC Ebola response included the following:
The Alliance for International Medical Action (ALIMA), the International Federation of Red Cross and Red Crescent Societies (IFRC), the Red Cross of the Democratic Republic of the Congo (DR Congo Red Cross), Médecins Sans Frontières (MSF), the Disaster Relief Emergency Fund (DREF), the Africa Centers for Disease Control and Prevention (Africa-CDC), the US Centers for Disease Control and Prevention (US-CDC), ECHO, the Department for International Development (DFID), Japan International Cooperation Agency (JICA), the World Food Programme (WFP), UNICEF, UNCERF, UNOCHA, MONUSCO, UNFPA, International Organization for Migration (IOM), the FAO Emergency Management Centre – Animal Health (EMC-AH), the International Humanitarian Partnership (IHP), Gavi, the Vaccine Alliance, the African Field Epidemiology Network (AFENET), the UK Public Health Rapid Support team, the EPIET Alumni Network (EAN), the International Organisation for Animal Health (OIE), the Emerging Diseases Clinical Assessment and Response Network (EDCARN), the World Bank and PATH. The Government of Guinea deployed more than 30 Ministry of Health staff to assist with the ring vaccination campaign, and Merck provided the Ebola vaccine. Additional coordination and technical support through the Global Outbreak Alert and Response Network (GOARN), Association pour le développement de l’épidémiologie de terrain (EPITER), European Mobile Laboratory (EMLab), Infection Control Africa Network (ICAN), Institut Pasteur (IP), National Institute for Communicable Diseases (NICD), South Africa, Robert Koch Institut (RKI), and Emergency Medical Teams (EMT).

25 July 2018
Ebola vaccine praised as Congo outbreak declared over
DRC government officially declares end of outbreak following the vaccination of over 3,000 people.
Geneva, 25 July 2018 – The first use of a vaccine to help contain an Ebola outbreak has been encouraging, Dr Seth Berkley, CEO of Gavi, the Vaccine Alliance, said as the outbreak in the Democratic Republic of Congo (DRC) was officially declared over.

The DRC government formally declared the Ebola outbreak over on Tuesday 24 July after no new cases were reported for 42 days. From the 4 April through 9 July there were 54 confirmed cases of Ebola reported, with 33 deaths. A total of 3,300 people received investigational doses of the vaccine as part of a ring vaccination protocol – the same used to eradicate smallpox.
The vaccination was implemented by the Government of DRC and partners including WHO, which supported national authorities in coordinating the international health response, and Medecins Sans Frontieres (MSF). Gavi provided $1 million towards the vaccination effort.

“As soon as Ebola moved from isolated rural areas into Mbandaka – a major town and regional hub – there was justified concern that this outbreak could spiral out of control,” said Dr Berkley. “It took months of hard work by a global coalition of UN agencies, NGOs and governments, led by the DRC government with WHO support, to carry out the surveillance, containment, contact tracing and public education needed to contain and defeat Ebola. This was the first time a vaccine was used as part of this wider response and it is encouraging that there were no cases of Ebola among those given the vaccine. We also now have valuable experience of how this vaccine can be used effectively in the field.”

The vaccine has gone through Phase 3 trials, which showed the vaccine to be safe and highly effective, but has not yet been licensed by relevant regulatory authorities. While the vaccine goes through the licensing process, an agreement between Gavi and Merck, the developer of the Ebola vaccine, ensures that 300,000 investigational doses of the vaccine are available in case of an outbreak. It is these doses that were used in the DRC.

This agreement, an Advance Purchase Commitment announced in January 2016, is the first of its kind. It was designed to incentivise the rapid development of the vaccine as well as guarantee investigational doses are available while licensure is being secured. Gavi committed US$5 million to buy doses of a fully licensed vaccine as and when it becomes available. In return, Merck agreed to create the emergency stockpile…

Children in fragile states missing out on lifesaving vaccines

Milestones :: Perspectives

Children in fragile states missing out on lifesaving vaccines – Gavi

New vaccination figures show millions more children being immunised in world’s poorest countries.

Geneva, 26 July 2018 – Children in fragile states are being left behind in the global effort to improve immunisation rates in the world’s poorest countries, an analysis by Gavi, the Vaccine Alliance of the latest global immunisation statistics has shown.

For the 68 developing countries in which Gavi works, the latest WHO/UNICEF Estimates of National Immunisation Coverage (WUENIC) show that coverage for the basic Diphtheria, Tetanus and Pertussis vaccine (DTP3) rose to 86% in 2017 from 80% in 2010, when fragile states are excluded.

However coverage has stagnated at 62% in fragile states. Five of the six Gavi-supported countries with less than 50% DTP3 coverage in 2017 were classed as fragile. The number of under-immunised children has also increased by 170,000 in Gavi-supported countries to 16.2 million children. Just under half of these children were in fragile countries.

In July 2017, Gavi introduced a new fragility, emergencies and refugee policy to boost the number of children receiving vaccines in fragile settings, especially among vulnerable populations. Bangladesh became the first country to take advantage of the policy in late 2017, carrying out Gavi-funded vaccination campaigns for Rohingya refugees in Cox’s Bazar.

“Over the last two decades we have made enormous progress in boosting vaccination coverage in many of the world’s poorest countries,” said Dr Seth Berkley, CEO of Gavi, the Vaccine Alliance. “Gavi is helping more children receive lifesaving vaccines than at any point in our history but millions of children are still being left behind, with half of these under-immunised children living in fragile countries. As an alliance we need to redouble our efforts and maintain our focus on routine immunisation as the most sustainable way to improve child health, strengthen health systems and boost economies.”..


China vaccine scandal: investigations begin into faulty rabies and DTaP shots

Milestones :: Perspectives

China: “Vaccine Scandal”
Editor’s Note:
See additional coverage in various publications in Media Watch below.
China vaccine scandal: investigations begin into faulty rabies and DTaP shots
BMJ 2018; 362 doi: (Published 25 July 2018)
Flynn Murphy
Trust in China’s authorities to guarantee the safety of medicines has been shaken after the nation’s second largest producer of rabies vaccines was found to have faked records.

Changsheng Biotechnology, based in the northeastern Jilin province, was ordered to cease producing a Vero cell based rabies vaccine on 15 July after China’s State Food and Drug Administration found that it had forged production and inspection data, the regulator said.1 Investigators reportedly acted on a tip-off from an ex-employee.

Changsheng issued an apology and announced a recall as shares in the company tumbled. It was not clear whether the batches had been released to market or how the substandard vaccine might affect people, but no injuries had been reported so far.

But days later Jilin’s provincial drug watchdog reported that the same company had last year sold over 250,000 faulty doses of a combined childhood shot for diphtheria, typhoid, and pertussis (DTaP), which it had uncovered in November. A local blogger apparently sent the story viral in a now deleted post that sparked confusion and anger among parents.

Local reports showed that police in Jilin swooped on the company on 23 July, arresting five executives including its chair, Gao Junfang, 64, who is also the company’s largest single shareholder. Gao and her family appeared on the Forbes 2016 rich list with combined assets of US$1bn (£0.76bn; €0.85bn).

China’s premier, Li Keqiang, said on 22 July that the incident had “crossed a moral line,” and he ordered an investigation. He was later joined by the president and Communist Party leader Xi Jinping, who called the scandal “vile in nature and shocking” and also ordered an investigation. Both urged severe punishment of those responsible.

At least four investigations are now under way, involving multiple regulators, police, securities inspectors, and the party’s feared anti-graft unit. Some people welcomed the strength of the response, in a nation where local reporting on such scandals has often been censored and whistleblowers jailed.

Others noted that it has been a decade since melamine laced powdered milk killed six babies and caused 54 000 others to be admitted for kidney damage, in a product safety case that still ripples today.2

In 2016 over 200 people were arrested over a different scandal involving expired and improperly refrigerated vaccines, which saw “middlemen” banned and provincial health bodies instructed to buy vaccines directly from manufacturers.

The Changsheng scandal is expected to trigger a renewed run on health services in Hong Kong, where parents were already travelling to secure vaccines for their children. One Hong Kong based biotech insider told The BMJ that his colleagues from the mainland were already “bringing their kids across the border for vaccinations.”

He said, “If you are in [neighbouring] Shenzhen you can bring your kids to Hong Kong, but I have no idea what parents in the interior of China are going to do. With the cold chain it’s much harder to get around than just importing tins of foreign powdered milk.”

The People’s Republic of China has the second highest number of reported rabies cases in the world, say data from the World Health Organization.3 But deaths from the disease more than halved from 2013 (1128 deaths) to 2017 (502) [WHO China, email communication]. Last year China reported no cases of diphtheria, 10 791 cases of typhoid (three fatal), and 10 390 cases of pertussis (none fatal), showed figures from China’s National Health Commission.4

[01] The person in charge of the State Food and Drug Administration introduced the Changchun Longevity Vaccine Case: ordered to suspend production, file an investigation, and organize flight inspections for all vaccine manufacturers. Xinhua News Agency 22 July 2018. [Translatable to English]
Google Scholar
[02] Parry J. China’s tainted milk scandal spreads around world. BMJ2008;337:a1890. doi:10.1136/bmj.a1890 pmid:18829644
FullTextFREE Full TextGoogle Scholar
[03] World Health Organization  Rabies.
Google Scholar
[04] National Health and Family Planning Commission. Overview of the national legal infectious disease epidemic in 2017. 26 Feb 2018. [Translatable to English]
Google Scholar

Evaluation of the impact of Shandong illegal vaccine sales incident on immunizations in China

Featured Journal Content
Human Vaccines & Immunotherapeutics (formerly Human Vaccines)
Volume 14, Issue 7 2018

Evaluation of the impact of Shandong illegal vaccine sales incident on immunizations in China
Lei Cao, Jingshan Zheng, Lingsheng Cao, Jian Cui & Qiyou Xiao
Pages: 1672-1678
Published online: 19 Jun 2018
A case of illegal vaccine sales in Shandong province, China, (hereinafter, the incident), which caused a lack of confidence among vaccination recipients and public panic, was uncovered in March 2016. We conducted a study comprising two cross-sectional surveys: at two months (May 2016) and seven months (October 2016) after the incident. The study aimed to evaluate the impact on immunizations; investigate the variation of the immunization coverage of the National Immunization Program Vaccines (NIPV) and the sales volume growth rate of Category II vaccines; and understand the reasons for non-vaccination and perspectives on immunization. The immunization coverage of NIPV decreased by 5.6 percentage points in the first survey, with a decline of 11.1 in the region of the incident, and decreased by 0.6 in the second survey compared to same period in 2015. The sales volume growth rate of Category II vaccines decreased by 25.8% in the study area and by 48.8% in the region of the incident in April 2016 compared to April 2015. Overall, 15.8% of respondents in the first survey and 7.0% in the second survey did not vaccinate their children according to the NIPV schedule because of the incident (X2=78.463, P<0.05). The vaccination was likely affected by the incident in varying degrees, especially in the involved region and particularly in relation to Category II vaccines. Overall, 34% of respondents avoided Category II vaccines for their children, indicating that it will take considerable time to eliminate the negative stigma associated with the incident.

Safety of dengue vaccine in the Philippines

Featured Journal Content

Dengue Vaccine –Philippines / GACVS
Safety of dengue vaccine in the Philippines

Extract from report of GACVS meeting of 6-7 June 2018, published in the WHO Weekly Epidemiological Record of 20 July 2018

GACVS last reviewed the CYD-TDV dengue vaccine at its meeting on 6–7 December 2017.5 The Committee noted that long-term follow-up in clinical efficacy trials indicated that, overall, vaccinated trial participants had a reduced risk of virologically confirmed severe dengue and hospitalization; however, a subset of trial participants who had not been infected with dengue virus before vaccination (i.e. dengue-naïve, seronegative according to the NS1 assay) had a higher risk of severe dengue and hospitalization. The new evidence presented at that meeting was based on a reanalysis of the clinical trial data by the manufacturer, with a new test that distinguishes individuals with and without previous exposure to wild dengue virus retrospectively.6 The WHO Strategic Advisory Group of Experts (SAGE) on immunization previously identified research on vaccine safety in this seronegative population as a priority.7

Following the December 6–7 meeting in 2017, GACVS recommended that CYD-TDV not be administered to individuals who have not been previously infected with wild dengue virus. GACVS also noted that no data are currently available to allow an analysis of risk according to the number of vaccine doses received by people who are seronegative at baseline.

At its meeting on 17–18 April 2018, SAGE advised countries considering CYD-TDV vaccination as part of their dengue control programme to include pre-vaccination screening, so that only dengue-seropositive persons are vaccinated; the limitations of such screening should be clearly communicated to those offered vaccination.8

WHO will release a revised position paper on dengue vaccine in September 2018. The purposes of an update of the GACVS statement on dengue vaccine are: (i) to review the reports on vaccine safety received by the Philippines Ministry of Health after announcement of the risk for severe dengue of vaccine recipients who were dengue-naïve at the time of vaccination; (ii) to review difficulties in determining whether, apart from vaccine failure, the cases of severe dengue in vaccine recipients who were dengue-naive at the time of CYD-TDV vaccination were due to vaccine-related immune enhancement; and (iii) to review the updated safety profile of CYD-TDV.

The Philippines Food and Drug Administration approved use of CYD-TDV in December 2015, and the Disease Prevention and Control Bureau proposed its introduction as part of the National Dengue Prevention and Control Program. Vaccine administration began in 2016, first as part of a school programme in highly endemic regions and then extended to community programmes in Octo¬ber 2016. Surveillance of the safety of all vaccines is well established in the country, as a part of integrated disease surveillance and response. Should a serious AEFI or cluster be detected, the epidemiology bureau of the Department of Health is notified within 24–48 h. Serious cases are investigated, and the results of the investigations are compiled and sent to the regional and national AEFI committees. Before the programme was suspended, over 875 000 children had received at least 1 dose, almost 350 000 had received all 3 doses, and about 400 000 had received 2 doses.

Post-marketing data were presented to GACVS by the manufacturer. CYD-TDV is registered in 20 countries, and most doses are distributed in Brazil (where it is used in a public programme in Parana State) and the Philippines. In Brazil, dengue cases are reported through a national reportable disease information system, and data on AEFI are collected through passive surveillance in a national immunization programme. Guidelines for enhanced reporting and training of vaccine centre workers were provided by local authorities in Parana State.

The 14 fatal case reports in the Philippines were first reviewed by the national AEFI committees and the Dengue Investigative Task Force (DITF). The reports included 3 cases of dengue shock syndrome and 6 cases with other clinical diagnoses and no clear causal link other than a temporal association. The other cases were coincidental (3) or unclassifiable (2). A further review of 12 cases (8 fatal and 4 non-fatal) was undertaken by the DITF after training in AEFI methodology by international specialists. Although the DITF found that most cases were indeterminate, coincidental or unclassifiable, it recognized several cases of dengue disease. GACVS maintained its earlier recommendation that CTD-TDV should not be administered to people who have not previously been infected with wild dengue virus. It concluded that, in the absence of criteria for distinguishing vaccine failure from vaccine-related immune enhancement, individual cases cannot be attributed to one or the other. As a result, such cases should be classified as indeterminate, irrespective of the time since vaccination.

Between December 2015 and March 2018, 1876 adverse events were reported to the manufacturer, mainly from Brazil and the Philippines; reporting was consistent with the pattern of dose distribution in both countries. The most frequently reported adverse events were fever, headache, dizziness, vomiting and rash. Of the 211 serious AEFI reported, most were consistent with an underlying infectious disease, including dengue fever. By 20 March 2018, 87 cases of dengue infection had been reported after vaccination with CYD-TDV; 23 were serologically confirmed, 61 suspected with no virological confirmation and 3 with negative virological tests. Of the 87 dengue cases, 14 were fatal. Of the 14 cases, 6 had completed the vaccination schedule, 3 had received 2 doses and 5 had received only 1 dose. All 9 cases for which the interval between vaccination and disease onset was known occurred within 6 months of the last vaccination.

Progress was reported in cohort event monitoring, sponsored by the manufacturer to obtain information on selected AEFI and serious adverse events in people vaccinated with CYD-TDV over 5 years in Brazil, Mexico and the Philippines. The target for enrolment in the study of post-authorization safety is 30 000 vaccinated participants. As of 5 April 2018, 12 573 participants had been enrolled and had received at least 1 dose of CYD-TDV.

One of the challenges in conducting post-market surveillance after vaccination with CYD-TDV is determining whether the vaccine gives rise to vaccine-related immune enhancement. An increasing number of AEFI were reported after suspension of the vaccination programme in the Philippines and media coverage. A task force was established by the Department of Health to review all fatal cases, and guidelines on AEFI reporting and response to vaccine recipients were issued by the Department of Health. In addition, the National AEFI Committee, established in 2012, was charged with reviewing all non-fatal AEFI.

GACVS also examined the possible risk of viscerotropic or neurotropic disease associated with the yellow fever backbone of the CYD-TDV vaccine. Although this remains a theoretical possibility, non-clinical and clinical evaluations do not provide evidence of an association. Viscerotropic and neurotropic diseases are rare serious reactions to yellow fever vaccination and occur only in close temporal association with vaccination. As severe dengue may also be accompanied by haemorrhagic systemic phenomena, a differential diagnosis can be made only if the vaccine strain is isolated from affected organs and if such syndromes occur within the accepted interval between vaccination and symptom onset (8 days).

5 See No. 3, 2018, pp. 21–25.

6 Sridhar S et al. Effect of dengue serostatus on dengue vaccine efficacy. N Engl J Med 2018. doi: 10.1056/NEJMoa1800820.

7 See No. 21, 2016, pp. 282–284.

8 See No. 23, 2018, pp. 337–340.

Full report of GACVS meeting of 6-7 June 2018, published in the WHO Weekly Epidemiological Record of 20 July 2018