Risk factors for the spread of vaccine-derived type 2 polioviruses after global withdrawal of trivalent oral poliovirus vaccine and the effects of outbreak responses with monovalent vaccine: a retrospective analysis of surveillance data for 51 countries in Africa.

BACKGROUND: Expanding outbreaks of circulating vaccine-derived type 2 poliovirus (cVDPV2) across Africa after the global withdrawal of trivalent oral poliovirus vaccine (OPV) in 2016 are delaying global polio eradication. We aimed to assess the effect of outbreak response campaigns with monovalent type 2 OPV (mOPV2) and the addition of inactivated poliovirus vaccine (IPV) to routine immunisation. METHODS: We used vaccination history data from children under 5 years old with non-polio acute flaccid paralysis from a routine surveillance database (the Polio Information System) and setting-specific OPV immunogenicity data from the literature to estimate OPV-induced and IPV-induced population immunity against type 2 poliomyelitis between Jan 1, 2015, and June 30, 2020, for 51 countries in Africa. We investigated risk factors for reported cVDPV2 poliomyelitis including population immunity, outbreak response activities, and correlates of poliovirus transmission using logistic regression. We used the model to estimate cVDPV2 risk for each 6-month period between Jan 1, 2016, and June 30, 2020, with different numbers of mOPV2 campaigns and compared the timing and location of actual mOPV2 campaigns and the number of mOPV2 campaigns required to reduce cVDPV2 risk to low levels. FINDINGS: Type 2 OPV immunity among children under 5 years declined from a median of 87% (IQR 81-93) in January-June, 2016 to 14% (9-37) in January-June, 2020. Type 2 immunity from IPV among children under 5 years increased from 3% (<1-6%) in January-June, 2016 to 35% (24-47) in January-June, 2020. The probability of cVDPV2 poliomyelitis among children under 5 years was negatively correlated with OPV-induced and IPV-induced immunity and mOPV2 campaigns (adjusted odds ratio: OPV 0·68 [95% CrI 0·60-0·76], IPV 0·82 [0·68-0·99] per 10% absolute increase in estimated population immunity, mOPV2 0·30 [0·20-0·44] per campaign). Vaccination campaigns in response to cVDPV2 outbreaks have been smaller and slower than our model shows would be necessary to reduce risk to low levels, covering only 11% of children under 5 years who are predicted to be at risk within 6 months and only 56% within 12 months. INTERPRETATION: Our findings suggest that as mucosal immunity declines, larger or faster responses with vaccination campaigns using type 2-containing OPV will be required to stop cVDPV2 transmission. IPV-induced immunity also has an important role in reducing the burden of cVDPV2 poliomyelitis in Africa. FUNDING: Bill & Melinda Gates Foundation, Medical Research Council Centre for Global Infectious Disease Analysis, and WHO. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Disposing of Excess Vaccines After the Withdrawal of Oral Polio Vaccine.

Until recently, waste management for national immunization programs was limited to sharps waste, empty vaccine vials, or vaccines that had expired or were no longer usable. However, because wild-type 2 poliovirus has been eradicated, the World Health Organization's (WHO's) Strategic Advisory Group of Experts on Immunization deemed that all countries must simultaneously cease use of the type 2 oral polio vaccine and recommended that all countries and territories using oral polio vaccine (OPV) "switch" from trivalent OPV (tOPV; types 1, 2, and 3 polioviruses) to bivalent OPV (bOPV; types 1 and 3 polioviruses) during a 2-week period in April 2016. Use of tOPV after the switch would risk outbreaks of paralysis related to type 2-circulating vaccine-derived poliovirus (cVDPV2). To minimize risk of vaccine-derived polio countries using OPV were asked to dispose of all usable, unexpired tOPV after the switch to bOPV. In this paper, we review the rationale for tOPV disposal and describe the global guidelines provided to countries for the safe and appropriate disposal of tOPV. These guidelines gave countries flexibility in implementing this important task within the confines of their national regulations, capacities, and resources. Steps for appropriate disposal of tOPV included removal of all tOPV vials from the cold chain, placement in appropriate bags or containers, and disposal using a recommended approach (ie, autoclaving, boiling, chemical inactivation, incineration, or encapsulation) followed by burial or transportation to a designated waste facility. This experience with disposal of tOPV highlights the adaptability of national immunization programs to new procedures, and identifies gaps in waste management policies and strategies with regard to disposal of unused vaccines. The experience also provides a framework for future policies and for developing programmatic guidance for the ultimate disposal of all OPV after the eradication of polio.

Financial Support to Eligible Countries for the Switch From Trivalent to Bivalent Oral Polio Vaccine-Lessons Learned.

The global switch from trivalent oral polio vaccine (tOPV) to bivalent oral polio vaccine (bOPV) ("the switch") presented an unprecedented challenge to countries. In order to mitigate the risks associated with country-level delays in implementing the switch, the Global Polio Eradication Initiative provided catalytic financial support to specific countries for operational costs unique to the switch. Between November 2015 and February 2016, a total of approximately US$19.4 million in financial support was provided to 67 countries. On average, country budgets allocated 20% to human resources, 23% to trainings and meetings, 8% to communications and advocacy, 9% to logistics, 15% to monitoring, and 5% to waste management. All 67 funded countries successfully switched from tOPV to bOPV during April-May 2016. This funding provided target countries with the necessary catalytic support to facilitate the execution of the switch on an accelerated timeline, and the mechanism offers a model for similar support to future global health efforts, such as the eventual global withdrawal of bOPV.

Implementing the Synchronized Global Switch from Trivalent to Bivalent Oral Polio Vaccines-Lessons Learned From the Global Perspective.

In 2015, the Global Commission for the Certification of Polio Eradication certified the eradication of type 2 wild poliovirus, 1 of 3 wild poliovirus serotypes causing paralytic polio since the beginning of recorded history. This milestone was one of the key criteria prompting the Global Polio Eradication Initiative to begin withdrawal of oral polio vaccines (OPV), beginning with the type 2 component (OPV2), through a globally synchronized initiative in April and May 2016 that called for all OPV using countries and territories to simultaneously switch from use of trivalent OPV (tOPV; containing types 1, 2, and 3 poliovirus) to bivalent OPV (bOPV; containing types 1 and 3 poliovirus), thus withdrawing OPV2. Before the switch, immunization programs globally had been using approximately 2 billion tOPV doses per year to immunize hundreds of millions of children. Thus, the globally synchronized withdrawal of tOPV was an unprecedented achievement in immunization and was part of a crucial strategy for containment of polioviruses. Successful implementation of the switch called for intense global coordination during 2015-2016 on an unprecedented scale among global public health technical agencies and donors, vaccine manufacturers, regulatory agencies, World Health Organization (WHO) and United Nations Children's Fund (UNICEF) regional offices, and national governments. Priority activities included cessation of tOPV production and shipment, national inventories of tOPV, detailed forecasting of tOPV needs, bOPV licensing, scaling up of bOPV production and procurement, developing national operational switch plans, securing funding, establishing oversight and implementation committees and teams, training logisticians and health workers, fostering advocacy and communications, establishing monitoring and validation structures, and implementing waste management strategies. The WHO received confirmation that, by mid May 2016, all 155 countries and territories that had used OPV in 2015 had successfully withdrawn OPV2 by ceasing use of tOPV in their national immunization programs. This article provides an overview of the global efforts and challenges in successfully implementing this unprecedented global initiative, including (1) coordination and tracking of key global planning milestones, (2) guidance facilitating development of country specific plans, (3) challenges for planning and implementing the switch at the global level, and (4) best practices and lessons learned in meeting aggressive switch timelines. Lessons from this monumental public health achievement by countries and partners will likely be drawn upon when bOPV is withdrawn after polio eradication but also could be relevant for other global health initiatives with similarly complex mandates and accelerated timelines.

Cessation of Trivalent Oral Poliovirus Vaccine and Introduction of Inactivated Poliovirus Vaccine - Worldwide, 2016.

Since the 1988 World Health Assembly resolution to eradicate poliomyelitis, transmission of the three types of wild poliovirus (WPV) has been sharply reduced (1). WPV type 2 (WPV2) has not been detected since 1999 and was declared eradicated in September 2015. Because WPV type 3 has not been detected since November 2012, WPV type 1 (WPV1) is likely the only WPV that remains in circulation (1). This marked progress has been achieved through widespread use of oral poliovirus vaccines (OPVs), most commonly trivalent OPV (tOPV), which contains types 1, 2, and 3 live, attenuated polioviruses and has been a mainstay of efforts to prevent polio since the early 1960s. However, attenuated polioviruses in OPV can undergo genetic changes during replication, and in communities with low vaccination coverage, can result in vaccine-derived polioviruses (VDPVs) that can cause paralytic polio indistinguishable from the disease caused by WPVs (2). Among the 721 polio cases caused by circulating VDPVs (cVDPVs*) detected during January 2006-May 2016, type 2 cVDPVs (cVDPV2s) accounted for >94% (2). Eliminating the risk for polio caused by VDPVs will require stopping all OPV use. The first stage of OPV withdrawal involved a global, synchronized replacement of tOPV with bivalent OPV (bOPV) containing only types 1 and 3 attenuated polioviruses, planned for April 18-May 1, 2016, thereby withdrawing OPV type 2 from all immunization activities (3). Complementing the switch from tOPV to bOPV, introduction of at least 1 dose of injectable, trivalent inactivated poliovirus vaccine (IPV) into childhood immunization schedules reduces risks from and facilitates responses to cVDPV2 outbreaks. All 155 countries and territories that were still using OPV in immunization schedules in 2015 have reported that they had ceased use of tOPV by mid-May 2016.(†) As of August 31, 2016, 173 (89%) of 194 World Health Organization (WHO) countries included IPV in their immunization schedules.(§) The cessation of tOPV use is a major milestone toward the global goal of eradicating polio; however, careful surveillance for polioviruses and prompt, aggressive responses to polio outbreaks are still needed to realize a polio-free world.

Diphtheria outbreak in Lao People's Democratic Republic, 2012-2013.

BACKGROUND: Diphtheria is a vaccine-preventable disease. When vaccination coverage and population immunity are low, outbreaks can occur. We investigated a diphtheria outbreak in Lao People's Democratic Republic that occurred during 2012-2013 and highlighted challenges in immunization services delivery to children in the country. METHODS: We reviewed diphtheria surveillance data from April 1, 2012-May 31, 2013. A diphtheria case was defined as a respiratory illness consisting of pharyngitis, tonsillitis, or laryngitis, and an adherent tonsillar or nasopharyngeal pseudomembrane. To identify potential risk factors for diphtheria, we conducted a retrospective case-control study with two aged-matched neighborhood controls per case-patient in Houaphan Province, using bivariate analysis to calculate matched odds ratio (mOR) with 95% confidence intervals (CI). Reasons for non-vaccination among unvaccinated persons were assessed. RESULTS: Sixty-two clinical cases of diphtheria and 12 diphtheria-related deaths were reported in seven of 17 provinces. Among case-patients, 43 (69%) were <15years old, five (8%) reported receiving three DTP doses (DTP3), 21 (34%) had received no DTP doses, and 35 (56%) had unknown vaccination status. For the case-control study, 42 of 52 diphtheria case-patients from Houaphan province and 79 matched-controls were enrolled. Five (12%) case-patients and 20 (25%) controls had received DTP3 (mOR=0.4, CI=0.1-1.7). No diphtheria toxoid-containing vaccine was received by 20 (48%) case-patients and 38 (46%) controls. Among case-patients and controls with no DTP dose, 43% of case-patients and 40% of controls lacked access to routine immunization services. CONCLUSION: Suboptimal DTP3 coverage likely caused the outbreak. To prevent continued outbreaks, access to routine immunization services should be strengthened, outreach visits need to be increased, and missed opportunities need to be minimized. In the short term, to rapidly increase population immunity, three rounds of DTP immunization campaign should be completed, targeting children aged 0-14years in affected provinces.

Hepatitis B vaccine stored outside the cold chain setting: a pilot study in rural Lao PDR.

BACKGROUND: Hepatitis B vaccine birth dose (HepB-BD) was introduced in Lao People's Democratic Republic (Lao-PDR) to prevent perinatal hepatitis B virus transmission. HepB-BD, which is labeled for storage between 2 and 8°C, is not available at all health facilities, because of some lack of functional cold chain; however, previous studies show that HepB-BD is stable if stored outside the cold chain (OCC). A pilot study was conducted in Lao-PDR to evaluate impact of OCC policy on HepB-BD coverage. METHODS: During the six month pilot, HepB-BD was stored OCC for up to 28 days in two intervention districts and stored in cold chain in two comparison districts. In the intervention districts, healthcare workers were educated about HepB-BD and OCC storage. A post-pilot survey compared HepB-BD coverage among children born during the pilot (aged 2-8 months) and children born 1 year before (aged 14-20 months). FINDINGS: In the intervention districts, 388 children aged 2-8 months and 371 children aged 14-20 months were enrolled in the survey; in the comparison districts, 190 children aged 2-8 months and 184 children aged 14-20 months were enrolled. Compared with the pre-pilot cohort, a 27% median increase in HepB-BD (interquartile range [IQR] 58%, p<0.0001) occurred in the pilot cohort in the intervention districts, compared with a 0% median change (IQR 25%, p=0.03) in comparison districts. No adverse reactions were reported. INTERPRETATION: OCC storage improved HepB-BD coverage with no increase in adverse reactions. Findings can guide Lao-PDR on implementation and scale-up options of OCC policy.

Polio endgame: the global switch from tOPV to bOPV.

Globally, polio cases have reached an all-time low, and type 2 poliovirus (one of three) is eradicated. Oral polio vaccine (OPV) has been the primary tool, however, in rare cases, OPV induces paralysis. In 2013, the World Health Assembly endorsed the phased withdrawal of OPV and introduction of inactivated poliovirus vaccine (IPV) into childhood routine immunization schedules. Type 2 OPV will be withdrawn through a globally synchronized "switch" from trivalent OPV (all three types) to bivalent OPV (types 1 and 3). The switch will happen in 155 OPV-using countries between April 17(th) and May 1(st), 2016. Planned activities to reduce type 2 outbreak risks post-switch include the following: tOPV campaigns to increase type 2 immunity prior to the switch, monovalent OPV2 stockpiling to respond to outbreaks should they occur, containment of both wild and vaccine type 2 viruses, enhanced acute flaccid paralysis (AFP) and environmental surveillance, outbreak response protocols, and ensured access to IPV and bivalent OPV.

Estimating the burden of scleroderma disease in Spain.

OBJECTIVE: Scleroderma (systemic sclerosis) is a rare disease that results in great suffering. We estimated the burden of disease posed by scleroderma and its relative importance in the health of the Spanish population. METHODS: We estimated scleroderma-based burden of disease following procedures developed for the Global Burden of Disease study to ensure comparability. RESULTS: Despite its low prevalence, scleroderma generated 1732 disability-adjusted life-years (DALY) in Spain in 2001, comprising 562 (32%) years of life lost and 1170 (68%) years lived with disability. Most scleroderma-related DALY (73%) occurred in the population aged 15-54 years. Estimated DALY accounted for 0.59% of other musculoskeletal disorder-related DALY in the European A subregion (countries with low mortality rate in both adults and children in the World Health Organization classification), a significant value in the overall burden of disease. CONCLUSION: The burden of scleroderma in Spain was high, with disability being the major contributing factor. Burden of disease is an important measure in rare diseases, and may be an important indicator to be considered as a health unit in developed countries.