VACCINE DELIVERY RESEARCH DIGEST

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1 VACCINE DELIVERY RESEARCH DIGEST UNIVERSITY OF WASHINGTON GLOBAL HEALTH START PROGRAM REPORT TO THE BILL AND MELINDA GATES FOUNDATION NOVEMBER 15, 2015 PRODUCED BY: LEVINE GA, ROWHANI- RAHBAR A

2 TABLE OF CONTENTS 1. Optimal allcatin f the limited ral chlera vaccine supply between endemic and epidemic settings 3 A mdeling analysis 2. Health and ecnmic cnsequences f different ptins fr timing the crdinated glbal cessatin f the three ral plivirus vaccine sertypes* 4 A mdeling analysis 3. Managing the risk f circulating vaccine- derived plivirus during the endgame: ral plivirus vaccine needs* 5 A mdeling analysis 4. Effects f Cmmunity Health Nurse- Led Interventin n Childhd Rutine Immunizatin Cmpletin in Primary Health Care Centers in Ibadan, Nigeria 6 A cluster randmized cntrlled trial in Nigeria 5. Feasibility and effectiveness f ral chlera vaccine in an urban endemic setting in Bangladesh: a cluster randmised pen- label trial 7 A cluster randmized cntrlled trial in urban Bangladesh 6. Reduced dse human papillmavirus vaccinatin: An update f the current state- f- the- art 8 A review f the literature 7. Early priming with inactivated plivirus vaccine (IPV) and intradermal fractinal dse IPV administered by a micrneedle device: A randmized cntrlled trial 9 A 5- arm cluster randmized cntrlled trial in Bangladesh 8. Threats t pli eradicatin in high- cnflict areas in Pakistan and Nigeria: a plling study f caregivers f children yunger than 5 years 10 A crss- sectinal survey in cnflict regins f Pakistan and Nigeria 9. Interventins t increase immunisatin cverage amng children mnths f age in India thrugh participatry learning and cmmunity engagement: pilt study fr a cluster randmised trial 11 A pilt cluster randmized cntrlled trial in India 10. The effect f immunizatin n measles incidence in the Demcratic Republic f Cng: Results frm a mdel f surveillance data 12 A chrt analysis f natinal passive- reprting surveillance data in the Demcratic Republic f Cng * These articles are part f a series in BMC Infectius Disease: Integrated mdeling and management f plivirus endgame risks and plicies Appendix: PubMed Search Terms 13 Vaccine Delivery Research Digest, START Prgram Nvember

3 1. OPTIMAL ALLOCATION OF THE LIMITED ORAL CHOLERA VACCINE SUPPLY BETWEEN ENDEMIC AND EPIDEMIC SETTINGS Mre SM, Lessler J. J R Sc Interface Oct 6;12(111). PMID: The Wrld Health Organizatin (WHO) recently established a glbal stckpile f ral chlera vaccine (OCV) t be preferentially used in epidemic respnse (reactive campaigns) with any vaccine remaining after 1 year allcated t endemic settings. Hence, the number f chlera cases r deaths prevented in an endemic setting represents the minimum utility f these dses, and the ptimal risk- averse respnse t any reactive vaccinatin request (i.e. the minimax strategy) is ne that allcates the remaining dses between the requested epidemic respnse and endemic use in rder t ensure that at least this minimum utility is achieved. Using mathematical mdels, we find that the best minimax strategy is t allcate the majrity f dses t reactive campaigns, unless the request came late in the targeted epidemic. As vaccine supplies dwindle, the case fr reactive use f the remaining dses grws strnger. Our analysis prvides a lwer bund fr the amunt f OCV t keep in reserve when respnding t any request. These results prvide a strategic cntext fr the fulfilment f requests t the stckpile, and define allcatin strategies that minimize the number f OCV dses that are allcated t subptimal situatins. WEB: IMPACT FACTOR: 3.92 CITED HALF- LIFE: 4.40 UW EDITORIAL COMMENT: The authrs find that the majrity f stckpile dses shuld be used fr reactive vaccinatin in epidemics where incidence is high, as ppsed t being distributed in endemic settings, t prevent mst cases f disease and death. Hwever, the maximum- benefit allcatin prprtins are highly sensitive t the delay in campaign initiatin in epidemic settings. T have maximum benefit using a strategy that relies primarily n epidemic distributin, the respnse must begin quickly, r the incremental benefit is attenuated. Figure 5 presents a heat map f the ptimal (maximum number f cases prevented) allcatin (percent allcatin t epidemic vs. endemic settings) f OCV dses, based n the expected delay in campaign initiatin and epidemic grwth rate. Figures 2-4 and Figures 6-8 prvide additinal scenaris and assciated maximum benefit allcatin. Vaccine Delivery Research Digest, START Prgram Nvember

4 2. HEALTH AND ECONOMIC CONSEQUENCES OF DIFFERENT OPTIONS FOR TIMING THE COORDINATED GLOBAL CESSATION OF THE THREE ORAL POLIOVIRUS VACCINE SEROTYPES THOMPSON KM, DUINTJER TEBBENS RJ. BMC INFECT DIS SEP 17;15(1):374. PMID: BACKGROUND: Wrld leaders remain cmmitted t glbally- crdinated ral plivirus vaccine (OPV) cessatin fllwing successful eradicatin f wild pliviruses, but the best timing and strategy fr implementatin depend n existing and emerging cnditins. METHODS: Using an existing integrated glbal plivirus risk management mdel, we explre alternatives t the current timing plan f crdinated cessatin f each OPV sertype (i.e., OPV1, OPV2, and OPV3 cessatin fr sertypes 1, 2, and 3, respectively). We assume the current timing plan invlves OPV2 cessatin in 2016 fllwed by OPV1 and OPV3 cessatin in 2019 and we cmpare this t alternative timing ptins, including cessatin f all three sertypes in 2018 r 2019, and cessatin f bth OPV2 and OPV3 in 2017 fllwed by OPV1 in RESULTS: If Supplemental Immunizatin Activity frequency remains sufficiently high thrugh cessatin f the last OPV sertype, then all OPV cessatin timing ptins prevent circulating vaccine- derived plivirus (cvdpv) utbreaks after OPV cessatin f any sertype. The varius OPV cessatin timing ptins result in relatively mdest differences in expected vaccine- assciated paralytic plimyelitis cases and expected ttal f apprximately billin pli vaccine dses used. Hwever, the expected amunts f vaccine f different OPV frmulatins needed changes dramatically with each OPV cessatin timing ptin. Overall health ecnmic impacts remain limited fr timing ptins that nly change the OPV frmulatin but preserve the currently planned year fr cessatin f the last OPV sertype and the glbal intrductin f inactivated plivirus vaccine (IPV) intrductin. Earlier cessatin f the last OPV sertype r later glbal IPV intrductin yield apprximately $1 billin in incremental net benefits due t saved vaccinatin csts, althugh the lgistics f implementatin f OPV cessatin remain uncertain and challenging. CONCLUSION: All cuntries shuld maintain the highest pssible levels f ppulatin immunity t transmissin fr each plivirus sertype prir t the crdinated cessatin f the OPV sertype t manage cvdpv risks. If OPV2 cessatin gets delayed, then glbal health leaders shuld cnsider ther OPV cessatin timing ptins. WEB: IMPACT FACTOR: 2.61 CITED HALF- LIFE: 3.80 UW EDITORIAL COMMENT: Authrs cnclude that a variety f timing ptins result in similar risk f circulating vaccine derived plivirus (cvdpvs) after cessatin f each sertype. Ecnmic implicatins f different cessatin ptins are small, but authrs nte that minimizing vaccine assciated paralytic plimyelitis (VAPP) is preferred by the public, even if aviding cases prvides minimal incremental net benefits. Authrs prpse that if OPV2 cessatin is delayed, it culd be pstpned until OPV1 and OPV3 cessatin can ccur. They advcate that a single cessatin activity is preferable t delayed OPV2 fllwed by OPV13, because the csts and crdinatin challenges f single- sertype cessatin culd be incurred nly nce, and the difference in VAPP cases is negligible. Tables 2 and 3 reprt VAPP cases, vaccines dses, and ecnmic utcmes f cessatin timing ptins, respectively. Vaccine Delivery Research Digest, START Prgram Nvember

5 3. MANAGING THE RISK OF CIRCULATING VACCINE- DERIVED POLIOVIRUS DURING THE ENDGAME: ORAL POLIOVIRUS VACCINE NEEDS Duintjer Tebbens RJ, Thmpsn KM. BMC Infect Dis Sep 24;15(1):390. PMID: BACKGROUND: The Glbal Pli Eradicatin Initiative plans fr crdinated cessatin f ral plivirus vaccine (OPV) use, beginning with sertype 2- cntaining OPV (i.e., OPV2 cessatin) fllwed by the remaining tw OPV sertypes (i.e., OPV13 cessatin). The risk f circulating vaccine- derived plivirus (cvdpv) utbreaks after OPV cessatin f any sertype depends n the sertype- specific ppulatin immunity t transmissin prir t its cessatin. METHODS: Based n an existing integrated glbal mdel f plivirus risk management plicies, we estimate the sertype- specific OPV dses required t manage ppulatin immunity fr a strategy f intensive supplemental immunizatin activities (SIAs) shrtly befre OPV cessatin f each sertype. The strategy seeks t prevent any cvdpv utbreaks after OPV cessatin, althugh actual events remain stchastic. RESULTS: Managing the risks f OPV cessatin f any sertype depends n achieving sufficient ppulatin immunity t transmissin t transmissin at OPV cessatin. This will require that cuntries with sub- ptimal rutine immunizatin cverage and/r cnditins that favr plivirus transmissin cnduct SIAs with hmtypic OPV shrtly befre its planned crdinated cessatin. The mdel suggests the need t increase trivalent OPV use in SIAs by apprximately 40% r mre during the year befre OPV2 cessatin and t cntinue bopv SIAs between the time f OPV2 cessatin and OPV13 cessatin. CONCLUSIONS: Managing the risks f cvdpvs in the pli endgame will require sertype- specific OPV SIAs in sme areas prir t OPV cessatin and lead t demands fr additinal dses f the vaccine in the shrt term that will affect managers and manufacturers. WEB: IMPACT FACTOR: 2.61 CITED HALF- LIFE: 3.80 UW EDITORIAL COMMENT: Authrs estimate frm mdels that trivalent OPV use will need be increased substantially using supplemental immunizatin activities (SIA) in the year prir t OPV2 cessatin, and that cntinued SIA with bopv after OPV2 cessatin and befre OPV13 cessatin is required. The authrs estimates suggest that the amunt f trivalent OPV vaccine needed t maintain ppulatin immunity and prevent cvdpv utbreaks at the time f OPV2 cessatin fr SIA shrtly befre cessatin is higher than what has currently been planned fr. Vaccine Delivery Research Digest, START Prgram Nvember

6 4. EFFECTS OF COMMUNITY HEALTH NURSE- LED INTERVENTION ON CHILDHOOD ROUTINE IMMUNIZATION COMPLETION IN PRIMARY HEALTH CARE CENTERS IN IBADAN, NIGERIA Brwn VB, Oluwatsin OA, Akinyemi JO, Adeyem AA. J Cmmunity Health Sep 22. [Epub ahead f print] PMID: Immunizatin cverage f vulnerable children is ften sub- ptimal in many lw- and middle- incme cuntries. The use f a reminder/recall (R/R) system has been ne f the strategies shwn t be effective in imprving immunizatin rates. In the resent study, we evaluated the effect f R/R and Primary Health Care Immunizatin Prviders Training (PHCIPT) interventin n rutine immunizatin cmpletin amng 595 infants in Ibadan, Nigeria. The design was a grup randmized cntrlled trial with Lcal Gvernment Area (LGA) being the unit f randmizatin. Fur randmly selected LGAs were randmized t receive a cellphne R/R nly (A), a PHCIPT nly (B); cmbined R/R and PHCIPT (C) interventin r serve as a cntrl grup (D). Children aged 0 12 weeks were cnsecutively recruited int each grup and fllwed up fr 12 mnths. The primary utcme measure was rutine immunizatin cmpletin at 12 mnths f age. At the study endpint, immunizatin cmpletin rates were: grup A, 98.6 %; grup B, 70 %; grup C, 97.3 %; and grup D, 57.3 %. Cmpared t the cntrl grup, the cellphne R/R grup was 72 % (RR 1.72, 95 % CI ) and the cmbined RR/PHCIPT grup 70 % (RR 1.70, 95 % CI ) mre likely t cmplete immunizatin. In cntrast, immunizatin cmpletin in the PHCIPT grup was marginally different frm the cntrl grup (RR 1.22, 95 % CI ). These findings remained rbust t adjustment fr ptential predictrs f immunizatin cmpletin as cvariates. In cnclusin, cellphne reminder/recall was effective in imprving immunizatin cmpletin in this Nigerian setting. Its use is recmmended fr large scale implementatin. WEB: IMPACT FACTOR: 1.39 CITED HALF- LIFE: 6.70 UW EDITORIAL COMMENT: The immunizatin cmpletin prprtin was 98.6% amng children in the grup whse parents received reminder/recall alne, 70% in health care prvider training grup, 97.3% in reminder/recall and prvider training grup and 57.3% amng usual care grup. Cell phne reminder/recall was assciated with the highest immunizatin cmpletin prprtin, thugh the cmbinatin f cell phne reminder/recall and prvider training als shwed benefit cmpared with usual care. The prprtin f children with cmplete immunizatin was nt statistically significantly higher in the grup that received prvider training than in the usual care grup. Statistical cmparisns f cmplete vaccinatin prprtin in the reminder/recall versus reminder/recall plus prvider training grups was nt cnducted, but the cnfidence intervals arund the pint estimates f effect fr reminder/recall and reminder/recall plus prvider training verlap; thus the additin f prvider training may add n additinal benefit n tp f caregiver reminder call/recall interventin delivered alne. Vaccine Delivery Research Digest, START Prgram Nvember

7 5. FEASIBILITY AND EFFECTIVENESS OF ORAL CHOLERA VACCINE IN AN URBAN ENDEMIC SETTING IN BANGLADESH: A CLUSTER RANDOMISED OPEN- LABEL TRIAL Qadri F, Ali M, Chwdhury F, Khan AI, Saha A, Khan IA, Begum YA, Bhuiyan TR, Chwdhury MI, Uddin MJ, Khan JA, Chwdhury AI, Rahman A, Siddique SA, Asaduzzaman M, Akter A, Khan A, Ae Yu Y, Siddik AU, Saha NC, Kabir A, Riaz BK, et al. Lancet Oct 3;386(10001): PMID: BACKGROUND Chlera is endemic in Bangladesh with epidemics ccurring each year. The decisin t use a cheap ral killed whle- cell chlera vaccine t cntrl the disease depends n the feasibility and effectiveness f vaccinatin when delivered in a public health setting. We therefre assessed the feasibility and prtective effect f delivering such a vaccine thrugh rutine gvernment services in urban Bangladesh and evaluated the benefit f adding behaviural interventins t encurage safe drinking water and hand washing t vaccinatin in this setting. METHODS We did this cluster- randmised pen- label trial in Dhaka, Bangladesh. We randmly assigned 90 clusters (1:1:1) t vaccinatin nly, vaccinatin and behaviural change, r n interventin. The primary utcme was verall prtective effectiveness, assessed as the risk f severely dehydrating chlera during 2 years after vaccinatin fr all individuals present at time f the secnd dse. This study is registered with ClinicalTrials.gv, number NCT FINDINGS Of peple present at baseline, we analysed : assigned t vaccinatin nly, assigned t vaccinatin and behaviural change, and assigned t nn- interventin. Vaccine cverage was 65% in the vaccinatin nly grup and 66% in the vaccinatin and behaviural change grup. Overall prtective effectiveness was 37% (95% CI lwer bund 18%; p=0.002) in the vaccinatin grup and 45% (95% CI lwer bund 24%; p=0.001) in the vaccinatin and behaviural change grup. We recrded n vaccine- related serius adverse events. INTERPRETATION Our findings prvide the first indicatin f the effect f delivering an ral killed whle- cell chlera vaccine t pr urban ppulatins with endemic chlera using rutine gvernment services and will help plicy makers t frmulate vaccinatin strategies t reduce the burden f severely dehydrating chlera in such ppulatins. WEB: IMPACT FACTOR: CITED HALF- LIFE: 9.2 UW Editrial Cmment: N statistically significant difference was fund in prtectin between vaccine nly and vaccine plus behaviural interventin grups, althugh the pint estimate f effect in the latter was slightly higher. Ttal effectiveness amng participants receiving tw dses f the vaccine was 53% in the vaccinatin nly grup and 58% in the vaccinatin and behaviural change grup. Prtectin did nt differ by age. Vaccine cverage was relatively mdest, which authrs attribute t lack f cmmunity- based media prmtins; strategies t enhance cverage may be required. Out- migratin f participants was extremely high; abut 58%, which authrs cite as a ptential explanatin fr mdest verall prtective effectiveness. Hwever, there was substantial prtective benefit bserved verall despite the high migratin in this urban ppulatin. Vaccine Delivery Research Digest, START Prgram Nvember

8 6. REDUCED DOSE HUMAN PAPILLOMAVIRUS VACCINATION: AN UPDATE OF THE CURRENT STATE- OF- THE- ART Th ZQ, Licciardi PV, Fng J, Garland SM, Tabrizi SN, Russell FM, Mulhlland EK. Vaccine Sep 22;33(39): PMID: Human papillmavirus (HPV) infectin is the primary cause f genital warts, sme rpharyngeal cancers and angenital cancers, including cervical, vagina, vulvar, anal and penile cancers. Primary preventin f cervical cancer requires the preventin f high- risk HPV infectins, particularly HPV gentypes 16 and 18. Bth Gardasil( ) and Cervarix( ) vaccines when administered by a three- dse schedule have been demnstrated t be effective against cervical, vulva, and vaginal cancer precursrs frm vaccine gentypes in phase III clinical trials, and pst- marketing studies; Gardasil( ) vaccine als ffers additinal prtectin against anal cancer precursrs. Hwever, high csts f HPV vaccines and the lgistics f delivering a three- dse schedule ver 6 mnths are challenging in cuntries with limited resurces. Several studies have demnstrated nn- inferirity in antibdy respnse between adlescents (9-15 years ld) wh received tw dses (6 mnths apart) and wmen (>15 years ld) wh received the standard three- dse schedule. These studies prvided evidence fr the Wrld Health Organizatin and Eurpean Medical Assciatin t revise its recmmendatin t give tw instead f three dses f HPV vaccine t adlescents belw 15 years f age, prvided the 2nd dse is given 6 mnths apart. Althugh reduced dse schedules can alleviate csts and lgistics assciated with HPV vaccinatin, especially in resurce- pr cuntries, there are still gaps in this area f research, particularly regarding lng- term prtectin. This review discusses the findings n antibdy respnse and clinical utcmes in studies evaluating reduced dse HPV schedules, and highlights the imprtant cnsideratins f its implementatin. In additin, ther imprtant immunlgical bimarkers that may be assciated with lng- term prtectin are highlighted and discussed. WEB: IMPACT FACTOR: 3.62 CITED HALF- LIFE: 5.5 UW EDITORIAL COMMENT: There are imprtant unanswered questins relating t ptential differences in duratin f prtectin assciated with reduced dse schedules, immune crrelates f clinical effectiveness, and the influence f reduced dse schedules n crss- prtectin fr ther HPV types. Tables 2 and 3 summarize the literature and majr findings fr antibdy respnse and clinical endpints (HPV infectin incidence and prevalence, incidence f cervical abnrmalities, incidence f genital warts) respectively, in studies f reduced dse HPV schedules. Authrs pint ut that in additin t the rle f antibdy in prtectin, ther T and B cells are als imprtant, particularly in influencing the duratin f prtectin. Table 4 summarizes what is knwn abut ptential nvel immunlgical crrelates f prtectin. Authrs pint t an imprtant gap in the literature in that immune crrelates f prtectin besides antibdy respnse have nt been well described in the cntext f reduced dse HPV vaccinatin. Additinal questins relate t whether a reduced dse schedule wuld be inferir t a three- dse schedule in thse abve 15 years f age and immun- cmprmised, and if s, whether implementatin f different schedules fr yunger and lder adlescents will be feasible in lw- incme cuntries. Vaccine Delivery Research Digest, START Prgram Nvember

9 7. EARLY PRIMING WITH INACTIVATED POLIOVIRUS VACCINE (IPV) AND INTRADERMAL FRACTIONAL DOSE IPV ADMINISTERED BY A MICRONEEDLE DEVICE: A RANDOMIZED CONTROLLED TRIAL Anand A, Zaman K, Estivariz CF, Yunus M, Gary HE, Weldn WC, Bari TI, Oberste MS, Wassilak SG, Luby SP, Heffelfinger JD, Pallansch MA. Vaccine Oct 14. [Epub ahead f print] PMID: INTRODUCTION: Inactivated plivirus vaccine (IPV) intrductin and phased ral plivirus vaccine (OPV) cessatin are essential fr eradicatin f pli. METHODS: Healthy 6- week ld infants in Bangladesh were randmized t ne f five study arms: receipt f trivalent OPV (topv) r bivalent OPV (bopv) at ages 6, 10 and 14 weeks, intramuscular IPV r intradermal ne- fifth fractinal dse IPV (f- IPV) at ages 6 and 14 weeks, r f- IPV at ages 6 and 14 weeks with bopv atage 10 weeks (f- IPV/bOPV). All participants received topv at age 18 weeks. RESULTS: Of 975 infants randmized, 95% (922) cmpleted fllw- up. Type 1 sercnversin after 3 dses at 6, 10 and 14 weeks was higher with bopv cmpared with topv (99% vs 94%, p = 0.019). Sercnversins t types 1 and 3 after 2 IPV dses at ages 6 and 14 weeks were n different than after 3 dses f topv r bopv at ages 6, 10 and 14 weeks. A priming respnse, sercnversin 1 week after IPV at 14 weeks amng thse wh did nt sercnvert after IPV at 6 weeks, was bserved against plivirus types 1, 2 and 3 in 91%, 84% and 97%, respectively. Cmpared with IPV, f- IPV failed nn- inferirity tests fr sercnversin with 1 r 2 dses and priming after 1 dse. DISCUSSION: The findings demnstrate cnsiderable priming with IPV at age 6 weeks, cmparable immun- genicity f topv and bopv, and inferir immungenicity f ne- fifth f- IPV cmpared with IPV. If IPV induced priming at age 6 weeks is similar t that at age 14 weeks, IPV culd be administered at a yunger age and pssibly with a higher cverage. WEB: IMPACT FACTOR: 3.62 CITED HALF- LIFE: 5.50 UW Editrial Cmment: Results indicate that IPV- induced priming at age 6 weeks and 14 weeks were similar ( 90% f children had either sercnverted r were primed against type2 plivirus with 1 dse f IPV at age 6 weeks ) and that topv and bopv had cmparable immungenicity fr plivirus types 1 and 3. They reprt that ne- fifth f- IPV was inferir t IPV. Figure 2 shws the differences in sercnversin and priming between f- IPV arm and intramuscular IPV arm by ser- type at different time pints. Table 2 shws humral and intestinal immungenicity by study arm. Figure 3 shws reverse antibdy titers at 18 weeks f age in each study arm. The indicatin f early priming with a single dse at 6 wks may have imprtant implicatins fr delivery, since early priming at 6 wks vs. 14 wks (current WHO SAGE recmmendatin) wuld influence the ppulatin- level immunity and prtect against utbreaks. Vaccine Delivery Research Digest, START Prgram Nvember

10 8. THREATS TO POLIO ERADICATION IN HIGH- CONFLICT AREAS IN PAKISTAN AND NIGERIA: A POLLING STUDY OF CAREGIVERS OF CHILDREN YOUNGER THAN 5 YEARS SteelFisher GK, Blendn RJ, Guirguis S, Brul A, Lasala- Blanc N, Cleman M, et al. Lancet Infect Dis Oct;15(10): PMID: BACKGROUND Eliminatin f plivirus frm endemic cuntries is a crucial step in eradicatin; hwever, vaccinatin prgrammes in these areas face challenges, especially in regins with cnflict. We analysed interviews with caregivers f children living in tw pli- endemic cuntries t assess whether these challenges are largely peratinal r als driven by resistance r misinfrmatin in the cmmunity. METHODS We designed and analysed plls based n face- t- face interviews f a randm sample f parents and ther caregivers f children yunger than 5 years in regins f Pakistan and Nigeria at high risk fr pli transmissin. In bth cuntries, the sample was drawn via a stratified multistage cluster design with randm rute husehld selectin. The questinnaire cvered awareness, knwledge, and attitudes abut pli and ral pli vaccine (OPV), trust in vaccinatin effrts, and caregiver pririties fr gvernment actin. We assessed experiences f caregivers in accessible higher- cnflict areas and cmpared their knwledge and attitudes with thse in lwer- cnflict areas. Differences were tested with tw- sample t tests. FINDINGS The pll cnsisted f 3396 caregivers frm Pakistan and 2629 frm Nigeria. Abut a third f caregivers wh respnded in higher- cnflict areas f Pakistan (Federally Administered Tribal Areas [FATA], 30%) and Nigeria (Brn, 33%) were unable t cnfirm that their child was vaccinated in the previus campaign. In FATA, 12% f caregivers reprted that they were unaware f pli, and in Brn 12% f caregivers reprted that vaccinatrs visited but their child did nt receive the vaccine r they did nt knw whether the child was vaccinated. Additinally, caregivers in higher- cnflict areas are less likely t hld beliefs abut OPV that culd mtivate acceptance and are mre likely t hld cncerns than are caregivers in lwer- cnflict areas. INTERPRETATION Beynd the difficulties in reaching hmes with OPV, challenges fr vaccinatin prgrammes in higher cnflict areas extend t limited awareness, negative attitudes, and gaps in trust. Vaccinatin effrts might need t address underlying attitudes f caregivers thrugh direct cmmunicatins and the selectin and training f lcal vaccinatrs. WEB: IMPACT FACTOR: CITED HALF- LIFE: 4.70 UW EDITORIAL COMMENT: Few differences were bserved in knwledge r attitudes abut pli in higher- versus lwer- cnflict areas f Pakistan and Nigeria, but knwledge and attitudes regarding pli vaccinatin differed by level f cnflict. There was less trust in vaccinatrs in higher- than lwer- cnflict areas in Pakistan and Nigeria: 25% vs. 61% and 48% vs. 70%, respectively, reprted a great deal f trust in vaccinatrs and 65% vs. 80% and 74% vs. 83% said the vaccine was very effective in higher- and lwer- cnflict regins f Pakistan and Nigeria, respectively. Rumrs abut negative vaccinatin effects were cmmn. Operatinal factrs (failure t be visited by vaccinatr/unknwn whether vaccinatr visited) were indicated as key barriers and were mre cmmn in higher- cnflict regins. The highest risk areas were excluded due t security cncerns, and thus differences may be an attenuatin f the true magnitude f difference assciated with intense cnflict. Vaccine Delivery Research Digest, START Prgram Nvember

11 9. INTERVENTIONS TO INCREASE IMMUNISATION COVERAGE AMONG CHILDREN MONTHS OF AGE IN INDIA THROUGH PARTICIPATORY LEARNING AND COMMUNITY ENGAGEMENT: PILOT STUDY FOR A CLUSTER RANDOMISED TRIAL Jhri M, Chandra D, Kne GK, Dudeja S, Sylvestre MP, Sharma JK, Pahwa S. BMJ Open Sep 18;5(9):e PMID: OBJECTIVE: With the aim f cnducting a future cluster randmised trial t assess interventin impact n child vaccinatin cverage, we designed a pilt study t assess feasibility and aid in refining methds fr the larger study. TRIAL DESIGN: Cluster- randmised design with a 1:1 allcatin rati. METHODS: Clusters were 12 villages in rural Uttar Pradesh. All wmen residing in a selected village wh were mthers f a child 0 23 mnths f age were eligible; participants were chsen at randm. Over 4 mnths, interventin grup (IG) villages received: (1) hme visits by vlunteers; (2) cmmunity mbilisatin events t prmte immunisatin. Cntrl grup (CG) villages received cmmunity mbilisatin t prmte nutritin. A tll- free number fr immunisatin was ffered t all IG and CG village residents. Primary utcmes were ex- ante criteria fr feasibility f the main study related t prcesses fr recruitment and randmisatin (50% f villages wuld agree t participate and accept randmisatin; 30 wmen culd be recruited in 70% f villages), and retentin f participants (50% f wmen retained frm baseline t endline). Clusters were assigned t IG r CG using a cmputer- generated randmisatin schedule. Neither participants nr thse delivering interventins were blinded, but thse assessing utcmes were blinded t grup assignment. RESULTS: All villages cntacted agreed t participate and accepted randmisatin. 36 wmen were recruited per village; 432 participants were randmised (IG n=216; CG n=216). N clusters were lst t fllw- up. The main analysis included 86% (373/432) f participants, 90% (195/216) frm the IG and 82% (178/216) frm the CG. CONCLUSIONS: Criteria related t feasibility were satisfied, giving us cnfidence that we can successfully cnduct a larger cluster randmised trial. Methdlgical lessns will infrm design f the main study. WEB: /bmjpen IMPACT FACTOR: 2.27 CITED HALF- LIFE: 2.00 UW EDITORIAL COMMENT: Table 1 summarizes the interventin cmpnents and study activities in each arm. Methdlgical lessns fr the planned main study summarizes imprtant lessns learned. Of nte, althugh the use f a tll- free phne line fr questins abut immunizatin was mre frequent in interventin cmmunities, verall use was lw. Hwever, qualitative research indicated cmmunity members viewed the line psitively. Authrs explain that questins may have been directed first t the cmmunity health wrkers, versus using the phne line. Prxy utcme measures indicate that sme, but nt all, interventin cmpnents were effective in influencing intermediate utcmes (knwledge and understanding f vaccinatin) n the individual level (Table 4). Nte that the effect f the interventin wuld be demnstrated by a statistically significant difference in the ORs fr change since baseline, cmparing OR in interventin t OR in cntrl grups, which is nt calculated in this descriptive analysis. The interventin was targeted t address rutine immunizatin, but authrs nte it may be pssible t adapt interventin cmpnents fr use in campaign settings. Vaccine Delivery Research Digest, START Prgram Nvember

12 10. THE EFFECT OF IMMUNIZATION ON MEASLES INCIDENCE IN THE DEMOCRATIC REPUBLIC OF CONGO: RESULTS FROM A MODEL OF SURVEILLANCE DATA Dshi RH, Shidi C, Mulumba A, Eckhff P, Nguyen C, Hff NA, Gerber S, Okitlnda E, Ilunga BK, Rimin AW. Vaccine Oct 14. [Epub ahead f print] PMID: BACKGROUND: Measles cntinues t be a leading cause f vaccine- preventable disease mrtality amng children under five despite a safe and efficacius vaccine being readily available. While glbal vaccinatin cverage has imprved tremendusly, measles utbreaks persist thrughut sub- Saharan Africa. Since 2010, the Demcratic Republic f Cng (DRC) has seen a resurgence f measles utbreaks affecting all 11 prvinces. These utbreaks are mainly attributed t gaps in rutine immunizatin (RI) cverage cmpunded with missed supplementary immunizatin activities (SIAs). We utilized natinal passive surveillance data frm DRC s Integrated Disease Surveillance and Respnse (IDSR) system t estimate the effect f immunizatin n measles incidence in DRC. METHODS: We investigated the decline in measles incidence pst- immunizatin with ne dse f measles cntaining vaccine (MCV1) with and withut the additin f supplementary immunizatin activities (SIAs) and utbreak respnse immunizatin (ORI) campaigns. Measles case cunts by health zne were btained frm the IDSR system between January 1, 2010 and December 31, The impact f measles immunizatin was mdeled using a randm effects multi- level mdel fr cunt data with RI cverage levels and mass campaign activities frm ne year prir. RESULTS: The presence f an SIA (airr [95% CI] 0.86 [ ]) and ORI (0.28 [ ]) in the year prir were bth assciated with a decrease in measles incidence. When interactin terms were included ur results suggested that the high levels f MCV1 reprted in the year prir and the presence f either mass campaign was assciated with a decrease in measles incidence. CONCLUSIONS: Our results highlight the imprtance f a tw- dse measles vaccine schedule and the need fr a strng rutine immunizatin prgram cupled with frequent SIAs. Repeated ccurrences f large- scale utbreaks in DRC suggest that vaccinatin cverage rates are grssly verestimated and signify the imprtance f the evaluatin and mdificatin f measles preventin and cntrl strategies. WEB: IMPACT FACTOR: 3.62 CITED HALF- LIFE: 5.50 UW Editrial Cmment: Vaccine cverage was varied acrss health znes, and many health znes reprted cverage ver 100%. In this study, MCV1 cverage level alne in the health zne was nt assciated with incidence f measles in the fllwing year in that zne, and the authrs reprt that the lack f bserved assciatin may be due t misclassificatin f cverage estimates and/r grss under- reprting f measles cases, particularly in regins f civil unrest. Hwever, higher measles immunizatin cverage was assciated with lwer measles incidence in znes where SIA and ORI were held in the previus calendar year. Authrs reprt data quality cncerns in immunizatin cverage estimates and measles case cunts. Vaccine Delivery Research Digest, START Prgram Nvember

13 APPENDIX: PUBMED SEARCH TERMS (((((vaccine[tiab] OR vaccines[tiab] OR vaccinatin[tiab] OR immunizatin[tiab] OR immunisatin[tiab] OR vaccine[mesh] OR immunizatin[mesh]) AND (lgistics[tiab] OR supply[tiab] OR "supply chain"[tiab] OR implementatin[tiab] OR expenditures[tiab] OR financing[tiab] OR ecnmics[tiab] OR "Cst effectiveness"[tiab] OR cverage[tiab] OR attitudes[tiab] OR belief[tiab] OR beliefs[tiab] OR refusal[tiab] OR "Prcurement"[tiab] OR timeliness[tiab] OR systems[tiab])) OR ("vaccine delivery"[tiab])) NOT ("in vitr"[tiab] OR "immune respnse"[tiab] OR gene[tiab] OR chemistry[tiab] OR gentx*[tiab] OR sequencing[tiab] OR nanparticle*[tiab] OR bacteriphage[tiab] OR exme[tiab] OR exgenus[tiab] OR electrpr*[tiab] OR "systems bilgy"[tiab] OR "animal mdel"[tiab] OR cattle[tiab] OR sheep[tiab] OR gat[tiab] OR rat[tiab] OR pig[tiab] OR mice[tiab] OR muse[tiab] OR murine[tiab] OR prcine[tiab] OR vine[tiab] OR rdent[tiab] OR fish[tiab])) AND (English[LA]) AND ("2015/09/15"[PDAT] : "2015/10/14"[PDAT])) *On Octber 29, 2015, this search f English language articles published between September 15, 2015 and Octber 14, 2015 and indexed by the US Natinal Library f Medicine resulted in 189 unique manuscripts. Vaccine Delivery Research Digest, START Prgram Nvember