BACKGROUND: In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration. METHODS: We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR(1)YF(1)), MMR followed by YF vaccine four weeks later (MMR(1)YF(2)), or YF followed by MMR vaccine four weeks later (YF(1)MMR(2)). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests. RESULTS: Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR(1)YF(1) group versus 96.3% in the MMR(1)YF(2) group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR(1)YF(1) versus 94.7% MMR(1)YF(2), a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR(1)YF(1) versus 97.9% MMR(1)YF(2), a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR(1)YF(1) versus 97.5% YF(1)MMR(2), a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted. CONCLUSION: Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration. TRIAL REGISTRATION: The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017.

The World Health Organization (WHO) has established a target to eliminate mother-to-child-transmission (EMTCT) of hepatitis B virus (HBV), defined as a prevalence of hepatitis B surface antigen (HBsAg) of ≤0.1% among children, by 2030. Using nationally representative serosurveys to verify achievement of this target requires large sample sizes and significant resources. We assessed the feasibility of a potentially more efficient two-phase method to verify EMTCT of HBV in Colombia. In the first phase, we conducted a risk assessment to identify municipalities at the highest risk of ongoing HBV transmission. We ranked the 1,122 municipalities of Colombia based on reports of HBV infection in pregnant women per 1,000 population. Municipalities with ≥0.3 reports per 1,000 persons (equating to the top quartile) were further assessed based on health facility birth rates, coverage with three doses of hepatitis B vaccine (HepB3), and seroprevalence data. Hepatitis B risk was considered to be further increased for municipalities with HepB3 coverage or health facility birth rate <90%. In the second phase, we conducted a multistage household serosurvey of children aged 5-10 years in 36 municipalities with the highest assessed HBV risk. HBsAg was not detected in any of 3,203 children tested, yielding a 90% upper confidence bound of <0.1% prevalence. Coverage with HepB3 and hepatitis B birth dose was high at 97.5% and 95.6%, respectively. These results support the conclusion that Colombia has likely achieved EMTCT of HBV.

Measles is endemic in Africa; measles mortality is highest among infants. Infant measles antibody titer at birth is related to maternal immune status. Older mothers are likelier to have had measles infection, which provides higher antibody titers than vaccine-induced immunity. We investigated the relationship between maternal age and measles susceptibility in mother-infant pairs in Mali through six months of infancy. We measured serum measles antibodies in 340 mother-infant pairs by plaque reduction neutralization test (PRNT) and calculated the proportion of mothers with protective titers (>120 mIU/mL) at delivery and the proportion of infants with protective titers at birth, and at three and six months of age. We explored associations between maternal age and measles antibodies in mothers and infants at the timepoints noted. Ten percent of Malian newborns were susceptible to measles; by six months nearly all were. Maternal and infant antibody titers were highly correlated. At delivery, 11% of mothers and 10% of newborns were susceptible to measles. By three and six months, infant susceptibility increased to 72% and 98%, respectively. Infants born to younger mothers were most susceptible at birth and three months. Time to susceptibility was 6.6 weeks in infants born to mothers with measles titer >120-<430 mIU/mL versus 15.4 weeks when mothers had titers ≥430 mIU/mL. Maternal and newborn seroprotective status were positively correlated. Improved strategies are needed to protect susceptible infants from measles infection and death. Increasing measles immunization coverage in vaccine eligible populations, including nonimmune reproductive-aged women and older children should be considered.

INTRODUCTION: Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated >100 million children in 2010. An increasing proportion of infections now occur among adults and there is concern that persistent susceptibility in adults is an obstacle to measles elimination in China. We performed a case-control study in six Chinese provinces between January 2012 to June 2013 to identify risk factors for measles virus infection and susceptibility among adults. METHODS: Persons ≥15 years old with laboratory-confirmed measles were age and neighborhood matched with three controls. Controls had blood specimens collected to determine their measles IgG serostatus. We interviewed case-patients and controls about potential risk factors for measles virus infection and susceptibility. Unadjusted and adjusted matched odds ratios and 95% confidence intervals (CIs) were calculated via conditional logistic regression. We calculated attributable fractions for infection for risk factors that could be interpreted as causal. RESULTS: 899 cases and 2498 controls were enrolled. Among controls, 165 (6.6%) were seronegative for measles IgG indicating persistent susceptibility to infection. In multivariable analysis, hospital visit and travel outside the prefecture in the prior 1-3 weeks were significant risk factors for measles virus infection. Occupation and reluctance to accept measles vaccination were significant risk factors for measles susceptibility. The calculated attributable fraction of measles cases from hospital visitation was 28.6% (95% CI: 20.6-38.8%). CONCLUSIONS: Exposure to a healthcare facility was the largest risk factor for measles virus infection in adults in China. Improved adherence to hospital infection control practices could reduce risk of ongoing measles virus transmission and increase the likelihood of achieving and sustaining measles elimination in China. The use of control groups stratified by serological status identified distinct risk factors for measles virus infection and susceptibility among adults.

BACKGROUND: Typhoid fever prevention and control efforts are critical in an era of rising antimicrobial resistance among typhoid pathogens. India remains one of the highest typhoid disease burden countries, although a highly efficacious typhoid conjugate vaccine (TCV), prequalified by the World Health Organization in 2017, has been available since 2013. In 2018, the Navi Mumbai Municipal Corporation (NMMC) introduced TCV into its immunization program, targeting children aged 9 months to 14 years in 11 of 22 areas (Phase 1 campaign). We describe the decision making, implementation, and delivery costing to inform TCV use in other settings. METHODS: We collected information on the decision making and campaign implementation in addition to administrative coverage from NMMC and partners. We then used a microcosting approach from the local government (NMMC) perspective, using a new Microsoft Excel-based tool to estimate the financial and economic vaccination campaign costs. RESULTS: The planning and implementation of the campaign were led by NMMC with support from multiple partners. A fixed-post campaign was conducted during weekends and public holidays in July-August 2018 which achieved an administrative vaccination coverage of 71% (ranging from 46% in high-income to 92% in low-income areas). Not including vaccine and vaccination supplies, the average financial cost and economic cost per dose of TCV delivery were $0.45 and $1.42, respectively. CONCLUSION: The first public sector TCV campaign was successfully implemented by NMMC, with high administrative coverage in slums and low-income areas. Delivery cost estimates provide important inputs to evaluate the cost-effectiveness and affordability of TCV vaccination through public sector preventive campaigns.

BACKGROUND: Bhutan is committed to eliminating hepatitis B and hepatitis C, though recent baseline estimates of disease burden in the general population are unknown. In 2017, we carried out a biomarker survey in the general population to estimate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) biomarkers to evaluate the impact of immunization and guide further efforts. METHODS: In 2017, a cross-sectional, population-based, three-stage cluster survey was undertaken of the general population (1-17 and 20+ years of age). We visited households, collected blood specimens and administered a standard questionnaire. Specimens were collected for hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) testing. We calculated prevalence of infection and selected characteristics, along with confidence intervals (CIs). RESULTS: Of 1372 individuals approached, 1358 (99%) participated. Of those, 1321 (97%) had a specimen tested for HBsAg, and among 1173 enrolled individuals 5 years of age or older, 1150 (98%) individuals were tested for anti-HCV. The prevalence of HBsAg was 2.0% in 775 persons 20 years of age or older (95% CI: 1.0-4.0) and 0.5% in 546 persons 1-17 years of age (95% CI: 0.1-1.8). The prevalence of anti-HCV was 0.3% (95% CI: 0.1-0.8) among persons >/=5 years. CONCLUSIONS: Universal hepatitis B immunization of infants has resulted in a low prevalence of chronic HBV infection in persons 1-17 years of age and the prevalence of anti-HCV is low among persons aged >/=5 years. Efforts should continue to reach high coverage of the timely birth dose along with completion of the hepatitis B vaccine series. To reduce the chronic liver disease burden among adults, HBV and HCV testing and treatment as indicated might be restricted to pregnant women, blood donors, individuals with chronic liver diseases, and other groups with history of high-risk exposures.

INTRODUCTION: Circulation of poliovirus in neighboring countries and mass population movement places Lebanon at risk of polio and other vaccine-preventable disease outbreaks. Determining population immunity levels is essential for guiding program planning and implementation of targeted supplementary immunization activities (SIAs) in governorates and subpopulations with low seroprevalence. METHODS: A cross-sectional multi-stage cluster survey was conducted during February-December 2016 in all six governorates of Lebanon adapted from the World Health Organization (WHO) recommended Expanded Progamme on Immunization (EPI) methodology. Sera from selected children aged 12-59 months were tested for poliovirus neutralizing antibodies. RESULTS: Of 2,164 children recruited in this study, 1,893 provided sufficient quantity of serum samples for laboratory testing. Seroprevalence for all three poliovirus serotypes was greater than 90% in all six governorates. Poliovirus vaccine coverage with three or more doses, based on vaccination cards or parental recall, ranged between 54.1% for children aged 36-47 months in the North and 83.5% for children aged 48-59 months in Beirut. CONCLUSION: Immunity to polioviruses was high in Lebanon in 2016 following a series of supplementary immunization activities. It is essential to continue strategies that increase vaccination coverage in order to sustain the considerably high immunity levels and prevent reintroduction and transmission of poliovirus. Educating caregivers and training health care workers on the standardized usage of home-based vaccination records is needed to guarantee the accuracy of records on children's vaccination status.

The Western Pacific Region (WPR) established a goal to decrease chronic hepatitis B virus (HBV) infection among children to <1% and to achieve >/=95% hepatitis B vaccine birth dose (HepB-BD) and >/=95% three-dose (HepB3) coverage by 2017. In 2016, we conducted a national serosurvey in the Solomon Islands among 6-7-year-old school children to assess progress towards the control goal and immunity to measles, rubella, tetanus and diphtheria. Eighty schools were selected systematically proportional to their 6-7-year-old population; all 6-7-year-olds were enrolled. We collected basic demographic information and vaccination history. Children were tested for HBV surface antigen (HBsAg) using a rapid test, and for immunity to measles, rubella, tetanus, and diphtheria using a multiplex bead assay. In total, 1,249 out of 1,492 children (84%) were enrolled, among whom 1,169 (94%) underwent HBsAg testing and 1,156 (93%) provided dried blood spots. Almost 80% (n = 982) of enrolled children had vaccination cards, among whom 59% (n = 584) received a timely HepB-BD (within 24 hours of birth), 95% (n = 932) received HepB3, and >90% received vaccines for diphtheria, tetanus, and measles (rubella vaccine was not available at the time). HBsAg prevalence was 3.1% (95% confidence interval (CI): 2.0%-4.9%), with 55% of identified cases from one province. Among 982 children with vaccination cards, HBsAg prevalence was higher among children who had not received a timely HepB-BD and at least two HepB doses compared to those who had (4% vs. 2%). Of 1,156 tested children, immunoprotection estimates were 99% (95% CI: 98%-99%) for measles, 99% (95% CI: 97%-100%) for rubella, 85% (95% CI: 83%-87%) for tetanus, and 51% (95% CI: 47%-55%) for diphtheria. Improving timely HepB-BD coverage and maintaining high HepB3 coverage could help Solomon Islands reach the regional HBV control goal. Low immunity to tetanus and diphtheria suggests the need to introduce booster doses to ensure long-term protection.

BACKGROUND: In 2015-2016, Mongolia experienced an unexpected large measles outbreak affecting mostly young children and adults. After two nationwide vaccination campaigns, measles transmission declined. To determine if there were any remaining immunity gaps to measles or rubella in the population, a nationally representative serosurvey for measles and rubella antibodies was conducted after the outbreak was over. METHODS: A nationwide, cross-sectional, stratified, three-stage cluster serosurvey was conducted in November-December 2016. A priori, four regional strata (Ulaanbaatar, Western, Central, and Gobi-Eastern) and five age strata (6 months-23 months, 2-7 years, 8-17 years, 18-30 years, and 31-35 years) were created. Households were visited, members interviewed, and blood specimens were collected from age-appropriate members. Blood specimens were tested for measles immunoglobulin G (IgG) and rubella IgG (Enzygnost(R) Anti-measles Virus/IgG and Anti-rubella Virus/IgG, Siemens, Healthcare Diagnostics Products, GmbH Marburg, Germany). Factors associated with seropositivity were evaluated. RESULTS: Among 4598 persons aged 6 months to 35 years participating in the serosurvey, 94% were measles IgG positive and 95% were rubella IgG positive. Measles IgG seropositivity was associated with increasing age and higher education. Rubella IgG seropositivity was associated with increasing age, higher education, smaller household size, receipt of MMR in routine immunization, residence outside the Western Region, non-Muslim religious affiliation, and non-Kazakh ethnicity. Muslim Kazakhs living in Western Region had the lowest rubella seroprevalence of all survey participants. CONCLUSIONS: Nationally, high immunity to both measles and rubella has been achieved among persons 1-35 years of age, which should be sufficient to eliminate both measles and rubella if future birth cohorts have >/= 95% two dose vaccination coverage. Catch-up vaccination is needed to close immunity gaps found among some subpopulations, particularly Muslim Kazakhs living in Western Region.

BACKGROUND: After successful meningococcal serogroup A conjugate vaccine (MACV) campaigns since 2010, Burkina Faso introduced MACV in March 2017 into the routine Expanded Programme for Immunization schedule at age 15-18 months, concomitantly with second-dose measles-containing vaccine (MCV2). We examined MCV2 coverage in pre- and post-MACV introduction cohorts to describe observed changes regionally and nationally. METHODS: A nationwide household cluster survey of children 18-41 months of age was conducted 1 year after MACV introduction. Coverage was assessed by verification of vaccination cards or recall. Two age groups were included to compare MCV2 coverage pre-MACV introduction (30-41 months) versus post-MACV introduction (18-26 months). RESULTS: In total, 15 925 households were surveyed; 7796 children were enrolled, including 3684 30-41 months of age and 3091 18-26 months of age. Vaccination documentation was observed for 86% of children. The MACV routine coverage was 58% (95% confidence interval [CI], 56%-61%) with variation by region (41%-76%). The MCV2 coverage was 62% (95% CI, 59%-65%) pre-MACV introduction and 67% (95% CI, 64%-69%) post-MACV introduction, an increase of 4.5% (95% CI, 1.3%-7.7%). Among children who received routine MACV and MCV2, 93% (95% CI, 91%-94%) received both at the same visit. Lack of caregiver awareness about the 15- to 18-month visit and vaccine unavailability were common reported barriers to vaccination. CONCLUSIONS: A small yet significant increase in national MCV2 coverage was observed 1 year post-MACV introduction. The MACV/MCV2 coadministration was common. Findings will help inform strategies to strengthen second-year-of-life immunization coverage, including to address the communication and vaccine availability barriers identified.

A community-based serosurvey was conducted among children ages 6-59 to assess population immunity in Jordan's high-risk areas following the Middle East polio outbreak response. The survey was a two-stage cluster-quota sample with high risk areas as the primary sampling units. High-risk areas included border and hard-to-reach areas, and areas with a high proportion of refugees, mobile communities and/or low coverage during previous immunization campaigns. Population immunity to poliovirus was high overall. In high-risk areas, Type 1 seroprevalence = 98% (95% CI = 96, 99), Type 2= 98 (95% CI = 96, 99) and Type 3= 96 (95% CI = 94, 98). Seroprevalence was higher in the refugee camps: Type 1 seroprevalence = 99.6 (95% CI = 97.9, 100); Type 2: 99.6 (95% CI = 97.9, 99.9), and Type 3: 100 (95% CI = 100,100). The vigilance that the Jordan Ministry of Health has placed on locating and vaccinating high-risk populations has been successful in maintaining high population immunity and averting polio outbreaks despite the influx of refugees from Syria.

INTRODUCTION: Limited evidence is available about the effectiveness of strategies to remind caregivers when to bring children back for future vaccinations in low- and middle-income country settings. We evaluated the effectiveness of two reminder strategies based on home-based vaccination records (HBR) in Indonesia. METHODS: In this cluster-randomized controlled trial involving 3616 children <1year of age, 90 health facilities were randomly assigned to either a control group or one of two intervention groups: (1) HBR-only group, where healthcare workers provided an HBR to any child without an HBR during a vaccination visit and instructed the caregiver to keep it at home between visits, or (2) HBR+sticker group, where, in addition to HBR provision, healthcare workers placed vaccination appointment reminder stickers on the HBR. The primary outcome was receipt of the third dose of diphtheria-tetanus-pertussis-containing vaccine (DTPcv3) within 7months and the secondary outcome was receipt of a timely DTPcv3 dose. RESULTS: Control group DTPcv3 coverage was 81%. In intention-to-treat analysis, neither intervention group had significantly different DTPcv3 coverage compared with the control group (RR=0.94, 95% confidence interval [CI] 0.87; 1.02 for HBR-only group; RR=0.97, 95% CI 0.90; 1.04 for HBR+sticker group) by study end. However, children in the HBR+sticker group were 50% more likely to have received a DTPcv3 vaccination (RR=1.46, 95% CI 1.02, 2.09) within 60days of DTPcv1 vaccination, compared with children in the control group; children in the HBR-only group were not more likely to have done so (RR=1.05, 95% CI 0.71, 1.55). DISCUSSION: Reminder stickers had an immediate effect on coverage by improving the proportion of children who received a timely DTPcv3 dose but no effect on the proportion who received DTPcv3 after 7months. Coupling reminder stickers with strategies to address other reasons why children do not return for vaccination visits should be further explored.

INTRODUCTION: In 2014, an oral cholera vaccine (OCV) campaign targeting 185,314 persons aged >/=1years was conducted in 3 departments via fixed post and door-to-door strategies. This was the first use of the global OCV stockpile in Haiti. METHODS: We conducted a multi-stage cluster survey to assess departmental OCV coverage. Target population estimates were projected from the 2003 Haiti population census with adjustments for population growth and estimated proportion of pregnant women. In the three departments, we sampled 30/106 enumeration areas (EAs) in Artibonite, 30/244 EAs in Centre, and 20/29 EAs in Ouest; 20 households were systematically sampled in each EA. Household and individual interviews using a standard questionnaire were conducted in each selected household; data on OCV receipt were obtained from vaccination card or verbal report. We calculated OCV campaign coverage estimates and 95% confidence intervals (CIs) accounting for survey design. RESULTS: Overall two-dose OCV coverage was 70% (95% CI: 60, 79), 63% (95% CI: 55, 71), and 44% (95% CI: 35, 53) in Artibonite, Centre, and Ouest, respectively. Two-dose coverage was higher in the 1-4years age group than among those>/=15years in Artibonite (difference: 11%; 95% CI: 5%, 17%) and Ouest (difference: 12%; 95% CI: 3, 20). A higher percentage of children aged 5-14years received both recommended doses than did those>/=15years (Artibonite: 14% (95% CI: 8%, 19%) difference; Centre: 11% difference (95% CI: 5%, 17%); Ouest: 10% difference (95% CI: 2%, 17%). The most common reason for not receiving any OCV dose was being absent during the campaign or not having heard about vaccination activities. CONCLUSIONS: While coverage estimates in Artibonite and Centre were comparable with other OCV campaigns in Haiti and elsewhere, inadequate social mobilization and outdated population estimates might have contributed to lower coverage in Ouest.

BACKGROUND: In 2017, measles elimination was verified in Bhutan, and the country appears to have sufficiently high vaccination coverage to achieve rubella elimination. However, a measles and rubella serosurvey was conducted to find if any hidden immunity gaps existed that could threaten Bhutan's elimination status. METHODS: A nationwide, three-stage, cluster seroprevalence survey was conducted among individuals aged 1-4, 5-17, and >20 years in 2017. Demographic information and children's vaccination history were collected, and a blood specimen was drawn. Serum was tested for measles and rubella immunoglobulin G (IgG). Frequencies, weighted proportions, and prevalence ratios for measles and rubella seropositivity were calculated by demographic and vaccination history, taking into account the study design. RESULTS: Of the 1325 individuals tested, 1045 (81%, 95% CI 78%-85%) were measles IgG seropositive, and 1290 (97%, 95% CI 95%-99%) were rubella IgG seropositive. Rubella IgG seropositivity was high in all three age strata, but only 47% of those aged 5-17 years were measles IgG seropositive. Additionally, only 41% of those aged 5-17 years who had documented receipt of two doses of measles- or measles-rubella-containing vaccine were seropositive for measles IgG, but almost all these children were rubella IgG seropositive. CONCLUSIONS: An unexpected measles immunity gap was identified among children 5-17 years of age. It is unclear why this immunity gap exists; however, it could have led to a large outbreak and threatened sustaining of measles elimination in Bhutan. Based on this finding, a mass vaccination campaign was conducted to close the immunity gap.

BACKGROUND: Intradermal administration of fractional inactivated poliovirus vaccine (fIPV) is a dose-sparing alternative to the intramuscular full dose. We aimed to compare the immunogenicity of two fIPV doses versus one IPV dose for routine immunisation, and also assessed the immunogenicity of an fIPV booster dose for an outbreak response. METHODS: We did an open-label, randomised, controlled, inequality, non-inferiority trial in two clinics in Dhaka, Bangladesh. Healthy infants were randomly assigned at 6 weeks to one of four groups: group A received IPV at age 14 weeks and IPV booster at age 22 weeks; group B received IPV at age 14 weeks and fIPV booster at age 22 weeks; group C received IPV at age 6 weeks and fIPV booster at age 22 weeks; and group D received fIPV at 6 weeks and 14 weeks and fIPV booster at age 22 weeks. IPV was administered by needle-syringe as an intramuscular full dose (0.5 mL), and fIPV was administered intradermally (0.1 mL of the IPV formulation was administered using the 0.1 mL HelmJect auto-disable syringe with a Helms intradermal adapter). Both IPV and fIPV were administered on the outer, upper right thigh of infants. The primary outcome was vaccine response to poliovirus types 1, 2, and 3 at age 22 weeks (routine immunisation) and age 26 weeks (outbreak response). Vaccine response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (>/=1:8) or four-fold increase in reciprocal antibody titres adjusted for maternal antibody decay and was assessed in the modified intention-to-treat population (infants who received polio vaccines per group assignment and polio antibody titre results to serotypes 1, 2, and 3 at 6, 22, 23, and 26 weeks of age). The non-inferiority margin was 12.5%. This trial is registered with ClinicalTrials.gov, number NCT02847026. FINDINGS: Between Sept 1, 2016 and May 2, 2017, 1076 participants were randomly assigned and included in the modified intention-to-treat analysis: 271 in Group A, 267 in group B, 268 in group C, and 270 in group D. Vaccine response at 22 weeks to two doses of fIPV (group D) was significantly higher (p<0.0001) than to one dose of IPV (groups A and B) for all three poliovirus serotypes: the type 1 response comprised 212 (79% [95% CI 73-83]) versus 305 (57% [53-61]) participants, the type 2 response comprised 173 (64% [58-70]) versus 249 (46% [42-51]) participants, and the type 3 response comprised 196 (73% [67-78]) versus 196 (36% [33-41]) participants. At 26 weeks, the fIPV booster was non-inferior to IPV (group B vs group A) for serotype 1 (-1.12% [90% CI -2.18 to -0.06]), serotype 2 (0.40%, [-2.22 to 1.42]), and serotype 3 (1.51% [-3.23 to -0.21]). Of 129 adverse events, 21 were classified as serious including one death; none were attributed to IPV or fIPV. INTERPRETATION: fIPV appears to be an effective dose-sparing strategy for routine immunisation and outbreak responses. FUNDING: US Centers for Disease Control and Prevention.

BACKGROUND: In China, measles-rubella vaccine and live attenuated SA 14-14-2 Japanese encephalitis vaccine (LJEV) are recommended for simultaneous administration at 8 months of age, which is the youngest recommended age for these vaccines worldwide. We aimed to assess the effect of the co-administration of these vaccines at 8 months of age on the immunogenicity of measles-rubella vaccine. METHODS: We did a multicentre, open-label, non-inferiority, two-group randomised controlled trial in eight counties or districts in China. We recruited healthy infants aged 8 months who had received all scheduled vaccinations according to the national immunisation recommendations and who lived in the county of the study site. Enrolled infants were randomly assigned (1:1) to receive either measles-rubella vaccine and LJEV simultaneously (measles-rubella plus LJEV group) or measles-rubella vaccine alone (measles-rubella group). The primary outcome was the proportion of infants with IgG antibody seroconversion for measles 6 weeks after vaccination, and a secondary outcome was the proportion of infants with IgG antibody seroconversion for rubella 6 weeks after vaccination. Analyses included all infants who completed the study. We used a 5% margin to establish non-inferiority. This trial was registered at ClinicalTrials.gov (NCT02643433). FINDINGS: 1173 infants were assessed for eligibility between Aug 13, 2015, and June 10, 2016. Of 1093 (93%) enrolled infants, 545 were randomly assigned to the measles-rubella plus LJEV group and 548 to the measles-rubella group. Of the infants assigned to each group, 507 in the measles-rubella plus LJEV group and 506 in the measles-rubella group completed the study. Before vaccination, six (1%) of 507 infants in the measles-rubella plus LJEV group and one (<1%) of 506 in the measles-rubella group were seropositive for measles; eight (2%) infants in the measles-rubella plus LJEV group and two (<1%) in the measles-rubella group were seropositive for rubella. 6 weeks after vaccination, measles seroconversion in the measles-rubella plus LJEV group (496 [98%] of 507) was non-inferior to that in the measles-rubella group (499 [99%] of 506; difference -0.8% [90% CI -2.6 to 1.1]) and rubella seroconversion in the measles-rubella plus LJEV group (478 [94%] of 507) was non-inferior to that in the measles-rubella group (473 [94%] of 506 infants; difference 0.8% [90% CI -1.8 to 3.4]). There were no serious adverse events in either group and no evidence of a difference between the two groups in the prevalence of any local adverse event (redness, rashes, and pain) or systemic adverse event (fever, allergy, respiratory infections, diarrhoea, and vomiting). Fever was the most common adverse event (97 [19%] of 507 infants in the measles-rubella plus LJEV group; 108 [21%] of 506 infants in the measles-rubella group). INTERPRETATION: The evidence of similar seroconversion and safety with co-administered LJEV and measles-rubella vaccines supports the co-administration of these vaccines to infants aged 8 months. These results will be important for measles and rubella elimination and the expansion of Japanese encephalitis vaccination in countries where it is endemic. FUNDING: US Centers for Disease Control and Prevention, US Department of Health and Human Services; China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases.

The genetic characterization of measles viruses is an important tool for measles surveillance. Reverse cold chain requirements for the transportation of samples to reference laboratories are challenging in resource-limited settings. FTA(R) cards facilitate transport of virologic samples at ambient temperature as non-infectious material; however, the utility of FTA(R) cards for detection and genotyping of measles virus from clinical samples had not been evaluated. Throat swabs (TS) and oral fluid (OF) samples were collected from suspected measles cases in the Democratic Republic of the Congo. Virus detection (RT-qPCR) and genotyping (end-point RT-PCR) were compared for samples from 238 suspected cases; these samples were either transported using the reverse cold chain or at ambient temperature on FTA(R) cards. Virus detection showed excellent positive agreement for OF compared to TS (95.3%, CI [91.6, 97.4]), in contrast to 79.4% (CI 73.5, 84.3) for TS on FTA, and 85.5% (CI 80.2, 89.6) for OF on FTA compared to OF. Genotyping results obtained for a subset of samples indicated that 77.3% of all TS and 71.0% of OF would produce genotype information compared to 41.6% of TS and 41.3% of OF on FTA(R) cards. Similar results were found for 16 measles-negative samples that were confirmed as rubella cases. Measles genotype B3 and rubella genotype 2B were detected. FTA(R) cards have limited utility for virologic surveillance of sporadic cases of measles; however, they can be a useful tool for the expansion of virologic surveillance in countries where the reverse cold chain is not available.

BACKGROUND: Afghanistan remains among the three countries with endemic wild poliovirus transmission, and high population immunity levels are required to interrupt transmission and prevent outbreaks. Surveillance and vaccination of children in Afghanistan have been challenging due to security issues limiting accessibility in certain areas. METHODS: A serosurvey was conducted in 2013 within accessible enumeration areas (EAs) among children aged <5years using samples collected for a national micronutrient assessment survey to assess poliovirus immunity in Afghanistan. Of 21194 total EAs in Afghanistan, 107 were inaccessible and therefore were excluded from the sampling frame. RESULTS: Population immunity was high overall but varied for the poliovirus serotypes, and was lowest for type 3 (95% [95% CI: 93%, 96%]) compared to type 1 (99% [95% CI:97%, 99%]) and type 2 (98% [95% CI:96%, 99%]). The proportion of the population immune to all three types was 93% (95% CI: 91%, 95%), and the proportion seronegative for all three types was 0.5% (95% CI: 0.2%, 1.7%). CONCLUSION: Except for regional differences in immunity to type 3 virus, there were no other apparent differences in seroprevalence by region or by any of the demographic or nutritional characteristics assessed in this study. The study was not powered to provide provincial level seroprevalence estimates, but Paktika Province, in the South region, had the largest proportion of seronegative specimens for type 1 (4 seronegative of 17 serum specimens compared to 14 seronegative of 673 for the remainder of the areas). Among accessible children in Afghanistan, seroprevalence of antibodies to poliovirus was high, with most seroprevalence reported at 95% or greater. Despite high seroprevalence in areas assessed in this study, the continued detection of poliovirus cases in the South and East regions indicate that overall regional vaccination coverage and performance is not sufficient to stop polio transmission.

BACKGROUND: In 2017, the Cambodia Ministry of Health introduced human papillomavirus (HPV) vaccine through primarily school-based vaccination targeting 9-year-old girls. Vaccination with a two-dose series of HPV vaccine took place in six districts in two provinces as a demonstration program, to better understand HPV vaccine delivery in Cambodia. METHODS: We conducted a community-based coverage survey using a one-stage sampling design to evaluate dose-specific vaccination coverage among eligible girls (those born in 2007 and residents in the areas targeted by the campaign). The household-level survey also assessed factors associated with vaccine acceptability and communication strategies. Trained data collectors interviewed caregivers and girls using a standard questionnaire; vaccination cards and health facility records were reviewed. RESULTS: Of the 7594 households visited in the two provinces, 315 girls were enrolled in the survey (188 in Siem Reap; 127 in Svay Rieng). Documented two-dose HPV vaccination coverage was 84% (95% confidence interval [CI]: 78-88%) overall [85% (95% CI: 78-90%) in Siem Reap; 82% (95% CI: 73-88%) in Svay Rieng.] Almost all girls (>99%) were reported to be enrolled in school and over 90% of respondents reported receipt of vaccine in school. Knowledge of HPV infection and associated diseases was poor among caregivers and girls; however, 58% of caregivers reported "protection from cervical cancer" as the primary reason for the girl receiving vaccine. No serious adverse events after immunization were reported. CONCLUSIONS: The HPV vaccine demonstration program in Cambodia achieved high two-dose coverage among eligible girls in both provinces targeted for vaccination in 2017, through primarily school-based vaccination. High school enrollment and strong microplanning and coordination were seen throughout the campaign. Cambodia will use lessons learned from this demonstration program to prepare for national introduction of HPV vaccine.

BACKGROUND: Parents' attitudes and beliefs in vaccination are important to understand for shaping vaccine acceptance and demand interventions. Little research has focused on developing a validated scale to measure parents' attitudes towards vaccinations in low and middle-income countries; Ghana provided an opportunity develop a caregiver vaccination attitudes scale (CVAS) validated against childhood vaccine compliance. METHODS: We conducted a cluster survey of 373 households with children aged 12-35months of age from Northern Region, Ghana. Caregivers responded to 22 vaccination behavior and belief survey items and provided the child's vaccination status. In exploratory factor analysis (EFA) to assess CVAS content validity, we used parallel analysis to guide the number of factors to extract and principal axis factor analysis for factor extraction. Reliability of the scale was assessed using McDonald's Omega coefficient. Criterion validity of scale and subscales was assessed against receipt of vaccinations by 12months of age and vaccination delay, using number of days undervaccinated. RESULTS: EFA of CVAS responses resulted in removing 11 of 22 survey items due to loadings <0.30 and development of a 5-factor structure with subscales for Vaccine-Preventable Disease (VPD) Awareness, Vaccine Benefits, Past Behavior, Vaccine Efficacy and Safety, and Trust. The 5 factors accounted for 69% of the common variance and omega coefficients were >0.73 for all subscales. Validity analysis indicated that for every unit increase in the parent's scale score, the odds of the child being vaccinated decreased by 0.58 (95% confidence interval [CI]: 0.37, 0.68) and the number of days under-vaccinated increased by 86 (95%CI: 28, 143). The final 3-factor scale included Vaccine Benefits, Past Behavior, and Vaccine Efficacy and Safety. DISCUSSION: The final CVAS included three factors associated with vaccine compliance in Ghana, although several survey items suggested for use in vaccine acceptance scales were dropped. Replicating this study in several country settings will provide additional evidence to assist in refining a tool for use in routine vaccine acceptance and demand surveillance efforts.

Background: The introduction of inactivated poliovirus vaccine (IPV) to the Philippines’ national immunization schedule meant the addition of a third injectable vaccine at a child's 14-week immunization visit. Although previous studies have shown that providing multiple vaccines at the same time affected neither the risk of severe adverse events nor vaccine efficacy, concerns were raised that providing three injections at a single visit, with two injections in one leg, might be unacceptable to health care providers (HCP) and infant caregivers. Methods: We conducted pre- and post-IPV introduction surveys on the acceptance and acceptability of the additional injectable vaccine in three of the Philippines’ 17 administrative regions. Regions 3 and 6 were included in the pre-introduction phase and Regions 3, 6 and 10 were included in the post-introduction phase. Thirty public health centers (PHCs) were randomly sampled from each region. HCPs and infant caregivers were interviewed. In addition, vaccination records from a minimum of 20 eligible children pre-introduction and 10 children post-introduction per PHC were reviewed. Results and discussion: We interviewed 89 HCPs and 286 infant caregivers during the pre-introduction phase and 137 HCPs and 455 caregivers during the post-introduction phase. Among 986 vaccination records reviewed post-introduction, 84% (n = 826) of children received all three recommended injections at one visit, with a range from 61% (209/342) in Region 10 to 100% (328/328) in Region 3. The proportion of HCPs reporting that they had administered three or more injectable vaccines and the proportion of caregivers that would be comfortable with their child receiving three or more injectable vaccines at one visit increased from pre- to post-introduction (p < 0.0001 for both). Eighty-seven percent of HCPs that had administered three or more injectable vaccines post-introduction reported being comfortable or very comfortable with the number of vaccines they had administered.

Background: In 2015, a large nationwide measles outbreak occurred in Mongolia, with very high incidence in the capital city of Ulaanbaatar and among young adults. Methods: We conducted an outbreak investigation including a matched case-control study of risk factors for laboratory-confirmed measles among young adults living in Ulaanbaatar. Young adults with laboratory-confirmed measles, living in the capital city of Ulaanbaatar, were matched with 2-3 neighborhood controls. Conditional logistic regression was used to estimate adjusted matched odds ratios (aMORs) for risk factors, with 95% confidence intervals. Results: During March 1-September 30, 2015, 20 077 suspected measles cases were reported; 14 010 cases were confirmed. Independent risk factors for measles included being unvaccinated (adjusted matched odds ratio [aMOR] 2.0, P < .01), being a high school graduate without college education (aMOR 2.6, P < .01), remaining in Ulaanbaatar during the outbreak (aMOR 2.5, P < .01), exposure to an inpatient healthcare facility (aMOR 4.5 P < .01), and being born outside of Ulaanbaatar (aMOR 1.8, P = .02). Conclusions: This large, nationwide outbreak shortly after verification of elimination had high incidence among young adults, particularly those born outside the national capital. In addition, findings indicated that nosocomial transmission within health facilities helped amplify the outbreak.

BACKGROUND: The effect of a third dose of the measles-mumps-rubella (MMR) vaccine in stemming a mumps outbreak is unknown. During an outbreak among vaccinated students at the University of Iowa, health officials implemented a widespread MMR vaccine campaign. We evaluated the effectiveness of a third dose for outbreak control and assessed for waning immunity. METHODS: Of 20,496 university students who were enrolled during the 2015-2016 academic year, mumps was diagnosed in 259 students. We used Fisher's exact test to compare unadjusted attack rates according to dose status and years since receipt of the second MMR vaccine dose. We used multivariable time-dependent Cox regression models to evaluate vaccine effectiveness, according to dose status (three vs. two doses and two vs. no doses) after adjustment for the number of years since the second dose. RESULTS: Before the outbreak, 98.1% of the students had received at least two doses of MMR vaccine. During the outbreak, 4783 received a third dose. The attack rate was lower among the students who had received three doses than among those who had received two doses (6.7 vs. 14.5 cases per 1000 population, P<0.001). Students had more than nine times the risk of mumps if they had received the second MMR dose 13 years or more before the outbreak. At 28 days after vaccination, receipt of the third vaccine dose was associated with a 78.1% lower risk of mumps than receipt of a second dose (adjusted hazard ratio, 0.22; 95% confidence interval, 0.12 to 0.39). The vaccine effectiveness of two doses versus no doses was lower among students with more distant receipt of the second vaccine dose. CONCLUSIONS: Students who had received a third dose of MMR vaccine had a lower risk of mumps than did those who had received two doses, after adjustment for the number of years since the second dose. Students who had received a second dose of MMR vaccine 13 years or more before the outbreak had an increased risk of mumps. These findings suggest that the campaign to administer a third dose of MMR vaccine improved mumps outbreak control and that waning immunity probably contributed to propagation of the outbreak. (Funded by the Centers for Disease Control and Prevention.).

Health facility (HF) and household (HH) data can complement each other to provide a better understanding of the factors that contribute to vaccination status. In 12 zones with low vaccination coverage within Kinshasa Province, Democratic Republic of Congo, we conducted 2 surveys: (1) a linked HH and HF survey among 6-11-month-old infants, and (2) a HH survey among 12-23-month-old children. Linked survey objectives were to identify factors associated with vaccination status and to explore methodological considerations for linked survey implementation. To provide linked HH and HF data, we enrolled 6-11-month-old infants in HH clusters in each zone and then surveyed HFs located within the 12 zones and cited by caregivers of the enrolled infants as the most recent HF visited for vaccination or curative care. To provide vaccination coverage estimates for the 12-zone area, we enrolled 12-23-month-old children in every fourth HH. Of the HHs with a child aged 6-23 months, 16% were ineligible because they had resided in the neighborhood for <3 months or were unavailable to be interviewed, 4% refused, and 80% were eligible and participated. Of 1224 enrolled infants 6-11 months of age, records of 879 (72%) were linked to one of the 182 surveyed HFs. For the coverage survey, 710 children aged 12-23 months participated. Home-based vaccination cards were available for 1210 of 1934 children (63%) surveyed. The surveys were successful in assessing HH information for 2 age groups, documenting written vaccination history for a large proportion of 6-23-month-old children, linking the majority of infants with their most recently visited HF, and surveying identified HFs. The implementation of the individually linked survey also highlighted the need for a comprehensive list of HFs and an analysis plan that addresses cross-classified clusters with only 1 child.

Background. Albania introduced inactivated polio vaccine (IPV) into its immunization system in May 2014, increasing the maximum recommended number of injectable vaccines given in a single visit from 2 to 3. Methods. Health-care providers and caregivers were interviewed at 42 health facilities in Albania to assess knowledge, attitudes, and practices regarding injectable vaccine administration. Immunization register data were abstracted from December 2014 to July 2015 at the same facilities to explore the number of injectable vaccines children received during their 2- and 4-month visits. Results. The majority of children (87%) identified in the record review at either their 2- or 4-month immunization visit received all 3 injectable vaccines in a single visit. Almost all children who did not receive the vaccines in a single visit were subsequently fully immunized, most within a 2-week period. Over half of caregivers whose children got 3 or more injectable vaccines in a single visit reported being only comfortable with 1 or 2 injectable vaccines in a single visit. Conclusions. Despite most caregivers expressing hesitation regarding children receiving multiple injectable vaccines in a single visit, most children received vaccines according to the recommended schedule. Almost all children eventually received all recommended vaccines.

BACKGROUND: Despite recent success towards controlling poliovirus transmission, Nigeria has struggled to achieve uniformly high routine vaccination coverage. A lack of reliable vaccination coverage data at the operational level makes it challenging to target program improvement. To reliably estimate vaccination coverage, we conducted district-level vaccine coverage surveys using a pre-existing infrastructure of polio technical staff in northern Nigeria. METHODS: Household-level cluster surveys were conducted in 40 polio high risk districts of Nigeria during 2014-2015. Global positioning system technology and intensive supervision by a pool of qualified technical staff were used to ensure high survey quality. Vaccination status of children aged 12-23 months was documented based on vaccination card or caretaker's recall. District-level coverage estimates were calculated using survey methods. RESULTS: Data from 7,815 children across 40 districts were analyzed. District-level coverage with the third dose of diphtheria-pertussis-tetanus vaccine (DPT3) ranged widely from 1-63%, with all districts having DPT3 coverage below the target of 80%. Median coverage across all districts for each of eight vaccine doses (1 Bacille Calmette-Guerin dose, 3 DPT doses, 3 oral poliovirus vaccine doses, and 1 measles vaccine dose) was <50%. DPT3 coverage by survey was substantially lower (range: 28%-139%) than the 2013 administrative coverage reported among children aged <12 months. Common reported reasons for non-vaccination included lack of knowledge about vaccines and vaccination services (50%) and factors related to access to routine immunization services (15%). CONCLUSIONS: Survey results highlighted vaccine coverage gaps that were systematically underestimated by administrative reporting across 40 polio high risk districts in northern Nigeria. Given the limitations of administrative coverage data, our approach to conducting quality district-level coverage surveys and providing data to assess and remediate issues contributing to poor vaccination coverage could serve as an example in countries with sub-optimal vaccination coverage, similar to Nigeria.

Oral cholera vaccines (OCVs) are relatively new public health interventions, and limited data exist on the potential impact of OCV use on traditional cholera prevention and control measures-safe water, sanitation and hygiene (WaSH). To assess OCV acceptability and knowledge, attitudes, and practices (KAPs) regarding cholera and WaSH, we conducted cross-sectional surveys, 1 month before (baseline) and 3 and 12 months after (first and second follow-up) a preemptive OCV campaign in Maela, a long-standing refugee camp on the Thailand-Burma border. We randomly selected households for the surveys, and administered questionnaires to female heads of households. In total, 271 (77%), 187 (81%), and 199 (85%) households were included in the baseline, first and second follow-up surveys, respectively. Anticipated OCV acceptability was 97% at baseline, and 91% and 85% of household members were reported to have received 1 and 2 OCV doses at first follow-up. Compared with baseline, statistically significant differences (95% Wald confidence interval not overlapping zero) were noted at first and second follow-up among the proportions of respondents who correctly identified two or more means of cholera prevention (62% versus 78% and 80%), reported boiling or treating drinking water (19% versus 44% and 69%), and washing hands with soap (66% versus 77% and 85%); a significant difference was also observed in the proportion of households with soap available at handwashing areas (84% versus 90% and 95%), consistent with reported behaviors. No significant difference was noted in the proportion of households testing positive for Escherichia coli in stored household drinking water at second follow-up (39% versus 49% and 34%). Overall, we observed some positive, and no negative changes in cholera- and WaSH-related KAPs after an OCV campaign in Maela refugee camp. OCV campaigns may provide opportunities to reinforce beneficial WaSH-related KAPs for comprehensive cholera prevention and control.

INTRODUCTION: Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated more than 100 million children in 2010. We performed a case-control study in six Chinese provinces during January 2012 through June 2013 to identify risk factors for measles infection among children aged 0-7 months. METHODS: Children with laboratory-confirmed measles were neighborhood matched with three controls. We interviewed parents of case and control infants on potential risk factors for measles. Adjusted matched odds ratios (mOR) and 95% confidence intervals (CIs) were calculated by multivariable conditional logistic modeling. We calculated attributable fractions for risk factors that could be interpreted as causal. RESULTS: Eight hundred thirty cases and 2303 controls were enrolled. In multivariable analysis, male sex (mOR 1.6 [1.3, 2.0]), age 5-7 months (mOR 3.9 [3.0, 5.1]), migration between counties (mOR 2.3 [1.6, 3.4]), outpatient hospital visits (mOR 9.4 [6.6, 13.3]) and inpatient hospitalization (mOR 107.1 [48.8, 235.1]) were significant risk factors. The calculated attributable fractions for hospital visits was 43.1% (95% CI: 40.1, 47.5%) adjusted for age, sex and migration. CONCLUSIONS: Hospital visitation was the largest risk factor for measles infection in infants. Improved hospital infection control practices would accelerate measles elimination in China.

BACKGROUND: Rubella-containing vaccines (RCV) are not yet part of the Democratic Republic of the Congo's (DRC) vaccination program; however RCV introduction is planned before 2020. Because documentation of DRC's historical burden of rubella virus infection and congenital rubella syndrome (CRS) has been minimal, estimates of the burden of rubella virus infection and of CRS would help inform the country's strategy for RCV introduction. METHODS: A rubella antibody seroprevalence assessment was conducted using serum collected during 2008-2009 from 1605 pregnant women aged 15-46years attending 7 antenatal care sites in 3 of DRC's provinces. Estimates of age- and site-specific rubella antibody seroprevalence, population, and fertility rates were used in catalytic models to estimate the incidence of CRS per 100,000 live births and the number of CRS cases born in 2013 in DRC. RESULTS: Overall 84% (95% CI 82, 86) of the women tested were estimated to be rubella antibody seropositive. The association between age and estimated antibody seroprevalence, adjusting for study site, was not significant (p=0.10). Differences in overall estimated seroprevalence by study site were observed indicating variation by geographical area (p0.03 for all). Estimated seroprevalence was similar for women declaring residence in urban (84%) versus rural (83%) settings (p=0.67). In 2013 for DRC nationally, the estimated incidence of CRS was 69/100,000 live births (95% CI 0, 186), corresponding to 2886 infants (95% CI 342, 6395) born with CRS. CONCLUSIONS: In the 3 provinces, rubella virus transmission is endemic, and most viral exposure and seroconversion occurs before age 15years. However, approximately 10-20% of the women were susceptible to rubella virus infection and thus at risk for having an infant with CRS. This analysis can guide plans for introduction of RCV in DRC. Per World Health Organization recommendations, introduction of RCV should be accompanied by a campaign targeting all children 9months to 14years of age as well as vaccination of women of child bearing age through routine services.

In 2013, the Government of Haiti implemented its first oral cholera vaccine (OCV) campaign in Petite Anse, an urban setting, and Cerca Carvajal, a rural commune. We conducted and compared responses to two independent cross-sectional knowledge and practices household surveys pre- (N = 297) and post- (N = 302) OCV campaign in Petite Anse. No significant differences in knowledge about causes, symptoms, and prevention of cholera were noted. Compared with precampaign respondents, fewer postcampaign respondents reported treating (66% versus 27%, P < 0.001) and covering (96% versus 89%, P = 0.02) their drinking water. Compared with precampaign, postcampaign survey household observations showed increased availability of soap (16.2% versus 34.5%, P = 0.001) and handwashing stations (14.7% versus 30.1%, P = 0.01), but no significant changes in handwashing practices were reported. Although there was no change in knowledge, significant decreases in water treatment practices necessary for cholera and other diarrheal diseases prevention were noted in the postcampaign survey. Future OCV campaigns in Haiti should be used as an opportunity to emphasize the importance of maintaining good water, sanitation, and hygiene practices, and include a comprehensive, integrated approach for cholera control.