Routine immunization coverage in Pakistan: a survey of children under 1 year of age in community-based vaccination areas.

Pakistan is one of two countries in which poliovirus remains endemic. Considering the high number of children born every year, reaching and vaccinating new birth cohorts by improving routine immunization coverage in children <1 year of age is crucial to halting virus transmission. In 2015, a community-based vaccination (CBV) strategy, using local community members to enhance vaccine acceptance and improve routine immunization service delivery, was introduced in areas of Pakistan that have never interrupted poliovirus transmission. In order to assess progress towards improving routine immunization, we performed house-to-house immunization surveys across ten CBV areas in 2017 and 2018. In each household, we determined age-appropriate routine antigen coverage for children <1 year of age based on vaccination card and caregiver recall. We surveyed 5,499 and 5,264 children in 2017 and 2018, respectively. Overall, coverage of inactivated poliovirus vaccine (IPV) at 14 weeks of age was 32% in 2017 and 39% in 2018 based on vaccination card and recall. Across the surveyed areas, coverage ranged from 7% in Killa Abdullah to 61% in Peshawar in 2018. Oral poliovirus vaccination coverage decreased with successive vaccination visits, ranging from 66% for the birth dose to 42% for the 14-week dose in 2018. No area reached the target of 80% coverage for any routine antigen. Our findings highlight the need for concerted efforts to improve routine immunization coverage in these critical areas of wild poliovirus transmission.

Needle-free injectors for mass administration of fractional dose inactivated poliovirus vaccine in Karachi, Pakistan: A survey of caregiver and vaccinator acceptability.

The first large-scale vaccination campaign using needle-free jet injectors to administer fractional doses of inactivated poliovirus vaccine (fIPV) was conducted in Karachi, Pakistan, in February 2019. Data on acceptability of jet injectors were collected from 610 vaccinators and 4898 caregivers during the first four days of the campaign. Of those with prior needle and syringe experience, both vaccinators and caregivers expressed a strong preference for jet injectors (578/592 [97.6%] and 4792/4813 [99.6%], respectively), citing ease of use, appearance, and child's response to vaccination. Among caregivers, 4638 (94.7%) stated they would be more likely to bring their child for vaccination in a future campaign that used jet injectors. Mean vaccine coverage among towns administering fIPV was 98.7% - an increase by 18.4% over the preceding campaign involving full-dose IPV. Our findings demonstrate the strong acceptability of fIPV jet injectors and highlight the potential value of this method in future mass campaigns.

Evidence for interventions to prevent and control obesity among children and adolescents: its applicability to India.

Childhood obesity is on the rise worldwide and its increasing prevalence in low and middle income countries is well-known. Obesity interventions have the potential to prevent adverse health outcomes; however, large gaps in research and knowledge about the efficacy and sustainability of such interventions remain. The objectives of this article were to review the evidence for interventions to prevent and control obesity among children and adolescents, evaluate their applicability in India, and discuss the challenges to sustain such interventions. The authors reviewed published research focusing on childhood obesity interventions, especially in India and other lower-resource countries. Nine observational and 10 interventional studies were reviewed. Most studies identified were from developed countries and took place at day-care settings, schools, and after school programs. Nineteen reported studies were grouped into categories: diet (2), physical activity (4), childcare programs (2), media-based programs (2), parental involvement (2), multi-component studies (1), and screen time (6). Most interventions were effective in reducing BMI, decreasing sedentary behaviors, and increasing physical activity. Sustainability of these interventions was not evaluated. While there is no one method or simple intervention to address obesity, multi-component approaches involving home and school environments are promising and warrant evaluation in India. Literature on obesity prevention and control in India and in lower-resource countries, however, is sparse. Existing gaps in knowledge about obesity should be addressed by conducting research in India and carrying out interventions to determine what strategies will be successful and sustainable locally.

Randomized trial of type 1 and type 3 oral monovalent poliovirus vaccines in newborns in Africa.

BACKGROUND: The Global Polio Eradication Initiative aims to eradicate wild poliovirus by the end of 2012. Therefore, more-immunogenic polio vaccines, including monovalent oral poliovirus vaccines (mOPVs), are needed for supplemental immunization activities. This trial assessed the immunogenicity of monovalent types 1 and 3, compared with that of trivalent oral poliovirus vaccine (tOPV), in South Africa. METHODS: We conducted a blinded, randomized, 4-arm controlled trial comparing the immunogenicity of a single dose of mOPV1 (from 2 manufacturers) and mOPV3 (from 1 manufacturer), given at birth, with the immunogenicity of tOPV. RESULTS: Eight hundred newborns were enrolled; 762 (95%) were included in the analysis. At 30 days after vaccine administration, seroconversion to poliovirus type 1 was 73.4% and 76.4% in the 2 mOPV1 arms, compared with 39.1% in the tOPV arm (P < .0000001), and seroconversion to poliovirus type 3 was 58.0% in the mOPV3 arm, compared with 21.2% in the tOPV arm (P < .0000001). The vaccines were well tolerated, and no adverse events were attributed to trial interventions. CONCLUSION: A dose of mOPV1 or mOPV3 at birth was superior to that of tOPV in inducing type-specific seroconversion in this sub-Saharan African population. Our results support continued use of mOPVs in supplemental immunization activities in countries where poliovirus types 1 or 3 circulate. Clinical Trials Registration. ISRCTN18107202.

Monovalent type 1 oral poliovirus vaccine among infants in India: report of two randomized double-blind controlled clinical trials.

BACKGROUND: To provide the polio eradication initiative with more immunogenic oral poliovirus vaccines (OPVs), we evaluated newly developed monovalent type 1 OPV (mOPV1) among infants in India. METHODS: Two double-blind randomized controlled clinical trials compared two mOPV1s (mOPV1 A and mOPV1 B) versus trivalent OPV (tOPV X) given at birth (trial I), or assessed two products of higher-potency mOPV1 (mOPV1 C and mOPV1 D) versus regular-potency mOPV1 (mOPV1 B) or tOPV Y given at birth and at 30 days (trial II). RESULTS: In trial I, 597 newborns were enrolled, 66 withdrawn or excluded, leaving 531 (88.9%) subjects for analysis. Seroconversion to poliovirus type 1 was 10.4% for mOPV1 A, 15.6% for mOPV1 B and 10.2% for tOPV X. In trial II, 718 newborns were enrolled, 135 withdrawn or excluded, leaving 583 (81.2%) subjects for analysis. Seroconversion to poliovirus type 1 following a birth dose was 15.1%, 19.7%, 18.0% and 10.6%, following the 30-day dose 87.1%, 89.2%, 84.4%, or 55.9%, and cumulative for both doses 90.4%, 90.3%, 89.5% and 61.9% for mOPV1s B, C, and D and tOPV Y, respectively. CONCLUSIONS: In both studies, seronconversion rates were unexpectedly low to poliovirus type 1 after mOPV1 or tOPV given at birth but high for all formulations of mOPV1 given at age 30 days. The cause for low immunogenicity of OPV at birth in India is not known.

Immunogenicity of bivalent types 1 and 3 oral poliovirus vaccine: a randomised, double-blind, controlled trial.

BACKGROUND: Poliovirus types 1 and 3 co-circulate in poliomyelitis-endemic countries. We aimed to assess the immunogenicity of a novel bivalent types 1 and 3 oral poliovirus vaccine (bOPV). METHODS: We did a randomised, double-blind, controlled trial to assess the superiority of monovalent type 2 OPV (mOPV2), mOPV3, or bOPV over trivalent OPV (tOPV), and the non-inferiority of bivalent vaccine compared with mOPV1 and mOPV3. The study was done at three centres in India between Aug 6, 2008, and Dec 26, 2008. Random allocation was done by permuted blocks of ten. The primary outcome was seroconversion after one monovalent or bivalent vaccine dose compared with a dose of trivalent vaccine at birth. The secondary endpoints were seroconversion after two vaccine doses compared with after two trivalent vaccine doses and cumulative two-dose seroconversion. Parents or guardians and study investigators were masked to treatment allocation. Because of multiple comparisons, we defined p≤0·01 as statistically significant. This trial is registered with Current Controlled Trials, ISRCTN 64725429. RESULTS: 900 newborn babies were randomly assigned to one of five vaccine groups (about 180 patients per group); of these 70 (8%) discontinued, leaving 830 (92%) for analysis. After the first dose, seroconversion to poliovirus type 1 was 20% for both mOPV1 (33 of 168) and bOPV (32 of 159) compared with 15% for tOPV (25 of 168; p>0·01), to poliovirus type 2 was 21% (35 of 170) for mOPV2 compared with 25% (42 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 12% (20 of 165) for mOPV3 and 7% (11 of 159) for bOPV compared with 4% (7 of 168) for tOPV (mOPV3 vs tOPV p=0·01; bOPV vs tOPV; p>0·01). Cumulative two-dose seroconversion to poliovirus type 1 was 90% (151 of 168) for mOPV1 and 86% (136 of 159) for bOPV compared with 63% (106 of 168) for tOPV (p<0·0001), to poliovirus type 2 was 90% (153 of 170) for mOPV2 compared with 91% (153 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 84% (138 of 165) for mOPV3 and 74% (117 of 159) for bOPV compared with 52% (87 of 168) for tOPV (p<0·0001). The vaccines were well tolerated. 19 serious adverse events occurred, including one death; however, these events were not attributed to the trial interventions. INTERPRETATION: The findings show the superiority of bOPV compared with tOPV, and the non-inferiority of bOPV compared with mOPV1 and mOPV3. FUNDING: GAVI Alliance, World Health Organization, and Panacea Biotec.

Fractional doses of inactivated poliovirus vaccine in Oman.

BACKGROUND: We conducted a clinical trial of fractional doses of inactivated poliovirus vaccine administered to infants in Oman, in order to evaluate strategies for making the vaccine affordable for use in developing countries. METHODS: We compared fractional doses of inactivated poliovirus vaccine (0.1 ml, representing one fifth of a full dose) given intradermally with the use of a needle-free jet injector device, with full doses of vaccine given intramuscularly, with respect to immunogenicity and reactogenicity. Infants were randomly assigned at birth to receive either a fractional dose or a full dose of inactivated poliovirus vaccine at 2, 4, and 6 months. We also administered a challenge dose of monovalent type 1 oral poliovirus vaccine at 7 months and collected stool samples before and 7 days after administration of the challenge dose. RESULTS: A total of 400 infants were randomized, of whom 373 (93.2%) fulfilled the study requirements. No significant baseline differences between the groups were detected. Thirty days after completion of the three-dose schedule, the rates of seroconversion to types 1, 2, and 3 poliovirus were 97.3%, 95.7%, and 97.9%, respectively, in the fractional-dose group, as compared with 100% seroconversion to all serotypes in the full-dose group (P=0.01 for the comparison with respect to type 2 poliovirus; results with respect to types 1 and 3 poliovirus were not significant). The median titers were significantly lower in the fractional-dose group than in the full-dose group (P<0.001 for all three poliovirus serotypes). At 7 months, 74.8% of the infants in the fractional-dose group and 63.1% of those in full-dose group excreted type 1 poliovirus (P=0.03). Between birth and 7 months, 42 hospitalizations were reported, all related to infectious causes, anemia, or falls, with no significant difference between vaccination groups. CONCLUSIONS: These data show that fractional doses of inactivated poliovirus vaccine administered intradermally at 2, 4, and 6 months, as compared with full doses of inactivated poliovirus vaccine given intramuscularly on the same schedule, induce similar levels of seroconversion but significantly lower titers. (Current Controlled Trials number, ISRCTN17418767.)

Monovalent type 1 oral poliovirus vaccine in newborns.

BACKGROUND: In 1988, the World Health Assembly resolved to eradicate poliomyelitis. Although substantial progress toward this goal has been made, eradication remains elusive. In 2004, the World Health Organization called for the development of a potentially more immunogenic monovalent type 1 oral poliovirus vaccine. METHODS: We conducted a trial in Egypt to compare the immunogenicity of a newly licensed monovalent type 1 oral poliovirus vaccine with that of a trivalent oral poliovirus vaccine. Subjects were randomly assigned to receive one dose of monovalent type 1 oral poliovirus vaccine or trivalent oral poliovirus vaccine at birth. Thirty days after birth, a single challenge dose of monovalent type 1 oral poliovirus vaccine was administered in all subjects. Shedding of serotype 1 poliovirus was assessed through day 60. RESULTS: A total of 530 subjects were enrolled, and 421 fulfilled the study requirements. Thirty days after the study vaccines were administered, the rate of seroconversion to type 1 poliovirus was 55.4% in the monovalent-vaccine group, as compared with 32.1% in the trivalent-vaccine group (P<0.001). Among those with a high reciprocal titer of maternally derived antibodies against type 1 poliovirus (>64), 46.0% of the subjects in the monovalent-vaccine group underwent seroconversion, as compared with 21.3% in the trivalent-vaccine group (P<0.001). Seven days after administration of the challenge dose of monovalent type 1 vaccine, a significantly lower proportion of subjects in the monovalent-vaccine group than in the trivalent-vaccine group excreted type 1 poliovirus (25.9% vs. 41.5%, P=0.001). None of the serious adverse events reported were attributed to the trial interventions. CONCLUSIONS: When given at birth, monovalent type 1 oral poliovirus vaccine is superior to trivalent oral poliovirus vaccine in inducing humoral antibodies against type 1 poliovirus, overcoming high preexisting levels of maternally derived antibodies, and increasing the resistance to excretion of type 1 poliovirus after administration of a challenge dose. (Current Controlled Trials number, ISRCTN76316509.)