Live attenuated seasonal and pandemic influenza vaccine in school-age children: a randomized controlled trial.

BACKGROUND: The novel influenza A(H1N1pdm09) virus emerged in North America in early 2009 and rapidly spread worldwide. In this study we report the efficacy of the live attenuated monovalent H1N1pdm09 vaccine and 2009-10 seasonal influenza vaccine in a randomized double-blind placebo-controlled trial. METHODS: We enrolled 703 children aged 7-11. Each child was randomly allocated in the ratio 3:2 to receive one dose of live attenuated monovalent H1N1pdm09 vaccine or saline placebo between November 2009 and January 2010, followed after 3-10 weeks by independent random allocation to one dose of live attenuated trivalent 2009-10 seasonal influenza vaccine or saline placebo in the same ratio. Children were followed up through September 2010 with biweekly telephone calls and symptom diaries. Seasonal and pandemic influenza infections were confirmed by virologic testing of nose and throat swabs collected during acute respiratory illnesses. RESULTS: Overall, 30 children had confirmed influenza including 3 (0.43%) H1N1pdm09, 10 (1.4%) seasonal A(H3N2), and 17 (2.4%) influenza B. There were no significant differences in incidence rates of H1N1pdm09 or A(H3N2) between the four study arms, but receipt of the seasonal influenza vaccine was associated with a significant reduction in risk of influenza B (p<0.01). Vaccine efficacy against confirmed H1N1pdm09 infection associated with receipt of the monovalent H1N1pdm09 vaccine was 65% (95% confidence interval, CI: -281%, 97%). Vaccine efficacies against confirmed seasonal influenza A(H3N2) and B infection associated with receipt of the seasonal influenza vaccine were 31% (95% CI: -138%, 80%) and 96% (95% CI: 67%, 99%) respectively. CONCLUSIONS: Vaccine efficacy was consistent with other studies of the monovalent H1N1pdm09 vaccine and seasonal influenza vaccines. Our study was underpowered to provide precise estimates of vaccine efficacy due to low incidence of influenza A viruses during the study period.

Asymptomatic wild-type poliovirus infection in India among children with previous oral poliovirus vaccination.

BACKGROUND: Mucosal immunity induced by oral poliovirus vaccine (OPV) is imperfect and potentially allows immunized individuals to participate in asymptomatic wild-type poliovirus transmission in settings with efficient fecal-oral transmission of infection. METHODS: We examined the extent of asymptomatic wild-type poliovirus transmission in India by measuring the prevalence of virus in stool samples obtained from 14,005 healthy children who were in contact with 2761 individuals with suspected poliomyelitis reported during the period 2003-2008. RESULTS: Wild-type poliovirus serotypes 1 and 3 were isolated from the stool samples of 103 (0.74%) and 104 (0.74%) healthy contacts, respectively. Among contacts of individuals with laboratory-confirmed poliomyelitis, 27 (12.7%) of 213 and 29 (13.9%) of 209 had serotypes 1 and 3, respectively, isolated from their stool samples. The odds ratio of excreting serotype 1 wild-type poliovirus was 0.13 (95% confidence interval, 0.02-0.87) among healthy children reporting 6 doses of OPV, compared with children reporting 0-2 doses. However, two-thirds of healthy children who excreted this virus reported >or=6 doses, and the prevalence of this virus did not decrease with age over the sampled range. CONCLUSIONS: Although OPV is protective against infection with poliovirus, the majority of healthy contacts who excreted wild-type poliovirus were well vaccinated. This is consistent with a potential role for OPV-vaccinated children in continued wild-type poliovirus transmission and requires further study.

Mucosal immunity after vaccination with monovalent and trivalent oral poliovirus vaccine in India.

BACKGROUND: Persistent wild-poliovirus transmission, particularly in India, has raised questions about the degree of mucosal immunity induced by oral poliovirus vaccine (OPV) in tropical countries. METHODS: Excretion of vaccine poliovirus after challenge with OPV was measured in stool samples collected from children identified by the acute flaccid paralysis surveillance program in India during 2005-2007. The effectiveness of trivalent and monovalent OPV against excretion of each poliovirus type was estimated. RESULTS: Vaccine poliovirus was isolated from 4994 (5.2%) of 96,641 children with 2 stool samples. The relative odds of excreting challenge poliovirus among children with 5 reported previous doses of trivalent OPV compared with 0 previous doses was 0.24 (95% confidence interval [CI], 0.12-0.45), 0.08 (95% CI, 0.04-0.14), and 0.40 (95% CI, 0.19-0.85) for serotypes 1, 2, and 3, respectively, but the relative odds increased to 0.62 (95% CI, 0.44-0.88), 0.44 (95% CI, 0.20-0.99), and 0.66 (95% CI, 0.41-1.06), respectively, in the northern states of Uttar Pradesh and Bihar. In these 2 states, the relative odds of excretion of serotype 1 was 0.32 (95% CI, 0.26-0.41) after 5 doses of type 1 monovalent OPV. CONCLUSIONS: The mucosal immunity induced by OPV in India varies by location, serotype, and vaccine formulation. These findings have implications for global eradication and the potential role played by inactivated vaccine in this setting.

Protective efficacy of a monovalent oral type 1 poliovirus vaccine: a case-control study.

BACKGROUND: A high-potency monovalent oral type 1 poliovirus vaccine (mOPV1) was developed in 2005 to tackle persistent poliovirus transmission in the last remaining infected countries. Our aim was to assess the efficacy of this vaccine in India. METHODS: We estimated the efficacy of mOPV1 used in supplementary immunisation activities from 2076 matched case-control pairs of confirmed cases of poliomyelitis caused by type 1 wild poliovirus and cases of non-polio acute flaccid paralysis in India. The effect of the introduction of mOPV1 on population immunity was calculated on the basis of estimates of vaccination coverage from data for non-polio acute flaccid paralysis. FINDINGS: In areas of persistent poliovirus transmission in Uttar Pradesh, the protective efficacy of mOPV1 was estimated to be 30% (95% CI 19-41) per dose against type 1 paralytic disease, compared with 11% (7-14) for the trivalent oral vaccine. 76-82% of children aged 0-23 months were estimated to be protected by vaccination against type 1 poliovirus at the end of 2006, compared with 59% at the end of 2004, before the introduction of mOPV1. INTERPRETATION: Under conditions where the efficacy of live-attenuated oral poliovirus vaccines is compromised by a high prevalence of diarrhoea and other infections, a dose of high-potency mOPV1 is almost three times more effective against type 1 poliomyelitis disease than is trivalent vaccine. Achieving high coverage with this new vaccine in areas of persistent poliovirus transmission should substantially improve the probability of rapidly eliminating transmission of the disease.

Detecting polio through surveillance for acute flaccid paralysis (AFP).

Accurate surveillance for polio is essential for eradication. Surveillance systems for polio has been developed under the guidance of the global polio eradication initiative. Surveillance of cases of acute flaccid paralysis among children less than 15 years of age is a key component for a well functioning polio surveillance system. The surveillance system works through a network of surveillance medical officers, the responsibility of them lies in assisting the health services departments of all states and maintaining a network of acute flaccid paralysis reporting sites and rapidly investigating the cases. Surveillance activities begin when a child comes in contact with a healthcare provider who in turn informs the officer in charge of acute flaccid paralysis surveillance. The goal of the polio network laboratories is to provide accurate and timely results of wild poliovirus detection in stool samples of cases of acute flaccid paralysis. Strong linkages have been established between the acute flaccid paralysis surveillance system and the laboratory network. Laboratories complete poliovirus isolation and if poliovirus is isolated, these are submitted for intratypic differentiations. Acute flaccid paralysis surveillance in India has demonstrated that the eradication activities implemented in India led to dramatic reduction and restriction in the number of cases and geographic spread of poliovirus transmission.

Compatible poliomyelitis cases in India during 2000.

OBJECTIVE: To describe the characteristics of compatible poliomyelitis cases and to assess the programmatic implications of clusters of such cases in India. METHODS: We described the characteristics of compatible poliomyelitis cases, identified clusters of compatible cases (two or more in the same district or neighbouring districts within two months), and examined their relationship to wild poliovirus cases. FINDINGS: There were 362 compatible cases in 2000. The incidence of compatible cases was higher in districts with laboratory-confirmed poliomyelitis cases than in districts without laboratory-confirmed cases. Of 580 districts, 96 reported one compatible case and 72 reported two or more compatible cases. Among these 168 districts with at least one compatible case, 123 had internal or cross- border clusters of compatible cases. In 27 districts with clusters of compatible cases, no wild poliovirus was isolated either in the same district or in neighbouring districts. Three of these 27 districts presented laboratory-confirmed poliomyelitis cases during 2001. CONCLUSION: Most clusters of compatible cases occurred in districts identified as areas with continuing wild poliovirus transmission and where mopping-up vaccination campaigns were carried out. As certification nears, areas with compatible poliomyelitis cases should be investigated and deficiencies in surveillance should be corrected in order to ensure that certification is justified.

Predictors of virologically confirmed poliomyelitis in India, 1998-2000.

As we progress toward eradication of polio, a growing proportion of cases of acute flaccid paralysis (AFP) reported are due to causes other than polio. AFP surveillance data from India for 1998-2000 were analyzed to determine the sensitivity and specificity of signs and symptoms present at initial case investigation and of residual weakness (which is used to classify AFP cases) for virologically confirmed poliomyelitis. Sensitivity was highest for age of <5 years (93%-97%) and residual weakness (74%-96%). Residual weakness was more sensitive among children aged <5 years. Cases of AFP in patients aged <5 years who have fever and asymmetrical paralysis are most likely to be confirmed as poliomyelitis. In countries with suboptimal surveillance for AFP, these results may help to prioritize investigation of AFP cases. The high sensitivity of residual weakness demonstrates the importance of 60-day follow-up examination for all patients with AFP, particularly those for whom the initial case investigation was inadequate or delayed.