Added value of the measles-rubella supplementary immunization activity in reaching unvaccinated and under-vaccinated children, a cross-sectional study in five Indian districts, 2018-20.

INTRODUCTION: Supplementary immunization activities (SIAs) aim to interrupt measles transmission by reaching susceptible children, including children who have not received the recommended two routine doses of MCV before the SIA. However, both strategies may miss the same children if vaccine doses are highly correlated. How well SIAs reach children missed by routine immunization is a key metric in assessing the added value of SIAs. METHODS: Children aged 9 months to younger than 5 years were enrolled in cross-sectional household serosurveys conducted in five districts in India following the 2017-2019 measles-rubella (MR) SIA. History of measles containing vaccine (MCV) through routine services or SIA was obtained from documents and verbal recall. Receipt of a first or second MCV dose during the SIA was categorized as "added value" of the SIA in reaching un- and under-vaccinated children. RESULTS: A total of 1,675 children were enrolled in these post-SIA surveys. The percentage of children receiving a 1st or 2nd dose through the SIA ranged from 12.8% in Thiruvananthapuram District to 48.6% in Dibrugarh District. Although the number of zero-dose children prior to the SIA was small in most sites, the proportion reached by the SIA ranged from 45.8% in Thiruvananthapuram District to 94.9% in Dibrugarh District. Fewer than 7% of children remained measles zero-dose after the MR SIA (range: 1.1-6.4%) compared to up to 28% before the SIA (range: 7.3-28.1%). DISCUSSION: We demonstrated the MR SIA provided considerable added value in terms of measles vaccination coverage, although there was variability across districts due to differences in routine and SIA coverage, and which children were reached by the SIA. Metrics evaluating the added value of an SIA can help to inform the design of vaccination strategies to better reach zero-dose or undervaccinated children.

Antagonism of coronary artery relaxation by adenosine A2A-receptor antagonist ZM241385.

We have tested the existence of functional A2A adenosine receptor in porcine coronary artery using, for the first time, the new A2A antagonist ZM241385. Nonselective agonist NECA and A2A-selective agonist CGS21680 produced concentration-dependent relaxation of prostaglandin F2alpha (PGF2alpha)-precontracted endothelium intact (E+) and denuded (E-) rings. Relaxation was significantly greater in E+ rings than in E-rings. A2A adenosine receptor-selective antagonist, ZM241385 (10(-6) M), significantly attenuated the relaxation responses. The antagonism of ZM241385 was compared with that of SCH58261 (10(-6)M), another A2A adenosine receptor-selective antagonist, which also significantly attenuated the relaxation response to both agonists. However, ZM241385 produced a significantly greater shift of the relaxation-response curves to the right compared with SCH58261 both in E+ and E- rings. The data show for the first time that ZM241385 is a potent A2A-receptor antagonist in porcine coronary artery and a useful tool to study A2A-receptor function.

Performance of the chronically hypoxic young rabbit heart.

Hearts isolated from 30 rabbits, raised from birth to approximately 5 weeks of age under either hypoxic (FIO2, 0.10) or normoxic (FIO2, 0.21) conditions, underwent retrograde aortic perfusion using a non-recirculating, well-oxygenated crystalloid solution. The left ventricular end diastolic pressure was initially set at approximately 5 mmHg. Aerobic performance was studied by measuring peak systolic pressure (PSP), coronary flow, glucose oxidation, and oxygen consumption. Anaerobic function was assessed by determining time for the onset of contracture (TOC) in the presence of zero coronary flow. Hypoxic vs normoxic hearts (mean+/-SEM): heart rate, 197+/-6 vs 190+/-5 beats per minute; PSP, 136+/-4* vs 108+/-4 mmHg; dP/dt(max), 2294+/-125* vs 1549+/-144 mmHg/sec; relaxation time constant (Tau), 26.9+/-1.1* vs 41.6+/-4.8 msec; (-) dP/dt(max), 1422+/-43* vs 1001+/-63 mmHg/sec; coronary flow, 86.3+/-4.2* vs 59.9+/-2.9 ml/min/g(dry); glucose oxidation, 3511+/-118* vs 2979+/-233 nmol/min/g(dry); oxygen consumption, 28.2+/-1.4* vs 22.7+/-1.4 micromol/min/g(dry); and TOC, 11.8+/-1.2* vs 22.9+/-2.2 min (*p < 0.05). Hearts isolated from young rabbits, exposed to hypoxia from birth, exhibited enhanced ventricular systolic and diastolic mechanical function, elevated coronary flow, retained capacity for aerobic metabolism, and a shorter TOC compared to their normoxic counterparts.