Lessons from Vaccine-Related Poliovirus in Israel, UK and USA.

Genetic variants of vaccine poliovirus type 2, imported from an unknown source, were detected in waste waters in Jerusalem, London and New York in early 2022. Wild poliovirus type 2 was globally eradicated in 1999, but vaccine virus type 2 continued for 16 more years; routine use of the vaccine was discontinued in 2016 and reintroduced occasionally on purpose. As an unintended consequence, type 2 vaccine virus variants (circulating vaccine-derived polioviruses, cVDPVs) that mimic wild viruses' contagiousness and neurovirulence, have been emerging and spreading. To illustrate, in just the past four years (2018-2021), 2296 children developed cVDPV polio in 35 low-income countries. Many assume that virus transmission is via the faecal-oral route. Sustained virus transmission was documented in London and New York, in spite of high standards of sanitation and hygiene. Here, virus transmission cannot be attributed to faecal contamination of food or drinking water (for faecal-oral transmission). Hence, contagious transmission can only be explained by inhalation of droplets/aerosol containing virus shed in pharyngeal fluids (respiratory transmission), as was the classical teaching of polio epidemiology. If transmission efficiency of VDPV is via the respiratory route where hygiene is good, it stands to reason that it is the same case in countries with poor hygiene, since poor hygiene cannot be a barrier against respiratory transmission. By extrapolation, the extreme transmission efficiency of wild polioviruses must also have been due to their ability to exploit respiratory route transmission. These lessons have implications for global polio eradication. It was as a result of assuming faecal-oral transmission that eradication was attempted with live attenuated oral polio vaccine (OPV), ignoring its safety problems and very low efficacy in low-income countries. Inactivated poliovirus vaccine (IPV) is completely safe and highly efficacious in protecting children against polio, with just three routine doses. Protecting all children from polio must be the interim goal of eradication, until poliovirus circulation dies out under sustained immunisation pressure. OPV should be discontinued under cover of immunity induced by IPV to stop the emergence of new lineages of VDPVs, not only type 2, but also types 1 and 3, to expedite the completion of polio eradication.

Timely use of Covid-19 vaccines could have saved thousands of lives.

Earlier we, TJJ and DD, had written in IJME, that during the pandemic with high case-fatality in those above 65 and younger adults with chronic lung, heart or kidney diseases or diabetes, vaccination must be administered early as a life-saving procedure (1). It was pointed out that protection delayed may be protection denied to drive home the urgency of vaccination for saving lives. At that time, Phase III vaccine trials were in progress and we had adequate data on safety, but efficacy had yet to be measured. Good immunogenicity had already been documented in Phases I and II in which there were no signals of safety problems. Efficacy was "on promise" when we argued for early vaccination of those at risk of death.

Covid-19 vaccine trials and ethics: Protection delayed is protection denied.

The Covid-19 pandemic is raging, taking heavy toll of lives and livelihoods. The need for safe and effective vaccine(s) is urgent. Vaccine research has progressed rapidly and a few vaccine candidates have passed trial Phases 1 and 2, confirming reasonable safety and immunogenicity parameters. They are ready for large scale Phase 3 trials to quantify protective efficacy, if any, and to detect uncommon but serious adverse effects, if any. These developments present unprecedented opportunities and challenges, scientific and ethical. Globally hundreds die every day due to Covid-19, and emergency/compassionate use of vaccine candidates that are ready for Phase 3 trials are likely to save lives. We perceive an ethical imperative to allow such vaccination for those at high risk of death and voluntarily make such informed choice - for them protection delayed will be tantamount to protection denied.

COVID-19 Eradication for Vaccine Equity in Low Income Countries.

The coronavirus disease 2019 (COVID-19) pandemic will transition into endemic phase with perpetual risk of severe disease and high mortality in vulnerable people - the elderly and those with co-morbidities, unless eradicated. Although several vaccines are already available to rich countries, low-income countries face gross vaccine inequity. We propose COVID-19 eradication to address both problems. An eradication program will ensure vaccine equity and international cooperation to establish public health surveillance and high quality laboratory diagnostic services in all countries. Eradication is biologically and technically feasible. We hope the World Health Organization will accept the proposition and design the necessary strategy without delay.

Acute encephalopathy in children in Muzaffarpur, India: a review of aetiopathogenesis.

The acute encephalopathy occurring in children in Muzaffarpur, India, also recognised in other litchi-cultivating areas of India, Bangladesh, Vietnam and China, had previously been linked to litchi consumption. Recently, it has been identified as hypoglycaemic encephalopathy of an unusual aetiology with three key factors: undernutrition, prolonged fasting and litchi consumption. A second set of investigators has independently reconfirmed the diagnosis and the three-factor aetiology. Skipping the evening meal with an intake of large amounts of litchi in undernourished children is causative. Early-morning hypoglycaemia with an inadequate glycogen store leads to initiation of gluconeogenesis and fatty acid ß-oxidation, but methylene cyclopropyl alanine and glycine present in the litchi aril block the fatty acid ß-oxidation cycle. The outcomes are uncorrected hypoglycaemia and encephalopathy due to the entry of metabolic intermediates that cross the blood-brain barrier and affect neuronal function. Suggested measures include early 10% dextrose infusion. Awareness about the disease is of prime importance. The diagnosis and aetiopathogenesis are still under question from a part of the scientific community. This review was undertaken to present a comprehensive view of hypoglycaemic encephalopathy and to remove some of the lingering doubts.

The moral dilemma of the polio eradication programme.

During the last five years, globally, cases of polio caused by vaccine viruses have outnumbered those of polio caused by natural (wild) polioviruses, posing a moral dilemma. Public health ethics should ensure the best interests of the community, with equity in sharing benefits and risks irrespective of socioeconomic disparities. Vaccine viruses in oral polio vaccine (OPV) cause vaccine-associated paralytic polio (VAPP), while paralytic polio is also caused by vaccine-derived polioviruses (VDPVs). By its policy of the use of OPV in low and middle-income countries, while rich countries use the safe inactivated polio vaccine (IPV), the Global Polio Eradication Programme has been responsible for social injustice. In 2017 and 2018, there were outbreaks of polio in Syria and Papua New Guinea due to circulating VDPVs, after many years of these countries remaining free of polio due to wild polioviruses. The only ethical way forward for global polio eradication is to replace OPV with IPV in all countries.

Should there be a World Health Assembly resolution for malaria eradication? Opinion against.

A resolution for eradicating malaria, if passed by the World Health Assembly (WHA), will have a distracting effect on all countries with malaria. The continued prevalence of malaria is indicative of weak public health infrastructure. True, smallpox was eradicated by international efforts following WHA resolution: the success factor was primary prevention using a safe and effective vaccine. A resolution to eradicate polio was passed in 1988, with a target year of 2000, but even in 2019 success is not within reach. Public health experts are hesitant to move forward with measles eradication before polio is eradicated. Country by country elimination of malaria is a better way, ensuring the strengthening of public health infrastructure, with many other health benefits.

An ethical appraisal of the choice of vaccines against Poliomyelitis.

Medical ethics is invoked for immunisation of children as it involves an interaction between a healthcare professional and the child. Immunisation under the national immunisation programme is a public health intervention and the common belief is that ethics is not relevant. Two vaccines with contrasting safety and efficacy profiles were available against polio before the national immunisation programme was launched: the inactivated poliovirus vaccine (IPV) and the live attenuated oral poliovirus vaccine (OPV). India chose OPV and excluded IPV. We carried out an ethical appraisal of that choice. Principles of medical ethics comprising four elements-non-maleficence, beneficence, autonomy and justice-was already in vogue at the time. Applying each of them, a head-to-head comparison between IPV and OPV is made. The results clearly show that the choice of vaccine was made without using ethical principles, resulting in serious adverse effects in hundreds of thousands of children. We recommend that medical ethics must be applied to all choices of public health interventions.