Milestones :: Perspectives :: Featured Journal Content

Milestones :: Perspectives :: Featured Journal Content

From coast to coast: Africa unites to tackle threat of polio
116 million children to be immunized from coast to coast across the continent, as regional emergency outbreak response intensifies
GENEVA/BRAZZAVILLE/NEW YORK/DAKAR, 24 March 2017 –  More than 190,000 polio vaccinators in 13 countries across west and central Africa will immunize more than 116 million children over the next week, to tackle the last remaining stronghold of polio on the continent.

The synchronized vaccination campaign, one of the largest of its kind ever implemented in Africa, is part of urgent measures to permanently stop polio on the continent. All children under five years of age in the 13 countries – Benin, Cameroon, Central African Republic, Chad, Côte d’Ivoire, Democratic Republic of Congo, Guinea, Liberia, Mali, Mauritania, Niger, Nigeria and Sierra Leone – will be simultaneously immunized in a coordinated effort to raise childhood immunity to polio across the continent. In August 2016, four children were paralysed by the disease in security-compromised areas in Borno state, north-eastern Nigeria, widely considered to be the only place on the continent where the virus maintains its grip.

“Twenty years ago, Nelson Mandela launched the pan-African ‘Kick Polio Out of Africa’ campaign,” said Dr Matshidiso Moeti, WHO Regional Director for Africa. “At that time, every single country on the continent was endemic to polio, and every year, more than 75,000 children were paralysed for life by this terrible disease. Thanks to the dedication of governments, communities, parents and health workers, this disease is now beaten back to this final reservoir.”

Dr Moeti cautioned, however, that progress was fragile, given the epidemic-prone nature of the virus. Although confined to a comparatively small region of the continent, experts warned that the virus could easily spread to under-protected areas of neighbouring countries. That is why regional public health ministers from five Lake Chad Basin countries – Cameroon, Central African Republic, Chad, Niger, and Nigeria – declared the outbreak a regional public health emergency and have committed to multiple synchronized immunization campaigns…

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New England Journal of Medicine
March 23, 2017  Vol. 376 No. 12
http://www.nejm.org/toc/nejm/medical-journal
Editorial
Rotavirus Vaccines — A New Hope
Mathuram Santosham, M.D., M.P.H., and Duncan Steele, Ph.D.
N Engl J Med 2017; 376:1170-1172 March 23, 2017 DOI: 10.1056/NEJMe1701347

Rotavirus gastroenteritis is the leading cause of diarrhea-associated hospitalization and death in children younger than 5 years of age,1 with more than 85% of the approximately 200,000 annual rotavirus deaths occurring in Africa and Asia.2 Since improvements in water, sanitation, and hygiene do not prevent rotavirus transmission, as they do with the spread of bacterial enteropathogens, the implementation of a rotavirus vaccine is essential to prevent death and complications from childhood diarrhea.

Two rotavirus vaccines — Rotarix (an attenuated G1P8 rotavirus manufactured by GlaxoSmithKline) and RotaTeq (containing five human–bovine reassortant rotaviruses, manufactured by Merck), attained prequalification by the World Health Organization (WHO) in 2008, which paved the way for UNICEF vaccine procurement through the financing mechanisms of the Gavi Alliance. These vaccines, which have been introduced in 42 Gavi-eligible countries and in 6 countries that have been designated as low-income and middle-income, have had a major effect on rotavirus deaths and hospitalizations in all settings.3

However, the uptake of rotavirus vaccines has slowed for various reasons, including supply constraints, high cost, and programmatic concerns for national immunization programs, particularly cold-chain capacity.4 Gavi countries have predominantly selected the attenuated G1P8 rotavirus vaccine,5 which has a smaller vaccine vial size and comes with a vaccine vial monitor for temperature monitoring. The two approved rotavirus vaccines have a liquid ready-to-use formulation. However, issues of cost of the vaccine and vaccine supply remain.
With Gavi support, low-income countries can procure rotavirus vaccines with a minimal copayment of 40 cents (in U.S. currency) per course, and Gavi cofinances the remainder of the UNICEF price (which ranges from $4.50 to $10.50). Low-income and middle-income countries, which are not Gavi-eligible, pay substantially higher costs for rotavirus vaccines.5 Gavi’s principles for vaccine-supply security emphasize the need for multiple manufacturers in the market to drive down prices while establishing sufficient vaccine supply. This protocol will become more critical as countries transition from Gavi support owing to socioeconomic development.

Fortunately, the situation is improving. In 2013, an indigenously developed rotavirus vaccine (ROTAVAC, Bharat Biotech International) was licensed in India and has been introduced in the routine childhood immunization program in four Indian states, with expanded rollout expected this year. This vaccine is under consideration for WHO prequalification, which would make it eligible for UNICEF procurement and Gavi subsidy. Bharat Biotech has committed to a cost of approximately $3.00 per course for global public markets.

In this issue of the Journal, Isanaka and colleagues6 document the safety and efficacy of an oral bovine rotavirus pentavalent vaccine (BRV-PV) developed by Serum Institute of India. The vaccine, which the investigators evaluated in an impoverished setting in Niger, had a reported efficacy of 66.7%,6 which is similar to that of other licensed rotavirus vaccines in similar settings. Efficacy data from an Indian study are pending. Despite this modest efficacy, the absolute public health benefits of vaccination are large, given the tremendous disease burden.

Estimates suggest that rotavirus vaccines have the potential to prevent 2.46 million childhood deaths and 83 million disability-adjusted life-years during the period from 2011 through 2030.7
The authors describe a rotavirus vaccine that is thermostable for 24 months at 37°C and for 6 months at 40°C, which may provide advantages for vaccine delivery in remote areas where cold-chain capacity is limited. However, this vaccine is freeze-dried, and practitioners in many countries may prefer other rotavirus vaccines that have liquid all-in-one formulations to simplify programmatic considerations. The projected cost of this heat-stable vaccine falls between the Gavi prices for the two currently used vaccines. The availability of vaccines from several manufacturers will increase global supply.

During the past three decades, remarkable progress has been made in reducing mortality from diarrheal disease, but the goal of ending such deaths cannot be achieved without aggressive implementation of a comprehensive approach to diarrhea prevention and treatment, including providing access of rotavirus vaccines to every child regardless of economic status. Increased availability of low-cost, programmatically suitable vaccines in abundant supply will be key to achieving this goal.

Original Article
Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger
Sheila Isanaka, Sc.D., Ousmane Guindo, M.D., Celine Langendorf, Pharm.D., M.P.H., Amadou Matar Seck, M.D., Brian D. Plikaytis, M.Sc., Nathan Sayinzoga-Makombe, M.P.H., Monica M. McNeal, M.Sc., Nicole Meyer, M.Sc., Eric Adehossi, M.D., Ali Djibo, M.D., Bruno Jochum, M.S., and Rebecca F. Grais, Ph.D.
N Engl J Med 2017; 376:1121-1130 March 23, 2017 DOI: 10.1056/NEJMoa1609462
Abstract
Background
Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa.
Methods
We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3.
Results
Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception.
Conclusions
Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000.)

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Editor’s Note:
Please note World TB Day announcements across this edition.