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Ghana is demanding that all adult travellers flying into the country provide proof of full vaccination, effective from midnight 12 December.
Ghanaian citizens and residents abroad are exempt for up to two weeks, but will be required to get jabbed upon landing at the airport.
The authorities say they are concerned about a surge of infections over the festive period.
These measure appear to be some of the strictest in the world.
Many other countries have avoided an outright blanket ban on unvaccinated arrivals, such as members of the European Union and the United States.
Unvaccinated travellers are often given the option of self-isolating on arrival.
Alongside the new measures, Ghanaian authorities will also still insist that all arrivals present a negative PCR test.
All Ghanaiansflying out of the country will also need to show proof of vaccination.
Less than 10% of Ghana's population have been fully vaccinated.
Ghana's authorities have expressed concern about the low vaccination rates and they are particularly worried about the new Omicron variant among international arrivals.
"The expected increase during the festive season calls for urgent actions to prevent a major surge in Covid-19 cases in Ghana," the head of the Ghana Health Service, Patrick Kuma-Aboagye, said in a statement.
He said that over the last two weeks, cases detected at Ghana's main airport, Kotoka, accounted for about 60% of all confirmed Covid cases in the country.
The authorities plan to ramp up efforts to immunize the population in January, by making it compulsory for government employees, students and health workers to get the vaccine, according to Reuters.
Vaccine passports will also be required to enter venues with large crowds like nightclubs and sports stadiums, Reuters says.
Since the start of the pandemic, Ghana has reported 131,246 cases and 1,228 Covid fatalities.