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The Kingsmead Test will also be Jacques Kallis' farewell Test match as the 38-year-old legend decided to say goodbye to the longest format of the game in a shock decision on Wednesday. (Read: Kallis wants to play 2015 World Cup)
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The Proteas are at a loss to explain their miserable run at one of the country's premier Test grounds, where they have not won since beating West Indies in 2008. (Also read: De Villiers says booing in Johannesburg has upset Steyn)
Australia, England, India and Sri Lanka have all enjoyed handsome triumphs in Durban over the world's top ranked test team since then and vice-captain AB de Villiers cannot fathom the poor run.
"I am confused about Durban. I don't know what to expect," he told reporters.
"I am going to play it like I always play my cricket. I am going to take it one ball at a time and use my experience to adapt as quickly as I can. So will the whole team."
De Villiers suggested it would be a good toss to win, with a lively pitch expected for the first part of the Test.
"I think there will be a bit of movement on the first day. Batting first always seemed the better option in the past.
"I don't expect as many cracks as there was at the Wanderers. It will probably be a bit more green, a bit firmer, and there may be a bit of turn towards the end of the Test."
South Africa's overall record at Kingsmead is symmetrical - they have won 13, lost 13 and been involved in 13 draws.
Durban-based fast-bowler Kyle Abbott should come into the side for Morne Morkel, who suffered an ankle ligament strain in the first test at the Wanderers, but it is the spin department that will give the selectors the most pause for thought.
Imran Tahir went at five runs an over in the first Test and was a pressure release for the Indian batsmen. De Villiers defended the Pakistan-born 34-year-old. (Also see: Pics - How the 1st Test ended in a tame draw)
"Immi (Imran Tahir) has bowled really well in the last few months. He didn't have a great game at the Wanderers but that is part of sport. We know what he is capable of," De Villiers said.
"It's always tempting to get Immi into your starting XI, even if you play on a road. Even on glass, he can get you wickets.
"He seems to run through the tail easily. It's a tough decision to make. We lacked control at the Wanderers, not just from Immi, from all the bowlers."
While there has been a furore at home over the team's decision to settle for a draw in the first Test where they were eight runs short of a world record victory target of 458, little has been made of India's inability to close the game out. (Related: Graeme Smith defends decision to draw 1st Test)
The tourists had 136 overs to take 10 wickets on a wearing pitch with variable bounce but managed just seven against a defiant display of batting by the hosts.
Questions around India's team selection also centre on the spinners, with Ravichandran Ashwin bowling 42 wicket-less and expensive overs.
Left-arm spinner Pragyan Ojha is the other option, though he has never bowled in test matches outside the sub-continent.
The workload of the entire Indian bowling unit in Johannesburg was heavy, with 35-year-old Zaheer Khan bowling over 60 overs. That might have a bearing on MS Dhoni's decision if the Indian captain wins the toss.