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Katlego Mphela was on target for the Bafana Bafana but Marcelo and Breitner saw Santos run out narrow winners in Sao Paulo.
Carlos Alberto Parreira's South Africans recently held a three-week training camp in Brazil as they prepare for the first World Cup to be hosted on African soil. Last Wednesday they held Paraguay 1-1 at Asunción.
They will move on to another training camp in Germany later this month before returing to South Africa in May to complete preparations for the World Cup opener against Mexico in Johannesburg on June 11.
France and Uruguay are the two other teams in South Africa's group.
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