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A brace from top star Lionel Messi secured Argentina their fourth win in four games as they now top the standings with a five-point advantage ahead of Uruguay.
Five-time world champions Brazil lost the lead to Argentina last week after playing out a 1-1 draw with Venezuela and now dropped to third following another setback against Uruguay.
Darwin Núñez broke the deadlock in the 42nd and Nicolas de la Cruz completed the win in the 77th.
Brazil forward Neymar was carted off the pitch shortly before the break due to a knee injury. The possible extent and the specific area of his injury are still unknown.
Elsewhere, Venezuela defeated Chile 3-0, Paraguay won 1-0 against Bolivia and Ecuador and Colombia played out a goalless draw.
In the South American qualifiers, each nation plays the nine others home and away. The top six teams after 18 rounds will qualify for the 2026 World Cup in Canada, Mexico and the United States.
Two more round of games will be played this year on Nov 16 and Nov 21 - BERNAMA