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The United States can no longer support a proposed Zimbabwean power-sharing deal that would leave Robert Mugabe, “a man who’s lost it,” as president, the top American envoy for Africa said Sunday.

Jendayi E. Frazer, the assistant secretary of state for African affairs, made the announcement in South Africa after spending the last several days explaining the shift in the American position to regional leaders.

The new stance will put pressure on Zimbabwe’s neighbors, South Africa in particular, to abandon its support for Mr. Mugabe. But South Africa said its position was unchanged.

The United States, Ms. Frazer said, has become convinced that Mr. Mugabe is incapable of sharing power. She cited political moves he has made since September without consulting the opposition, reports that his government has continued to harass and arrest opposition and human rights activists, and the continued deterioration of Zimbabwe’s humanitarian and economic situation.

Particularly worrying, she said, is the rapid spread of cholera, an easily treatable and preventable disease that has killed at least 1,000 Zimbabweans since August.

Accusations by the Mugabe government that the West deliberately started the cholera epidemic are an indication that Mr. Mugabe is “a man who’s lost it, who’s losing his mind, who’s out of touch with reality,” she said.

If Zimbabwe’s neighbors were to unite and “go to Mugabe and tell him to go, I do think he would go,” she said.

But South Africa said Sunday that the only way forward was the agreement under which Mr. Mugabe would remain president and the opposition leader Morgan Tsvangirai would take a new prime minister’s post. “Our position has not changed,” said Thabo Masebe, a spokesman for South Africa’s president, Kgalema Motlanthe.

South Africa is the region’s diplomatic leader. Its former president Thabo Mbeki mediated the power-sharing agreement in September and has worked since then to break an impasse over how to divide cabinet posts.

When the power-sharing agreement was announced, the United State gave it crucial support, offering to lift sanctions and help Zimbabwe renegotiate relations with international lenders if the deal was implemented.

“We’re not prepared to do any of that now,” Ms. Frazer said Sunday.