The winelands and the “good” animals are at different ends of the country.
I’d pick one and do really very well if I could afford it.
I’d think the safari/bush camp holiday in the north could be extremely relaxing and very doable on your own. A lot of the camps are super luxurious and you’ve got no reason to leave camp, other than the actual game drives which are organised by the camp anyway.
flying in to OR Tambo and getting a same day connection to somewhere like Hoedspruit - you can arrange be collected from there by the bush camp so no reason to worry about being on your own. There’s a lot less to juggle in terms of logistics.
Thornybush is glorious, as is The Royal Madikwe, if that is in your price range.
The only thing I’d worry about is a) whether the malaria meds would interfere with your condition and b) proximity to a good hospital if anything should happen.
There are safari lodges in non-malaria zones. Shamwari is one that comes to mind but I’ve never been.
The winelands is great but there is a lot to coordinate in terms of logistics - plus the need for safe and reliable transport around the various farms as you’re on your own.
I’d do business class if I could afford it. It’s a long overnight flight and it’s really nice to be comfortable, particularly if you’ve been unwell.