I bought a hunting package for a safari in South Africa at a Whitetails Unlimited banquet. Probably go next August or Sept. This will be my second African hunt, the first was in Namibia.
I can use a handgun in SA, so I am looking at my options. I have a 12"44 mag Encore, and a 12" 375 Win Contender. I am leaning towards the 44 right now. It shoots well with 240 grain Hornady XTP's and 270 grain Speer Deep curls, both my handloads. Hard cast are another option.
Also considering getting a 30-30 Contender barrel or 308 Win Encore barrel. I also load for 308.

African plains game has a tenacity of life, and are much tougher than our deer, antelope, and elk. I wanted to hunt the entire hunt with a scoped revolver, but the long ranges required me to use a 375 caliber, that was capable if loosing heavy hunting bullets at long ranges. 2 animals taken at 250+ yards.
Go with the largest and heaviest hitting, you can shoot well. Accuracy is truly the key.

The outfitter where I am going also caters to archery hunters. My shots will be 100 yards and under. I already have a Kudu and a Gemsbok, so I will be mostly after Impala and smaller game, but if opportunity is there could take another.

I would take either straight-all case, and I would choose the 308

I really like the .375 Win. I have been using Volmer 220 grain bullets in mine. They do a great job and wouldn't hesitate using them on elk sized game. If you are thinking of a new encore barrel don't rule out the 30-06. My 06 Encore shoots 1/2" groups and gets 150fps more than my friends .308. Nothing wrong with the .308 but every little bit helps with short barrels.

Reflex - What kind of velocity are you getting with the 220's.

I have been using the Sierra Pro Hunter 200 grain JFN. Don't have info with me, but think I was getting 1800 fps with 36 grains of RL-7.
I got a box of 185 grain Lehigh Controlled Fracturing bullets but haven't loaded any yet.

I found a few 300 grain XTP's that I had loaded for a rifle. They are going 1300fps from my Encore 44.

My 5" Super Redhawk likes 240 grain XTP's and the 270 Deep Curls.

1950fps with 35.5grs RL7 and a GM210M primer in Starline brass. Start with 32grs and work up. It is pretty warm but still within the the book.

My 6.5/.284 XP and .475 Linebaugh have handled everything except elephant,hippo, croc, Cape buff, lion, eland. Took 2 800# kudu with it at 201 & 368 yds. Many smaller game. Never a problem. Everything was one shot.
Used a .375/.284 XP before I got my 6.5, but could have taken about everything with it.