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He can jungle, but is not recommended. Thus I will not worry about a jungle guide here.
Passive: Deadly Venom - Twitch's attacks infect the target with Deadly Venom, which deals damage each second, stacks up to 6 times, and lasts up to 6 seconds.
Ambush - Twitch hides in the shadows, waiting for a nearby enemy. If he attacks, he will gain bonus attack speed.
After 1.25 seconds, Twitch becomes stealthed for 10/20/30/40/50 seconds. If Twitch attacks a unit while Stealthed, he gains 30/40/50/60/70% attack speed for up to 10 seconds, depending on how long he was stealthed before attacking.
Cost: 60 mana at all levels
Debilitating Poison - Infects all nearby champions with Debilitating Poison, slowing their movement speed.
Slows nearby enemy champions' move speed by 30%, plus 6% per Deadly Venom they have.
2/2.6/3.2/3.8/4.4 second duration.
80 Mana at all levels
Expunge - All nearby enemies secrete Twitch's toxic venoms from their bodies, dealing damage for each stack.
Deals 30/60/90/120/150 (+1) magic damage to each nearby poisoned enemy, plus 20/30/40/50/60 additional damage per stack of Deadly Venom applied to them.
90 Mana at all levels
*** Ultimate*** Spray and Pray - Twitch closes his eyes and fires his crossbow, spraying powerful piercing arrows ahead of him.
Twitch's attacks become long range, passing through units, and he gains 15/25/35 Attack Damage.
Lasts 12 seconds or 5/6/7 attacks.
150 Mana at all levels
3 points in deadliness, 1 in archmages savy (or improved exhaust if you take it), 4 points in sorcery, 4 in alacracity
Go ahead and pick up archaic knowledge, the 15% spell pen can help with expunge damage.
3 in sunder, 3 in brute force, 3 in lethality, 1 in havoc.
On the utility side, get 3 in perseverance, 1 in good hands (get improved ghost if you run ghost), 4 in awareness
Reds- Armor pen
Quints- Armor pen
Marks- Attack speed, or armor
Glyphs- Attack speed
Using these setups, you will start games with 31 armor pen, 58 attack damage, and about .75 attack speed. End game with a complete build you are looking at around 375 AD, 2.5 AS when attacking from stealth, 76 flat armor pen(after 3 hits, BC procs), 57% crit, and 25% lifesteal.
If you are starting mid, start with boots + 3 hp pots. Do Dorans blade if you are in a side lane, you will need the HP with 2 champs possibly jumping you.
I build my twitch pure glass cannon. He is going to die if he gets focused, no matter how tanky you build him, so i figure i may as well take some one to hell with me. I run a balance of attack damage/speed, lifesteal, crit and armor pen.
If it looks like Im going to be ganking a lot(which you should be), get boots of mobility, otherwise, attack speed boots are not a bad choice for some early game damage.
I build executioners calling next, Its a pretty underestimated item, its cheap, gives lifesteal and crit, has a Dot, and an on use with a short cooldown, that will help vs champs that regain health.
Next i build a zeal. Next i go for a BF sword, then finish infinity edge in whatever order you want. Next we turn that zeal into a phantom dancer.
If you are against a tanky team, I will go for madreds bloodrazor, starting with the swift bow. If the enemy isnt very tanky, go BF sword into a Black Cleaver.
If you built a madreds, you are going black cleaver next. If the game still isnt over at that point, sell the executioners calling for a bloodthirster.
If you didnt build a madreds and went cleaver, go ahead and build a bloodthirster. If the game isnt over, sell executioners calling for a 2nd bloodthirster.
Flash- is an absolute must have, no question.
2nd spell can be ghost, exhaust, ignite, or teleport. This is personal preference.
Heal is also an option if you go mid. I know, it sounds dumb. You would be surprised how many people dont look at summoners spells. Its pretty much only good for 1st blood, but 1st blood can give you the edge to own mid the rest of the laning phase.
Level 1- take expunge. I know you will want to take stealth, but level 1 stealth only lasts 10 seconds, and twitch doesnt have enough early game damage to kill without expunge.
If you have melee champs who are overextending, go ahead and take your AoE slow at level 2(easy kill with a Jax or Garen with you), if not, take stealth.
1 rank in your slow is enough to last till end game, focus on your expunge and stealth. Personally I dont take spray and pray until around level 10, as i primarily use it for team fights.
Ok now down to the nitty gritty. If you get mid, focus on last hits, poke at the enemy when you can, if they try and get too aggressive, poke them a few times then expunge. The worst matchups you can get mid are Caitlyn, Anivia, and Lux. Trade out for a side lane if you see these champs mid. Side lanes are best played with a champ with a stun, aka Taric, Sion, etc. They stun, you smash, you both profit. When you have stealth level 2-3, you can start ganking, anything less doesnt give you time to setup.
Do not be afraid to leave your lane and go ganking. That doesnt mean ignore your lane and let the enemy smash your towers, but you are a champ your team should expect to be our ganking. Go gank a lane or 2, go buy, then come back and gank your own lane. Do not underestimate farming with twitch. With your ability to stealth away from a gank, you can easily farm a couple creep waves, stealth and move on. Twitch needs massive farm and kills to complete his build, so always be making money.
Make sure when you are ready to gank, you have enough time left on your stealth to position yourself. Nothing worse than going to gank and your stealth runs out, and the enemy sees you and can get away. This is why theres no reason to gank before level 6 or so.
Twitch's stealth takes about 1.5 seconds to turn on from when you hit it, so dont expect instant stealth. It is your greatest tool for escape, so if you see someone coming to gank you, hit your Q and head for a bush, that should give you enough time for your stealth to kick in, and you can just stroll away.
Youll notice that twitch's abilities are all 1200 range, which is huge. A champ running away with 6 stacks of your poison is begging to be expunged for a kill. His AOE slow will slow for 66% with 6 stacks of poison, the best AoE slow in the game. This means you need to be at the back of team fights, staying as far away from people as you can. Twitch wilts under pressure, so you have to be very good in your placement, and when and where you engage.
It can sometimes be tempting to open a team fight when you are BEHIND the enemy team, but dont do it. If they all turn to you, you will die in mere seconds, and your team wont make it to you in time. If your team has engaged, open from the side of them, or in the back with your ranged carries, pop spray n pray, then use your AoE slow, then expunge, and watch the kills rack up. If the enemy clumps, its very easy to get Quadra kills from spray n prays damage, with expunge cleaning up.
Your job in team fights is to assassinate the enemy carries, so focus them first. If a carry with low HP like Annie or Ryze isnt paying attention, you can easily kill them before they know what hit them. If you can kill 2-3 carries while your tank is engaged, you just turned the fight into a 2/3v5, even if you die, your team can clean up from there.
Now for the bad news. You have several hard counters. Oracles- the little floating eyeball over a champ, costs 400 g, and allows the enemy to see through your stealth, and lasts till you kill them. If the enemy team has oracles, those champs have to die, or you may as well not even bother stealthing (except for the AS bonus).
Thornmail- You might notice twitch only has 3 ways to do damage. 1) His stacking poison is true damage(ie cant be mitigated by armor or MR), 2) auto attacks. 3) Expunge.
Auto attacks make up about 95% of your damage, and as such, you are hard countered by Thornmail. You will take 30% of your auto attack damage back as reflective magic damage, which is enough to eat you alive when your build is complete. Avoid auto attacking any and all champs with Thornmail. Typically this will be the enemy tank, but Ive seen plenty of carries build one to counter me. Must also be careful using spray n pray around champs with Thornmail, as your auto attacks from spray n pray WILL trigger Thornmail.
My best game with twitch was 42/6/7, and i had a streak where i had 20+ kills for like 14 of 15 games. Games like those are few and far between at level 30, as so many people have seen, and know how to counter him. Still, Twitch is a snowball, once he gets rolling, hes hard to stop. He can easily 3 shot enemy carries in just over 1 second at end game. If he gets slowed down early game, farm farm farm, get caught up on items, try and snipe some kills on low hp champs, and dont get discouraged.
If the enemy team builds Thornmail and oracles to counter you, then you are doing your job. They arent spending that gold on finishing off their own builds, making it easier for your team. In those cases, try and help your team by pushing towers, if team fights break out, be very careful in your target selection, and remember you dont have your stealth to get you out of trouble. Situational awareness is invaluable with twitch(and any champ for that matter).
Let me know if you have any questions, and hope this gives you a little insight into the plagued rat.