Often, in fact virtually in every case, in an HiE which proposes deliberate contact between humans and ponies, almost no attention is given to the risk of microbial contamination.
Now, I know this is a really boring subject for those who aren't astrobiologists or epidemiologists, but if you're putting a serious effort into a serious dramatic story, you MUST consider the basics of logistics and common knowledge.
As far as the ponies go, they're the weakest link. They do have a basic comprehension of infectious disease... but would they know to be wary of alien germs? Would they make the intuitive leap that microbes in another world might react badly in their bodies, and that their microbes might behave like bad neighbors in our bodies? That's a tough one and it would depend on what sort of pony you put in charge in your story. If it's Twilight Sparkle, she might be expected to figure it out. If it's a stuffed-shirt noble... prepare for the "Andromeda Strain" happening.
As for humans initiating contact (this is especially important if they are humans purportedly from our world and our time or in the future) we already do know the risks of contamination AND we also try rather hard not to contaminate other worlds.
In fact, way back in 1958 the Intenational Council for Science formed the Committee on Space Research. One of the objectives included protecting other planets from 'accidental invasion' by whatever little critters and germs we and our probes carry.
We can look at a perfect example of this with the 1976 Viking lander on Mars: before launch, every component was heated to several hundred degrees, assembled in a clean room, and shipped to the lauchpad in a bioshield... all the prevent the chance of Earth bacteria getting to Mars, which even then was assumed to be virtually, if not completely, lifeless.
Now, with that extreme caution in mind concerning a planet in out own solar system, how much more paranoid would be the steps taken when venturing out into interstellar space or (as with the most frequent HiE use) interdimensionally?
And if alien ponies showed up on Earth, NASA would be having conniption fits and freaking out about quarantine. Again, with very strong justification! Always remember, the worst alien microbes will likely NOT be ones that routinely cause disease. They will be the ones that simply require a warm, moist place with nutrients to thrive... and which the immune system cannot recognize. Think of the virulence of some of the new antibiotic-resistant strains of E. coli and MRSA for case studies of what can occur when even ubiquitous terrestrial bacteria mutate into more virulent forms.
There are about 9 types of deliberate-contact types of HiE that come to mind which I find are internally plausible or passable:
1. Pre-modern age humanity. They wouldn't know to be careful. The only way this doesn't end tragically for everyone is if we ignore the alien microbe problem entirely.
2. World's gonna asplode, or otherwise end. When faced with an apocalypse, caution tends to go out the window since yer kinda doomed if you sit around doing nothing.
3. HAZMAT-type stories of contact, sci-fi type plotlines about a realistic first-contact situation.
4. Terrorists invade our imaginations... er... Equestria. They rush the Stargate or whatever we have in an insane attempt to infect everything with everything on both sides of the portal.
5. We try to kill them off or they try to kill us off. In this plot, one or both sides ends up with the 'all x are evil bastards' label. That being said, Space Hitlers are pretty common, and a reasonable storyline for an imperialist alien race or future/alternate Earth of xenophobic, imperialist/fascist human rulers. However, in those cases, always remember that resistances ALWAYS exist unless the baddies are using some seriously F'd up stuff to maintain absolute power: brain implants that control the mind completely or explode if you think of rebelling, for example.
6. Magic/science filters out germs. It's plot-convenient, yes. BUT!!! It's also a plausible sci-fi trope to easily take care of the problem. It also lays the groundwork for stories about super-germs and alien lifeforms/energy entities/spirits/etc. which can sneak around the quick fix, as was frequently the plot of "Star Tre: TNG" episodes.
7. Comedies. Not meant to be taken seriously, thus the issue is off the table right off the bat. You can even use this to makeup all sorts of weird magical ailments. One I thought of was that the disease turns all human-like life forms into ponies... and now all dimensions are populated by ponies. Alternatively, it could turn all ponies into humans! It's a plot that works for straigh-up comedy, sci-fi satire, or a farce of the epidemic trope.
8. Social drama. The science isn't important to the plot. But this must be handled carefully since in the modern age the science will always be play a role in the decision-making process. No one in the story can simply dismiss the risk unless they are portrayed as especially stupid and resistant to the warnings of their more-intelligent but less-influential colleagues and advisors. It is best here to stay away from science if it's not going to be part of the story, because inevitably you MUST address the infection risk if you venture in that direction at all. Regardless, it leaves a bit of disingenuity since common knowledge tells us this risk exists. Framing of the story must be done with exquisite care to distract the reader from thinking about the obvious.
9. The ponies and humans try REALLY hard not to infect each other... but everything goes pear-shaped regardless. This is VERY plausible and tragic, since we have already found some organisms that are staggeringly resistant to dying under harsh conditions. A little single-celled critter called Serratia liquificans... found EVERYWHERE it's damp (ponds, swamps, ditches, even cheese!) can survive in a Mars-like environment provided it gets some liquid water now and then and shade from UV rays. And the biggest contaminant-carriers of all: HUMANS and PONIES themselves. We are so fundamentally intertwined with microbial life that biologist Ed Yong has described himself (and all animal life, basically) as "trillions of microbes in a human-shaped sack".
And with that, I leave you with these final words: OMGEBOLAWILLDOOMUSALL!!!RUNFOREQUESTRIANOWS!!! *and so, both worlds were destroyed*