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In the lives of common folk becoming afflicted with a disease poses as great a threat as monsters or magic. Pestilence can ravage a population directly or it can destroy crops, sicken livestock, and foul sources of drinking water, leaving famine and political turmoil in its wake. A settlement in the grips of a plague might develop oppressive customs that last long after the outbreak has passed, and ghouls and other terrors often take advantage of the hardships diseases bring.

Even mighty heroes can fall victim to disease, particularly illnesses supernatural in origin. An evil mage might afflict adventurers with a sickness only magic can cure, or while exploring an ancient tomb the party might contract a plague that saps their strength. High-level PCs may even encounter diseases of extraplanar origin—for example, demon fever is an ailment from the realms infernal that night hags intentionally spread amongst their enemies.

The rules for handling diseases are unique to each disease. Whereas one affliction might have an incubation period of several weeks, others can prove lethal within minutes. Some diseases infect only certain types of creatures or affect their hosts in different ways. While victims of disease can sometimes recover naturally, supernatural diseases often require magic to cure (such as a lesser restoration spell). Particularly virulent diseases might resist even magical healing. Only rare medicines or the intervention of the gods can halt such plagues. 

Treating Diseases

Treating a diseased creature over the course of a short rest with a successful Medicine check (tier 1: DC 10, tier 2: DC 14, tier 3: DC 18, tier 4: DC 22) grants advantage on its next saving throw against the disease.

Sample Diseases

Each of the following example diseases includes a general range of adventurers it is intended to be used against: tier 1 (1st–4th level), tier 2 (5th–10th level), tier 3 (11th–16th level), or tier 4 (17th–20th level). Narrators that want to introduce a disease above or below the party’s current tier can adjust the specifics of the disease to match their resilience and capabilities. Such adjustments might include raising or lowering the saving throw DCs of the disease, changing the disease’s symptoms, or making the disease easier (or more difficult) to cure.

Adverse Ascension (Tier 2)

Being exposed to too much unfiltered godly glory is deadly to mortals, the simple matter of their flesh and their paltry souls too small to contain such radiance.  

The most common way to contract adverse ascension is by use of the commune spell, becoming afflicted once every time the caster does not receive an answer. A creature that takes radiant damage equal to triple its total hit dice from a celestial can also be afflicted. 

Any creature overexposed to the divine makes a DC 15 Wisdom saving throw or becomes infected with adverse ascension. In the first phase of adverse ascension the infected creature’s dreams and daydreams start featuring more of the deity’s aspects and iconography. 

After 1d4 days of the disease’s first stage the infected creature makes a DC 12 Charisma saving throw or proceeds to the second stage of infection, gaining a short-term mental stress effect whenever it commits an act of devotion to any other god than the one worshiped by the celestial that afflicted it. On a success, the creature recovers from the disease.

At the end of each long rest, an infected creature makes a Charisma saving throw against a DC determined by infection stage (first stage DC 12, second stage DC 13, third stage DC 14). The saving throw is made with disadvantage if within the last 24 hours the infected creature witnessed divine spellcasting by any follower of the same deity as the one it is being drawn to. 

On a success while suffering from the second or third stage of infection, the infected creature regresses to the previous stage of infection. 

On a failure while suffering from the second stage of infection, the infected creature gains an ideal of, “All must know how great my deity is.” This can manifest in many ways, such as muttered whispered scriptures, or as proudly trying to convert everyone around, depending on the person. The infected creature begins to show a miraculous understanding of the Outer Planes that gives it advantage on Religion checks. An infected creature that fails a second saving throw progresses to the third stage of adverse ascension.

On a failure while suffering from the third stage of infection, the infected creature can cast shield of faith once between rests. For the spell’s duration, the infected creature begins to gently fade into the Astral Plane as it is drawn to the divine. At the start of each of its turns, the infected creature makes death saving throws as if dying. The infected creature still acts on its turn as normal, but after three failures it materializes into the heavens never to be seen again. Other creatures can use the Help action to grant the infected creature advantage on these saves by speaking encouraging words to it.

After a priest of the same or a similar faith has spent 7 days in one-on-one theology seminars with the infected creature, it makes a DC 12 Charisma saving throw, curing the disease on a success. 

Arcane Autophagy (Tier 4)

Magic takes a toll on even the most resilient mortal body. Arcane autophagy occurs when the energy of a powerful spell devours the consciousness of the creature casting it. Despite this disease’s name mages, the servants of the gods, and champions of nature are all vulnerable to arcane autophagy.

Whenever a creature casts a 9th-level spell, roll 1d20. On a result greater than the creature’s spellcasting level, it may become afflicted with arcane autophagy. The creature makes a DC 20 saving throw using its spellcasting ability. On a failed save, the creature becomes infected with arcane autophagy and suffers 1 level of strife , or 2 levels on a failure by 5 or more.

Once infected, the creature repeats the saving throw each time it finishes a long rest. The creature must also repeat the save whenever it casts the spell that triggered the disease. On a failed save, the creature suffers another level of strife, or 2 levels on a failure of 5 or more.

Lesser restoration has no effect on arcane autophagy. A greater restoration spell removes 1 level of strife from the afflicted creature but does not end the disease. To fully recover, the infected creature must purge all traces of the triggering spell from its mind. To do so, the creature must spend 24 hours without casting spells or cantrips, using class features or other abilities involving magic, or activating magic items. If these conditions are met, the next time the creature saves against the disease, it recovers on a success. A recovered creature no longer needs to make saving throws against the disease and can reduce levels of strife as normal. On a failed save, the creature’s condition worsens, although it can attempt to recover again by repeating the purging process.

Cackle Fever (Tier 3)

Also known as ‘the shrieks’, cackle fever can afflict any humanoids except gnomes, who are mysteriously immune to the affliction. The disease’s symptoms include fever, disorientation, and fits of laughter that are literally contagious.

A creature infected with cackle fever suffers 1 level of fatigue 1d4 hours after contracting the disease. Until the disease is cured, the creature cannot recover from this level of fatigue. Whenever the creature experiences stress (including entering combat or taking damage), it makes a DC 13 Constitution saving throw . On a failed save, it takes 5 (1d10) psychic damage and is incapacitated as it cackles maniacally for 1 minute. At the end of each of its turns, a cackling creature can repeat the saving throw to stop laughing and end the incapacitated condition.

When a creature starts its turn within 10 feet of a cackling creature, it makes a DC 10 Constitution saving throw. On a failed save, it also becomes infected with cackle fever, or on a success it becomes immune to infection from that creature’s cackle fever for 24 hours.

A creature infected by cackle fever makes a DC 13 Constitution saving throw whenever it finishes a long rest. On a success, the DC of this saving throw and the saving throw to avoid a cackling fit are reduced by 1d6. The creature recovers from the disease when the DC drops to 0. If the creature fails three such saving throws before the disease ends, it gains a long-term mental stress effect.

Gnolls are particularly susceptible to cackle fever and have disadvantage on saving throws made against the disease. However, a gnoll is not incapacitated while in the grips of a cackling fit and instead gains advantage on attack rolls.

Delver’s Lung (Tier 1)

Delver’s lung is caused by inhaling the spores of mold that often infest dungeons and other subterranean spaces. Though pernicious, delver’s lung is rarely fatal.

A beast or humanoid exposed to delver’s lung makes a DC 12 Constitution saving throw or it becomes infected. Whenever an infected creature takes the Dash or Sprint action, it repeats the saving throw or suffers 1 level of fatigue .

Each time an infected creature finishes a long rest, it repeats the saving throw, with advantage if the rest was completed in an environment with clean, fresh air. After succeeding on three consecutive saving throws, the disease ends. A creature that finishes a long rest on the Elemental Plane of Air automatically recovers from the disease.

Demon Fever (Tier 2)

Ghouls native to the infernal realms carry an illness known as demon fever in their bile. Night hags (who are immune to this disease) sometimes smear ghoul bile on their lips to infect their mortal lovers.

A humanoid exposed to demon fever makes a DC 14 Constitution saving throw or it becomes infected. Terrifying dreams plague an infected creature’s sleep. Whenever the creature attempts to take a long rest, it makes a DC 14 Wisdom saving throw or it gains no benefit from the rest.

A protection from evil and good or magic circle spell cast on an infected creature prevents the nightmares for 24 hours, allowing it to benefit from a long rest. A heal spell or more powerful magic permanently cures demon fever. When afflicted by a night hag, the creature can choose to end the infection at any time.

Fey Longings (Tier 2)

The Dreaming is a wondrous realm, so enchanting that some start to long for it without ever having been there. After any personal, intimate interaction with a fey, a creature makes a DC 10 Wisdom saving throw or becomes infected. Fey aware of this danger can take special precautions to prevent it using wards made from special plants and oils and though most know this, few care. Creatures with fey ancestry (such as elves, gnomes, and half-elves) are immune.

It takes 1d4 days for the symptoms of fey longings to take hold. The infected creature sees fey wherever they look. At first it’s the giggling sound of pixies just behind the next tree, but after several days it’s not uncommon for the delusions to include being surrounded by thick vines, glistening psychedelic rains, or riding a colorfully-feathered frog (while in fact the infected creature might be tangled in ropes, showered in blood, or standing on a swift-moving boat). While these vivid hallucinations are complete, they do not directly lead to a creature being harmed or put into harm’s way.

When the infected creature makes an opposed Deception, Insight, Intimidation, or Persuasion check, it makes a DC 12 Wisdom saving throw. On a failure, the infected creature is charmed by one random creature it can see. This creature cannot be an ally of the infected creature. If there’s no viable target, the infected creature instead has disadvantage on attack rolls and ability checks as it sees and tries to interact with a world beyond the veil. 

The best cure for fey longings is to bring the infected creature to the Dreaming to interact with its denizens and environment. At the end of each day spent in the Dreaming, an infected creature makes a DC 10 Wisdom saving throw to recover from the disease. Otherwise fey longing naturally fades after 1 month.

Fractured Rift Disorder (Tier 2)

Every being is tied to the plane it is native to, both the realm’s physical laws and the dimension’s place in the multiverse. On rare occasions that connection can weaken—and perhaps even be severed. Frequent travel beyond the Inner and Outer Planes dilutes a soul’s tether to its original plane of existence. Spells such as plane shift and well-made portals are generally safe, allowing for a smooth transition between dimensions, but journeying by other means can have ill effects. Whenever a creature travels between planes using a naturally occurring portal or dangerous magical item (like a well of many worlds), it makes a DC 15 Constitution saving throw or becomes infected with fractured rift disorder.

Whenever the infected creature suffers a level of fatigue or strife, its connection to the Material Plane is tested and it makes a DC 12 Constitution saving throw . On a failure, the infected creature is teleported 1d20 feet away in a random horizontal direction as its connection to the here and now shifts slightly.

Unless treated (see below) the rift continues to fracture and the infection worsens. At the end of every week during which a creature with a basic or mild infection does more than rest, it makes a DC 15 Constitution saving throw or the disease worsens as per Table: Fractured Rift Disorder. On a success, its infection is reduced by one stage (from mild to basic, or basic to recovered).

All of this disease’s effects manifest only while on the Material Plane. 

Restoration and similar magic have no effect on fractured rift disorder since the problem can’t be fixed with positive energy. Instead the infected creature needs to strengthen its connection to the world. A druid or similarly nature-oriented person can diagnose the disease with a DC 18 Nature check and prescribe a long-term treatment, usually requiring a month of peaceful meditation in an ancient grove or cave at the end of which the infected creature recovers.

There are legends about living with fractured rift disorder as well, the most popular claiming that an old dwarven hero infected with it crafted a pair of magical iron boots to keep himself grounded. 

Fracture Level Cumulative Effect   Worsens when...
  Basic Make a DC 12 Constitution save after suffering a level of fatigue or strife , or teleport 1d20 feet in a random direction. Failing a DC 15 Constitution saving throw at the end of a week of adventuring.
  Mild Make a DC 12 Constitution save after scoring or taking a critical hit, teleporting 1d20 feet in a random direction on a failure. Failing a DC 17 Constitution saving throw at the end of a week of adventuring.
  Severe Become ethereal (as the blink spell) whenever the infected creature rolls a natural 1 on a d20. Make a DC 12 Dexterity saving throw to avoid dropping held items just before the transition. Automatically worsens after several weeks not spent resting.
  Deadly When the infected creature has been targeted by a magical effect that changes its form or location within the last round and it makes a Strength check, melee attack roll, or attacks with a thrown weapon, it makes a DC 10 Constitution saving throw or it is transported to a random plane of existence.

Netherblight (Tier 3)

Being raised from the dead often has a deleterious effect upon a mortal’s soul. Netherblight is the term scholars use to describe this spiritual malady.

Whenever a dead humanoid is restored to life (via a raise dead spell, for example), roll 1d20. On a result greater than the creature’s level (or challenge rating), it may become afflicted with netherblight. The creature makes a DC 17 Charisma saving throw or it becomes infected.

Netherblight affects its victims in different ways. Whenever a creature infected with netherblight finishes a long rest, it makes a DC 17 Charisma saving throw . On a failure, it gains a randomly determined malady as per Table: Netherblight.  If this would result in an effect the creature already suffers from, the victim’s malady does not worsen but it has disadvantage on its next saving throw against the disease.

Only powerful magic (such as a wish spell), a divine miracle, or the completion of a quest determined by the Narrator can cure a creature afflicted with netherblight.

Table: Netherblight (1d6)

  1. The creature’s voice becomes flat and lifeless, and it has disadvantage on Deception and Persuasion checks made to influence living creatures.
  2. The creature’s zest for life fades, and it becomes unable to gain inspiration or benefit from Bardic Inspiration.
  3. The creature’s type changes to undead. At the Narrator’s discretion, mindless undead (such as skeletons or zombies) may ignore the creature’s presence.
  4. The gods themselves shun the creature. Whenever a spell or magical effect would restore the creature’s hit points, the creature regains only half the hit points it would have normally regained.
  5. The creature’s grip on life becomes tenuous and it has disadvantage on death saving throws.
  6. Death calls for the creature’s return. The creature gains the doomed condition, dying at a time determined by the Narrator. A spell of 7th-level or higher (such as resurrection) can remove the doomed condition but does not cure the disease.

Pastrasite (Tier 3)

This chrono-active parasite is native to Limbo, a result of the ever-shifting environment in which even time is malleable. Unfortunately pastrasites are drawn to the Material Plane where the rigid temporal structure of past, present, and future provides an excellent foundation to cling to, akin to a caterpillar climbing up and down a tree’s bark. They are usually contracted in places of historical significance where they exist in a dormant state around the time of the event itself, looking into the future in search of visitors who have an especially interesting past—adventurers. 

There’s no certainty as to what a pastrasite looks like as they can only be detected by their symptoms. They never come in contact with the infected creature itself, instead consuming the creature’s background, subsiding on the temporal backlash that results when the timeline snaps back.

When an adventurer enters an area with pastrasites they make a DC 15 Charisma saving throw as their psyche instinctively tries to maintain their personal timeline. 

On a success, the pastrasite immediately retreats, choosing another adventurer to infect until there are none at which point it can no longer maintain its temporal existence, disappearing and leaving behind a strong sense of imminence within its would-be victims. For the next several hours the adventurers have advantage on Intelligence checks made to recall information.

On a failure, the adventurer becomes infected and the pastrasite immediately destroys several years of their past. The infected adventurer loses its background and gains a randomly determined background. This new background is now—and always has been—the adventurer’s past. The adventurer is vaguely aware of what happened with blurred recollection of things being somehow different than before becoming infected. Only spells that contact other planes can reveal information from the infected adventurer’s previous timeline. Most facts change as little as possible to remain consistent with the infected adventurer’s new past, but some friction remains. Whenever an inconsistency between the old and new timelines is first spoken of in front of the infected adventurer, it takes 10 (3d6) psychic damage. 

The new timeline gradually settles, and the true past can only be restored through powerful magic such as wish. Once a pastrasite has altered an adventurer’s timeline, although its effects remain the adventurer recovers from the disease. Spells like remove disease or features like a herald’s Lay on Hands have no effect on pastrasites.

Rotter Plague (Tier 1)

Some zombies are creations of magic but others are the spawn of an affliction known as rotter plague. Whether this disease developed naturally or is the result of some mad necromancer’s experiment is unknown.

Zombies infected with rotter plague hunger for living flesh. A rotter zombie has a Speed of 35 feet, advantage on initiative checks, and gain the following attack:

 Bite. Melee Weapon Attack: +3 to hit, reach 5 ft., one target. Hit: 3 (1d4+1) piercing damage. If the target is a living creature, it makes a Constitution saving throw (DC 10 + the damage dealt) or it becomes infected with rotter plague.

A living creature infected with rotter plague suffers no negative effects from the disease and cannot transmit it unless it dies. An infected creature that dies rises as a rotter zombie after 1 minute. Sprinkling the creature’s corpse with holy water or dealing it at least 1 damage prevents this transformation. A gentle repose spell cast on the body also prevents it from rising as a rotter zombie for the spell’s duration.

Lesser restoration cures rotter plague. Casting lesser restoration on an infected zombie removes its ability to transmit rotter plague but has no other effect.

Scree Scale (Tier 2)

Prolonged exposure to the Elemental Plane of Earth sometimes results in the extraplanar malady known as scree scale. Though slow acting, an untreated case of scree scale can be debilitating.

A beast or humanoid exposed to scree scale makes a DC 15 Constitution saving throw or it becomes infected. After 1d10 days, an infected creature’s skin develops pebble-like growths that spread for as long as the disease persists. Every 1d10 days, the infected creature repeats the saving throw, curing itself of the disease after three successful saves. A lesser restoration spell also cures the disease.

An infected creature that fails the saving throw three times before the disease ends becomes a creature of living stone. In this form, the creature’s type changes to elemental, and it gains resistance to bludgeoning, piercing, and slashing damage from nonmagical weapons that aren’t adamantine. Once scree scale has progressed to this stage, only greater restoration or more powerful magic can reverse the effect.

A creature of living stone repeats the saving throw every 1d10 days. On a failure, the creature becomes petrified until the disease is cured. If the infected creature makes three successful saving throws before becoming petrified , the disease’s progression halts and it remains in its living stone form until cured.

Sewer Plague (Tier 1)

Unsanitary conditions give rise to all manner of pestilence generically referred to as sewer plague. Contact with rotting waste or stagnant water can transmit sewer plague, as can the bites of rats and other creatures that live amid such filth.

A humanoid exposed to sewer plague makes a DC 11 Constitution saving throw or it becomes infected. After 1d4 days, an infected creature experiences cramps and exhaustion. The creature suffers 1 level of fatigue, it recovers only half the normal amount of hit points when spending Hit Dice, and it regains no hit points upon completing a long rest.

An infected creature repeats the saving throw whenever it finishes a long rest . On a failure, it suffers an additional level of fatigue . On a success, the creature instead recovers from 1 level of fatigue. The creature is cured of this disease when it has no levels of fatigue.

Sight Rot (Tier 1)

A beast or humanoid that drinks water tainted with sight rot makes a DC 15 Constitution saving throw or it becomes infected. After 24 hours, an infected creature’s vision begins to blur, imposing a –1 penalty to attack rolls and sight-based ability checks. Each time the creature finishes a long rest, the penalty worsens by 1. Once the penalty reaches –5, the creature is blind for as long as it remains diseased.

A lesser restoration spell or similar magic cures sight rot, as does the application of an ointment extracted from eyebright (a rare flower found in some swamps). An hour of work with a single eyebright flower and a DC 14 herbalism kit check produces one dose of the ointment. Applying the ointment to an infected creature’s eyes during a long rest prevents the disease from worsening, and three applications of the ointment cures sight rot.

Spectral Thought-Worms (Tier 4)

Spectral thought-worms are tiny parasitic creatures native to the Astral Plane. Their prefered habitat is a conscious mind where they subside on thoughts and ideals. When a creature interacts with the Astral Plane (via the astral projection spell or magic item mishaps) without the protection of a mind blank spell, or when it suffers prolonged exposure to the less stable areas of the Astral Plane’s wild energies, roll 1d20. On a result equal to or less than its level (or CR), it may become afflicted with this disease. Spectral thought-worms can also be carried along a detect thoughts spell, telepathic connections, and similar effects. A creature exposed to a spectral thought-worm or an infected creature’s mind makes a DC 16 Charisma saving throw or it becomes infected. 

In 1d4 days the spectral thought-worm’s symptoms manifest in an infected creature. The parasite infestation spreads and they eat the infected creature’s psyche, creating a mental space into which they lay eggs. An infected creature has its memories altered (as the modify memory spell with no save), completely forgetting the events within 1d4 hours before and 1d4 hours after its affliction.

When an infected creature finishes a long rest , it repeats the saving throw. 

On a success, the infected creature’s mind fights against the spectral thought-worms and in the resulting struggle its memory is altered, forgetting the events within the last 2d4 hours. 

On a failure, the worm clears enough space to lay eggs that hatch in 1d4 days. These start eating the infected creature’s personality, reducing its Charisma by 1 at the end of each long rest. When an infected creature’s Charisma score is reduced to 0 and it dies, the spectral thought-worms escape to the Astral Plane through the tiny planar opening created by the departing soul.

Spectral thought-worms are susceptible to psychic damage (thus their penchant to hide within minds as a shield against astral energies). When an infected creature is targeted by lesser restoration, or takes psychic damage equal to or more than its Charisma score, the parasite goes dormant for 1 week. A dormant spectral thought-worm is destroyed when the infected creature takes psychic damage equal to or more than its Charisma score. Upon destruction a spectral thought-worm dissolves into stray thoughts that are expelled throughout the next day as semi-insightful sayings that float through the creature’s mind.

Troll Pox (Tier 2)

This virulent disease originated in trolls but has since spread to other creatures. Troll pox manifests as an outbreak of boils that are rapidly replaced by tumorous growths.

Whenever a creature infected with troll pox takes bludgeoning, piercing, or slashing damage, each living creature within 5 feet of it makes a DC 17 Constitution saving throw or becomes infected. After 1d4 hours, an infected creature’s skin erupts with boils.

Though unpleasant, the initial stage of troll pox is harmless to the victim. However, each time the creature finishes a long rest, it repeats the saving throw. On a failure, the boils burst to reveal a host of fast-growing tumors. The creature’s hit point maximum is reduced by 5 (1d10). Each time the creature fails the Constitution saving throw , its hit point maximum is reduced by an additional 5 (1d10) points. The target dies if this effect reduces its hit point maximum to 0.

In addition, the creature gains the following trait:

Regeneration. The creature regains 10 hit points at the start of its turn. If the creature takes acid or fire damage, this trait doesn’t function at the start of its next turn. The creature dies only if it starts its turn with 0 hit points and doesn’t regenerate.

Infected creatures can live with troll pox for extended periods, but they never recover naturally. Only a greater restoration spell or similar magic can cure the disease.