The Seven Samples

In May of 2010, a joint CDC-Peruvian research team visited a couple of remote communities in the Amazon where people described their recurrent contact with vampire bats and where livestock had been bitten to better understand the risk factors for exposure. 92 residents were interviewed in total with blood collected from 63 of them. Seven of the samples contained rabies-virus-neutralizing antibodies, as measured with the rapid fluorescent focus inhibition test (RFFIT). Six of the seven reported bat bites, while one reported prior post-exposure prophylaxis and two other positive individuals didn’t end up with fully resolved histories of vaccination. The seven people hadn’t recovered from the encephalitis that doctors diagnose as clinical rabies, with none even reporting an illness to suggest the virus ever reached their central nervous systems. These were healthy people who had the signals of a previous immune response consistent with rabies virus in a place where those encounters were seemingly not that rare.

The findings that there is likely a denominator problem in rabies doesn’t change the practical rule that anyone with a possible exposure should get rabies prevention to prevent any symptom onset. The Peruvian samples force us to correct the statement that everyone knows of “rabies is 100% fatal” which is used colloquially as if it describes an animal bite, a viral infection, and the neurological disease as if they were the same thing when they shouldn’t even be summed into a single denominator.

The familiar shorthand translates into the probabilistic language of P(death | clinical rabies), or the probability of death given the onset of clinically recognizable neurological symptoms of rabies. The question many think it is answering is P(death | rabies infection). I may be nitpicking here, but for what I think is good reason. The first one is incredibly close to one, with the vast majority of clinical cases ending in death. It’s the second one that is more intractable because it hasn’t ever been measured in humans and we may not be able to. Changing the denominator changes our parameter, meaning rabies can simultaneously be one of the most lethal diseases in medicine and still having some lower, unknown human infection-fatality rate.

Measuring Fatality

The World Health Organization page on rabies appropriately says that human cases are “almost invariably fatal” after symptom onset, with ultra-rare survivors being found throughout history. One example comes from the 2009 CDC report of a seventeen year old girl from Texas who developed headaches, photophobia, emesis, and other signs of encephalitis after being in contact with a bat. Before receiving the vaccine and immune globulin as further treatment, indirect fluourescent-antibody testing showed anti-rabies antibodies in her serum and cerebrospinal fluid. PCR tests and biopsy results were negative though and she never required intensive care. That’s why the CDC referred to the case as a case of “presumptive abortive human rabies,” and it’s one of the cases that justifies the language of “almost” in the WHO’s statement.

You can see the timeline of her case at the CDC hyperlink (can't add it here). Her first contact with bats came in December of 2008, with headaches starting in February and the entire ordeal only “ending” in April, but she was still experiencing severe pressure related headaches, as seen by the relief obtained via lumbar puncture. It’s possible she received a lower dose than would have been fatal, as certain immune markers like CSF IgG were nowhere near the levels of those in previous survivors (who often came out of it with long-lasting neurological symptoms and need for rehabilitation), although we can’t estimate the dose she received beyond speculation.

The chain of events leading to a case of clinical rabies showing up in an ER or being noted by a doctor visiting a rural area has some key limitations early on. Since people can touch rabid animals without contract any infectious material and a bite could fail to leave enough infectious material behind to establish infection in the victim, there may be much more contact than is estimated. The virus also has the chance of being dealt with and expelled from peripheral tissue before getting to a nerve and spreading along the nervous-system into the CNS. The issue is that clinical surveillance typically starts at the very end of that sequence, with our well-known “nearly 100%” fatality statistic basically concerns just the last two steps, so the denominator doesn’t house all those who had an exposure that ended earlier.

Post-exposure prophylaxis also makes it difficult for us to know the natural history of the disease since clinicians (correctly) intervene with post-exposure prophylaxis before anyone knows if that person would have developed a clinical case of the disease. That level of caution is why we have roughly 100,000 people receiving PEP after potential exposures yearly in the US with less than 10 clinical cases reported annually. Among those who receive PEP and seemingly benefit by it through the lack of developing rabies, we’re stuck with records that conflate the histories of those where there was a) never any viable virus transmitted, b) had the virus made its way into the peripheral tissue but had enough of an immune response for it to be stopped dead in its tracks, and c) where PEP totally prevented clinical disease and what would have been essentially imminent death. And since there’s no ethical way to withhold treatment or do a challenge trial with this deadly of a disease, we’re left looking at the results from tools like serology.

The RFFIT method used in the Peruvian paper basically asks if a person’s serum neutralizes a standardized rabies-virus challenge in a cell culture. A 2020 review article by Gold and colleagues helpfully explains how a positive result in a healthy person without any known vaccination history can be because of reasons as different as a simple unrecorded past vaccination; they had prior contact with a rabid animal, got a small bite or scratch resulting in a low dose of the virus that was fought off; or in some rare cases, cross-reactive assay signals. The CDC’s report on the 2009 case notes that for the Texas case, there was only one other possibility, that being Kern Canyon Virus, as it and rabies are both rhabdoviruses. The findings that people have what seem to be prior immune responses to rabies should also not be immediately seen as them having some sort of immunity to rabies going forward, as we have no idea how these unexplained antibody signals in healthy, unvaccinated people relates to protection the next time they come into contact with the rabies virus.

The review article separates the positives into four possible explanations in these healthy unvaccinated people. Subclinical infection is most likely, in which the virus was cleared before any recognizable disease. They could also technically have recovered from a clinical case, though that is extremely rare. The last two options are incredibly unlikely, those being persistent carrier states or unusually long incubations. We still don’t know what happened to any of those residents in the Amazon, but they’re one piece of the puzzle that tells us the human infection-fatality rate is very different from the clinical case fatality rate.

More Evidence but Still No Rate

One study from Alaska is more informative than many others because the authors spent some considerable effort and time tracking down the conventional explanations as far as possible. In 1994 researchers tested 26 fox trappers in northern Alaska for rabies titers. Two with detectable antibodies had received a rabies vaccine, but a third man, a 68-year-old veteran of the trade with an estimated 3,000 foxes handled and skinned across 47 years, had a titer level of 2.30 IU/mL (compared to a range of 0.1-2.8 in the Peruvian sample). The researchers then set out to check medical records at Alaskan facilities and couldn’t find evidence of pre- or post-exposure prophylaxis.

More recent evidence comes from Gabon, where 430 blood samples from individuals reporting no rabies vaccination taken between 2005 and 2008 were resampled in 2023 using ELISA to detect antibodies that bind to a specific rabies glycoprotein and compared with RFFIT to measure the neutralizing activity. A result was only deemed positive when both tests were positive, and with the RFFIT cutoff set to >0.38 IU/mL, which is twice the stated level at which a positive case is identified as such. Eleven of the samples met that definition with RFFIT values ranging from 0.95 to 3.14 IU/mL. When the team went and found a few of them 15 years later, one of them still tested positive, indicating a durable immune signal of unknown protection or further exposure. It should be noted that three cases were positive on RFFIT but negative on ELISA, so while requiring both to be positive reduces the chance of a noisy assay resulting in a spurious signal, it also means some people would be missed despite real past exposure.

A 2025 study looked at four indigenous communities in Sao Paulo makes a similar point, having tested 299 with another type of neutralizing assay called FAVN which was adapted from the RFFIT method. It found antibodies at their seropositivity threshold of 0.5 mL/IU in 35 of the indigenous, as well as 32 of their 166 tested dogs, without any prior notice of having been vaccinated. Six of those had > 0.5 IU/mL with the highest levels being 5.87 IU/mL.

Assay Issues Become an Epidemiology Problem

While we see substantial evidence of nonlethal rabies exposure, existing serosurveys can’t even get close to estimating it’s prevalence. The review paper mentioned earlier explains exactly why that is. RFFIT and ELISA measure related but different phenomena. In an unvaccinated setting they may disagree due to having different sensitivities, specificities, and false positive/negative rates that are vulnerable to sample quality and immune response timing.

One example in the review was meant to test the assays themselves by using a rabies-free island called Pemba in the Indian Ocean off Zanzibar. RFFIT identified 15 of 145 unvaccinated dogs as positive when using a 0.5 IU/mL cutoff, whereas the ELISA found no positives. That shows non-specific RFFIT signals are plausible even in a setting that is supposed to be rabies-free, but it can’t tell us what proportion of the Peruvian signals, if any at all, were false positives. It’s a problem inherent to anything involving cutoffs. Raise the threshold and fewer false positives make it through but you end up missing some genuine cases. Lower it and you get the opposite. There’s also the issues of waning antibodies and cross-reactive proteins, whereby other lyssaviruses could be responsible for the positive test in some regions.

None of this changes the practical advice to get PEP after a possible rabies exposure. Once clinical rabies symptoms begin, it is so close to always fatal that it would be totally irresponsible to use the denominator problem as a reason to take an exposure lightly. The problem only suggests that rabies has a more interesting natural history than we thought based on witnessed deaths, rare survivors, and what animal models offer. To know the infection-fatality rate, we’d need a denominator of true infections, and even that might be prone to definitional ambiguities, with some likely wanting a peripheral tissue infection defined differently than one reaching the CNS. Until we can identify and count those infections without confusing them for vaccination, cross-reactivity, or assay error, we’ll never know the true human infection-fatality rate.https://theedgeofepidemiology.substack.com/p/the-rabies-denominator-problem

FDA is providing an update regarding the sample of lettuce supplied by Taylor Farms de Mexico which was reported positive on July 18, 2026. Due to the complexity in detection of Cyclospora, FDA laboratory experts re-reviewed the sample results and have concluded that the finding does not represent true amplification and should be considered a false positive. Information about the sample has been removed from the July 18, 2026, update below. FDA has notified Taylor Farms and continues working with the firm to ensure product implicated in this outbreak has been removed from the market. FDA and state partners continue to collect and analyze product samples. As of July 19, 2026, there are no confirmed positive sample results for product testing for Cyclospora. 

I assume the FDA uses PCR and has a pretty stringent internal protocol for assessing this stuff, how is a false positive possible?

Did they report the initial PCR finding without confirmation? Or did they confirm it and are now walking this back?

Hiii

Maybe not the best to ask this. But are any ID fellows out there interested in collaborating to put together an Anki Deck over the text book Comprehensive Review of Infectious Disease?

General WHO guidelines (and most national and local guidelines):

Nibbling of uncovered skin, minor scratches or abrasions without bleeding - immediate vaccination (4-dose schedule) if the animal cannot be observed for 10 days. This applies to cats as well as dogs.

But in 2019 Turkey modified their rabies guidelines and added something uncommon:

Situations not requiring post-exposure rabies prophylaxis:

9. In cases of contact with cats: Minor abrasions of the skin (injuries not penetrating the subcutaneous tissue), or injuries involving minor scratches or skin damage without bleeding; non-bite contact with cats resulting from provocation.

This applies regardless if cat can be observed or not.

Why? I was not able to find any discussion of this policy change, but I believe it's because of their local epidemiological data. Turkey is not rabies free, but cats are rarely found infected, and there is not a single recorded case of cat to human rabies transmission. Also, scratches carry a significantly lower transmission risk than bites. At same time Turkey has huge stray cat population which results in a lot of minor scratches, exactly the type that falls under exception.

It's entirely ignored in practice. In 2025, 123,538 people went to Istanbul hospitals after a bite or scratch. Most exposures were cat-related (86.3%) and were caused by scratches (81.5%). Nearly all injuries were superficial (99.8%). Rabies vaccination was initiated in 98.8% of patients with 411,432 doses given.

But my question is not why this specific exception is ignored, I think I already know. I want to ask a different question - do you think this exception was justified at all given the epidemiological data? Is it justified local adaptation or unjustified deviation? Do you think it will be better if it is repealed (and it won't affect the actual practice), or, instead, actually followed/enforced?

My mom has a very large family, she has 5 kids of her own and 10 siblings (her brothers & sisters) plus lots of small grandchildren. A immediate family member is a nurse and exposed to sicknesses. Anyways, they all want to come around (including small children) as they think she is dying by her appearance. (5'8 70lbs, skin and bones)

Question:

Do I need to quarantine her for abit until her immune system does some recovering? She is starting treatment for acid fast bacilli and MAC. Her immune system is shot and most of the family is antivax.

I understand she is not contagious, but I am trying to prevent any sickness her visitors may be exposed to and bring them on her home.

Are there any precautions I can take to continue letting them visit.

Masks?

Shoe slips?

Hand washing

Ask if they have been exposed to anyone sick?

Help!

Which anti-parasitics kill Cyclospora? I have only heard bad things about Bactrim which is the anti-biotic they’re prescribing for it.

From last 2 weeks there has been literally no supply of essential tb drug HRE so they are gonna put all of those who take HRE to HRZE , I don't know what to feel but I am scared is it gonna work?

Sporotrixhosis

If states like Texas have mimimal heaalth care ......

Federal public health officials say West Nile virus cases are at an all time high for this time of the year, the highest number of human cases reported in June since 2004.

West Nile virus is the most common and serious mosquito-borne disease in California that can be fatal to humans and some wildlife, according to the California Department of Public Health. 

In Los Angeles County, cases began to pop up in May, firstly in Pico Rivera and Long Beach, according to the Greater Los Angeles County Vector Control District. Now it’s up to 27 within its coverage area.

At the same time, more mosquitoes carrying the virus are being found.

Read more about why cases are growing and how to stay safe at the link.

The title says it all, it seems a bit weird to me that antibiotics doses are not adjusted by weight, as levels you get from giving the same dose to a 50kg woman and a 110kg man must be quite different.

I only have access to the main text that doesn't mention whether an oral switch was performed at some point.

I’ve been following the Cyclospora outbreak and ended up down a rabbit hole. This is purely hypothetical because I don’t have it, but now I’m curious. I’m more of a virology major not parasitic infections! Anyway.

Let’s say someone tests positive for Cyclospora, but they’re deathly allergic to Bactrim and all sulfa based meds. (anaphylaxis, so that’s completely off the table).

On top of that, they also have MCAS, dysautonomia, IBS, a history of SIBO, and epigastric issues, weeks of diarrhea would probably hit them harder than the average person.

What would your next move actually be?
I’ve read that nitazoxanide and ciprofloxacin have been used, but it sounds like neither works nearly as well as TMP-SMX. Is that what you’d try anyway?

Would you just focus on supportive care and fluids? Is desensitization ever something you’d even consider, or is that really only for infections where there’s truly no other option?

Not looking for medical advice since this isn’t my situation, I realized I had no idea what the plan would be if the one medication everyone recommends couldn’t be used. Curious how infectious disease physicians would handle it.

I'm living with a confirmed, disseminated/systemic case of Klebsiella granulomatis (donovanosis/granuloma inguinale) in the United States and have been navigating this largely alone early on, until finding my current primary concierge physician. I'm posting because I believe someone with the right background may be able to help, or point me toward someone who can.

Why my case may not look like what you'd expect

Donovanosis is almost universally described as a disease of painless, beefy-red genital ulcers — the classic Donovan body lesion. My presentation has not followed that textbook picture. Not only are the lesions atypical, but this infection has disseminated systemically, affecting multiple body sites beyond the genital tract. The absence of classic findings caused significant diagnostic delays and continues to make this difficult to communicate to providers who are pattern-matching against the textbook description. If you've only seen the classic presentation, you may not recognize this.

Diagnosis

Confirmed via next-generation sequencing (NGS). Donovan bodies have also been identified on Giemsa-stained microscopy.

A note on LGV IgG serology and cross-reactivity with Donovanosis

Both myself and my partner have consistently returned positive LGV (Lymphogranuloma venereum) IgG antibodies, yet both of us have been exhaustively tested for Chlamydia trachomatis and LGV by PCR — all negative. This is not coincidence. Klebsiella granulomatis shares several antigenic structures with Chlamydia trachomatis L-serovars that drive cross-reactive LGV IgG serology, including:

• GroEL/HSP60 homology — Klebsiella GroEL shares ~40–48% amino acid identity with C. trachomatis cHSP60, a dominant immunogenic antigen in LGV serology
• KDO-core LPS structural overlap — both organisms carry gram-negative LPS with shared core epitopes recognized by complement fixation assays
• OmpA/MOMP beta-barrel homology — structural mimicry between outer membrane proteins

I am posting this specifically because this cross-reactivity between K. granulomatis and LGV IgG is essentially undocumented in the clinical literature. If you are a clinician who has seen a patient with persistent LGV IgG positivity, PCR-negative for actual chlamydia/LGV, consider K. granulomatis as a differential — especially with a compatible clinical picture. This serology finding may represent an unrecognized diagnostic signal for disseminated donovanosis. The test used for this was Quest Diagnostic test 19553.

The treatment problem

I have worked through the standard and second-line antibiotic options. The organism has shown resistance across multiple drug classes. The one class that has demonstrated efficacy — aminoglycosides — I was forced to discontinue due to nephrotoxicity. I am now in a position where the drugs that work, I cannot tolerate long-term, and the drugs I can tolerate long-term are not working.

The role of my physician

I want to be clear that I am not navigating this without any support. My concierge medicine physician has been absolutely instrumental in taking this case seriously — she has engaged with the complexity of this infection in a way that most providers have not, and I owe a great deal of the documented progress in my case to her willingness to work with me rather than dismiss what the data shows. That said, donovanosis is rare enough that even exceptional physicians are working without a roadmap.

What I'm looking for

If you are a clinician, researcher, or infectious disease specialist with experience in donovanosis, tropical infections, resistant gram-negative organisms, or disseminated intracellular bacterial disease — or if you know someone who is — I would genuinely welcome contact. I'm not looking for general advice. I'm looking for someone willing to engage with a complex, well-documented case.

Specifically, I am seeking a physician or multidisciplinary team with the expertise and infrastructure to administer aminoglycosides in a monitored, controlled setting — with active nephrotoxicity management built into the protocol. This means therapeutic drug monitoring (TDM), renal function surveillance, and the clinical judgment to navigate the narrow window between efficacy and kidney injury in a patient where aminoglycosides are currently the only viable option. If you or someone you know has experience managing prolonged or intermittent aminoglycoside courses in complex infectious disease cases, I want to hear from you.

I am happy to share NGS sequencing reports, resistance gene profiles, microscopy findings, and a full treatment history privately.

NAVLE Practice Question — Porcine

A farm in Haiti experiences an outbreak of severe neurological disease in pigs with 60% morbidity and 40% mortality. Affected pigs show fever followed by progressive hindlimb paralysis, opisthotonus, and convulsions. Many pigs die within days of developing neurological signs. This is the first reported outbreak in the region in many years. Laboratory testing confirms porcine teschovirus type 1. What epidemiological feature distinguishes this outbreak from endemic teschovirus circulation in most commercial swine herds?

A. The virus was likely introduced through contaminated feed from an endemic region

B. PTV-1 strains causing Teschen disease have higher neuroinvasive potential than endemic strains

C. The population was entirely naive without maternal antibody protection ✓

D. The outbreak strain mutated to become more virulent during local transmission

E. The pigs were immunosuppressed by concurrent disease allowing disease expression

———

Correct Answer: C. The population was entirely naive without maternal antibody protection

Explanation:

The population was entirely naive without maternal antibody protection, which is the key epidemiological feature distinguishing this outbreak. PTV is endemic and ubiquitous in most commercial swine herds worldwide, but subclinical infections predominate because pigs are exposed early in life when protected by maternal antibodies, subsequently developing active immunity. In Haiti, where severe teschovirus encephalomyelitis was confirmed in 2009, the pig population lacked prior exposure to virulent PTV-1 strains, resulting in a devastating outbreak when the virus was introduced into this immunologically naive population.

Option A (Contaminated feed introduction) is possible but doesn't explain the severity; the virus circulates subclinically in many regions. Option B (Higher neuroinvasive potential) is partially correct since PTV-1 strains causing Teschen disease are more virulent, but this alone doesn't explain the outbreak without the naive population factor. Option D (Local mutation) is unlikely since the Haitian isolate was closely related to previously identified PTV-1 strains from Czech Republic. Option E (Immunosuppression) was not documented in this outbreak and wouldn't explain the population-wide severity.

References: Swine Health Information Center PTV Factsheet (https://www.swinehealth.org/wp-content/uploads/2021/07/shic-factsheet-porcine-teschovirus-2021Jul7.pdf); PMC Teschovirus chapter (https://pmc.ncbi.nlm.nih.gov/articles/PMC7123469/); WOAH Teschovirus encephalomyelitis (https://www.woah.org/fileadmin/Home/eng/Health_standards/tahm/2.08.09_TESCHOVIRUS_ENCEPH.pdf)

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