Why is Leptospirosis so rare?

[Isaacson]

I'm curious as to why Leptospirosis is so rare in the UK (under 70 cases a year). It's physiology and mode of transmission do not seem to provide an explanation. It's survival in the environment would imply that any wet surface, puddle or patch of mud that has been visited by any rodent at any time in the past few weeks has at about a 40% chance of being contaminated (using the upper estimate of prevalence in the rodent population). In farmyards and dense urban areas this could well be just about every puddle, patch of mud etc.. The case studies would seem to suggest that low doses are infectious (urine diluted by an entire lakeful of water in America, a single hedgehog polluting a water fountain in Italy). Case studies also suggest that such doses do not require any immune suppression or physiological weakness to be infectious (an Olympic athlete having succumbed in Britain recently). I imagine how many times children living on a farm might fall over in a muddy puddle and graze their hands, how many farmers and land worker must forget, or not bother to wash their hands when they should?

It seems to compare to something like Norovirus; a large carrier population (humans/rats), lots of contact opportunities (public surfaces/muddy puddles), high environmental survival rates (12 days/several weeks), and low infectious dose. Yet the difference between them in terms of epidemiology is 4-5 orders of magnitude (several hundred thousand/<40).

Can anyone explain what it is about Leptospira which explains the extremely rare and sporadic nature of cases in the UK?

[StringJunky]

Did a bit of reading. Leptospira is fragile to dry heat and being frozen, slow-growing and needs to pass through the mucus membrane or cuts. Thinking about puddles; how long does one last usually? A few days at most. A rat's got to pee in it and someone has to fall in it with a break in their skin when the bacteria population has sufficient infectious potential (our climate is generally cool) and all this before the puddle dries out.

 

I think it's a combination of the bacteria's relatively fragile traits, slow growth and the weather conditions in the UK.

 

This was one of my sources: Leptospira as an emerging pathogen: a review of its biology, pathogenesis and host immune responses

Edited August 15, 2016 by StringJunky

[Isaacson]

That seems to be what most authors suggest, I just can't quite see it.

 

Take a farm for example. Leptospira can live in mud or water for weeks, on a farm you can be pretty sure a rat's been almost everywhere at some time over the last few weeks and rats are incontinent, so it's definitely urinated on that surface, in winter everything can stay wet for days. About 40% of rats have leptospires and about 10% of cases are severe enough to need hospital treatment. That should mean that everyone who has any contact with any wet surface that a rat has visited at any point in that past few weeks should have an 4% (40%x10%) chance not just of contracting Leptospirosis, but of contracting a version serious enough to require hospitalization. Even if we were to take a very conservative estimate that only 10% of the 500,000 people employed on farms in the UK ever found themselves in this situation, we should see 2,000 severe case a year, instead we see fewer than 10, nearly half of which are contracted abroad.

 

I can't seem to get around that fact that actual incidence is several thousand times less than the published risk factors would appear to suggest.

Edited August 15, 2016 by Isaacson

[sethoflagos]

That seems to be what most authors suggest, I just can't quite see it.

 

Take a farm for example. Leptospira can live in mud or water for weeks,....

Is this typically true for the UK?

 

Examples of European outbreaks quoted by Wasiński B, Dutkiewicz J (2013). "Leptospirosis—current risk factors connected with human activity and the environment".Ann Agric Environ Med. 20) seem to correlate with periods of continuous high temperature (>18 C) coupled with high rainfall. This is situation normal for the tropics but not for the UK, If a cool night is enough to kill off any bacterium not kept warm by a mammalian body, then standing water is not going to remain infective for very long.

[John Cuthber]

Rats and people have immune systems that are fairly good at destroying bacteria.

[dimreepr]

Sorry for this wanton display of flippancy; "why is leptospirosis so rare?" because it doesn't happen very often ...

[CharonY]

There are many aspects that determine how likely/effective the spread of bacterial infections are. These include whether they can replicate outside the host (Leptospira) can't. How effective they are at establishing infections, the infectious dose, and modes of host to host transfer. Since it is mostly zoonotic transfer is rarer and regular hygiene is often sufficient to avoid infection. Norovirus can be transmitted by being close to a human and can lead to rapid spread (and detection). Likewise leptospirosis can also be underreported as the non-severe cases may be confused with other infections.

[John Cuthber]

Wiki tells me that "Noroviruses are transmitted directly from person to person (62–84% of all reported outbreaks)^[17] and indirectly via contaminated water and food. They are extremely contagious, and fewer than twenty virus particles can cause an infection^[2] (some research suggests as few as five).^[9] "

 

and

"The norovirus can survive for long periods outside a human host depending on the surface and temperature conditions: it can stay for weeks on hard surfaces,^[57] and up to twelve days on contaminated fabrics, and it can survive for months, maybe even years in contaminated still water.^[58] A study done in 2006 found the virus still on several surfaces used for food preparation seven days after contamination.^[59]"

Those factors will help it enormously. Also sever vomiting and diarrhoea will increase the probability of human to human transfer

 

However, I have a recollection of hearing somewhere that about 20% of the human population are substantially immune to it.

(that might be what this bit means)

"A non-functional fucosyltransferase FUT2 provides high protection from the most common norovirus GII.4.^[65]Functional FUT2 fucosyltransferase transfers a fucose sugar to the end of the Histo-blood group ABO(H) precursor in gastrointestinal cells and saliva glands. The ABH antigen produced is thought to act as receptors for human norovirus. Homozygous carriers of any nonsense mutation in the FUT2 gene are called non-secretors, as no ABH antigen is produced. Approximately 20% of Caucasians are non-secretors due to the G428A and C571T nonsense mutations in FUT2 and therefore have strong although not absolute protection from the norovirus GII.4.^[66] Non-secretors can still produce ABH antigens in erythrocytes, as the precursor is formed by FUT1.^[67] Some norovirus genotypes (GI.3) can infect non-secretors.^[68]"
Which led me to this interesting snippet

"Robust fucosyltransferase activity discourages bacterial adherence in the urethra of women.[3]

This is also mediated by the presence of few bacterial adhesion sites in the bladder and urethra.

Women with these receptors who do not have mucosal secretion of the fucosyltransferase enzyme

to help block bacterial adherence are more likely to have colonization of E coli and other coliforms

from the rectum and less likely to have lactobacilli in the periurethral area, resulting in frequent episodes of cystitis.[4]"

So it appears that women who are immune to Norovirus are susceptible to UTI and vice versa.

This, in turn suggests that, if there's a God, he has a strange sense of humour.

[Isaacson]

Is this typically true for the UK?

 

Examples of European outbreaks quoted by Wasiński B, Dutkiewicz J (2013). "Leptospirosis—current risk factors connected with human activity and the environment".Ann Agric Environ Med. 20) seem to correlate with periods of continuous high temperature (>18 C) coupled with high rainfall. This is situation normal for the tropics but not for the UK, If a cool night is enough to kill off any bacterium not kept warm by a mammalian body, then standing water is not going to remain infective for very long.

This is part of the aspect which puzzles me. The disease is so much more prevalent in the tropics which would correlate with the case studies you mention. The problem is, nowhere in the literature can I find any reference to Leptospires being unable to survive below a certain temperature. The pathogen safety sheets only mention inactivation above 50C no lower limit.

 

A low tolerance of low temperatures would certainly explain literally all of the anomalies I've found, but it just doesn't seem to have any physiological evidence that I can find.

[StringJunky]

This is part of the aspect which puzzles me. The disease is so much more prevalent in the tropics which would correlate with the case studies you mention. The problem is, nowhere in the literature can I find any reference to Leptospires being unable to survive below a certain temperature. The pathogen safety sheets only mention inactivation above 50C no lower limit.

 

A low tolerance of low temperatures would certainly explain literally all of the anomalies I've found, but it just doesn't seem to have any physiological evidence that I can find.

I think you are looking for a single decisive factor but it seems their relative rarity in the UK is the result of a multiplicity of inhibiting factors.

 

Here's a few, most alreay mentioned, and I'm sure there are quite a few more:

 

- Temperatures generally low for rampant Leptospira activity

- Average UK hygiene is better

- Wide humidity range - Can’t tolerate arid conditions

- Can’t replicate outside of the host

- Average human proximity to rat-infested areas is less

Edited August 16, 2016 by StringJunky

[Isaacson]

We seem to have got caught up in a discussion about the UK's climate, hygiene etc., which is not really the query I had. What I'm asking about are the physiological factors. I thought of an example which will eliminate all the other factors and I would be curious to see if anyone could answer.

 

Rodents getting into the cold water tank is a problem described by various plumbing books as "frequent" and "quite common" (I can reference if you like but I thought that could be taken for granted). People, wash, bathe, brush teeth and occasionally drink this water. The incidence of Leptospirosis from unknown sources in the UK is fewer than ten (eliminating foreign travel, water-sports and occupational exposure). So the question is, how do we get from a "quite common" situation which provides direct water-bourne exposure to rodents, in a country of 70,000,000, to fewer than ten (if any) case of Leptospirosis?

 

No issues of climate, hygiene, contact, flooding events, aridity or any previously mentioned factor plays a part here. I've found two studies cultivating Leptospires in tap-water, so it doesn't seem to be the chlorine (though it's still a possibility I suppose, if those studies were flawed in some way).

 

Any ideas?

Edited August 19, 2016 by Isaacson

[sethoflagos]

I've found two studies cultivating Leptospires in tap-water, so it doesn't seem to be the chlorine (though it's still a possibility I suppose, if those studies were flawed in some way).

 

Any ideas?

 

What temperature of tap water were the Leptospires cultivated in? The 10 degrees C typical of British mains water supply?

 

BS 6700 Legionella rules prescribe a maximum 20 degrees for any cold potable water system, and householders will tend to object anyway if its much warmer than 10 degrees.

[Isaacson]

 

What temperature of tap water were the Leptospires cultivated in? The 10 degrees C typical of British mains water supply?

 

BS 6700 Legionella rules prescribe a maximum 20 degrees for any cold potable water system, and householders will tend to object anyway if its much warmer than 10 degrees.

 

You may be on to something, both experiments were at room temperature, quoted as 27-30C in one paper (quite hot for room temperature I thought). Would it make a difference to how the chlorine works, or just the organism itself?

[sethoflagos]

 

You may be on to something, both experiments were at room temperature, quoted as 27-30C in one paper (quite hot for room temperature I thought). Would it make a difference to how the chlorine works, or just the organism itself?

 

Did they measure free chlorine levels? My own experience of water disinfection is mainly with hypochlorite and chlorine dioxide systems, and they were certainly active in the more elevated temperature associated with process water systems in the paper industry (where I served my apprenticeship). AFAIK UK water companies tend to run around 1 mg/l active chlorine.

 

Separating the chlorination effect from the temperature sensitivity of the organism would probably require a decent research grant. My impression is that these are in short supply for tropical diseases lacking obvious military potential.