Day 6: lepto, bucella, anthrax, scrub typhus

Today’s lectures started with a breakdown of leptospirosis, I think the take away message is that this can look like a vasculitis (in a sense it is – invading endothelial cells), much like Rickettsia diseases. It can enter the body through mucosa, skin cuts/abrasions and the organism has burrowing motility. Just about any organ is fair game – liver, CNS, kidneys, and lungs.

The organism is often transmitted from rodents, and can stay in rat kidneys for years. The bacteria can survive in fresh water and soil for many weeks, especially with neutral or alkaline pH, thus people at risk are sewage workers, people that work on rice farms, soldiers, people going rafting, and triathalon-ers.

Rodents are the reservoir but there are over 150 animal reservoirs including cattle, pigs, and dogs. Thus it being labelled as the champion of zoonoses.

The study above was done in India at several hospitals, the above are a list of undifferentiated fever of people presenting, notice leptospirosis was 5^th on the list!

The seroprevalence is up to 15-20% in some areas, and increase rates of disease are associated with flooding (Philippines in 2009)

Given the severity of illness, and patients with jaundice with renal failure, it previously was confused with yellow fever. During one of the clinical rounds, it was discussed how often they have an elevated bilirubin, but not associated high level enzymes – relating to a canniculitis (inflammation of bile canniculi in the liver). It has many different presentations (aspetic mengingitis, weil’s disease; thrombocytopenia, jaundice, renal failure, and pulmonary hemorrhage) it can often be confused with other diseases.

One interesting feature some of the experienced physicians had noticed, which is calf pain, that can be very severe. This in addition to conjunctival suffusion can be tip offs to think about leptospirosis. It should be mentioned that many patients may just have a flu like illness that resolves on its own.

Also, it is though that an out protein effects the ascending limb in the loop of henle (the same channel lasix works on) in the kidneys initially causing hypokalemia. Most cases will have low WBC count, similar to most rickettsial disease however interestingly SCRUB typhus often has a high WBC count. CK elevation is a relatively common feature in severe disease as well.

In terms of diagnosing, the Microagglutination test is the best test, but often IgM ELISA is employed.

Treatment: penicillin, ceftriaxone, doxycycline and azithromycin can be used. However given that initially presentation can look very similar to scrub typhus, empiric doxycycline would probably be reasonable while patient is getting worked. Generally thought to be effective if giving early in the course.  A study in Thailand showed equivalence of azithromycin for 3 days equivalent to doxycycline for 7 days.

A vaccine is available for animals, but issues with this relates to the >250 serovars. Weekly prophylaxis with doxycycline can be done in people at high risk in endemic areas (people going rafting), a study from 1984 showed effectiveness of this in US troops in Panama jungle.

ANTRHAX:

We were given a brief talk on anthrax, 90% being cutaneous which presents as a painless ulcer (edema factor from the bacteria). I think of think of this in contrast to Y. pestis which gives a painful ulcer. Initially it starts as a papule to vesicle – to ulcer and to an eschar. Mortality of this with effective therapy is very low, but up to 20% without therapy.

Other forms are GI (eating uncooked meat), pulmonary (inhalation of spores), and meningitis (dissemination from other causes). The issue with anthrax is that spores can be quite resistant and can hang around for a long time.

Pulmonary anthrax may appear as influenza, and can be hard to distinguish, uptodate suggests they are sicker, but classically have a CXR with mediastinal widening +/- pleural effusions.

Treatment: generally patients are given

If patient’s have are at risk of inhalational anthrax, PEP is usually given for 60 days (as spores are resistant). PEP with doxy or Cipro are given to non-pregnant people. Cipro for pregnant women, and doxycycline for children. The organisms is typically susceptible to many antibiotics, but NOT cephalosporins and septra. A vaccine is recommended by CDC for exposure to inhalation anthrax.

Post exposures:

Cutaneous exposure? i.e. handling an infected hide, only monitoring

GI exposure? Eating meet from an animal found to be infected with anthrax? PEP for 7 to 14 days recommended.

Bioterrorism exposure (aerosolized), 60 days of PEP

Anthrax is NOT contagious, although there have been reports regarding cutaneous anthrax.

The second talk was on brucellosis, a patient presenting with chronic fever, SI joint involvement found to be blood cultures positive with brucellosis. Three main organisms infecting humans. B. melitensis, B. suis, and B. abortus

It is small, coccobacilli and is intracellular.

Infection in humans is typical of ingesting unpasteurized milk, lassi, or cheeses. The products of abortion/placentae from an infected animal are highly infections and farmers and vets can get infected by aersol transmission. There have been reports form breast milk, sexual transmission, and rarely blood products.

Features include prolonged fever, undulating fever followed by afebrile period may occur. A typical feature that may different prolonged fever is focal MSK symptoms, often difficulty waking. Studies have suggested that different species can cause variable symptoms, (peripheral arthritis vs spine involvement).

Diagnosing it can be a challenge, typical blood cultures are held for ~5 days, this can take longer to grow and so it is important to warn the lab that you are suspecting this also because it can infect lab workers via aersolization. A bone marrow culture often has higher yield than 3 sets of blood cultures, and useful when working up a fever of unknown origin especially when antibiotics have been given.

If joints that are suspicious of being infected are tapped, lab should also be made aware of possible brucellosis.

Labs still employ standard agglutination test (SAT), which often may demonstrate prozone phenomenon and need to be further diluted. Brucella antigen supplied with the kit is added to successive dilutions of patients serum, cut-off may vary from those from an endemic place vs traveller.

Treatment: three things to consider

1.     Acute (<1 month) vs relapsing/chronic (>6 months)

2.     Is there focal disease of bone or joints?

3.     Has TB been definitely excluded?

Acute non-focal disease requires 6 weeks, chronic/focal disease requires 3 months.

Treat typically with doxycycline 100 mg BID for full duration, with 2 weeks of gent (vs streptomycin).

For severe infections (meningitis, endocarditis, severe spine disease), triple therapy – doxy, aminoglycoside and rifampicin is typically used.

Scrub typhus:

Dr. Varghese gave us a lecture on scrub typhus (orentsia tsutsugamushi). Interestingly we had seen a 40 year old female admitted with this, with fever for 10 days, myalgias, and an eschar on her chest. Her labs had shown elevated liver enzymes, bilirubin, thrombocytopenia and leukocytosis – all which is characteristic.  One feature of the labs which seems unique to me is elevated WBC count where in many rickettsia infections you will have leukopenia.  Incubation is 1-3 weeks.

Historically, this killed many people during world war II, and currently 55% of the world’s population is at risk.

It is mainly located in what has been termed the tsutsugamushi triangle

It extends from northern Japan, Korea, and far-eastern Russia in the North, to northern Australia in the South and to Pakistan and Afghanistan in the West, as well as the islands of the western Pacific and Indian Oceans, including Taiwan, Philippines, New Guinea, Indonesia, and Sri Lanka.

This is transmitted by a mite, called a chigger at the larval stage. Different from other similar diseases, it is only the larval stage that transmits this and it ONLY takes one blood meal its entire life, which means the mite gets the infection from its mother and can then pass it to humans.  The size of these larva are extremely small, so it is unlikely to be noticed, but still worthwhile checking if in an endemic area.

Bites occur around the ankles, crotch, groin, behind the knees and armpits. The mechanism of feeding is it ingesting enzymes to digest. Once it migrates to an optimal area, it inserts its feeding structure into the skin and injects enzymes that destroy tissue, the chigger larvae then feeds on the destroyed tissue, this results in a very puritic lesion. The feeding process can last from 2 to 10 days for infected mites (when studied in a lab). It is believed that >6 hours is needed to transmit the bacterium.

 The organisms doesn't actually go into our bodies, hence often termed an ectoparasite.

Only the larva (6 legs) can infect humans, they take one bite in there lifetime.

 the larva typically only seen with a magnifying glass.

Infections occur typically between August to Feb, having bush or shrubs at home, city parks, and in the vicinity of riverside or mountain areas.

Like rickettsia disease, it as a vasculitis, infected endothelium, and can infect a large variety of organs, including causing ARDS, liver failure, renal failure, etc.

Treatment: doxycycline, as mentioned previously, a treatment for many rickettsia diseases in addition to leptospirosis. 

I have come across some recommendations for individuals at risk to receive prophylactic doxycycline in high endemic areas.