Haverhill fever
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Haverhill fever (or epidemic arthritic erythema) is a systemic illness caused by the
bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
'' Streptobacillus moniliformis'', an organism common in rats and mice. If untreated, the illness can have a mortality rate of up to 13%. Among the two types of
rat-bite fever Rat-bite fever (RBF) is an acute, febrile human illness caused by bacteria transmitted by rodents, in most cases, which is passed from rodent to human by the rodent's urine or mucous secretions. Alternative names for rat-bite fever include stre ...
, Haverhill fever caused by '' Streptobacillus moniliformis'' is most common in North America. The other type of infection caused by ''
Spirillum minus ''Spirillum minus'' is an organism associated with rat-bite fever (specifically sodoku) that has never been fully identified and was assigned to the genus ''Spirillum'' in 1887 based on morphology, although it is not a validly published name. A ...
'' is more common in Asia and is also known as Sodoku. The initial non-specific presentation of the disease and hurdles in culturing the causative microorganism are at times responsible for a delay or failure in the diagnosis of the disease. Although non-specific in nature, initial symptoms like relapsing fever, rash and migratory polyarthralgia are the most common symptoms of epidemic arthritic erythema. Bites and scratches from rodents carrying the bacteria are generally responsible for the affliction. However, the disease can be spread even without physical lacerations by rodents. In fact, the disease was first recognized from a milk-associated outbreak which occurred in
Haverhill, Massachusetts Haverhill ( ) is a city in Essex County, Massachusetts, United States. Haverhill is located 35 miles north of Boston on the New Hampshire border and about 17 miles from the Atlantic Ocean. The population was 67,787 at the 2020 United States Cen ...
in January, 1926. The organism ''S. moniliformis'' was isolated from the patients and epidemiologically, consumption of milk from one particular dairy was implicated in association with the infection. Hence, ingestion of food and drink contaminated with the bacteria can also result in the development of the disease.


Symptoms and signs

The illness resembles a severe influenza, with a moderate fever (38-40 °C, or 101-104 °F), sore throat, chills,
myalgia Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likel ...
, headache, vomiting, and a diffuse red rash (
maculopapular A maculopapular rash is a type of rash characterized by a flat, red area on the skin that is covered with small confluent bumps. It may only appear red in lighter-skinned people. The term "maculopapular" is a compound: '' macules'' are small, flat ...
,
petechia A petechia () is a small red or purple spot (≤4 mm in diameter) that can appear on the skin, conjunctiva, retina, and Mucous membrane, mucous membranes which is caused by haemorrhage of capillaries. The word is derived from Italian , 'freckle,' ...
l, or purpuric), located mostly on the hands and feet. The incubation period for the bacteria generally lasts from three-ten days. As the disease progresses. almost half the patients experience migratory
polyarthralgia Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication. According to MeS ...
s.


Mechanism

Although the specific form of pathogenesis is still a subject of ongoing research, the bacteria has been observed to result in morphological symptoms that are atypical of bacterial infection. Autopsy of the victims vividly exhibit erythrophagocytosis,
hepatosplenomegaly Hepatosplenomegaly (commonly abbreviated HSM) is the simultaneous enlargement of both the liver (hepatomegaly) and the spleen (splenomegaly). Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis, and hist ...
,
interstitial pneumonia Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD), is a group of respiratory diseases affecting the interstitium (the tissue and space around the alveoli (air sacs)) of the lungs. It concerns alveolar epithelium, pulmona ...
, and lymph node sinus
hyperplasia Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferati ...
. In addition,
Myocarditis Myocarditis, also known as inflammatory cardiomyopathy, is an acquired cardiomyopathy due to inflammation of the heart muscle. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The ...
and
Endocarditis Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...
have also been demonstrated in such patients. Synovial and
serosal The serous membrane (or serosa) is a smooth membrane, tissue membrane of mesothelium lining the contents and inner walls of body cavity, body cavities, which secrete serous fluid to allow lubricated sliding (motion), sliding movements between op ...
surfaces may be more suited for the growth of the bacteria within the body. Furthermore, leukocytoclastic vasculitis has been observed in the skin lesions.


Diagnosis

The microaerophilic conditions needed for the bacteria to grow, makes its detection incredibly difficult. Trypticase soy agar or broth enriched with 20% blood, serum, or ascitic fluid is necessary for the optimal growth of the bacteria under laboratory conditions. The organism may take up to seven days to grow and the colonies generally have a circular, grayish and shiny appearance on agar. Once the microbe has grown, primary identification can be carried out via
biochemical Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology an ...
and carbohydrate fermentation analysis. Biochemical tests such as
oxidase In biochemistry, an oxidase is an enzyme that catalyzes oxidation-reduction reactions, especially one involving dioxygen (O2) as the electron acceptor. In reactions involving donation of a hydrogen atom, oxygen is reduced to water (H2O) or hydro ...
,
catalase Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting t ...
,
indole Indole is an aromatic heterocyclic organic compound with the formula C8 H7 N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indole is widely distributed in the natural environmen ...
, and
nitrate Nitrate is a polyatomic ion A polyatomic ion, also known as a molecular ion, is a covalent bonded set of two or more atoms, or of a metal complex, that can be considered to behave as a single unit and that has a net charge that is not zer ...
can be used to detect the bacteria. However, ''S. moniliformis'' can be biochemically differentiated from similar bacteria by their negative production of indole, catalase, and oxidase, while reduction of nitrate to
nitrite The nitrite polyatomic ion, ion has the chemical formula . Nitrite (mostly sodium nitrite) is widely used throughout chemical and pharmaceutical industries. The nitrite anion is a pervasive intermediate in the nitrogen cycle in nature. The name ...
. PCR assay specific for '' Streptobacillus moniliformis'' can also be used to detect the bacteria in a patient sample with high accuracy. The PCR assay utilizes primers based on the 16S
rRNA Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosoma ...
gene base sequences of human and rodent strains of ''S. moniliformis'' ( forward primer, 5′ GCT TAA CAC ATG CAA ATC TAT 3′ and reverse primer, 5′ AGT AAG GGC CGT ATC TCA 3′). These primers exhibit 100% complementarity to ''S. moniliformis'' ATCC 14674T and ''S. moniliformis'' ANL 370-1. The PCR assay generates a 296-bp product which upon treatment with BfaI restriction enzyme, leads to the generation of three distinct fragments (128, 92, and 76 bp), which are specific to ''S. moniliformis''. Hence, this assay can be used to detect ''S. moniliformis'' with great accuracy.


Prevention

Although rare, the disease is certainly seeing a spike in the number of incidences because of various reasons. The most important among them is the fact that rodents are increasingly finding their way into our homes either as a pet or as a pest. In fact, the number of children who are affected by rat bite fever has been specifically on the rise. Therefore, wild rats should not be brought home and if there is an infestation, appropriate measures for extermination must be undertaken to prevent the disease from spreading.


Treatment

The bacteria are susceptible to a number of antibiotics. They are: cephalosporins, carbapenems, aztreonam, clindamycin, erythromycin, nitrofurantoin, bacitracin, doxycycline, tetracycline, teicoplanin, and vancomycin. However, the data suggests that treatment with erythromycin can be less efficient. Intravenous penicillin G (400000–600000 IU/day) should be administered for 7 days and then a dosage of oral penicillin must be prescribed. Children should receive a much lesser dose: 20,000–50,000 IU, per kg of body weight per day. However, if somebody is allergic to penicillin, streptomycin and tetracycline can be administered as they have also been observed to provide efficacious results. In case of complications such as
endocarditis Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...
, a combination therapy with both intravenous penicillin G and streptomycin or gentamicin is necessary.


References


External links

{{DEFAULTSORT:Haverhill Fever Rodent-carried diseases Infectious diseases pl:Gorączka od ugryzienia szczura