Chart 7.10 Biochemical reactions of some enterobacteria and other enteric organisms
7.18.35 Rickettsia species and related organisms
Note: The basic features of rickettsial organisms are summa- rized in subunit 7.2.
Pathogenicity
Rickettsia species are divided into three main groups:
Typhus group: Includes R. prowazekii which causes epidemic typhus (louse-borne typhus) and R. typhi which causes endemic typhus (murine, or flea-borne typhus).
Scrub typhus group: Contains O. tsutsuga- mushi which causes mite-borne scrub typhus, also known as Japanese river fever and Kedani mite disease.
Spotted fever group:Includes those rickettsiae
that cause Rocky Mountain spotted fever, African and Indian tick typhus, Fièvre bouton- neuse, rickettsialpox, and other spotted fevers.
The group includes R. rickettsii, R. conorii, R. akari and R. africae.
Rickettsiaspecies of importance in tropical countries, their arthropod vectors, (lice, ticks, fleas, mites), main reservoir hosts, and the diseases they cause are sum- marized in Chart 7.14. A person becomes infected either by being bitten by an infected vector or by scratching vector faeces containing rickettsiae into the skin.
Rickettsial infections
The symptoms of rickettsial infections are due to the invasion and multiplication of rickettsiae in the endothelial cells of small blood vessels, smooth muscle cells, and histiocytes. The tissues most affected are those of the skin, heart, brain and lungs.
There is a local cellular response with the infected cells becoming inflamed and severely damaged. Capillaries become blocked and bleeding may occur in severe infections.
Most infections are characterized by high continuous fever, severe headache and body pains, marked weakness, and an enlarged spleen and liver. A macula or maculopapular rash, which usually appears towards the end of the first week,
7.18.35
may become haemorrhagic especially in Rocky Mountain spotted fever, louse-borne typhus, and occasionally in tick typhus. There may also be oedema.
The eyes are frequently affected, the face flushed, and nosebleeds may occur. There is often severe vomiting. In about the second week of infection, the patient may become very ill with signs of brain damage including mental dullness and confusion which may lead to delirium and coma.
In severe infections, death can occur from general toxaemia, encephalitis, myocarditis, or pneumonia. The most severe symptoms are found in louse-borne typhus, scrub typhus, and Rocky Mountain spotted fever.
With scrub typhus, tick typhus and rickettsialpox, a black scab (eschar) may form at the site of infection and the sur- rounding lymph glands become inflamed. These features, however, are not always seen in those living in endemic areas.
Brill-Zinsser disease is a relapsing form of typhus caused by R. prowazekii. It is milder than primary epidemic typhus and the early antibody response is IgG rather than IgM.
LABORATORY FEATURES
Most rickettsial diseases are diagnosed serologically by testing paired sera (acute and convalescent samples).
Note: Because rickettsiae are obligate intracellular organisms, the techniques used for culturing viruses can also be used for isolating rickettsiae. Such tech- niques, however, can only be performed in Reference Laboratories.
Morphology
Rickettsiae are pleomorphic organisms, forming coccal or rod-like forms. They are very small, mea- suring less than 0.5 àm in diameter. In smears of infected tissue stained with Giemsa, Castaneda, or Macchiavello stains, rickettsiae can sometimes be detected in groups within the nuclei of infected cells or close to cells.
Serology
In most rickettsial infections, antibodies can usually be detected only in the later stages of illness. IgM antibodies are produced first followed by IgG anti- bodies which persist in the serum for several years.
Immunity against louse-borne typhus and the spotted fever group of rickettsiae lasts for about 1 year after infection. Reinfection with scrub typhus is rare.
Antibody tests
Paired sera should be tested to demonstrate a rise in titre during illness. A range of antibody tests to investigate rickettsial infections is available from PanBio Ltd. They include indirect flu- orescence antibody tests (IFAT) and enzyme linked
Chart 7.14 Medically important Rickettsiaspecies in tropical countries
Organism Disease Vector Reservoir
Distribution Host(s)
R. prowazekii Epidemic Body Humans
Africa, Asia, typhus louse Flying
South America Brill-Zinsser squirrels
R. typhi Endemic Fleas Rats
Worldwide typhus Mice
O. tsutsugamushi Scrub Trombiculid Mites,
India, SE Asia, typhus mite rodents
South Pacific (chigger)
R. rickettsii Rocky Mt Ixodid Rodents,
USA, South spotted fever tick dogs
America
R. conorii Tick typhus Ixodid Wild
Africa, India, Fièvre tick mammals,
Mediterranean boutonneuse dogs
R. akari Rickettsial Mites Rodents
Asia, S. Africa pox USA, Russia
Notes:
In recent years a new Rickettsiaspecies called R. africaehas been recognized also as causing African tick bite fever.
Reservoir hosts are rodents.
R Rickettsia, O Orientia
immunosorbent assays (ELISA). Details of these can be obtained from PanBio (see Appendix 11).
Weil-Felix reaction
This non-specific test is based on cross-reactions which occur between antibodies produced in acute rickettsial infections and the OX 19, OX 2, and OXK strains of Proteus species. Dilutions of patient’s serum are tested against suspensions of the different Proteusstrains.
Proteus OXK strain agglutinins are produced in scrub typhus and OX 2 and OX 19 agglutinins in other rickettsial diseases (see following Chart). The Weil-Felix reactions give a high percentage of false negative results. These are particularly common in scrub typhus. False positive results are obtained in other diseases such as leptospirosis and relapsing fever (diseases which require differentiating from rickettsial infections), Proteus infections, brucellosis and acute febrile illnesses. The predictive value of the Weil-Felix test increases when both acute and convalescent samples can be tested to look for a rise in antibody titre. Whenever possible an IFAT, ELISA, or immunochromatographic assay should be used instead of the Weil-Felix test.
typhus and murine typhus, there is usually a slight leucocytosis in the later stages of infection with an increase in mononuclear cells. A leucocytosis with neutrophilia may occur in severe tick-bite fever and other rickettsial diseases with serious complications.
Platelets: Thrombocytopenia is usually found in severe infections.
Coagulation tests: These may be abnormal, especially in severe infections. Serum fibrin degra- dation products (FDP’s) are raised when there is disseminated intravascular coagulation (DIC).
Cerebrospinal fluid: With encephalitis, the fluid contains cells (mainly lymphocytes) and an increase in total protein.
Blood urea and serum creatinine: These may be raised, especially when there is abnormal renal function.
Urine: This contains protein and in severe infections, red cells and casts may also be found.
FURTHER INFORMATION
Readers are referred to Chapter 50 Rickettsial infections in 21st edition Mansons Tropical Diseases, 2003, Saunders, Elsevier.
Coxiella burnetii
C. burnetiicauses Q (‘query’) fever which has a worldwide dis- tribution. In Zaire it is known as Red River Fever. Natural reservoir hosts include cows, sheep, goats, rodents, wild mammals and several species of bird.C. burnetiiis transmitted by ticks but unlike rickettsiae, it can also be transmitted without a vector via placental tissue, dust particles, faeces and infected milk. Human infection is commonly by inhaling con- taminated aerosols and dust and occasionally by drinking untreated milk or by handling infected animals or their tissues.
C. burnetiiinfects the cells of the spleen and liver causing enlargement of these organs. Q fever resembles influenza with high fever, severe headache, fatigue, and body pains. Usually there is no rash or only a slight one. Serious complications of Q fever include pneumonitis, chronic infective endocarditis, and liver disease.
Serological tests used to assist in the diagnosis of Q fever (usually performed in a Reference Laboratory) include complement fixation test (CFT) and indirect microimmuno- fluorescence test (IFAT). Microimmunofluorescence is more sensitive than CFT in the early stages of infection.
During infection, C. burnetii undergoes antigenic vari- ation. In the early stages of infection the organisms exist in phase 2 and the antibody body response is to phase 2. In sero- logical tests, phase 2 antigen is therefore used to diagnose acute Q fever. In chronic infections, antibodies to phase I are present and can be tested using phase I antigen.
Organism Weil-Felix Reactions
OX 19 OX 2 OXK
Typhus Group:
R. prowazekii* / –
R. typhi / –
Scrub Typhus Group:
O. tsutsugamushi – – /
Spotted Fever Group:
R. conorii / / –
R. rickettsii / / –
*In louse-borne typhus, the antibody titre against OX 19 may rise to 1 in 500 or more in the third or fourth week of infec- tion, but rarely in Brill-Zinsser disease.
Important: In endemic areas, district laboratories wishing to test for rickettsial infections should consult their Regional or Central Public Health Laboratory regarding the most appropriate test to use and how to interpret test results.
Other laboratory findings in rickettsial infections
White blood cell count: In scrub typhus this is usually low with an absolute lymphocytosis. In louse-borne
Agglutinins to Proteusstrains are not produced in Q fever and therefore the Weil-Felix reaction (as used to investigate rickettsial infections) is negative.
Bartonella quintana and Bartonella hensele B. quintana(formerly Rochalimaea quintana): Causes trench fever, a louse-borne infection (originally associated with epi- demics among troops in the First World War) which can be found in Mexico, some parts of Africa and the Far East. Most infections are mild with fever, headache, muscle pain, macular rash, nausea and vomiting. The fever may be recurring (e.g.
quintan fever, occurring every 5 days). More serious infec- tions have been reported in those infected with HIV. Most infections are diagnosed clinically. Laboratory investigations include blood culture and testing serum for antibody (in Reference Laboratory).
B. hensele(previously Rochalimaea hensele): Causes oppor- tunistic infections in those with immunosuppression, e.g. HIV disease. It is associated with fever, bacteraemia and a con- dition called cutaneous bacillary angiomatosis, (vascular lesions resembling Kaposi’s sarcoma in the skin and visceral organs). Infections can be diagnosed by blood culture (in Reference Laboratories). B. hensele also causes cat-scratch disease, a mild self-limiting lymphadenopathy, usually found in children following contact with cats.