African Tick Bite Fever
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African tick bite fever (ATBF) is a
bacterial infection Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and many are beneficial but others can cause infectious diseases. The number of t ...
spread by the bite of a
tick Ticks are parasitic arachnids of the order Ixodida. They are part of the mite superorder Parasitiformes. Adult ticks are approximately 3 to 5 mm in length depending on age, sex, and species, but can become larger when engorged. Ticks a ...
. Symptoms may include fever, headache, muscle pain, and a rash. At the site of the bite there is typically a red skin sore with a dark center. The onset of symptoms usually occurs 4–10 days after the bite. Complications are rare but may include joint inflammation. Some people do not develop symptoms. Tick bite fever is caused by the bacterium '' Rickettsia africae''. The bacterium is spread by
tick Ticks are parasitic arachnids of the order Ixodida. They are part of the mite superorder Parasitiformes. Adult ticks are approximately 3 to 5 mm in length depending on age, sex, and species, but can become larger when engorged. Ticks a ...
s of the '' Amblyomma'' type. These generally live in tall grass or bush rather than in cities. The diagnosis is typically based on symptoms. It can be confirmed by
culture Culture ( ) is a concept that encompasses the social behavior, institutions, and Social norm, norms found in human societies, as well as the knowledge, beliefs, arts, laws, Social norm, customs, capabilities, Attitude (psychology), attitudes ...
, PCR, or
immunofluorescence Immunofluorescence (IF) is a light microscopy-based technique that allows detection and localization of a wide variety of target biomolecules within a cell or tissue at a quantitative level. The technique utilizes the binding specificity of anti ...
. There is no
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...
. Prevention is by avoiding tick bites by covering the skin, using
DEET ''N'',''N''-Diethyl-''meta''-toluamide, also called diethyltoluamide or DEET (, from DET, the initials of di- + ethyl + toluamide), is the oldest, one of the most effective, and most common active ingredients in commercial insect repellents. ...
, or using
permethrin Permethrin is a medication and an insecticide. As a medication, it is used to treat scabies and lice. It is applied to the skin as a cream or lotion. As an insecticide, it can be sprayed onto outer clothing or mosquito nets to kill the insects ...
treated clothing. Evidence regarding treatment, however, is limited. The
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
doxycycline Doxycycline is a Broad-spectrum antibiotic, broad-spectrum antibiotic of the Tetracycline antibiotics, tetracycline class used in the treatment of infections caused by bacteria and certain parasites. It is used to treat pneumonia, bacterial p ...
appears useful.
Chloramphenicol Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by intravenous, injection into a vein, it is used to treat meningitis, pl ...
or
azithromycin Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of several bacterial infections. This includes otitis media, middle ear infections, strep throa ...
may also be used. The disease will also tend to resolve without treatment. The disease occurs in
sub-Saharan Africa Sub-Saharan Africa is the area and regions of the continent of Africa that lie south of the Sahara. These include Central Africa, East Africa, Southern Africa, and West Africa. Geopolitically, in addition to the list of sovereign states and ...
, the
West Indies The West Indies is an island subregion of the Americas, surrounded by the Atlantic Ocean, North Atlantic Ocean and the Caribbean Sea, which comprises 13 independent island country, island countries and 19 dependent territory, dependencies in thr ...
, and
Oceania Oceania ( , ) is a region, geographical region including Australasia, Melanesia, Micronesia, and Polynesia. Outside of the English-speaking world, Oceania is generally considered a continent, while Mainland Australia is regarded as its co ...
. It is relatively common among travelers to
sub-Saharan Africa Sub-Saharan Africa is the area and regions of the continent of Africa that lie south of the Sahara. These include Central Africa, East Africa, Southern Africa, and West Africa. Geopolitically, in addition to the list of sovereign states and ...
. Most infections occur between November and April. Outbreaks of the disease may occur. The earliest descriptions of the condition are believed to be from 1911. African tick bite fever is a type of
spotted fever A spotted fever is a type of tick-borne disease which presents on the skin. They are all caused by bacteria of the genus '' Rickettsia''. Typhus is a group of similar diseases also caused by ''Rickettsia'' bacteria, but spotted fevers and typhus a ...
. It has previously been confused with Mediterranean spotted fever.


Signs and symptoms

African tick bite fever is often asymptomatic or mild in clinical presentation and complications are rare. The onset of illness is typically 5–7 days after the tick bite, although in some cases it may take up to 10 days for symptoms to occur. Symptoms can persist for several days to up to three weeks. Common presenting symptoms include: * Fever * Headache * Muscle aches * Inoculation
eschar Eschar (; ; ; or ''an'' eschar) is a slough or piece of necrosis, dead tissue that is cast off from the surface of the skin, particularly after a Burn, burn injury, but also seen in gangrene, Ulcer (dermatology), ulcer, mycosis, fungal infection ...
, which is dead, often black, tissue around a bite site (see photo above) ** Eschars may or may not be present. ''Amblyomma'' ticks actively attack cattle or humans and can bite more than once. In African tick bite fever, unlike what is typically seen with other Rickettsial spotted fevers when only one eschar is identified, multiple eschars may be seen and are considered pathognomonic. * Swollen lymph nodes near the site of the bite *
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, fla ...
and/or vesicular rash


Complications

Complications are rare and are not life-threatening. No deaths due to African tick bite fever have been reported. Reported complications include: * Prolonged fever > 3 weeks in duration *
Reactive arthritis Reactive arthritis, previously known as Reiter's syndrome, is a form of inflammatory arthritis that develops in response to an infection in another part of the body (cross-reactivity). Coming into contact with bacteria and developing an infect ...
* Moderate to severe headache


Cause


Bacteriology

'' Rickettsia africae'' is a gram-negative, obligate intracellular, pleomorphic bacterium. It belongs to the genus ''
Rickettsia ''Rickettsia'' is a genus of nonmotile, gram-negative, nonspore-forming, highly pleomorphic bacteria that may occur in the forms of cocci (0.1 μm in diameter), bacilli (1–4 μm long), or threads (up to about 10 μm long). The genus was n ...
'', which includes many bacterial species that are transmitted to humans by arthropods.


Vectors

Two species of hard ticks,  Amblyoma variegatum and  Amblyomma hebraeum are the most common vectors of R. africae. Typically, Amblyomma hebraeum transmits the bacteria in South Africa while Amblyoma variegatum carries R. africae throughout West, Central and East Africa and through the French West Indies. Other species of ''Amblyomma'' in sub-Saharan Africa can also transmit ''R. africae'' and it may be that up to 100% of ''Amblyomma'' ticks in sub-Saharan Africa carry ''R. africae.'' ''Amblyomma'' ticks are most active from November to April. These tick species frequently feed on cattle and other livestock, but can also be found feeding on wild animals in areas where farm animals are not found. Unlike other hard tick species, which passively seek hosts by clinging to plants and waiting for a potential host to brush by in passing, the Amblyomma hard ticks actively seek out hosts. Groups of tourists visiting Africa have returned to their own countries and were diagnosed there as having been infected. Up until 1998, it was thought that only ticks in sub-Saharan Africa carried ''R. africae''. However, a case of locally transmitted African tick bite fever in the French West Indies led to the discovery of ''R. africae'' carried by ''Amblyomma varigatum'' ticks introduced through cattle shipped from
Senegal Senegal, officially the Republic of Senegal, is the westernmost country in West Africa, situated on the Atlantic Ocean coastline. It borders Mauritania to Mauritania–Senegal border, the north, Mali to Mali–Senegal border, the east, Guinea t ...
to Gaudeluope more than a century ago. ''R. africae'' has been isolated from ticks on several Caribbean islands, though the only cases in humans in the Caribbean have occurred in the French West Indies. ''R. africae'' has also been found in ''Amblyomma loculosum'' ticks in Oceania.


Pathogenesis

After the rickettsia bacteria infects humans through a tick bite, it invades
endothelial cells The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the res ...
in the circulatory system (veins, arteries, capillaries). The body then releases chemicals that cause
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
, resulting in the characteristic symptoms like headache and fever. The hallmark of all rickettsial diseases is a
histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...
(cellular) finding called lymphohistiocytic vasculitis that involves immune cell deposition into the
endothelial The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the res ...
cells that make up vessels. This occurs secondary to the chemicals mentioned above, as well as damage from the infection, and involves signals to immune cells (T cells and macrophages) to come to the site of the infection. Rickettsia bacteria species like ''R. africae'' replicate around the area of the initial tick bite, causing
necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who i ...
(cell death) and lymph node inflammation. This is the cause of the characteristic
eschar Eschar (; ; ; or ''an'' eschar) is a slough or piece of necrosis, dead tissue that is cast off from the surface of the skin, particularly after a Burn, burn injury, but also seen in gangrene, Ulcer (dermatology), ulcer, mycosis, fungal infection ...
.


Diagnosis

Many patients with ATBF who live in areas with a high number of infections (Africa and the West Indies) do not visit a doctor, as most patients only have mild symptoms. This disease can, however, cause more serious symptoms in travelers who have never been exposed to the ''Rickettsia africae'' bacterium before and are not immune. Travelers who present to a doctor after a trip to affected areas can be hard to diagnose, as many
tropical disease Tropical diseases are diseases that are prevalent in or unique to tropical and subtropical regions. The diseases are less prevalent in temperate climates, due in part to the occurrence of a cold season, which controls the insect population by forc ...
s cause a fever similar to that of ATBF. Other diseases that may look similar are malaria, dengue fever, tuberculosis, acute HIV and respiratory infections. In addition to questions about symptoms, doctors will ask patients for an accurate travel history and whether he/she was near animals or ticks. Microbiological tests are available for doctors, but are expensive and often must be done by special laboratories. The antibiotic treatment available for rickettsiae infections has very few side effects, so if a doctor has a high suspicion of the disease, he or she may simply treat without doing more laboratory tests.


Blood tests

Diagnosis of ATBF is mostly based on symptoms, as many laboratory tests are not specific for ATBF. Common laboratory test signs of ATBF are a low white blood cell count (
lymphopenia Lymphocytopenia is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system. It is also called lymphopenia. The opposite is lymphocytosis, which r ...
) and low platelet count (
thrombocytopenia In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coag ...
), a high
C-reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin ...
, and mildly high liver function tests.


Microbiological tests

Biopsies or cultures of a person's tick wound (eschar) are used to diagnose ATBF. However, this requires special culture media and can only be done by a laboratory with
biohazard A biological hazard, or biohazard, is a biological substance that poses a threat (or is a hazard) to the health of living organisms, primarily humans. This could include a sample of a microorganism, virus or toxin that can adversely affect huma ...
protection. There are more specialized laboratory tests available that use quantitative
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...
s (qPCR), but can only be done by laboratories with special equipment.
Immunofluorescence Immunofluorescence (IF) is a light microscopy-based technique that allows detection and localization of a wide variety of target biomolecules within a cell or tissue at a quantitative level. The technique utilizes the binding specificity of anti ...
assays can also be used, but are hard to interpret because of cross-reactions with other rickettsiae bacteria.


Prevention

Prevention of ATBF centers around protecting oneself from tick bites by wearing long pants and shirt, and using insecticides like
DEET ''N'',''N''-Diethyl-''meta''-toluamide, also called diethyltoluamide or DEET (, from DET, the initials of di- + ethyl + toluamide), is the oldest, one of the most effective, and most common active ingredients in commercial insect repellents. ...
on the skin. Travelers to rural areas in Africa and the West Indies should be aware that they may come in contact with ATBF tick vectors. Infection is more likely to occur in people who are traveling to rural areas or plan to spend time participating in outdoor activities. Extra caution should be taken in November - April, when ''Amblyomma'' ticks are more active. Inspection of the body, clothing, gear, and any pets after time outdoors can help to identify and remove ticks early.


Treatment

African tick bite fever is usually mild, and most patients do not need more than at-home treatment with antibiotics for their illness. However, because so few patients with this infection visit a doctor, the best antibiotic choice, dose and length of treatment are not well known. Typically doctors treat this disease with antibiotics that have been used effectively for the treatment of other diseases caused by bacteria of similar species, such as
Rocky Mountain Spotted Fever Rocky Mountain spotted fever (RMSF) is a bacterial disease spread by ticks. It typically begins with a fever and headache, which is followed a few days later with the development of a rash. The rash is generally Petechial rash, made up of small s ...
. For mild cases, people are usually treated with one of the following: *
doxycycline Doxycycline is a Broad-spectrum antibiotic, broad-spectrum antibiotic of the Tetracycline antibiotics, tetracycline class used in the treatment of infections caused by bacteria and certain parasites. It is used to treat pneumonia, bacterial p ...
*
chloramphenicol Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by intravenous, injection into a vein, it is used to treat meningitis, pl ...
*
ciprofloxacin Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin ...
If a person has more severe symptoms, like a high fever or serious headache, the infection can be treated with doxycycline for a longer amount of time. Pregnant women should not use doxycycline or ciprofloxacin as both antibiotics can cause problems in fetuses. Josamycin has been used effectively for treatment of pregnant women with other rickettsial diseases, but it is unclear if it has a role in the treatment of ATBF.


Epidemiology

Cases of African tick bite fever have been more frequently reported in the literature among international travelers. Data examining rates in local populations are limited. Among locals who live in endemic areas, exposure at a young age and mild symptoms or lack of symptoms, as well as decreased access to diagnostic tools, may lead to decreased diagnosis. In Zimbabwe, where ''R. africae'' is endemic, one study reported an estimated yearly incidence of 60-80 cases per 10,000 patients. Looking at published data over the past 35 years, close to 200 confirmed cases of African tick bite fever in international travelers have been reported. The majority (~80%) of these cases occurred in travelers returning from South Africa.


See also

* Boutonneuse fever *
Rocky Mountain spotted fever Rocky Mountain spotted fever (RMSF) is a bacterial disease spread by ticks. It typically begins with a fever and headache, which is followed a few days later with the development of a rash. The rash is generally Petechial rash, made up of small s ...
* Flea-borne spotted fever


References


External links

{{Bacterial cutaneous infections Bacterium-related cutaneous conditions Rickettsioses Wikipedia medicine articles ready to translate