Trypanosoma species	Mastigote length	Vertebrate hosts	Disease	Insect vector	Distribution
CYCLIC TRANSMISSION (parasite development within vector)
SALIVARIA (anterior station development)
T. b. gambiense	16-30µm	man, domestic animals	sleeping sickness	tsetse fly	West Africa
T. b. rhodesiense	18-30µm	man, some ruminants	sleeping sickness	tsetse fly	East Africa
T. b. brucei	18-42µm	ruminants, monogastrics	nagana	tsetse fly	tropical Africa
T. congolense	9-18µm	cattle, domestic animals	nagana	tsetse fly	tropical Africa
T. vivax	14-27µm	ruminants, horses	souma	tsetse fly	tropical Africa
T. simiae	12-24µm	pigs, some ruminants	virulent trypanosomiasis	tsetse fly	Africa
STERCORARIA (posterior station development)
T. cruzi	15-24µm	man, domestic/wild animals	Chagas’ disease	reduviid bugs	Americas
T. theileri	25-120µm	cattle	nonpathogenic	tabanid flies	worldwide
T. melophagium	25-70µm	sheep	nonpathogenic	sheep ked	worldwide
T. lewisi	20-35µm	rats	nonpathogenic	rat fleas	worldwide
T. rangeli	25-32µm	man, rats	nonpathogenic	reduviid bugs	Sth America
NON-CYCLIC TRANSMISSION (no parasite development within vector)
MECHANICA (mechanical transmission)
T. evansi	18-34µm	ruminants, horses, dogs	surra, murrina	biting flies/bats	Asia, America
T. equinum	20-30µm	horses, ruminants	mal de caderas	biting Diptera	America
T. equiperdum	18-30µm	horses	dourine	coitus	tropics

Site of infection: Trypomastigotes are found extracellularly in the blood and lymph of infected individuals (including lymph nodes and spleen) but may invade the central nervous system and other tissues.

Pathogenesis: The disease is known as Old World (African) trypanosomiasis. Although there are many regional common names given depending on the parasite subspecies and hosts involved, the disease is often called sleeping sickness in humans, and nagana in animals. Parasites injected into the host by the insect vector first cause an inflammatory reaction characterized by a localized tender reddish swelling (known as a chancre). Trypanosomes then multiply in the plasma and interstitial fluid causing acute to subacute febrile illness. A classic sign of T. b. gambiense infection is the enlargement of the cervical lymph glands at the back of the neck (known as Winterbottom’s sign). T. b. rhodesiense infections in humans usually cause acute systemic disease with haemolymphatic involvement, swollen lymph nodes, fever and rapid weight loss. T. b. gambiense usually causes chronic disease with neurological involvement, meningoencephalitis, lethargy and coma (hence ‘sleeping’ sickness). Parasite development occurs in cyclic waves moderated by host immune responses. Trypanosomes have a glycoprotein coat on the outer surface of the cell membrane which is highly antigenic and leads to the production of host antibodies which act, together with complement, to lyse parasites. Trypanosomes, however, repeatedly change the molecular arrangement of the coat so some individuals avoid immune destruction and divide to produce a new wave of infection. This antigenic variation is under genetic control and while synthesis of successive variant surface glycoproteins does not occur in a fixed sequence, it is not entirely random. The repeated cycles of host antibody production and parasite destruction leads to cyclic fevers, macroglobulinemia, microvascular damage, coagulopathy, and perivascular inflammation. When parasites penetrate the blood-brain barrier (within weeks for T. b. rhodesiense or up to years for T. b. gambiense), they cause encephalitis, coma and death. The clinical course of T. b. brucei infections depends on the susceptibility of the host species. Horses and dogs are particularly susceptible and may succumb within 2-3 weeks Cattle and pigs are more refractory to disease and may survive for several months. Clinical signs include anaemia, fever, oedema and progressive paralysis. Native animal species (antelope and other wild ruminants) are trypanotolerant and may act as asymptomatic carriers.

Mode of transmission: All salivarian trypanosomes are transmitted by tsetse fly vectors (Glossina spp.). Metacyclic trypomastigotes ingested during feeding transform into procyclic trypomastigotes in the midgut. These stages migrate through gut membranes and invade the salivary glands where they transform into epimastigotes which undergo anterior station development to produce infective metacyclic trypomastigotes which are injected during feeding.

Differential diagnosis: Infections were conventionally diagnosed by the direct detection of parasites in blood, bone marrow or cerebrospinal fluid by microscopic examination before or after centrifugation. In vitro cultivation has proven difficult and in vivo inoculation into laboratory animals yields variable results. More recently, a variety of immunoserological tests have been developed to detect host antibodies using fluorescent, agglutination or enzyme markers. Card-agglutination and dot-spot tests are available for field use. Molecular characterization techniques utilizing polymerase chain reaction (PCR) amplification of parasite DNA have yielded good results in species/strain differentiation with certain genes (e.g. SRA gene, serum-resistant-associated).

Treatment and control: Historically, arsenical drugs have been used despite major toxicity problems. Melarsoprol and trypursamide are used to treat chronic infections (involving CNS signs). Other drugs have proven more effective against systemic infections (suramin, pentamidine) and neurological infections (berenil, eflornithine, difluoromethylornithine). Prevention involves avoiding being bitten by tsetse flies, but this can be difficult as they are persistent daytime feeders and can bite through thin clothing. Control measures based on vector eradication (using insecticidal sprays, fly traps, or clearing vegetation) and managing wild game reservoirs of infection (by fencing, culling or creating wildlife corridors) have only proven partially effective. Some recent success has been recorded in breeding trypanotolerant domestic livestock (e.g. Ndama cattle).