Table of contents :

• coprozoa : protozoa which are found in fecal matter outside the body, but which do not inhabit the intestine

 
• Acanthamoebidae
• Acanthamoeba : genus of free-living ameboid protozoa found usually in fresh water or moist soil
• Acanthamoeba astronyxis
• Acanthamoeba castellanii
• Acanthamoeba culbertsoni
• Acanthamoeba  hatchetti
• Acanthamoeba polyphaga
• Acanthamoeba  rhysodes
They form acanthopodia.
=> acanthamebiasis : opportunistic infections from stagnant water (cutaneous ulcers, conjunctivitis and Acanthamoeba keratitis (expecially in contact lenses carriers, the temperature and moist environment of the eye serve as a good medium for the growth and proliferation of the amebas and is not necessarily associated with immunosuppression but rather with trauma) ==olfactory nerve (?) or hematogenous spread==> primary amebic meningoencephalitis (PAM)
• acute, sometimes associated with spontaneous recovery
• subacute
• chronic granulomatous amebic encephalits (GAE) in chronically ill and debilitated individuals. Subclinical infections due to free-living amebas are probably common in healthy individuals with the protozoa living as "normal flora" in the nose and throat.
• Euglenozoa [Euglenida : an order of plantlike, flagellate protozoa (class Phytomastigophorea, subphylum Mastigophora) having green chromatophores when present; 1-2, rarely more, flagella protruding from an anterior invagination; and a small stigma located anteriorly in colored forms. The organisms are usually found in fresh water, although some inhabit salt or brackish water, and a few are parasitic]
• Kinetoplastida / Protomastigida / Protomonadina : an order of flagellate protozoa (class Zoomastigophorea, subphylum Mastigophora), many species of which are free living, although most are parasites of plants, invertebrates, and vertebrates. Kinetoplastids have 1-2flagella arising from a depression in the cell body and usually contain a conspicuous kinetoplast located near the flagellar basal bodies. The order comprises two suborders:
• Bodonina
• Trypanosomatidae (1 only flagellum) [Trypanosomatina : a suborder of parasitic protozoa (order Kinetoplastida, class Zoomastigophorea) comprising the hemoflagellates, which are found in the hosts' blood, lymph, and tissues, and are characterized by a leaflike or rounded body with one nucleus, one flagellum that is free or attached to the body by an undulating membrane, and a relatively small compact kinetoplast. All trypanosomatids have morphologically distinct stages in their life cycles during which the organisms of one genus may pass through forms characteristic of other genera of the suborder. These forms include: amastigote, choanomastigote, epimastigote, opisthomastigote, promastigote, and trypomastigote. Not all species pass through all of the stages, but all have at least 2 such forms during their development.

amastigote (in invertebrates) => metacyclic trypomastigote (in vector) => promastigote (the free flagellum and kinetoplast are anterior to the nucleus) => epimastigote (a short undulating membrane) => blood stream trypomastigote (the undulating membrane and kinetoplast are located posterior to the nucleus). Representative genera include :
• Blastocrithidia : a genus of protozoa parasitic in arthropods and other invertebrates, which pass through epimastigote, amastigote, and presumably promastigote developmental stages in their life cycle.
• Crithidia
• Leishmania : a genus of flagellate protozoa (suborder Trypanosomatina, order Kinetoplastida) comprising parasites of worldwide distribution, several species of which are pathogenic for humans. The organisms have 2 morphologic stages in their life cycle: amastigote (Leishman-Donovan body), found intracellularly in the vertebrate (i.e., human) host; and promastigote (leptomonad), found in the digestive tract of the invertebrate host (i.e., phlebotomine sandfly) and in cultures. Because all species are morphologically indistinguishable, the organisms have usually been assigned to species and subspecies according to their geographic origin, the clinical syndrome they produce, and their ecologic characteristics, or they have been separated on the basis of their tendency to cause visceral, cutaneous, or mucocutaneous leishmaniasis.
Epidemiology : collectively, the diseases are now routinely found in 88 countries across 5 continents, with an estimated 350 million people at risk. Around 1.5 million new cases of cutaneous leishmaniasis occur every year. Up to 90% of these occur in Afghanistan, Brazil, Iran, Peru, Saudi Arabia and Syria.
Transmission : they are transmitted into mammalian hosts in their promastigote form and are soon phagocyted by macrophages : they can replicate in phagolysosomes of RES cells throughout the body, especially in the liver, spleen, bone marrow, lymph nodes, and skin. Although lipophosphoglycan (LPG) is involved in the transient inhibition of phagolysosomal fusion soon after Leishmania enters the host cells, this inhibition is not essential for Leishmania survival within macrophages : rather it is important in resisting the effects of intracellular oxidants. Localization (cutaneous, mucocutanous or visceral) depends on strength (high, moderate or weak, respectively) and T_h polarization (T_h1 or T_h2, respectively) of immune response.
• Leishmania aethiopica species complex
• Leishmania aethiopica (a.k.a. Leishmania tropica aethiopica)
Transmission : reservoirs : Procavia capensis, Heterohyrax brucei ; vectors : Phlebotomus pedifer in Kenya and Phlebotomus longipes in Ethiopia
Epidemiology : highlands of Ethiopia and Kenya. The rate of leishmanin positivity in 10 villages in Upper Awash, northeastern Ethiopia ranged from 16 to 65 %, with the overall prevalence of 33%^ref; the figure was 5% in the Ethiopian Rift Valley province^ref. Leishmania is transmitted by sandflies; various animals -- especially rodents -- act as reservoirs
=> Old World cutaneous leishmaniosis / Aden ulcer : erythema on face (zygoma, temples, nose), hand palms and foot backs => macule => papule on bite point => nodule => indolent ulcer => heals, leaving an atrophic scar, or undergoes bacterial overinfection, nausea and vomiting, and lymphadenitis
• Ethiopian cutaneous leishmaniasis : lesions are less inflamed and more chronic than those of other Old World forms, and generally last for several years; the condition is usually self-limited but may develop into ...
• diffuse or anergic cutaneous leishmaniasis : local and hematogenous spread from a primary lesion to produce generalized nodular lesions resembling those of lepromatous leprosy in the skin and sometimes involving the nasal mucosa and laryngopharynx. Individuals with this form of the disease do not develop an effective immune response to the infection.
• leishmaniasis recidivans : a relapsing form of either wet or dry cutaneous leishmaniasis, resembling tuberculosis of the skin, in which the ulcer heals incompletely, scarring centrally but spreading peripherally, or heals and recrudesces at the edge of the ulcer; it may last for many years
• Leishmania donovani species complex : all multiply in the reticuloendothelial cells and spread to the lymph nodes and then hematogenously throughout the body. The subspecies can be distinguished only by differences in the epidemiology, clinical features, and response to treatment
• Leishmania donovani
Epidemiology : tropical and subtropical regions of the world. It has traditionally been divided into 3 different forms according to geographical distribution, vector, and other factors, but such a distinction may prove to be invalid. VL is largely found in the eastern part of India mainly in Bihar state and to some extent in its bordering states like West Bengal and Uttar Pradesh. The main vector in India is Phlebotomus argentipes. VL decreased in India during the 1950's after extensive spraying with DDT as part of the malaria control programme, but has been increasing again since the 1960's. A large epidemic occurred in Bihar state in the 1990's. VL is typical in rural areas and it is not known whether the 2 cases in this report have been residents in endemic areas primarily Bihar state or have been long-term residents in Mumbai^ref. Most of the approximately 500,000 cases of VL reported worldwide affect the rural poor in India, Nepal, Bangladesh, Sudan, and Brazil^ref. Georgia : only 1-5 cases of VL were recorded annually before 1995, but 174 cases of leishmaniasis were registered in  in 2006, including 103 cases in Tbilisi. According to the experts, the most dangerous territories for leishmaniasis are the central districts of Tbilisi: Vake, Vera and Mtatzminda.
=> visceral leishmaniosis (VL) / kala-azar / tropical splenomegaly / black, cachectic, cachexial, or Dumdum fever : after 4-10 months incubation =>
• gradual onset, prolonged, irregular fever with chills that often rises and falls twice/day
• nausea and vomiting
• diarrhea
• fatigue
• weight loss, emaciation, cachexia / phthisis
• anemia
• leukopenia
• hypergammaglobulinemia
• diffuse skin hyperpigmentation (earth-gray color) on forehead, abdomen, hands, and feet in light-skinned persons
• cutaneous nodule may or may not appear at the site of the bite
• dizziness
• cough
• pronounced splenomegaly (hard, non-tender)
• hepatomegaly (granulomatous hepatitis), jaundice and ascites
• generalized lymphadenitis
• skin lesions in dark-skinned persons
• signs of bleeding (petechiae, epistaxis, bleeding gums)
Onset may also be acute, with the above manifestations appearing a few weeks after infection
=> post–kala-azar dermal leishmaniasis (PKDL) / dermal leishmanoid, leishmanoid, and post–kala-azar dermal leishmanoid : a condition associated with visceral leishmaniasis, commonly characterized by the appearance of hypopigmented or erythematous macules on the face and sometimes on the extremities and trunk; the facial lesions gradually progress to papules or nodules that resemble those of lepromatous leprosy. It is seen in about 20% of Indian patients, usually occurring years after the treatment of or spontaneous recovery from visceral leishmaniasis, and it may last for as long as 20 years. When the condition affects patients in East Africa (2% and China (rare), it usually occurs shortly after or during treatment and usually does not persist
Death within 2 years due to infections.
• Leishmania donovani chagasi
Epidemiology : South America, Central America, and Mexico. Human and canine visceral leishmaniasis, VL, is well known but rare in Venezuela. The incidence of human VL was 0.2 cases per 100 000 population 1995 to 2000, or 242 cases. However, 26% of the cases originated from Isla Margarita. In the same period, up to 25% of dogs tested on the island were seropositive for Leishmania (PAHO)^ref.
Transmission : a zooanthroponosis : reservoirs are Canis familiaris (may become infected and even infectious without showing any signs of the disease), Vulpes spp., Felis catus; vector : Lutzomyia longipalpis, but also other species such as Lutzomyia intermedia may be vectors
=> South-American visceral leishmaniasis
• Leishmania donovani donovani (a.k.a. Leishmania donovani)
Epidemiology : older children or young adults in eastern India, Bangladesh, and Hyderabad, Sind province, Pakistan
Transmission : a zooanthroponosis transmitted by the sandfly Phlebotomus argentipes, a sandfly that commonly rests in houses and cattle sheds. Consequently spraying the interior surfaces of these structures with DDT, or other insecticides, should do much to kill the vectors. Incidentally this is one of the very few sandflies whose larval habitats are reasonably well known, namely moist soil with organic content in and close to houses. During the Malaria Control and Malaria Eradication campaigns in India in the 1960s, there was almost a cessation of visceral leishmaniasis transmission, because indoor residual spraying against the Anopheline mosquito vectors of malaria also resulted in killing endophilic sandfles. But with the deterioration of the malaria campaigns sandflies returned, and in 1977 there were some 100 000 cases of visceral leishmaniasis in Bihar state . There are no reservoir hosts of L. d. donovani in India, although in other countries such as Sudan and Ethiopia various rodents and Serval cats (Felis serval) and genets (Genetta genetta) can be reservoir hosts of L.d.donovani
=> Indian visceral leishmaniosis (VL) / classic visceral leishmaniosis
Treatmentoptions for visceral leishmaniasis are limited and have traditionally been unsatisfactory because of drug toxicities, poor responses, multiple disease syndromes, and other factors - including recently, the emergence of antimony-resistant strains. Sodium stibogluconate (10÷60 days course depending on where the disease was contracted and whether illness is first or second episode), a historically effective and affordable pentavalent antimonial compound, is associated with fatal toxic effects^{ref1, ref2, ref3}, and in some regions its use has led to the development of resistant strains of Leishmania donovani^ref, with the result that fewer than 50% of treated patients are cured^{ref1, ref2, ref3, ref4}. In regions where antimony resistance is prevalent, intravenous amphotericin B (desoxycholate) (Fungizone, Sarabhai Piramel Pharmaceuticals) is used, but it is expensive and may require weeks of hospitalization with intensive clinical and laboratory monitoring. Liposomal formulations of amphotericin B, which require a shorter treatment course (5 days) and have fewer side effects, remain unaffordable at nearly 30 times the cost of conventional formulations^{ref1, ref2}. Miltefosine, the first effective oral therapy for visceral leishmaniasis (20 days course (leishmaniasis major responds in 10 days))^ref, is expensive^ref, is potentially teratogenic, and has significant gastrointestinal side effects^ref. Safe, effective, and affordable treatments for visceral leishmaniasis in regions where the disease is endemic are urgently needed, particularly in formulations that are compatible with rural settings. Because humans are the reservoir for visceral leishmaniasis in the Indian subcontinent, the infection could be eliminated with widespread treatment of patients and rigorous vector control^ref (although elimination may not be possible in regions where zoonotic visceral leishmaniasis is prevalent, such as Brazil). Paromomycin, an aminoglycoside antibiotic, has been shown to have a dose–response efficacy in the treatment of visceral leishmaniasis when administered intramuscularly at a dose of 12, 16, or 20 mg of sulfate per kilogram of body weight daily for 21 days^{ref1, ref2}. A phase 3, multicenter, noninferiority clinical trial showed that paromomycin was noninferior to amphotericin B for the treatment of visceral leishmaniasis in India^ref
• Leishmania infantum species complex
• Leishmania infantum (a.k.a. Leishmania donovani infantum)
Epidemiology : children between ages 1 and 4 in Mediterranean region (in Italy expecially zymodeme MON-1 / LON-49), sub-Saharan and East Africa, the Middle East, and China. Human and canine leishmaniasis in asymptomatic and symptomatic population in Northwestern Greece^ref.
• China : visceral leishmaniasis or Kala Azar was highly prevalent in  but has been effectively controlled since 1958. Only sporadic cases occur in the hilly and newly reclaimed desert areas in northwestern China^ref. Genetic typing of recent cases from Xinjiang province has found that Kala Azar from eastern China is similar to that from India^ref. A review of leishmaniasis in China concluded that apart from sporadic cases in Xinjiang and western Inner Mongolia, leishmaniasis had been brought under control in China^ref. It should be noted that leishmaniasis is also found in neighboring Kazakhstan
Transmission : zooanthroponoses; reservoir : Canis familiaris, Vulpes spp., jackals, and Rodentia; vectors: Phlebotomus perniciosus and Phlebotomus major in the Mediterranean littoral, Phlebotomus ariasi Middle East (usual vectors Phlebtomus papatasi and Phlebotomus caucasicus), sub-Saharan and East Africa (usual vectors Phlebotomus orientalis and Phlebotomus martini), and China (reservoir : Canis familiaris; usual vectors Phlebotomus chinensis and Phlebotomus sergenti).
=> Mediterranean or infantile visceral leishmaniasis
=> Chinese leishmaniosis
=> viscerotropic cutaneous leishmaniasis : a rare type of infection found in northeastern Saudi Arabia; after infection, instead of the usual cutaneous symptoms, fever and other systemic symptoms are seen and Leishmania can be detected in internal organs.
=> wet cutaneous (exception in this complex !) leishmaniasis / rural cutaneous leishmaniasis / Oriental sore / Aleppo boil / tropical sore or ulcer / Delhi boil / Biskra stud (reservoirs : desert Rodentia such as ground squirrels and gerbils (particularly Rhombomys opimus and Meriones spp.); vector : Phlebtomus papatasi, Phlebotomus sergenti) : infection is acute, rapidly evolving, and characterized by multiple sores with inflammation, ulcer, and crusting.
=> leishmaniasis recidivans : a relapsing form of either wet or dry cutaneous leishmaniasis, resembling cutaneous tuberculosis, in which the ulcer heals incompletely, scarring centrally but spreading peripherally, or heals and recrudesces at the edge of the ulcer; it may last for many years
• Leishmania major species complex
• Leishmania major (a.k.a. Leishmania tropica major)
Epidemiology : first discovered in rodents in south-central Asian areas of the former USSR; central to southwest Asia extending into northern Afghanistan, Pakistan, and northwest India
Transmission : zooanthroponosis; reservoirs : Rhombomys opimus, Psammomys obesus, Arvicanthis niloticus. In Sind (Pakistan). Meriones spp. (gerbils), which are granivorous and nocturnal in their habits. In north-west India Meriones hurrianae and Meriones lybicus (> Meriones crassus and Tatara indica) are thought to be the main vertebrate hosts, and may prove to be the reservoir hosts in the Sind area of Pakistan; vectors : Phlebotomus caucasicus, Phlebtomus papatasi, Phlebotomus salehi, Phlebotomus mongolensis, Sergentomyia clydei
Pathogenesis : infection with Leishmania major induces a protective immune response and long-term resistance to reinfection, which is thought to depend upon persistent parasites. Although effector CD4⁺ T cells are lost in the absence of parasites, central memory CD4⁺ T (T_CM) cells are maintained. Upon secondary infection, these central memory T cells become tissue-homing effector T cells and mediate protection. Thus, immunity to L. major is mediated by at least 2 distinct populations of CD4⁺ T cells: short-lived pathogen-dependent effector cells and long-lived pathogen-independent central memory cells. These data suggest that central memory T cells should be the targets for nonlive vaccines against infectious diseases requiring cell-mediated immunity^ref.
=> Old World rural cutaneous leishmaniosis / Aden ulcer / Oriental sore wet variety in Eastern Europe and Northern Africa : macule => papule on bite point => nodule => indolent ulcer => heals, leaving an atrophic scar, or undergoes bacterial overinfection, nausea and vomiting, and lymphadenitis
• dry or urban zoonotic cutaneous leishmaniasis (ZCL) : a type found mainly in large urban areas in the Middle East, the Mediterranean region, and the Indian subcontinent, transmitted by the vectors Phlebotomus sergenti and Phlebotomus papatasi. The reservoir may be either human or Canis familiaris. A slowly developing single lesion that persists for a year or more is typical
• leishmaniasis recidivans : a relapsing form of either wet or dry cutaneous leishmaniasis, resembling cutaneous tuberculosis, in which the ulcer heals incompletely, scarring centrally but spreading peripherally, or heals and recrudesces at the edge of the scar; it may last for many years
• sometimes causing viscerotropic cutaneous leishmaniasis
Prevention : it is generally agreed that in most cases, compulsory treatment of those infected with Leishmania major (ZCL) is the best strategy to control outbreaks. However, if the vector proves to be Phlebotomus papatasi, then it may be appropriate to spray the internal surfaces of houses and outhouses with residual insecticides. In fact, spraying was believed to have greatly reduced leishmaniasis in India when used to kill the indoor-resting anopheline vectors of malaria. However, such an approach will not kill sandfly adults resting outside homes, such as in rodent borrows. Although it might be argued that aerial spraying is more appropriate, this approach has rarely (if ever) been successful in controlling sandfly populations; even when used against mosquito vectors of malaria and dengue, aerial spraying has often failed. Moreover, it requires considerable organization and high costs, which most would consider totally unjustified, especially as the actual sandfly vector and their habits (such as resting places) have not actually been identified. Furthermore, outdoor spraying does not usually remain effective for more than 2 to 3 months. I would be surprised if there were "continuous migration" of sandflies from Afghanistan into the Sindh or other areas of Pakistan, as suggested in the report. Although they have been known to fly up to 2.2 km over a few days and might be dispersed considerable distances with the wind, sandflies generally fly very short distances. Nevertheless, human population movements, such as migration of labour forces and/or changes in rodent populations are more likely to have aided the reported increases in leishmaniasis.
Leishmania tropica species complex
• Leishmania tropica (a.k.a. Leishmania nilotica, Leishmania tropica minor, and Leishmania tropica tropica)
Epidemiology : in eastern Mediterranean sea, including Iran, Iraq, India, and Israel (95 cases, 24 of them Tiberias residents (increased by 150% in 2003 compared to 2002. The most dramatic rise was in Tiberias, where the Health Ministry registered 44 cases in the past 5 years. Ha'emek Hospital in Afula reported 40 cases since September 2002 -- 10 times more than in the previous 3.5 years). It was once prevalent in the Arava, the Dead Sea area and the Jordan Valley), India, Pakistan, Afghanistan. Leishmaniasis is endemic in Iraq : high-risk areas for visceral Leishmaniasis are Greater Bagdad area, Missan, Thi-Qar, and Basrah governates. The Iraqi health authorities reported in 2001 10.9 cases per 100 000 population of visceral leishmaniasis, which extrapolated mean that about 25 cases can be expected in returning US troops. The above numbers suggest a significantly higher transmission rate than reported in 2001. An incidence of cutaneous leishmaniasis as high as 200 cases out of 750 men in a single unit has been reported : it is not impossible with soldiers staying outside in a highly endemic area at the height of the transmission season. So far, there have been 2 cases of visceral leishmaniasis reported. Around 4% of Afghans are infected by leishmaniasis, and Kabul is home to 33% of these cases (67,500 people) : in Muslim countries, such as Afghanistan, affected women are often forbidden to breast-feed or have sex. Afghanistan's once-effective control programme has been destroyed by 20 years of conflict.
Transmission : an anthroponosis with vector : Phlebtomus papatasiin southern France, Italy, and certain Mediterranean islands, Phlebotomus sergenti in Iran, Iraq, and India (a domestic species that lives and breeds in and around houses and therefore has often been controlled by spraying the inside surfaces of houses with residual insecticides), Phlebotomus arabicus (the Galilee region of northern Israel^ref; Procavia capensis as probable reservoir hosts : the disease may break out in areas where new neighborhoods are being built. Large rocks are moved, and such circumstances bring the hyraxes close to human beings). Because Canis familiaris can become infected and develop canine leishmaniasis, they are sometimes referred to as alternative hosts, but not reservoir hosts. Since the sand fly is a low-flying insect, many leishmaniasis victims are children, who get bitten in the face; adults usually are affected in their lower exposed limbs, particularly their legs. Human to human transmission may also occur.
=> Old World cutaneous leishmaniosis / Aden ulcer / Oriental sore dry variety / Aleppo button / Biskra stud / the Lily of Jericho : incubation period of 6 months => macule => papule on bite point => nodule => indolent ulcer => heals, leaving an atrophic scar, or undergoes bacterial overinfection, nausea and vomiting, and lymphadenitis. By taking away the crust many protuberances appear (Montpellier sign or nail sign)
Prognosis : self-limiting within 6-12 months.
Prevention : in Middle-East immunization is obtained by injecting promastigotes in skin of covered body regions in order to prevent infection on exposed regions. Bed nets should be offered to those most at risk: the families and neighbours of infected people.
• Leishmania mexicana species complex
• Leishmania mexicana
• Leishmania mexicana amazonensis
Epidemiology : Amazon region of Brazil and neighboring countries (extreme northeast of Paraguay) and in Trinidad
Transmission : reservoirs : Oryzomys capito, Oryzomys concolor, Oryzomys macconnelli, Proechimys guyanensis, Heteromys anomalus, Neacomys spinosus, Nectomys squamipes, Dasyprocta spp., Marmosa murina, Marmosa mitis, Marmosa fuscata, Caluromys philander, Metachirus nudicaudatus; vector : Lutzomyia flaviscutellata.
A single lesion is usually present but a few cases of diffuse cutaneous leishmaniasis have been reported.
• Leishmania mexicana mexicana
Epidemiology : south-central Texas
Transmission : reservoirs : Ototylomys phyllotis, Heteromys desmarestianus, Nyctomys sumichrasti, Sigmodon hispidus; vector : Lutzomyia olmeca, Lutzomyia diabolica. The transmission
cycle involves rodents, especially Neotoma micropus, and the vector in this instance is possibly Lutzomyiaanthophora. In southern Texas, seropositive coyotes have been found, and there has been a report of an infected domestic cat. As leishmaniasis is common from Mexico down through much of South America, it is not surprising that it is occasionally reported in Texas. In contrast, the chances of transmission of leishmaniasis from people (or pets) infected in Iraq, Afghanistan, or the Middle East entering  the USA are minimal, although obviously health authorities should be aware of the possibility of transmission and  human cases so that rapid diagnosis and treatment can be made.
=> chicle, chiclero or chicheros ulcer : an endemic, zoonotic form of New World cutaneous leishmaniasis, found mainly in forest workers in the Yucatan and adjacent areas of Mexico, Belize, and Guatemala. It is characterized by one or a few lesions that are usually self-limited and heal within 6 months, except when the pinna of the ear is involved, in which case over a period of many years the chronic lesion invades and slowly destroys the cartilage of the ear.
• Leishmania mexicana venezuelensis
Transmission : in Leishmania mexicana-infected Lutzomyia longipalpis sand flies the anterior midgut is blocked by a gel of parasite origin, the promastigote secretory gel, including the filamentous proteophosphoglycan (fPPG)^ref
• Leishmania pifanoi (a.k.a. Leishmania mexicana pifanoi) in Venezuela and certain areas of Brazil
Proteomics : lipophosphoglycan (LPG) binds to CD209 / DC-SIGN
Transmission : vector : Lutzomyia longipalpis (in Venezuela parasite rates in caught vectors range from 0.15% (Isla Margarita) to 3% (Aragua State))
=> New World cutaneous leishmaniosis / American cutaneous leishmaniasis : their lesions develop and heal similarly to those of the Old World forms but tend to be less nodular and more ulcerative and destructive
=> diffuse or anergic cutaneous leishmaniasis : local and hematogenous spread from a primary lesion to produce generalized nodular lesions resembling those of lepromatous leprosy in the skin and sometimes involving the nasal mucosa and laryngopharynx. Individuals with this form of the disease do not develop an effective immune response to the infection.
=> leishmaniasis recidivans : a relapsing form of either wet or dry cutaneous leishmaniasis, resembling tuberculosis of the skin, in which the ulcer heals incompletely, scarring centrally but spreading peripherally, or heals and recrudesces at the edge of the scar; it may last for many years
• Viannia
• Leishmania braziliensis species complex (a.k.a. Leishmania viannia, Leishmania brasiliensis) : a taxonomic complex comprising the subspecies that cause mucocutaneous leishmaniasis in its various forms; all of the subspecies develop in the midgut, foregut, and hindgut of their sandfly vectors
• Leishmania braziliensis (a.k.a. Leishmania viannia brasiliensis)
Epidemiology : Brazil, Peru, Ecuador, Bolivia, Venezuela, Paraguay, and Columbia
Transmission : reservoirs : domestic animals (Oryzomys concolor, Oryzomys nigripes, Oryzomys capito, Proechimys guyanensis, Canis familiaris, Rattus norvegicus); vectors : Psychodopygus amazonensis, Psychodopygus paranensis, Psychodopygus wellcomei, Lutzomyia anduzei, Lutzomyia intermedia, Lutzomyia longipalpis (Paraguay^ref). Lutzomyia miganei, Lutzomyia pessoai, Lutzomyia shannoni, Lutzomyia whitmani
=> New World cutaneous leishmaniosis : macule => papule on bite point => nodule => indolent ulcer => heals, leaving an atrophic scar, or undergoes bacterial overinfection, nausea and vomiting, and lymphadenitis
• diffuse or anergic cutaneous leishmaniasis : local and hematogenous spread from a primary lesion to produce generalized nodular lesions resembling those of lepromatous leprosy in the skin and sometimes involving the nasal mucosa and laryngopharynx. Individuals with this form of the disease do not develop an effective immune response to the infection. It spreads to the nasal or oral mucosa, with naso-oropharyngeal symptoms sometimes appearing several years after resolution of the primary lesion(s) and sometimes while the primary lesions are present. Manifestations include chronic nasal symptoms, especially of the anterior nasal septum, progressing to erythema => papule on nose ("tapir nose")=> naso-oropharyngeal destruction. Secondary bacterial (or fungal) infections and associated problems are common
• mucocutaneous leishmaniasis / espundia : chronic, progressive metastatic spread of the lesions to the nasal, pharyngeal, and buccal mucosa months to years after the appearance of the initial cutaneous lesion, which has usually healed. It is often associated with mutilating destruction of the nasal septum, palate, lips, pharynx, and larynx
Leishmania peruviana (a.k.a. Leishmania viannia peruviana)
Epidemiology : in the Peruvian Andes only at altitudes of 900 to 3000 meters
Transmission : reservoir : Canis familiaris; vectors : Lutzomyia verrucarum, Lutzomyia peruensis)
=> New World cutaneous leishmaniosis / American cutaneous leishmaniasis / uta : their lesions develop and heal similarly to those of the Old World forms but tend to be less nodular and more ulcerative and destructive
• Leishmania guyanensis species complex
Leishmania guyanensis (a.k.a. Leishmania viannia guyanensis)
Transmission : reservoirs : Choloepus spp., Tamandua tetradactyla, Didelphys marsupialis; vector : Lutzamyia umbratilis
=> New World cutaneous leishmaniosis / American cutaneous leishmaniasis / pian bois / forest yaws : their lesions develop and heal similarly to those of the Old World forms but tend to be less nodular and more ulcerative and destructive
• Leishmania panamensis (a.k.a. Leishmania viannia panamensis)
Epidemiology : Panama and adjacent areas of Central America and Colombia.
Transmission : reservoirs : Choloepus hoffmanni, Bradypus infuscatus; vector : Lutzomyia trapidoi
=> New World cutaneous leishmaniosis : spread to the nasal or oral mucosa, with naso-oropharyngeal symptoms sometimes appearing several years after resolution of the primary lesion(s) and sometimes while the primary lesions are present. Manifestations include chronic nasal symptoms, especially of the anterior nasal septum, progressing to erythema => papula on nose ("tapir nose")=> naso-oropharyngeal destruction. Secondary bacterial (or fungal) infections and associated problems are common.
• mucocutaneous leishmaniasis / espundia : chronic, progressive metastatic spread of the lesions to the nasal, pharyngeal, and buccal mucosa months to years after the appearance of the initial cutaneous lesion, which has usually healed. It is often associated with mutilating destruction of the nasal septum, palate, lips, pharynx, and larynx
• Leishmania garnhami (a.k.a. Leishmania (Viannia) garnhami) : a species similar to L. mexicana amazonensis isolated from cases of cutaneous leishmaniasis in the region of the Venezuelan Andes
Mucocutanous leishmaniosis occurs in individuals with TNF-a-308 polymorphism.
• unclassified Leishmania
• Leishmania archibaldi
Transmission : vectors : Phlebotomus orientalis, Phlebotomus martini, Phlebotomus celiae
=> visceral leishmaniosis / black fever / Dumdum fever
East-African or Sudan leishmaniosis
Epidemiology : leishmaniasis is known to occur in outbreaks facilitated by famine and HIV co-infection. The last major outbreak of leishmaniasis in the southern Sudan was from 1984 to 1994, when the WHO estimated that 100 000 people died out of a population of 300 000 in the Western Upper Nile State. The highest prevalence of leishmaniasis in Paraguay is found in the southeastern part, and both cutaneous and mucocutaneous forms are seen : > 90% of cases come from the 3 departments of Caaguzu, Canendiya and San Pedro with reported incidence of about 50 per 100 000 population per year. > 250 cases of cutaneous leishmaniasis have been reported from January to May 2004. Between 30 and 40% of dogs tested positive in a recent survey. Visceral leishmaniasis is very rare, which makes these cases unusual.
Pathogenesis : negative leishmanin skin test, CD3 and CD4 lymphocytopenia, and significantly reduced numbers of memory CD4⁺ T cells were found in visceral leishmaniasis (VL) patients compared to treated VL patients or persons with self-limiting asymptomatic infection. The proportion of CD4⁺ and CD8⁺ T cells that produced IFN-g and IL-4 after stimulation with PMA and ionomycin was significantly reduced in VL patients compared to sub-clinical and asymptomatic infections or healthy controls. Plasma concentrations of IFN-g and IL-10 were elevated in VL^ref
Laboratory examinations :
• normocytic anemia, leukopenia, thrombocytopenia
• May-Grunwald and Giemsa staining
• culturing in Novy-Mac Neal-Nicolle (NNN) medium
• leishmanin Montenegro intradermoreaction or Napler formol-gellification test (due to high [Ab])
Therapy : intramuscular antimony (Sb-GlcNMe) or intravenous amphotericin B. The primary unmet need is for oral therapy. Of the several drugs in clinical development, miltefosine is unique in being an oral agent with efficacy against both visceral and cutaneous disease. Sitamaquine is an oral agent with substantial but not sufficient efficacy against visceral disease. Oral fluconazole has been shown to be more effective than placebo in one instance: for Leishmania major cutaneous disease from Saudi Arabia. Paromomycin is in widespread trial. Topical paromomycin formulations are being tested for cutaneous disease, and intramuscular paromomycin is in Phase III trial for Indian visceral disease. The most likely replacements for present therapy are oral miltefosine for many of the visceral and cutaneous syndromes, intramuscular paromomycin for visceral disease and topical paromomycin for some forms of cutaneous disease^ref. Over 30 days of intense feeding (?)
Prevention : there is no vaccine
Web resources : Leishmania genome network
• Leptomonas
• Trypanosoma (10-1200 mm) : a genus of protozoa comprising hemoflagellates parasitic in invertebrates and vertebrates, including humans; several species are pathogenic. Their life cycle involves amastigote, promastigote, epimastigote, and trypomastigote stages; the first 3 stages are found in the vector (usually a bloodsucking invertebrate) and the last in the vertebrate (definitive) host.
• in some systems of classification, trypanosomes are categorized in 2 groups according to where they develop in the digestive system of the vector:
• salivaria, including the subgenera Duttonella, Nannomonas, and Trypanozoon
• stercoraria, including the subgenera Megatrypanum, Herpetosoma, and Schizotrypanum
• another system classifies them into 4 groups based on biological similarities:
• (1) lewisi group, including T. lewisi, T. duttoni, T. theileri, T. cruzi, T. nabiasi, T. melophagium, and T. rangeli;
• (2) vivax group, including T. vivax and T. uniforme;
• (3) congolense group, including T. congolense, T. dimorphon, and T. simiae;
• (4) brucei group, including T. brucei, T. gambiense, T. rhodesiense, T. evansi, T. equinum, and T. equiperdum
• Trypanosoma melophagium : a nonpathogenic stercorarian species commonly found in sheep worldwide and transmitted by the sheep ked, Melophagus ovinus.
• Trypanosoma neotomae : a species found in wood rats in California, possibly identical with T. cruzi.
• Trypanosoma rangeli : a nonpathogenic, stercorarian species infecting humans and various animals, especially cats and dogs, primarily in Venezuela, Brazil, Colombia, Costa Rica, El Salvador, Guatemala, and Panama, and usually transmitted by reduviid flies of the genus Rhodnius.
• Trypanosoma rotatorium : the type species of the genus, and found in the blood of several species of frogs.
• Trypanosoma simiae : a salivarian species found especially in East Africa and eastern Zaire, first reported from the monkey although its natural reservoir is the warthog, and usually transmitted by tsetse flies (Glossina spp.) but sometimes also by bloodsucking flies. It causes nagana in various domestic animals, being highly pathogenic for camels (causing death in several days), mildly pathogenic for goats, and apparently nonpathogenic for cattle, horses, and dogs.
• Trypanosoma suis : a species that causes nagana in pigs.
• Trypanosoma theileri : a large stercorarian species found in the blood of cattle worldwide, transmitted by tabanid flies, and usually nonpathogenic although under stressful conditions it may be associated with illness and perhaps death.
• Trypanosoma theodori : a nonpathogenic, stercorarian species similar to (and perhaps the same as) T. melophagium that is found in goats and has the hippoboscid Lipoptena caprina as an intermediate host.
• Trypanosoma uniforme : a tsetse fly–transmitted salivarian species similar to but smaller than T. vivax that is a cause of nagana in cattle, goats, sheep, and antelopes in Zaire.
• Duttonella
• Trypanosoma vivax : a tsetse fly–transmitted salivarian species found in many animals, including cattle, sheep, goats, camels, horses, antelopes, and giraffes in Africa, Central and South America, the West Indies, and Mauritius. It is a cause of nagana, the severity of which depends on the species affected, being fatal in certain types of cattle in certain areas.
• Nannomonas
• Trypanosoma congolense (a.k.a. Trypanosoma nanum) a tsetse fly–transmitted salivarian species found in Central Africa that is a cause of nagana in domestic animals, which is especially severe in cattle
• Trypanosoma dimorphon a tsetse fly–transmitted salivarian species widely distributed in Central Africa, which was formerly thought to be identical with T. congolense but has been shown to be a distinct species. It is found in horses, pigs, goats, sheep, cattle, and dogs, in the latter three of which it has been shown to be more pathogenic than T. congolense.
• Herpetosoma (Stercoraria section => replication in lower tract of vector digestive apparatus => transmission via vector stools)
• Trypanosoma lewisi (a.k.a. Trypanosoma (Herpetosoma) lewisi) a stercorarian species commonly found in the blood of rats worldwide, usually nonpathogenic in adults but causing lethal infection in sucklings, and transmitted by the rat flea, Nosopsyllus fasciatus. The species is much used in laboratory research.
• Trypanosoma rangeli
=> non pathogenic ? (reservoir : Canis familiaris, Felis catus, Cebus spp., Tamandua spp.; vectors : Rhodnius prolixus, Triatoma dimidiata : they can transmit it even through saliva)
• Schizotrypanum (Stercoraria section => replication in lower tract of vector digestive apparatus => transmission via vector stools)
• Trypanosoma cruzi (a.k.a. Trypanosoma triatomae and Schizotrypanum cruzi)^ref
• Trypanosoma cruzi cruzi
• Trypanosoma cruzi marinkellei
Only zymodemes Z1, Z2 and Z3 are pathogenic for Homo. Also schizodemes (genovars detected by DNA fingerprinting using EcoRI on ktDNA) exist. Obliged intracellular parasite.
Epidemiology : 18 countries on the American continent in 2 different ecological zones:
• the Southern Cone region, where the main vector lives inside human homes and in peridomiciliary areas
• Central America and Mexico where the main vector species lives both inside dwellings and in uninhabited areas
• Peru : a total population of 600 000 is estimated to live in areas of Chagas disease transmission. In 1999, the screening of donated blood yielded a rate of 0.8% positive results^ref. Endemic in 3 regions: southwest, including Arequipa, Moquegua, Tacna, and Ica Departments, sharing characteristics with Northern Chile and Bolivia, since Triatoma infestans is the only recognized vector; the Northeastern area, including coastal regions from La Libertad, Lambayeque, Piura, and Tumbes Departments, where house-based vectors such as Rhodnius ecuadoriensis have been identified; and the third area corresponds to the Northeastern region, including Amazonas, Cajamarca, and San Martin Departments, all of them in the basins of rivers tributary of Amazonas river, where the most important vector is Panstrongylus herreri, which also colonizes households.
Country-wide cross-sectional surveys in the 1980s found an overall prevalence of 17 million cases, with 4.8-5.4 million people exhibiting clinical symptoms, an annual incidence of 700,000-800,000 new cases and 45,000 deaths every year due to the cardiac form of the disease At present, estimates indicate an infection prevalence of 13 million, with 3.0-3.3 million symptomatic cases and an annual incidence of 200,000 cases in 15 countries; population exposed at risk : 90 millions. The suspicion that a patient in India may present a patent infection of some form of trypanosomiasis is not entirely improbable. On the contrary, suspected human cases of Trypanosoma lewisi, another murine parasite, have been reported in India (2 cases, 1974) and Malaysia (1 case, 1933). There have been other incidental reports as well. However, unlike T. cruzi, T. lewisi is transmitted by Xenopsylla cheopis and Nosopsylla fasciatus. The morphology of T. lewisi can be easily distinguished from T. cruzi. Moreover, assuming no travel-related exposure or blood transfusions in the recent case, it appears nearly impossible that T. cruzi, and most certainly the 2 African trypanosomes, would be endemic in India. Trypanosome parasites are found in a great variety of mammals, but less well known trypanosomes are found in fish (vectors being leeches), amphibians (vectors are mainly leeches), reptiles (vectors are phlebotomine sandflies, tsetse flies and leeches), and finally, avian trypanosomes transmitted by mosquitoes, simuliid black-flies, hippoboscid flies and the chicken mite (Dermanyssus gallinae)
Genomics : gene exchange between clones of different genotypes occurs via multiple and unusual mechanisms
Proteomics :
• Trypanosoma decay accelerating factor (T-DAF) prevents C-mediated lysis until it is neutralized by host Abs
• Tc52 protein binds to TLR2
• trans-sialidase (both membrane-bound and shed) has anti-AICD and costimulatory effects on CD4⁺ T cells, both depending on CD43
• pore-forming protein showing immunological crossreactivity to complement C9
Transmission :
• a percutaneous zooanthroponoses; reservoir : over 150 species from 24 families of domestic and wild mammals, including Canis familiaris, Felis catus, Rattus norvegicus, Mus musculus, Didelphis spp., Dasypus spp., Tamandua spp., Desmodes spp., Glossophaga spp., Carollia spp., Aotus spp., Saimiri spp., Ateles spp. (in the vertebrate host, it infects many different cells, but in the human host, the disease is conspicuously limited to the myocardium and to gut nerve fibres); vectors : Rhodnius prolixus, Triatoma infestans, Triatoma dimidiata, Triatoma sordida, Triatoma brasiliensis, Panstrongylus megistus, Rhodnius pallescens, Dipetalogaster maximum^ref
• transplacental transmission
• blood transfusion : only 5 cases of blood transfusion infections have been confirmed in the US (3) and Canada (2 : both immunocompromised by chemotherapy for cancer). The risk of infections through blood transfusions has been estimated to be between 1 per 43 to 1 per 1072 transfusions in different countries. However, the risk of being infected if receiving blood from a T.cruzi seropositive donor is most probably overestimated. Recent seroprevalence studies showed that approximately 0.1% of blood donors likely to have been born in or have traveled to disease-endemic countries were seropositive for T. cruzi. Moreover, American Red Cross studies of recipients of T. cruzi­seropositive blood and blood products showed no evidence of transmission. Travellers are rarely exposed to infection, and T.cruzi infection in travellers is exceedingly rare. The triatomid bug lives in cracks and crevices in mud walls, and it is therefore immigrants living under poor conditions for a prolonged time who may carry the infection and pass it on through blood transfusion. A study conducted in the same geographic area of the U.S. documents ratios of Chagas- seropositive blood donors ranging from one positive in 9,900 in 1996, to one in 7,200 in 1997, to one in 5,400 in 1998^ref.A new study, completed in November 2006, documents the ratio of Chagas-seropositive blood donors at approximately one in 2,000 (Dr. Susan L. Stramer, Executive Scientific Officer, American Red Cross; presentation at 2006 American Association of Blood Banks (AABB) "Ongoing Clinical Evaluations of a Chagas' ELISA in US Blood Donors; Trypanosoma cruzi Antibody Prevalence in Three Regions of the American Red Cross" 23 October 2006)
• solid organ transplantation : although routine serologic testing of organ and blood donors is performed in areas of Latin America where Chagas disease is endemic, no T. cruzi screening test is licensed in the USA. However, seroprevalence studies using research tests have documented the presence of T. cruzi antibodies in U.S. blood^ref and organ donor populations^ref. 2 cases of acute Chagas disease in heart transplant recipients were reported by 2 Los Angeles County hospitals in February 2006^ref. In the USA, one previous report documented T. cruzi transmission through solid organ transplantation, in which 3 organ recipients were infected^ref. Persons born outside endemic areas by infected mothers can be infected in utero with congenital Trypanosoma cruzi and may remain infectious
• oral transmission can cause microepidemics of acute Chagas disease^ref. No doubt oral transmission to humans has been occurring for a long time. However, in the context of high levels of vector transmission, these cases went unnoticed. In the 1990s human cases acquired by the oral route were reported.
• Shikanai-Yasuda et al. reported 3 cases by oral transmission, apart from one possibly by breast-feeding^ref.
• A year later, the same group reported an outbreak in 1986, with 26 patients that acquired Chagas´ disease with acute phase symptoms after a family gathering in the Northeastern state of Paraiba^ref.
• Brazil : since the decline of vector-transmitted disease in Brazil, 1st in the State of Sao Paulo in the 1970s and then in other states in the 1990s, oral transmission has been a subject of growing concern
• Santa Catarina : this Southern state has never been an endemic area for Chagas´disease. Although Panstrongylus megistus can be found in forest areas, they have not moved into homes, as in Bahia or Minas Gerais, states well North of Santa Catarina. Chagas´ disease in wildlife is common in Santa Catarina, as well as in coastal areas in South and Southeastern Brazil. A rather recent paper^ref reported that oral sporadic transmission seems to be rather common in certain rural areas. This has been reported also from the Amazon, associated with acai, a rain-forest fruit that is rather a fad in urban areas, causing a small boom in the acai industry. This fruit is processed much in the same way as sugar-cane, in order to obtain a paste. As the fruit is found in palm-like trees, a favorite habitat of triatomid bugs, the result is a fruit paste contaminated with Trypanosoma cruzi. The most probable explanation for the outbreak in Santa Catarina is that sugar-cane was harvested and kept in some kind of makeshift shed that harbored triatomid bugs, and the droppings of these bugs contaminated the sugarcane, resulting in a juice with T.cruzi. As sugarcane juice (locally called "garapa") is drunk fresh, immediately after processing, the risk of infection is high. Oral transmission of T.cruzi to mammals was first demonstrated experimentally in 1958 (Phillips NR, Thesis, University of London, cited by Hoare CA in "The Trypanosomes of mammals, Blackwell Scientific Publ., London 1972), when 50% of mice became infected after being fed T.cruzi-infected triatomid bugs. Ingestion of infected vectors was also found to be the main mode of transmission among wood-rats in north America (Ryckman & Olsen, J Med Entomol 1972,2:99). Triatomid bugs have a preference for feeding from the face of sleeping humans and shed the parasites in their feces after the blood meal. The parasites are then thought to infect humans through the mucus membranes in the mouth or the conjunctiva. There is no information on how long the epimastigotes of T.cruzi remain infective after being passed in bug feces, which seems to be a key parameter for food-borne transmission. Sugar cane juice, also known as "garapa," is a very common beverage all over the country and is made by crushing the cane. The triatomid insect vector may have been crushed during this process, or the cane could have become contaminated with infected bugs' feces. So far there have been 31 confirmed cases and  5 deaths; additional 64 suspected cases under investigation. There may have been > 50 000 possible exposures (which includes international travellers). All cases were apparently related to drinking garapa in cities along the northern beaches of the State (to name all the suspicious cities:  Itapoa, Garuva,  Joinville, Araquari, Sao Francisco do Sul, Balneario Barra do Sul, Barra Velha, Picarras, Penha, Navegantes, Itajai, Balnearion Camboriu, Camboriu, and Itapema) : 91% of the cases had ingested sugar cane juice at the Kiosk Barracao da Penha 2, between the municipalities of Navegantes and Pen-ha, on the side of the BR-101 highway by Kilometer 111. The test, conducted by the Department of Microbiology and Parasitology of the Federal University of Santa Catarina, proved the presence of the protozoan in a triatomid bug hidden in a towel -- a product that is also sold in this kiosk. Norms aimed specifically for the sale of sugar cane juice will take effect on 31 Mar 2005. ANVISA (the National Sanitary Surveillance Unit) announced that all persons who drank sugar cane juice from the kiosks along highway BR-101, between Picarras and Italjai, during the period 1 Feb 2005 through 23 Mar 2005 are to be considered inappropriate for blood donation.  There are 2 research papers referring to previous outbreaks of Chagas disease associated with the oral route of transmission (1968 in Teutonia RS^ref and 1991 - Catole do Rocha PB^ref), the larger of which presents 26 confirmed cases. Incubation period seems to be around 7-28 days, and the main signs and symptoms include high fever for > 5 days; myalgia; headache; orbital swelling and hepatosplenomegaly. In such cases diagnosis must be confirmed with serology (remember that many labs perform only IgG); IgM and direct visualization on smears. Treatment with either benzonidazol or nifurtimox must be provided ASAP for all acute cases, especially symptomatic ones. Cure rates are around 70%. For diagnosis in asymptomatic cases, we are recommending just serology IgG and IgM. In negative cases with > 30 days elapsed from exposure, close the case; < 30 days, repeat serology within 2-4 weeks. All positive cases must be confirmed with a 2nd serological exam or direct visualization of T. cruzi. The main factor for the risk of spreading Chagas disease by food and drink is the survival of the trypanosomes after they have left the intestine of the triatomid bug. How sensitive are they to changes in temperature, pH, and osmolarity? This will determine how long they can stay infective in bug feces on sugar cane. In 1968, a member of a farming community in Teotonia (Rio Grande do Sul) fell ill with a severe febrile illness. No one suspected Chagas disease, as there were no Reduviid bug vectors in the local dwellings. After much investigation, food borne transmission through vegetables served in the common dining-room was accepted as the cause. Possibly, marsupials had contaminated the vegetables by droppings from their anal glands, usually rich in T.cruzi. In 1986, another outbreak occurred, this time in Catole do Rocha (Paraiba). A large wedding anniversary party had been held on a farm. Days later, some of the guests fell ill with a febrile illness, similar to the one in Teotonia. Sugarcane juice and other foodstuffs or beverages had been contaminated by animal droppings. The couple that had celebrated their 50th anniversary eventually died as a consequence of Chagas disease acquired at the party. Recently, oral transmission of T.cruzi has been responsible for small outbreaks in the state of Para. Entire families acquired Chagas disease in the absence of insect vectors in their homes. These insects live in palm trees and, attracted by the lights, fall into the machinery used to grind acai to obtain juice (much the way sugarcane juice is obtained). The insects are ground and contaminate the juice with T.cruzi, transmitting the infection to those drinking it. All of these cases in Rio Grande do Sul, Paraiba and Para attracted the attention of scientists. The question which was brought forward was why didn't gastric juice destroy T.cruzi ? The physician Sonia Gomes Andrade from CPqGM, who specializes in experimental pathology, formulated an experiment: she introduced T.cruzi through a tube directly into the stomach of mice,. She studied the strains isolated from cases in Paraiba and Para. She observed that the parasite not only survived gastric juice but was able to infect the mice. They developed disease identical to the one produced when mice are infected directly via the bloodstream. The findings of the researcher confirm that T.cruzi, when swallowed, can cause infection through the digestive system. In the most common manner of infection, scratching, T.cruzi is able to penetrate the skin. It is easy to imagine that, when someone ingests a large quantity of parasites, the infection will be more severe. There is no reason to stop eating vegetables or drinking sugarcane or acai juice. The problem lies not with the kind of food but with T.cruzi. These are mainly parasites of biodem type III -- from wildlife -- that are able to cause infection through the digestive system. A biodem is a group of genetically close T.cruzi strains with similar characteristics. Biodem type III strains are, as a rule, highly pathogenic. In the experiment, a strain of this type showed a higher capacity to cross the gastric barrier and cause infection in mice than strains from biodems I and II.  It is significant to point out that biodem III strains are associated with wildlife disease cycles, causing outbreaks in places where Reduviid bugs are not domiciled. It seems beyond doubt that T.cruzi can infect hosts, including humans, by the oral route, but it still remains unclear how important this route of transmission is for maintaining infections in humans and causing outbreaks like the present one. The mouse experiment cited above confirms previous reports Hoft et al. Infect Immun 1996,64:3800-10] that T.cruzi can indeed infect the host through the gastric mucosa. The key question is how long a time T.cruzi can survive in feces outside the triatomid bug, and how long a time in different forms of fluids after the triatomid bugs have been crushed. Oral transmission, either from bug feces or from crushed bugs, presumes that T.cruzi can survive for at least several hours, possibly days, in juice. Information on this survival time is key to determining whether the present outbreak is a rare coincidence or just part of a more widespread problem.
• In Santarem township, in western Para state, 780 km from Belem (near the mouth of the Amazon river), 20 cases of Chagas' disease were confirmed by the Division of Health Surveillance (DVS) of the municipal health secretariat in July 2006 :  DVS believes the appearance of the new cases is due to drinking bacaba wine, made from the fruit of a palm (Oenocarpus bacaba) similar to that of the acai palm. The hemipteran vector was found in bunches of the berry-like fruit and could have been ground up with the fruit^ref.
During the past decades, after urban migrations, Chagas disease became frequent in cities and a health problem in non-endemic countries, where it can be transmitted vertically and by blood transfusion or organ transplantation.
Pathogenesis : parasite-derived danger signal (parasitokines, ...) => breakdown of self-tolerance => autoimmunity. It induces up-regulation of both Fas and FasL on parasite-specific IgG⁺ B cells and renders them susceptible to B cell-B cell killing (fratricide). Integration of T.cruzi kinetoplast DNA (kDNA) into the genomes of infected patients, as well as chicken and rabbit animal models, suggesting that horizontal gene transfer may play a role in T.cruzi host–parasite interactions. In the human chromosomes, 5 loci were identified as integration sites, and the beta-globin locus and LINE-1 retrotransposons were frequently targeted. Short repeated sequences in the parasite and the target host DNAs favor kDNA integration by homologous recombination. Introduced kDNA was present in offspring of chronically infected rabbits and in chickens hatched from T. cruzi-inoculated eggs. kDNA incorporated into the chicken germline was inherited through the F₂ generation in the absence of persistent infection. If this process involves the germline, integrated kDNA could theoretically alter human genetics through disruption of protein-coding sequences and promotion of recombination events between kDNA integration sites. kDNA integration represents a potential cause for the autoimmune response that develops in a percentage of chronic Chagas patients, which can now be approached experimentally^ref
=> Chagas' disease / American trypanosomiasis :
• 90% asymptomatic
• 10% symptomatic :
• acute phase : after 8-14 days incubation remitting or continuous fever appears. Infection through skin causes erythema nodosum (sometimes evolving to ulcer : chagoma) while infection through conjunctiva causes unilateral ophthalmia with palpebral edema, conjunctivitis and preauricular lymphadenitis(Romaña sign), replication in ...
• smooth muscle cells
• skeletal muscle cells
• cardiomyocytes => acute myocarditis
• CNS neurons => meningoencephalitis (10 %) and Castellani-Low symptom : a fine tremor of the tongue seen in sleeping sickness
Self-limiting or lethal within a month due mainly to heart failure. If pregnants are infected within month 3 => abortion. Congenital infection : splenomegaly.
• latency (from months up to 20 years)
• chronic phase (33%) : Chagas disease has a cronic course in various regions of the body. Replication in
• vegetative nervous system neurons causes functional incompetence and dilatations known as mega formations :
• chronic chagasic cardiomyopathy (CCC) (myocarditis => 25 % undergo cardiomegaly => congestive heart failure(1^st cause of heart failure in Latin America, 10% total mortality) => oedemas => sudden death)
• urinary apparatus
• megapelvis
• megaloureter
• megabladder
• bronchiectasis
• megabronchus
• digestive apparatus
• megapharynx (?)
• achalasia of the LES => megaesophagus and dysphagia
• achalasia of the pylorus / hypertrophic pyloric stenosis => megastomach / gastromegaly
• megaduodenum
• mega-gallbladder
• mega-common bile duct
• megaintestine (mega-small bowel)
• dilated forms have not been described in the jejunum and in the ileum. This may be due to the fact that these two segments of the digestive tract, because of their essential functions, are very resistant to infection.
• megappendix
• megacolon => constipation
• megasigmoid
• megarectum
• hypertrophy of the salivary glands (parotid)
• mesenteric and sciatic nerves necrosis due to type II and IV hypersensitivities
• nyctalopia : under bright conditions, the Chagas patients performed comparably to 50 healthy control individuals. But in the dark, 37 of 45 (82%) Chagas patients had trouble seeing with at least one eye, and 19 of 45 (42%) had trouble with both eyes. It turns out that molecular mimicry can also upset the delicate machinery inside retinal cells. Antibodies geared to attack T. cruzi also block rhodopsin, a molecule that converts light into electrical impulses sent to the brain^ref.
Laboratory examinations :
• PCR, Giemsa staining, Machado-Guerreiro complement fixation, xenodiagnosis in Triatominae infected with patient's serum (looking for parasites in stools after 30-60 days)
• ORTHO^®T.cruzi ELISA Test System (source : Ortho-Clinical Diagnostics) is the first blood-screening test for Chagas' disease approved by the FDA for use in the USA
Therapy :
• nifurtimox 8-10 mg/kg/day po qid for 90-120 days or benznidazole 5 mg/kg/day po for 60 days, exachlorocycloesan, allopurinol (?). These long-term therapies are toxic to some patients. TAK-187 is effective at a dose that is both 10 times lower and administered less frequently than that of benznidazole in preventing CCC.
• autologous bone marrow transplantation into the circulation of patients with severe chagasic cardiomyopathy improves cardiac functions of up to 30%, in one case occurring one month after transplantation
Prevention : blood for transfusions can be sterilized by using methylene blue and KMnO₄, then removed by PVA resin.
• Trypanozoon (in some systems of classification, a subgenus of salivarian trypanosomes (Salivaria section), including Trypanosoma evansi, Trypanosoma equinum, and Trypanosoma equiperdum  => replication in upper tract of vector digestive apparatus (metacyclic trypomastigote in salivary glands) => transmission via vector saliva or regurgitated hemolymph)
• Trypanosoma brucei : 3 morphologically indistinguishable subspecies or varieties</