Various forms are clinically distinguished, the most important of which are :
Localised cutaneous leishmaniasis: skin ulcers that heal very slowly or nodular lesions, limited in extent and number. These chronic sores have regional names: clou de Biskra in Algeria and Aleppo boil in Syria.
Diffuse cutaneous leishmaniasis: cutaneous nodules and plaques that do not ulcerate but can sometimes spread over the entire body.
Recurrent cutaneous leishmaniasis

Attempts should be made to detect the parasite microscopically in a biopsy or smear from the edge of the wound. The biopsy will, if possible, be divided up for pathology (seldom available, not very sensitive, is principally used more for exclusion of another cause) and cultures (bacteria, mycobacteria, fungi, Leishmania) and an impression preparation should also be made. Lesions on the face can be injected with 0.1 ml physiological saline and aspirated again while moving the small, thin needle back and forth in the skin. Serology is usually negative. Differential diagnosis includes ulcers due to mycobacteria, cutaneous diphtheria, tertiary syphilis, yaws, cutaneous carcinoma and deep or subcutaneous mycosis. Acid fast bacilli can be made visible using the method of Ziehl-Neelsen. Field sore (cutaneous diphtheria) and tropical ulcers (fusobacteria + Borrelia) are painful, particularly in the early phase.

The response to treatment varies according to the species. Drugs for systemic and topical treatment can be used. There is an urgent need for better and cheaper drugs.
Indications for local treatment
lack of risk of developing mucosal lesions
Old World cutaneous leishmaniasis
small, single lesion
absence of lymph node metastasis
Indications for systemic treatment

physical methods: cryotherapy (liquid nitrogen) for 15-20", repeated 2-3 times. Blistering will occur.
application of local heat (e.g. infrared lamp). Heat-induced skin bullae are common.
ointment with 15% paromomycin and 12% methylbenzethonium chloride in soft white paraffin (e.g. Leishcutan® ointment). Urea can be added as a keratolytic. Twice daily application is advised, for a duration of 20-30 days.
skin infiltration with pentavalent antimony with a fine gauge needle. Blanching of the lesions should be obtained. Treatment is repeated every 5-7 days, in general 2-5 times, sometimes more.

Pentavalent antimonials (meglumine antimonate [85 mg Sb/ml, IM] or sodium stibogluconate [100 mg/ml, IV]. Duration of treatment is not standarised (e.g. 14 to 28 days).
Pentamidine. First line against L. guyanensis (French Guyana). Check glycaemia. Several treatment schemes exist and the cure rate is dose-dependent. Some short-courses use 1200 mg as a total dose. In Guyana 3 mg/kg/day every other day is often used (4 injections).
Imidazoles, triazoles. Fluconazole promising against L. major. Ketoconazole 600 mg per day x 28 days is moderately effective for L. mexicana, but much lower against L. braziliensis.

At present 90% of all mucocutaneous leishmaniasis occurs in Bolivia, Peru and Brazil. Illustrations of skin lesions and disfigurements suggestive of leishmaniasis are encountered on pre-Inca earthenware. These indicate that the disease was already in existence in Peru and Ecuador in the 1st century AD. Texts dating from the 15-16th century Inca period and the Spanish conquest mention the risk of cutaneous ulcers in seasonal farmers. Espundia was also described as "white leprosy".

When skin and mucosae are affected the disease is known as mucocutaneous leishmaniasis. This is very rare in East Africa but frequent in South America, where it is known as "espundia". After an initial skin lesion, that slowly but spontaneously heals, chronic ulcers appear after months or years on the skin, mouth and nose, with destruction of underlying tissue (nasal cartilage, for example). Tissue destruction with disfigurement can be very severe. Parasites are usually rare in the lesions. A substantial part of the disfigurement is possibly due to immunological mechanisms. One hypothesis is a relationship between the occurrence of mucocutaneous lesions and the presence of certain alleles of polymorphic tumour necrosis factor  and  genes.

The lesions often contain few parasites. Diagnosis is sometimes made solely on a clinical basis. Culture of the parasites is possible, but not really feasible in primitive rural conditions. Serology in espundia can be positive or negative (the quality of the antigen is of crucial importance). A practical problem in South America is whether a certain skin lesion with Leishmania amastigotes is caused by L. braziliensis or not. The geographical origin of the lesion or PCR and/or zymodeme analyses may give an answer here, though these laboratory techniques are not available in rural areas.

Differential diagnosis includes skin cancer, tertiary syphilis and yaws, leprosy, rhinoscleroma (a very chronic granulomatous infection with Klebsiella rhinoscleromatis), rhinosporidiosis, midline granuloma (a form of T-cell lymphoma), Wegener's granulomatosis, sarcoidosis, skin tuberculosis, infection with the free-living amoeba Balamuthia mandrillaris, chronic nasal cocaine abuse, noma, and fungal infections such cryptococcosis, histoplasmosis and South American blastomycosis (paracoccidioidomycosis). With this last disease, which is a very chronic infection, the lungs are frequently affected in a manner that can mimic tuberculosis. The yeast has typical oval cells with ectospores and can be detected in sputum.

Systemic drugs should be given. In South America meglumine antimonate® (20 mg Sb/kg/day for 30 days) is first choice. Beware: the dose is expressed in mg antimony (Sb). Alternatives are amphotericin B (Fungizone®), pentamidine and allopurinol. Ketoconazole can be used in L. mexicana infections. Plastic surgery is sometimes necessary in espundia in case of disfigurement. The use of pentoxyphylline (a xanthine derivative) plus antimony in refractory mucosal leishmaniasis is still in the experimental phase. Pentoxyphylline 400 mg t.i.d. orally for 30 days should have an anti-TNF-α effect. It is better known for its vasodilating effects (use in chronic occlusive diseases of the legs).

arly case-detection, treatment and reporting of the case. Control of leishmaniasis is sometimes restricted to these "minimal control initiatives" owing to, for example, financial reasons.
Vector control with insecticides in and around dwellings. This can be coordinated with malaria and/or Chagas’ disease control.
Use of a fine gauze mosquito net impregnated with permetrine if transmission is taking place via a nocturnal biting vector
Biotope modification: environmental sanitation in order to destroy the sandflies’ breeding sites. An area of 300 metre radius is sometimes cleared of vegetation around villages (Amazonia, French Guyana).

General Occurrence of abdominal complaints together with peripheral hypereosinophilia with or without increased IgE values and/or Charcot-Leydig crystals in the faeces is a frequent problem after travel in the (sub)tropics. A problem that occurs during or after a trip does not necessarily need to have a causal connection with that trip. It may be an incidental combination of eosinophilia and abdominal discomfort (no causal relationship). It occasionally is a cosmopolitan condition, though there is often an exotic cause.
Worm infestations are often responable for eosinophilia and abdominal complains. As a rule it can be stated that protozoa do not cause eosinophilia, with the exception of Sarcocystis (eosinophilic enteritis) and Isospora belli, although this is controversial.

General There is sometimes an incidental combination of eosinophilia and pruritus (no causal relation). In a traveller to the (sub)tropics, it occasionally concerns a cosmopolitan disease, though there is often an exotic cause. Scabies (Sarcoptes sp.) and pubic lice (Phthirus pubis) are a frequent cause of pruritus, but do not so frequently cause eosinophilia.
Reactions to bites and stings Reactions to insect bites and stings (Culicoides sp, bedbugs, etc.), trombiculosis (harvest mites), contact dermatitis (e.g. to plants) and allergic reactions to medications taken during a trip sometimes raise diagnostic problems. Itching dermatitis can be elicited by the hairs of caterpillars of certain Lepidoptera. The hairs of certain bird spiders can also cause prolonged, severe pruritus.

There may be an incidental combination of eosinophilia and respiratory symptoms (no causal relationship). A cosmopolitan disease (e.g. asthma) may occasionally be involved, but there is often an exotic cause in travellers with recent onset respiratory problems and eosinophilia.
Among the exotic causes we mention paragonomiasis (lung flukes), Katayama syndrome (acute schistosomiasis) and occult filariosis (Weingarten syndrome or tropical pulmonary eosinophilia syndrome). Migration of various nematode larvae (Ancylostoma, Strongyloides, Ascaris, Toxocara) through the lung can result in Loeffler's syndrome. Strongyloides infections tend to be very persistent (beware of steroids and HTLV-1 infections). Chronic schistosomiasis can also cause pulmonary lesions and eosinophilia. Pulmonary echinococcosis tends to be asymptomatic although narrowing of a bronchial lumen can occur due to external compression.

Know the mechanism of formation of congenital and acquired diverticula. congenital--may be due to a focal failure of development of the normal musculature or to some urinary tract obstruction during fetal development
acquired--seen most often w/prostatic enlargement, producing obstruction to urine outflow & marked muscle thickening of the bladder wall; increased intravesical pressure causes outpouching of bladder wall & formation of diverticula
Know the complications of bladder diverticula: stone and urinary infection.

Know the causes (table 22-1 p.999 Robbins) & consequences of ureteral obstruction. causes
intrinsic: calculi, strictures, tumorous masses, blood clots, neurogenic causes
extrinsic: pregnancy, periureteral inflammation, endometriosis, tumors
consequences--hydroureter, hydronephrosis, sometimes pyelonephritis
Know sites where stones are most frequently impacted in the ureter.
places of ureteral narrowing--uretoro-pelvic junction, where ureters cross iliac vessels, & where they enter bladder

What is the clinical significance of renal hamartoma?
usually an incidental finding at autopsy; no malignant properties
Which disease is/can be assoc. w/ angiolopoma?
these are present in 25-50% of pts w/tuberous sclerosis, a disease characterized by lesions of the cerebral cortex that produce epilepsy and mental retardation as well as a variety of skin abnormalities
What is oncocytoma?
epithelial tumor thought to arise from intercalated cells of collecting ducts; not uncommon

Know the pathogenesis of type I and type II MPGN Type I - Chronic Immune Complex GN
Granular deposits of IgG and C3 in subendothelial and mesangial distributions
Activation of classic complement pathway
Presence of cryoglobulins and circulating Igs
Similar lesions produced in animal studies utilizing foreign serum proteins
Type II – Dense deposit disease

Know the pathology, clinical manifestations, classification, and prognosis of lupus nephritis
Class I – normal kidneyClass II –Minimal/Mesangial Lupus NephritisEarliest and mildest form of renal involvementCharacterized by mesangial deposits of Ig and C3Proteinuria and hematuria presentNephrotic syndrome and renal insufficiency are very uncommonEM – IC deposits in mesangiumIF – appears similar to IgAClass IIA – mesangial proliferative changeClass IIB – no proliferative changeClass III – Focal proliferative Lupus Nephritis

What is ANCA?
Antineutophil cytoplasmic antibodies
Autoantibodies with specificity for constituents of neutrophil primary granules and monocyte lysosomes
Where are ANCA antigens in normal conditions and after activation of neutrophils?
Detected in serum using IF – 2 types
C-ANCA (cytoplasmic) – most commonly seen in Wegener’s
P-ANCA (perinuclear) – specificity for myeloperoxidase and reacts w/ neutophil elastase, seen in renal-limited disease

Know the glomerular lesions in DM. Which one is the most characteristic of diabetic nephropathy?
Nodular intercapillary glomerulosclerosis Most characteristic, but not diagnostic (amyloidosis)
Acellular
Located in mesangial/intercapillary regions of glomerular tufts
Laminated appearance and are eosinophilic on H&E stain
PAS+ and argyrophillic
Almost always seen with diffuse intercapillary glomerulosclerosis

Know the characteristics of HIVAN at the level of light microscopy
Glomeruli
FSG w/ hyalinosis
Collapse of capillaries around mesangia
Swelling of epithelial cells w/ accumulation of hyaline droplets in cytoplasm
Dilation of capsular space containing cast-like material
Tubule
Dilation, flattening of epithelium, hyaline droplets, necrosis

Know the age and gender of patients with essential mixed cryoglobulinemia
Middle-age and female associations
Know the systemic symptoms associated with essential mixed cryoglobulinemia
Dependent vascular purpura
Raynaud’s phenomenon
Arthralgias
Weakness
Know the LM, IF, and EM findings

In 1907 the physician Carlos Chagas (1879-1934) was working in Lassance, a small poverty-stricken town on the Sao Francisco river in the state of Minas Gerais, Brazil. The town had been built along the railway from Rio de Janeiro to Belem. Chagas treated the workmen for injuries, syphilis, malaria etc. He noticed that cardiac arrhythmias occurred frequently. One day an engineer brought him an insect, of the type which was known to often suck the blood of humans at night. Chagas wondered if this creature could also transmit malaria, like the Anopheles mosquitoes. In the bug he discovered a unicellular parasite. In April 1908 he found the same parasite in a sick cat. Two weeks later, in the same house, the parasite was found in the blood of a 3-year-old child (Rita), who was ill with fever. Her face, liver, spleen and lymph nodes were swollen and the child died shortly afterwards. In the house there were countless bugs which tested positive for the parasite. He sent bugs to Rio, to Oswaldo Cruz, his former teacher (Brazilian physician 1872-1917). In the laboratory the parasite caused an infection in marmoset monkeys (Callithrix sp.), rodents and puppies. The disease caused by this parasite, American trypanosomiasis, was named after Chagas. The parasite was given the name Trypanosoma cruzi. The parasite did not always trigger disease, however. In 1908 Chagas also discovered the parasite in another person (Bernice). This woman died in 1989, still infected, but without signs of organ involvement.

The infection only occurs in America in endemic regions. It is a disease associated directly with poverty. The severity varies from region to region. In the South of Texas there are very few cases. Infections occur in Central America sporadically. Although the disease is endemic in large areas of South America, the majority of those infected have no symptoms. Until recently it was thought that approximately 16 million persons were infected, but these figures are under review (see Prevention). The disease is transmitted via the faeces of an infected bug. These are blood-sucking insects which are widely distributed. The illness is characterised by an acute and a chronic phase. Not all infections lead to disease. Untreated, the infection can lead to a great deal of suffering.

The parasite, Trypanosoma cruzi, occurs in more than 100 species of mammal (opossums, guinea pigs, goats, dogs, cats, rats, mice, and so on). There are several known (and probably also some unknown) subtypes, each of which has its own distribution and probably also its own pathogenic features. In view of the extent of the animal reservoir, eradication of the parasite will not be possible. This does not mean that the disease and the transmission cannot themselves be controlled. At present the strains are divided into two groups. Trypanosoma cruzi I has an extensive sylvatic reservoir, of which opossums appear the most important. This group is not very common in the “Southern Cone” countries (Argentina, Brazil, Chile, Paraguay, Uruguay), but it is virtually the only form which occurs north of the Amazon region. T. cruzi II seems to be chiefly associated with rodents and is common in the Southern Cone.

Transmission occurs chiefly via infected bugs. These large insects like to bite sleeping humans at night (a mosquito net gives protection). They have a sharp proboscis which at rest is folded below the head like a jack-knife. When biting they inject anticoagulants and an anaesthetic substance into the wound. Since this makes their bite quite painless (kissing bugs), people seldom wake up and several bites may take place unnoticed in the course of one night. The parasite is not inoculated directly by the bite, as Chagas initially thought. In 1913 Brumpt showed that the parasite is found in the faeces of the insect. While the animals suck blood, they defecate. By scratching, a bitten person can bring the faeces into the bite wound or rub them into the conjunctiva. The parasites multiply in humans and appear in the blood. The cycle is completed when a subsequent bug drinks infected blood. In the bug the parasite undergoes further changes and after 2 to 3 weeks is excreted with the faeces during a subsequent bite. It is estimated that the risk per bite by an infected Triatoma is one in a thousand. The existence of a totally different infection route was demonstrated in animals and is assumed in some human cases. Food or drink infected with the faeces of infected bugs or containing dead bugs may lead to infection in experimental animals. It is not known whether this also occurs in humans, and how common oral transmission then is. Congenital infection (1 to 2 % risk) and transmission via blood transfusion also occur (poor people often sell their blood). Transmission via transfusion is particularly important in urban zones. The risk of infection after an infected blood transfusion is estimated at one in five. There are sporadic cases of accidental contamination of laboratory staff (finger prick, aerosol) and after organ transplantation.

The bugs are also known locally as “vinchucas” or “barbeiros”. The latter common name refers to the blood-sucking (since in the olden days the barber carried out blood letting as well as shaving). Of the approximately 120 vector species only about 7 are important. Each species has its own region of distribution:
Central America and northern South America: Triatoma dimidiata and Rhodnius prolixus
South America (south of 5 S): T. infestans, T. braziliensis, T. sordida, Panstrongylus megistus

In stained blood preparations the parasites are C- or S-shaped with a prominent kinetoplast towards the rear (trypomastigotes). The nucleus is elongated and the undulating membrane is usually not clearly visible. After infection, multiplication of the parasite in the human is solely intracellular. They form microscopic pseudocysts in the tissues (similar to toxoplasmosis and sarcocytosis). This occurs mainly in the heart, muscle cells, some nerve cells and the lymphatic system. In the cell the parasite is small and rounded, with no flagellum (amastigote). When the infected cell ruptures, the parasites are released into the blood circulation where they become elongated and develop a flagellum. These forms can then infect other cells or be ingested by a bug.

If the parasites penetrate via the conjunctiva, there is unilateral redness and oedema of the upper and lower eyelids after 4 to 12 days. This is Romaña’s sign, named after the Argentinean physician Cecilio Romaña, who described the oedema in 1935. This swelling may last for weeks. Sometimes there is also swelling of the ipsilateral lymph nodes (including the pre-auricular lymph nodes). Trypanosomes may be found in the tears at this stage. If inoculation is in the skin there is local oedema and redness (chagoma) in 75% of cases. This remains for 1 to 4 months. From these sites the infections spreads. In the case of an infected blood transfusion, the incubation time may be 20 to 40 days.

Most infections are initially asymptomatic. Acute symptoms occur more frequently in children than in adults. Dissemination of the parasite from the inoculation site may go unnoticed but may also give rise to acute illness with muscle pain, local or generalised oedema, swollen liver, spleen and lymph nodes. Moderate fever is almost always present in symptomatic cases and may persist for a long time, two or even four months. Sometimes there is also acute inflammation of the heart (myocarditis) with arrythmias, decreased blood pressure, and heart failure. As with other forms of myocarditis the echocardiogram is frequently abnormal. There is low QRS-voltage, prolonged PR- and/or QT-interval, T-wave abnormalities. Rarely there are ventricular extrasystoles or atrial fibrillation (the prognosis is poor if this occurs). Acute inflammation of the brain and meninges (meningo-encephalitis) occurs, chiefly in young children. Inflammation of the heart and brain may be fatal. There is pronounced lymphocytosis and monocytosis. It is at this stage that therapy with nifurtimox or benznidazole is generally still capable of destroying the parasite.

If the patient survives the initial phase (which is usually the case), a latent period occurs of indeterminate duration. The patient is asymptomatic, seropositive and the parasitaemia is very low. Focal lesions are found in 60% of endomyocardial biopsies from patients in the latent phase. A positive xenodiagnosis can be obtained in 50% to 100% of these patients. For xenodiagnosis 10 to 40 non-infected bugs (e.g. Dipetalogaster maxima or Triatoma infestans) feed on blood from the patient. The faeces from these animals are investigated after 30, 60 and 90 days. In the event of immunosuppression there may be an acute flare-up, including meningo-encephalitis associated with AIDS or heart transplantation.

Gradually the patient develops symptoms. These vary greatly from region to region. Lesions of the heart, oesophagus and colon are the most common.
Chronic heart problems
Chronic damage to the heart muscle cells and the cardiac conduction system (including that caused by auto-immune mechanisms) leads to heart failure. There is dyspnoea during exertion, orthopnoea and sometimes paroxysmal nightly dyspnoea, oedema of the feet and ankles, congestion of the neck veins, enlarged liver, crepitations over the base of the lungs. Cheyne-Stokes respiration may occur in advanced heart failure. This phenomenon is characterised by periodic respiration in which apnoea episodes alternate with hyperventilation. It is assumed that the prolonged lung-to-brain circulation time plays a role in Cheyne-Stokes with a long cycle (e.g. 3 minutes) [Other causes of this phenomenon are for example brain stem lesions or compression]. Sometimes there is pulsus alternans: the peripheral arterial pulsations are alternately strong and weak.

About 1 to 2 % of babies born to seropositive mothers are infected. They may be asymptomatic (rarely) or may develop hepatosplenomegaly, neurological involvement, myocarditis, oedema and a bleeding tendency. The babies may be dysmature and/or premature. Fever is rare in these children. The mortality may be as high as 50% and they tend to die within a week. Those who survive will generally have permanent residual neurological damage.

In the acute stage the parasite may be found in the blood via a thin blood smear, thick smear or buffy coat. As a concentration technique an anion-exchange minicolumn may be used (Woo’s technique similar to Lanham’s column, but with a different buffer, see African sleeping sickness). Strout’s concentration technique includes the double centrifugation of serum (from 10-20 ml of blood), after which the motile trypanosomes can be detected in the sediment. PCR techniques for T. cruzi exist, but can only be carried out in better equipped laboratories. The serology is positive from the fourth week. To know whether the neonate from a seropositive mother is infected, PCR is performed and IgM antibodies in its blood are determined. A positive serology (IgG) 6 months after birth also indicates infection. In-vitro and in-vivo culture is possible, but usually not available. Biopsies of lymph nodes, heart and muscles sometimes show parasitic pseudocysts (amastigotes in the cells). This is quite an aggressive technique, however, and not very sensitive. Several chronic cases have been described where the parasites were seen on a blood smear, the PCR was positive, but the classical serological tests (ELISA, IFA, HAI) as well as anti-cruzipain antibodies were negative. How frequent this situation is, is not clear at present.

Chagas’ cardiomyopathy. Differentiation from ischaemic, hypertensive or idiopathic cardiomyopathy is not always easy. The differential diagnosis includes high-output heart failure (anaemia, beriberi, hyperthyroidism, large AV-fistula and Paget’s disease of the bone), postpartum heart failure, acute rheumatic fever, valvular disease, congenital abnormalities, pericardial disorders and the sequelae of acute myocarditis (e.g. Coxsackie virus). A cor pulmonale is usually obvious. It is useful to have an electrocardiogram available and if possible an ultrasound evaluation.
Mega-oesophagus: Achalasia of the oesophagus may be very similar to Chagas’ oesophageal dilation. Strictures, benign and malignant tumours should be ruled out.

In an endemic region an asymptomatic person with positive serology is probably a carrier (xenodiagnosis positive in 50 to 100 % of cases). The percentage of seropositive persons who develop symptoms is highly dependent on the geographical region (e.g. 10 to 30%). Asymptomatic mega-organs occur. If the ECG is abnormal, the mortality is 40% after 10 years.

Acute phase
The acute phase lasts up to 60 days. All patients who are in this phase should be treated.
Congenital infection
All infected children should be treated. The earlier therapy is begun, the better the results.
Chronic phase
Aetiological drug treatment is indicated for "recent" chronic infections (a few years). In practice all children younger than 10 years are treated. If mega-oesophagus is already present, the dysphagia should be treated (the passage and absorption of oral medication may be severely impeded). Aetiological treatment in these latter patients was not advised formerly, but more recent data have brought this into question. In a study in Argentina, 131 patients with chronic Chagas’ disease were treated with benznidazole. After an average follow up of 8 years, 4.2% exhibited ECG changes compared to 30% in the untreated group. There was also considerably less clinical deterioration in the treated group (2.1% compared to 17%).

There are several problems. The drugs have an unsatisfactory cure rate. The chronic lesions may be caused by auto-immune mechanisms and might not be improved by eradicating parasites. [Nevertheless the role of auto-immune mechanisms should not be exaggerated: the disease worsens during immune suppression as in transplantation and in HIV]. The drugs should be given long term. Results vary from country to country, possibly due to a difference in sensitivity of the parasites. Side effects occur, more often in adults than in children. It is best to avoid steroids and possibly tetracyclines, since these may exacerbate the infection.

The animal reservoir of Trypanosoma cruzi cannot be eradicated. There is no vaccine. Chagas’ disease is typically a disease of poverty. Improvements in housing (brick or plaster walls, corrugated iron roofs, long-acting insecticides on house walls) diminish the insect population. A mosquito net has also proved its usefulness here. Serological testing of the blood used for transfusion is very helpful. In 1953 it was discovered that adding gentian violet kills the trypanosomes in 24 hours (0.25 g/litre of blood = 1/4000). This colours the blood purple, however. If 2 mg/ml of ascorbic acid (vitamin C) is also added and the blood is illuminated with a 75 Watt fluorescent lamp, the time necessary to sterilise the blood is greatly shortened (30'). To date the various biological methods of eradication of the vectors which have been tested (increasing natural enemies) have not been effective because a new ecological balance is very quickly achieved.

This programme was begun in Brazil in 1975. The intention was to reach the whole country and the strategy included spraying houses with insecticides. In Sao Paulo the vector Triatoma infestans was eliminated in 1982. Between 1983 and 1993 reductions of house infestation, ranging between 100% (Mato Grosso) and 80% (Goias) were observed in 8 of the 11 endemic states. In the states Bahia, Tocantins and Rio Grande do Sul the results were less spectacular. Nevertheless further successes are expected in the coming years. The total incidence of seropositivity in children from 7-14 years fell by 96% between 1980 and 1994. In 1998 there was still one T. infestans per 10,000 houses. A much higher frequency would be required to maintain transmission of T. cruzi. It is reasonable to expect the transmission will be interrupted.

In 1991-92 the "Southern Cone Initiative" project was launched by Argentina, Bolivia, Brazil, Chile, Paraguay and Uruguay, with the objective of stopping the transmission of Chagas’ disease. In 1997 Peru joined the project. After an initial phase for preparation (charting the foci, programming the activities, calculating the costs), there was an attack phase with insecticides, repeated after 3 to 6 months. Insecticide-containing paint is cheaper than the traditional insecticides which are applied by spraying. Insecticides dispersed by fumigant canisters were also used. These are locally produced, e.g. in Argentina, are cheap, effective and also active against Aedes aegypti, the important dengue vector. At present there are effective colourless long acting insecticides. The fact that people see the bugs, cockroaches, etc. lying dead after spraying, is a bonus which makes it easier to accept the spraying procedure. In the Southern Cone Initiative, 1,800,000 houses were treated with pyrethroids (deltametrine, lambda-cyhalotrine, cyflutrine) by the year 2000.

The Southern Cone Initiative began in 1991-92. Many countries have now been declared free from transmission by the PAHO [Pan-American Health Organization].
The Central American Initiative was begun in 1997-98 in Guatemala, Honduras, Nicaragua, El Salvador, Panama.
The Andean Pact Initiative was set up in 1997-98 in Venezuela, Colombia, Ecuador. Northern Peru began surveys during the same period.
The Mexican Initiative was begun in 2000-1. In 2001 this was still at a very early stage.

Trypanosoma cruzi, only in the New World
Transmission via bugs, blood transfusion and congenitally, rarely orally
Importance of poverty (housing)
Acute (especially children): chancre, Romaña’s sign, fever, lymphadenophathy, myocarditis, hepatosplenomegaly
Chronic: cardiac arrhythmias, heart failure, emboli, apical aneurysms
Chronic: dysphagia, constipation (mega-syndrome)
Diagnosis: clinical + thick smear/buffy coat (early), serology, xenodiagnosis, ECG, X-ray (late), PCR

Microangiopathic hemolytic anemia
Thrombocytopenia
Increased numbers of reticulocytes
Elevated bilirubin levels
Reduced haptoglobin levels
Elevated level of fibrin split products – less elevated in TTP

What are the causes of HUS in children and adults?
Children
Gastroenteritis (verotoxin producing E. coli)
Viral URTI
Adults
Associated with complications of pregnancy or post-partum period
Use of contraceptives / chemotherapeutic / immunosuppressive drugs
Systemic diseases such as scleroderma, SLE, and malignant HTN

Probably involves glomerular endothelial cell injury with subsequent fibrin deposition and thrombosis
Decreased endothelial cell production of prostaglandin I2 and NO
Release of endothelin
Activation of endothelial cells, increasing their adhesiveness to leukocytes, contributing to thrombosis

More common occurrence of TTP in young adults
Fever is a more frequent manifestation of TTP
Neurologic abnormalities that tend to predominate and cause death in TTP
Lesser degree if renal involvement in TTP
TTP has a worse prognosis than HUS

Concentric cellular thickening of intima of arterioles and interlobular arteries
Thickening of glomerular capillary walls by endothelial swelling
Deposits of fibrin-related material in the capillary lumina, subendothelially, and in the mesangium.
Intracapillary fibrin thrombi
Sometimes cortical necrosis

Type I Surface pili ® adhesin molecules bind to mannose on uroepithelium ® UTI ® stimulation of T-helper cells ® stimulation of phagocytes ® scarring and release of lysozyme
Type P Surface pili ® adhesin molecules bind galactose ® pyelonephritis

Indicates significant bacteriuria (fresh clean catch)
Significant as well if <100,000/ml>
From suprapubic aspiration
Bladder catheterization
Same species is repeatably isolated