Trematodes (flukes)
These leaf-shaped worms are parasitic to humans and animals. Their complex life cycles may involve one or more intermediate hosts, often freshwater molluscs.Schistosomiasis
Schistosomiasis is one of the most important causes of morbidity in the tropics. There are five species of the genus Schistosoma which commonly cause disease in humans: S. haematobium, S. mansoni, S. japonicum, S. mekongi and S. intercalatum.
Pathology
This depends on the species and the stage of infection. Most disease is due to the passage of eggs through mucosa and to the granulomatous reaction to eggs deposited in tissues. The eggs of S. haematobium pass mainly through the wall of the bladder, but may also involve rectum, seminal vesicles, vagina, cervix and uterine tubes. S. mansoni and S. japonicum eggs pass mainly through the wall of the lower bowel or are carried to the liver.
Clinical features
Recent travellers, especially those overlanding through Africa, may present with allergic manifestations and eosinophilia; residents of schistosomiasis-endemic areas are more likely to present with chronic urinary tract pathology or portal hypertension.
During the early stages of infection there may be itching lasting 1–2 days at the site of cercarial penetration. After a symptom-free period of 3–5 weeks, acute schistosomiasis (Katayama syndrome) may present with allergic manifestations such as urticaria, fever, muscle aches, abdominal pain, headaches, cough and sweating.
On examination hepatomegaly, splenomegaly, lymphadenopathy and pneumonia may be present. These allergic phenomena may be severe in infections with S. mansoni and S. japonicum, but are rare with S. haematobium. The features subside after 1–2 weeks.
Chronic schistosomiasis is due to egg deposition and occurs months to years after infection. The symptoms and signs depend upon the intensity of infection and the species of infecting schistosome.
Schistosoma haematobium
Humans are the only natural hosts of S. haematobium, which is highly endemic in Egypt and East Africa, and occurs throughout Africa and the Middle East. Infection can be acquired after a brief exposure, such as swimming in freshwater lakes in Africa. Painless terminal haematuria is usually the first and most common symptom. Frequency of micturition follows, due to bladder neck obstruction. The severity of S. haematobium infection varies greatly, and many with a light infection are asymptomatic. However, as adult worms can live for 20 years or more and lesions may progress, these patients should always be treated.
Schistosoma mansoni
S. mansoni is endemic throughout Africa, the Middle East, Venezuela, Brazil and the Caribbean. Characteristic symptoms begin 2 months or more after infection. They may be slight, no more than malaise, or consist of abdominal pain and frequent stools which contain blood-stained mucus. With severe advanced disease, increased discomfort from rectal polyps may be experienced. The early hepatomegaly is reversible, but portal hypertension may cause massive splenomegaly, fatal haematemesis from oesophageal varices, or progressive ascites.
In addition to humans, the adult worm of S. japonicum infects the dog, rat, field mouse, water buffalo, ox, cat, pig, horse and sheep.
The pathology of S. japonicum is similar to that of S. mansoni, but as this worm produces more eggs, the lesions tend to be more extensive and widespread.
Investigations
There is marked eosinophilia. Serological tests (ELISA) are useful as screening tests but remain positive after chemotherapeutic cure.
In S. haematobium infection, dipstick urine testing shows blood and albumin. The eggs can be found by microscopic examination of the centrifuged deposit of terminal stream urine. Ultrasound is useful for assessing the urinary tract; bladder wall thickening, hydronephrosis and bladder calcification can be detected. Cystoscopy reveals ‘sandy’ patches, bleeding mucosa and later distortion.
In a heavy infection with S. mansoni or S. japonicum the characteristic egg with its lateral spine can usually be found in the stool. When the infection is light or of long duration, a rectal biopsy can be examined. Sigmoidoscopy may show inflammation or bleeding. Biopsies should be examined for ova.
Management
The object of specific treatment is to kill the adult schistosomes and so stop egg-laying. Praziquantel is the drug of choice for all forms of schistosomiasis. The drug produces parasitological cure in 80% of treated individuals and over 90% reduction in egg counts in the remainder. Side-effects are uncommon but include nausea and abdominal pain. Praziquantel therapy in early infection reverses pathologies such as hepatomegaly and bladder wall thickening and granulomas.
Surgery may be required to deal with residual lesions such as ureteric stricture, small fibrotic urinary bladders, or granulomatous masses in the brain or spinal cord. Removal of rectal papillomas by diathermy or by other means may provide symptomatic relief.
Prevention
So far no satisfactory single means of controlling schistosomiasis has been established. The life cycle is terminated if the ova in urine or faeces are not allowed to contaminate fresh water containing the snail host.
Liver flukes
Liver flukes infect at least 20 million people and remain an important public health problem in many endemic areas. They are associated with abdominal pain, hepatomegaly and relapsing cholangitis. Clonorchis sinensis is a major aetiological agent of bile duct cancer. The three major liver flukes have similar life cycles and pathologies.
Cestodes (tapeworms)
Cestodes are ribbon-shaped worms which inhabit the intestinal tract. They have no alimentary system and absorb nutrients through the tegumental surface. The anterior end, or scolex, has suckers for attaching to the host. From the scolex arises a series of progressively developing segments, the proglottides, which, when shed, may continue to show active movements. Cross- fertilization takes place between segments. Ova, present in large numbers in mature proglottides, remain viable for weeks and during this period they may be consumed by the intermediate host. Larvae liberated from the ingested ova pass into the tissues, forming larval cysticerci.
Tapeworms cause two distinct patterns of disease, Either intestinal infection or systemic cysticercosis.
Taenia saginata (beef tapeworm) and Diphyllobothrium latum (fish tapeworm) cause only intestinal infection, following human ingestion of intermediate hosts that contain cysticerci (the larval stage of the tapeworm). Taenia solium causes intestinal infection if a cysticerci-containing intermediate host is ingested, and cysticercosis (systemic infection from larval migration) if ova are ingested. Echinococcus granulosus (dog tapeworm) does not cause human intestinal infection, but causes hydatid disease (which is analogous to cysticercosis) following ingestion of ova and subsequent larval migration.
Intestinal tapeworm
Humans acquire tapeworm by eating undercooked beef infected with the larval stage of T. saginata, undercooked pork containing the larval stage of T. solium, or undercooked freshwater fish containing larvae of D. latum. Usually only one adult tapeworm is present in the gut but up to ten have been reported. The ova of T. saginata and T. solium are indistinguishable microscopically.
However, examination of scolex and proglottides can differentiate between them.
Taenia saginata
Infection with T. saginata occurs in all parts of the world. The adult worm may be several metres long and produces little or no intestinal upset in human beings, but knowledge of its presence, by noting segments in the faeces or on underclothing, may distress the patient. Ova may be found in the stool. Praziquantel is the drug of choice; niclosamide or nitazoxanide are alternatives.
Prevention depends on efficient meat inspection and the thorough cooking of beef.
Taenia solium T. solium, the pork tapeworm, is common in central Europe, South Africa, South America and parts of Asia.It is not as large as T. saginata. The adult worm is foundonly in humans following the eating of undercooked pork containing cysticerci. Niclosamide, followed by a mild laxative (after 1–2 hours) to prevent retrograde intestinal autoinfection, is effective for intestinal infection. Cooking pork well prevents intestinal infection. Great care must be taken by nurses and other adults while attending a patient harbouring an adult worm to avoid ingestion of ova or segments.
Cysticercosis
Human cysticercosis is acquired by ingesting T. solium tapeworm ova, from either contaminated fingers or food. The larvae are liberated from eggs in the stomach, penetrate the intestinal mucosa and are carried to many parts of the body where they develop and form cysticerci, 0.5–1 cm cysts that contain the head of a young worm. They do not grow further or migrate. Common locations are the subcutaneous tissue, skeletal muscles and brain.
Clinical features
When superficially placed, cysts can be palpated under the skin or mucosa as pea-like ovoid bodies. Here they cause few or no symptoms, and will eventually die and become calcified. Heavy brain infections, especially in children, may cause features of encephalitis. More commonly, however, cerebral signs do not occur until the larvae die, 5–20 years later. Epilepsy, personality changes, staggering gait or signs of internal hydrocephalus are the most common features.
Investigations
Calcified cysts in muscles can be recognised radiologically. In the brain, however, less calcification takes placeand larvae are only occasionally visible by plain X-ray; usually CT or MRI will show them. Epileptic fits starting in adult life suggest the possibility of cysticercosis if the patient has lived in or travelled to an endemic area. The subcutaneous tissue should be palpated and any nodule excised for histology. Radiological examination of the skeletal muscles may be helpful. Antibody detection is available for serodiagnosis.
Management and prevention
Albendazole, 15 mg/kg daily for a minimum of 8 days, has now become the drug of choice for parenchymal neurocysticercosis. Praziquantel is another option, 50 mg/kg in three divided doses daily for 10 days. Prednisolone, 10 mg 8-hourly, is also given for 14 days, starting 1 day before the albendazole or praziquantel. In addition, anti-epileptic drugs should be given until the reaction in the brain has subsided. Operative intervention is indicated for hydrocephalus. Studies from India and Peru suggest that most small solitary cerebral cysts will resolve without treatment.
Echinococcus granulosus (Taenia echinococcus) and hydatid disease
Dogs are the definitive hosts of the tiny tapeworm E. granulosus. The larval stage, a hydatid cyst, normally occurs in sheep, cattle, camels and other animals that are infected from contaminated pastures or water. By handling a dog or drinking contaminated water, humans may ingest eggs . The embryo is liberated from the ovum in the small intestine and gains access to the blood stream and thus to the liver. The resultant cyst grows very slowly, sometimes intermittently. It is composed of an enveloping fibrous pericyst, laminated hyaline membrane (ectocyst) and inner germinal layers (endocyst) which gives rise to daughter cysts, or germinating cystic brood capsule in which larvae (protoscolices) develop. Over time some cysts may calcify and become non-viable. The disease is common in the Middle East, North and East Africa, Australia and Argentina.
Clinical features
A hydatid cyst is typically acquired in childhood and may, after growing for some years, cause pressure symptoms. These vary, depending on the organ or tissue involved. In nearly 75% of patients with hydatid disease the right lobe of the liver is invaded and contains a single cyst. In others a cyst may be found in lung, bone, brain or elsewhere.
Investigations
The diagnosis depends on the clinical, radiological and ultrasound findings in a patient who has lived in close contact with dogs in an endemic area. Complement fixation and ELISA are positive in 70–90% of patients.
Management and prevention
Hydatid cysts should be excised wherever possible. Great care is taken to avoid spillage and cavities are sterilized with 0.5% silver nitrate or 2.7% sodium chloride. Albendazole (400 mg 12-hourly for 3 months) should also be used. The drug is now often combined with PAIR (percutaneous puncture, aspiration, injection of scolicidal agent and re-aspiration) to good effect. Praziquantel 20 mg/kg 12-hourly for 14 days also kills protoscolices perioperatively. Prevention is difficult in situations where there is a close association with dogs and sheep. Personal hygiene, satisfactory disposal of carcasses, meat inspection and deworming of dogs can greatly reduce the prevalence of disease.
Malaria
Malaria in humans is caused by Plasmodium falciparum, P. vivax, P. ovale, P. malariae . It is transmitted by the bite of female anopheline.
Pathology
Red cells infected with malaria are prone to haemolysis. This is most severe with P. falciparum, which invades red cells of all ages but especially young cells; P. vivax and P. ovale invade reticulocytes, and P. malariae normoblasts, so that infections remain lighter. Anaemia may be profound and is worsened by dyserythropoiesis, splenomegaly and depletion of folate stores.
In P. falciparum malaria, red cells containing trophozoites adhere to vascular endothelium in post-capillary venules in brain, kidney, liver, lungs and gut. The vessels become congested, resulting in widespread organ damage which is exacerbated by rupture of schizonts, liberating toxic and antigenic substances.
P. falciparum has influenced human evolution, with the appearance of protective mutations such as sickle-cell(HbS), thalassaemia, G6PD deficiency and HLA-B53. P. falciparum does not grow well in red cells that contain haemoglobin F, C or especially S. Haemoglobin S heterozygotes (AS) are protected against
Clinical features
The clinical features of malaria are non-specific and the diagnosis must be suspected in anyone returning from an endemic area who has features of infection. P. falciparum infection This is the most dangerous of the malarias and patients are either ‘killed or cured’. The onset is often insidious, with malaise, headache and vomiting. Cough and mild diarrhea are also common. The fever has no particular pattern. Jaundice is common due to haemolysis and hepatic dysfunction. The liver and spleen enlarge and may become tender. Anaemia develops rapidly, as does thrombocytopenia. A patient with falciparum malaria, apparently not seriously ill, may rapidly develop dangerous complication. Cerebral malaria is manifested by confusion, seizures or coma, usually without localizing signs. Children die rapidly without any special symptoms other than fever. Immunity is impaired in pregnancy and the parasite can preferentially bind to a placental protein known as chondroitin sulphate A. Abortion and intrauterine growth retardation from parasitisation of the maternal side of the placenta are frequent. Previous splenectomy increases the risk of severe malaria.
P. vivax and P. ovale infection In many cases the illness starts with several days of continued fever before the development of classical bouts of fever on alternate days. Fever starts with a rigor. The patient feels cold and the temperature rises to about 40 °C. After half an hour to an hour the hot or flush phase begins. It lasts several hours and gives way to profuse perspiration and a gradual fall in temperature. The cycle is repeated 48 hours later. Gradually the spleen and liver enlarge and may become tender. Anaemia develops slowly. Relapses are frequent in the first 2 years after leaving the malarious area and infection may be acquired from blood transfusion.
P. malariae infection This is usually associated with mild symptoms and bouts of fever every third day. Parasitaemia may persist for many years with the occasional recrudescence of fever, or without producing any symptoms. Chronic P. malariae infection causes glomerulonephritis and long term nephrotic syndrome in children.
Investigations
Giemsa-stained thick and thin blood films should be examined whenever malaria is suspected. In the thick film erythrocytes are lysed, releasing all blood stages of the parasite.
Immunochromatographic tests for malaria antigens, such as OptiMal® (which detects the Plasmodium lactate dehydrogenase of several species) and ParasightF® (which detects the P. falciparum histidine-rich protein 2), are extremely sensitive and specific for falciparum malaria but less so for other species. They should be used in parallel with blood film examination but are especially useful where the microscopist is less experienced in examining blood films (e.g. in the UK).
DNA detection (PCR) is used mainly in research and is useful for determining whether a patient has a recrudescence of the same malaria parasite or a reinfection with a new parasite.
Management
Mild P. falciparum malaria Since P. falciparum is now resistant to chloroquine and sulfadoxine- pyrimethamine (Fansidar) almost worldwide, an artemisinin-based treatment is recommended.
Co-artemether (CoArtem® or Riamet®) contains artemether and lumefantrine
Management includes early and appropriate antimalarial chemotherapy, active treatment of complications, correction of fluid, electrolyte and acid–base balance, and avoidance of harmful ancillary treatments.
Exchange transfusion has not been tested in randomized controlled trials but may be beneficial for nonimmune patients with persisting high parasitaemias (> 10% circulating erythrocytes).
Management of non-falciparum malaria
P. vivax, P. ovale and P. malariae infections should be treated with oral chloroquine: 600 mg chloroquine base followed by 300 mg base in 6 hours, then 150 mg base 12- hourly for 2 more days. Some chloroquine resistance has been reported from Indonesia.
Prevention
Clinical attacks of malaria may be preventable with chemoprophylaxis using chloroquine, atovaquone plus proguanil (Malarone), doxycycline or mefloquine.
African trypanosomiasis (sleeping sickness)
African sleeping sickness is caused by trypanosomes conveyed to humans by the bites of infected tsetse flies, and is unique to sub-Saharan Africa. Trypanosoma brucei gambiense trypanosomiasis has a wide distribution in West and Central Africa. T. brucei rhodesiense trypanosomiasis is found in parts of East and Central Africa, where it is currently on the increase. In West Africa transmission is mainly at the riverside, where the fly rests in the shade of trees; no animal reservoir has been identified for T. gambiense.
Clinical features
A bite by a tsetse fly is painful and commonly becomes inflamed, but if trypanosomes are introduced, the site may again become painful and swollen about 10 dayslater (‘trypanosomal chancre’) and the regional lymph nodes enlarge (‘Winterbottom’s sign’). Within 2–3 weeks of infection the trypanosomes invade the blood stream. The disease is characterised by an early haematolymphatic stage and a late encephalitic stage in which the parasite crosses the blood–brain barrier and chronic encephalopathy develops.
Management
Unfortunately, therapeutic options for African trypanosomiasis are limited and most of the antitrypanosomal drugs are toxic and expensive. The prognosis is good if treatment is begun early before the brain has been invaded. At this stage intravenous suramin, after a test dose of 100–200 mg, should be given for rhodesiense infections (1 g on days 1, 3, 7, 14 and 21). For gambiense infections, intramuscular or intravenous pentamidine 4 mg/kg for 10 days is given .
American trypanosomiasis (Chagas’ disease)
Chagas’ disease occurs widely in South and Central America. The cause is Trypanosoma cruzi, transmitted to humans from the faeces of a reduviid bug in which the trypanosomes have a cycle of development before becoming infective to humans.
Clinical features
Acute phase
Clinical manifestations of the acute phase are seen in only 1–2% of individuals who are infected before the age of 15 years. Young children (1–5 years) are most commonly affected. The entrance of T. cruzi through an abrasion produces a dusky-red firm swelling and enlargement of regional lymph nodes. A conjunctival lesion, although less common, is characteristic; the unilateral firm reddish swelling of the lids may close the eye and constitutes ‘Romaña’s sign’. In a few patients an acute generalised infection soon appears, with a transient morbilliform or urticarial rash, fever, lymphadenopathy and enlargement of the spleen and liver. In a small minority of patients acute myocarditis and heart failure or neurological features, including personality changes and signs of meningoencephalitis, may be seen. The acute infection may be fatal to infants.
Chronic phase
About 50–70% of infected patients become seropositive and develop an indeterminate form when no parasitaemia is detectable. They have a normal lifespan with no symptoms, but are a natural reservoir for the disease and maintain the life cycle of parasites. After a latent period of several years, 10–30% of chronic cases develop low-grade myocarditis, and damage to conducting fibres causes a cardiomyopathy characterised by cardiac dilatation, arrhythmias, partial or complete heart block and sudden death. In nearly 10% of patients, damage to Auerbach’s plexus results in dilatation of various parts of the alimentary canal, especially the colon and oesophagus, so-called ‘mega’ disease. Dilatation of the bile ducts and bronchi is also a recognised sequela. Autoimmune processes may be responsible for much of the damage. There are geographical variations of the basic pattern of disease. Reactivation of Chagas’ disease can occur in patients with HIV if the CD4 count falls lower than 200 cells/mm3 (p. 390).
Investigations
T. cruzi is easily detectable in a blood film in the acute illness. In chronic disease it may be recovered in up to 50% of cases by xenodiagnosis, in which infection-free, laboratory-bred reduviid bugs are allowed to feed on the patient; subsequently, the hind gut or faeces of the bug are examined for parasites. Parasite DNA detection by PCR in the patient’s blood is a highly sensitive method for documentation of infection and, in addition, can be employed in faeces of bugs used in xenodiagnosis tests to improve sensitivity. Antibody detection is also highly sensitive (99%).Management and prevention Parasiticidal agents are used to treat the acute phase, congenital disease and early chronic phase (within 10 years of infection). Nifurtimox is given orally. The dose, which has to be carefully supervised to minimize toxicity while preserving parasiticidal activity, is 10 mg/ kg divided into three equal doses, daily by mouth for 60–90 days. The paediatric dose is 15 mg/kg daily. Cure rates of 80% in acute disease are obtained. Benznidazole is an alternative, given at a dose of 5–10 mg/kg daily by mouth, in two divided doses for 60 days; children receive 10 mg/kg daily. Both nifurtimox and benznidazole are toxic, with adverse reaction rates of 30–55%. Specific drug treatment of the chronic form is now increasingly favoured, but in the cardiac or digestive ‘mega’ diseases it does not reverse established tissue damage. Surgery may be needed.
Preventative measures include improving housing and destruction of reduviid bugs by spraying of houses with insecticides. Blood donors should be screened.
Leishmaniasis
Leishmaniasis is caused by unicellular flagellate intracellular protozoa belonging to the genus Leishmania (order Kinetoplastidae). There are 21 leishmanial species which cause several diverse clinical syndromes, which can be placed into three broad groups:
• visceral leishmaniasis (VL, kala-azar)
• cutaneous leishmaniasis (CL)
• mucosal leishmaniasis (ML).
Visceral leishmaniasis (VL, kala-azar)
VL is caused by the protozoon Leishmania donovani complex (comprising L. donovani, L. infantum and L. chagasi). India, Sudan, Bangladesh and Brazil account for 90%of cases of VL, while other affected regions include the Mediterranean, East Africa, China, Arabia, Israel and other South American countries . In addition to sandfly transmission, VL has also been reported to follow blood transfusion and disease can present unexpectedly in immunosuppressed patients—for example, after renal transplantation and in HIV infection. The great majority of people infected remain asymptomatic.
In visceral diseases the spleen, liver, bone marrow and lymph nodes are primarily involved.
Clinical features
On the Indian subcontinent adults and children are equally affected; on other continents VL is predominantly a disease of small children and infants, except in adults with HIV co-infection. The incubation period ranges from weeks to months (occasionally several years).
The first sign of infection is high fever, usually accompanied by rigor and chills. Fever intensity decreases over time and patients may become afebrile for intervening periods ranging from weeks to months. This is followed by a relapse of fever, often of lesser intensity. Splenomegaly develops quickly in the first few weeks and becomes massive as the disease progresses. Moderate hepatomegaly occurs later. Lymphadenopathy is seen in the majority ofcases in Africa, the Mediterranean and South America, but is rare on the Indian subcontinent. Blackish discoloration of the skin, from which the disease derived its name, kala-azar (the Hindi word for ‘black fever’), is a feature of advanced illness and is now rarely seen. Pancytopenia is a common feature. Moderate to severe anaemia develops rapidly, and can result in congestive cardiac failure and associated clinical features. Thrombocytopenia, often compounded by hepatic dysfunction, may result in bleeding from the retina, gastrointestinal tract and nose. In advanced illness, hypoalbuminaemia may manifest as pedal oedema, ascites and anasarca (gross generalised oedema and swelling).
Investigations
Pancytopenia is the most dominant feature, with granulocytopenia and monocytosis. Polyclonal hypergammaglobulinaemia, chiefly IgG followed by IgM, and hypoalbuminaemia are seen later. Demonstration of amastigotes (Leishman–Donovan bodies) in splenic smears is the most efficient means of diagnosis.
Parasites may be demonstrated in buffy coat smears, especially in immunosuppressed patients. Sensitivity can be improved by culturing the aspirate material or by PCR for DNA detection and species identification, but these tests can only be performed in specialised laboratories. Serodiagnosis, by ELISA or immunofluorescence antibody test, is employed in developed countries.
Management
Pentavalent antimonials Antimony (Sb) compounds were the first drugs to be used for the treatment of leishmaniasis and remain the mainstay of treatment in most parts of the world.
Leishmaniasis Cutaneous leishmaniasis (CL)
CL (oriental sore) occurs in both the Old World and the New World (the Americas).
In the Old World, CL is mild. It is found around the Mediterranean basin, throughout the Middle East and Central Asia as far as Pakistan, and in sub-Saharan West Africa and Sudan . The causative organisms for Old World zoonotic CL are L. major, L. tropica and L. aethiopica (Box 13.61). Anthroponotic CL is caused by L. tropica, and is confined to urban or suburban areas of the Old World. Afghanistan is currently the biggest focus, but infection is endemic in Pakistan, the western deserts of India, Iran, Iraq, Syria and other areas of the Middle East. In recent years there has been an increase in the incidence of zoonotic CL in both the Old and the New World due to urbanisation and deforestation which led to peridomestic transmission (in and around human dwellings).
Clinical features
The incubation period is typically 2–3 months (range 2 weeks to 5 years). In all types of CL, the common feature is development of a papule followed by ulceration of the skin with raised borders, usually at the site of the bite of the vector. Lesions, single or multiple, start as small red papules that increase gradually in size, reaching 2–10 cm in diameter. A crust forms, overlying an ulcer with a granular base . These ulcers develop a few weeks or months after the bite. There can be satellite lesions, especially in L. major and occasionally in L. tropica infections. Regional lymphadenopathy, pain,
pruritus and secondary bacterial infections may occur. Clinically, lesions of L. mexicana and L. peruviana closely resemble those seen in the Old World,
Management of CL and ML
Small lesions may self-heal or are treated by freezing with liquid nitrogen or curettage. There is no ideal antimicrobial therapy. Treatment should be individualized on the basis of the causative organism, severity of the lesions, availability of drugs, tolerance of the patient for toxicity, and local resistance patterns. In CL, topical application of paromomycin 15% plus methylbenzethonium chloride 12% is beneficial. Intralesional antimony (Sb: 0.2–0.8 mL/lesion) up to 2 g seems to be rapidly effective in suitable cases, well tolerated and economic, and is safe in patients with cardiac, liver or renal diseases.