Antimicrobial Chemotherapy, 4th Edition

The therapeutic use of antimicrobial agents

31

Parasitic diseases

  1. C. B. Slack

The organisms considered as ‘parasites’—that is, the pathogenic protozoa and helminths—tend to cause chronic disease and many individuals, once infected, may become long-term carriers. This ensures that in the warmer countries of the world, where poorer standards of hygiene often prevail, there is a high prevalence of infection and a high incidence of new cases all the time. The areas with the highest parasitic burden tend to have the poorest medical care because of poverty, a legacy of inadequate facilities, and the logistics of reaching the majority of people living in scattered rural communities. In many countries the total annual health care budget would not be sufficient to treat a fraction of their population even if it were all spent on antiparasitic drugs.

Host–parasite relationship

One of the peculiarities of treating parasitic infections is the varied relationship between man and microbe. The life cycles often ensure that at some stage the organism is not susceptible to a particular drug because it is either in a resting phase or in an inaccessible site. In many cases the host and parasite reach a steady state of co-existence with no symptoms at all. Parasites restricted to the gut lumen such as the protozoon Giardia lamblia (also known as G. intestinalis) or many helminths often reach this stage and the intruder is only discovered when stools are examined. In other cases, for example filariasis, the disease becomes ‘burnt-out’ after years. All these late asymptomatic cases may be diagnosed by chance during routine investigations or as part of mass screening campaigns. The contribution of the parasite burden to overall health is usually impossible to estimate and if the only available drug is potentially toxic the decision to treat an apparently healthy individual is difficult to make. Another factor in making such a decision is the likelihood of re-infection from the community or environmental reservoirs. Intestinal parasites are found in over 70 per cent of

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the population in some tropical countries and a child living in a rural environment will inevitably be quickly in contact with the parasite again. Treatment of an individual case without taking care to prevent re-infection is wasting resources and is not good practice. If the drug is non-toxic and inexpensive there is some justification in treating asymptomatic individuals, especially if the infection may at some stage cause further problems.

Some intestinal protozoa such as Entamoeba coli may be classed as true commensals for there is no evidence to incriminate them in human disease. Their only significance may be in misidentification in stool microscopy. Similarly, some helminths, such as the whipworm Trichuris trichiura, rarely cause problems in adults. However, many other parasites do clearly have a pathogenic role and in those cases an accurate laboratory diagnosis is essential if antiparasitic therapy is to be useful.

Therapeutic difficulties

In addition to the factors peculiar to treating parasitic infections, many of the general principles mentioned in Chapter 15 apply. Any therapy of extended duration in relatively healthy individuals in the community will be difficult to monitor and compliance may be a problem, especially if the drug is unpleasant to take and has conspicuous side-effects. This can occur even with well-educated travellers taking antimalarials.

Many of the remedies for the major parasitic infections are potentially toxic and it is always necessary to weigh the consequences of iatrogenic disease against the benefit of therapy which might not always be able to effect a complete cure. These considerations must still be borne in mind nowadays, even though less toxic compounds are gradually becoming available for some parasitic diseases.

Protozoan infections

Malaria

Fig. 31.1 shows the world-wide distribution of malaria, which is the most important of all parasitic diseases in terms of mortality. Although indigenous malaria is now virtually restricted to the tropics and subtropics, it is commonly imported into many temperate countries because of the rapid increase in world travel, and the threatened climate change may further extend the boundaries. The volume of international business travel continues to expand each year, and ‘long-haul’ package holidays to east and west Africa or other tropical destinations are becoming increasingly popular. It is therefore not surprising that the importance of imported malaria in non-malarious countries continues to grow. About 2000 cases of imported malaria are recorded in the UK each year; the figure is likely

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to be grossly underestimated because of considerable under-reporting. Each year fatalities from malaria are reported; the tragedy is that these are all preventable. However, this is insignificant compared with the damage malaria inflicts on the populations of the tropical world; in parts of west Africa it is estimated that at least 10 per cent of children die of falciparum malaria before they reach the age of 5.

 

Fig. 31.1 Distribution of malaria (Adapted, by permission, from WHO Weekly Epidemiological Record 34 (1993), 246.)

Acute malaria

Until recently the drug of choice in the treatment of acute malaria was always chloroquine, a 4-aminoquinoline derived from the traditional remedy, quinine. These agents are active against the blood forms of the parasite, which is important in the symptomatic stage of the disease when rapidly dividing schizonts cause red cell lysis; it is particularly important in falciparum malaria when infected erythrocytes block small cerebral blood vessels to give rise to the rapidly fatal form of cerebral malaria. In such a medical emergency parenteral therapy is necessary in spite of the hazards of infusion. In its time, chloroquine revolutionized the treatment and prophylaxis of malaria, but we are now beginning to pay the penalty for its extensive use by the appearance of resistant strains of Plasmodium falciparum. Although other species of Plasmodium usually retain susceptibility to the drug, chloroquine resistance in P. falciparum has become a major clinical problem in south-east Asia, central and South America, and Africa. The spread seems inexorable and it has become clear that resistance now has a firm foothold in tropical west Africa where falciparum malaria is hyperendemic and responsible for many thousands of deaths each year. Many chloroquine-resistant strains are also resistant to alternative drugs such as the combinations of pyrimethamine with sulphonamides (Fansidar) or dapsone (Maloprim). Indeed, quinine has returned to favour as the drug of first choice in severe falciparum malaria if chloroquine resistance is thought to be possible. Resistance to quinine is presently quite rare, but resistance to other antimalarials throughout the world has become such a problem that the need for new antimalarial compounds has become acute.

Mefloquine, a quinolinemethanol derivative developed by the Walter Reed Army Institute of Research in Washington, is active against resistant strains and has been successfully used for treatment. However, resistance to mefloquine is known to emerge readily and there are fears that widespread use will quickly negate its value. Moreover, mefloquine use has been associated with neuropsy-chiatric side-effects that may persist for some time owing to the very long plasma half-life of the drug. Halofantrine, another Walter Reed derivative, may have advantages over mefloquine since it has a shorter half-life (1–4 days, compared to 2–4 weeks) and fewer adverse reactions, but concern has been expressed over possible cardiotoxicity.

Derivatives of a Chinese herbal remedy, qinghaosu (artemisinin) are now in use in severe malaria in the tropics. Various formulations, including artesunic

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acid, arteether, and artemether (the ethyl and methyl ethers, respectively), are used for oral, intravenous, and intramuscular administration. A suppository formulation is also available and is particularly useful in children. Artemisinin derivatives have aroused considerable interest since they are more rapidly effective than any other drug in severe malaria. Clinical trials have shown these compounds to be relatively non-toxic, but animal experiments have revealed a potential for neurotoxicity and their future as antimalarial agents is not yet secure.

Recurrent malaria

To effect a radical cure in recurrent malarias with a latent exoerythrocytic phase, such as ‘benign tertian’ malaria due to Plasmodium vivax, it is necessary to employ an 8-aminoquinoline. Primaquine is the most commonly used drug for this purpose. It is necessary first to make an accurate diagnosis by examining thin and thick blood films. Secondly, it is important to treat the acute erythrocytic attack with chloroquine before administering primaquine. Thirdly, patients must be screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Low levels of this red blood cell enzyme occur in many populations in endemic areas and administration of primaquine to such individuals may lead to an acute haemolytic crisis worse than the original malaria. Iatrogenic reactions of this sort have given 8-aminoquinolines a bad name in India. Laboratory screening tests for G6PD deficiency are not difficult to perform and should be available widely in endemic areas. Primaquine should not be used during pregnancy.

Antimalarial prophylaxis

Advice on prophylaxis against malaria presents a great problem because of the difficulty in predicting drug resistance. Chloroquine has been widely used, but its usefulness has been seriously undermined by the spread of resistance in P. falciparum. Moreover, it has a bitter taste and more serious side-effects, such as skin photosensitization and retinal damage, may become apparent after prolonged use. For these reasons and because of the danger of further encouraging the emergence of chloroquine resistance, it is probably unwise to use the drug as a long-term prophylactic, even in areas known to be free of resistance. In general, it is preferable to use an antifolate agent (pyrimethamine or proguanil) whenever possible, but the unpredictability of resistance has led some authorities to recommend combinations of antifolates with chloroquine in an attempt to reduce the chances of breakthrough of protection. Mefloquine is a reliable prophy-lactic agent for short-term use in areas in which chloroquine resistance is prevalent, and is widely recommended despite its neurotoxicity.

Advice on the choice of prophylactic regimen has changed radically in the last few years and may alter again depending on drug resistance and the availability of new agents. It is therefore wise for anyone counselling a traveller to a malarious area to seek advice from a specialist, or make use of the excellent databases held nationally by travel clinics and the expert tropical medicine institutes. The

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choice of agent—or the decision to take any antimalarial—is a risk assessment that depends on the duration and likelihood of exposure against toxicity. One of the most difficult decisions is what to use for travellers to south-east Asia. Currently, doxycycline and clindamycin, antibacterial agents with modest anti-plasmodial activity, are often recommended because of widespread drug resistance to conventional antimalarials. Pregnant women and elderly patients on extensive medication might be well advised to travel to less exotic parts of the world if the reason for their journey is tourism.

The most important aspect of prophylaxis is regular medication and continuance of therapy for at least 4 weeks after the last possible exposure. Although it is not essential to premedicate patients it is advisable to start a routine a week or two before travelling in order to ensure acceptability and to enable adequate drug concentrations to be achieved before exposure. In highly endemic areas where the risk of malaria is high a double dose may be given. With weekly drugs such as pyrimethamine or chloroquine a dose can be given in the middle of the week. This should not be continued long term with chloroquine owing to chronic toxicity.

Sulphonamide and sulphone-containing mixtures should be avoided in persons known to be hypersensitive to these compounds. If antifolate agents are used during pregnancy, folic or folinic acid supplements should also be given. Of great importance, but often neglected, are practical hints to minimize exposure: wearing long clothes, using insect repellants such as diethyltoluamide (DEET), and sleeping under mosquito nets impregnated with insecticide (permethrin). It is also important to stress to all travellers that prophylaxis may not be effective, so that any fever should be treated with suspicion until malaria has been excluded by examination of adequate blood slides.

Amoebiasis

Entamoeba histolytica may live harmlessly in the lumen of the gut, usually in the cyst form, or may invade the gut mucosa to cause amoebic dysentery. The factors that govern the transformation from harmless commensal to invasive pathogen are poorly understood, although it is now clear that not all strains of E. histolytica have pathogenic potential. Secondary spread from the primary intestinal focus sometimes occurs to give rise to abscess formation in various parts of the body, usually the liver.

The treatment of symptomless cyst-passers, especially those living in endemic areas, is not worthwhile unless there is evidence of recurrent attacks of dysentery. Acute intestinal amoebiasis is characterized by bloody diarrhoeic stools. Motile amoebae with phagocytosed red cells are seen on direct microscopy of a freshly passed specimen. This is an indication for therapy to relieve symptoms and prevent possible complications: either local haemorrhage or invasion. Metro-nidazole is the agent of choice in a high initial dose which should be continued for 3–5 days. This drug gives a high cure rate; if there is a relapse and cysts

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are seen in the stool an agent more active against them such as diloxanide furoate should be given for 10 days.

Invasion of trophozoites into tissues, especially into the liver, may occur without dysentery and the first indication of amoebiasis may be an hepatic abscess. Metronidazole therapy needs to be of longer duration than with uncomplicated disease; although most cases respond within 72 h, treatment for 5–10 days is recommended. Where there is a large abscess or one that is easily drained, surgical aspiration speeds recovery. There is no evidence of drug resistance in amoebae. Metronidazole is easy to administer and gives rise to few adverse reactions. The only drawback in the poorer countries of the world where amoebiasis is hyperendemic is cost and availability. In such situations emetine hydrochloride or chloroquine may be given.

Giardiasis

The flagellate protozoon G. lamblia is found only in the intestinal lumen. There is no invasion of the surface, the trophozoite being attached to the mucosa of the small intestine, especially the jejunum. Cysts are passed in the stools and infection is transmitted by contamination of food and water. Giardia is a frequent cause of chronic diarrhoea and is often underestimated as a pathogen. However, many infections are asymptomatic and, even with a heavy infection in adults, the symptoms may be mild: nausea, flatulence, and steatorrhoea. In young children the condition may give rise to malabsorption. Although world-wide in distribution this intestinal infection, like most, is more common in less hygienic communities. Giardiasis is common in the UK as well as being the most frequently imported parasitic disease.

Metronidazole is the treatment of choice, administered in a similar regimen to that used to treat amoebic dysentery although lower doses may suffice. Cases which do not respond to metronidazole require mepacrine after re-infection has been excluded.

Cryptosporidiosis

Cryptosporidium parvum is an intestinal zoonotic protozoon that is now recognized as a common cause of acute diarrhoea in people who have had direct contact with animals or drunk contaminated water. The disease is generally mild and self limiting in otherwise healthy individuals, but in the immunosuppressed, especially those with AIDS, it causes a life-threatening prolonged enteritis. Many agents have been tried to combat infection, but none has been found to be reliably effective. Some success has been claimed with paromomycin, and the macrolide antibiotics spi-ramycin and azithromycin. A nitrothiazole derivative, nitazoxanide, is under trial.

African trypanosomiasis

Human trypanosomiasis due to Trypanosoma brucei rhodesiense is a sporadic disease in east and central Africa although occasional outbreaks occur. The clinical

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course of the disease found in this area is more acute than that caused by T. bru-cei gambiense, which is a major health hazard in rural west Africa. Both parasites eventually infect the brain to give the clinical manifestations of ‘sleeping sickness’. Before this stage a clinical diagnosis is difficult because of the non-specific nature of the symptoms. However, an early diagnosis is important as treatment is more effective and less toxic at this stage. Laboratory confirmation may be difficult to obtain except in specialized centres because the trypanosomes are often scanty in peripheral blood. Before CNS involvement suramin or pentamidine may be used in therapy, but when a lumbar puncture indicates meningoencephalitis it is necessary to use an organic arsenical. Melarsoprol has replaced the more toxic tryparsamide for this purpose. All the antitrypanosomal drugs are toxic; treatment should be given in hospital and expert advice sought.

An important advance in the treatment of sleeping sickness caused by T. brucei gambiense has been achieved with the introduction of eflornithine (p. 68). This drug appears to be effective even in the late meningoencephalitic stages of the disease, but, unfortunately, T. brucei rhodesiense appears to be refractory to treatment.

Chagas' disease

This form of trypanosomiasis is widespread in South America. The causative organism, T. cruzi, invades heart muscle causing myocardial damage which may be fatal. The condition had no known therapy until the nitrofuran agent nifur-timox appeared. This drug may succeed in eradicating parasites in the acute stage of the disease at the expense of some toxicity. Its value in established infection is more dubious. Similar considerations appear to apply to the nitro-imidazole derivative benznidazole, which some specialists prefer to nifurtimox.

Leishmaniasis

Kala azar

Visceral leishmaniasis is a chronic, often fatal, condition characterized by fever, anaemia, and gross splenomegaly. Microscopy and culture of bone marrow or splenic aspirate confirm the diagnosis. Pentavalent antimonials have been traditionally used although relapse due to drug resistance or inadequate dosage and duration of treatment is not uncommon, especially in India. Sodium stiboglu-conate (Pentostam) is given by the parenteral route in high dosage for at least 30 days and preferably longer. Drug resistance may be suppressed by use of high-dose antimonials for extended periods, but toxic effects such as cardiac irregularities are inevitable. Pentamidine has been used as an alternative for many years but patients fare little better on this toxic compound.

In an effort to reduce the toxicity of sodium stibogluconate, attempts have been made to package the drug in artificial liposomes—minute fat globules that

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are phagocytosed by cells of the reticuloendothelial system, where they release drug at the target site. Unfortunately, preparation of a suitable carrier that is stable in tropical conditions, and other problems, have militated against the success of this tactic. More success has been achieved with a liposome-encapsulated formulation of the antifungal agent amphotericin B, which is also useful in kala azar.

Treatment of leishmaniasis continues to evolve. Claims have been made for the efficacy of antifungal imidazoles, including itraconazole, ketoconazole, and fluconazole, and for the aminoglycoside antibiotic paromomycin. Miltefosine, a compound originally developed as an anticancer agent, is under trial in India.

Cutaneous and muco-cutaneous leishmaniasis

These forms of the disease are less serious and can be treated with lower total doses of pentavalent antimonial. Most respond to local excision.

Co-infection with HIV

In parts of the world in which both infections are common, disseminated leishmaniasis is an increasing problem in patients with HIV. In Mediterranean countries, relatively minor cutaneous lesions that would respond to topical treatment or self-heal in the immunocompetent person present as disseminated disease that is difficult to cure. Indeed, in HIV-positive patients, suppression is all that may be achievable, and control of disease with antiretroviral agents is as important as antileishmania therapy.

Toxoplasmosis

Toxoplasma gondii is a ubiquitous organism that normally passes harmlessly from rodents to cats, but can cause human infection by ingestion with contaminated food or close contact with infected cats. Toxoplasmas may cause death or abnormalities in the fetus by transplacental spread during pregnancy. However, many infections pass unrecognized and the parasite may encyst in muscle or brain. Latent organisms then re-emerge in immunocompromised individuals to cause cerebral toxoplasmosis, which may present like a brain abscess in AIDS patients.

The antifolate combination pyrimethamine–sulphadiazine is the usual treatment except during pregnancy, when spiramycin is used. Neither of these agents is particularly efficacious in HIV-infected patients, in whom clindamycin, and macrolides such as azithromycin have been tried. Co-trimoxazole used to prevent pneumocystis pneumonia in HIV (p. 342) also suppresses toxoplasma.

Other protozoan infections

Intestinal protozoa, such as Isospora (p. 71) and microsporidia (p. 72) cause minimal disease in healthy individuals, but are implicated in diarrhoeal illness

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in the immunodeficient, especially those with HIV. Treatment is poorly defined, although co-trimoxazole (isosporiasis) and albendazole (microsporidiosis) have been successfully used. These opportunist infections, like cryptosporidiosis, remit when the CD4 lymphocyte count improves on antiretroviral therapy.

Treatment of infection with the flagellate protozoon Trichomonas vaginalis is considered in Chapter 30 (p. 351).

Nematode infections

Filariasis

In some areas of the tropics nearly the whole population is infected with filarial worms. Diagnosis is made by microscopical demonstration of the larval forms (microfilariae) in blood or, in the special case of Onchocerca volvulus, in super-ficial shavings of skin. Some of the blood microfilariae exhibit a curious periodicity in that they are found in peripheral blood during only the day (Loa loa) or the night (Wuchereria bancrofti). Brugia malayi usually exhibits a less complete nocturnal periodicity. W. bancrofti and B. malayi cause a clinically identical condition resulting in severe cases of elephantiasis owing to blockage of the lymphatics of the lower trunk. This condition is seen in many parts of the tropics and probably over 250 million people are affected. The clinical syndrome is due to a variety of factors depending on degree of exposure and host reaction to the worms, and in any area a small proportion will have gross elephantiasis. Often by this stage the disease may be ‘burnt out’ and an anthelminthic may do little to improve the patient's condition, for which surgical and supportive measures are all that is left.

It is important to recognize B. malayi (which is restricted to south-east Asia) because therapy with diethylcarbamazine (DEC) produces severer reactions than with Bancroftian filariasis. One of the factors limiting individual and mass therapy of filariasis is the frequent occurrence of hypersensitivity reactions to dead worms. This problem is seen particularly in the treatment of filariasis due to O. volvulus, the causative parasite of river blindness, which affects large numbers of people in west Africa and central America. As with the other filariases, many infected persons exhibit only minor symptoms such as skin swelling and itching.

The decision to treat is tempered by a knowledge of the natural history of the disease, the patient's complaints, and the likelihood of re-infection in a hyperen-demic community. The chances and severity of possible reactions must be balanced against any possible benefit. This was particularly true when DEC was the only effective microfilaricide. The introduction of ivermectin and albendazole has changed the therapy of filariases. These relatively non-toxic drugs are now preferred for the treatment of onchocerciasis and lymphatic filariasis respectively. One of the benefits of their use is that reactions to treatment are a good deal milder than with DEC. Ivermectin is administered as a single oral dose which, in the

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control of onchocerciasis, is repeated annually in endemic areas. Mass treatment with ivermectin, together with vector control, has virtually eradicated onchocer-ciasis in some areas, and there are hopes that lymphatic filariasis will be similarly controlled with albendazole.

Toxocariasis

Infection with the dog roundworm Toxocara canis may cause a condition known as visceral larva migrans which may result in serious eye infection usually presenting as a visual loss in childhood. Although not a common disease it is found world-wide and is probably under-recognized. The larvae of the worm migrate to the retina, setting up an inflammatory response. Treatment with DEC has been recommended but hypersensitivity reactions may require steroids to be given as well. Mebendazole or albendazole may offer an effective and less toxic alternative.

Intestinal helminth infections

Single doses of the common agents such as piperazine, levamisole, and pyrantel pamoate give acceptable cure rates. Table 31.1 shows the differential activity of these and the oral benzimidazole derivatives, which have a broader spectrum and have largely superseded them, but are more expensive. Among benzimida-zoles, albendazole exhibits the best broad-spectrum anthelminthic activity. In warm countries with poor water supplies and inadequate methods of sewage disposal re-infection is almost inevitable, yet a few words of health education such as advice on wearing shoes to prevent hookworm may be extremely valuable.

Table 31.1 Spectrum of activity of drugs used in the treatment of intestinal helminthiasis

Drug

Ancylostoma duodenale

Necator americanus

Ascaris lumbricoides

Strongyloides stercoralis

Trichuris trichiura

Enterobius vermicularis

 

Piperazine

-

-

+++

-

-

+++

Levamisole

++

++

+++

-

-

-

Pyrantel pamoate

++

++

+++

+

++

+++

Thiabendazole

++

++

+++

++

-

++

Mebendazole

++

++

+++

+

++

+++

Albendazole

+++

++

+++

++

++

+++

 

+++, Highly effective; +, poorly effective;-, no useful activity.

Trematode (fluke) infections

Schistosomiasis

Schistosomes (also known as bilharzia, or blood flukes) give rise to a chronic debilitating condition with hepatosplenomegaly and diarrhoea or haematuria. The adult worms adopt a more-or-less benign relationship with the host, and it is fibrosis and tissue damage arising from the deposition of eggs which is responsible for most of the unpleasant manifestations of schistosomiasis. In the days when trivalent antimonials were the only available agents for therapy of bilharzia, the decision to treat a specific case would depend on similar factors to those mentioned for filariasis: balancing the toxic effects of treatment with the severity of the patient's illness and the likelihood of rapid re-infection. With several effective and safer compounds now available, treatment has become more routine. One drug, praziquantel, is effective against all the major types of schistosomiasis and offers the possibility of single-dose therapy for mass treatment campaigns. Less useful alternatives include oxamniquine, which is active only against Schisto-

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soma mansoni, and metriphonate, which is effective against the urinary form, S. haematobium.

With the advent of these relatively safe and cheap antischistosomal drugs, it has become possible to use chemotherapy as a means of control of the disease, in conjunction with the use of molluscicides to control the snail host and the provision of safe means of disposal of excreta. Unless there is development of drug resistance on a wide scale, such methods offer a good hope for the control of one of the major parasitic scourges of mankind.

Other trematode infections

Praziquantel has also transformed the treatment of most other trematode infections, including those caused by the Chinese liver flukeClonorchis sinensis and the lung fluke Paragonimus westermani. However, the liver fluke Fasciola hepatica does not usually respond to praziquantel. The treatment of fascioliasis is problematic, but the veterinary anthelminthic triclabendazole may be effective.

Cestode infections

Tapeworms

In addition to its use in trematode infections, praziquantel has emerged as an important agent in the treatment of tapeworm infections, including those caused by Taenia saginataT. soliumDiphyllobothrium latum and Hymenolepis nana. A single oral dose is usually effective, although more prolonged therapy is needed in cerebral cysticercosis caused by T. solium. In intestinal tapeworm infection, niclosamide is a suitable alternative.

Hydatid disease

Surgery to remove hydatid cysts after injection of a scolicide such as hypotonic saline remains the treatment of choice in hydatid disease, but is not without risk. Therapy with benzimidazole derivatives, particularly albendazole, has been successful in some cases and may be the only option in inoperable conditions, including disease caused by Echinococcus multilocularis.

Ectoparasites

A variety of arthropods feed on human skin. Some, such as ticks and mosquitoes, act as vectors of disease; others, such as mites, fleas, and lice are more of a nuisance. These parasites of the ectoderm are often visible and may produce skin lesions and itching after biting. In hygienic surroundings they are very emotive,

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even though it is estimated that over half the children in UK schools have head lice at some time and scabies is very common in the elderly in institutions.

Scabies

The mite, Sarcoptes scabiei, causes scabies in man and is spread by close contact. The commonest sites of infection are the hands, wrists, forearm, and axillae, or the genitalia after sexual contact. The mite burrows into the skin to form tunnels, which are diagnostic of the condition. There is often a more generalized hypersensitivity rash away from the area of penetration. All areas are itchy and scratching can lead to secondary bacterial infections, including impetigo.

Benzyl benzoate is effective, but is unpleasant to use, frequently causes irritation, and is not recommended for children. This has led to the use of hexachloro-cyclohexane (Lindane; now discontinued in the UK), the organophosphorus compound, malathion, and the pyrethroid, permethrin. Neither malathion nor Lindane should be used repeatedly over a short period.

The key to treatment of scabies is careful, complete application of the lotion and reapplication if hands have been washed during the period the insecticide is in contact with the skin. The whole body should be covered, with particular attention to hands, fingers, and nails, and left to act overnight, or preferably 24 h.

Immunocompromised patients, such as those with HIV and old people, may develop a very heavy infestation that may crust over—so-called Norwegian scabies. Oral treatment with ivermectin has been tried with some success.

Lice

The most common infestation in the developed world is due to head lice (Pediculus capitis) The adult lice pass from person to person during close contact and attach their eggs (nits) to the hairs. The infestation may spread in schools and the community and total eradication is probably impossible, though most people develop resistance to re-infection.

There is no ideal insecticide for treatment of head lice. Among agents that are used, resistance to permethrin, phenothrin, and malathion occurs; carbaryl is usually effective, but there are fears about possible toxicity. ‘Wet combing’, by passing a fine-tooth comb through hair which has just been washed with conditioner, is useful, but should be repeated 2–3 times a week for several weeks to remove all the lice. Various herbal shampoos, such as tea tree oil, have advocates, but there is little evidence that they are effective. Shaving the head is a drastic measure, which is not recommended.

Pubic lice (Phthirus pubis; ‘crab’ lice) hold tenaciously to pubic hair, but can also be found on the head and eyelashes. Aqueous preparations of insecticides, such as malathion, should be applied overnight to all parts of the body. They are generally easier to treat than head lice, but it is important to find and treat sexual contacts and to remember that other sexually transmitted infections may be present.