Antimicrobial Chemotherapy, 5th Edition
Part 4 - Therapeutic Use of Antimicrobial Agents
The organisms considered as ‘parasites’—that is, the protozoa, helminths, and arthropods that have an obligatory relationship to human beings or other animals—tend to cause chronic disease and many individuals, once infected, remain so for long periods. 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 continual high incidence of new cases. 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 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.
Parasitic diseases are, however, far from being restricted to the tropics. Some parasites such as Trichomonas vaginalis and threadworm are at least as common in developed countries. Moreover, the speed and extent of international travel ensures that infections acquired in the tropics may present therapeutic challenges to medical practitioners everywhere.
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% of 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 asymptomatic case without taking care to prevent re-infection is wasting resources and is not good practice. Moreover, 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 that might not always be able to effect a complete cure. Even though relatively safe compounds are now available for some parasitic diseases these considerations must still be borne in mind. 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.
Accurate laboratory diagnosis is essential if antiparasitic therapy is to be useful, since treatment of most parasitic infections is specific to the pathogen. Acute malaria is a medical emergency and demands immediate laboratory confirmation where facilities exist. Although various rapid diagnostic tests are available, microscopic diagnosis still remains the gold standard. Some intestinal protozoa such as Entamoeba coliare innocuous commensals. If they are misidentified in stool microscopy as Entamoeba histolytica the patient may be subjected to unnecessary treatment and the risk of side effects.
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.
Figure 30.1 shows the worldwide 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 international business travel and tourism to Africa or other tropical destinations. About 2000 cases of imported malaria are recorded in the UK each year—a figure likely to be an underestimate because of considerable under-reporting. Each year preventable fatalities from malaria occur in countries that are otherwise free of the disease. However, this is insignificant compared with the damage malaria inflicts on the populations of the tropical world, particularly in parts of Africa where many children die of falciparum malaria before they reach the age of 5.
Fig. 30.1 Distribution of malaria 2004. Reproduced from http://www.who.int/malaria with permission from The World Health Organisation.
After the Second World War chloroquine replaced the traditional remedy quinine as the drug of choice for the treatment of acute malaria. 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 cases urgent parenteral therapy is necessary in spite of the hazards of infusion.
In its time, chloroquine revolutionized the treatment and prophylaxis of malaria, but extensive use led to the appearance of resistant strains of Plasmodium falciparum in most areas in which the parasite occurs. Many chloroquine-resistant strains are also resistant to alternative drugs such as the combinations of pyrimethamine with sulphonamides or dapsone. Surprisingly for such an ancient remedy, resistance to quinine remains quite rare and the drug has returned to favour for severe falciparum malaria. Because of the possibility of reduced susceptibility to quinine, treatment with doxycycline or clindamycin, antibacterial antibiotics that also exhibit antimalarial activity, is also usually included. Species of Plasmodium other than P. falciparum generally retain susceptibility to chloroquine and it still remains the drug of choice in benign tertian and quartan malarias.
Derivatives of a Chinese herbal remedy, qinghaosu (artemisinin) are increasingly being used for the treatment of malaria in the tropics. Although animal experiments revealed a potential for neurotoxicity, extensive trials and increasing clinical experience have shown these compounds to be relatively safe and their future as antimalarial agents appears progressively more secure. Various formulations, including artesunic acid (artesunate), artemotil (β-arteether) and artemether are used for intravenous or intramuscular administration. Artesunate can also be given by mouth. Suppository formulations are also available and are particularly useful in children. Artemisinin derivatives are now being recommended as the drugs of choice in uncomplicated falciparum malaria; since they are more rapidly effective than any other drug, they are also now being used as an alternative to quinine in severe forms of the disease. Because of the risk of encouraging the development of resistance, it is strongly recommended that artemisinin derivatives should be used together with other antimalarial drugs: artemether with lumefantrine can be given orally if the patient is able to swallow and retain the medication. Alternatively combinations with amodiaquine, mefloquine, or sulphonamide-pyrimethamine are sometimes used, though the possibility of resistance to these agents should be borne in mind.
Mefloquine, a quinolinemethanol derivative, is usually active against chloroquine-resistant strains and has been successfully used for treatment. However, resistance to mefloquine emerges readily and there are fears that widespread use will quickly negate its value. Moreover, mefloquine use has been associated with neuropsychiatric side-effects that may persist for some time owing to the very long plasma half-life of the drug. Halofantrine has a shorter half-life (1-4 days, compared with 2-4 weeks) and fewer adverse reactions, but concern has been expressed over possible cardiotoxicity. The related lumefantrine is safer, but is available only in a combination product with artemether.
To effect a radical cure in recurrent malarias with a latent exo-erythrocytic phase—benign tertian malaria caused by P. vivax or P. ovale—it is necessary to use the 8-aminoquinoline primaquine. An accurate diagnosis should first be made by examining thin and thick blood films, and the acute erythrocytic attack is treated with chloroquine before primaquine is administered. Importantly, patients must be screened for glucose-6-phosphate dehydrogenase 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. Primaquine should not be used during pregnancy.
Reactions to primaquine have given the drug a bad name in India, where P. vivax infection and glucose-6-phosphate dehydrogenase deficiency are both common. To overcome this problem a primaquine analogue, bulaquine, has been developed in India and marketed there in a combination product with chloroquine for the treatment and radical cure of malaria caused by P. vivax. Bulaquine is said to lack the haemolytic potential of primaquine, although it appears to be at least partially metabolized to primaquine in the bloodstream.
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. Chloroquine should not be continued long term owing to chronic toxicity. 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. Sulphonamide and sulphone-containing mixtures should be avoided in persons known to be hypersensitive to these compounds or to suffer from glucose-6-phosphate dehydrogenase deficiency. If antifolate agents are used during pregnancy, folic or folinic acid supplements should be given. The combination of pyrimethamine with sulfadoxine has been associated with some fatal reactions and is no longer recommended as a prophylactic agent.
Mefloquine is a reliable prophylactic drug for short-term use in areas in which chloroquine resistance is prevalent, and is widely recommended despite its neurotoxicity. Atovaquone-proguanil and doxycycline also appear effective. Doxycycline is unsuitable for pregnant women and young children.
Advice on the choice of prophylactic regimen is under constant review depending on information on drug resistance in individual travel destinations 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 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. 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 aspects of prophylaxis are 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. Of great importance, but often neglected, is practical advice to keep exposed parts of the body covered, especially in the evening when mosquitoes are active, and to use insect repellants such as diethyltoluamide (DEET). Screening windows and sleeping under mosquito nets impregnated with insecticide (permethrin) is also a wise precaution. It is important to stress to all travellers that prophylaxis may not be effective, so that any fever developing within 2 years of visiting an endemic area should be treated with suspicion until malaria has been excluded by examination of adequate blood slides.
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 some strains of E. histolytica (morphologically identical forms now often classified as E. dispar) do not 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 such as local haemorrhage or invasion. Metronidazole 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 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.
The flagellate protozoon Giardia 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 worldwide in distribution this intestinal infection, like most, is more common in less hygienic communities. Giardiasis is fairly 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 that do not respond to metronidazole require albendazole or mepacrine (quinacrine) after re-infection has been excluded.
Cryptosporidium parvum is a common cause of acute diarrhoea in people who have had direct contact with animals or have drunk contaminated water. The disease is generally mild and self-limiting in otherwise healthy individuals, and fluid replacement is all that is usually required. Nitazoxanide appears to be effective if treatment is thought to be necessary. Various drugs, including the macrolide azithromycin and the aminoglycoside paromomycin, have been used (alone or in combination) with modest results against the more severe disease seen in patients with AIDS. Whether nitazoxamide therapy is effective in these patients is presently unclear. Fortunately, the incidence of the disease has declined in this group since effective antiretroviral therapy has become available.
Human trypanosomiasis due to Trypanosoma brucei rhodesiense is a sporadic disease in east and central Africa, although occasional outbreaks occur. The clinical course of the disease found in this area is more acute than that caused by T. brucei 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 central nervous system involvement suramin or pentamidine may be used in therapy, but when a lumbar puncture indicates meningo-encephalitis 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. This drug is effective even in the late meningo-encephalitic stages of the disease, but, unfortunately, T. brucei rhodesienseappears to be refractory to treatment.
This form of trypanosomiasis is widespread in South America. The causative organism, T. cruzi, invades heart muscle causing myocardial damage, which may eventually be fatal. The nitrofuran agent nifurtimox 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 nitroimidazole derivative benznidazole, which some specialists prefer to nifurtimox.
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 stibogluconate or meglumine antimonate 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 but patients fare little better on this toxic compound.
In an effort to reduce the toxicity of antimony derivatives, attempts have been made to package the drugs in artificial liposomes—minute fat globules that are phagocytosed by cells of the reticulo-endothelial 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. Miltefosine, a compound originally developed as an anticancer agent, is now in successful use in India, where kala azar is a major problem. Claims have been made for the efficacy of antifungal imidazoles, including itraconazole, ketoconazole, and fluconazole, and for the aminoglycoside antibiotic paromomycin.
Cutaneous and mucocutaneous leishmaniasis
Cutaneous leishmaniasis is usually localized and often resolves spontaneously. Topical paromomycin or injections of sodium stibogluconate into the margins of the lesion aid resolution. Mucocutaneous leishmaniasis requires systemic treatment with antimonials and may also need surgical intervention. Miltefosine is showing promise and may replace earlier therapies for these conditions.
Co-infection with HIV
In parts of the world in which both infections are common, disseminated leishmaniasis may cause a serious problem in patients with HIV. 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. Where it is available, effective antiretroviral therapy has reduced the incidence of this complication. Elsewhere, suppression is all that may be achievable in HIV-positive patients.
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-sulfadiazine 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. 404) also suppresses toxoplasma.
Treatment of infection with the ciliate Balantidium coli has not been properly defined, but tetracyclines and metronidazole appear to be effective.
Infections in splenectomized patients, usually caused by Babesia divergens, is life-threatening and requires urgent treatment, but experience is limited. There is evidence that the combination of clindamycin and quinine is useful, but exchange transfusion may also be needed. Infection with B. microti in previously healthy persons is usually self-limiting, but clindamycin and quinine can be used if therapy is warranted. The combination of azithromycin and atovaquone has also been used with success.
Other protozoan infections
Treatment of infection with intestinal protozoa such as Isospora belli, Cyclospora cayetanensis, and various microsporidia is poorly defined, although co-trimoxazole (isosporiasis and cyclosporiasis) and albendazole (microsporidiosis) have been successfully used. In patients with AIDS these opportunist infections usually remit when the CD4 lymphocyte count improves on antiretroviral therapy.
Treatment of infection with the flagellate protozoon Trichomonas vaginalis is considered in Chapter 29 (p. 418).
Well over 200 million people harbour filarial worms and in some areas of the tropics nearly the whole population is infected. Diagnosis is made by microscopical demonstration of the larval forms (microfilariae) in blood or, in the special case of Onchocerca volvulus, in superficial 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 (which is restricted to South-east Asia) usually exhibits a less complete nocturnal periodicity. W. bancrofti and B. malayi cause a clinically identical condition (lymphatic filariasis) sometimes resulting in elephantiasis owing to blockage of the lymphatics of the lower trunk. 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. O. volvulus, the causative parasite of river blindness, 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 introduction of ivermectin and albendazole has revolutionized the therapy of filarial infections. 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 the traditional drug, diethylcarbamazine, although ivermectin sometimes gives rise to an encephalopathy in individuals co-infected with Loa loa. Ivermectin is administered as a single oral dose, which is repeated annually in endemic areas. Mass treatment with ivermectin, together with vector control, has virtually eradicated onchocerciasis in some districts, and there are hopes that lymphatic filariasis will be similarly controlled with a combination of ivermectin and albendazole. The manufacturers of these drugs are providing them free for control programmes in countries where the diseases are endemic.
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 worldwide and is probably under-recognized. The larvae of the worm migrate to the retina, setting up an inflammatory response. Treatment with diethylcarbamazine has been recommended but hypersensitivity reactions may require steroids to be given as well. Albendazole (or mebendazole) appears to offer an effective and less toxic alternative.
Intestinal nematode infections
Single doses of the common agents such as piperazine, levamisole, and pyrantel pamoate give acceptable cure rates. Table 30.1 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 benzimidazoles, albendazole exhibits the best broad-spectrum anthelminthic activity. Tiabendazole (thiabendazole) is often poorly tolerated and is best avoided if possible.
In warm countries with poor water supplies and inadequate methods of sewage disposal re-infection with intestinal worms is almost inevitable, though simple health education advice on preventive measures may be valuable.
Table 30.1 Spectrum of activity of drugs used in the treatment of intestinal helminthiasis
Trematode (fluke) infections
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 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 Schistosoma mansoni, and metrifonate (trichlorfon), 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.
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 saginata, T. solium, Diphyllobothrium 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.
Surgery to remove hydatid cysts after injection of a scolicide such as hypotonic saline, formalin, or cetrimide into the cyst 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.
A variety of arthropods feed on human blood. Some, such as ticks, lice, and mosquitoes, may act as vectors of disease; others, including most mites and fleas, 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, even though it is estimated that over half the children in UK schools have head lice at some time and scabies is common in the elderly in institutions.
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 the pyrethroid, permethrin, and the organophosphorus compound, malathion. Malathion should not be used repeatedly over a short period. Lindane (hexachlorocyclohexane; now discontinued in the UK) is strongly suspected to be carcinogenic and should not be used.
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.
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 hair. 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 that has just been washed with conditioner, is useful, but should be repeated two to three 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.
World Health Organization. WHO Model Prescribing Information: drugs used in parasitic disease. 2nd edition. WHO, Geneva, 1995.
World Health Organization. Guidelines for the Treatment of Malaria. WHO, Geneva, 2006. Available at: http://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf