Dialogue on Diarrhoea, Issue 42, September 1990

ISSUE No. 42

The international newsletter on the control of diarrhoea1 diseases

are really needed. Third, in some coun- Drugs and childhood diarrhoea tries, widespread use of antimicrobials has led to high levels of antibiotic resistance - this means that the antibiotics are no Oral rehydration therapy should be the commonly used to treat diarrhoea, explain- longer effective. On page 5, DD describes priority treatment for childhood diarrhoea. ing why they are not appropriate for acute how antibiotic resistance develops and why Ninety five per cent of acute childhood diarrhoea in children. The next two issues it is a serious problem. diarrhoea, whatever the cause, can be suc- will include reviews of antimotility drugs cessfully treated with ORT and continued and adsorbents. Working together feeding, and does not require treatment To reduce inappropriate use of drugs for with drugs. Despite widespread promotion Unnecessary prescribing diarrhoea, a co-ordinated response is of this message, doctors continue to Unnecessary prescribing has several needed. This involves legislation, training prescribe ineffective, expensive and important disadvantages. First, giving and education of doctors and the public, unnecessary drugs to treat diarrhoea; powerful drugs to small children does not and ensuring that messages about drug families continue to ask their doctors for stop the diarrhoea, may cause dangerous treatment for diarrhoea are consistent. The them or buy them over the counter from side effects and can result in families article on page 7 describes the coordinated pharmacists; and manufacturers continue neglecting to rehydrate and feed a sick approach being taken in Peru, where the to promote and market a wide range of child. Second, drugs are expensive for Ministry of Health, health professionals anti-diarrhoeals. In many countries, drugs families and for the health system. The and activists are working together to tackle are used more than ORT to treat diarrhoea resources saved by reducing unnecessary the problem of widespread over-use of (see pages 6 and 7). On pages 2, 3 and 4, prescribing could-be better-used in other anti-hiarrhoeal drugs in children. DD reviews some of the antibiotics most ways and the drugs saved for when they KME, WAMC and KA

Use of ORS and druas for diarrhoea _ it? 60 50 40 30 20 10

0 c Africa Americas South East East Western Asia Mediterranean Pacific n ORS use rate Drug use rate Information from 140 household surveys in 47 countries, up to 1989 Source: WHO Programme for Control of Diarrhoea1 Diseases Seventh Programme Report (1988-l 989) WHOICDDl90.34

In this issue: 0 Drugreviews and resources

0 Antibiotic resistance Appropriate Health Resources & Technologies Action Group Ltd 0 Reports from Peru, Pakistan and Indonesia

Dialogue on Diarrhoea, issue 42, September 1990. Published quarterly by AHRTAG, 1 London Bridge Street, London SE1 9SG, UK. 1 Drugs and diarrhoea

In most cases of childhood diarrhoea, drugs are The role of some antibiotics in treating unnecessary and inappropriate. The WHO CDD shigellosis is well established, but not all antibiotics are equally effective. Some programme has reviewed the literature on the early uncontrolled studies reported good efficacy and side effects of the most widely used results from treating shigellosis with oral drugs. In this issue DD previews the information aminoglycosides. Others showed bacterial and clinical cure rates of less than 50 per available on three types of antimicrobial agents - cent, and two suggested that streptomycin neomycin, streptomycin and hydroxyquinolines. and neomycin were no better in shigellosis therapy than simple supportive care. A double blind trial comparing neomycin 1 Diarrhoea can be caused by: with ampicillin provided further evidence Neomycin of the ineffectiveness of non-absorbable 8 0 Viruses - mostly rotavirus antibiotics such as neomycin in shigellosis Nzmycin, an antibiotic contained in 0 Bacteria - virtually all are Gram- treatment. many oral anti-diarrhoeal preparations, negative aerobic pathogens Studies have also shown that antibiotic has not been proved to be effective in the 0 Protozoa - especially Cryptosporidia, therapy can actually prolong the carrier treatment of acute diarrhoea. Neomycin Giardia and amoeba state in Salmonella gastroenteritis, and given by mouth has been associated with clinical relapse may be more frequent in 2 Antibiotics are, in general, only useful for toxic effects on the gut and may worsen patients treated with antibiotics. Placebo or prolong diarrhoea. Widespread use bacteria. lltey are ineffective for viruses and have very limited value for protozoa, controlled trials of neomycin, ampicillin, of antibiotics such as neomycin can and amoxycillin have confirmed that these increase antimicrobial resistance. Oral e.g. tetracycline is partly eflective for amoeba. There are, however, anti- antibiotics are ineffective in treating preparations containing neomycin are protozoals for amoeba and Giardia. Salmonella gastroenteritis. not recommended for use in the treatment of diarrhoea. 3 Antibiotics are ineffective for many food Adverse effects poisoning Salmonella. i%y are not prac- Neomycin can damage the structure of the Formulations tical for other bacterial diarrhoeas, except gut and interfere with its normal function. Neomycin is an aminoglycoside antibiotic cholera and shigellosis, because one can- It can cause malabsorption of fats, sugars used either alone or in combination with not determine clinically what bacten’um and calcium. After as little as three days, intestinal adsorbents, antimotility agents, is involved, if any, and thus what destruction of the microvilli lining the sur- antibiotic to give. or other antibiotics*. face of the small intestine can appear; and after seven days, invasion of the sub- Pharmacology duce enterotoxin. Widespread use of mucosal layer of the small bowel by Neomycin is classified as non-absorbable neomycin may therefore not only increase wsinophilic white cells has been Observed. - most of a dose given by mouth is the frequency of antibiotic resistant micro- Controlled trials have demonstrated that excreted unchanged in the stool, although organisms, but may also help bacteria that extended courses of neomycin prolonged some absorption does occur in the cause diarrhoea through enterotoxin to sur- the duration of diarrhoea. gastrointestinal tract. What is absorbed is vive and spread. When given by injection, amino- primarily excreted in the urine. glycosides are known to produce toxic Efficacy effects on the kidneys and ears. Because How it works Studies of neomycin in acute diarrhoea (of neomycin is usually given by mouth in Neomycin is rapidly bactericidal (it kills unknown aetiology) have reported ‘cure’ diarrhoea treatment and is poorly and inhibits reproduction of bacteria rates ranging from 50-100 per cent. absorbed, these complications are uncom- quickly). It is active against most aerobic However, none included placebo controls, mon, but there have been reports of toxic Gram-negative organisms (see box) and and since most acute diarrhoeas are self- effects with prolonged therapy or high staphylococci, but resistant strains of limiting, these reports of ‘cures’ are not doses, especially when kidney function is Escherichia colt, Klebsiella, Proteus, meaningful. already impaired. Shigella, and Salmonella are common. One double blind, placebo-controlled Streptococci and Gram-positive bacilli are trial (see box, page 4) of neomycin in acute Source: the text on pages 2 to 4 has been also largely resistant. diarrhoea indicated that neomycin may adapted by DD from draft material prepared The mechanism of resistance of Gram- actually increase the severity and prolong by the Control of Diarrhoeal Diseases Pro- gramme of the World Health Organization negative organisms to neomycin can also the duration of the disease. There are no reported trials assessing neomycin in the (WHO). A series of nine reviews is in confer resistance to other antibiotics (see preparation covering drugs commonly used page 5). These resistance factors, which treatment of diarrhoea caused by enterotoxigenic , entero-adherent, entero- in the treatment of diarrhoea. They will be can be transferred between bacteria, can grouped in three sections: antimicrobials, haemorrhagic or entero-invasive E. coli. sometimes also convey the ability to pro- antimotility drugs and adsorbents, and Some uncontrolled clinical observations published together as a WHO publication have reported good response of EPEC entitled l7re rational use of drugs in the *With all drug preparations it is important infections to neomycin therapy, but others management of acute diarrhoea in children, to look carefully at the contents or ingre- have noted little difference between to be available early in 1991 from: dients as well as the brand name. neomycin and supportive therapy alone. CDD/WHO, 1211 Geneva 27, Switzerland.

2 Dialogue on Diarrhoea, issue 42, September 1990. Published quarterly by AHRTAG, 1 London Bridge Street, London SE1 9SG, UK. Drugs and diarrhoea

Formulations and drug interactions Neomycin is usually sold in combination with a variety of adsorbents or other antibiotics. None of these combination products has been shown to be effective in clinical trials. The hydroxyquinolines contained in many of them have been withdrawn and prohibited in many countries because of their dangerous effect on the nervous system, while kaolin and pectin components can interfere with the absorption of certain useful antibiotics and antimalarials.

a/ Streptomycin Streptomycin (or dihydrostreptomycin) has no proven value in the treatment of any diarrhoea. It may increase the severity or prolong the duration of some cases of diarrhoea. The widespread use of antibiotics such as streptomycin pro- motes resistance to a variety of antimicrobial agents. Streptomycin (and dihydrostreptomycin) are not recommended for the treatment of diarrhoea.

Formulations Streptomycin is an aminoglycoside antibiotic which is important in tuberculosis (given by injection), but which is also widely marketed as an oral prepara- Families and health workers need to know that ORT, not drugs, should be given for most tion for diarrhoea treatment. It is often childhood diarrhoea. combined with a variety of adsorbents, vitamins, or other antibiotics. Dihydro- range from 36 per cent for Escherichia coli shigellosis; but other reports showed high streptomycin is a related antibiotic with and 67 per cent for Shigella in Boston, failure rates or detected no difference similar properties but greater toxicity. USA, to almost 100 per cent for entero- between streptomycin and supportive Despite the absence of studies on its pathogenic E. cofi in New Delhi, India. As therapy alone. Some treatment failures efficacy in diarrhoea, it is also widely with neomycin, widespread use may also have been attributed to high rates of marketed as a diarrhoea treatment. lead to selection of organisms with microbial resistance, but failure rates of 60 enhanced pathogenicity . per cent in the treatment of Shigella Pharmacology dysentery have been noted even when the Streptomycin is not absorbed from the Efficacy infecting organisms are sensitive to strep- gastrointestinal tract, except when the Most trials to assess the efficacy of oral tomycin when tested in the laboratory. mucosa is damaged. Most of the drug is streptomycin in the treatment of acute diar- Comparison of ampicillin and neomycin excreted unchanged in the stool. rhoea have been uncontrolled, hence the suggest that non-absorbable antibiotics*, results are not useful. In one controlled such as neomycin and streptomycin, do not How it works trial, streptomycin therapy was associated have much effect on organisms that invade Like neomycin, streptomycin kills and with increased severity and duration of the intestinal mucosa, and hence are of lit- inhibits reproduction of many bacteria diarrhoea. tle use in treating Shigella infections. (*Zr quickly. Streptomycin is extremely useful Despite the lack of evidence of efficacy is better to use an absorbable antibiotic - in the treatment of tuberculosis. It is also from controlled clinical trials, strep- one that can get into the blood and tissues.) active against aerobic Gram-negative tomycin was widely used in the 1950s to High failure rates have also been bacteria and some strains of Staphylo- treat diarrhoea due to Escherichia coli. reported with streptomycin in the treatment coccus aureus. Extensive use of strep- Since the emergence of widespread of Salmonella gastroenteritis. Antibiotic tomycin to treat other infections is resistance, other antibiotics have been used therapy alone can actually prolong the car- associated with the development of to treat E. coli infections. rier state in acute gastroenteritis due to widespread antimicrobial resistance. Cur- Early uncontrolled trials suggested that salmonella. (In contrast, Sulmonella rent reports of streptomycin resistance streptomycin might be effective to treat typhae, the organism that causes typhoid

Dialogue on Diarrhoea, issue 42, September 1990. Published quarterly by AHRTAG, 1 London Bridge Street, London SE1 9SG, UK. 3 Drugs and diarrhoea

most of these antibiotics are not How do we know if a drug really works? amoebicidal, and the rationale for com- Drugs need to be tested objectively; the pro- If there is no effective treatment for the bination therapy is therefore unclear. No per way to do this is a ‘controlled clinical illness, test the new drug against a well-controlled trials have compared these trial’. The steps are as follows: ‘placebo’ (an inert substance, with no combinations with metronidazole, the cur- Define the patients to be treated, mak- pharmacological action, but which looks rent treatment standard for amoebiasis. ing sure that they have the disease for like the treatment drug). Hydroxyquinolines have also been which they are to be treated, not some If a recognised effective drug exists and advocated to treat asymptomatic amoebic other illness. the trial is to see whether a new product cyst passers, but failure rates of up to 25 Randomly allocate patients to two (or is better, the standard and new drugs per cent have been seen and therapy for more) treatment groups. should be compared with each other in a up to three weeks is usually needed. It is best if treatments are given ‘blind’, ‘double blind’ assessment. Metronidazole produces comparable cure I i.e. neither the patients nor the health Assess the results of the two groups (stan- rates after only ten days of treatment. dard treatment or placebo versus new workers know which treatment is given However, therapy for asymptomatic cyst to specific individuals. This is called a treatment) statistically, to see whether any passers is not recommended because most ‘double blind’ clinical trial. difference in outcome is likely to be are colonised with non-pathogenic E. Assess recovery by objective caused by the drug, and not to have occur- histolytica and up to 90 per cent of infec- measurements (such as duration of red by chance. symptoms, amount of stool passed, etc.) Unless trials of drugs are done following tions terminate spontaneously without rather than because patients say they these rules, it is not likely that their results treatment. Moreover, in areas of high ‘feel better’. will be valid. endemicity, the probability of reinfection is high. fever, requires appropriate antibiotic treat- and toxic: they are no longer used at all With nitroimidazoles such as metro- ment. Typhoid fever is not normally in developed countries. For amoebic nidazole (now available as a low cost associated with diarrhoea.) dysentery, less toxic, more effective generic), tinidazole, ornidazole and amoebicides are available and are much nimorazole widely available, hydroxy- Adverse effects preferred. quinolines are not needed to treat amoebic Streptomycin, like neomycin, if given by diseases. injection, may have toxic effects on the Formulations Hydroxyquinolines are still used widely ears and kidneys. If given orally, these A range of products is available, the most and non-selectively in acute diarrhoea, complications are unlikely, but the extent popular being clioquinol (iodochlor- even though no studies have shown them of drug absorption, and its toxicity in hydroxyquinoline) and iodoquinol to be effective. The results of different children with acute diarrhoea, have not (di-iodohydroxyquinoline); also dibromo- trials give no basis for recommending been fully evaluated. hydroxyquinol (broxyquinoline) and chlor- hydroxyquinolines for prevention or treat- quinaldol (dichloromethylhydroxy- ment of traveller’s diarrhoea or other diar- Formulations and drug quinoline). These are sold under various rhoeas interactions trade names, either alone or combined with For diarrhoea treatment, streptomycin is vitamins, antibiotics or other agents. Adverse effects usually sold in combination with other Adverse effects include abdominal discom- ingredients such as kaolin, pectin, Pharmacology fort, diarrhoea, skin rash, acne, headaches and enlargement of the thyroid gland. hydroxyquinolines, sulphonamides, or Hydroxyquinolines are well absorbed by More serious are the many reports of chloramphenicol. These combination pro- the body. Though most of the drug is neurological complications linked to ducts have not been shown to be effective excreted in the stools, up to 25 per cent hydroxyquinolines. Between 1955 and and the multiple agents they contain cause of an oral dose is broken down in the liver 1970, about 10,000 cases of subacute optic additional side effects or undesirable drug and can be recovered in the urine. interactions. neuropathy (SMON) were diagnosed in Japan: five per cent of affected persons How they work died and up to 15 per cent were left com- The way in which hydroxyquinolines work pletely disabled; 75 per cent of the cases is unknown. They are active against both Hydroxyquinolines were associated with taking clioquinol. I w motile and cyst forms of amoeba. They SMON is characterised by abdominal pain Hydroxyquinolines are useful in the have also been shown to be active against or diarrhoea followed by painful sensations \ treatment of some parasitic infections. a number of enteric bacteria in the in the arms and legs and impaired vision. They are, however, widely used for the laboratory, but their effect on the bacteria Removal of clioquinol from the Japanese routine treatment of diarrhoea, even within the gut is not well understood. market led to a dramatic fall in the number though they have not been shown to be of cases of SMON. Similar neurological effective. They have some effect on Effkacy disorders associated with hydroxy- amoebic dysentery, but must be used Hydroxyquinolines function only within quinolines have been reported from with other drugs to obtain satisfactory the intestinal lumen. When used alone to Europe, the USA, Australia and India. results. Side effects include severe eye treat amoebic dysentery, failure rates are and nervous system disorders. Hydroxy- high; in combination with antibiotics such References for the studies referred to in quinolines are not recommended for as tetracycline or erythromycin, treatment these reviews are available from diarrhoea because they are ineffective seems to be more successful, although DD/AHRTAG and CDD/WHO.

4 Dialogue on Diarrhoea, issue 42, September 1990. Published quarterly by AHRTAG, 1 London Bridge Street, London SE1 9SG, UK. Questions and answers

What the patient can do: Antibiotic resistance 0 remember that ORT is the correct treatment for most diarrhoea; 0 never use antibiotics for diarrhoea unless they are prescribed by a doctor or health bacteria are resistant to cotrimoxazole, Q What is an antibiotic? worker, never give antidiarrhoeal drugs tetracyclines and other antimicrobials; and to children or infants; A Antibiotics are drugs that prevent or most Shigella to ampicillin. 0 if an antibiotic is prescribed, be certain restrict bacterial growth, and so they are you understand the instructions for its useful in treating infections caused by use and follow them carefully: take it for How does resistance develop? bacteria. Some antibiotics have a ‘broad Q the recommended time, and do not stop spectrum’ of action, that is they work even if the symptoms clear up; against a wide variety of micro-organisms. A There are two main ways in which 0 never try to save money by buying less Others work only against specific groups bacteria can resist the effects of antibiotics. than the prescribed amount. of organisms, and are not effective against 1. The bacteria themselves can change so What the doctor can do: others. This is because many bacteria are that antibiotics are no longer effective naturally insensitive to some antibiotics. 0 never prescribe antibiotics or against them - they become drug-tolerant. antibacterial agents unless they are Antibiotics have no effect on viral infec- Because bacteria reproduce rapidly they absolutely necessary; for diarrhoea, give tions such as rotavirus diarrhoea. are very adaptable and able to change fast antibiotics only for dysentery or when in order to survive. When antibiotics are cholera is suspected; 0 explain to the patient that they must com- When should antibiotics be given for given, the more sensitive bacteria are Q plete the full course of treatment, even diarrhoea? rapidly eliminated, but if a few adapt and become resistant, these tiill reproduce and though the symptoms may go away or soon replace the ones that were sensitive. become less before the end of the A Antibiotics are useful for diarrhoea treatment. treatment if there is blood in the stool, 2. The bacteria can develop ways to reduce indicating that Shigella is the likely cause; the effectiveness of the antibiotics - they What the health authority can do: or cholera (diarrhoea caused by Vibrio become drug-destroying. For example, 0 do not allow ‘prescription only’ cholerue) is suspected: the patient has bacteria can produce substances which medicines (such as antibiotics) to be sold severe dehydration due to watery diar- inhibit the action of some antibiotics e.g. without a prescription; rhoea, is over two years old, and cholera betalactamases which make penicillins 0 ensure that antibiotics are only prescribed by trained health workers, is known to be occurring in the area. ineffective, and cephalosporinases or Antibiotics should never be given and that advice is given on their use; aminoglycoside-inactivating enzymes 0 ensure that drug legislation is adequate routinely for diarrhoea: they can be harm- which make cephalosporin antibiotics ful, especially in young children, and may and that it is enforced; (gentamicin and kanamycin) ineffective. 0 as part of the strategy to control diar- prolong an episode of diarrhoea. Resistance is more likely to develop if rhoeal disease, make sure that ORT is antibiotics are widely and frequently used; promoted as the best and most important Q What is antibiotic resistance? and antibiotics are used in doses which are treatment for diarrhoea. not large enough or are used for too short A Bacteria that were originally sensitive a time, so that not all the disease-causing because resistance becomes more likely if to an antibiotic may become resistant to it. bacteria are destroyed. a drug is used more widely. Antibiotics Resistance can be demonstrated in the Antibiotic resistance often develops should always be taken in the right doses laboratory, but may also be seen clinically because a bacterium acquires a component and for the recommended amount of time. because the antibiotic will have little or no known as a plasmid. A bacterium which If a drug is prescribed to be taken for beneficial effect on the illness. is resistant to an antibiotic because it five days, it is important to continue tak- possesses a resistance factor (R-factor) can ing it for five days. Often a patient may pass this on, by means of a plasmid, to a begin to feel better and symptoms may be Why is antibiotic resistance Q bacterium which was previously sensitive lessened in only two or three days, but the important? to the antibiotic. The plasmid contains bacteria are unlikely to have been fully genetic material which is transferred from eliminated in this time. Stopping the drug If bacteria become resistant to par- ? A one bacterium to another. If antibiotics are early helps resistance to develop, and ticular antibiotics, then those drugs will be used after a resistant strain develops, that symptoms may return because the bacteria ineffective - they will no longer treat the strain survives, continues to multiply and are able to grow again. Often, people will infection caused by the bacteria. Because can quickly become predominant. be tempted to take less than the recom- of this, some antibiotics are no longer mended amount of a drug if it is cheaper useful in many parts of the world. Newer for them to buy less, and they do not antibiotics which are effective may not be What can be done to prevent Q understand why a full course is needed. available, or may be very expensive. Some resistance from developing? strains of bacteria have adapted to new With thanks to Professor P D’Arcy, The antibiotics almost as soon as they become A The correct use of antibiotics is School of Pharmacy, University of Lon- available, thus greatly limiting their extremely important. Antibiotics should don, 29139 Brunswick Square, London usefulness. In many countries, most E. coli never be used when they are not needed, WClN lAX, UK.

Dialogue on Diarrhoea, issue 42, September 1990. Published quarterly by AHRTAG, 1 London Bridge Street, London SE1 9SG, UK. 5 Country reports

Only one company carried out promo- PAKISTAN Anti-diarrhoeallantibacterial tion of ORS . This company was responsi- combinations ble for 80 per cent of ORS sales, and Should ORS be marketed (6, cllO) ,,/-----~-‘-...\ \ employed 41 ‘detailmen’ to visit doctors. i like other drugs? In urban areas, company staff visited drug Why do people use ‘anti- retailers and wholesalers to encourage diarrhoeal’ drugs when ORS is orders for ORS packets, as well as to pro- Intestinal mote ORS by talking to doctors. In rural better and cheaper? Camille adsorbents areas, a further 120 sales staff worked with Saade and Maggie Huff- (17%) a network of regional distributors, and also Rousselle argue that under- with paramedical workers. The relatively weak market position of standing commercial sales Motility ORS may be one reason why it is not used techniques could help to inhibitors 0% packets more often. In many places, increased increase the use of ORS. (12%) (9%) marketing of ORS might help to increase Commercial marketing is a powerful force. both its sales and use. Health workers and It is, for example, a factor in persuading Figure 1: the market shares of commercial others concerned with public health can women to use powdered milks and infant treatments for diarrhoea in Pakistan also take action. Those targeted by formulas instead of breastfeeding. To pro- representatives promoting ‘anti-diarrhoeal’ mote ORT successfully, it is essential to tions of kaolin and pectin. drugs must understand that these drugs are understand the commercial forces used to The best-selling ‘anti-diarrhoeal’ drugs promoted to increase sales, not necessarily promote the drugs which are often used in Pakistan are all produced by subsidiaries because they have proven value for treating instead of ORT. Figure 1 shows the results of multinational companies with tremen- diarrhoea. This is especially important of a study in Pakistan (carried out by the dous marketing strength and experience. because ‘anti-diarrhoeal’ drugs are poten- PRITECH project) on the market for com- The main marketing technique in Pakistan tially dangerous. Also their high costs mercial treatments for diarrhoea. It is is ‘detailing’, which involves members of waste health service resources, and the estimated that at least US$7.5 million is the 50 to 80 person sales force of each over-use of antibiotics encourages the spent on these products each year, with company making regular visits to most development of resistant strains of only about nine per cent of this spent on doctors in the country. bacteria. Those involved in marketing of ORS packets (of which eight different Before and during the diarrhoea season, ORS need to analyse the competition in the brands are available). Over 90 per cent of company representatives increase the commercial sector, and develop strategies the total was spent on ‘anti-diarrhoeal’ emphasis on ‘an&diarrhoea1 drugs by to increase the demand for ORS. drugs which are ineffective and potentially handing out promotional literature and free Camille Saade, AED, PRITECH Pro- dangerous. As well as the 82 different samples. This activity is backed up by ject, Washington DC, USA; and Maggie combination drugs which include advertising in medical journals and by Huff-Rousselle, Initiatives Inc, 239 antibiotics in their formula, this 90 per cent techniques aimed at pharmacists: giving Commonwealth Avenue, Boston, MA share included motility inhibiting drugs free goods, bonus offers and sales 02116, USA. and intestinal adsorbents such as combina- incentives. INDONESIA PERU Drug prescribing for diarrhoea Co-ordinated national action the average prescription was for only In 1987 the Ministry of Health (with sup Inappropriate use of drugs for port from USAID) began a study of drug two days. selection and procurement procedures for Specifically for diarrhoea treatment, childhood diarrhoea is a major health facilities. Part of the study looked the average number of drugs prescribed problem in Peru. Patricia at the prescribing of drugs in 4,060 cases per case was similar (4.0 for children Paredes and Hildebrand Haak of childhood illness, including diarrhoea. under five, 3.8 for older children). Also: report on recent steps taken to The results of the study”’ revealed that: 0 antibiotics were prescribed more than improve the situation. 0 nearly 60 per cent of all patients twice as often as ORS, and over 50 For ten years, the national Control of Diar- received prescriptions for four or per cent of cases that received an rhoeal Diseases (CDD) Programme in more drugs; antibiotic were given two or more of Peru has promoted oral rehydration these agents; therapy (ORT) for diarrhoea, and the use 0 the average number of drugs per case 0 more vitamins and minerals were of a few selected antimicrobials for for all diagnoses was 3.8, and one in prescribed than ORS. dysentery only. National surveys have, four drugs used was given by - 1. Child Survival Pharmaceuticals of however, found that ORT use is still low, injection; Indonesia, Part II (“CSP-II”), 1988. Jakarta, while the use of drugs for diarrhoea in 0 88 per cent of children under five Ministy of Health. Source: WHO/CDD/W. 34 children under five is very high.“,” were treated with an antibiotic, but Seventh Annual Report. To address the problem, a workshop was organised in Lima by scientific profes-

6 Dialogue on Diarrhoea, issue 42, September 1990. Published quarterly by AHRTAG, 1 London Bridge Street, London SE1 9SG, UK. Country reports

sionals and the Pan American Health country where correct case management of Organization (PAHO) in collaboration diarrhoea and the disadvantages of ‘anti- with the Ministry of Health. Health pro- diarrhoeal’ drugs were discussed with doc- fessionals, health administrators, interna- tors, nurses, pharmacists and students. tional agencies, Peruvian researchers, 3. Messages about ORT and inappropriate health activist groups and others attended, drugs were reinforced through additional contributing much information on drug use teaching sessions and radio interviews. for childhood diarrhoea. 4. Inappropriate use of antibiotics and other drugs during diarrhoea is now Research findings recognised as important by the Ministry of Workshop participants presented results of Health, and there are plans to focus on the research studies. Two national surveys problem in the next update of the national showed that, in 1984, 50 per cent, and in diarrhoea treatment guidelines. 1986,62 per cent of all diarrhoeal episodes 5. A local health activists group, in col- in children under five were treated with laboration with the Ministry of Health, has some kind of drug. The drugs most fre- organised several forums for medical and quently used were antibiotics such as pharmaceutical students on inappropriate chloramphenicol, tetracycline, neomycin drug use. This group has also prepared a and cotrimoxazole, and antimotility agents popular information folder on ‘anti- like loperamide”“. A study of beliefs and diarrhoeals’, which includes, among other behaviour, conducted in the outskirts of printed materials, the workshop report and Lima in 1987-88, showed that traditional a WHO document on proper case manage- remedies were widely used for diarrhoea, ment of diarrhoea. but that modem pharmaceuticals were 6. The workshop report has also been used often also used in combination with them. as a basis for discussion in regional Loperamide was the most widely used seminars of the National Pharmacists drug, followed by a combination tablet Association. The Association has containing chloramphenicol and recognised the problem and is willing to Many children in Peru are prescribed tetracycline. These tablets can easily be collaborate in efforts to reduce the inap- inappropriate drugs for diarrhoea. bought without prescription in local shops. propriate dispensing of pharmaceuticals for Inappropriate drug use for diarrhoea is tions, most of which differ substantially childhood diarrhoea. not just a result of so-called ‘self- from the approved formula.“’ medication’ by families. Doctors also fre- During discussion of these data it Working together quently prescribe ineffective drugs. A became clear that inappropriate drug use One strength of this effort has been the survey of patterns in drug prescribing is a complex problem involving many willingness of the scientific community, found that, of patients attending a health interests. For example, even when the Ministry of Health, international agen- facility or a private surgery for diarrhoea mothers, pharmacists and doctors are cies and health activist groups to work treatment, 57 per cent received a prescrip- aware of ORT and correct diarrhoea together and recognise the seriousness of tion for antibiotics, and 55 per cent for an management, they give a variety of reasons the problem. The positive attitude of those ‘anti-diarrhoeal’ drug.“’ for using other treatments which seem to involved in trying to find solutions, each them to be better. Although there is still in their own field and in collaboration with Dangerous and expensive no safe treatment which stops the diarrhoea others, deserves special attention and has Most of the medicines described above are quickly, doctors will prescribe a remedy been one of the most encouraging results never appropriate for diarrhoea, and the which claims to give a rapid ‘cure’, of the initial workshop. remainder are being greatly over- because this is what the mother wants. prescribed. Over-use of antibiotics However, there is little awareness of the Dr Patricia Paredes, Instituto de increases the chances of resistant bacterial possible dangers of these drugs, of their Investigation Nutritional, Av. la Univer- strains developing, and drugs such as unnecessary cost, especially for poor sidad S/N, Apto 18-0191, Lima 18, Peru; loperamide are dangerous and may be fatal families, and the role they play in delay- and Dr Hildebrand Haak, PAHO/ in young children. ing the use of effective rehydration WHO, Lima, Peru. With thanks to Dr Mary Penny, HN Research Director. As well as being ineffective or harmful, therapy. such overprescribing and over-use of drugs is also extremely expensive. Data from the Action 1. ENNSA: INE: Informe General Peru pharmaceutical industry show that between The workshop led to a series of actions. 1986. pp 145-146. June 1988 and June 1989, approximately 1. PAHO/WHO published a report of the 2. ENNSA: INE: Informe General Peru US$2.5 million was spent on drugs to treat data and the discussion which has been 1988. pp 118-121. diarrhoea. Only 1.4 per cent of spending distributed within Peru and in the PAHO 3. Medicamentos inapropiados en diarrea: on rehydration solutions was on official region.“‘The workshop is presented as an la magnitud de1 problema. PAHO/WHO, ORS packets, which are cheap and made example for other national pro- Lima, 1989. according to the WHO formula. The rest grammes.“’ 4. Programme for Control of Diarrhoea1 was spent on more expensive commercial 2. The Ministry of Health organised a Diseases. Seventh Programme Report. preparations of glucose-electrolyte solu- series of paediatric forums throughout the WHO, 1988-l 989.

Dialogue on Diarrhoea, issue 42, September 1990. Published quarterly by AHRTAG, 1 London Bridge Street, London SE1 9SG, UK. 7 Resources

More information on drugs, including managing acute diarrhoea in infants drugs for diarrhoea, can be obtained and young children. All-India Inst of from the organisations and publications Medical Sciences, 25 pages. listed below. 0 Laing, R 0, 1990. Rational drug use: an unsolved problem. Tropical Doctor All India Drug Action Network 20(3): 101-103. A short and recent (AIDAN). Contact: Voluntary Health overview. Association of India, 40 Institutional 0 Merson, M H, 1987. Proper treatment Area, South of ITT, New Delhi 110016, of diarrhoea: role of the pharmacist. India. AIDAN is a network of health, International Pharmacy Journal 1: consumer, legal aid, and human rights 52-56. organisations. 0 Quinby Rush, C and White, K, 1988. Drug Disease Doctor. Subscription. Control of diarrhoea1 diseases: an Published by Drug Action Forum, P annotated bibliography of PRITECH 254, Block B, Lake Town, Calcutta holdings. PRITECH, 333 pages. 700089, India. Quarterly journal on 0 Rylance, G (ed), 1987. Drugs for rational drug therapy and prescribing children. Non-serial publication practice. available from WHO. 185 pages. The Drug Monitor. Free. Published by 0 Banned and Bannable Drugs, 1986 the Health Action Information Network (third revised edition, 1989). The (HAIN), 9 Cabanatuan Road, Philam Voluntary Health Association of India Homes, Quezon City, Philippines. (VHAI), 40 Institutional Area, South of Drug Information. Free. Published by IIT, New Delhi 110016, India. 106 the Pharmaceuticals Unit, World Health pages. Available from VHAI. Organization, 1211 Geneva 27, 0 Drugs in the management of acute diar- Switzerland. A bulletin for the interna- rhoea in infants and young children, tional transfer of information on current INRUD is a co-operative organisation 1989. Bull. WHO 67(l): 94-96. A short drug topics. of health workers, administrators and overview. Based on the unpublished Essential Drugs Monitor. Free. researchers in developing countries document WHO/CDD/CMT/86.1 Published by the World Health aiming to improve drug use. There are Rev 1 (1988). Organization, 1211 Geneva 27, several different national groups. 0 WHO, 1988. lIzheuse of essential drugs: Switzerland. The newsletter of the WHO Drug Information. Subscription. third report of the WHO expert com- WHO Action Programme on Essential Published in English and French by the mittee. Technical report series 770. 63 Drugs and Vaccines. World Health Organization, 12 11 pages. Includes a model list of essen- HAI News. Subscription. Published by tial drugs designed for individual coun- Geneva 27, Switzerland. Journal of Health Action International (HAI), tries to use to develop their own lists. drug development and regulation. IOCU, PO Box 1045, 10830 Penang, WHO CDD Programme. 0 WHO, 1988. Essential drugs for Malaysia. Regional offices at HAI- primary health care: a manual for Europe, Jacob van Lennepkade 334 T, Further reading health workers in South-East Asia. 1053 NJ Amsterdam, Netherlands; and Chetley, A, - 1987. Antibiotics: the SEAR0 Regional Health Papers No 16, IOCU Regional Office for Latin wrong drugs for diarrhoea. Health 105 pages. SwFIO/US$8, order no. America and the Caribbean, Casilla Action International. Available from 1580016. 10993, Sucursal 2, Montevideo, HA1 Europe. 0 WHO, 1987. Use of drugs in the treat- Uruguay. The newsletter of HAI, a net- Cutting, WA M, 1989. Selfpresctibing ment of diarrhoea. CDD/TAG/87.5. work of consumer, development action andpromotion of antidiarrhoeal drugs. 0 WHO, 1987. 7Ire rational use of drugs. and other public interest groups Lancet 8646: 1080. Report of the Conference of Experts, worldwide. Dean, P and Ebrahim, G J, 1986. Prac- Nairobi, 25-29 November 1985, 329 INRUD News. Free. Published by tical care of sick children: a manual for pages. SwF52/US$41.60, order no. the International Network for Rational use in small tropical hospitals. Mac- 1150271. Use of Drugs, 165 Alla&ale Road, millan, 348 pages. 0 WHO, 1988. The world drug situation. Boston, Massachusetts 02130, USA. Ghai, 0 P, 1987. Understanding and 123 pages. SwF20/US$16.00.

Scientific editors: Dr Katherine Elliott (UK) and Dr William Cutting (UK) Editor: Kathy Attawell. Assistant editor: Nina Behrman Editorial advisers: Professor J Assi Adou (Ivory Coast), Professor AG Billoo (Pakistan), Professor David Candy (UK), Professor Richard Feachem (UK), Dr Shanti Ghosh (India), Dr Michael Gracey (Australia). Dr N Hirschhorn IUSAI. Dr Claudio Lanata (Peru). Professor Leonardo Mata (Costa kica), Dr Jon Rohde (USA), Dr Mike’Rowland (UK), Ms EC Sulk&ta (Philippines), Professor Andrew Tomkins (UK), Dr Paul Vesin (France) Dialogue on Diarrhoea is published by With support from AID (USA), ODA (UK), UNICEF, WHO. AHRTAG at 1 London Bridge Street, Dialogueon Diarrhoeais free to readers in developing countries. There is an annual subscription London SE1 9SG. Tel: 071-378 1403. of UKflO.OO (US$20.00) for readers in Western Europe, North America, Australia and Japan. Reductions are available for bulk orders.

8 Dialogue on Diarrhoea, issue 42, September 1990. Printed in the United Kingdom by Boume Offset Limited. ISSN 0950-0235