CLINICAL UPDATE: March1991 SHIGELLOSIS Shigellosis, or ‘baciliary dysentery’, is an intestinal infection that is a major public health problem in many developing countries, where it causes about 5 to IO per cent of childhood diarrhoea. This special DD insert provides an overview of shigellosis, including cause, effect and treatment.

Shigellosis is characterised by the frequent fluenced by nutritional status, and environ- and painful passage of stools that consist mental factors affecting transmission such largely of blood, mucus and pus, accom- as rainfall and temperature. Shigella infec- panied by fever and stomach cramps. In tions can occur throughout the year, but in some developing countries more people most communities the incidence is highest die from shigellosis than from watery diar- when the weather is hot and dry. This may rhoea. As many as 25 per cent of all diar- be because the scarcity of water limits rhoea related deaths can be associated with handwashing and other hygiene measures Shigella. that reduce transfer of the very small num- ber of bacteria needed to cause infection. Health workers are usually aware of the number of shigellosis cases, because symptoms are severe, and therefore children with Shigella infections are more likely to be brought to hospitals or clinics. Case fatality rates, even in hospitalised cases of dysentery, are six to eight times greater than for watery diarrhoea. Dysentery is associated with persistent diarrhoea. In rural north India, for example, Inflammation and tissue damage causes nearly a third of all persistent diarrhoeal painful straining to pass stools, which can episodes are dysenteric. lead to rectal prolapse. Blood and mucus in the stool are signs of During disease epidemics caused by shigellosis. Shigella dysenteriae type 1, as many as one late in the course of the illness. Young in ten people in affected communities will children and elderly people are most likely What causes shigellosis? become infected, and as many as 10 to 15 to die from the effects of shigellosis. At the The symptoms of shigellosis result from per cent of these will die. At the Diarrhoea ICDDR,B Treatment Centre, children infection with the Shigella bacterium. Two Treatment Centre of the International under 12 months of age account for 21 per of the four species of Shigella are common Centre for Diarrhoea1 Disease Research in cent of shigellosis admissions but up to 33 in developing countries. Shigellajlexneri is Bangladesh (ICDDR,B), over 700 patients per cent of all fatal cases. Dysentery is endemic (present at all times) in most com- a year with shigellosis are admitted to an especially severe and more likely to be munities. Shigella dysenteriae type 1 often in-patient unit. Ten per cent of these fatal in young infants, the malnourished, occurs in an epidemic pattern; the organism patients die while in hospital. Although children who are not breastfed, and follow- can be absent for a number of years, only these are patients with the most severe ing measles. Acute and particularly to reappear and infect a large proportion of illness, their high mortality rate shows the prolonged episodes of dysentery often the population. These two species of difficulties in treating patients with shigel- change marginal malnutrition to overt Shigella generally produce the most severe losis, especially when they come for care protein energy malnutrition, and can lead illness. In developed countries Shigella to vitamin A deficiency. sonnei is the most common and is the least virulent Shigella bacterium. Shigella What are the effects of boydii causes disease of intermediate Shigella infection? severity and is least common of the four, Shigella infect the cells of the lining of the except in the Indian sub-continent. large intestine (colon). The bacteria invade and damage these cells, producing breaks Who gets shigellosis, and (ulcers) in the mucous membrane lining the how common is it? intestine. These ulcers are most common in Shigellosis is found throughout the world, the rectum, which is the lowest part of the mostly in children aged under five. Rates A microscopic view of bloody diarrhoea, large intestine. Ulceration of the intestinal of Shigella infection are highest where showing red and white blood cells (from the lining results in increased production of sanitation is poor. They are also in- ulcerated intestinal wall). mucus, and the loss of blood and serum

Produced by Dialogue on Diarrhoea, AHRTAG. 1 London Bridge Street. London SE1 9SG, UK. and the Applied Diarrhoea1 Disease Research Project (ADDR), Harvard Institute for International Development, Cambridge, MA 02138, USA SHIGELLOSIS

proteins into the intestinal cavity. This of those infected. If antibiotics are given to Table 1: Percentage of stool causes the symptoms of dysentery, which children with shigellosis before they come culture showing positive for include blood and mucus in the stool to the clinic, the drugs may eliminate the Shigella taken from children (bloody diarrhoea); fever is also common. bacteria from their stools. In most studies The effects of Shigella infection on the that have been conducted in developing with dysentery intestine usually differ from those of or- countries, Shigella were recovered from a Study site Year of Per cent of ganisms such as enterotoxigenic E. coli and stool culture in half or more of all children (community study cases Vibrio cholerae, which cause watery diar- who had dysentery (see Table 1). and hospital showing rhoea, without fever. These organisms in- based) Shigella fect only the small intestine and cause little l Clinical signs and symptoms or no damage to the cells lining the intes- The use of clinical signs and symptoms is Dhaka, 1979 55 tine. Dehydration is the main complication therefore very important in identifying Bangladesh resulting from these infections. Oc- patients with shigellosis. Dysentery casionally Shigella causes only watery (bloody diarrhoea) is a very reliable in- Nonthaburi, 1986 44 diarrhoea and this will cause dehydration dicator of the infection in the majority of Thailand (unless appropriate rehydration fluids are cases. In many developing countries given). Shigella infection is the most common, and Rmgpur, 1988 50 Shigella dysentery may also lead to a potentially the most severe, cause of Bangladesh number of dangerous complications. These dysentery. After Shigella, Campylobacter include: jejuni and Salmonella are the next most Bangkok, 1991 37 . severe anorexia (loss of appetite) common causes of dysentery, but these Thailand . hypoproteinaemia (a low concentration usually produce self-limited illness that is sufficient for a diagnosis of amoebiasis. of blood protein) rarely as serious or life-threatening as shigellosis. The parasite Entamoeba his- Treatment of dysentery should therefore l hyponatraemia (a low concentration of tolytica, responsible for amoebic focus on the management of shigellosis. blood sodium) dysentery, is a rare cause of dysentery in Mothers are usually accurate observers . dilation of the large intestine children, accounting for less than 5 per cent of their children’s stools. If a mother of all episodes. Stool microscopy for reports that her child’s stools contain blood . seizures protozoa may not be available and it is and mucus, then it is reasonable to assume 0 anaemia often unreliable. Amoebiasis can only be that the child is infected with Shigella.

l kidney damage diagnosed with certainty when Many communities have local terms used trophozoites of E. histolytica containing to describe different types of diarrhoea, . persistent diarrhoea red blood cells are seen in fresh stools. The including dysentery, and health workers . weight loss and malnutrition microscopic detection of cysts alone is not should become familiar with these terms. How can shigellosis be identified? Table 2: Appropriate antibiotics for shigellosis

0 Stool culture &htibiotic’ Children Adults Comments The most accurate way to find out if a person with diarrhoea is infected with (Zotrimoxazole TMP Smg/kg and TMP 16Omg and Not recommended Shigella is to make a culture of the stool, to (also called SMX 25mg/kg SMX 8OOmg twice for use in jaundiced check if the bacterium is present. But this rimethoprim twice a day for 5 a day for 5 days and premature is often impractical in developing !;TMP)- days infants under countries. Making a culture is expensive 'S;ulfamethoxazole 1 month old and facilities are often unavailable in the (SMX) rural communities and urban slums where the incidence of shigellosis is greatest. W: Moreover, the results are usually only !‘ available after two or three days, and treat- ttipicillin 25mg/kg 4 times a 1g 4 times a day for Safe for infants, and ment should not be delayed - a decision day for 5 days 5 days pregnant or regarding antibiotic use must be made im- lactating women mediately. Stool microscopy for pus cells to identify shigellosis is not necessary Alternative if Sbigella in the local area are resistant: when visible blood is present in stools. It may help to identify cases of mild shigel- Nalidixic acid 15mgJkg 4 times a lg 3 times a day for Not recommended losis, when stools are mucoid without day for 5 days 5 days for infants under blood, but this is too non-specific to be of two months any practical value. Shigella bacteria are not always found in 1. All doses are for oral administration. If a liquid form of the drug is not available foi the stool cultures of children who are in- children, give the approximate dose as crushed tablets. fected. Even in the best conditions, a stool culture may only identify about 70 per cent L

Produced by Dialogue on Diarrhoea, AHRTAG. 1 London Bridge Street. London SE1 9SG, UK, and the Applied Diarrhoea1 Disease Research Project (ADDR). Harvard Institute for International Development, Cambridge, MA 02138, USA SHIGELLOSIS

Treatment of shigellosis in Bangladesh: Treatment scheme used for children with bloody diarrhoea children ACUTE DIARRHOEA Children with visible blood in stools should be presumed to have shigellosis and be treated accordingly. The key com- Assess for and treat dehydration ponents of shigellosis treatment are: l giving an effective antibiotic Check for blood in stools . continued feeding l replacement of fluid losses . follow up $ $ Yes No Children treated early in their illness with an appropriate antibiotic will be con- siderably better 48 hours after therapy has Is a microsc&ic examination Shigelli infection begun. Those who do not receive effective of the stool possible? not present drug treatment may develop persistent diarrhoea, malnutrition, and other life- I threatening complications. t Those who are infected with Shigella Yes who are already malnourished need special attention, as do infants under 12 months 4 old, and those already dehydrated. The Are there E. histolytica trophozoites with most severely ill should be cared for in ingtsted red blood cells present (not cysts alone)? hospital and the others should be followed up at least once every 48 hours until they are better. Infection of the bloodstream is f Ic common in these patients, and is caused by No Yes bacteria, other than Shigella, normally found in the gut. The signs of bloodstream infection are shock, low urine output and lethargy. Intravenous antibiotics such as rreat for shigellosis with antibiotic Treat with &etronidazole gentamicin and ampicillin should be given ;&able for the community or alternative in addition to an oral antibiotic for treat- ment of shigellosis. However, if ampicillin is given intravenously, it should not also be exceeds 25 per cent, nalidixic acid is used Studies are being carried out to determine given orally. as an alternative (see Table 2). This drug is how important this is in humans. An- more expensive than cotrimoxazole and tibiotics known to be less effective and

l Antibiotic treatment ampicillin but is similarly effective. Unfor- therefore not recommended include Antibiotic treatment should be started as tunately, in areas where nalidixic acid is neomycin, gentamicin, the first generation soon as acute dysentery is identified. The widely used, Shigella bacteria often rapidly cephalosporins, kanamycin, amoxycillin chosen dmg must be safe for use in children become resistant. It is important to use and sulphaguanidine. In many parts of the and inexpensive; a liquid formulation is these drugs carefully to minimise the prob- world, a significant proportion of Shigella preferable but not essential. Most strains of lem of resistance. Their use should be strains show in vitro sensitivity to Shigella in the community must be sensi- restricted to patients with dysentery: furazolidine and many doctors who use it tive to the drug, and it should have been patients with watery diarrhoea do not re- as initial therapy in India report anecdotal shown to be effective in controlled clinical quire an antibiotic unless cholera is favourable results. However, controlled trials. Ampicillin and cotrimoxazole fulfil suspected. Health workers need to know clinical trials are lacking. these criteria, and for the last 15 years have the resistance pattern of Shigella in their The diagram above shows a scheme been the drugs of choice for treatment of community in order to make the right which was developed for health workers to shigellosis. Some doctors wrongly decision about which drug to use. Stool use when treating children with bloody prescribe metronidazole, believing that the cultures should be obtained on a regular diarrhoea in Bangladesh. Similar schemes drug will cure both shigellosis and amoebic basis, and isolates of Shigella tested for could be established and evaluated for dysentery. Metronidazole should be used sensitivity to drugs commonly used for other countries. only if E. histolytica has been positively treatment. identified, or if treatment for shigellosis has The new fluoroquinolines (e.g. l Continued feeding failed. ciprofloxacin and ofloxacin) are highly ac- Nutrient absorption continues during Recently, however, resistant strains of tive and clinically effective when given by shigellosis, because the disease does not Shigella have become common in some mouth, but because they cause cartilage affect much of the small intestine, where countries, such as Bangladesh. Where damage in young animals, there is still con- most absorption takes place. However, the resistance to ampicillin and cotrimoxazole cern about their safety in young children. inflammation in the large intestine affects

Produced by Dialogue on Diarrhoea, AHRTAG, 1 London Bridge Street, London SE1 9SG, UK, and the Applied Diarrhoea1 Disease Research Project (ADDR), Harvard Institute for International Development. Cambridge. MA 02138, USA SHIGELLOSIS contrast, thousands of Vibrio cholerae are required to cause disease. Once a member of the family has dysentery, infection can spread from person to person very quickly. Community health education must in- clude information on hygiene. The most effective way to reduce the incidence of shigellosis is to ensure proper washing of hands following defecation, and adequate disposal of faeces. It is not only adults who need to wash their hands. Children are probably the most common carriers of in- fection, and they must also be shown how to wash their hands. Adults caring for children need to wash their hands often too. Even if soap is not available, a good scrub- bing with water, and use of an abrasive such as sand, is helpful in reducing the spread of infection. Household food and Handwashing after defecation is the best way to prevent the spread of shigellosis. water also have to be protected from faeces and unwashed hands. There are no effec- tive vaccines for the prevention of shigel- nutritional status. Early effective an- solution contains enough salt (sodium) to losis, although research into vaccines, timicrobial therapy cures the infection and increase the level of salts in the patient’s especially ones for oral use, is being carried inflammation and the child’s appetite will blood, if it is low. out. return, soon followed by weight gain. It is important to feed and/or breastfeed . Follow up Steps to eradication patients with shigellosis frequently to Follow up is important to determine Of all the diarrhoeal illnesses, shigellosis is prevent them developing hypoglycaemia whether patients have responded to treat- the one most closely linked with under- (low blood sugar) and losing weight during ment. Ask the mother to bring her child development. Features of underdevelop- their illness. This can be difficult because back to the health centre within 48 hours if ment that produce a high incidence of they are often severely anorexic (suffering the child is less than one year old, shigellosis include poor housing and in- from loss of appetite). However, children dehydrated when first seen, or still has sanitary conditions, overcrowding, ab- need not eat as much at each feeding as they blood in the stool. Diarrhoea may take sence of adequate water supplies for normally would. Small amounts of food longer than two days to stop altogether, but cleaning and washing, and childhood mal- should be given every three to four hours. the visible blood in stools should disappear nutrition. In all countries where economic This will also keep up the blood sugar within that time. If the blood does persist, and social conditions have improved, the level. Foods rich in potassium, such as the child may be infected with a strain of most virulent forms of shigellosis, caused bananas, are recommended. One extra Shigella that is resistant to the drug used. by Shigella dysenteriae type 1 and Shigella meal should be given to the child every day Such patients should be treated with a dif- flexneri, have virtually disappeared. Thus for at least two weeks after the diarrhoea ferent agent for shigellosis unless another the prevention of shigellosis is closely stops. cause of dysentery is found. If there is still linked to efforts to improve the economic Continued feeding also helps to prevent no improvement after two days of treat- and social conditions of people living in the acute weight loss that occurs during ment with an alternative drug, the child areas where shigellosis is now endemic. diarrhoea. If a severely ill patient in hospi- should be taken to hospital. Amoebiasis On a national level, Diarrhoea1 Disease tal refuses to eat or to breastfeed, it may be should be considered. Control Programmes need to research pat- necessary to feed with a nasogastric tube terns of antibiotic use, investigate resis- initially. How can shigellosis be tance of Shigella strains to drugs in prevented? different regions, develop treatment schemes appropriate for local conditions, l Replacement of fluid losses Shigella bacteria infect only humans and and train doctors in the correct case Mild to moderate dehydration is common monkeys, and do not survive for long out- in patients with shigellosis. Dehydration is side the body. Therefore, for infection to management of dysentery. caused by loss of fluid in stools, evapora- occur, Shigella bacteria must pass quickly Acknowledgements tion of water through the skin due to fever, from one person to another. This usually and reduced fluid intake because of occurs through ‘faecal-oral’ transmission. This supplement is based on material anorexia. Hyponatraemia (low levels of This takes place when a person with shigel- prepared by Drs M Bennish and J Griffuhs sodium in the blood) is a particular prob- losis defecates, does not wash his or her of the New England Medical Center (Tufts University), Dr A Salam of the International lem for those infected with S. dysenreriae hands adequately afterwards, and transfers Centre for Diarrhoea1 Disease Research, type 1. Oral rehydration therapy should be Shigella germs to food (or water). The bac- Bangladesh and Dr M Bhan, of the All-India given and in most cases fluids do not need teria are then swallowed when the con- Institute of Medical Sciences, New Delhi, to be given intravenously. Giving in- taminlted food is eaten by another person. India; and developed by the ADDR Project, travenous fluids increases the risk of infec- Fewer than ten ingested bacteria are Harvard Institute for International Develop- tion and is expensive. Oral rehydration enough to cause a Shigella infection; in ment.

Produced by Dialogue on Diarrhoea, AHRTAG. 1 London Bridge Street, London SE1 9SG, UK, and the Applied Diarrhoea1 Disease Research Project (ADDR). Harvard Institute for International Development, Cambridge, MA 02138. USA