• Shigellosis
  • What causes shigellosis?
  • Who gets shigellosis, and how common is it?
  • What are the effects of
  • How can shigellosis be identified?
  • Treatment of shigellosis in children
  • Appropriate antibiotics for shigellosis
  • How can shigellosis be prevented?
  • Steps to eradication

DDOnline Shigellosis supplement to DD44 Page 1 2

Clinical Update 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 I0 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 and painful passage of stools that consist largely of blood, mucus and pus, accompanied by fever and stomach cramps.

Blood and mucus in the stool are signs of shigellosis. In some developing countries more people die from shigellosis than from watery diarrhoea. As many as 25 per cent of all diarrhoea related deaths can be associated with Shigella.

What causes shigellosis? The symptoms of shigellosis result from infection with the Shigella bacterium. Two of the four species of Shigella are common in developing countries. Shigella flexneri is endemic (present at all times) in most communities. Shigella dysenteriae type 1 often occurs in an epidemic pattern; the organism can be absent for a number of years, only to reappear and infect a large proportion of the population. These two species of Shigella generally produce the most severe illness. In developed countries Shigella sonnei is the most common and is the least virulent Shigella bacterium. Shigella boydii causes disease of intermediate severity and is least common of the four, except in the Indian sub-continent. Who gets shigellosis, and how common is it? Shigellosis is found throughout the world, mostly in children aged under five. Rates of Shigella infection are highest where sanitation is poor. They are also influenced by nutritional status, and environmental factors affecting transmission such as rainfall and temperature. Shigella infections can occur throughout the year, but in most communities the incidence is highest when the weather is hot and dry. This may be because the scarcity of water limits handwashing and other hygiene measures that reduce transfer of the very small number 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, nearly a third of all persistent diarrhoeal episodes are dysenteric. During disease epidemics caused by Shigella dysenteriae type 1, as many as one in ten people in affected communities will become infected, and as many as 10 to 15 per cent of these will die. At the Diarrhoea Treatment Centre of the International Centre for Diarrhoeal Disease Research in Bangladesh (ICDDR, B), over 700 patients a year with shigellosis are admitted to an in-patient unit. Ten per cent of these patients die while in hospital.

A microscopic view of bloody diarrhoea, showing red and white blood cells (from the ulcerated intestinal wall). Although these are patients with the most severe illness, their high mortality rate shows the difficulties in treating patients with shigellosis, especially when they come for care late in the course of the illness. Young children and elderly people are most likely to die from the effects of shigellosis.

At the ICDDR, B Treatment Centre, children under 12 months of age account for 21 per cent of shigellosis admissions but up to 33 per cent of all fatal cases. Dysentery is especially severe and more likely to be fatal in young infants, the malnourished, children who are not breastfed, and following measles. Acute and particularly prolonged episodes of dysentery often change marginal malnutrition to overt protein energy malnutrition, and can lead to vitamin A deficiency. What are the effects of Shigella infection? Shigella infect the cells of the lining of the large intestine (colon). The bacteria invade and damage these cells, producing breaks (ulcers) in the mucous membrane lining the intestine.

Inflammation and tissue damage causes painful straining to pass stools, which can lead to rectal prolapse. These ulcers are most common in the rectum, which is the lowest part of the large intestine. Ulceration of the intestinal lining results in increased production of mucus, and the loss of blood and serum proteins into the intestinal cavity. This causes the symptoms of dysentery, which include blood and mucus in the stool (bloody diarrhoea); fever is also common.

The effects of Shigella infection on the intestine usually differ from those of organisms such as enterotoxigenic E. coli and Vibrio cholerae, which cause watery diarrhoea, without fever. These organisms infect only the small intestine and cause little or no damage to the cells lining the intestine. Dehydration is the main complication resulting from these infections. Occasionally Shigella causes only watery diarrhoea and this will cause dehydration (unless appropriate rehydration fluids are given). Shigella dysentery may also lead to a number of dangerous complications. These include:

• severe anorexia (loss of appetite)
• hypoproteinaemia (a low concentration of blood protein)
• hyponatraemia (a low concentration of blood sodium)
• dilation of the large intestine
• seizures
• anaemia
• kidney damage
• persistent diarrhoea
• weight loss and malnutrition

Produced by Dialogue on Diarrhoea and the Applied Diarrhoeal Disease Research Project (ADDR), Harvard Institute for International Development, Cambridge, MA 02138, USA

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How can shigellosis be identified?

• Stool culture
  
  The most accurate way to find out if a person with diarrhoea is infected with Shigella is to make a culture of the stool, to check if the bacterium is present. But this is often impractical in developing countries. Making a culture is expensive and facilities are often unavailable in the rural communities and urban slums where the incidence of shigellosis is greatest. Moreover, the results are usually only available after two or three days, and treatment should not be delayed - a decision regarding antibiotic use must be made immediately. Stool microscopy for pus cells to identify shigellosis is not necessary when visible blood is present in stools. It may help to identify cases of mild shigellosis, when stools are mucoid without blood, but this is too non-specific to be of any practical value.
  
  Shigella bacteria are not always found in the stool cultures of children who are infected. Even in the best conditions, a stool culture may only identify about 70 per cent of those infected. If antibiotics are given to children with shigellosis before they come to the clinic, the drugs may eliminate the bacteria from their stools. In most studies that have been conducted in developing countries, Shigella were recovered from a stool culture in half or more of all children who had dysentery (see Table 1).
  

Table 1: Percentage of stool culture showing positive for Shigella taken from children with dysentery
Study site (community and hospital based)	Year of study	Per cent of cases showing Shigella
Dhaka, Bangladesh	1979	55
Nonthaburi, Thailand	1986	44
Rangpur, Bangladesh	1988	50
Bangkok, Thailand	1991	37

• Clinical signs and symptoms
  
  The use of clinical signs and symptoms is therefore very important in identifying patients with shigellosis. Dysentery (bloody diarrhoea) is a very reliable indicator of the infection in the majority of cases. In many developing countries Shigella infection is the most common, and potentially the most severe, cause of dysentery. After Shigella, Campylobacter jejuni and Salmonella are the next most common causes of dysentery, but these usually produce self-limited illness that is rarely as serious or life-threatening as shigellosis. The parasite Entamoeba histolytica, responsible for amoebic dysentery, is a rare cause of dysentery in children, accounting for less than 5 per cent of all episodes. Stool microscopy for protozoa may not be available and it is often unreliable. Amoebiasis can only be diagnosed with certainty when trophozoites of E. histolytica containing red blood cells are seen in fresh stools. The microscopic detection of cysts alone is not sufficient for a diagnosis of amoebiasis. Treatment of dysentery should therefore focus on the management of shigellosis. Mothers are usually accurate observers of their children's stools. If a mother reports that her child's stools contain blood and mucus, then it is reasonable to assume that the child is infected with Shigella. Many communities have local terms used to describe different types of diarrhoea, including dysentery, and health workers should become familiar with these terms.

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Treatment of shigellosis in children Children with visible blood in stools should be presumed to have shigellosis and be treated accordingly. The key components of shigellosis treatment are:

• giving an effective antibiotic
• continued feeding
• replacement of fluid losses
• follow up

Children treated early in their illness with an appropriate antibiotic will be considerably better 48 hours after therapy has begun. Those who do not receive effective drug treatment may develop persistent diarrhoea, malnutrition, and other life-threatening complications. Those who are infected with Shigella who are already malnourished need special attention, as do infants under 12 months old, and those already dehydrated. The most severely ill should be cared for in hospital and the others should be followed up at least once every 48 hours until they are better. Infection of the bloodstream is common in these patients, and is caused by 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 gentamicin and ampicillin should be given in addition to an oral antibiotic for treatment of shigellosis. However, if ampicillin is given intravenously, it should not also be given orally.

• Antibiotic treatment
  
  Antibiotic treatment should be started as soon as acute dysentery is identified. The chosen drug must be safe for use in children and inexpensive; a liquid formulation is preferable but not essential. Most strains of Shigella in the community must be sensitive to the drug, and it should have been shown to be effective in controlled clinical trials. Ampicillin and cotrimoxazole fulfil these criteria, and for the last 15 years have been the drugs of choice for treatment of shigellosis. Some doctors wrongly prescribe metronidazole, believing that the drug will cure both shigellosis and amoebic dysentery. Metronidazole should be used only if E. histolytica has been positively identified, or if treatment for shigellosis has failed.

Table 2: Appropriate antibiotics for shigellosis

1. All doses are for oral administration. If a liquid form of the drug is not available for children, give the approximate dose as crushed tablets.

Recently, however, resistant strains of Shigella have become common in some countries, such as Bangladesh. Where resistance to ampicillin and cotrimoxazole exceeds 25 per cent, nalidixic acid is used as an alternative (see="#Table 2">Table 2). This drug is more expensive than cotrimoxazole and ampicillin but is similarly effective. Unfortunately, in areas where nalidixic acid is widely used, Shigella bacteria often rapidly become resistant. It is important to use these drugs carefully to minimise the problem of resistance. Their use should be restricted to patients with dysentery: patients with watery diarrhoea do not require an antibiotic unless cholera is suspected. Health workers need to know the resistance pattern of Shigella in their community in order to make the right decision about which drug to use. Stool cultures should be obtained on a regular basis, and isolates of Shigella tested for sensitivity to drugs commonly used for treatment. The new fluoroquinolines (e. g. ciprofloxacin and ofloxacin) are highly active and clinically effective when given by mouth, but because they cause cartilage damage in young animals, there is still concern about their safety in young children. Studies are being carried out to determine how important this is in humans. Antibiotics known to be less effective and therefore not recommended include neomycin, gentamicin, the first generation cephalosporins, kanamycin, amoxycillin and sulphaguanidine. In many parts of the world, a significant proportion of Shigella strains show in vitro sensitivity to furazolidine and many doctors who use it as initial therapy in India report anecdotal favourable results. However, controlled clinical trials are lacking. The diagram below shows a scheme which was developed for health workers to use when treating children with bloody diarrhoea in Bangladesh. Similar schemes could be established and evaluated for other countries.

Bangladesh: Treatment scheme used for children with bloody diarrhoea ACUTE DIARRHOEA

• Assess for and treat dehydration
• Check for blood in stools
• Yes No
• Is a microscopic examination of the stool possible?
• Shigelli infection not present
• No Yes
• Are there E. histolytica trophozoites with ingested red blood cells present (not cysts alone)?
• No Yes
• Treat for shigellosis with antibiotic suitable for the community
• Treat with metronidazole or alternative

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• Continued feeding
  
  Nutrient absorption continues during shigellosis, because the disease does not affect much of the small intestine, where most absorption takes place. However, the inflammation in the large intestine affects nutritional status. Early effective antimicrobial therapy cures the infection and inflammation and the child's appetite will return, soon followed by weight gain. It is important to feed and/or breastfeed patients with shigellosis frequently to prevent them developing hypoglycaemia (low blood sugar) and losing weight during their illness. This can be difficult because they are often severely anorexic (suffering from loss of appetite). However, children need not eat as much at each feeding as they normally would. Small amounts of food should be given every three to four hours. This will also keep up the blood sugar level. Foods rich in potassium, such as bananas, are recommended. One extra meal should be given to the child every day for at least two weeks after the diarrhoea stops.
  
  Continued feeding also helps to prevent the acute weight loss that occurs during diarrhoea. If a severely ill patient in hospital refuses to eat or to breastfeed, it may be necessary to feed with a nasogastric tube initially.

• Replacement of fluid losses
  
  Mild to moderate dehydration is common in patients with shigellosis. Dehydration is caused by loss of fluid in stools, evaporation of water through the skin due to fever, and reduced fluid intake because of anorexia. Hyponatraemia (low levels of sodium in the blood) is a particular problem for those infected with S. dysenteriae type 1. Oral rehydration therapy should be given and in most cases fluids do not need to be given intravenously. Giving intravenous fluids increases the risk of infection and is expensive. Oral rehydration solution contains enough salt (sodium) to increase the level of salts in the patient's blood, if it is low.

• Follow up
  
  Follow up is important to determine whether patients have responded to treatment. Ask the mother to bring her child back to the health centre within 48 hours if the child is less than one year old, dehydrated when first seen, or still has blood in the stool. Diarrhoea may take longer than two days to stop altogether, but the visible blood in stools should disappear within that time. If the blood does persist, the child may be infected with a strain of Shigella that is resistant to the drug used. Such patients should be treated with a different agent for shigellosis unless another cause of dysentery is found. If there is still no improvement after two days of treatment with an alternative drug, the child should be taken to hospital. Amoebiasis should be considered.

How can shigellosis be prevented?

Shigella bacteria infect only humans and monkeys, and do not survive for long outside the body. Therefore, for infection to occur, Shigella bacteria must pass quickly from one person to another. This usually occurs through 'faecal-oral' transmission. This takes place when a person with shigellosis defecates, does not wash his or her hands adequately afterwards, and transfers Shigella germs to food (or water). The bacteria are then swallowed when the contaminated food is eaten by another person.

Handwashing after defecation is the best way to prevent the spread of shigellosis. Fewer than ten ingested bacteria are enough to cause a Shigella infection; in 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 include 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 infection, 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 scrubbing with water, and use of an abrasive such as sand, is helpful in reducing the spread of infection. Household food and water also have to be protected from faeces and unwashed hands. There are no effective vaccines for the prevention of shigellosis, although research into vaccines, especially ones for oral use, is being carried out.

Steps to eradication Of all the diarrhoeal illnesses, shigellosis is the one most closely linked with underdevelopment. Features of underdevelopment that produce a high incidence of shigellosis include poor housing and insanitary conditions, overcrowding, absence of adequate water supplies for cleaning and washing, and childhood malnutrition. In all countries where economic and social conditions have improved, the most virulent forms of shigellosis, caused by Shigella dysenteriae type 1 and Shigella flexneri, have virtually disappeared. Thus the prevention of shigellosis is closely linked to efforts to improve the economic and social conditions of people living in areas where shigellosis is now endemic. On a national level, Diarrhoeal Disease Control Programmes need to research patterns of antibiotic use, investigate resistance of Shigella strains to drugs in different regions, develop treatment schemes appropriate for local conditions, and train doctors in the correct case management of dysentery. Acknowledgements This supplement is based on material prepared by Drs M Bennish and J Griffiths of the New England Medical Center (Tufts University), Dr A Salam of the International Centre for Diarrhoeal Disease Research, Bangladesh and Dr M Bhan, of the All-India Institute of Medical Sciences, New Delhi, India; and developed by the ADDR Project, Harvard Institute for International Development.

Produced by Dialogue on Diarrhoea, AHRTAG, UK, and the Applied Diarrhoeal Disease Research Project (ADDR). Harvard Institute for International Development, Cambridge, MA 02138. USA