UEU-co logo

Ovid: Oxford Handbook of Tropical Medicine

Editors: Eddleston, Michael; Pierini, Stephen; Wilkinson, Robert; Davidson, Robert Title: Oxford Handbook of Tropical Medicine, 2nd Edition Copyright ©2005 Oxford University Press (Copyright 2005 by M. Eddleston, S. Pierini, R. Wilkinson, and R. Davidson) > Table of Contents > Chapter 2 > Chapter 2D – Diarrhoeal diseases > Acute diarrhoea without blood Acute diarrhoea without blood See box opposite for causes. Rotavirus In developed countries, viral infections account for up to 60% of all gastro-enteritis in children < 5 yrs. In contrast, rotavirus cause < 5% of all episodes of diarrhoea in developing countries, but of episodes requiring hospitalization, 40–50% are due to rotavirus. Nearly all children in the tropics have been infected with rotavirus at least once before the age of 2 yrs. Clinical features: vomiting is an early feature; fever is common; the diarrhoea is usually watery and large volume. Colicky abdominal pains, ill-defined tenderness, and exaggerated bowel sounds are common. The stool may have a characteristic smell. Management: is supportive, aiming to prevent dehydration. Since rotavirus infection is common in infants, dietary management is especially important to avoid growth faltering and malnutrition. Continue breastfeeding. Lactose malabsorption is common but intolerance is usually only a clinical problem in severe cases. Children with mild diarrhoea should be encouraged to continue eating a normal diet in order to limit weight loss. If diarrhoea continues or is severe, lactose can be reduced by mixing milk with cereals or changing to a lactose free diet but calorie intake should be maintained. As with all diarrhoeal episodes, once the child improves or is hungry extra food should be given in order to make up for weight loss. Beware confusion with surgical causes of diarrhoea in the neonate such as Hirschsprung’s disease, intussusception, and bowel atresia. Prevention: highly contagious, rotavirus infection is difficult to prevent and is a frequent nosocomial infection. A rotavirus vaccine effective in reducing severe disease was developed and marketed but later withdrawn because of reports that risk of intussusception was increased. Alternative vaccines are being tested. Other viral causes of diarrhoea Astrovirus: are single-stranded RNA viruses that cause diarrhoea mainly in children and the elderly, with a worldwide distribution. Infection is indistinguishable from rotavirus but generally milder. Diagnosis is by electron microscopy only. Management is oral rehydration as necessary Norwalk virus: is a human enteric calicivirus and the most important viral cause of food-borne diarrhoeal outbreaks in both developing and developed countries. It is also called ‘winter vomiting’ disease. Clinical features: vomiting is usual at onset and may be severe; watery diarrhoea is rarely severe and usually lasts 12–24 hrs. Diagnosis is by PCR or ELISA. Management: supportive. Enteric adenovirus: two serotypes, 40 and 41, cause diarrhoea but seem more common in developed countries. Clinical features and management are similar to other viral diarrhoeas. Diagnosis is by electron microscopy or ELISA P.131
Causes of acute diarrhoea without blood

  • Malaria, especially P. falciparum (see Chapter 2A)
  • Viruses
    • Rotavirus
    • Astrovirus
    • Norwalk virus
    • Enteric adenovirus
  • Bacteria
    • Early stage or mild shigellosis, Salmonella, or campylobacter infections
    • Enterotoxigenic E. coli (ETEC) (commonly causing traveller’s diarrhoea)
    • Enteropathogenic E. coli (EPEC)
    • Enteroaggregative E. coli (EAEC)
    • Enterotoxin-producing strains of Staphylococcus aureus
    • Cholera
    • Clostridia spp
  • Protozoa
    • Giardiasis
    • Cryptosporidiosis
    • Cyclospora cayetenesis
  • Strongyloidiasis
  • Food toxins

Enterotoxigenic E. coli (ETEC) ETEC accounts for 20% of diarrhoeal cases, second only to rotavirus as a cause of inpatient gastroenteritis in developing countries. Transmission is by the faeco-oral route either directly or via contaminated food or water. It may account for up to 80% of ‘traveller’s diarrhoea’ which is said to affect between 20–50% of the estimated 12 million travellers from industrialized countries to the tropics/subtropics annually. Clinical features: toxins stimulate Cl-, Na+, and water efflux into the intestinal lumen, resulting in voluminous, watery diarrhoea after an incubation period of 1–2 days. Vomiting and abdominal cramps are frequently a feature and up to 10 motions per day may be passed. Diagnosis: depends upon culture of E. coli from the faeces and identification of the toxin which is usually only possible in specialist laboratories. By the time this is done, symptoms have usually subsided. Management: rehydration. Trimethoprim or ciprofloxacin are most likely to be effective in severe disease. Enteropathogenic E. coli (EPEC) EPEC refer to strains of E. coli that include the classic pathogens O111 and O55 and other serotypes which display distinct localized adhesion to Hep-2 cells in culture and human intestinal mucosal cells. In severe infections, the mucosal brush border is lost by a process of vesiculation resulting in malabsorption and osmotic diarrhoea. EPEC are a major cause of infantile diarrhoea that can be devastating. Transmission is by the faeco-oral route. Epidemics of hospital-acquired infection occur and recent hospitalization is a risk factor for infection. It is also associated with traveller’s diarrhoea. Diagnosis: diagnosis rests upon culture of EPEC from the stool or duodenal aspirate. Serology is not reliable but may be the only tool available; DNA probes are available in specialist centres. Clinical features: range from acute watery diarrhoea to relapsing severe and prolonged diarrhoea, usually with mucus but no blood. Initially there may be vomiting and fever. Epidemics can occur affecting mainly babies, and fatality in untreated epidemics can reach 50%. Management: rehydration. If the diarrhoea is prolonged, special diets and, rarely, parenteral feeding and antibiotics may be necessary. Co-trimoxazole is recommended since ampicillin is unlikely to be effective, resistance being a problem. Bovine milk immunoglobulin concentrate from immunized cows is a promising new advance. Prevention: no vaccine is yet available P.133
Causes of traveller’s diarrhoea

Enterotoxigenic E. coli 30–80%
Campylobacter jejuni ~20%
Shigella spp. 5–15%
Salmonella spp. 3–15%
Giardia intestinalis 0–3%
Unknown 15–20%

Enteroaggregative E. coli (EAEC) These bacteria are recognized by their characteristic adherence pattern to Hep-2 cells. Recently identified, they are now known to be important pathogens in developing countries and seem to be particularly prone to cause persistent diarrhoea. Children of all ages are affected. Clinical features: vary from asymptomatic to watery diarrhoea, often persistent. EAEC cause travellers’ diarrhoea. Diagnosis: definitive diagnosis is by Hep-2 cell assay Management: supportive; ciprofloxacin is the most effective antibiotic. Enterotoxin-producing S. aureus Commonly spread from the milk of cows with staphylococcal mastitis, but may also grow in prepared foods. The incubation time is short; 2–6 hrs (since the enterotoxin is preformed). Clinical features: vomiting rapidly followed by diarrhoea which may be very severe, though usually short-lived. Management: supportive; antibiotics are useless P.134
Cholera The enterotoxic Vibrio cholerae is the main cause of dehydrating diarrhoea in adults. Infections range from asymptomatic to acute fulminant watery diarrhoea, often described as a rice-water stool, which if untreated may be fatal. Vibrios are Gram-negative, aerobic, comma-shaped rods that are oxidase positive and ferment both sucrose and glucose but not lactose. They can be divided into several serovars with V. cholerae 01 causing cholera. V. cholerae is killed by heating at 55°C for 15 mins and by most disinfectants, yet it can survive in saline conditions for up to two weeks at ambient temperatures. In most cases, the bacteria survive for only limited periods on foodstuffs, with the notable exception of chitinous shellfish upon which they may survive for 14 days if refrigerated. Transmission: humans are the only known natural host. Infection usually requires a large infective dose and occurs via contaminated food or water. The incubation period ranges from a few hours to 5 days. Only a minority of infected people develop symptoms — studies suggest that there are ~40 asymptomatic carriers of El Tor to every symptomatic case (~5:1 for classical biotype). This is true both in endemic areas and during outbreaks; hence the need for meticulous hygiene. Clinical features: symptomatic infection varies between mild self-limiting diarrhoea and severe watery diarrhoea of up to 30 litres per day. Even severe diarrhoea is painless; it leads to electrolyte imbalances, metabolic acidosis, prostration, and can cause death from dehydration within hours. Vomiting starts shortly after the onset of diarrhoea in 80% of cases. Shock typically follows ~12 hrs later, with impaired consciousness due to hypovolaemia and hypoglycaemia. This is particularly serious in children who, unlike adults, may have a mild fever. Renal failure, ileus, and cardiac arrhythmias accelerate death; the elderly or those with low gastric acid, such as alcoholics, are especially vulnerable. Muscular and abdominal cramps are common owing to loss of Ca2+ and Cl- ions. Diagnosis: in epidemics, the diagnosis may be made on clinical grounds alone. In non-epidemic periods or places, acute watery diarrhoea resulting in severe dehydration or the death of a patient over 5 yrs should suggest cholera. Dark field microscopy of faecal material shows comma-shaped bacteria darting about; this is quickly halted upon addition of diluted 01 antisera. Transportation of samples should be in alkaline peptone water and kept cool. Culture requires selective media such as TCBS agar. If possible, specimens should be sent to a reference laboratory for bio- and serotyping. Management

  • In all but a few cases, treatment consists solely of meticulous attention to rehydration, usually with oral preparations. This will reduce mortality to less than 1%. See below for rehydration management. The most common error is underestimation of the volume of ORS or intravenous fluid required. In some emergency cases, where ORS was not available, sucrose and rice-water-based solutions have been given with success.
  • P.135

  • Antibiotics should be given to severe cases, where they have been shown to reduce both the volume and duration of diarrhoea.
    • Doxycycline is the drug of choice for adults (except pregnant women) in whom a single dose of 300 mg is sufficient.
    • Tetracycline 500 mg PO qds for 3 days can be given to adults, although resistance has been reported in central Asia and Africa.
    • Follow local guidelines based on susceptibilities.
    • Give children or pregnant women co-trimoxazole 30 mg/kg PO od. This may also be used for adults: 960 mg PO bd for 3 days.

Prevention: public health measures aimed at improving food and water hygiene and sanitation are the most important factors. Currently, oral killed whole-cell vaccines and a live attenuated vaccine are available. Their use in outbreaks has not been fully evaluated and should not deflect resources from treatment facilities and prevention of spread. Health education: plays a major role in both preventing outbreaks and limiting the spread of infection once one occurs. This should not only concentrate upon ensuring food and water hygiene, but also measures such as disinfecting patients’ clothing by boiling for 5 mins, drying out bedding in the sun, burying stools, etc. In larger health centres, patient excreta may be mixed with disinfectant (e.g. cresol) or acid before disposal in pit latrines. Semi-solid waste should be incinerated. Funerals have been a source of spread and preventive measures should be instigated to minimize the risk of mourners arriving from uninfected areas, and potential contamination from ritual washing of the dead and funeral feasts. The cholera outbreak It is obligatory to notify the WHO of all cholera cases. Suspected cases should be reported immediately by health authorities and laboratory confirmation sent as soon as it is obtained. This should be followed by weekly reports containing the number of new cases and deaths since the last report, the cumulative totals for the year, and if possible the age distribution and number of patients admitted to hospital, recorded by region or other geographical division. This data should be sent to WHO headquarters as well as to the appropriate regional office. Usually there is a national co-ordinating committee to implement and regulate control and prevention measures, though often it is up to the front-line doctors to initiate the process and frequently they remain in close collaboration with national and international bodies. Mobile control teams may be needed in inaccessible areas or in countries with no national co-ordination and these are responsible for establishing and operating temporary treatment centres, training local staff, educating the public, carrying out epidemiological studies, collecting stool, food, and water samples for laboratory analysis, and providing emergency logistical support to health posts and laboratories. Emergency treatment centres may be needed if appropriate facilities do not exist or are swamped with patients. Strict isolation or quarantine measures are not needed. The most crucial factor affecting survival is access to treatment centres with trained staff and intravenous and oral rehydration capability. P.137
Epidemiology of V. cholerae V. cholerae serovar 01 is the causative agent of cholera. There are two biotypes of the 01 serovar: classical and El Tor. Each of these biotypes is further divided into three serotypes: Ogawa, Inaba, and Hikojima. The classical biotype caused the first six cholera pandemics in south Asia during the 19th and early 20th centuries. The El Tor biotype was first recognized in 1906 but until 1963 was restricted to Sulawesi. During the 1960s, the seventh pandemic started with spread of the El Tor biotype, Inaba serotype, out of Indonesia into South Asia, Africa, and, since 1991, Latin America. This biotype has now replaced the classical biotype throughout much of the world, except Bangladesh. Other V. cholerae serovars cause a cholera-like illness. The 0139 serotype first appeared in southern India in 1992. Unlike other non-01 strains, it causes cholera with similar epidemiological and clinical pictures to 01 cholera. The major difference noted in Bangladesh is that it tends to affect adults. Previous exposure to the 01 serovar does not confer protection. Estimated minimum supplies needed to treat 100 patients during a cholera outbreak1

  • 650 packets of ORS solution (1 litre)
  • 120 bags of 1 litre Ringer’s lactate solution2, with giving sets
  • 10 scalp vein sets
  • 3 NG tubes, 5.3 mm outside diameter (16 French), 50 cm long for adults
  • 3 NG tubes; 2.7 mm outside diameter (8 French), 38 cm long for children.

For adults:

  • 60 capsules of doxycycline 100 mg (3 caps per severely dehydrated adult patient) or
  • 480 capsules of tetracycline 250 mg (24 capsules per severely dehydrated patient).

For children or pregnant women:

  • 300 tablets of co-trimoxazole 120 mg

If selective chemoprophylaxis is planned: The additional requirements for 4 close contacts per severely dehydrated patient (~80 people) are:

  • 240 capsules of doxycycline 100 mg (3 capsules per person) or
  • 1920 capsules of tetracycline 250 mg (24 capsules per person).

Other necessary supplies:

  • 2 large water dispensers with tap for bulk ORS manufacture
  • 20 1-litre bottles, 20 half-litre bottles for ORS dispensing
  • 40 200 ml cups
  • 20 teaspoons
  • 5 kg cotton wool
  • 3 reels of adhesive tape.

Footnote 1 The supplies listed are sufficient for IV fluid followed by oral rehydration salts for 20 severely dehydrated patients and for ORS alone for 80 patients. 2 If Ringer’s lactate solution or similar solution is unavailable, physiological saline may be substituted P.138
Clostridium perfringens Clostridium perfringens produces two forms of gastrointestinal disease: simple food poisoning (caused by type A) and necrotic enterocolitis (type C).

  • Food poisoning — see Table 2D.2
  • Necrotic enterocolitis (pigbel)

This is common in Uganda, South-East Asia, China, and the highlands of Papua New Guinea. It occurs when C. perfringens type C is eaten, normally in meat, by people who are malnourished, heavily infected with Ascaris lumbricoides, or have a diet rich in sweet potatoes. The latter two are associated with high levels of heat-stable trypsin inhibitors that inhibit the luminal proteases, preventing them inactivating the toxin. Clinical features: symptoms usually begin 48 hrs following ingestion but may start up to one week later. It is classified into 4 types:

  • Type I (acute toxic) presents with fulminant toxaemia and shock. It usually occurs in young children and carries an 85% mortality rate.
  • Type II (acute surgical) presents as mechanical or paralytic ileus, acute strangulation, perforation, or peritonitis. It has 40% mortality.
  • Type III (subacute surgical) presents later, with features similar to type II. Mortality is also ~40%.
  • Type IV is of mild diarrhoea only, though it may progress to type III. In types II and III a thickened segment of bowel is sometimes palpable. Blood and pus are passed with the stool in severe disease.

Diagnosis: isolation of C. perfringens from stool or peritoneal fluid culture. Serological diagnosis is also possible. Management: type I and II disease require urgent surgery after appropriate resuscitation. Give IV chloramphenicol or benzylpenicillin and C. perfringens type C antiserum, where available. Milder cases may require glucose and electrolyte infusions, with IV broad-spectrum antibiotics if there are signs of extraintestinal spread. Give an antihelminthic effective against Ascaris. Oral food intake should begin after 24 hrs. Prevention: immunization with type C toxoid has greatly reduced the incidence and severity of the disease in Papua New Guinea.

Table 2D.2 Food poisoning from bacteria or their toxins
Organism/toxin Principal foods Time after food Clinical features
Staph. aureus Meat, poultry, dairy produce 1–6 hrs D, V, AP
B. cereus Fried rice, sauces, vegetables 1–5 hrs
6–16 hrs
Red bean toxin 1–6 hrs D, V
Scombrotoxin Fish 1–6 hrs D, flushing, sweating, mouth pain
Mushroom toxin 1–6 hrs D, V, AP
Ciguatera Fish 1–6 hrs Fits, coma, renal/liver failure
Salmonella spp. Meat, poultry, dairy produce 8–72 hrs (mean 12–36 hrs) D, V, AP, fever
Campylobacter spp Poultry, raw milk, eggs 1–10 days (mean 2–5 days) D, AP
C. perfringens A Cooked meat 8–24 hrs (mean 8–15 hrs) D, AP, V
Vibrio parahaemolyticus Seafood 4–96 hrs (mean 12 hrs) D, V, AP, cramp, headache
Shigella spp. Faecal contamination 1–7 days (mean 1–3 days) D(bloody), V, fever
C. botulinum Poorly canned food, smoked meats 2 hrs–8 days (mean 12–36 hrs) Diplopia, paralysis
L. monocytogenes Dairy produce, meat, vegetables, seafood 1–7 weeks Septicaemia, septic abortion
E. coli Dirty water 8–44 hrs D, V, cramps
Y. enterocolitica Pork and beef 24–36 hrs Fever, AP, D
V = vomiting, D = diarrhoea, AP = abdominal pain

Giardiasis Giardia intestinalis (also known as G. lamblia, G. duodenalis) is the most common human protozoan GI pathogen, having a worldwide distribution. Its prevalence rates can reach ~30% in the tropics, with infection being highest in infants and children. It causes 3% of traveller’s diarrhoea. Transmission: the cysts can survive for long periods outside the host in suitable environments (e.g. surface water). They are notably NOT killed by chlorination. Infection follows ingestion of cysts in faecally contaminated water (rarely food) or through direct person to person contact. Partial immunity may be acquired through repeated infections. Clinical features: in endemic areas, the asymptomatic carrier state is common. Symptoms of acute disease usually begin within 3–20 days of infection; most patients recover within 2–4 weeks, although in 25% of travellers symptoms persist for up to 7 weeks. Diarrhoea is the major symptom; it is watery initially, becoming steatorrhoeic and often associated with nausea, abdominal discomfort, bloating, weight loss, and sometimes sulfurous, offensive burps. Some patients develop a chronic diarrhoea associated with weight loss of up to 20% of ideal body weight, fat malabsorption, deficiencies (particularly of vitamins A and B12), and in some cases 2° hypolactasia. Complications: in hyperendemic settings, infections are universal and usually asymptomatic but some studies have documented retardation of growth and development in severely affected infants and children, in whom malabsorption exacerbates malnutrition. Chronic giardiasis is associated with allergic and inflammatory conditions such as lymphoid nodular hyperplasia. Protein-losing enteropathy, lactose intolerance, and irritable bowel syndrome can also occur. Diagnosis: detection of cysts (and occasionally trophozoites) in faecal samples by light microscopy. Examine 3 separate samples, since cysts are excreted only intermittently, and diagnostic sensitivity is low. Trophozoites may be detected in biopsies of small intestine mucosa. ELISA tests now exist for faecal Giardia antigens. Since mixed enteric infections and asymptomatic carriage of Giardia is so common, identification of the parasite does not guarantee that it is the causative agent of the diarrhoea. Serology is not useful because of cross-reactivity in non-infected individuals in endemic areas. Management

  • Rehydration and symptomatic relief are usually sufficient.
  • If symptoms persist, an anti-giardial drug will decrease the severity and duration of symptoms. Drug failure due to resistance is increasing. Recommended drugs include metronidazole and tinidazole.

Prevention: attention to personal hygiene, appropriate treatment of water supplies, encouraging breastfeeding (shown to partially protect against infection). P.141
Cryptosporidiosis The protozoan Cryptosporidium parvum is a common opportunistic infection in HIV +ve patients. It is also a common cause of childhood diarrhoea in the immunocompetent. Transmission is mainly through contaminated water. It accounts for up to 17% of childhood diarrhoea in the developing world, and infections contribute to growth faltering during the first year of life. Although usually mild, severe or persistent diarrhoea may occur. Clinical features: acute diarrhoea is indistinguishable from other aetiologies. Cryptosporidium should be sought in persistent (chronic) diarrhoea; in AIDS patients it may be severe, mimicking cholera, and/or very prolonged. Diagnosis: faecal detection of the oocysts (4-6µm in diameter red spheres on modified ZN stain). Oocysts can also be seen in sputum on occasions. Management: rehydration with symptomatic relief; as yet, no drug has been shown to be effective against this organism. Cyclospora Cyclospora cayetanensis is a protozoan coccidian parasite now recognized to be a frequent cause of diarrhoea in developing and developed countries. Transmission is via contaminated water or food; the largest outbreaks in USA were caused by contaminated imported raspberries. Diagnosis: is by finding typical oocysts in faeces which are 7–10µm diameter and contain a ‘morula’ of 8 spherical bodies. The oocysts are also irregularly acid-fast when stained with modified Zn stain. Clinical features: watery diarrhoea which is most severe in non-immune travellers. Mild fever, fatigue, anorexia, and weight loss may occur. The illness can last for weeks. Management: co-trimoxazole 960 mg bd for 7–10 days.

Fig. Trophozoites of Giardia spp in stool isolates

Strongyloidiasis The nematode Strongyloides stercoralis commonly infects humans worldwide, particularly in parts of S. America and S.E. Asia. It is a serious condition in the immunosuppressed and may cause acute, relapsing, or persistent diarrhoea. There are two adult forms of the worm and two larval forms, one of which is infective. Life cycle: Complex, since reproduction can take place in either of two cycles: an external cycle involving free-living worms or an internal cycle involving parasitic worms. Contamination of skin or buccal mucosa with larvae-containing soil permits initial penetration of larvae and infection. The larvae travel to the lungs and enter the bronchi, eventually passing into the small intestine, where they mature into adults. Eggs produced by the female pass out in the faeces and continue the external cycle. Autoinfection occurs by either bronchial larvae producing progeny or filariform larvae not passing out in the stool but reinvading bowel or perianal skin. This can produce indefinite (up to 30 yrs) multiplication within the host, not requiring further infection. The pre-patent period from infection to the appearance of larvae in the stools is ~1 month. Clinical features: Infection is asymptomatic in most instances, except for autoinfection through perianal skin. The immune response limits the infection to the small bowel and also the number of adult worms. Larval penetration causes petechial haemorrhages and pruritis at the site of entry, frequently with a linear, red eruption (larva currens) as the larvae migrate under the skin. This is normally transient, but may be followed by congestion and oedema. A creeping urticarial rash may occur in pre-sensitized individuals following reinfection. Symptoms similar to bronchopneumonia with consolidation may result from larval invasion of the lungs which, together with eosinophilia, may resemble TPE. Watery diarrhoea with mucus is a frequent symptom; its intensity is dependent upon the worm burden. It often alternates with constipation. In severe cases, chronic diarrhoea with malabsorption may ensue. In the immunosuppressed, malnourished, or debilitated, massive tissue invasion may occur. Complications include severe diarrhoea, ileus, hepatomegaly, and multi-system disease due to blood/lymphatic spread. Granulomas and/or abscesses occur in the liver, kidneys, and lungs; CNS involvement produces pyogenic meningitis and encephalopathy. Death is usually a result of septicaemia with E coli. Diagnosis: detection of adults or rhabditiform larvae in the stool. Also modified Baermann technique agar plate culture, ELISA, serology, and stool culture using charcoal. Look for infection in the immunosuppressed or those who are about to be (e.g. on steroids). Management: treat all infected patients, not just the symptomatic.

  • Albendazole 400 mg PO bd for 3 days (Alternatives: ivermectin 200 mcg/kg PO as a single dose or tiabendazole 25 mg/kg PO bd for 3 days)
  • Massive infection also responds well to albendazole.

Prevention: requires improving hygiene and education on a community level, as well as monitoring and evaluation. P.143

Fig. 2D.6 S. Stercoralis larva in stool sample. Size 200–300×15µm

Leave a Reply

Time limit is exhausted. Please reload the CAPTCHA.


apply_now Pepperstone Group Limited