ENTERIC FEVER

10.8

TABLE 10.11: Complications of W. cough

• Respiratory

Early : Pneumonia, atelectasis, pneumothorax

Late : Bronchiectasis, reactivation of TB

Others : Otitis media, subcutaneous emphysema

• Neurological

Early : Hypoxic seizures, intracranial hemorrhage Late : Motor deficits, aphasia, blindness, deafness

• Hemorrhagic: Subconjunctival hemorrhage, epistaxis

• Gastrointestinal: Rectal prolapse, hernia

• Malnutrition, due to vomiting and 4 intake

Enteric fever, systemic infection due to Salmonella organisms, is a leading cause of prolonged pyrexia in children.

Enteric fever is an endemic illness in India with occasional outbreaks and annual incidence of ~1% in population lt;17 years of age.

Epidemiology: S. typhi is a gram-negative, mainly intracellular organism, having 3 major antigens (O, H, Vi) and over 80 phage types. Phage typing is necessary to trace the source of epidemic.

Reservoir of infection is a case or carrier, who excretes the bacilli in urine or stools.

Modes of transmission is fecooral, due to contamination of food/water, either directly by hands of infected food handlers or indirectly via flies. Raw vegetables grown in sewage farms or washed with contaminated water are common sources of infection. Eggs with cracked shells may get contaminated during storage/transport. Transplacental and intrapartum infection due to fecal contamination of amniotic fluid in carrier mothers is known.

Risk factors: Enteric fever is more common in school­age and adolescents (5-19 years) and in males. It is rare during first two years of life due to less risk of exposure.

Pathogenesis: On ingestion, Salmonella attach to microvilli of ileal brush borders and invade intestinal epithelium through Peyer's patches, to reach and proliferate in mesenteric lymph nodes (local lymphoid hyperplasia). From here, they enter blood stream via thoracic duct leading to asymptomatic primary bacteremia and seedling of reticuloendothelial tissues, e.g. liver, spleen, bone marrow, for further proliferation. After an incubation period of 7-14 days, secondary bacteremia develops from these sites, marking the onset of fever as well as infection of other tissues including gallbladder- the most important reservoir of infection, responsible for carrier state.

Pathology: Important pathological changes in enteric fever include:

• Typical typhoid ulcers-shallow oval ulcers along the axis of intestines, due to hyperplasia of Peyer's patches and slough of overlying epithelium,

• Lymphoid hyperplasia in mesenteric nodes, liver and spleen with mononuclear infiltration.

• Metastatic micro-abscesses in deeper tissues, due to secondary bacteremia.

Clinical manifestations: After incubation period of ~10-14 days, enteric fever presents with: (a) typical remittent fever with step-ladder pattern (gradual rise in first week), though many cases have continuous fever, (b) constitutional symptoms, e.g. malaise, anorexia, myalgia, headache, and (c) GIT symptoms, e.g. abdominal pain, constipation or diarrhea. Important clinical signs include: • Ill or toxic general appearance,

• Relative bradycardia,

• Dry and coated tongue,

• Tympanic abdomen with mild to moderate hepato- splenomegaly, and

• Typhoid rash (rose spots)—discrete macular blanching lesions over trunk on 7^th-10^th day, rarely visible in dark-skinned Indians.

Clinical manifestations are usually mild in younger children (lt;5 year) and paratyphoid fever.

Complications: Although fever and physical findings may resolve spontaneously in 2-4 weeks, complications are common in untreated cases, usually during 2nd-3^rd weeks of illness (Table 10.12). Mortality is lt;1% in treated cases.

Diagnosis should be considered in any case with: (a) prolonged fever without localizing signs, and (b) toxic appearance with coated tongue and tympanic abdomen. Confirmation requires:

• Bacterial cultures: Blood cultures are positive in 60-80% cases during first week, but positivity declines in later weeks. Multiple cultures, with volume not less than 5 ml on different days, are preferable as typhoid bacteremia is low-grade and intermittent. Bone marrow culture is more sensitive (85-90% positivity), even after antimicrobial therapy. Stool and urine cultures turn positive by 3^rd-4^th weeks and help in diagnosis of carrier state.

• Serological tests: Classical Widal test measures titers of agglutinin antibodies against O and H antigens and turns positive only after 5-7 days of fever. Generally, anti-O titers of gt;1:160 or rising anti-H titers on second test after a week, are considered as suggestive (but not diagnostic) of enteric fever. Single anti-H titers may be false-positive due to anamnestic response to other fevers, e.g. malaria and rickettsial infections. Anti-O titers do not differentiate between typhoid and paratyphoid infection.

Rapid serodiagnosis tests, e.g. Typhidot to measure IgM antibodies against outer membrane protein of

TABLE 10.12: Complications of enteric fever

• Gastrointestinal:

- Intestinal bleeding (1-10%)

- Perforation, peritonitis

• Hepatobiliary: Hepatitis, cholecystitis

• Respiratory: Pneumonia, bronchitis

• Neurological:

- Encephalitis, meningitis, psychosis

- Acute cerebellar ataxia,

- Peripheral neuritis, Guillain-Barre syndrome (rare)

• Skeletal: Osteomyelitis, arthritis

• Deep tissue abscesses in liver, spleen, etc.

• Blood: Aplastic anemia, thrombocytopenia

• Miscellaneous:

- Parotitis

- Rare: Myocarditis, acute nephritis

organism using ELISA technique have a sensitivity and specificity of ~80%.

• Direct detection of S. typhi specific antigens in serum using monoclonal antibodies is possible but not routinely available.

• PCR testing is expensive but most specific and sensitive diagnostic method for early diagnosis, even in cases with very low bacteremia.

• Other investigations are largely supportive, to detect complications or exclude other causes of prolonged pyrexia and include: (a) hemogram (leucopenia with relative lymphocytosis), (b) platelet counts (thrombocytopenia), (c) stool examination for occult blood to exclude GIT bleeding, (d) chest X-ray to exclude pneumonia or tuberculosis (e) standing X-ray abdomen to exclude perforation, and (f) USG abdomen to exclude peritonitis, cholecystitis and metastatic abscesses in children with prolonged illness.

Management aims to: (a) eradicate infection as well as carrier state, (b) provide nutritional support and symptomatic relief, and (c) diagnose and treat complications promptly.

Hospitalization is indicated in cases with acute toxemia, poor intake or suspected complications. Important treatment modalities include:

• Antimicrobial therapy: Conventional antibiotics, e.g. chloramphenicol, ampicillin or cotrimoxazole are rarely used at present due to widespread resistance. Quinolones are the drugs of choice for treatment of enteric fever in adults, but not uniformly approved in children. Current IAP recommendation (2022) are as follows:

- For uncomplicated enteric fever, PO Cefixime (20 mg/ kg/day q12hr 7-14 days) is the preferred choice, the alternative being PO Azithromycin (20 mg/kg/day q24hr 7-14 days).

- For complicated or severe disease, IV Ceftriaxone (100 mg/kg/day q12hr) or Cefotaxime (150-200 mg/ kg/day q12hr) is the preferred choice, to be given for 10-14 days. Alternatives include IV Aztreonam (50-100 mg/kg/day q12hr) or Azithromycin (20 mg/kg/day q12hr) for 7 days, in cases of penicillin allergy or poor response.

• Supportive treatment includes: (i) bed rest, (ii) soft diet, (iii) fluid and electrolyte therapy, and (iv) general nursing care, especially for oral hygiene.

• Treatment of relapse: Relapses are common after partial treatment, usually within two weeks of stopping antibiotics. Each relapse should be treated as a fresh case, but for longer duration.

• Eradication of carrier state: Persistent excretion of Salmonella in stool/urine after defervescence defines a ‘carrier state', which includes convalescent carriers (lt;3 months) and chronic carriers (gt;3 months). Carrier state is less common in children (1-5%) than adults. Reservoir of infection in carriers is gallbladder and treatment includes: (a) medical therapy with PO ampicillin or amoxicillin for 2-4 weeks till at least two stool cultures are negative, and (b) surgery, i.e. cholecystectomy in chronic carriers (gt;1 year) refractory to repeated antibiotics therapy for 4-6 weeks, to remove the reservoir of infection

Prevention against enteric fever includes—(a) general sanitation and supply of safe drinking water, (b) personal and food hygiene awareness, (c) immunization, and (d) detection, treatment and follow-up of carriers. Stool/ urine cultures are indicated in all cases after 3-4 months of recovery to exclude carrier state.

Currently, two types of typhoid vaccines are available:

(a) Vi polysaccharide vaccine and (b) conjugate vaccine. Polysaccharide vaccines are less effective, cannot be used lt; 2 years and need boosters every 3 years.

While Typhoid vaccination is not included in universal immunization program, IAP recommends a single dose of typhoid conjugate vaccine (TCV) at the age 6-9 months, with catch-up immunization upto 18 years (Ch 9.2.2).

Non-typhoidal salmonellosis due to other Salmonella species, e.g. S. enteritidis, S. choleraesuis, S. typhimurium,

S. newport, etc., is usually acquired by use of contaminated animal products, e.g. eggs or raw vegetables/water.

Clinically these cases present as: (a) acute gastroenteritis (food poisoning) with crampy abdominal pain after ~ 24 hours of consumption, or (b) extraintestinal disease, e.g. osteomyelitis, arthritis or meningitis, which is more common in newborns, severe malnutrition, sickle cell anemia, malignancy and immunodeficiency states.

Diagnosis rests on culture and phage typing, though serological tests, e.g. latex agglutination test or immunofluorescence test are available for early diagnosis.

Treatment of Salmonella gastroenteritis is sympto­matic, without antibiotics, which may prolong carrier state. Extraintestinal disease should be treated like enteric fever, but more intensively, via parenteral route only.

10.9