THM1) Enteric fever includes infection by S. typhi, S. paratyphi A, S. paratyphi B and S. paratyphi C. S. paratyphi C is rare with occasional cases in Guyana and Eastern Europe.
THM2) Incidence of Salmonella typhi infection (typhoid fever) was traditionally said to be 10 times more than that of Salmonella paratyphi A and B (paratyphoid A and B) infection. However, the incidence of paratyphi B is increasing.
THM3) Relative bradycardia is a sign usually associated with enteric fever. Other not-so-uncommon causes of relative bradycardia are drug-induced fevers and leptospirosis.
THM4) Relative bradycardia won’t be seen in typhoid patients who are dehydrated or anxious or those who have rare complications like GI haemorrhage or perforation.
THM5) In typhoid, the bacteria localize principally in the lymphoid tissue (Peyer patches) of the ileum particularly within 60cm of ileocaecal junction. This is why area of maximum tenderness is the right iliac fossa; and also why ultrasound and CT scan show distal ileal thickening and enlarged adjacent nodes.
THM6) Constipation occurs in the first few days of enteric fever because of enlargement of Peyer patches which narrows the ileal lumen. Following the first few days of constipation, diarrhea may occur and the cause is necrosis and sloughing off of the inflamed Peyer patches.
THM7) In crime detection terminology, a ‘red herring clue’ is a misleading clue that distracts the detective from the identity of the real criminal. In enteric fever, two symptoms can act as red herring clues. One is a dry cough often seen in the 1st week. The other misleading symptom is diarrhea at the onset of fever.
THM8) The gall bladder is the 2nd most common organ affected by typhoid after Peyer (or Peyer’s) patches. The resultant cholecystitis is usually sub-clinical. Hence the detection of cholecystitis on USG (thickened (>4mm) GB wall or pericholecystic fluid) may serve as a clue to the diagnosis of enteric fever.
THM9) Incidence of relapse of typhoid is 10-20%. A factor favoring it is very early institution of antibiotic treatment because this suppresses an immune response. Relapse typically occurs a week after stoppage of treatment though it may occur as late as 70 days after. Relapses are generally milder than 1st illness.
THM10) it’s amazing that though we have nearly stopped using chloramphenicol which was introduced in 1948, we still use the Widal test which originated in 1896. I hate the Widal. It should be banned. I want the Hippocratic Oath to have an extra line. ‘I shall never ever, while investigating fever, do the Widal’!
THM11) Widal stands up there with TB IgG/IgM as having the poorest sensitivity and specificity of all tests. It misleads more than it guides. It harms. Dump it!
THM12) Though the textbook quoted ratio of typhoid to paratyphoid is 10:1, many microbiologists of Mumbai are reporting a ratio of at least 1:1 in some seasons. This increase in incidence of paratyphoid has one major significance – there is no vaccine yet against paratyphoid.
THM13) Foreigners travelling to India often take (2 weeks before arriving) the typhoid vaccine. Hence in travelers the ratios of typhoid to paratyphoid is 1:4.
THM14) Chronic carrier state occurs in about 3% of patients of enteric fever. It is defined as excretion of the bacilli (usually in stool) for one year or longer. Risk factors for becoming a carrier include age <1 or >60 years and biliary diseases like gallstones. Chronic carriers may never have suffered overt infection.
THM15) Conventional non-automated methods of blood culture have been largely replaced by automated methods like ‘BACTEC’. These are costlier but quicker.
THM16) Automated culture for enteric fever costs ~ Rs.800/-(+Rs.400/- if culture is +ve and antibiotic sensitivity done). Growth can be detected as early as 24 hours.
THM17) Do send blood culture in more fever cases especially in 1st week and before starting antibiotics. Do call the lab at 24 hours to ask if culture has ‘flashed’ +ve.
THM18) Newer tests that detect IgM antibodies to S. Typhi antigens are now available (eg. Typhidot). These are better than Widal and much poorer than cultures.
THM19) Typhidot (cost ~Rs. 500/-) is a rapid card test and result is available in a few hours. I have not yet used the test and would use it as a ‘placebo’ to satisfy patients.
THM20) If you have diagnosed an adult with enteric fever, clinically or on the basis of investigations, the following guidelines (my suggestions) may help you.
- First send blood for culture even if some antibiotics have been taken.
- Don’t hesitate in admitting the patient. Injectable antibiotics are more effective.
- If using orals, use 2 antibiotics together. You can choose from a cephalosporin (typically cefixime), a quinolone (eg. ofloxacin) and azithromycin. Resistance to quinolones is rampant.
- Other orals that may work are chloromycetin, amoxicillin and cotrimoxazole
- I like to co-prescribe probiotics like lactobacilli.
- Treat for 14 days. Shorter treatment favours early relapse and carrier state.
- Don’t advise prolonged rest and leave from work. Exertion does not cause relapse.
- Dose of ofloxacin is 15mg/kg/day upto a maximum 800mg/d. Dose of cefixime is minimum 15mg/kg/day and ideally 20mg/kg/day.
- Thus a typhoid antibiotic prescription for a 60kg adult with enteric fever is T.OFLOXACIN 400mg BD plus T.CEFIXIME 400mg TDS for 14 days at least.
- There is no need to use clavulanate with cefixime (eg. Zifi CV) as salmonella do not produce beta lactamases. Such combinations increase cost
- I use azithromycin only if there is intolerance/ contradiction to cefixime or quinolone. Adult dose of azithromycin is 500mg BD for 14 days.
- Resistance to quinolones is detected commonly on +ve blood cultures. Resistance to injection ceftriaxone is rare.
THM21) Typhium Vi (Sanofi-Aventis) and Typherix (GSK) are multinational brands of inactivated injectable typhoid vaccine. Cost approx Rs.250/-. Typhar (Bharat Biotech) and Biotyph (biomed) are Indian typhoid vaccines available even as multidose vials. A five dose vial costs about 525/-.
THM22) The Indian Academy of Paediatricians recommends injectable vaccine be taken every 3 years. The American CDC recommends travelers to take it every 2 years.
THM23) Injectable vaccine can be given IM to everybody above age 2 including the immunocompromised. Protection rate is 55-75%. It does not protect against paratyphoid.
(The above page is written in 2014)