Infectious Diseases

1. What this chapter covers, and how NEET PG actually tests it

Stems give a febrile patient with a blood count and an exposure, a cerebrospinal fluid profile, or a septic patient requiring an immediate management decision.

The organising principle is that fever is the least discriminating feature of a febrile illness.

Three things separate the causes of acute undifferentiated fever, and none of them is the temperature.

Malaria must be excluded in every febrile patient in India before anything else is considered, not because it is always the diagnosis but because it is the one that kills fastest and is confirmed or excluded within minutes.

2. Acute undifferentiated fever

Scrub typhus is now recognised as one of the commonest causes of acute undifferentiated fever in much of India, and the eschar must be actively searched for in the axilla, groin and other folds, since patients do not report it.

Doxycycline is the treatment for both scrub typhus and leptospirosis, which is why it is often started empirically in an undifferentiated fever after malaria and dengue have been addressed.

Weil disease is the severe form of leptospirosis, combining jaundice, acute kidney injury and haemorrhage, and its jaundice is characteristically out of proportion to the transaminase rise.

2.1 Managing dengue

The illness has three phases, and almost all serious complications occur at the transition between the second and third.

The febrile phase lasts a few days, the critical phase begins as the fever settles and lasts about one to two days, and the recovery phase follows with reabsorption of extravasated fluid.

Deterioration occurs as the fever falls rather than at its height, which is counterintuitive and is the reason patients are sent home at exactly the wrong moment.

Warning signs mandating admission include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy, an enlarged liver and a rising haematocrit with a falling platelet count.

The rising haematocrit with falling platelets is the most objective of these, because it measures the plasma leak directly rather than its consequences.

Management is fluid replacement titrated against haematocrit and urine output, and the volume must be reduced during the recovery phase or the reabsorbed fluid causes pulmonary oedema.

Platelet transfusion is not given for a low count alone, but only for significant bleeding, because the thrombocytopenia is transient and transfused platelets are consumed rapidly.

Non-steroidal anti-inflammatory drugs and aspirin are avoided because of bleeding risk, and paracetamol is used for fever.

3. Enteric fever

Blood culture is the diagnostic test and is most productive in the first week, while stool and urine cultures become positive later.

Bone marrow culture remains the most sensitive test of all and stays positive despite prior antibiotics, which is why it is used when the diagnosis is critical and cultures have failed.

The Widal test is unreliable and should not be used to make the diagnosis. It cross-reacts with other organisms, remains positive after previous infection or vaccination, and a single titre without a paired convalescent sample cannot be interpreted.

Ceftriaxone and azithromycin are the usual treatments, because fluoroquinolone resistance is now widespread and extensively drug-resistant strains have emerged in the subcontinent.

Relative bradycardia, in which the pulse does not rise as expected for the temperature, is a classical clue shared with a small number of other infections.

Intestinal perforation and haemorrhage occur in the third week, when Peyer patch ulceration is deepest, which is why the risk period is late rather than at the height of the fever.

4. Sepsis

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, and the older systemic inflammatory response criteria are no longer used to define it.

Septic shock is sepsis in which vasopressors are needed to maintain an adequate mean arterial pressure together with a raised lactate despite adequate fluid resuscitation.

Cultures are taken before antibiotics but must never delay them, and if venous access is difficult the antibiotic is given first, because the mortality cost of delay exceeds the diagnostic cost of a sterilised culture.

Lactate reflects tissue hypoperfusion and anaerobic metabolism, and a failure to clear it during resuscitation predicts poor outcome better than any single pressure reading.

Source control is the step most easily forgotten in the rush of resuscitation, and no quantity of antibiotic will treat an undrained abscess, an infected collection or an infected line.

Antibiotics work on organisms in tissue and blood, not on organisms in pus, because a collection has no blood supply through which the drug can reach them.

Identifying and removing the source therefore takes equal priority with the drug, and imaging is arranged early rather than after the antibiotics have been seen to fail.

A patient who fails to improve within forty-eight hours of appropriate antibiotics almost always has either an undrained source, a resistant organism or the wrong diagnosis.

5. Meningitis

5.1 Reading the cerebrospinal fluid

Glucose is the most useful single parameter, because viruses do not consume it while bacteria, mycobacteria and fungi do.

The cerebrospinal fluid glucose is interpreted against a simultaneous blood glucose, since a low value means nothing in a hypoglycaemic patient.

5.2 Management sequence

Imaging before lumbar puncture is required only with focal neurological signs, papilloedema, new seizures, marked depression of consciousness or significant immunosuppression.

In everyone else the puncture is done immediately, because imaging delays antibiotics without adding information.

Dexamethasone is given with or just before the first antibiotic dose in suspected pneumococcal meningitis, since it reduces neurological sequelae only if it precedes the inflammatory burst caused by bacterial lysis.

Given after the antibiotic has already lysed the organisms, the steroid has nothing left to prevent, which is why the timing rather than the drug is what is examined.

6. Infective endocarditis

Diagnosis uses the modified Duke criteria, requiring two major criteria, or one major with three minor, or five minor.

Three sets of blood cultures are taken from separate sites before antibiotics, because the bacteraemia is continuous and the requirement is to demonstrate persistence rather than to catch a single peak.

Culture-negative endocarditis is usually caused by prior antibiotics, and otherwise by organisms that grow poorly, including Coxiella, Bartonella and the fastidious oral group.

Native valve endocarditis in India frequently occurs on rheumatic valves, which changes the pretest probability compared with populations where degenerative disease and prosthetic material dominate.

7. Tuberculosis at the bedside

Roughly a fifth of Indian cases are extrapulmonary, and those forms are where diagnosis is missed, because the classical cough and cavitation are absent.

Disc space is preserved until late in spinal tuberculosis, whereas pyogenic infection destroys it early, because mycobacteria lack the proteolytic enzymes that digest cartilage.

Nucleic acid amplification is used on extrapulmonary samples as well as sputum, because it is far more sensitive than smear and simultaneously reports rifampicin resistance.

A negative tuberculin or interferon test does not exclude active disease, since both measure immune sensitisation rather than the presence of the organism, and both are frequently negative in severe or disseminated disease.

That paradox matters clinically: the sicker the patient, the less reliable the immunological test becomes, because anergy accompanies overwhelming infection.

Tuberculous pleural effusion typically shows few or no organisms on smear or culture, since the fluid is a hypersensitivity reaction rather than a collection of infected material.

8. Resistance and stewardship

Extended-spectrum beta-lactamase production confers resistance to most cephalosporins, and carbapenems have been the standard response.

Carbapenem resistance is now the central problem in Indian hospitals, mediated by carbapenemases including the metallo-beta-lactamase first described from this region, and it leaves very few therapeutic options.

Methicillin-resistant Staphylococcus aureus resistance is conferred by an altered penicillin-binding protein, so it applies to all beta-lactams rather than to methicillin alone, which is why the name is misleading.

Stewardship rests on a small number of practices: culture before treatment, de-escalate once sensitivities return, treat for the shortest effective duration, and avoid antibiotics entirely in viral illness.

De-escalation is the step most often omitted, because starting broad therapy feels safe and narrowing it later feels risky, though the opposite is true for both the patient and the population.

9. Infection in the immunocompromised host

The CD4 count predicts the opportunistic infection in human immunodeficiency virus, with tuberculosis the Indian exception occurring at any count.

Immune reconstitution inflammatory syndrome is the complication that surprises clinicians, in which starting antiretroviral therapy causes an apparent worsening as the recovering immune system mounts a response to an existing infection.

The patient looks worse precisely because treatment is working, so the correct response is to continue antiretroviral therapy and treat the unmasked infection rather than to stop.

Screening for and treating cryptococcal and tuberculous disease before starting therapy reduces the risk, which is why antiretroviral treatment is deliberately delayed for a short period in cryptococcal meningitis.

Neutropenia predisposes to bacterial and fungal infection, defective cell-mediated immunity to intracellular organisms and fungi, and complement or splenic dysfunction to encapsulated bacteria.

Asplenic patients therefore require vaccination against pneumococcus, meningococcus and Haemophilus influenzae type b, and they are at risk of overwhelming sepsis from a trivial-seeming illness.

9.1 Occupational exposure

After a needlestick the wound is washed, the source assessed and post-exposure prophylaxis started as soon as possible.

Transmission risk differs greatly by organism, being highest for hepatitis B, intermediate for hepatitis C and lowest for human immunodeficiency virus.

Prophylaxis for the virus is three drugs for twenty-eight days, started within hours and ideally under two, since efficacy falls rapidly with delay.

Hepatitis B is prevented by vaccination and, in an unvaccinated exposed person, by immunoglobulin with vaccine, while no prophylaxis exists for hepatitis C, which is instead monitored and treated if transmission occurs.

10. Fever of unknown origin

The classical definition requires a fever above a threshold lasting more than three weeks with no diagnosis after an appropriate initial evaluation.

The three-week requirement exists to exclude self-limiting viral illness, which otherwise dominates any list of undiagnosed fevers.

In India tuberculosis remains the single commonest cause, particularly in extrapulmonary and disseminated forms that produce few localising signs.

Drug fever is easy to miss because the patient looks well and the offending drug has usually been given for a long time without problems.

The most productive step in an undiagnosed fever is usually to repeat the history and examination rather than to order another test, since the diagnosis in most series was available in information that had already been obtained but not acted upon.

A trial of empirical antibiotics or steroids is avoided while investigation continues, because a partially treated infection becomes far harder to diagnose and a steroid can mask a lymphoma for weeks.

11. Worked examples

Example 1. A febrile patient has leucopenia with thrombocytopenia and severe retro-orbital pain. What is the likely diagnosis?

Dengue. The combination of low white cells with low platelets is characteristic, and a rising haematocrit indicates plasma leakage and a need for close monitoring.

Example 2. A septic patient has difficult venous access and cultures cannot be obtained quickly. What should be done?

Give the antibiotics. Cultures should precede treatment when possible, but the mortality cost of each hour of delay outweighs the diagnostic value of a culture taken before therapy.

Example 3. A patient with suspected pneumococcal meningitis receives ceftriaxone, and dexamethasone is given four hours later. What is the problem?

The steroid works by suppressing the inflammatory response to bacterial lysis, so it must be given before or with the first antibiotic dose. Given afterwards it cannot prevent the burst that has already occurred.

Summary

Fever is the least discriminating feature; the blood count, one physical sign and the exposure history do the work.

Exclude malaria in every febrile Indian patient first, because it kills fastest and is excluded in minutes.

Dengue gives leucopenia with thrombocytopenia and a rising haematocrit.

Scrub typhus is a leading cause of undifferentiated fever, and the eschar must be actively searched for in skin folds.

Leptospirosis gives conjunctival suffusion with jaundice out of proportion to the transaminases.

Doxycycline covers both scrub typhus and leptospirosis, which is why it is often started empirically.

Blood culture diagnoses enteric fever in the first week; bone marrow culture is the most sensitive and survives prior antibiotics.

The Widal test cross-reacts, persists after vaccination and cannot be interpreted on a single titre.

Enteric perforation occurs in the third week when Peyer patch ulceration is deepest.

Fluoroquinolone resistance means ceftriaxone or azithromycin is used for enteric fever.

Sepsis is organ dysfunction from a dysregulated response, not a set of inflammatory criteria.

Septic shock requires vasopressors plus a raised lactate despite fluid resuscitation.

Cultures precede antibiotics but must never delay them.

Noradrenaline is the first-line vasopressor, and lactate clearance predicts outcome.

Glucose is the most useful cerebrospinal fluid parameter, since viruses do not consume it.

Interpret cerebrospinal fluid glucose against a simultaneous blood glucose.

Tuberculous meningitis gives very low glucose, very high protein and a cobweb clot.

Image before lumbar puncture only for focal signs, papilloedema, seizures, depressed consciousness or immunosuppression.

Dexamethasone must precede or accompany the first antibiotic dose in pneumococcal meningitis.

Duke criteria require two major, or one major with three minor, or five minor.

Three culture sets from separate sites demonstrate the continuous bacteraemia of endocarditis.

Culture-negative endocarditis usually follows prior antibiotics or fastidious organisms.

Carbapenem resistance is the central problem in Indian hospitals.

Methicillin resistance is an altered binding protein and therefore applies to all beta-lactams.

De-escalation is the most often omitted stewardship step, though it benefits both patient and population.

Tuberculosis remains the commonest cause of fever of unknown origin in India.

Dengue deteriorates as the fever falls, not at its height, which is when patients are wrongly sent home.

A rising haematocrit with falling platelets measures plasma leak directly and is the key warning sign.

Platelets are transfused in dengue only for significant bleeding, never for a low count alone.

Immune reconstitution syndrome means treatment is working, so antiretroviral therapy is continued and the unmasked infection treated.

Asplenic patients need vaccination against the encapsulated organisms and can deteriorate from a trivial illness.

Disc space is spared until late in spinal tuberculosis but destroyed early by pyogenic infection.

A negative tuberculin or interferon test does not exclude active tuberculosis, and anergy accompanies severe disease.

In an undiagnosed fever, repeating the history and examination is more productive than ordering another test.

Avoid empirical antibiotics or steroids during investigation, since both make the eventual diagnosis harder.