Differentials
Dengue fever
SIGNS / SYMPTOMS
Abrupt onset of symptoms. Headache and retrobulbar pain that worsens with eye movements is typical. A rash may be present in about half of patients and may be petechial or otherwise haemorrhagic.
INVESTIGATIONS
Leukopenia and thrombocytopenia are common.
Combined non-structural protein 1 (NS1) and IgM antibody rapid tests are useful.
Polymerase chain reaction may detect dengue virus in serum early in the illness. Isolation of virus by tissue culture is less common.
Zika virus infection
SIGNS / SYMPTOMS
Residence in/travel from Zika-endemic region or unprotected sexual contact with infected individual.
Maculopapular, pruritic rash is characteristic.
Non-purulent conjunctivitis or conjunctival hyperaemia may be present.
Often asymptomatic.
INVESTIGATIONS
Reverse transcriptase-polymerase chain reaction is positive for Zika.
Serology is positive for Zika.
Chikungunya virus
SIGNS / SYMPTOMS
Residence in/travel from chikungunya-endemic region.
Prominent joint symptoms (e.g., polyarthritis and carpal tunnel syndrome are common).
Hyperpigmentation of skin and intertriginous lesions are common.
Ocular symptoms (e.g., photophobia, retro-ocular pain, conjunctival inflammation).
INVESTIGATIONS
Enzyme-linked immunosorbent assay/indirect fluorescent antibody is positive for chikungunya antibodies.
Reverse transcriptase-polymerase chain reaction is positive for chikungunya viral RNA.
Yellow fever
SIGNS / SYMPTOMS
Residence in/travel from yellow fever-endemic region.
Lack of yellow fever immunisation.
Haemorrhagic complications.
Biphasic illness (i.e., acute febrile illness lasting 2-6 days, followed by a 24-48 hour remission period, and then a more severe form of illness in some patients, with jaundice, renal failure, hepatic failure, and haemorrhagic complications).
INVESTIGATIONS
Reverse transcriptase-polymerase chain reaction (RT-PCR) is positive for yellow fever virus RNA in viraemic phase (within 5 days of symptom onset).
Serology is positive for yellow fever virus antibodies and increasing IgG titres in postviraemic phase (day 5 onwards).
Both RT-PCR and serology are recommended for samples taken between days 5 and 7.
Oropouche virus disease
SIGNS / SYMPTOMS
Residence in/travel from Oropouche virus-endemic region (or area with an ongoing outbreak). Endemic to the Amazon region, but has spread to other countries in the Americas in recent years.
Clinical signs and symptoms are similar to other arboviral diseases so it is difficult to differentiate without laboratory testing.[97]
Most cases are mild; however, haemorrhagic manifestations or neuroinvasive disease can occur rarely.
Vertical transmission has been reported with adverse pregnancy outcomes, including fetal deaths and congenital abnormalities.[97]
INVESTIGATIONS
Reverse transcriptase-polymerase chain reaction: positive for oropouche virus RNA.
Serological testing: positive. Plaque reduction neutralisation testing to detect virus-specific neutralising antibodies in serum or cerebrospinal fluid, with titers ≥10 considered positive.[98]
South American haemorrhagic fevers
SIGNS / SYMPTOMS
Residence in/travel from endemic region.
Exposure to rodent excreta.
Haemorrhagic complications.
INVESTIGATIONS
Reverse transcriptase-polymerase chain reaction (RT-PCR) is positive for Junin virus, Guanarito virus, Machupo virus, Chapare virus, or Sabia virus RNA.
Serology is positive for IgM or IgG to Junin virus, Guanarito virus, or Machupo virus. Usually ordered only when RT-PCR is unavailable.
Pneumonia
SIGNS / SYMPTOMS
Respiratory symptoms prominent, (e.g., cough, haemoptysis, dyspnoea, chest pain).
Respiratory examination may reveal focal coarse crackles or consolidation. Hypoxia is common. Signs of pleural effusion may be present (e.g., dullness to percussion, decreased breath sounds over affected area).
INVESTIGATIONS
Neutrophilia is often present. CRP may be markedly elevated.
Chest x-ray may demonstrate infiltrates or consolidation with or without effusion.
Sputum culture may reveal the causative organism.
Less commonly, blood cultures may be positive for Streptococcus pneumoniae.
Urinary antigen testing is available for certain organisms (e.g., Legionella).
Influenza
SIGNS / SYMPTOMS
Important to consider current epidemiological situation, (e.g., pandemics, epidemics, winter months). May give history of ill contacts. Short incubation period (1-2 days) with abrupt onset. Mild upper respiratory tract symptoms common (e.g., non-productive cough, pharyngitis, coryza).
Wheezing or rhonchi may be audible on auscultation.
INVESTIGATIONS
Polymerase chain reaction of nasopharyngeal swabs, often including other respiratory viruses, is commonly used, providing a rapid and sensitive diagnosis.
Serological diagnosis rests on demonstrating a change in titre between acute and convalescent samples and is not helpful in the acute period.
Coronavirus disease 2019 (COVID-19)
SIGNS / SYMPTOMS
Important to consider current epidemiological situation. May give history of unwell contacts.
Respiratory symptoms may be prominent.
INVESTIGATIONS
Real-time reverse transcription polymerase chain reaction (RT-PCR) is positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA.
Rapid antigen tests may also be used.
Enteric fever (typhoid infection)
SIGNS / SYMPTOMS
Most common on Indian subcontinent. Incubation period 1-3 weeks. Gradual onset of sustained fever. Rigors uncommon. Abdominal pain and headache common.
Relative bradycardia unreliable. May have a blanching erythematous maculopapular rash (rose spots).
INVESTIGATIONS
Isolation of SalmonellaTyphi (or Salmonella entericaserovar Typhi) or SalmonellaParatyphi in blood, stool, or urine cultures. Occasionally bone marrow culture is necessary.
The Widal test is widely used but has poor sensitivity and specificity.
Pyogenic infection
SIGNS / SYMPTOMS
Focal symptoms and signs depend on site affected. May also have prominent systemic symptoms with Group A streptococcal infection or pyelonephritis.
INVESTIGATIONS
Neutrophilia and markedly elevated CRP. Investigations depend on site affected.
Leptospirosis
SIGNS / SYMPTOMS
Conjunctival congestion may be helpful if present. Symptoms and signs of meningitis may be present (e.g., headache, neck stiffness, photophobia). Weil's disease is a syndrome of hepatosplenomegaly with jaundice, bleeding diatheses, and renal failure.
INVESTIGATIONS
Detection of specific IgM response by the end of the first week of the illness. Polymerase chain reaction may also be useful.
Isolation of leptospires from blood or cerebrospinal fluid requires special media and is not routinely done.
Infectious mononucleosis
SIGNS / SYMPTOMS
Clinical syndrome usually caused by Epstein Barr virus.
Characterised by fever, pharyngitis, and lymphadenopathy in older children and young adults.
INVESTIGATIONS
Peripheral lymphocytosis seen in 70% of cases.[99] Lymphocytes appear atypical on blood film.
Heterophile antibodies positive in 90% at some point, but false positives occur.
Serology for specific antibodies is widely available and is highly sensitive and specific.
HIV seroconversion
SIGNS / SYMPTOMS
History of unprotected sexual contact or sexually acquired infection. Lymphadenopathy and widespread erythematous rash.
INVESTIGATIONS
HIV combined antibody/antigen test positive (may be negative in window period).
Leukopenia common.
Amoebic liver abscess
SIGNS / SYMPTOMS
Preceding history of dysentery in fewer than 50% of patients. More common in young males.
Right upper quadrant pain, possibly referred to the right shoulder. Tender hepatomegaly and right pleural effusion present.
INVESTIGATIONS
Neutrophilia and elevated alkaline phosphatase.
Serology helpful.
Stool microscopy may show Entamoeba cysts. Aspirated material contains trophozoites, and polymerase chain reaction is sensitive.
Abdominal ultrasound or CT will demonstrate abscess.
Chest x-ray may show pleural effusion.
African trypanosomiasis (sleeping sickness)
SIGNS / SYMPTOMS
History of a tsetse fly bite.
Detection of a chancre at the site of the bite, and enlarged lymph nodes. There may be a patchy erythematous rash.
INVESTIGATIONS
Microscopy indicates the presence of trypomastigotes in peripheral blood, lymph node aspirates, or cerebrospinal fluid.
Rickettsial infection
SIGNS / SYMPTOMS
May have a history of a tick bite or of spending time on safari.
Headache is prominent. May have an eschar or rash.
INVESTIGATIONS
Possible leukopenia and/or abnormal LFTs.
IgM antibody rapid tests are useful, as is polymerase chain reaction of buffy coat. Positive serology, but results will not be available in real time.
Legionnaires' disease
SIGNS / SYMPTOMS
Acquired by inhalation of aerosolised bacteria or, rarely, microaspiration of contaminated drinking water.
Presentation includes respiratory symptoms such as cough (may not be productive) and shortness of breath, fever, chills, and chest pain. Other symptoms include headache, nausea, vomiting, abdominal pain, or diarrhoea.
INVESTIGATIONS
Sputum Gram stain may show gram-negative rods suggestive of Legionella species.
Cultures of lower respiratory tract secretions, pleural fluid, lung, blood, or extrapulmonary tissue or fluids show positive growth of Legionella species.
Chest x-ray shows a lobar infiltrate.
Pulmonary tuberculosis
SIGNS / SYMPTOMS
Recent travel to endemic area, exposure to tuberculosis-infected person.
INVESTIGATIONS
Sputum cultures with acid-fast bacilli stains positive, or polymerase chain reaction positive for Mycobacterium tuberculosis.
A cavity on the chest-x-ray may be observed.
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