Fever identi cation charts This document Visual summary A quick guide to dierentiation and diagnosis is designed to be printed on three in tropical and subtropical regions sheets of ordinary A4 Acute undifferentiated febrile illnesses (AUFIs) are characterised by fever of less than two weeks duration without organ-specific symptoms paper, which can be at the onset. This document provides an approach to the diagnosis of common AUFIs in children older than five years as well as in adults in mounted vertically low resource settings, with a focus on early recognition of the most severe non-malarial illnesses.

Local Disease Prevalence Asia North Africa South Africa East Africa West Africa Central Africa Latin America South and East Asia Australia and Oceania and Caribbean South-East Asia New Zealand Protozoal Malaria Limited risk Malaria Malaria Malaria Malaria Malaria Limited risk Malaria Malaria Parts of China Malaria Some countries East African Acute African West African Acute American trypanosomiasis trypanosomiasis trypanosomiasis trypanosomiasis Bacterial Enteric fever Enteric fever Enteric fever Enteric fever Enteric fever Enteric fever Enteric fever Enteric fever Brucellosis Brucellosis Brucellosis Brucellosis Brucellosis Brucellosis Brucellosis Brucellosis Q fever Meningococcal Meningococcal Meningococcal Oroya fever Melioidosis Melioidosis Melioidosis Melioidosis disease (epidemic) disease (epidemic) disease (epidemic) (Bartonellosis) Rickettsial Murine Typhus Murine Typhus Murine Typhus Murine Typhus Murine Typhus Murine Typhus Murine Typhus Murine Typhus Epidemic Typhus Scrub typhus Scrub typhus Scrub typhus Australian tick typhus African tick bite fever African tick bite fever African tick bite fever African tick bite fever Q fever Mediterranean Rocky Mountain In Asia, Scrub typhus is more spotted fever spotted Fever common than Murine typhus Spirochetal Leptospirosis Leptospirosis Leptospirosis Leptospirosis Leptospirosis Leptospirosis Leptospirosis Leptospirosis Leptospirosis Tick/louse-borne African tick bite fever Tick-borne Tick-borne relapsing fever relapsing fever relapsing fever Q fever Arboviruses No yellow fever risk, Dengue Dengue Dengue Dengue Dengue Dengue Dengue Dengue limited risk of other Chikungunya Chikungunya Chikungunya Chikungunya Chikungunya Chikungunya Chikungunya(limited) Chikungunya arboviral infections Zika Zika Zika Zika Zika Yellow fever Yellow fever Yellow fever Ross River virus Ross River virus Other viruses Crimean-Congo Crimean-Congo Crimean-Congo Hantavirus Crimean-Congo Crimean-Congo Hemorrhagic Fever Hemorrhagic Fever Hemorrhagic Fever pulmonary syndrome Hemorrhagic Fever Hemorrhagic Fever Rift valley fever Ebola Ebola Hemorrhagic fever Kyasanur Forest Hemorrhagic fever with renal syndrome disease with renal syndrome Lassa Marburg Other viral Hantavirus hemorrhagic fevers: Junin, Machupo, Sabia, Guanarito Helminthic Filariasis Filariasis Filariasis Filariasis Filariasis Filariasis Filariasis Filariasis Filariasis Acute schist- Acute schist- Acute schist- Acute schist- Acute schist- Acute schist- Acute schist- Acute schist- osomiasis osomiasis osomiasis osomiasis osomiasis osomiasis osomiasis (SE Asia) osomiasis TrichinosisDRAFTTrichinosis Trichinosis

DRAFT Clinical features of common and important causes of Legend Non-severe disease acute undi erentiated febrile illnesses Severe disease

Frequency of Occurrence Rare Uncommon Occasional Common Arbitrary cut-offs <5% 6–10% 10–30% >30%

Malaria Enteric fever Scrub typhus Leptospirosis Dengue

Rash Rash suggests alternative diagnosis

Eschar

Jaundice

Conjunctival suffusion

Lymphadenopathy Lymphadenopathy suggests alternative diagnosis Signs on examination Muscle tenderness

Enlarged spleen

Dyspnoea

Encephalopathy

Acute renal failure

Shock

Systemic complications Bleeding

White blood cell Normal High Normal High Normal High Normal High Normal Low count or low or low or low Thrombocytopenia (< 150,000) Diagnostics DRAFT

DRAFT Excluders and predictors in clinical ndings and basic laboratory tests Rule out features Rash and lymphadenopathy Generalised rash or Fever >12 days, combination Presence of these features generalised lymphadenopathy of normal tourniquet test and suggest alternative normal leucocyte count diagnosis (LR- 0.12) Rule in features Fever >40 degrees. Fever in endemic areas >3 Eschar virtually Combination of suffusion, Leukopenia and Associated with an Splenomegaly, days duration & presence pathognom onic for scrub icterus and conjunctival thrombcytopenia. Positive increase in probability thrombocytopenia and of abdominal tenderness is typhus (OR 46). Eschar seen hemorrhage is characteristic tourniquet test is a good of disease hyperbilirubinemia are associated with moderate in 17–86% of patients in of leptospirosis. predictor of infection (OR: associated with moderate to increase in probability of recent series 4.86) and ascites is a good large increase in probability disease predictor of severe dengue of disease (OR:13.91)

Con rming a diagnosis Serological tests based on antibody detection are confirmatory only on demonstration Accuracy and interpretation of speci c tests of fourfold rise in titre in IgG or seroconversion in IgM in paired specimens

Rapid tests Malarial antigen test Antibody test Specific Immunoglobulin Immunoglobulin M test NS1 antigen test Request malarial testing (ICT format) Sensitivity 47-98% M test (ICT format) Sensitivity 13-22% in 1st week Sensitivity 66% 2-4 hours Minutes and routine blood tests Sensitivity 95% Specificity 58-100% Sensitivity 66% Rapid ~60% in 2nd week Specificity 98% in all patients Specificity 95% Minutes Specificity 92% ~80% afterward for P. falciparum Specificity low Immunoglobulin M test ELISA for specific Hours Sensitivity 83% Immunoglobulin M using Minutes recombinant antigens Specificity 86% Sensitivity variable $$ Medium Specificity 90-100%

Confirmatory tests Microscopy Culture Immunofluorescent or Microscopic agglutination Culture The results of blood Detects as Sensitivity 40-87% Immunoperoxidase assay test for antibody Sensitivity ~40% 20-30 Minutes 3-6 days for antibodies 1-2 weeks culture or serological few as 5-10 Specificity 100% Sensitivity 41% in 1st week Specificity 100% parasites per 82% in 2nd-4th week $$$ Expensive tests may confirm the $ Inexpensive Sensitivity variable μl of blood Specificity variable diagnosis and guide Widal test (100% with paired specimens) $$$ Expensive Nucleic acid amplification further therapy Sensitivity depends on local $$$ Expensive prevalence Sensitivity 60-100% Nucleic acid amplification Same day Specificity 100% (paired specimens) Weil-Felix Test Specificity >95% Specificity >95%, even in 1st week $$$ Expensive $ Inexpensive Sensitivity variable $$$ Expensive high (paired specimens) Specificity Serology low (single specimens) Culture Specificity 100% $ Inexpensive Retrospective Sensitivity low Very slow in severe cases Medium Specificity 100% $$ $$$ Expensive

Malaria Enteric fever Scrub typhus Leptospirosis Dengue

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DRAFT