Malaria vs dengue on the topics of investigation needed to diagnosis, signs symptoms
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Malaria vs Dengue: Clinical Comparison
Overview
Both are tropical mosquito-borne febrile illnesses that can present similarly at onset, making distinction challenging in the early stages. The key differences lie in their vectors, causative agents, clinical progression, and diagnostic approach.
| Feature | Malaria | Dengue |
|---|---|---|
| Pathogen | Plasmodium spp. (protozoan parasite) | Dengue virus serotypes 1-4 (Flavivirus) |
| Vector | Female Anopheles mosquito | Aedes aegypti (mainly), Aedes albopictus |
| Biting time | Night-biting | Day-biting |
| Incubation | 7-30 days (varies by species) | 4-10 days |
Signs and Symptoms
Malaria
General (all species):
- Fever - classic and most prominent symptom; may be continuous early on
- Headache (sensitivity >95% alongside fever in low-endemicity areas)
- Myalgias and arthralgias
- Nausea, vomiting, diarrhea
- Fatigue and malaise
- Splenomegaly (with repeated or prolonged infection)
- Anemia (pallor, fatigue - from RBC destruction)
Classic periodicity (species-dependent):
- P. vivax and P. ovale: paroxysmal fevers every 48 hours (tertian)
- P. malariae: paroxysms every 72 hours (quartan)
- P. falciparum: often continuous/irregular fever, no classic periodicity
Severe/Complicated Malaria (mainly P. falciparum):
- Cerebral malaria: altered consciousness, coma, seizures
- Hyperparasitemia (>5% parasitised RBCs)
- Hypoglycemia (parasite metabolic activity + quinine effect)
- Lactic acidosis
- Acute renal failure
- Acute Respiratory Distress Syndrome (ARDS)
- Severe anaemia
- Disseminated intravascular coagulation (DIC)/coagulopathy
- Jaundice (hepatic involvement)
- Blackwater fever (massive haemolysis + haemoglobinuria - dark urine)
- Rosen's Emergency Medicine, p. 2660; Washington Manual of Medical Therapeutics, p. 571
Dengue
Dengue is classified into 3 severity phases (WHO 2009):
Phase 1 - Febrile Phase (Days 1-3):
- Abrupt high fever (2-7 days)
- Severe headache
- Retro-orbital pain (pain behind the eyes - characteristic)
- Severe myalgias and arthralgias ("breakbone fever")
- Facial erythema and injected oropharynx
- Macular or maculopapular rash
- Leukopenia (early)
- Petechiae or minor bleeding
- Nausea and vomiting
Phase 2 - Critical Phase (Days 3-7, around defervescence):
- Sudden drop in fever (defervescence) - can falsely appear as improvement
- Increased vascular permeability - plasma leakage
- Rising haematocrit (haemoconcentration)
- Thrombocytopenia (rapid platelet decline)
- Warning signs (need hospitalisation):
- Abdominal pain or tenderness
- Persistent vomiting
- Fluid accumulation (ascites, pleural effusion)
- Mucosal bleeding (gum bleeding, epistaxis, haematemesis)
- Lethargy/restlessness
- Liver enlargement >2 cm
- Rapid decline in platelet count with rising haematocrit
Phase 3 - Severe Dengue:
- Dengue haemorrhagic fever (DHF): severe plasma leakage leading to shock
- Dengue shock syndrome (DSS): hypotension, circulatory collapse
- Severe bleeding (internal or external)
- Severe organ involvement: AST/ALT ≥1000 IU/L, impaired consciousness, cardiac failure
- Less common: myocarditis, pancreatitis, meningoencephalitis, haemophagocytic lymphohistiocytosis
- Red Book 2021 (Committee on Infectious Diseases), p. 520-521; Washington Manual, p. 570; Robbins & Cotran Pathologic Basis of Disease, p. 336
Key Distinguishing Clinical Features
| Feature | Malaria | Dengue |
|---|---|---|
| Fever pattern | Cyclical/paroxysmal (esp. vivax, ovale) | Continuous high fever then sudden defervescence |
| Retro-orbital pain | Absent | Present - characteristic |
| Rash | Usually absent | Maculopapular rash common |
| Muscle/bone pain | Moderate | Severe ("breakbone fever") |
| Bleeding | Rare (DIC in severe falciparum) | Common in severe dengue (DHF) |
| Jaundice | Can occur | Less common |
| Anaemia | Prominent (haemolytic) | Mild if present |
| Splenomegaly | Common | Less prominent |
| Plasma leakage/shock | Rare | Hallmark of severe dengue (DSS) |
| Neurological | Cerebral malaria (falciparum) | Rare encephalitis |
Investigations
Malaria
First-line/Gold Standard:
-
Peripheral blood smear (thick and thin films) - stained with Giemsa or Wright stain
- Thick film: increased sensitivity for detecting parasites (screening)
- Thin film: species identification and parasitaemia quantification
- Serial smears every 12-24 hours if initial smear is negative (parasitaemia may be low early)
- Diagnose based on intraerythrocytic morphology
-
Rapid Diagnostic Tests (RDTs) - e.g., Alere BinaxNOW
- Antigen-based (detects Plasmodium-specific antigens, including HRP-2 for P. falciparum)
- Qualitative, available for ~$5 per test
- Faster but less sensitive than microscopy; a positive RDT must always be confirmed with microscopy for species identification and severity assessment
Supporting investigations:
3. FBC (Full Blood Count): normocytic anaemia, thrombocytopenia, leukopenia or normal WBC
4. Blood glucose: hypoglycaemia common in severe falciparum
5. Renal function (U&E, creatinine): renal failure in severe disease
6. Liver function tests (LFTs): elevated bilirubin, transaminases
7. Lactate: lactic acidosis in severe malaria
8. Coagulation profile (PT, APTT, fibrinogen): DIC screening
9. Blood cultures: to exclude concurrent bacteraemia
10. PCR (molecular testing): most sensitive for species identification and drug resistance; used when smear is negative but malaria still suspected
11. G6PD enzyme assay: required before giving primaquine (for P. vivax/ovale)
12. Urinalysis: haemoglobinuria in blackwater fever
13. Chest X-ray: if ARDS suspected
- Rosen's Emergency Medicine, p. 2661; Washington Manual, p. 571
Dengue
Timing of tests is critical - different tests are useful at different phases:
| Test | When useful | Notes |
|---|---|---|
| RT-PCR (viral RNA) | Days 1-7 (febrile phase) | Most sensitive early; detects virus directly |
| NS-1 antigen (ELISA) | Days 1-7 (febrile phase) | Detects non-structural protein 1; available as rapid test |
| IgM antibody (ELISA) | From Day 3-5 onwards | >99% positive by Day 10; peaks at 2 weeks |
| IgG antibody | Convalescent phase | Lifelong elevation; fourfold rise between acute and convalescent (≥15 days) confirms diagnosis |
Practical approach:
- Single specimen in first 10 days: test both NS-1 antigen AND IgM - identifies ≥90% of primary and secondary cases
- PCR: most specific and useful in first 5 days
- Note: IgM and IgG can cross-react with other flaviviruses (Zika, West Nile, yellow fever, Japanese encephalitis) - interpret with clinical context
Supporting/monitoring investigations:
- FBC: leukopenia (early), then rapid thrombocytopenia (platelet count is the key monitoring parameter)
- Haematocrit/PCV: rising haematocrit = haemoconcentration = plasma leakage = progression to severe dengue
- LFTs: ALT/AST elevation; ≥1000 IU/L = criterion for severe dengue
- Tourniquet test (Rumpel-Leede): inflate BP cuff midway between systolic and diastolic for 5 min; ≥10-20 petechiae per sq. inch = positive; simple, bedside test used in resource-limited settings
- Blood glucose and electrolytes
- Chest X-ray / Ultrasound abdomen: to detect pleural effusion and ascites (plasma leakage)
- Coagulation studies (PT/APTT): if significant bleeding
- Blood cultures: to exclude bacterial co-infection
- Red Book 2021, p. 522-523; Washington Manual, p. 570
Summary Comparison Table: Investigations
| Investigation | Malaria | Dengue |
|---|---|---|
| Definitive test | Peripheral blood smear (Giemsa-stained) | RT-PCR or NS-1 antigen (Days 1-7) |
| Rapid bedside test | RDT (antigen-based, e.g., BinaxNOW) | NS-1 rapid antigen test; Tourniquet test |
| Serology | Not routinely used for acute diagnosis | IgM (Day 3+), IgG (convalescent) |
| FBC | Anaemia, thrombocytopenia, normal/low WBC | Leukopenia then thrombocytopenia |
| Key monitoring parameter | Parasitaemia % on smear | Platelet count + haematocrit trend |
| Glucose | Low (hypoglycaemia - severe falciparum) | Usually normal |
| Liver function | Bilirubin raised (haemolysis) | AST/ALT raised (hepatitis) |
| Renal function | Creatinine raised in severe disease | Usually preserved |
| PCR | Species ID and drug resistance | Serotype ID, Days 1-5 |
| Specific pre-treatment test | G6PD assay (before primaquine) | Not required |
| Imaging | CXR (ARDS) | Ultrasound/CXR for effusions and ascites |
Important Caveats
- Concurrent infection: malaria and dengue can co-exist in endemic areas - one diagnosis does not exclude the other
- Cross-reactivity: dengue serology can cross-react with Zika, West Nile, yellow fever, and Japanese encephalitis viruses
- Travel history is essential for both diagnoses - the specific region of travel influences pre-test probability
- Serial smears: if initial malaria smear is negative but malaria is clinically suspected, repeat every 12-24 hours for 48-72 hours before excluding the diagnosis
- Dengue defervescence trap: patients can appear to improve when the fever breaks on days 3-5, but this marks the start of the dangerous critical phase - close monitoring is needed
Hiv and aids
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HIV and AIDS: Comprehensive Overview
1. What is HIV vs AIDS?
HIV (Human Immunodeficiency Virus) is a retrovirus that targets and destroys CD4+ T-lymphocytes (helper T-cells), progressively dismantling cell-mediated immunity.
AIDS (Acquired Immunodeficiency Syndrome) is the end-stage of HIV infection, defined as:
- CD4+ T-cell count <200 cells/µL (normal: 500-1500 cells/µL), OR
- The development of one or more AIDS-defining conditions regardless of CD4 count
HIV attaches to the CD4 receptor on T-helper lymphocytes, infects them, and uses reverse transcriptase to convert its RNA genome into DNA, integrating into the host cell nucleus. This allows the virus to replicate and gradually deplete CD4+ T-cells, leaving the body unable to fight opportunistic infections and certain cancers.
- Kanski's Clinical Ophthalmology, p. 488; Sherris & Ryan's Medical Microbiology, p. 739
2. Transmission
| Route | Details |
|---|---|
| Sexual contact | Most common globally; receptive anal intercourse carries highest risk |
| Blood-to-blood | Sharing needles/syringes (injection drug use), blood transfusions |
| Mother-to-child (vertical) | In utero, during delivery, or via breastfeeding; ART reduces risk to <1% |
| Occupational | Needlestick or mucocutaneous exposure (healthcare workers) |
| Not transmitted | Airborne, casual contact, sharing utensils, mosquitoes |
HIV is present in blood, semen, vaginal secretions, breast milk, tears, and saliva. Transmission risk is highest during the first 3 months of infection when viral load peaks and patients are often unaware they are infected.
- Essentials of Forensic Medicine and Toxicology, p. 153
3. Stages of HIV Infection and Clinical Features
Stage 1: Acute Retroviral Syndrome (Primary HIV Infection)
- Occurs 2-4 weeks after exposure
- 50-90% of patients develop symptoms
- Resembles infectious mononucleosis ("mono-like illness")
Symptoms (present in >50% of symptomatic patients):
- Fever (most common)
- Fatigue
- Maculopapular rash (trunk and upper body)
- Headache
- Lymphadenopathy (generalised)
- Pharyngitis / sore throat
- Myalgia and arthralgia
- Nausea, vomiting, diarrhoea
- Weight loss
Less common but distinctive:
- Painful mucocutaneous ulcerations (oral mucosa, anus, penis, oesophagus) - shallow and sharply demarcated
This phase corresponds to an initial explosive rise in viral load (often >100,000 copies/mL) and a transient drop in CD4 count. Symptoms resolve spontaneously within 2-4 weeks.
Stage 2: Clinical Latency (Asymptomatic / Chronic HIV)
- Average duration: 8-10 years (without treatment)
- Patient may appear well but the virus continues replicating and CD4 count slowly falls
- May have Persistent Generalised Lymphadenopathy (PGL) - enlarged lymph nodes in ≥2 extra-inguinal sites lasting >3 months without other explanation
- Minor recurrent infections may appear (oral candidiasis, recurrent herpes, seborrhoeic dermatitis)
- Without ART, about 50% progress to AIDS within 10 years
Stage 3: Symptomatic HIV (Pre-AIDS)
As CD4 count falls (typically 200-500 cells/µL), increasing infections appear:
- Oral candidiasis (thrush)
- Hairy leukoplakia (white corrugated patches on tongue - EBV-related)
- Recurrent bacterial pneumonias
- Herpes zoster (shingles) - often multidermatomal
- Chronic diarrhoea and weight loss
- Peripheral neuropathy
- Cervical intraepithelial neoplasia (CIN)
Stage 4: AIDS (CD4 <200 cells/µL or AIDS-defining illness)
AIDS-Defining Conditions (CDC Classification)
Opportunistic Infections:
| Infection | CD4 threshold | Key Features |
|---|---|---|
| Pneumocystis jirovecii pneumonia (PCP) | <200 | Progressive dyspnoea, dry cough, hypoxia; classic "ground-glass" on CXR |
| Oesophageal candidiasis | <200 | Dysphagia, odynophagia |
| Cytomegalovirus (CMV) retinitis | <50 | "Pizza pie" retinopathy; can cause blindness |
| Cryptococcal meningitis | <100 | Headache, neck stiffness, raised ICP; accounts for AIDS-defining illness in 40-60% of patients at AIDS diagnosis |
| Toxoplasma encephalitis | <100 | Focal neurological deficits, ring-enhancing lesions on CT/MRI |
| Mycobacterium avium complex (MAC) | <50 | Fever, night sweats, diarrhoea, hepatosplenomegaly |
| Cryptosporidiosis | <200 | Chronic profuse watery diarrhoea (>1 month) |
| M. tuberculosis | Any CD4 | Cough, fever, night sweats, weight loss; extrapulmonary TB common |
| Herpes simplex (chronic) | <200 | Ulcers >1 month |
| Progressive multifocal leucoencephalopathy (PML - JC virus) | <200 | Focal neurological deficits, dementia |
AIDS-Defining Malignancies:
- Kaposi sarcoma (HHV-8): purple/brown skin lesions, mucosal and visceral involvement
- Non-Hodgkin lymphoma (especially primary CNS lymphoma and Burkitt lymphoma - EBV-related)
- Invasive cervical carcinoma (HPV-related)
Other AIDS-defining conditions:
- HIV wasting syndrome: involuntary weight loss >10% body weight + chronic diarrhoea or fever >30 days
- HIV encephalopathy (AIDS dementia complex): cognitive impairment, motor dysfunction, behavioural changes
- Recurrent Salmonella septicaemia
- Kanski's Clinical Ophthalmology, p. 488; Cummings Otolaryngology, p. 323; Sherris & Ryan's Medical Microbiology, p. 739
4. Investigations
Diagnostic Testing (Confirming HIV Infection)
A. 4th-Generation Combination Immunoassay (HIV Ag/Ab combo test) - First-line recommended
- Detects both HIV-1/2 antibodies AND p24 antigen simultaneously
- Can detect HIV as early as 18 days after infection (window period much shorter than older tests)
- Sensitivity: 99-100%; Specificity: 98-100%
- Older ELISA and Western blot tests have a longer window period and are no longer recommended as first-line
B. HIV Viral Load (HIV RNA PCR)
- Detects viral RNA in plasma
- Detectable as early as 11 days after infection
- Patients with acute retroviral syndrome typically have viral loads >100,000 copies/mL
- A false-positive result should be suspected if viral load is <10,000 copies/mL
- Sensitivity: 95-98%
- Essential for: confirming acute HIV when antibody test is negative/indeterminate, monitoring treatment response
C. CD4+ T-Cell Count
- Not a diagnostic test for HIV itself, but determines disease stage and immune status
- Guides when to start prophylaxis for opportunistic infections
- Key thresholds:
- <500: start ART if not already on it
- <200: AIDS diagnosis; start PCP prophylaxis (co-trimoxazole)
- <100: start MAC and toxoplasma prophylaxis
- <50: highest risk for CMV, MAC, PML
D. Confirmatory Testing Algorithm (CDC/WHO 2014 Recommended Flow)
- Screen with 4th-gen Ag/Ab combo test
- If reactive: differentiate HIV-1 vs HIV-2 with HIV-1/HIV-2 antibody differentiation immunoassay
- If antibody-indeterminate or negative but Ag positive: HIV-1 RNA NAT (viral load) to confirm acute infection
E. Genotype (Drug) Resistance Testing
- Recommended in ALL patients with newly diagnosed HIV - even before starting ART
- Transmission of drug-resistant HIV strains is well-documented
- Guides selection of effective ART regimen
Baseline Investigations at HIV Diagnosis
| Investigation | Purpose |
|---|---|
| CD4+ T-cell count | Stage disease, guide prophylaxis |
| HIV viral load (RNA PCR) | Baseline before ART; monitor response |
| FBC | Anaemia, thrombocytopenia, leukopenia (lymphopenia) |
| Renal function (U&E, creatinine, eGFR) | Baseline before tenofovir (nephrotoxic) |
| Liver function tests | Hepatitis co-infection, drug toxicity baseline |
| Hepatitis B serology (HBsAg, anti-HBs, anti-HBc) | Co-infection common; affects ART choice |
| Hepatitis C antibody | Co-infection (especially PWID) |
| Syphilis serology (VDRL/RPR + TPHA) | STI co-infection screen |
| Gonorrhoea/Chlamydia screen | STI screen |
| Cervical smear (women) | Cervical cancer screening (HPV-related CIN common) |
| Toxoplasma IgG | Latent infection status; prophylaxis planning if CD4 <100 |
| CMV IgG | Latent infection status |
| Tuberculin skin test (TST) / IGRA | Latent TB detection |
| Varicella-zoster IgG | Vaccination need assessment |
| Fasting glucose and lipid profile | Metabolic baseline before ART (metabolic complications) |
| Urinalysis | Proteinuria (HIV nephropathy) |
| Chest X-ray | Baseline; TB screening |
| Genotype resistance test | Before starting ART |
| HLA-B*5701 testing | Before using abacavir (hypersensitivity reaction risk) |
| Glucose-6-phosphate dehydrogenase (G6PD) | Before dapsone/primaquine for PCP prophylaxis |
Ongoing Monitoring on ART
| Test | Frequency |
|---|---|
| HIV viral load | At 4-8 weeks after ART start, then every 3-6 months. Goal: undetectable (<20-50 copies/mL) |
| CD4+ T-cell count | Every 3-6 months until stable; then annually |
| Renal function | Every 3-6 months (tenofovir monitoring) |
| Liver function | Every 3-6 months |
| Fasting lipids and glucose | Annually (metabolic ART complications) |
| Blood pressure | Each visit |
5. Treatment: Antiretroviral Therapy (ART)
ART is recommended for all HIV-positive individuals regardless of CD4 count, and should be started as soon as possible after diagnosis.
Drug Classes
| Class | Mechanism | Examples |
|---|---|---|
| NRTIs (Nucleoside/Nucleotide Reverse Transcriptase Inhibitors) | Block reverse transcriptase (chain terminators) | Tenofovir (TDF/TAF), Emtricitabine (FTC), Lamivudine (3TC), Abacavir (ABC), Zidovudine (AZT) |
| NNRTIs (Non-Nucleoside RTIs) | Allosteric inhibition of reverse transcriptase | Efavirenz, Nevirapine, Rilpivirine, Doravirine |
| PIs (Protease Inhibitors) | Block viral protease; prevent maturation | Darunavir, Atazanavir (boosted with ritonavir or cobicistat) |
| INSTIs (Integrase Strand Transfer Inhibitors) | Block integration of viral DNA into host genome | Dolutegravir, Bictegravir, Raltegravir, Cabotegravir |
| Fusion/Entry Inhibitors | Block viral entry into CD4 cells | Enfuvirtide (T-20), Maraviroc (CCR5 antagonist), Ibalizumab (CD4 antagonist) |
| Capsid Inhibitor | Disrupts viral capsid assembly | Lenacapavir |
Standard First-line Regimen
Typically 2 NRTIs + 1 INSTI (preferred due to high potency, good tolerability, high barrier to resistance):
- Bictegravir/Tenofovir alafenamide/Emtricitabine (Biktarvy) - single tablet daily
- Dolutegravir + Tenofovir + Emtricitabine or Dolutegravir + Abacavir + Lamivudine (requires HLA-B*5701 negative)
- Two-drug regimen: Dolutegravir + Lamivudine (for treatment-naive patients with HIV RNA <500,000 copies/mL who are hepatitis B-negative)
Goal of ART
Suppress viral load to undetectable levels (<50 copies/mL). This:
- Prevents disease progression and AIDS
- Restores immune function (CD4 count rises)
- Prevents transmission (U=U: Undetectable = Untransmittable)
- Reduces AIDS-defining conditions and mortality
- Harrison's Principles of Internal Medicine 22E, p. 2041-2047; Sherris & Ryan's Medical Microbiology, p. 739
6. Prevention
| Strategy | Details |
|---|---|
| PrEP (Pre-Exposure Prophylaxis) | Tenofovir/Emtricitabine (Truvada) daily for HIV-negative high-risk individuals; reduces sexual transmission by ~90% |
| PEP (Post-Exposure Prophylaxis) | INSTI-based regimen started within 72 hours of exposure, for 28 days |
| PMTCT (Prevention of Mother-to-Child Transmission) | ART throughout pregnancy; reduces MTCT to <1% |
| Condom use | Reduces sexual transmission |
| Harm reduction | Needle exchange programs for PWID |
7. ART Complications (Important to Monitor)
- Immune Reconstitution Inflammatory Syndrome (IRIS): paradoxical worsening of existing opportunistic infections when immune system recovers after starting ART. Common with TB, cryptococcal meningitis, CMV, MAC
- Metabolic effects: lipodystrophy (fat redistribution), dyslipidaemia, insulin resistance, cardiovascular disease
- Bone effects: osteopenia, osteoporosis, osteonecrosis
- Renal toxicity: tenofovir disoproxil fumarate (TDF) can cause proximal tubular dysfunction and nephropathy
- Hepatotoxicity: especially with nevirapine
- Lactic acidosis: with older NRTIs (AZT, stavudine)
- Abacavir hypersensitivity: severe reaction in HLA-B*5701 positive patients - test before prescribing
- Sherris & Ryan's Medical Microbiology, p. 739; Harrison's Principles of Internal Medicine 22E
Summary: HIV vs AIDS at a Glance
| HIV Infection | AIDS | |
|---|---|---|
| Definition | Presence of HIV virus | CD4 <200 cells/µL OR AIDS-defining illness |
| CD4 count | Falling over years | <200 cells/µL |
| Symptoms | Acute syndrome then latency | Opportunistic infections, malignancies, wasting |
| Infectious | Yes | Yes (even higher risk during acute phase) |
| Treatable | Yes (ART) | Yes (ART + treat OIs) |
| Reversible to HIV? | N/A | Yes - CD4 can recover above 200 with ART |
| Life expectancy | Near-normal with ART | Reduced if untreated; near-normal if treated |
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