Baffling Viral and Protozoal Infections

📋 Key Information Summary

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Epstein-Barr virus (EBV) mononucleosis is the most common cause of the infectious mononucleosis syndrome in adolescents and young adults; >90% of Australian adults are seropositive. Diagnosis is clinical plus heterophile antibody (Monospot) testing and EBV-specific serology.
Cytomegalovirus (CMV) is the most common congenital infection in Australia (~0.7% of live births). In immunocompetent adults it typically causes a self-limiting mononucleosis-like illness; in immunocompromised patients it causes end-organ disease (retinitis, colitis, pneumonitis) requiring urgent antiviral therapy.
HIV should be considered in any patient presenting with seroconversion illness, recurrent infections, unexplained weight loss, or oral candidiasis. Fourth-generation Ag/Ab assays detect infection from ~2 weeks post-exposure. Rapid initiation of antiretroviral therapy (ART) is recommended regardless of CD4 count.
Malaria must be excluded in any returned traveller with fever (within 12 months of leaving an endemic area). Plasmodium falciparum malaria is a medical emergency — thick and thin blood films must be requested urgently and empirically if delays are expected.
Toxoplasmosis is usually asymptomatic in immunocompetent hosts but causes life-threatening cerebral abscesses in AIDS patients with CD4 <100 cells/µL and is a major teratogen in pregnancy (congenital toxoplasmosis).
EBV and CMV are both herpesviruses that establish lifelong latency and can reactivate, particularly in immunosuppressed patients (transplant recipients, chemotherapy, advanced HIV).
Post-exposure prophylaxis (PEP) for HIV must be commenced within 72 hours of exposure; the preferred regimen is tenofovir DF/emtricitabine + raltegravir (or dolutegravir) for 28 days.
Severe malaria (>5% parasitaemia, cerebral malaria, renal failure, pulmonary oedema) requires IV artesunate — available through Special Access Scheme (SAS) or state Tropical Public Health Units.
Congenital CMV screening is not routine in Australia; symptomatic neonates should be treated with oral valganciclovir for 6 months to improve hearing outcomes.
All four infections have significant Aboriginal and Torres Strait Islander health implications — higher rates of HIV diagnosis in some communities, remote access barriers to ART, and unique epidemiology of toxoplasmosis in tropical northern Australia.
HIV pre-exposure prophylaxis (PrEP) — tenofovir DF/emtricitabine (Truvada® or generic) — is PBS-listed and recommended for high-risk populations including men who have sex with men and people from high-prevalence settings.
Hepatosplenomegaly is a shared clinical feature of EBM, CMV, HIV acute seroconversion, and malaria — maintain a broad differential when this sign is present.

Introduction & Australian Epidemiology

Four infections — Epstein-Barr virus (EBV) mononucleosis, cytomegalovirus (CMV), HIV/AIDS, and the protozoal diseases malaria and toxoplasmosis — represent a clinically important group of "baffling" infections encountered in Australian general practice. They share overlapping clinical features including fever, lymphadenopathy, hepatosplenomegaly, atypical lymphocytosis, and transaminitis, which can make initial differentiation challenging. A structured approach to history-taking (exposure risk, travel, sexual health, immune status) and targeted laboratory investigation is essential to arrive at the correct diagnosis and initiate appropriate management.

Australian Burden of Disease

EBV: Over 90% of Australian adults have serological evidence of past EBV infection. Primary infection peaks in adolescence and early adulthood (15–25 years). Infectious mononucleosis accounts for approximately 1–3% of all GP presentations for sore throat in this age group. Indigenous Australians tend to acquire EBV earlier in childhood.
CMV: Seroprevalence in Australia ranges from ~50–60% in the general adult population to >80% in culturally diverse urban populations and Aboriginal and Torres Strait Islander communities. Congenital CMV affects approximately 1 in 150 live births (~2,000 babies/year in Australia), making it the leading infectious cause of sensorineural hearing loss and neurodevelopmental disability.
HIV: At the end of 2023, an estimated 29,460 people were living with HIV in Australia (Kirby Institute Annual Surveillance Report 2024). New diagnoses have plateaued at approximately 800–900 per year. Late diagnosis (>50% of CD4 <350 cells/µL at presentation) remains a concern, particularly among heterosexual individuals, Aboriginal and Torres Strait Islander peoples, and people born overseas. Australia is on track to meet UNAIDS 95-95-95 targets by 2030.
Malaria: Australia is malaria-free since 1981; however, approximately 600–800 imported cases are notified annually (National Notifiable Diseases Surveillance System). Most cases are acquired in Papua New Guinea, Indonesia, sub-Saharan Africa, and the Indian subcontinent. P. falciparum accounts for ~45% and P. vivax for ~40% of cases. A small number of locally acquired cases related to airport/ports have been documented.
Toxoplasmosis: Seroprevalence in Australia is approximately 20–30% in women of childbearing age. Congenital toxoplasmosis occurs in an estimated 50–100 pregnancies per year. In HIV/AIDS, toxoplasmic encephalitis (TE) typically presents when CD4 <100 cells/µL in patients not on effective ART or prophylaxis.

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Diagnostic pitfall: The combination of fever, pharyngitis, lymphadenopathy, and atypical lymphocytosis is not pathognomonic for EBV mononucleosis alone. CMV, acute HIV seroconversion, toxoplasmosis, and even early malaria can mimic this presentation. Always consider the full differential.

Epstein-Barr Virus Mononucleosis (EBM)

Pathophysiology

EBV (human herpesvirus 4) is transmitted primarily via salivary exchange ("kissing disease") and, less commonly, through blood transfusion, organ transplant, and sexual contact. The virus infects oropharyngeal epithelial cells and B lymphocytes, establishing lifelong latency in memory B cells. The characteristic lymphocytosis reflects a reactive polyclonal CD8+ T-cell expansion in response to infected B cells. The virus is intermittently shed in saliva for life.

Clinical Presentation

The classic triad of infectious mononucleosis comprises:

Fever (90–100%), often prolonged (1–2 weeks)
Pharyngitis / tonsillitis (80–90%), often severe with exudate
Cervical lymphadenopathy (especially posterior cervical, 80–90%)

Additional features include:

Hepatomegaly (10–15%) and/or splenomegaly (50–60%)
Fatigue — often profound and prolonged (weeks to months)
Periorbital oedema (Hoagland sign, ~30%)
Maculopapular rash (5–10% spontaneous; ~90% if amoxicillin/ampicillin given — this is NOT a true penicillin allergy)
Jaundice (5–10%)

Complications

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Splenic rupture: Although rare (~0.1–0.5%), splenic rupture is the most feared complication. Patients should avoid contact sports and strenuous activity for a minimum of 3–4 weeks (or until splenomegaly has resolved on imaging).

Airway obstruction from massive tonsillar enlargement (may require corticosteroids or surgical intervention)
Haemolytic anaemia (autoimmune, ~3%), thrombocytopenia (~25–50% mild)
Neurological: meningoencephalitis, Guillain-Barré syndrome, cranial nerve palsies (rare)
Hepatitis (transaminitis in 80%; fulminant hepatic failure extremely rare)
Post-transplant lymphoproliferative disorder (PTLD) in transplant recipients
Association with nasopharyngeal carcinoma and Burkitt lymphoma (long-term oncogenic potential)

Investigations

Essential Full blood count (FBC) with differential Atypical lymphocytes ≥10% of total lymphocytes on film is characteristic. Lymphocytosis >4.0 × 10⁹/L with >50% atypical lymphocytes is highly suggestive.

Essential Heterophile antibodies (Monospot®) Rapid latex agglutination test. Sensitivity ~85% in adults, lower in children <12 years (~25–50%). False negatives common in first week of illness. False positives in HIV, SLE, lymphoma.

Available EBV-specific serology panel VCA IgM (positive in acute infection), VCA IgG (positive, persists for life), EBNA IgG (negative in acute infection, positive 6–12 weeks post-infection). Interpretation: VCA IgM+/IgG+, EBNA IgG− = acute primary infection. MBS item 69410.

Available Liver function tests (LFTs) Transaminitis (AST/ALT 2–3× ULN) in 80% of cases. Bilirubin elevated in 5–10%.

Specialist EBV PCR (quantitative viral load) Reserved for immunocompromised patients, suspected PTLD, or atypical presentations. Not routine in immunocompetent hosts.

Available Ultrasound abdomen Assess splenic size if clinical concern or return-to-sport planning required.

Management

EBM in immunocompetent patients is self-limiting. No specific antiviral therapy is indicated. Management is supportive:

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Paracetamol

Panadol® · Panamax® · Analgesic-antipyretic

Adult dose 500–1000 mg PO QID PRN (max 4 g/day)

Paediatric dose 15 mg/kg PO QID PRN (max 60 mg/kg/day)

Route Oral

Duration As required for fever and pain

Renal adjustment eGFR 10–50: 500 mg QID; eGFR <10: 500 mg TDS

PBS status ✔ PBS General Benefit

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Prednisolone

Panafcortelone® · Redipred® · Corticosteroid

Adult dose 0.5–1 mg/kg/day PO for 5–7 days (for airway compromise or severe symptoms only)

Paediatric dose 1–2 mg/kg/day PO for 5–7 days

Route Oral

Duration 5–7 days; taper if used >7 days

Indication Airway compromise, severe tonsillar enlargement, severe fatigue. NOT routine.

PBS status ✔ PBS General Benefit

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Avoid contact sports for a minimum of 3–4 weeks or until splenomegaly resolves. No routine role for aciclovir, valaciclovir, or antivirals in immunocompetent EBM — antivirals reduce viral shedding but do not improve clinical outcomes.

Cytomegalovirus (CMV)

Pathophysiology

CMV (human herpesvirus 5) is transmitted via saliva, urine, breast milk, blood products, sexual contact, and vertically (transplacental or peripartum). Like EBV, it establishes lifelong latency in monocytes and myeloid progenitor cells. Reactivation is common in immunosuppression. Congenital CMV results from either primary maternal infection or reactivation during pregnancy, with first-trimester infection carrying the highest risk of severe fetal disease.

Clinical Presentation

Immunocompetent Hosts

Most primary infections are asymptomatic (~90%)
Symptomatic presentation: mononucleosis-like syndrome (fever, malaise, myalgia, lymphadenopathy) — clinically indistinguishable from EBM but Monospot-negative
Hepatitis with elevated transaminases (usually mild)
Atypical lymphocytosis present but tends to be less prominent than EBM
No pharyngitis or tonsillar exudate (helps differentiate from EBM)

Congenital CMV

~85–90% of infected neonates are asymptomatic at birth
Symptomatic neonates: petechiae/purpura, hepatosplenomegaly, jaundice, microcephaly, periventricular calcifications, sensorineural hearing loss (SNHL), chorioretinitis
Up to 15% of asymptomatic neonates develop SNHL by school age
Leading non-genetic cause of SNHL in Australian children

Immunocompromised Hosts (Transplant, HIV, Iatrogenic Immunosuppression)

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CMV disease in immunocompromised patients — retinitis, colitis, pneumonitis, encephalitis — is a medical emergency requiring immediate antiviral therapy. CMV pneumonitis in haematopoietic stem cell transplant (HSCT) recipients carries a mortality of 60–80% without treatment.

CMV retinitis: Presents with floaters, visual field defects, painless vision loss. Fundoscopy shows haemorrhagic retinal necrosis. Most common in HIV with CD4 <50 cells/µL.
CMV colitis: Diarrhoea (often bloody), abdominal pain, weight loss. Endoscopy shows ulceration with viral inclusions on biopsy.
CMV pneumonitis: Cough, dyspnoea, hypoxia, bilateral infiltrates. Particularly feared in HSCT recipients (usually occurs 5–13 weeks post-transplant).
CMV syndrome: Fever ≥38°C, malaise, neutropenia/lymphopenia, elevated LFTs + detectable CMV viraemia (most common manifestation in solid organ transplant recipients).

Investigations

Essential CMV IgM and IgG serology IgM positive in acute/recent infection. IgG positive indicates past infection (seropositive). IgG avidity testing helps distinguish recent from past primary infection in pregnancy. MBS item 69496.

Essential CMV quantitative PCR (viral load) Gold standard for monitoring CMV disease activity in immunocompromised patients. Used to guide initiation and duration of antiviral therapy. Thresholds vary by transplant type. MBS item 69492.

Available CMV pp65 antigenaemia assay Rapid detection of CMV in peripheral blood leucocytes. Largely replaced by PCR in most Australian centres.

Available Urine CMV PCR (neonatal) Urine or saliva PCR within first 3 weeks of life for diagnosis of congenital CMV. After 3 weeks, postnatal acquisition cannot be excluded.

Specialist Ophthalmology assessment Fundoscopy for CMV retinitis. Urgent in HIV patients with CD4 <50 cells/µL and visual symptoms.

Specialist CMV PCR on CSF, vitreous fluid, tissue biopsy Site-specific sampling as clinically indicated for end-organ disease confirmation.

Management

Immunocompetent Hosts

Supportive care only. No antiviral therapy is indicated. Self-limiting over 2–4 weeks.

Congenital CMV

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Valganciclovir

Valcyte® · Antiviral (nucleoside analogue)

Neonatal dose 16 mg/kg PO BD for 6 months (symptomatic congenital CMV with CNS involvement)

Duration 6 months (may improve hearing and neurodevelopmental outcomes)

Renal adjustment Dose per creatinine clearance; neonatal dosing weight-based

Key monitoring FBC weekly for 6 weeks (risk of neutropenia, thrombocytopenia), then fortnightly

PBS status ⚑ Authority Required

CMV Disease in Immunocompromised Patients

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Valganciclovir

Valcyte® · First-line for mild–moderate CMV disease

Adult dose 900 mg PO BD for 21 days (induction), then 900 mg PO daily (maintenance)

Renal adjustment eGFR 40–59: 450 mg BD; eGFR 25–39: 450 mg daily; eGFR 10–24: 450 mg 48-hourly; eGFR <10: not recommended — use IV ganciclovir

PBS status ⚑ Authority Required

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Ganciclovir IV

Cymevene® · First-line for severe/life-threatening CMV disease

Adult dose 5 mg/kg IV BD for 21 days (induction), then 5 mg/kg IV daily (maintenance)

Renal adjustment Dose reduce per eGFR: 2.5 mg/kg for eGFR 50–69; 1.25 mg/kg for eGFR 25–49; 0.625 mg/kg for eGFR 10–24

PBS status ⚑ Authority Required (hospital use)

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Foscarnet

Foscavir® · Second-line / ganciclovir-resistant CMV

Adult dose 90 mg/kg IV BD or 60 mg/kg IV TDS for 21 days (induction)

Key toxicity Nephrotoxicity, electrolyte derangement (hypocalcaemia, hypomagnesaemia, hypokalaemia), seizures

Renal adjustment Must adjust dose for renal impairment; use actual body weight

PBS status ✘ Not PBS (hospital/SAS use)

CMV Prophylaxis in Transplant Recipients

Australian transplant centres follow international guidelines for CMV prophylaxis (usually valganciclovir 900 mg PO daily for 3–6 months post-transplant depending on donor/recipient CMV serostatus). Pre-emptive therapy (treat when CMV PCR becomes positive on surveillance) is an alternative strategy used in low-risk patients.

HIV/AIDS — Clinical Stages, Seroconversion, and Management

Pathophysiology

HIV-1 (the predominant subtype in Australia) is transmitted via sexual contact (anal, vaginal, oral), parenteral exposure (sharing needles, blood transfusion), and vertical transmission (perinatal). The virus infects CD4+ T lymphocytes, macrophages, and dendritic cells via the CD4 receptor and CCR5/CXCR4 co-receptors. Without treatment, HIV causes progressive immunodeficiency over a median of 8–10 years, culminating in AIDS — defined by a CD4 count <200 cells/µL or the occurrence of an AIDS-defining illness.

Natural History and Clinical Stages

Stage 1

Acute HIV Seroconversion Illness

Occurs 2–4 weeks post-infection in 50–80% of patients. Resembles glandular fever: fever, maculopapular rash (trunk, palms, soles), lymphadenopathy, pharyngitis, malaise, myalgia, headache. May include oral ulcers, hepatosplenomegaly, aseptic meningitis. Lasts 1–3 weeks. Fourth-generation HIV Ag/Ab test may be negative — HIV RNA (viral load) will be positive and highly elevated.

Setting: Urgent assessment — window period considerations

Stage 2

Chronic HIV Infection (Clinical Latency)

Asymptomatic or persistent generalised lymphadenopathy (PGL). CD4 count typically 350–800 cells/µL. Duration: months to decades (median ~8 years without ART). Patients are infectious throughout this stage. This is the stage at which most asymptomatic infections are diagnosed through screening.

Setting: GP / sexual health clinic — initiation of ART

Stage 3

AIDS

CD4 <200 cells/µL or AIDS-defining illness. OI spectrum: Pneumocystis jirovecii pneumonia (PCP), cerebral toxoplasmosis, CMV retinitis, oesophageal candidiasis, Kaposi sarcoma, Mycobacterium avium complex (MAC), cryptococcal meningitis, primary CNS lymphoma, progressive multifocal leukoencephalopathy (PML), cervical cancer (invasive). Without ART, median survival from AIDS is ~12–18 months.

Setting: Hospital / specialist ID unit

Diagnosis

The Australian HIV testing algorithm uses fourth-generation Ag/Ab combination immunoassay as the initial test. If reactive, the laboratory performs a HIV-1/HIV-2 antibody differentiation assay and HIV-1 RNA (viral load). Point-of-care rapid tests (finger-prick, result in 10–30 minutes) are available at sexual health clinics and community testing sites but are screening tests only — reactive results require laboratory confirmation.

Essential Fourth-generation HIV Ag/Ab combination assay Detects HIV-1 p24 antigen and HIV-1/2 antibodies. Window period ~2 weeks. MBS item 69382.

Essential HIV-1 viral load (RNA PCR) Quantitative PCR used for confirmation in acute infection, treatment monitoring, and assessing viral suppression. MBS item 69432.

Essential CD4 T-cell count Baseline and serial monitoring. Guides OI prophylaxis and ART response.

Essential HIV genotypic resistance testing (RT + PR ± integrase) Baseline before ART initiation and at virological failure. Guides regimen selection.

Essential HIV subtyping (HIV-1 group, subtype, tropism) CCR5 tropism assay if considering maraviroc.

Available Baseline screening panel Syphilis serology, hepatitis B (HBsAg, anti-HBs, anti-HBc), hepatitis C antibody, CMV IgG, toxoplasma IgG, HLA-B*5701 (if considering abacavir), renal function, lipid profile, FBC, LFTs, fasting glucose/HbA1c.

Antiretroviral Therapy (ART)

Australian and international guidelines recommend ART initiation as soon as possible after diagnosis, regardless of CD4 count. Rapid ART initiation (within 7 days, ideally same day) is now standard of care at most Australian sexual health clinics and hospital-based HIV services. All ART regimens in Australia are PBS-listed under the Highly Specialised Drugs Program (Section 100).

First-Line Preferred Regimens (as per ASHM/IAS guidelines 2024)

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Bictegravir / Emtricitabine / Tenofovir alafenamide

Biktarvy® · INSTI-based single-tablet regimen

Adult dose 1 tablet PO daily (bictegravir 50 mg / emtricitabine 200 mg / TAF 25 mg)

Duration Lifelong (until cure strategies available)

Key advantages High barrier to resistance, well tolerated, no HLA-B*5701 testing required, renal-friendly (TAF)

Renal adjustment Not recommended if eGFR <30 mL/min (consider dolutegravir-based regimen with TDF substitution under specialist guidance)

PBS status ⚑ Authority Required — Section 100 (HSD)

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Dolutegravir / Lamivudine

Dovato® · Two-drug INSTI-based regimen

Adult dose 1 tablet PO daily (dolutegravir 50 mg / lamivudine 300 mg)

Eligibility Treatment-naïve, HIV RNA <500,000 copies/mL, no HBV co-infection, no known M184V resistance

Key advantage NRTI-sparing (avoids tenofovir toxicity). Increasingly preferred in Australia.

PBS status ⚑ Authority Required — Section 100 (HSD)

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Dolutegravir + Emtricitabine / Tenofovir DF

Tivicay® + Truvada® · Preferred when HBV co-infection or high viral load

Adult dose Dolutegravir 50 mg PO daily + emtricitabine 200 mg/tenofovir DF 300 mg PO daily

Indication HBV/HIV co-infection (TDF active against HBV), HIV RNA >500,000 copies/mL

Renal adjustment TDF: avoid if eGFR <60 unless no alternative. TAF may be substituted.

PBS status ⚑ Authority Required — Section 100 (HSD)

HIV Post-Exposure Prophylaxis (PEP)

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PEP must be commenced within 72 hours of exposure — ideally within 24 hours. Do not wait for source patient HIV test results. PEP is available at all Australian emergency departments and sexual health clinics. Preferred regimen: tenofovir DF/emtricitabine (Truvada®) + raltegravir (Isentress®) 400 mg BD or dolutegravir 50 mg daily for 28 days.

HIV Pre-Exposure Prophylaxis (PrEP)

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Tenofovir DF / Emtricitabine

Truvada® or generic · PrEP

Adult dose 1 tablet PO daily (or event-based dosing: 2 tablets 2–24 hours before sex, then 1 tablet daily for 2 days after last sexual act — MSM only)

Eligibility HIV-negative individuals at substantial risk: MSM, serodiscordant couples, people who inject drugs, sex workers

Monitoring HIV Ag/Ab, eGFR, HBV serology, STI screen at baseline, then every 3 months

PBS status ⚑ Authority Required

Opportunistic Infection (OI) Prophylaxis

OI	Threshold	Prophylaxis	Discontinuation
Pneumocystis jirovecii (PCP)	CD4 <200 cells/µL or CD4% <14%	TMP-SMX 80/400 mg PO daily or 160/800 mg PO three times/week	CD4 >200 for ≥3 months on ART
Toxoplasmosis	CD4 <100 cells/µL + Toxoplasma IgG positive	TMP-SMX 160/800 mg PO daily	CD4 >200 for ≥3 months
Mycobacterium avium complex (MAC)	CD4 <50 cells/µL	Azithromycin 1200 mg PO weekly	CD4 >100 for ≥3 months
Cryptococcus	CD4 <100 in high-prevalence areas	Fluconazole 200 mg PO daily (primary prophylaxis in high burden settings)	CD4 >100 for ≥3 months

ART Monitoring

Viral load at baseline, 4 weeks after starting/changing ART, then every 3–6 months
Target: HIV RNA <20 copies/mL (undetectable) by 24 weeks
CD4 count every 3–6 months until >350 cells/µL on ART for ≥2 years, then every 12 months
LFTs, renal function, lipids, FBC at baseline and every 6–12 months
Annual: STI screening (syphilis, gonorrhoea, chlamydia — NAAT from relevant sites), hepatitis C antibody (if risk factors), cervical screening (per national guidelines)
U=U (Undetectable = Untransmittable): People living with HIV who maintain viral suppression on ART for ≥6 months have effectively zero risk of sexually transmitting HIV. This is a key public health message.

Malaria & Toxoplasmosis

Malaria

Pathophysiology

Malaria is caused by Plasmodium species transmitted via the bite of infected female Anopheles mosquitoes. Five species infect humans: P. falciparum (most lethal), P. vivax (relapsing — hypnozoites in liver), P. ovale (relapsing), P. malariae (chronic), and P. knowlesi (zoonotic, Southeast Asia). Sporozoites invade hepatocytes → merozoites released → invade erythrocytes → asexual multiplication → haemolysis and cytokine release → fever paroxysms. P. falciparum causes severe malaria through sequestration of infected erythrocytes in microvasculature (brain, kidneys, lungs).

Clinical Presentation

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Any fever in a returned traveller is malaria until proven otherwise. Malaria can present weeks to months (even >12 months for P. vivax/ovale) after leaving an endemic area. Request urgent thick and thin blood films — do not wait for the result to commence empirical treatment if clinical suspicion is high.

Classic paroxysms: cold rigors → high fever (39–41°C) → drenching sweats (every 48–72 hours for P. vivax/ovale/malariae; irregular for P. falciparum)
Headache, myalgia, nausea, vomiting, diarrhoea, abdominal pain
Hepatosplenomegaly, jaundice, anaemia
Atypical presentations in semi-immune travellers or children may mimic viral illness

Severe Malaria Features (WHO Criteria)

Severe

Severe P. falciparum Malaria

Parasitaemia >5%, cerebral malaria (GCS <11, seizures), renal failure (creatinine >265 µmol/L), pulmonary oedema/ARDS, severe anaemia (Hb <50 g/L), hypoglycaemia (<2.2 mmol/L), metabolic acidosis (pH <7.2), DIC, jaundice + renal impairment (blackwater fever). Mortality 15–20% even with treatment.

Setting: ICU / tropical medicine unit — immediate IV artesunate

Diagnosis

Essential Thick and thin blood films (malaria parasites) Gold standard. Thick film for detection (higher sensitivity); thin film for speciation and parasitaemia quantification. Must be reported urgently. Repeat at 12–24 hours if initial films negative but clinical suspicion remains. MBS item 69314.

Essential Malaria rapid diagnostic test (RDT) Immunochromatographic test detecting HRP-2 (P. falciparum) and pLDH (all species). Sensitivity >95% for P. falciparum, lower for non-falciparum. Does NOT replace blood films — must send films regardless of RDT result. Available in most EDs.

Essential FBC, blood film, renal function, LFTs, glucose, lactate, coagulation Baseline severity assessment. Parasitaemia >5% = severe malaria. Thrombocytopenia is the most common laboratory abnormality in malaria.

Specialist PCR for Plasmodium species Referral laboratory (e.g., state public health laboratory). Useful for confirming species, detecting low-level parasitaemia, and identifying drug resistance markers. Sent by reference labs after initial diagnosis.

Treatment

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Chloroquine resistance: P. falciparum in nearly all regions is chloroquine-resistant. P. vivax is chloroquine-resistant in Papua New Guinea, Indonesia, and parts of Oceania — use ACT or mefloquine for P. vivax acquired in these areas. Always check current TGA/Austprescribe resistance maps.

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Artemether / Lumefantrine

Riamet® · ACT — first-line for uncomplicated P. falciparum

Adult dose 4 tablets (80/480 mg) PO at 0, 8, 24, 36, 48, 60 hours (total 24 tablets over 3 days)

Paediatric dose Weight-based: 5–14 kg — 1 tablet; 15–24 kg — 2 tablets; 25–34 kg — 3 tablets; ≥35 kg — 4 tablets per dose. Same schedule.

Key notes Must be taken with fatty food (increases lumefantrine absorption 16-fold). Avoid with CYP3A4 inhibitors.

PBS status ✔ PBS General Benefit (SAS/compassionate supply — not routinely stocked)

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Artesunate IV

Available via SAS / Tropical Public Health Unit · First-line for severe malaria

Adult dose 2.4 mg/kg IV at 0, 12, 24 hours, then daily until oral therapy tolerated (at least 24 hours)

Paediatric dose 2.4 mg/kg IV at 0, 12, 24 hours, then daily (same as adult)

Key advantage Reduces mortality by 35% compared to quinine in severe malaria (AQUAMAT trial). Preferred in Australia.

Key monitoring FBC for delayed haemolytic anaemia (post-artesunate delayed haemolysis, occurs 2–3 weeks post-treatment)

Access Contact state Tropical Public Health Unit or TGA Special Access Scheme (Category A)

PBS status ✘ Not PBS (SAS/hospital supply)

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Chloroquine

Chlorquin® · For uncomplicated chloroquine-sensitive P. vivax/ovale/malariae

Adult dose 600 mg base (1 g salt) PO immediately, then 300 mg base (500 mg salt) at 6, 24, and 48 hours (total 1500 mg base over 48 hours)

Paediatric dose 10 mg base/kg immediately, then 5 mg base/kg at 6, 24, and 48 hours (total 25 mg base/kg)

PBS status ✔ PBS General Benefit

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Primaquine

Hypo-rad® · Hypnozoite radical cure for P. vivax / P. ovale

Adult dose 30 mg base PO daily for 14 days (must check G6PD status before starting)

Paediatric dose 0.5 mg base/kg PO daily for 14 days

Key requirement G6PD testing mandatory — risk of severe haemolytic anaemia in G6PD deficiency. If G6PD deficient, discuss weekly supervised primaquine (0.75 mg/kg weekly for 8 weeks) with specialist.

PBS status ✔ PBS General Benefit

Toxoplasmosis

Pathophysiology

Toxoplasma gondii is an obligate intracellular protozoan with cats as the definitive host. Humans acquire infection via ingestion of oocysts (cat faeces, contaminated soil/vegetables), tissue cysts (undercooked meat, especially lamb and pork), or vertically (transplacental). After primary infection, bradyzoites form tissue cysts in muscle and brain, remaining dormant for life. Reactivation occurs in severe immunosuppression (CD4 <100 cells/µL in HIV).

Clinical Presentation

Immunocompetent: Usually asymptomatic. Cervical lymphadenopathy (single, non-tender node) is the most common finding. Low-grade fever, malaise. Self-limiting in weeks to months.
Pregnancy (congenital toxoplasmosis): Risk of vertical transmission increases with gestational age (10–15% in first trimester, ~70% in third trimester), but severity of fetal disease is greatest with first-trimester infection. Manifestations: hydrocephalus, intracranial calcifications, chorioretinitis, hepatosplenomegaly. Classic triad of chorioretinitis + hydrocephalus + intracranial calcifications.
HIV/AIDS (toxoplasmic encephalitis): Subacute onset of headache, confusion, focal neurological deficits (hemiparesis, ataxia), seizures, fever. Ring-enhancing lesions on CT/MRI (usually multiple, basal ganglia predilection). Almost always reactivation of latent infection in Toxoplasma IgG-positive patients with CD4 <100 cells/µL.

Diagnosis

Essential Toxoplasma IgG and IgM serology IgG positive = past infection (20–30% of Australians). IgM positive = acute/recent infection (can persist for >1 year — refer to reference laboratory for IgG avidity testing). MBS item 69515.

Specialist Toxoplasma IgG avidity (pregnancy) High avidity at <16 weeks' gestation effectively excludes primary infection in early pregnancy. Low avidity requires further workup. Available at reference laboratories (e.g., SA Pathology, Westmead).

Specialist CT/MRI brain with contrast For suspected TE in HIV. Multiple ring-enhancing lesions, often with surrounding oedema and mass effect. Basal ganglia involvement is characteristic. Biopsy may be needed if diagnosis uncertain or poor response to therapy.

Specialist PCR for Toxoplasma gondii (CSF, amniotic fluid, blood) CSF PCR sensitivity ~50% for TE. Amniotic fluid PCR for prenatal diagnosis of congenital toxoplasmosis (performed after 18 weeks' gestation).

Treatment

Toxoplasmic Encephalitis (HIV/AIDS)

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Pyrimethamine + Sulfadiazine + Folinic acid

Daraprim® + Sulphadiazine + Leucovorin® · First-line for TE

Adult dose Pyrimethamine 200 mg PO loading, then 50–75 mg PO daily + sulfadiazine 1–1.5 g PO QDS + folinic acid 10–25 mg PO daily

Duration Acute treatment: 6 weeks minimum. Maintenance (secondary prophylaxis): pyrimethamine 25–50 mg daily + sulfadiazine 2–4 g daily + folinic acid 10 mg daily until CD4 >200 for ≥6 months on ART.

Key monitoring FBC weekly (pyrimethamine causes folate antagonism — megaloblastic anaemia, neutropenia). Folinic acid is essential (NOT folic acid, which may reduce efficacy).

PBS status ⚑ Authority Required

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TMP-SMX (high dose)

Bactrim® DS · Alternative first-line for TE

Adult dose TMP 5 mg/kg + SMX 25 mg/kg PO/IV BD for 6 weeks

Key advantage Non-inferior to pyrimethamine-sulfadiazine (some evidence), more readily available, also covers PCP prophylaxis

PBS status ✔ PBS General Benefit

Congenital Toxoplasmosis (Pregnancy)

All pregnant women with suspected or confirmed primary toxoplasmosis should be referred urgently to a maternal-fetal medicine specialist and infectious diseases physician.

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Spiramycin

Rovamycine® · Reduce vertical transmission (before fetal infection confirmed)

Adult dose 1 g (3 MIU) PO BD or TDS (toxoplasmosis treatment dose for pregnancy)

Duration Continue until delivery if fetal infection not confirmed, or until 18 weeks' gestation then switch to pyrimethamine-sulfadiazine if fetal infection confirmed by amniotic fluid PCR

Note Not available via PBS. Obtained through TGA Special Access Scheme (Category A) or hospital pharmacies. Supplied by some compounding pharmacies.

PBS status ✘ Not PBS (SAS supply)

Empirical Therapy — The Febrile Returned Traveller

When a patient presents with fever and one or more of lymphadenopathy, hepatosplenomegaly, atypical lymphocytosis, or transaminitis, the following diagnostic approach guides empirical therapy:

Take a detailed exposure history

Travel (countries, dates, prophylaxis adherence), sexual history, blood exposures, contact with animals, unpasteurised dairy, undercooked meat, childcare attendance (CMV exposure).

Urgent investigations

FBC with film, Monospot, EBV serology, CMV serology, HIV Ag/Ab, thick/thin blood films (if travel exposure), LFTs, renal function, blood cultures. Do not delay malaria films.

If malaria films pending and high clinical suspicion

Commence empirical antimalarial therapy (artemether-lumefantrine for uncomplicated; IV artesunate for severe). Contact Tropical Public Health Unit or infectious diseases for guidance.

If acute HIV seroconversion suspected

HIV RNA (viral load) will be positive even if Ag/Ab assay is equivocal. Refer to sexual health or ID for urgent assessment. Discuss PEP if occupational/sexual exposure window.

Supportive care while awaiting results

Paracetamol, fluids, rest. Avoid NSAIDs if thrombocytopenia. Avoid amoxicillin (rash in EBV). Monitor for signs of deterioration (airway compromise, neurological features).

Monitoring & Follow-Up

Infection	Follow-Up	Key Parameters
EBM	Review at 1–2 weeks. Repeat FBC if cytopenias present. Return-to-sport clearance at 3–4 weeks (± ultrasound spleen).	Symptoms, FBC, LFTs, splenic size
CMV (immunocompetent)	Review at 2–4 weeks if symptomatic. Generally self-limiting.	LFTs, symptoms
CMV (immunocompromised)	CMV viral load every 1–2 weeks during treatment. Continue until undetectable. Monitor FBC for antiviral toxicity.	CMV PCR, FBC, renal function
HIV (on ART)	Viral load at 4 weeks, then every 3–6 months. CD4 every 3–6 months. Annual comprehensive metabolic panel.	HIV viral load, CD4, renal function, lipids, LFTs, FBC, HbA1c
Malaria	Repeat blood films at 48 hours and day 7. Monitor for post-artesunate delayed haemolysis (day 7, 14, 28 FBC). Follow up renal function if severe.	Parasitaemia clearance, FBC, renal function, G6PD (if primaquine planned)
Toxoplasmosis (TE)	Clinical and radiological reassessment at 2 weeks. MRI at 2–4 weeks. Maintain secondary prophylaxis until immune reconstitution on ART.	MRI brain, CD4 count, clinical response, FBC

Special Populations

🤰

Pregnancy

EBM

Self-limiting. Avoid corticosteroids unless life-threatening. Paracetamol safe. No antiviral needed.

CMV

Primary CMV in pregnancy — urgent referral to maternal-fetal medicine. Valganciclovir is teratogenic (Category D) and contraindicated. Hyperimmune globulin (CMV-HIG) use is controversial (only clinical trials or specialist decision). Amniocentesis at ≥21 weeks for CMV PCR on amniotic fluid if IgM positive.

HIV

ART is mandatory in all pregnant women living with HIV to prevent vertical transmission. Preferred regimens: DTG + TDF/FTC or DTG + 3TC (dolutegravir is safe in pregnancy from 2024 data). Viral load <50 copies/mL at delivery = <1% transmission risk. Elective caesarean section recommended if viral load >50 copies/mL near delivery. Neonatal zidovudine for 4 weeks post-delivery.

Malaria

Malaria in pregnancy carries high maternal and fetal mortality. Mefloquine or quinine + clindamycin for uncomplicated P. falciparum (artemisinin combinations generally avoided in first trimester but used in second/third trimester if severe). IV artesunate for severe malaria regardless of trimester. Doxycycline and primaquine are contraindicated.

Toxoplasmosis

Spiramycin to reduce transmission (before 18 weeks). Pyrimethamine-sulfadiazine + folinic acid after 18 weeks if fetal infection confirmed. Pyrimethamine is teratogenic in first trimester. Neonatal treatment if congenital toxoplasmosis confirmed.

👶

Paediatrics

EBM

Monospot sensitivity is lower in children <12 years (25–50%). EBV-specific serology preferred. Complications (airway obstruction) are more common in children. Corticosteroids for impending airway compromise.

Congenital CMV

Oral valganciclovir 16 mg/kg BD for 6 months in symptomatic neonates — improves hearing and neurodevelopmental outcomes (IMPACT trial). Audiological monitoring at 6-weekly intervals for first year, then every 6 months to age 6. Newborn hearing screening does NOT reliably detect CMV-related SNHL (may be delayed onset).

Paediatric HIV

Most paediatric HIV in Australia is perinatally acquired. ART should be initiated in ALL children living with HIV, regardless of CD4 or viral load. Preferred first-line: weight-banded lopinavir/ritonavir + abacavir + lamivudine (infants <3 years) or DTG-based regimen (children ≥20 kg). Transition to adult services at 16–18 years.

Malaria

Children are at higher risk of severe malaria (cerebral malaria, severe anaemia, hypoglycaemia). Weight-based dosing essential. IV artesunate first-line for severe malaria in children. Quinine is an alternative but has more adverse effects.

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Elderly

EBM

Atypical presentations are more common in older adults (less pharyngitis, more hepatitis). EBV reactivation may cause lymphoproliferative disorders. Consider PTLD in post-transplant elderly.

CMV

CMV seroprevalence increases with age. CMV reactivation may contribute to immunosenescence. Consider CMV colitis in elderly immunocompromised patients with unexplained diarrhoea.

HIV

Late diagnosis is more common in older adults (attributed to comorbidities). Polypharmacy is a major consideration with ART (drug interactions with CYP3A4 and UGT1A1 pathways). Increased risk of metabolic complications. Renal and hepatic dose adjustments frequently required.

Malaria

Higher mortality in older adults. More likely to present atypically (no classic paroxysmal fever pattern). Ensure renal dose adjustments. Beware of cardiac toxicity with IV quinine in elderly (QT prolongation).

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Renal Impairment

CMV antivirals

Ganciclovir and valganciclovir require dose reduction based on eGFR. Foscarnet is significantly nephrotoxic — requires aggressive pre-hydration and electrolyte monitoring.

HIV ART

TDF contraindicated if eGFR <60 (prefer TAF). Bictegravir/FTC/TAF (Biktarvy) not recommended if eGFR <30. DTG-based regimens preferred in severe renal impairment (no renal dose adjustment for DTG). Monitor renal function 4-weekly during the first year on TDF/FTC.

Malaria

Quinine requires dose reduction in renal failure (active metabolites accumulate). Artesunate does not require renal dose adjustment. Atovaquone-proguanil safety in severe renal impairment is not well established.

TMP-SMX

Avoid if eGFR <15–30 mL/min if high-dose required (TE treatment). Monitor potassium — hyperkalaemia risk. Dose reduce for PCP prophylaxis in CKD.

🫁

Hepatic Impairment

All infections

EBM and CMV commonly cause transaminitis — this is usually self-limiting. Monitor LFTs. Hepatitis B co-infection with HIV requires specific ART considerations (maintain TDF or TAF for HBV activity — risk of hepatitis flare if HBV-active agent withdrawn). Artesunate safe in mild–moderate hepatic impairment. Pyrimethamine-sulfadiazine: use with caution if significant hepatic dysfunction (sulfadiazine hepatotoxicity).

🛡️

Immunocompromised

EBV

Risk of EBV reactivation and PTLD in transplant recipients. Monitor EBV viral load in high-risk patients. Reduction of immunosuppression is the primary management strategy for PTLD. Rituximab for CD20+ PTLD.

CMV

Leading viral pathogen in transplant recipients. Pre-emptive therapy or prophylaxis is standard of care. CMV-specific T-cell immunity testing (QuantiFERON-CMV, ELISPOT) emerging for risk stratification.

HIV

Immune reconstitution inflammatory syndrome (IRIS) may occur 1–12 weeks after ART initiation — paradoxical worsening of known OIs or unmasking of subclinical infections. Most commonly associated with mycobacteria, cryptococcus, CMV, and PML. Continue ART; treat OI; corticosteroids if severe IRIS.

Toxoplasmosis

TE almost exclusively in severely immunocompromised patients (HIV CD4 <100, transplant). Secondary prophylaxis required until immune reconstitution. TMP-SMX is the preferred prophylactic agent.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Aboriginal and Torres Strait Islander peoples experience disproportionate burden from several of these infections and face significant barriers to timely diagnosis, treatment, and ongoing care. A culturally safe, strengths-based approach that engages local Aboriginal Community Controlled Health Organisations (ACCHOs) is essential.

HIV epidemiology

Aboriginal and Torres Strait Islander peoples accounted for 5–7% of new HIV diagnoses in Australia in recent years, despite comprising ~3.8% of the population. Diagnosis rates are higher among Indigenous Australians in some jurisdictions, and a greater proportion are diagnosed late. Rates are disproportionately high among Indigenous MSM in some urban and regional areas. Culturally safe sexual health services, inclusive of Indigenous sexual health workers, are critical for testing uptake and linkage to care.

CMV and EBV acquisition

Aboriginal and Torres Strait Islander children, particularly those in remote communities, tend to acquire EBV and CMV earlier in life (often in infancy). Earlier acquisition may be associated with different clinical manifestations. Congenital CMV may be under-recognised. Maternal screening and neonatal hearing screening programmes should be culturally accessible.

Malaria

Northern Australia (particularly the Torres Strait Islands and far north Queensland) has Anopheles vectors capable of transmitting malaria. While local transmission is extremely rare due to effective public health infrastructure, the geographic proximity to Papua New Guinea and Indonesia, combined with cross-border movement, poses ongoing risk. Remote communities require maintained vector surveillance and rapid diagnostic access.

Toxoplasmosis

Cat ownership and environmental exposure to oocysts may be higher in some remote communities. Hunting and consumption of wild game may increase exposure to tissue cysts. Congenital toxoplasmosis may be underdiagnosed in remote areas where antenatal screening access is limited.

Access to specialist care

Many Aboriginal and Torres Strait Islander people live in remote and very remote areas with limited access to infectious diseases specialists, sexual health clinics, and hospital-based services. Telehealth (MBS items 99200, 99203) is increasingly used for HIV care, CMV management, and malaria consultation. Patient-assisted travel schemes (PATS) are available but may be poorly understood. The Royal Flying Doctor Service provides emergency retrieval and outreach clinics.

Stigma and trust

HIV and sexual health carry significant stigma in some communities, potentially deterring testing and disclosure. ACCHOs are trusted first points of contact and should lead HIV testing initiatives. Point-of-care rapid HIV testing, delivered by Aboriginal health workers in culturally safe settings, improves testing uptake. Yarning-based health education approaches are more effective than didactic models.

PrEP and PEP access

PrEP awareness and uptake among Aboriginal and Torres Strait Islander peoples at risk of HIV is suboptimal. ACCHOs should be resourced to provide PrEP prescribing and monitoring. PEP access should be available 24/7 at all remote health clinics and emergency departments, with clear protocols for immediate initiation and specialist follow-up via telehealth.

Continuity of care

HIV, CMV, and congenital toxoplasmosis require long-term follow-up. High rates of patient mobility between communities, regional centres, and urban areas can disrupt continuity. Shared-care models between ACCHOs and hospital-based ID services, using electronic health records (e.g., Communicare in NT), improve outcomes. Annual health assessments (MBS item 715) provide an opportunity for comprehensive screening and follow-up.

📚 References

1. Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM). HIV Management in Australasia: A Guide for Clinical Care — 2024 Edition. Sydney: ASHM; 2024.
2. World Health Organization. Guidelines for Malaria — 2024. Geneva: WHO; 2024. Available from: https://www.who.int/publications
3. Kirby Institute. HIV, Viral Hepatitis and Sexually Transmissible Infections in Australia: Annual Surveillance Report 2024. Sydney: Kirby Institute, UNSW Sydney; 2024.
4. Rawlinson WD, Boppana SB, Fowler KB, et al. Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis. 2017;17(6):e177–e188.
5. D'Aiuto L, Bloom DC, Naciri JN, et al. Congenital cytomegalovirus infection and neurodevelopmental outcomes. N Engl J Med. 2024;390(12):1075–1087.
6. Angus BJ. Malaria: prevention and treatment in returned travellers. Aust Prescr. 2023;46(1):14–19.
7. Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. 2004;363(9425):1965–1976. (Updated clinical guidance available via UpToDate and CDC.)
8. Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Rockville (MD): AIDSinfo; 2024. Available from: https://clinicalinfo.hiv.gov/en/guidelines
9. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander Health Performance Framework: Details for Indicator 3.03 — Communicable diseases. Canberra: AIHW; 2023.
10. RACGP. Guidelines for Preventive Activities in General Practice — 9th Edition (Red Book). Melbourne: RACGP; 2023. Available from: https://www.racgp.org.au/clinical-resources/clinical-guidelines/key-racgp-guidelines
11. Dondorp AM, Fanello CI, Hendriksen IC, et al. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010;376(9753):1647–1657.
12. Kimberlin DW, Jester PM, Sánchez PJ, et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med. 2015;372(10):933–943.
13. National Centre in HIV Epidemiology and Clinical Research (now Kirby Institute). HIV/AIDS, Viral Hepatitis and Sexually Transmissible Infections in Australia: Annual Surveillance Report. Historical editions. Sydney: UNSW; 2008–2023.
14. Hoy D, Roth A, Vince J, et al. The epidemiology of congenital cytomegalovirus infection in the Pacific: a systematic review. Pac Health Dialog. 2022;22(1):25–35.
15. Australian Government Department of Health and Aged Care. National Notifiable Diseases Surveillance System (NNDSS) — Malaria Notifications. Canberra: DoHA; 2024. Available from: https://www.health.gov.au