Yellow fever is a mosquito-borne flavi-virus endemic and epidemic in South America, and Sub-Saharan Africa.1 Wild type disease incidence is between 100 to 1200 cases per annum worldwide,2 with mortality 20–50%. Whilst South America has instituted mass immunisation campaigns, the highest incidence is reported in Africa, where vaccination coverage is poor.

All vaccines currently in use are a live attenuated form of the virus prepared from the 17D strain of the virus, which induces seroconversion in over 95% of recipients.3 It is contraindicated in the immunocompromised, infants under 6 months, and those with known egg allergy. It is not contraindicated in pregnant or lactating women, but caution should be exercised.

Given the severity of disease, certain endemic countries mandate yellow fever vaccination as a condition of entry. Current CDC guidelines for travellers recommend vaccination in at risk travellers and in those requiring entry into a country with mandatory vaccination4. Since vaccination was introduced, there have been only 10 recorded cases of naturally acquired yellow fever recorded in travellers.4

Vaccine-derived yellow fever is a multisystem illness that was first described in 2001.5There are two syndromes: vaccine associated neurotropic (YEL-AND) and viscerotropic (YEL-AVD) disease.5,6 To date, there are 57 described cases, most commonly described in older age groups5 and those with underlying immunocompromise.

YEL-AVD appears to occur after the first dose of yellow fever vaccine, rather than with booster doses. The onset of YEL-AVD is 1–8 days after vaccination and reported case-fatality ratio is 65%. The incidence of YEL-AVD in the United States is 0.4 cases per 100,000 doses of vaccine administered. The rate is highest in those older than 60 years, with a rate of 1.0 per 100,000 doses in people aged 60–69 years and 2.3 per 100,000 doses in those older.7

Here we describe a case of YEL-AVD, with discussion of guidelines and cautions for vaccination in light of the risks of vaccine-derived disease.

Case report

A 66-year-old retired male administrative worker, presented to hospital with a 1-day history of diarrhoea, fevers and epistaxis . Seven days prior he received a yellow fever vaccination in anticipation of a trip to South America.

Initial examination revealed a diaphoretic, man, with a BP of 90/50 mmHg, HR 130, atrial fibrillation, temperature 38.5°C and oxygen saturations of 98%.

Chest auscultation revealed bibasal inspiratory crackles, and abdominal and neurological examination were unremarkable.

Figure 1. Chest X-ray on admission

Chest X-ray (CXR) demonstrated an opacity in the upper mediastinum. A computerised tomography (CT) scan of the thorax confirmed an 11 cm ×10 cm × 6 cm anterior mediastinal mass with associated hilar and mediastinal lymphadenopathy.

Admission laboratory testing showed a normal WCC, thrombocytopaenia (platelets 17×109L), hepatitis (ALT 214 U/L, ALP 58 U/L, bilirubin 38 umol/L), coagulopathy (INR 1.4, APTT 36 seconds), renal impairment (creatinine 117 mmol/L), and a CRP of 245 mg/L.

He was resuscitated with IV fluids and antibiotics. On day 2 of admission , he had persistent tachycardia , hypotension, low urine output and increasing oxygen requirements. Bleeding from phlebotomy sites and macroscopic haematuria were noted.

On day 3 he developed respiratory compromise. Bedside echocardiography demonstrated a small left ventricle with good systolic function. CXR suggested acute respiratory distress syndrome (ARDS), and renal failure ensued (creatinine 239 mmol/L).

He was transferred back to the High Dependency Unit (HDU) with multiorgan failure. He developed a DIC picture (APTT > 180, INR 1.6, fibrinogen 1.5). Despite maximal inotropic support and haemofiltration multiorgan failure progressed, and on day 5 support was withdrawn. He died shortly thereafter.

Blood, sputum and urine cultures were sterile and Legionella, leptospiral, hepatitis A, B and C serology negative. Serum tested positive for yellow fever IgM, and a blood sample (tested by CDC, Atlanta, USA) detected yellow fever viral RNA.

Scientists at the Institute of Environmental Science and Research (ESR) , New Zealand amplified by PCR the envelope protein of the patient’s YF strain and confirmed a 100% match with the 17D vaccine strain.

Our patient had a multisystem illness with clinical and biochemical features mirroring those of wild type yellow fever virus infection. The illness was temporally related to his yellow fever vaccine, with positive serology and PCR for yellow fever, suggesting a causal link between vaccination and his fatal illness. A post mortem examination was not undertaken, but it is likely the mediastinal findings represented a thymic mass.

Discussion

In a previous case series of 24 cases of vaccine derived yellow fever, 4 had previous thymectomies or thymic disease.8 The possibility of thymic disease coupled with advancing age put our case at higher risk of vaccine related disease—from current literature the risk in the over-60 age group is increased seven-fold5.

Whilst yellow fever vaccine adverse events are extremely rare,9 and the vaccine is highly effective at inducing immunity to an often fatal disease, we suggest that patients especially over 60 years of age should be adequately counselled prior to vaccination.

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