Dr Albie de Frey and Mrs Lee Baker
A 30-yr old male returned from a 14-day holiday in Italy having spent 4 days in Rome and 10 days on the Amalfi beach. He stayed in a privately rented apartment with a balcony where he often sat in the late afternoon/early evening.
On the last two days of the holiday he noted the skin lesions (see photo) on his feet and lower legs.
Four days back in Johannesburg he developed a febrile illness with night sweats and chills, headache, muscle and joint pain and malaise. His transaminases were mildly raised but FBC was normal.
He had all his childhood vaccines but an unremarkable past medical history since. He did not seek pre-travel advice prior to departing for Italy as he deemed it unnecessary.
Question 1: Discuss the differential diagnosis in this patient with particular reference to the geographic area from which the patient returned?
Answer to Q1
Differential diagnosis of: skin lesions on the legs, febrile systemic illness and mild raised liver enzymes in a returning traveller from Rome and the Amalfi coast?
Skin rashes in returning travellers are as common as in the general population anywhere in the world. One could consider an allergic rash/ fixed drug eruption – from a change in detergent or from the vegetation in that area. This does not however present with raised liver enzymes and febrile illness.
Malaria - Malaria should always be considered in the febrile returning traveller. However, although it has recently been reported in Greece, Italy is not recognized as an endemic country. The history of rash would not fit and would suggest a second pathology. It is however worth considering that malaria was at one time endemic throughout much of Italy. P. falciparum transmission ceased in 1950 after an intensive vector control campaign; The last autochthonous case of P. vivax was documented in 1955 in Calbria. The last endemic focus of P. vivax was reported in Sicily in 1956. Much of southern and central rural Italy remains receptive to malaria transmission due to the presence of capable malaria vectors such as An. labranchiae. While the overall malariogenic potential appears to be low and the reintroduction of malaria unlikely, the densities of An. labranchiae remain very high, along with other potential vectors as An. maculipennis, An. atroparvous and An. superpictus. Most of these species are not particularly receptive to African strains of P. falciparum. However, after a 20 year absence, P vivax was reintroduced in Maremma, Italy in 1977 diagnosed in a woman with no history of travel. Investigation identified a 7-year-old girl who had travelled to India as carrying P vivax. Her parents were also infected.
In the absence of a definitive diagnosis based on the available laboratory tests in South Africa, the authors conferred with two Italian infectious disease specialists with an interest in travel health. They confirmed that Pappataci fever has been documented in the Amalfi area in the recent past. The fact that the patient was by then recovering fitted the typical clinical outcome of the disease. They did not feel that there was any reason to go to great lengths to make a laboratory diagnosis.
Currently laboratory diagnosis is not available in the private or public sector in South Africa.
Pappataci is the Italian word for sandfly. Three serotypes of Phlebovirus, Naples virus, Sicilian virus and Toscana virus are known causative agents.Epidemiology of Pappataci Fever
Pappataci fever, or Sandfly Fever as it is commonly known is common in the subtropical zone of the Eastern Hemisphere between 20°N and 45°N, particularly in Southern Europe, North Africa, the Balkans, Eastern Mediterranean, Iraq, Iran, Pakistan, Afghanistan and India.
Distribution of Pappataci Fever by serotype. (T, Toscana, S, Sicilian, N, Naples).
Naples and Sicilian are the viruses largely responsible. Both were isolated by Sabin (of Polio fame) during World War II. The two infections frequently overlap. They were the cause of a very large number of illnesses among troops operating in the endemic area during both World Wars. After the Second World War and with the application of DDT residual sprays for the control of malaria vectors, Sicilian and Naples viruses virtually disappeared. The incidence of these two viruses remains high in most of their other endemic areas. Toscana virus is now known to be widely distributed in Italy, and has been reported from Portugal, Cyprus and Spain;
The sandfly-transmitted viruses are all Phleboviruses within the Bunyavirus group. Globally, some 45 viruses are associated with sandflies. Some Phleboviruses are transmitted by mosquitoes, e.g. Rift Valley fever, whereas others are transmitted by ticks.
Important vectors include Phlebotomus papatasi (see photo), Phlebotomus perniciosus and Phlebotomus perfiliewi. The sandfly becomes infected when biting an infected human in the period between 48 hours before the onset of fever and 24 hours after the end of the fever, and remains infected for its lifetime. Besides this ‘horizontal’ virus transmission from man to sandfly, the virus can be transmitted transovarially, from an infected female sandfly to its offspring.
Pappataci fever is seldom recognised in endemic populations because it is mixed with other febrile illnesses of childhood, but it is better known among immigrants and military personnel from non-endemic regions.Clinical course
There is a high rate of asymptomatic infection. In those that develop symptoms a few days after the infective bite, a feeling of lassitude, abdominal distress and chills develop followed by fever of 39°C to 40°C, severe frontal headaches, muscle and joint aches, flushing of the face and tachycardia. After two days the fever begins to subside and the temperature returns to normal. Fatigue, bradycardia and subnormal blood pressure may persist from a few days to several weeks but complete recovery is the rule.
Although normally a mild self-limiting disease, Pappataci fever has been associated with acute neurologic disease, and clinical cases of aseptic meningitis or meningo-encephalitis. Toscana virus may be responsible for up to 80% of acute viral CNS infections during the Italian summer.
The importation of sandfly fevers by tourists and soldiers returning from endemic areas is a growing problem with less than 20% of actual infections correctly diagnosed by physicians.
Diagnosis: Commercial tests are not readily available - diagnosis can only be confirmed by serology-based assays or real-time PCR in laboratories that have developed assays to perform such identification.
Treatment is symptomatic only.
Prevention of sandfly bites, and control of sandflies and their breeding grounds with insecticides are the principal methods for prevention. Mosquito nets are not effective to prevent sandfly bites as they are not only night biting and occur on sandy areas - such as beaches and desert dunes. DEET is an effective insect repellent that will also decrease sand fly bites.
Question 2: How would you investigate this patient?
Answer to Q2
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