Fever in a recently returned traveller is a consultation that can be interesting and daunting. This article explains how we test for malaria in Australia today.

A fever or history of fever such as shakes, chills or rigors is present in the majority of travellers with malaria. Making a diagnosis, however, is not always straightforward because the symptoms are non-specific and can mimic influenza, gastroenteritis or respiratory infection.

Malaria testing in WA
EDTA (purple top) tube blood samples are used. Samples taken in association with a rising fever are generally most sensitive. Initial diagnostic tests are a combination of microscopy of thick and thin blood films (still considered the gold standard) and rapid diagnostic tests (RDTs). Molecular methods (PCR) may assist in species identification, as an adjunct to the microscopy, but do not yet replace the initial microscopic examination of thick and thin films. Malaria serology has no role in the diagnosis of acute malaria, due to the time delay for antibodies to appear.

Interpreting the results
While the thick film improves the sensitivity of microscopy, the thin film is used to determine the species of malaria because the morphology of the parasite and its host red cell are visible. The thin film can also be the basis for calculation of parasite load. The number of parasites required to elicit a febrile reaction in Caucasians was investigated in early studies of malaria therapy for neuro-syphilis and can be very low. The pyrogenic threshold for P. vivax is much lower than that for P. falciparum. Most people with clinical malaria have parasitaemia well above the lower limit of detection for microscopy. This lower limit, however, is dependent on the experience of the microscopist but should be below 2 parasites per 200 white cells (80 parasites/μL). If analysis proves negative but clinical suspicion remains, repeat specimens should be considered.

The role of rapid tests
Malaria rapid diagnostic tests (RDTs) are useful adjuncts to malaria diagnosis, but negative results especially in the setting of travelers with possible P. vivax infection should be interpreted with caution. Most are immuno-chromatographic tests that detect a protein called PfHRP-2 that is specific to P. falciparum. Some also contain a test line that allows detection of non-falciparum malaria species. Typically, when P. falciparum parasitaemia is above 2000/μL they perform well. Some brands also perform well down to 200/ μL. However, RDT detection rates for P. vivax and other non-falciparum species are highly variable. For a comprehensive comparison of RDT performance visit here.

Because RDTs can remain positive for weeks they are not useful for monitoring disease progression or response to treatment.

Treatment
Treatment is a topic in itself however consultation with the laboratory and/or an infectious disease physician is recommended for assistance regarding resistance and therapeutic options.

Malaria Tips
• Five plasmodium species cause malaria in humans: P. falciparum, P. vivax, P. ovale, P. malariae. P. knowlesi, a species previously recognized as affecting monkeys, is now the major cause of human malaria in Malaysia.

• Immigrants who visit friends and family in their country of origin now make up more than half of imported malaria cases.

• Not all malaria endemic countries have the same transmission intensity. Travel to West Africa carries a risk of up to 2% per month. The risk for travel in the Americas and North Africa is lower than travel to Melanesia or Sub-Saharan Africa.

• Business travellers spending most time in urban environments are at lower risk than those visiting rural areas.

• No chemotherapeutic prophylaxis provides 100% protection against malaria. Late infections presenting more >2 months after exposure are well documented in people who have taken appropriate anti-malarials.

• The most diagnostic clinical signs are an enlarged spleen and thrombocytopaenia.

• A rash is rare with malaria and normally indicates another pathology such as dengue, Chikungunya or other viruses.

References available on request.

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Laurens Manning is an Infectious Diseases physician with an academic interest in tropical paediatrics. He completed advanced training in infectious diseases in New Zealand and Australia. In addition to working with Perth Pathology, he has clinical duties at Royal Perth Hospital and is active in malaria research with UWA.

Schistosomiasis (also known as Bilharzia) is a parasitic disease caused by several species of blood flukes of the genus Schistosoma, found in Africa, South America, China and South East Asia. Schistosomiasis, after malaria, is one of the most common parasitic diseases in humans, and generally rates second only to malaria, in terms of socioeconomic impact. With changing patterns of travel and migration, Schistosomiasis may be increasingly encountered in Australian general practice.

Host cycle
After excretion of eggs into fresh water via stool or urine from infected individuals, fresh water snails effectively amplify these into the free-living larval forms known as cercariae. The cercariae then penetrate unbroken skin, enter the circulation and migrate through the lungs, before the adult worms settle in the perirectocolic (S. mansoni, S. intercalatum, S. japonicum and S. mekongi) or perivesical (S. haematobium) venous plexuses. Adult worms produce large numbers of ova that migrate through the bowel or bladder wall to be excreted back into the environment.

Clinical aspects
Generally, clinical disease is associated with acute or chronic inflammatory responses to ova as they pass transmurally or are embolised to the liver or elsewhere in the body. In general practice, the clinical presentation maybe broadly separated into two groups: the returned traveller; and, migrants from endemic countries.

Schistosomiasis in the returned traveller:
• Is usually acquired from fresh water lakes (e.g. Lake Malawi, Lake Victoria and Lake Tanganyika) in Africa, where S. haematobium predominates.

• May be diagnosed in up to 76% of at risk asymptomatic travellers on routine post travel screening.

• May be preceded by a history of ‘swimmers itch’ in up to a third of cases. This transient rash is caused by skin penetration of cercariae.

• May present with acute illness called ‘Katayama fever’, characterised by fever, nonproductive cough, peripheral eosinophilia and/or gastrointestinal symptoms.

• Is generally associated with a low worm burden and therefore long term sequelae and disease specific mortality are rare.

In migrants with schistosomiasis:
• Infection is often asymptomatic or chronic, with symptoms related to urinary schistosomiasis (from areas where S. haematobium is transmitted): dysuria, urinary frequency, haematuria or haematospermia indicate symptomatic urinary schistosomiasis.

• Intestinal disease presents with bloody diarrhoea, occult faecal blood loss or vague gastrointestinal symptoms.

• Hepatic manifestations include early granulomatous hepatosplenomegaly and portal hypertension caused by late fibrotic disease.

Diagnosis
Microscopic examination of urine or faeces remains the gold standard diagnostic test for schistosomiasis. Detection of eggs allows identification of the infecting species and quantitative egg counts correlate well with overall worm burden. At low worm burdens egg counts are often low and may escape detection even after optimisation of specimens.

Urine and stool samples should be taken between 10 am and 2 pm as egg production fluctuates during the day. A terminal urine sample, rather than the traditional MSU, is recommended as the last muscular contraction increases the recovery of ova in the urine sample. It is important to note that ova may not be detectable until at least 6 weeks after initial infection. Multiple specimens should be considered, if initial samples are negative.

Schistosoma serology may be useful with a sensitivity of up to 90%. However, antibody may not be detectable until 4-12 weeks after infection, and may therefore be negative with the onset of acute Katayama fever. In addition, serology does not allow differentiation between different species nor between active and previous treated infection.

Treatment
Praziquantal (Biltricide) is an effective and safe treatment, with two doses of 20mg/kg, 4 hours apart recommended. Artemisinin antimalarial compounds also show promise for post exposure prophylaxis as they have an effect on the developing worm prior to egg production and sero-conversion.

References available on request.

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……………….
Laurens Manning is an Infectious Diseases physician with an academic interest in tropical paediatrics. He completed advanced training in infectious diseases in New Zealand and Australia. In addition to working with Perth Pathology, he has clinical duties at Royal Perth Hospital and is active in malaria research with UWA.