Case of the Month

December 2012

Fever in an expatriate traveller - Dr J Klotnick, SASTM

A 59 year old socio economic consultant, working in the Philippines (mainly in Manila) for the past six years, felt unwell one morning. He took his own temperature and found it to be 38.6oC. He decided to return to South Africa for medical assistance.

He has no medical history of note and was not on any chronic medication. He was not on malaria chemoprophylaxis. Details of the findings on clinical examination are scanty other than he reported that his sinuses were painful.

A blood count was performed and this was normal apart from a thrombocytopaenia. He was diagnosed as having sinusitis and placed on moxifloxacin 400 mg daily.

He did not improve and was seen two days later by another practitioner (day 3). He reported that his throat was sore and his sinuses still felt inflamed. He was nauseous and was retching. There was no diarrhoea. He did not have any myalgia or arthralgia.

On examination he was pyrexial (38.3 oC) and fully orientated. No abnormalities were noted on examination. His urine was of a normal colour and there was no indication of a urinary tract infection on urine dipstix testing.

Question 1: Was sinusitis an appropriate diagnosis in the first instance?

Answer to Q1

Sinusitis was not an appropriate diagnosis. He had not reported a preceding upper respiratory tract infection and the onset of illness was too short to entertain, clinically, a diagnosis of sinusitis. A worrying feature was the thrombocytopenia. Admittedly he had a low total white cell count and a neutropenia, which could indicate a viral infection. The treatment with moxifloxacin was likewise inappropriate.

Question 2: What differential diagnosis should be considered in this expatriate?

Answer to Q2

It is important to consider and to have knowledge of the infectious diseases occurring in the Philippines that would place this expatriate at risk, and this would include information on recent outbreaks occurring there.

  • Malaria: must be considered, despite the fact that he worked mostly in Manila, which is a low risk for malaria (P falciparum) and chemoprophylaxis is usually not advised. However, the clinical picture was not that convincing of Malaria.
  • Hepatitis A: His vaccination history is unknown. He had symptoms of nausea and retching and he could be presenting at the early stages. The thrombocytopaenia though would not be supportive of the diagnosis. The incidence of Hepatitis A in the Philippines is unknown and no outbreaks have been reported.
  • Leptospirosis: The main outbreaks of this disease were reported in July 2011 and prior to that in 2009 and 2008, and did occur in Metro Manila. It is unlikely in this case as there are no recent reported outbreaks.
  • Dengue fever: Outbreaks of Dengue fever are reported regularly from the Philippines. More than 45,000 cases were reported nationwide for the first seven months of 2011, more than half of them from Luzon. The most recent outbreaks were reported in October 2011 from Aklan province, in August 2011 from Metro Manila, Central Luzon, Quezon City, La Union province, and Eastern Visayas, and in July 2011 from Pampanga province, Kalinga province, Batanes, Cordillera Administrative Region, southwestern Mindanao, and Laoag city, Ilocos Norte province. At this stage he did not have myalgia or severe arthralgia. However, the thrombocytopaenia, which was noted should raise suspicion of possible Dengue fever.
  • Other viral infections: Epstein Barr virus infection - In the undifferentiated stage of an illness it is always difficult to exclude many viral infections. In view of the fact that there was no lymphadenopathy or splenomegaly it is unlikely that he had contracted EBV infection. Cytaomegalovirus infection - His HIV status is unknown but he had no manifestations clinically of full blown AIDS.

Question 3: What tests should be requested at this stage?

Answer to Q3

  • Repeat FBC to follow the thrombocytopaenia
  • Malaria
  • Dengue
  • It is important to base one’s test request on the clinical findings and with the knowledge of outbreaks in the Philippines to target that, which occurs commonly.

He consulted the following day (Day 4) and a fine petechial rash was noted over the lower limbs. Blood tests confirmed a diagnosis of Dengue Fever.


The incidence of dengue has increased dramatically around the world in recent decades. Over 2.5 billion people – 40% of the world's population – are now at risk from dengue. WHO currently estimates there may be 50–100 million dengue infections worldwide annually. Severe dengue (previously known as Dengue Haemorrhagic Fever) was first recognized in the 1950s during dengue epidemics in the Philippines and Thailand. Today, severe dengue affects most Asian and Latin American countries and has become a leading cause of hospitalization and death among children in these regions.9

Before 1970, only nine countries had experienced severe dengue epidemics. The disease is now endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, South-east Asia and the Western Pacific. South-east Asia and the Western Pacific regions are the most seriously affected.

Cases across the Americas, South-east Asia and Western Pacific have exceeded 1.2 million cases in 2008 and over 2.2 million in 2010 (based on official data submitted by Member States). Recently the number of reported cases has continued to increase. In 2010, 1.6 million cases of dengue were reported in the Americas alone, of which 49 000 cases were severe dengue.

Not only is the number of cases increasing as the disease spreads to new areas, but explosive outbreaks are occurring. The threat of a possible outbreak of dengue fever now exists in Europe and local transmission of dengue was reported for the first time in France and Croatia in 2010 and imported cases were detected in three other European countries.

There are four distinct, but closely related, serotypes of the virus that cause dengue (DEN-1, DEN-2, DEN-3 and DEN-4). Recovery from infection by one provides lifelong immunity against that particular serotype. However, cross-immunity to the other serotypes after recovery is only partial and temporary. Subsequent infections by other serotypes increase the risk of developing severe dengue.

The Aedes aegypti mosquito is the primary vector of dengue. The virus is transmitted to humans through the bites of infected female mosquitoes. After virus incubation for 4–10 days, an infected mosquito is capable of transmitting the virus for the rest of its life.

Infected humans are the main carriers and multipliers of the virus, serving as a source of the virus for uninfected mosquitoes. Patients who are already infected with the dengue virus can transmit the infection (for 4–5 days; maximum 12) via Aedes mosquitoes after their first symptoms appear.

The A. aegypti mosquito lives in urban habitats and breeds mostly in man-made containers. Unlike other mosquitoes, A. aegypti is a daytime feeder; its peak biting periods are early in the morning and in the evening before dusk. Female A. aegypti bites multiple people during each feeding period.

Aedes albopictus, a secondary dengue vector in Asia, has spread to North America and Europe largely due to the international trade in used tyres (a breeding habitat) and other goods (e.g. lucky bamboo). A. albopictus is highly adaptive and therefore can survive in cooler temperate regions of Europe. Its spread is due to its tolerance to temperatures below freezing, hibernation, and ability to shelter in microhabitats.

Dengue should be suspected when a high fever (40°C/ 104°F) is accompanied by two of the following symptoms: severe headache, pain behind the eyes, muscle and joint pains, nausea, vomiting, swollen glands or rash. Symptoms usually last for 2–7 days, after an incubation period of 4–10 days after the bite from an infected mosquito.

At present, the only method to control or prevent the transmission of dengue virus is to combat vector mosquitoes through:

preventing mosquitoes from accessing egg-laying habitats by environmental management and modification; disposing of solid waste properly and removing artificial man-made habitats; covering, emptying and cleaning of domestic water storage containers on a weekly basis; applying appropriate insecticides to water storage outdoor containers; using of personal household protection such as window screens, long-sleeved clothes, insecticide treated materials, coils and vaporizers; improving community participation and mobilization for sustained vector control; applying insecticides as space spraying during outbreaks as one of the emergency vector control measures; active monitoring and surveillance of vectors should be carried out to determine effectiveness of control interventions

An estimated 500 000 people with severe dengue require hospitalization each year, a large proportion of whom are children. About 2.5% of those affected die.

Severe dengue is a potentially fatal infection due to plasma leakage, fluid accumulation, respiratory distress, severe bleeding, or organ impairment. Warning signs occur 3–7 days after the first symptoms in conjunction with a decrease in temperature (below 38°C/ 100°F) and include: severe abdominal pain, persistent vomiting, rapid breathing, bleeding gums, fatigue, restlessness, blood in vomit. The next 24–48 hours of the critical stage can be lethal: proper medical care is needed to avoid complications and risk of death. Changes in the haematocrit are known to predict for severity of the disease. In the case presented above, the patient’s haematocrit remained stable, which in this case predicted for recovery and not severe Dengue.

There is no specific treatment for dengue fever.

For severe dengue, medical care by physicians and nurses experienced with the effects and progression of the disease can save lives – decreasing mortality rates from more than 20% to less than 1%. Maintenance of the patient's body fluid volume is critical in severe dengue care.

There is no vaccine to protect against dengue. Developing a vaccine against dengue/ severe dengue has been challenging although there has been recent progress in vaccine development.7,8 WHO provides technical advice and guidance to countries and private partners to support vaccine research and evaluation. Several candidate vaccines are in various phases of trials.

References and Resources:

  1. WHO (2009). Dengue Guidelines for Diagnosis, Treatment, Prevention and Control. Geneva: World Health Organization. ISBN 92-4-154787.page 3.
  2. Gubler DJ 2010).”Dengue viruses”. In Mahy BWJ, Van Regenmortel MHV. Desk Encyclopedia of Human and Medical Virology. Boston Academic Press. pp 377
  3. Jelinek T, et al. Epidemiology and clinical features of imported dengue fever in Europe. Clin Infect Dis 2002;35:1047-52
  4. WHO (2009). Dengue Guidelines for diagnosis, Treatment, Prevention and Control. Geneva: World Health Organization. ISBN 92-4-154787. page 137
  5. Reiter P. Yellow Fever and Dengue: a Threat to Europe. Euro surveill 15(10):19509
  6. Das S, Pinyte MR, Munoe-Jordan JL, Rundell MS, et al(2008). Detection and serotyping of dengue virus in serum samples by multiple reverse transcriptase PCR-ligase detection assay. J. Clin. Microbiology 46: 3276-3284
  7. Farrar J, Focks D, Gubler D, Barrera R,Guzman MG, Simmons C (2007) WHO/TDR Dengue scientific working group, towards a global Dengue research agenda. Tropical Medicine and International Health. June 12 (6) 695-699
  8. Global strategy for dengue prevention and control. WHO 2012. ISBN 9789241504034 pp 16-17
  9. Ranjit s,Kissoon N. Dengue haemorrhagic fever and shock syndrome. Paediatr Crit. Care Med. 12(1):90-100
  10. Varatharaj A . Encephalitis in the clinical spectrum of Dengue infection. Neuro India 58(4):585-91
  11. Simmons CP, Farrar JJ, Nguyen W, Wilt B. Dengue. N Engl J. Med. 366(15):1423-32
  12. WHO (2009). Dengue Guidelines for Diagnosis, Treatment, Prevention and Control. Geneva: World Health Organization. ISBN 92-4-154787. p25
  13. Chen LH, Wilson ME (October 2010) Dengue and chikungunya infections in travelers. Curr Opin. Infect. Dis 23(5) 438-44
  14. Webster DP, Farrar J, Rowland JS . Progress towards a Dengue vaccine. Lancet Infect Dis.9 (11) 678-87
  15. Guy B, Barrere B, Malinowskic C,Saville M, Teyssou R, Lang J (23 Sept 2011) Research phase 3 preclinical, industrial and clinical development of the Sanofi Pasteur tetravalent dengue vaccine. Vaccine 25(42):7229-41
  16. Halstead SB, Deen J. The future of dengue vaccines . Lancet 2002. 30:1243-5
Outcome of the Case

The patient made a full symptomatic recovery.

Lessons learnt

The importance of a thorough history, careful examination, correct interpretation of special investigations and knowledge of outbreaks that occur in countries where the expatriate is working is essential to formulate a working clinical diagnosis.

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