FIDSSA

Case of the Month

June 2017

MISERY ACQUAINTS A MAN WITH STRANGE BEDFELLOWS

William Shakespeare

Ms Lee Baker, Amayeza Info Centre, President, SASTM

Albie de Frey, Travel Doctor Johannesburg, Executive Committee Member, SASTM

A 57-year-old previously healthy Caucasian South African man was medevaced to a private hospital in Johannesburg from Lubumbashi in the Democratic Republic of Congo in mid-December 2016.

He travelled to the DRC on 18 November 2016 where he had been working at a mine in Kakunda, Katanga for several months.

His home is in Sasolburg but he had been working as an expatriate for several years in Mozambique, Botswana, Mali, Ghana, Zambia, Burkina Faso, Liberia and Namibia. During the course of his expatriation he had been fully vaccinated against yellow fever, hepatitis A and B, typhoid, meningococcal disease, tetanus, polio, diphtheria and pertussis. He does not take malaria prophylaxis and does not keep any animals at home in a residential suburb in southern Gauteng.

He had documented malaria 3 years prior to this episode and was on methyl-dopa 500mg 8 hourly for hypertension. He smokes 20 per day for the last 20 years and drinks two units of alcohol per day.

On 6 December 2016, he presented to the mine clinic with severe headache, fatigue and myalgia. He was given Vitamin B1 and B6 injections and diclofenac per rectum… The next day he developed a high fever, yellow diarrhoea and “black urine”. Malaria screening was apparently negative.

On the third day of illness he was referred to a private clinic in Lubumbashi where he was diagnosed with “2 +” Plasmodium falciparum malaria, put on an intravenous infusion, given azithromycin orally and received a series of artemether injections. On Day 5 he was sent back to the mine as his malaria smear was now allegedly negative - he still had a severe, persistent headache and vomited on the evening of the fifth day. He was given Mypaid® (Ibuprofen / paracetamol) on the seventh day and with still no improvement on Day 8 he flew to Johannesburg on a commercial flight.

On examination he appeared generally well, was apyrexial with normal vital signs. He had no meningism, jaundice, clubbing, lymphadenopathy or pallor but a fine macular rash was noted on the all four limbs including the palms and soles. He had no eschars or other insect bites, no conjunctival congestion and the rest of the examination was unremarkable.

He had a normal chest X-ray and abdominal sonar, normal resting ECG and his urine was clear.

Laboratory screening was as follows:

Full Blood Count

Salmonella and Rickettsia serology was negative. Dengue screening was negative but the Brucella IgM was considered positive with a value of 3,6 (Normal ration 0.0 – 0.7) Brucdlla IgG was negative.

On clinical grounds, in the face of the positive IgM, in the absence of laboratory evidence of any other infectious disease and in lieu of the seriousness of chronic brucellosis he was commenced on doxycycline and rifampicin for a month.

A month after his admission in Johannesburg the IgM, IgG and PCR for Brucellosis was repeated. It was all negative…

Question 1 - Did the patient have malaria?

Answer to Question 1

The fact that the patient had a normal white cell count, normal platelet count and negative malaria smear AND antigen test within a week of being treated for alleged malaria argues against the likelihood that he had malaria. Platelets are not always low in malaria and may have recovered a week later - but the antigen test or histidine-2-rich protein remains positive for up to two weeks after successful treatment - especially if the patient had a high parasite count (“2 plus” quoted in the referral letter). There was no accompanying laboratory evidence from the clinic in Lubumbashi to support the diagnosis and the patient persisted with a severe headache and vomiting after discharge from there arguing against a “cure”.

Question 2 - Did the patient have brucellosis?

Answer to Q2

The classical presentation of brucellosis is not classical… it can present with a variety of symptoms in the acute phase and with a range of signs and symptoms once the disease becomes chronic. The incubation period varies between five days and five months after infection. The patient may then present with fever, myalgia, headache, fatigue and night sweats - classically “malodourous” ... They may present with abdominal pain and cough. Rash is a feature of the disease but not always present. Focal infection may occur in most parts of the anatomy.

The clinician initially considered a rickettsial disease on the basis of a febrile illness with prominent headache, malaise and a rash. The initial positive IgM for Brucellosis was an “incidental” finding but the clinical features could fit in with this diagnosis.

Laboratory diagnosis of the disease is difficult: Blood culture is the diagnostic gold standard but not always positive. If culture of blood, bone marrow or other clinical specimens is requested the laboratory must be alerted to the clinical suspicion as the bacterium takes longer to grow and laboratory personnel must take extra precautions as brucellosis poses an occupational hazard and may even be inhaled.

Serum agglutination is the most common serological approach but ELISA and PCR may be used to make the diagnosis.

he patient did not have a positive blood culture - but prolonged culture was not requested initially. The IgM was positive on the initial tests even though the clinician was more suspicious of a rickettsial disease at the time of the request. The fact that the IgG and IgM as well as the PCR was negative a month later is disappointing but does not rule out the diagnosis out and may indicate that timeous treatment of the acute infection prevented chronic brucellosis and its complications.

Question 3 - What else should be considered in the diagnosis of a febrile illness with rash?

Answer to Q3

The differential diagnosis of a fever and a skin rash includes: African Tick-bite Fever, Measles, Acute HIV, Dengue, Infective Mononucleosis, Varicella, Typhoid fever, Spotted-fever or other typhus group rickettsiosis, Coxsackie virus and Parvovirus B19 amongst others.

Question 4 - How can malaria and brucellosis be confused?

Answer to Q4

Brucellosis was first diagnosed on the island of Malta where it was known as Undulating, Malta or Mediterranean Fever. It was often confused with malaria that was still prevalent in large parts of Europe in the late 1800’s. The disease was a major cause of long term disability and recognised as a sexually transmitted disease amongst British troops stationed on Malta. It is ironic that malaria and brucellosis are still confused when at least the laboratory confirmation of P falciparum malaria should be commonplace on the continent that bears the global brunt of malaria.

Question 5 - How does one prevent brucellosis in travellers?

Answer to Q5

Brucellosis is not vaccine preventable in humans although several vaccines have been tried in the past. Veterinary vaccines are widely used for the eradication and control of brucellosis in goats and cattle. The disease is still endemic in large parts of the Mediterranean basin, Asia, Africa and the Middle East and travellers should be educated to avoid consuming unpasteurised milk and milk products including cheese in those areas. This patient MAY have been exposed to unpasteurised milk on the mine in the DRC although the authors have no evidence of this.

Lessons learned
The title of the talk refers to the fact that malaria and brucellosis or Malta Fever are both miserable diseases that at face value should not easily be confused and seem to be geographically far removed. This case shows that history repeats itself and that we can always learn from history - even in medicine.

Acknowledgements
Dr G Brink for reviewing the article and providing comments
Dr C Smith, Morningside Clinic for sharing his notes on the case

REFERENCES

Brucellosis Therapy: A Historical Overview, Thomas G. Benedek, BS, MS, M.D, University of Pittsburgh.http://www.antimicrobe.org/h04c.files/history/Brucellosis.asp , (Accessed 22 May 2017.)
http://www.medicinenet.com/script/main/art.asp?articlekey=9306 (Accessed 29 May 2017)
http://www.emedicinehealth.com/brucellosis/article_em.htm
Lessons from the history of brucellosis. Rev. sci. tech. Off. int. Epiz., 2013, 32 (1), 17-25. H.V. Wyatt. https://www.oie.int/doc/ged/D12396.PDF
USAID - PREDICT Programme http://www.vetmed.ucdavis.edu/ohi/local_resources/pdfs/predict-drc.pdf
http://www.promedmail.org (Accessed 29 May 2017)

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