Clinical presentation

A film with an unexpected twist

Learning points1. Take an extensive travel history going beyond a few months and refer to NaTHNaC for local outbreaks. It is also important to consider risk factors for delayed presentation as well as previous use of chemoprophylaxis.

2. Always rule out malaria in an unwell patient if there has been travel to malarious area or where there have been recent outbreaks.

3. It is reassuring that the laboratory and its standardised practices provide safety net when it comes to establishing a diagnosis.

After three days of antibiotics, the patient showed no clinical improvement and his CRP remained elevated.

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0 1 2 3NEWS KEY

NAME: D.O.B. ADMISSION DATE:

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≥2521-2412-209-11≤8

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≥2521-2412-209-11≤8

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>14013012011010090807060504030

2302202102001901801701601501401301201101009080706050

≥39°38°37°36°≤35°

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2302202102001901801701601501401301201101009080706050

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≥39°38°37°36°≤35°

Additional

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Pain Score Pain Score

National Early Warning Score: July 2012

© Royal College of Physicians 2012

Observation chart for the National Early Warning Score (NEWS)

Please see next page for explanatory text about this chart.

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It was also noted that he had a persistent low grade temperature of above 37.5°C with two temperature spikes above 38°C, one on ad-mission (39.1°C) and one approximately 48 hours after his first spike. Because there were no signs of clinical improvement, his antibiotics were escalated to gentamicin and metronidazole.

Progression of disease

Given this, his history was revisited and a travel history was taken. The patient reported no foreign travel in the last year. His last trip abroad - to Islamabad, Jhelum and Karachi in Pakistan – had been 13 months previously. He reported his wife having had malaria during their trip and upon his return his GP had requested a blood film which came back as negative.

Travel history revisited

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5-day histroy of pyrexia, rigors and flank pain

• Pre-diabetes• High cholesterol

Past medical history

• Chest X-ray: clear• Urine dip: negative• Bloods: Normal U&Es Normal Hb Low platelets (36) Elevated CRP (123) Deranged liver function tests• Ultrasound abdo: normal

Investigations

• Never smoker• No ETOH• Works in office job

Social history

UrosepsisBiliary sepsis

Co-amoxiclav started to cover both

Initial diagnosis

The patient’s initial low platelet count (< 50 x 109/L) prompted the lab-oratory to do a blood film leading to the diagnosis. Both thick and thin film, as well as the antigen test confirmed the diagnosis of malaria. This was then subsequently confirmed by the reference laboratory.

Malaria is present in all areas (incl. all cities) <2500m

Malaria is present

DiscussionMalaria is not on the top of the list of differentials when a patient presents with fevers and flank pain. It was a combination of low platelets, that prompted the laboratory to request a blood film and a patient who was spiking temperatures despite receiving broad-spectrum antibiotics caus-ing the clinicians to revisit the history and the working diagnosis, that led to the correct diagnosis.

Cases of delayed onset malaria in travel-lers have been reported numerous times in the literature. The majority of P. falciparum cases present within 2 months of return . Dauby et al did not specify the incubation time, but reported after reviewing 32 cases in their literature review that the time of onset ranged from 3 months to 120 months with a median of 36 months for P. falcipar-um. For P. vivax and P. ovale, most cases had an onset of more than two months after return from travel with a range be-tween 61 days to four and a half years .

Cases of delayed onset

Whilst travelling to a malarious area is the biggest risk factor, au-tochtonous malaria cases have been reported in Europe, resulting in local outbreaks . The website of the National Travel Health Net-work And Centre (NaTHNaC) gives clinicians up-to-date information on local outbreaks of infections diseases all over the world to aid diagnosis based on travel history.

Autochtonous Malaria

Interestingly, delayed onset may be related to whether the patient has previously taken chemoprophylaxis and which drug was taken. The life cycle of the parasite in humans consists of two stages. The first stage is the liver phase, where parasites multiply in hepatocytes and cause them to rupture. The second stage is the blood stage, where parasites are released into the blood stream and invade erythro-cytes, which causes critical illness. Drugs can be divided into blood-stage schizon-ticides (Mefloquine, doxycycline, chloroquine) and liver-stage schizonticides (Primaquine, atovaquine + chloroguanide). Late relapses caused by P. ovale and vivax may be attributable to both vivax and ovale having persistent liver stages which can emerge and cause illness months to years after primary infection. Blood-stage schizonticides will not prevent these relapses and may even mask symptoms of initial infection.

Chemoprophylaxis: A risk factor for delayed presentation

1,792 cases of malaria in the UK in 2017

> 200 million cases worldwide in 2016445,000 deathsMost deaths attributable to P. falciparum

Cases of increased severity of P. vivax reported

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References https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/722591/Malaria_imported_into_the_United_Kingdom_2017.pdf

World malaria report 2005. Geneva: World Health Organization. (2005). Ac-Cessed September, 159–192. https://doi.org/10.1071/EC12504

Price, R. N., Douglas, N. M., & Anstey, N. M. (2009, October). New developments in Plasmodium vivax malaria: Severe disease and the rise of chloroquine resistance. Current Opinion in Infectious Diseases. https://doi.org/10.1097/QCO.0b013e32832f14c1

Javelle, E., Madamet, M., Gaillard, T., Velut, G., Surcouf, C., Michel, R., … Pradines, B. (2016, April 1). Delayed onset of plasmodium falciparum malaria after doxycycline prophylaxis in a soldier returning from the Central African Republic. Antimicrobial Agents and Chemotherapy. American Society for Microbiology. https://doi.org/10.1128/AAC.01858-15

Schwartz, E., Parise, M., Kozarsky, P., & Cetron, M. (2003). Delayed Onset of Malaria — Implications for Chemoprophylaxis in 4,5,6Travelers. New England Journal of Medicine, 349(16), 1510–1516. https://doi.org/10.1056/NEJMoa021592

Stuiver, JB, van R., & Visser. (1996). Delayed Onset of Malignant Tertian Malaria Through the Inappropriate Use of Doxycycline: Another Threat to Patients Returning from Malarious Areas. Journal of Travel Medicine, 3(3), 193. https://doi.org/10.1111/j.1708-8305.1996.tb00743.x

Dauby, N., Ferreira, M. F., Konopnicki, D., Nguyen, V. T. P., Cantinieaux, B., & Martin, C. (2018). Case report: Delayed or recurrent plasmodium falciparum Malaria in migrants: A report of three cases with a literature review. American Journal of Tropical Medicine and Hygiene, 98(4), 1102–1106. https://doi.org/10.4269/ajtmh.17-0407

Siala, E., Gastli, M., Essid, R., Jemal, S., Ben Abdallah, R., Ben Abda, I., … Bouratbine, A. (2015). Late relapse of imported plasmodium ovale malaria: A case report. Tunisie Medicale, 93(6), 347–350.

Mellon, G., Ficko, C., Thellier, M., Kendjo, E., Aoun, O., Adriamanantena, D., & Rapp, C. (2014). Two cases of late plasmodium ovale presentation in military personnel. Journal of Travel Medicine, 21(1), 52–54. https://doi.org/10.1111/jtm.12077

Davis, T. M. E., Singh, B., & Sheridan, G. (2001). Parasitic procrastination: Late-presenting ovale malaria and schistosomiasis. Medical Journal of Australia, 175(3), 146–148. https://-doi.org/10.1001/archpediatrics.2009.106

Waksman, J. C., Huminer, D., Keller, N., & Pitlik, S. D. (1999). Delayed synchronous outbreak of Plasmodium vivax malaria in four travelers. Journal of Travel Medicine, 6(2), 142–143. https://-doi.org/10.1111/j.1708-8305.1999.tb00847.x

Olaso, A., Ramos, J. M., López-Ballero, M. F., & Olaso, I. (2017). Malaria en Europa: seguimiento de la malaria autóctona en Grecia y nuevos riesgos. Enfermedades Infecciosas y Microbiologia Clinica, 35(8), 543–544. https://doi.org/10.1016/j.eimc.2016.11.003

Image mosquito: https://svgsilh.com/image/1465064.htmlMap Pakistan: https://simplemaps.com/resources/svg-pkMap UK: http://mapsvg.com/maps/united-kingdom/Malaria blood film: https://pixnio.com/science/microscopy-images/malaria-plasmodi-

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Islamabad (620m)

Jhelum (233m)

Karachi (8m)

T N T Nguyen, A See, B Dickinson, J Democratis, K Van Den AbbeeleFrimley Health Foundation Trust

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