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\begin{document}

\title{Rare Association of Plasmodium Vivax Malaria with Pulmonary
Thromboembolism: A Case Report}



\author[1]{Gashaw Solela }%
\author[2]{Merga Daba}%
\author[2]{Zerubabel  Geahun}%
\author[2]{Yared  Getachew }%
\author[3]{Dejene Girma}%
\affil[1]{Yekatit 12 Hospital}%
\affil[2]{Addis Ababa University College of Health Sciences}%
\affil[3]{St Paul's Hospital Millennium Medical College}%


\vspace{-1em}



  
  \date{May 19, 2024}


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\textbf{Rare Association of Plasmodium Vivax Malaria with Pulmonary
Thromboembolism: A Case Report}

Gashaw Solela\textsuperscript{1} Merga Daba\textsuperscript{2} Zerubabel
Getahun\textsuperscript{2} Yared Getachew\textsuperscript{2} Dejene
Girma\textsuperscript{3}

\textsuperscript{1}Department of Internal Medicine, Yekatit 12 Hospital
Medical College, Addis Ababa, Ethiopia

\textsuperscript{2}Department of Internal Medicine, College of Health
Sciences, Addis Ababa University, Addis Ababa, Ethiopia

\textsuperscript{3}Department of Internal Medicine, St. Paul's Hospital
Millennium Medical College, Addis Ababa, Ethiopia

\textbf{Abstract}

\textbf{Introduction:} The hypercoagulable complications of malaria
typically manifest in the microvasculature. However, there are several
cases of intracranial venous thrombosis caused by Plasmodium falciparum
and Plasmodium vivax malaria and there was one case report of pulmonary
thromboembolism due to Plasmodium falciparum. To the best of our
knowledge, there have not been case reports of plasmodium vivax
associated with pulmonary thromboembolism.

\textbf{Case Presentation:} A 30-year-old Ethiopian male patient
presented with sudden onset shortness of breath of 3 days duration. He
had also high grade fever, chills and rigors associated with loss of
appetite and fatigue of similar duration. He was from malaria endemic
area. He had a pulse rate of 108 beats per minutes, respiratory rate of
32 breaths per minute, oxygen saturation of 82\% with atmospheric air
and temperature of 38.9 degree Celsius. Further examination revealed
accentuation of pulmonary component of second heart sound. Complete
blood count revealed mild anemia and peripheral blood film showed
trophozoites of Plasmodium vivax. Pulmonary CT angiography showed
filling defects on the right and left pulmonary arteries. The patient
was diagnosed to have plasmodium vivax malaria complicated with
pulmonary thromboembolism. He was managed with intranasal oxygen,
antimalarial agent and anticoagulation. Upon serial evaluations on the
3\textsuperscript{rd} week and 2\textsuperscript{nd} month of follow up,
he did not have complaints and physical examination was non-remarkable.

\textbf{Conclusion:} Malaria is a protozoan disease with high mortality
and morbidity. For a long time, severe cases of malaria were thought to
be mostly caused by Plasmodium falciparum. However, recent evidences
have shown a paradigm shift and we should remember that Plasmodium vivax
can also cause severe malaria and this can be complicated by
hypercoagulable conditions.

\textbf{Key words} : Malaria, Pulmonary thromboembolism, Plasmodium
vivax

\textbf{Key Clinical Message}

Low threshold is required to suspect complications of Plasmodium vivax.
For any patient from malaria endemic area presenting with acute febrile
illness and shortness of breath, emphasis should be given to both
malaria and pulmonary thromboembolism.

\textbf{Introduction}

The 2022 World Malaria Report published by the World Health Organization
showed that there were 247 million malaria cases and 619,000 deaths in
84 malaria endemic countries. In the African region, there were 234,000
malaria cases and 593,000 deaths in 2021. This region accounted for
approximately 95\% of cases and 96\% of malaria deaths {[}1{]}. Malaria
is caused by infection with a protozoan parasite of the genus Plasmodium
and is transmitted by female Anopheles mosquitoes {[}2{]}.

For a long time, people believed that Plasmodium vivax is not very
harmful, but sometimes it can cause serious problems such as severe
anemia and ARDS {[}3{]}. Falciparum malaria can cause changes in the
coagulation cascade, including disseminated intravascular coagulation.
Hypercoagulable complications of malaria usually occur in the
microvasculature. However, there are several cases of intracranial
venous thrombosis due to Plasmodium falciparum and Plasmodium vivax
malaria {[}4-6{]} and there was also one case report of pulmonary
thromboembolism due to Plasmodium falciparum {[}7{]}.

To the best of our knowledge, there have not been case reports of
plasmodium vivax associated with pulmonary thromboembolism. Here, we
presented the case of a 30-year-old Ethiopian male patient who was
diagnosed to have plasmodium vivax malaria and pulmonary
thromboembolism.

\textbf{Case Presentation}

A 30-year-old Ethiopian male patient presented with sudden onset
shortness of breath of 3 days duration. He had also high grade fever,
chills and rigors associated with loss of appetite and fatigue of
similar duration. He was from malaria endemic area of the country.
Otherwise, he had no history of recent surgery or trauma, no known
chronic medical illness and no family history of similar illness.

He was acute sick looking with blood pressure of 100/70 mmHg, pulse rate
of 108 beats per minutes, respiratory rate of 32 breaths per minute and
body temperature of 38.9 degree Celsius. His oxygen saturation was 82\%
with atmospheric air improving to 92\% with 3 liters of oxygen support
through nasal cannula. Further examination revealed accentuation of
pulmonary component of second heart sound. Otherwise, there were no
pertinent positive findings on other systems.

Upon investigations, complete blood count revealed mild anemia with
hemoglobin of 11g/dl (reference range: 12-16 g/dl) and normal white
blood cell and platelet counts. Renal and liver function tests were
within normal ranges. Peripheral blood film showed trophozoites of
Plasmodium vivax with amoeboid cytoplasm and large chromatin dot (Figure
1). ECG was remarkable for sinus tachycardia, right ventricular strain
pattern and S1T3Q3 pattern (Figure 2). Pulmonary CT angiography showed
filling defects on the right and left pulmonary arteries (Figure 3) with
dilatations of the IVC, right atrium and right ventricle (Figure 4).

After the patient was diagnosed to Plasmodium vivax malaria, he was
started on chloroquine phosphate, which was taken for a total of 3 days
(1000mg on day 1 and day 2 followed by 500mg on day 3) with paracetamol
1000mg PO per need. The cause of the respiratory distress was not
initially clear and with the impression of acute respiratory distress
syndrome to rule out pulmonary thromboembolism, he was put on intranasal
oxygen maintaining at 3 liters per minute and empirically started on
anticoagulation with unfractionated heparin 5000 IU IV stat followed by
17, 500 SC BID. Pulmonary CT angiography was done subsequently and the
presence of pulmonary thromboembolism was confirmed. The final working
diagnosis was Plasmodium vivax malaria complicated with pulmonary
thromboembolism. On the 3\textsuperscript{rd} day after initiation of
the antimalarial and anticoagulation therapy, the patient showed
significant improvement and he started to maintain his oxygen saturation
with atmospheric air. Finally, anticoagulation was changed to
rixaroxaban 15mg PO BID and he was discharged with appointment. Upon
serial evaluations on the 3\textsuperscript{rd} week and
2\textsuperscript{nd} month of follow up, he did not have complaints and
physical examination was non-remarkable.

\textbf{Discussion}

The five species of Plasmodium that cause malaria in humans are
Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium
malariae, and Plasmodium knowlesi. Plasmodium falciparum causes the
highest disease burden, followed by Plasmodium vivax {[}8, 9{]}. Severe
malaria is usually caused by Plasmodium falciparum; however, severe
malaria and even death can occur in patients infected with Plasmodium
vivax {[}3, 10{]}.

The traditional thought that Plasmodium vivax is a benign disease is
changing, and severe Plasmodium vivax malaria has been reported in
recent years. Reported serious manifestations include liver dysfunction,
cerebral malaria, death, severe anemia, severe thrombocytopenia,
respiratory distress, disseminated intravascular coagulation, renal
dysfunction, hypoglycemia, generalized seizures, shock, and
hemoglobinuria and metabolic acidosis {[}11{]}.

Three cases of intracranial venous thrombosis (a case of cerebral venous
thrombosis and two cases of sagittal sinus thrombosis) caused by
Plasmodium falciparum and Plasmodium vivax have been reported from
India. Two of the three patients had mixed Plasmodium faciarum and vivax
infection. A hypercoagulable state secondary to severe malaria is
thought to have been the cause of this rare and potentially fatal
complication {[}4{]}. In addition, there were additional case reports of
cerebral venous thrombosis in patients with Plasmodium vivax malaria
among patients from India {[}5{]} and there was a case report sagittal
sinus thrombosis associated with severe Plasmodium vivax in a patient
from from Columba {[}6{]}.

There was only a case report of massive venous thromboembolism caused by
disseminated intravascular coagulation due to severe Plasmodium
falciparum malaria {[}7{]}. In contrast to this case report, our patient
had Plasmodium vivax malaria and no evidence of disseminated
intravascular coagulation. Although the pathogenesis of pulmonary
thromboembolism in our patient remained unclear, it may be related to
hypercoagulable conditions with a pathophysiological mechanism similar
to Plasmodium falciparum malaria {[}4{]}.

Our patient was young, and he had no identified risk factors for
thrombosis. Hence, we believe that our patient's pulmonary
thromboembolism is most likely secondary to hypercoagulabe state induced
by Plasmodium vivax malaria.

\textbf{Conclusion}

Malaria is a protozoan disease with high mortality and morbidity. For a
long time, severe cases of malaria were thought to be mostly caused by
Plasmodium falciparum. However, recent evidences have shown a paradigm
shift and we should remember that Plasmodium vivax can also cause severe
malaria and this can be complicated by hypercoagulable conditions.

\textbf{Author Contributions}

\textbf{Gashaw Solela:} Conceptualization; data curation; formal
analysis; resources; writing -- original draft; writing -- review and
editing. \textbf{Merga Daba} : Conceptualization; data curation;
resources, writing -- original draft. \textbf{Zerubabel Getahun} : Data
curation, resources and writing -- original draft. \textbf{Yared
Getachew:} Data curation, resources and writing -- original
draft.\textbf{Dejene Girma} : Data curation and writing -- original
draft

\textbf{Acknowledgements}

The authors would like to thank the patient for approving the
publication of his case details.

\textbf{Funding information}

There was no specific grant received from any funding agency in the
public, commercial, or not- for- profit sectors.

\textbf{Conflict of Interest Statement}

The authors declared no potential conflicts of interest.

\textbf{Data Availability Statement}

The data that support this case report are available from the
corresponding author upon reasonable request.

\textbf{Ethics Statement}

Ethical clearance including publication of this patient's case details
was obtained from the Institutional Review Board of Tikur Yekatit 12
Hospital Medical College.

\textbf{Consent}

The patient gave an informed written consent for the publication of his
case details and accompanying images.

\textbf{References}

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