Correspondence:
Andri Baftahul Khairi
Email: [email protected]
INTRODUCTION
Plasmodium knowlesi is one of the most common causes of
Malaria in humans. The
definitive hosts of this parasite are Macaca fascicularis (long tail) and
Macaca nemestrina (pigtail) in Southeast Asia. Since 2004, researchers have begun studying the
increasing number of P. knowlesi infections in Kapit Division, Sarawak,
Malaysia (Singh & Daneshvar, 2013). Since then, there have been many reports of cases of
plasmodium infection in other countries in Southeast Asia. Several pieces of P.
knowlesi malaria infection cases in Indonesia, especially in Kalimantan. There have only been 4 cases of severe and fatal knowlesi
malaria infection in humans in the world (Ompusunggu et al., 2015)(Daneshvar et al., 2018).
Malaria
is a protozoan infection caused by the genus Plasmodium. Currently, more than
150 species of Plasmodium infect mammals, birds and reptiles (Sato, 2021). Of the 20
species of Plasmodium that infect macaques, five can infect humans under
natural or experimental conditions: P. simium, P. brazilianum, P. cynomolgi, P.
inui and P. knowlesi. Plasmodium knowlesi (P. knowlesi) was first isolated in
1931 in India in a long-tailed macaque imported from Singapore. Sinton and
Mulligan first studied morphological features in experimental infections in
macaques.3 Around 1920-1950, P. knowlesi began to replace P. vivax in treating
neurosyphilis by inducing fever. This treatment method was malaria therapy (Singh & Daneshvar, 2013).
The
first case of P. knowlesi malaria infection in humans occurred in 1965 in an
American citizen who had just returned from working in the forests of
peninsular Malaysia. Initially, the patient was thought to have falciparum
malaria infection. The second case occurred in 1971 when a Malaysian citizen
was diagnosed using molecular methods. Initially, the patient was suspected of
having malaria malaria infection microscopically. Since then, there have been
no more cases of natural disease with P. knowlesi in humans until 2004. This is
probably because diagnosing P. knowlesi infection is challenging to establish
and requires rhesus monkeys as experimental animals, so it is rarely studied
anymore (Nelwan & Subbagian,
2013; Lee & Vythilingam,
2013).
Plasmodium
knowlesi is a common plasmodium that infects long-tailed macaques, Macaca
fascicularis (long tail) and pig-tailed macaques, Macaca nemestrina (pigtail)
in Southeast Asia. Plasmodium knowlesi usually causes mild infection in Macaca
fascicularis and severe infection in rhesus monkeys (Macaca mulata). Since
2004, Balbir Singh and colleagues began to study natural infection with P.
knowlesi, which was increasing in incidence in Kapit Division, Sarawak,
Malaysia.5 Since then, there have been many case reports of plasmodium knowlesi
infection in other countries in Southeast Asia. In Indonesia, there have been several
case reports of P. knowlesi malaria infection, especially in Kalimantan Island.
To date, there have only been 4 cases of severe and fatal knowlesi malaria
infection in humans in the world (Ompusunggu et al., 2015; Daneshvar et al., 2018).
Dengue fever and Malaria are endemic
diseases that often occur in Southeast Asia, including Indonesia. However, only
a few cases of malaria and dengue infections co-occurring in Southeast Asia
have been reported (Sahu et al., 2016). The clinical
manifestations
in this case are generally more severe, accompanied by different laboratory
images (Mushtaq et al., 2013). A thorough history, physical
examination, and supporting studies are needed to diagnose these two conditions
simultaneously. Diagnosis yang tepat dan cepat akan memberikan tatalaksana yang
sesuai dan memberikan luaran pasien yang lebih baik. Precise diagnosis will provide
appropriate treatment and provide better patient outcomes.
Plasmodium knowlesi, a
causative agent of Malaria in humans, has attracted considerable research
attention in recent years, especially in Southeast Asia. The novelty of this
study lies in its focus on the emerging epidemiological patterns of P. knowlesi
infections, particularly in regions like Kapit Division, Sarawak, Malaysia,
where the prevalence has witnessed a noticeable rise since 2004. The
investigation extends beyond the initial hotspot to explore the expanding
geographic footprint of P. knowlesi infections in Southeast Asia, shedding
light on its occurrence in Indonesia, precisely in Kalimantan.
Furthermore, the rarity of
severe and fatal P. knowlesi malaria infections in humans globally adds another
layer of novelty to the research. With only four documented cases worldwide,
understanding the factors contributing to the severity of these infections
becomes imperative from both clinical and public health perspectives.
The concurrent occurrence of
dengue fever and P. knowlesi malaria represents an intriguing aspect of this
study. While both diseases are endemic in Southeast Asia, reports of their
simultaneous infections are scarce. The novelty of investigating coinfections
lies in the potential exacerbation of clinical manifestations and distinctive
laboratory findings, presenting a unique challenge in diagnosis and management.
By
investigating the co-occurrence of these diseases, the study seeks to improve
diagnostic precision, facilitating timely and appropriate treatment.
Ultimately, achieving accurate diagnoses is expected to enhance patient
outcomes, reduce morbidity and mortality rates, and inform public health
strategies in the region. This research aims to contribute to understanding the
epidemiology and clinical aspects of concurrent P. knowlesi malaria and dengue
fever infections, particularly in Southeast Asia.
METHOD
A
36-year-old man came to the emergency room at Meuraxa Regional Hospital with a
fever for the last five days. Fever tends to be high, fluctuating, and
accompanied by chills and profuse sweating. Patients also complain of nausea,
joint pain, pain throughout the body, and dizziness. History of spontaneous bleeding was denied. Micturition and defecation
are normal. The patient has a history of travelling and staying overnight in
the mountains in the Lhoknga area. No family members experienced complaints
similar to the patient's. History of systemic
diseases such as hypertension, type II diabetes mellitus, heart disease, kidney
disease, and others are not found in this patient. His friends who
travelled to the mountains also had complaints similar to the patients.
RESULTS AND DISCUSSION
On physical examination, hemodynamics was stable, but the
temperature reached 38.5 degrees. The biological study revealed hyperemic
conjunctiva, and signs of hemolytic anaemia, such as anaemic conjunctiva and
icteric sclera, were absent. There were no signs of spontaneous bleeding, such
as petechiae, hematemesis, or hematochezia. Laboratory examinations carried out
in the emergency room gave Hb results of 13.4; erythrocytes 5.67 million; Ht
39.5; MCV 69.7; MCH 23.6; MCHC 33.9; leukocytes 6700; platelets 60,000;
peripheral blood 3/1/76/14/6; GDS 147 mg/dL. On serological examination, it was
found that NS-1 was reactive, and dengue IgG was positive.
The patient was diagnosed with dengue hemorrhagic fever grade 1.
The patient was then given treatment in the form of bed rest, IVFD 20 drops per
minute, and the administration of intravenous paracetamol 1 gr and intravenous
omeprazole 40 mg. The patient is planned for hospitalization and routine
haematological examination every 24 hours.
On the second day of treatment, the fever was felt to have
disappeared. However, the patient complained more about pain throughout the
body. Signs of bleeding, such as epistaxis and petechiae, were not found. The
results of the physical examination were within normal limits. Second day's lab
examination showed Hb 13.3; erythrocytes 5.58 million; Ht 38.5 ; MCV 69.0; MCH
23.8 ; MCHC 34.5 ; leukocytes 6100 ; platelets 56,000; peripheral blood
3/1/76/14/6 ; GDS 147 mg/dL
On
the third day of treatment, the patient complained of fever again, accompanied
by vomiting. Signs of bleeding, such as epistaxis petechiae, were not found.
The results of the physical examination were within normal limits. The third
day's lab examination showed Hb 13.3; erythrocytes 5.58 million; Ht 38.5; MCV
69.0; MCH 23.8; MCHC 34.5; leukocytes 6100; platelets 56,000; peripheral blood
3/1/76/14/6; GDS 147 mg/dL. SADT Results: Microcytic
hypochromic anaemia + thrombocytopenia ec Plasmodium knowlesi and Malaria
Examination Results (microscopic): Positive for Plasmodium knowlesi
trophozoite, schizont, gametocyte stages.
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Stadium schizont
Figure 1. Microscopic Malaria
The patient complained
of fluctuating fever and profuse sweating from the fourth to the eighth day of
treatment. The patient's temperature was in the range of 37.8-38.5 degrees
Celsius. There were no signs of bleeding on physical examination, such as
epistaxis, hematemesis, hematochezia, or bleeding from the gums. The following
graphic depicts the patient's Hb and platelet values from days 1 to 11.
Figure 2.
Platelet chart during treatment
Figure 3. Hb chart during treatment
Because the fever did not improve and additional
symptoms appeared, such as chills and sweating, on the eighth day of treatment,
the patient had a blood smear. A picture of Plasmodium knowlesi in the
trophozoite, schizont, and gametocyte stages was obtained.
From the eighth day of
treatment, the patient was given an anti-malaria regimen in the form of DHF 1x4
tablets for three days and primaquine 1x1 tab. After administering the
anti-malarial drug regimen, the patient's clinical course improved. Complaints
of fever and sweating were reduced, and platelet and Hb values were also
enhanced. The patient
had a final diagnosis of dengue fever accompanied by Malaria Knowles. After being hospitalized for
ten days, the patient improved and showed no complications.
Malaria and dengue are diseases spread through
mosquito vectors, which play a significant role in the mortality and morbidity
of tropical diseases (Chawla et al., 2014). Malaria is
a parasitic infection caused by the plasmodium parasite and transmitted by the
Anopheles mosquito. There are several Malaria species, but Plasmodium knowlesi
is the most commonly found in Southeast Asia. Malaria will grow and reproduce
in the human body in liver cells/hepatocytes and red blood cells (Shah & Mehta, 2017; Kotepui et al., 2020). Dengue is
an ssRNA virus infection that is spread through the Aedes Aegipty. The dengue
virus is divided into several serotypes, namely DENV 1, 2, 3, and 4, which are
included in the flaviviridae family (Shah & Mehta, 2017; Kotepui et al., 2020).
Concurrent infection between these cases of
dengue and Malaria can appear and provide similarities in clinical
manifestation so that they are often underdiagnosed, which also causes
undertreatment conditions. In some cases, The clinical images are more severe
in concurrent infection conditions (Mushtaq et al., 2013). Several
case reports found that many infections often occur due to dengue coinfection
with other agents, including flavivirus, chikungunya, salmonella typhoid,
shigella sonnet, and leptospira. The first case report of concurrent infection
between dengue with plasmodium falciparum first appeared in 2005 after the
patient travelled to Senegal and Guinea and was followed by the emergence of a
case report of dengue coinfection with plasmodium vivax in 2006, which appeared
in South Asia (India) (Mushtaq et al., 2013).�
Based on a study conducted by Mohsin in 2013 in
Guinea, it was found that the specificity level for concurrent infection
between dengue and Malaria was 99%, which indicates a high rate of coinfection
in that area (Garg et al., 2016). Dengue
coinfection with Malaria is often found in Southeast Asia, such as Indonesia.
Of the 36 cases of coinfection between dengue and Malaria, Indonesia is in
fourth position in the number of reported cases (Mushtaq et al., 2013).
The clinical picture of malaria and dengue
infections is similar. The symptoms that appear, especially in coinfection
cases, are high fever accompanied by thrombocytopenia, which can occur in some
cases of Malaria (Balaji et al., 2020). The
symptoms that occur mainly in topics of coinfection are high fever and
thrombocytopenia, which can appear in some cases of Malaria (Shah & Mehta, 2017; Sedger & McDermott, 2014). Anaemia is
the main sign or symptom that occurs in malaria cases due to the malaria life
cycle, which causes intravascular hemolysis (Balaji et al., 2020). Other
clinical manifestations that can arise from Malaria are myositis,
rhabdomyolysis, and acute renal failure. This is thought to be due to an
increase in mediators in the form of TNF-a (tumour necrosis factor-alpha),
which will trigger inflammatory processes in various areas and increase the
synthesis of metabolic toxins and lactic acidosis which causes myositis,
skeletal muscle necrosis, and myoglobinuria (Shah & Mehta, 2017; Sedger & McDermott, 2014).
In a case report conducted in Brazil, it was
found that a patient with a case of dengue and malaria coinfection experienced
severe thrombocytopenia and was still getting worse after being observed for
several days (Tejo et al., 2023). However,
after being given anti-malarial, both clinically and in terms of laboratory
values, improvements were obtained. Using Hb as a coinfection marker is
difficult because of the hemoconcentration effect, so Hb and Ht are
incompatible (Magalh�es et al., 2014).
Malaria and dengue give signs of high fever, although
Malaria gives fever symptoms that last longer than dengue (Sahu et al., 2016). A
haematological triad, such as atypical lymphocytosis, hemo concentration, and
thrombocytopenia, is the main sign in diagnosing dengue based on blood
findings. It also can be used as a consideration for malaria exclusion (Kotepui et al., 2020).
In most cases, the diagnosis of dengue is made
based on the presence of IgM. In contrast, the diagnosis of Malaria must be
based on a microscopic examination in the form of a blood smear (Assir et al., 2014). Several
studies state that positive IgM antibody titers using ELISA in dengue cases can
provide similar results in malaria cases. Apart from that, false adverse claims
can also be found in secondary infections of dengue patients (Magalh�es et al., 2014; Miri et al., 2021).
These two
conditions have similar clinical manifestations. Careful anamnesis, physical
examination, and supporting studies are needed to diagnose these two conditions
simultaneously. Precise diagnosis will provide appropriate treatment and
provide better patient outcomes.
CONCLUSION
Based
on the results and discussion above, it can be concluded that the patient's
clinical condition improved after starting the anti-malarial regimen,
underscoring the importance of considering multiple infections in areas where
dengue fever and Malaria are common. This case highlights the need for a
comprehensive diagnostic approach, including a thorough history, physical
examination, and supporting laboratory tests to accurately identify and treat
coinfections, ultimately ensuring appropriate and timely treatment for better
patient outcomes.
Additionally,
this case highlights the challenges posed by the overlapping clinical
manifestations of dengue fever and Malaria, making correct diagnosis critical.
This study also emphasizes the limitations of relying on specific diagnostic
markers alone, such as IgM antibody titers for dengue fever and microscopic
examination for Malaria. In regions such as Southeast Asia, where both diseases
are endemic, health practitioners must remain alert to the possibility of
coinfection. This awareness and multidimensional diagnostic strategies are
critical to improving diagnostic accuracy, tailoring treatment plans, and
preventing potential complications in patients suffering from dengue and
malaria infections.
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Received: 28-11-2023 �������������������� ������������� Accepted: 12-12-2023 �������������������� ��������������Published: 02-01-2024����� 