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CASE REPO
RT

Severe malaria vivax with sepsis

bacterial : a case report
Ginting Fransiscus
Tarigan Pulung
Division of Infectious and Tropical Diseases,
Department of Internal Medicine, Haji Adam Malik
Hospital, North Sumatera, University of Sumatera
Utara.Indonesia
Abstract: Malaria still remains as a neglected case indeed in
tropical areas like Indonesia. Some cases show overlapping signs
and symptoms with another infection that are common in tropical
areas such as tyhpoid, dengue and leptospirosis. It can be
misdiagnosed in practice and led to a wrong management that
can end fatally. Severe malaria is usually caused by Plasmodium
Falciparum . Plasmodium vivax (P. vivax) can also cause severe
malaria but the cases reported are rare.
Since infections with severe P. vivax that generally result in
serious disease is quite rare in Indonesia, their identification and
management is important. We report a case of severe malaria
patient with sepsis and renal injury associated with malaria in a
70-year-old male. Clinical manifestations included anemia,
oliguria, sepsis, and also elevated serum of creatinine, urea and
procalcitonin. The rapid diagnostic test for malaria and
microscopic examination of blood smears were positive for P.
vivax.. The patient was treated as malaria with intravenous
artesunate for 6 days, followed by oral treatment of primaquin
for 14 days. Volume expansion, antipyretic, anti malaria and
antibiotic treatment were administered. The patient was stable
and then discharged from the hospital. This outcome is not
always the case. The prognosis depends much on early diagnosis
and appropriate supportive treatment.
Keywords: malaria vivax, oliguric kidney injury, sepsis,
artesunate
Introduction
Malaria still remains as neglected cases indeed in tropical areas
area like Indonesia. Some cases show overlapping signs and
symptoms with another infection that are common in tropical
areas such as tyhpoid, dengue and leptospirosis. Today malaria is
still a general health problem worldwide, especially in Indonesia.
Five types of Plasmodium have been found to infect human;
Plasmodium vivax (P.vivax), P. ovale, P. malariae, P.falciparum
and P. knowlesi.. Infections by P.vivax and P.falciparum
represent the two most frequent types found. Although infection
by P.falciparum is more likely to show more severe clinical
manifestations than P. Vivax, P.vivax can also cause severe
disease in several cases. P vivax is the most widely distributed
human malaria parasite with risk population of 2.5 billion
persons1,7 The latest WHO estimates, released in December 2016
said that there were 212 million cases of malaria in 2015 and
429000 deaths. In Indonesia, malaria disease is still a highly
infective disease, particularly in the east region of the country.
According to the basic health research of Indonesia
(RISKESDAS) in 2013, the prevalence of malaria was 6 %, and
it has declined globally from 2,9 % to 1,9 %. In North Sumatera,
the prevalence was 5,2 % . Datas from the North Sumatera health
profile also showed that in 2013, North Tapanuli, one area in the
province, had 463 of suspected malaria cases, with 38 to be
found malaria positive5. From that data, it was found that the
incidence for malaria in North Tapanuli was 8,21% 6. Severe
malaria is life-threatening, and can cause death. Treatment of this
malaria according to WHO is artesunate injection 2,4mg/kb BW
until the patient can tolerate oral drugs 1. Sepsis is a one of
condition that add up morbidity and mortality to the patients with
malaria. In sepsis, serum procalcitonin (PCT) levels correlate
well with the severity of sepsis and the later outcome. PCT is a
prohormone of calcitonin that is found elevated in any bacterial
infection.9 Serum PCT levels increase during severe generalized
bacterial, parasitic or fungal infections with systemic
manifestation. In severe viral infections, or inflammatory
reactions of non-infectious origin, serum PCT levels do not
increase or only show a moderate increase10. PCT cut off point in
malaria disease is 10,0 ng/ml with sensitivity 67%, specificity
94%. The higher increase of PCT is related to fatal outcome9.
Figure 1. Schizont and Sporozoit Plasmodium vivax

Treatment was begun with Intravenous (IV)fluids, followed by

Case report
A 70-year-old male, Asian, was initially admitted to Haji Adam
Malik Center hospital in August 2017 with a 14-day history of
intermittent fevers, headaches, rigors, and chills, and a 1-day
history of nausea, vomiting, and diffuse abdominal pain..When
he subsequently developed fever and chills symptoms, he came
to the hospital. He had yellowish color in sclera since the
previous 7 days. In admission, the patient was alert and well
oriented. The temperature was 38,2°c, heart rate of 90x/min,
blood pressure of 110/70 mm/Hg, and respiratory rate 28 x/min.
Physical examination findings were significant for diffuse
abdominal tenderness and yellowish in sclera orbital. Laboratory
studies showed a white blood cell (WBC) count of 12280/µL,
hemoglobin of 10 g/dL, and a platelet count of 15000/µL. The
total bilirubin concentration was 9.8 mg/dL with a direct bilirubin
of 7.3 mg/dL. Ureum was elevated 261 mg/dl, creatinin 4,16
mg/dl.Procalcitonin was 24,48ng/ml. Transaminases were normal
with a serum aspartate aminotransferase (AST) level of 22 U/L,
an alanine aminotransferase (ALT) 20 of U/L, and an alkaline
phosphatase level of 64 U/L. Examination of a blood thin smear
revealed ringed trophozoites typical of the P. vivax. Density
plasmodium malaria of patient was +++ ( found 1-10 parasites in
high power field) in malaria vivax blood checked. Abdominal
ultrasound showed a thickened gallbladder wall diameter
common bile duct, but showed no gallstones or biliary ductal
dilatation.Cholecystitis was diagnosed.
injections of Ceftriaxone 1gr/12 H for 4 days, which then
switched to ampicillin-sulbactam 1,5 gr/8H, omeprazole
40mg/12H, artesunate 2,4 mg/kg Body weight daily and then 1,2
mg/kg body weight for six day , and also oral primaquin 15mg
one time daily. Over 3 days after initiation of antimicrobial
therapy, the patient’s clinical condition improved. Injection of
ampicillin-sulbactam were discontinued after the patient’s fever
resolved. By the fourth day of treatment, his serum of ALT and
AST, though still mildly elevated, had declined, and his serum
alkaline phosphatase and total bilirubin total levels declined to
2,6. By the fifith day of treatment, his WBC count returned
within normal limits and platelet began to rise up to 85000
mg/dl, ureum had declined to 163 mg/dl and creatinin had
declined to 2,82 mg/dl and by the ninth day ureum had declined
to 66 mg/dl and creatinin to 2.00 mg/dl. A repeated blood smear
on the third day after treatment with artesunate showed clearance
of parasitemia. The hemoglobin concentration, however,
declined to 6.7 g/dL initially then by the fourth day it began to
rise up to 8.3g/dl. In the seventh day of treatment, the clinical
symptoms started to improve and had finally resolved completely
by the ninth day. The patient was discharged with instructions to
complete a 2-week course of oral treatment of primaquine.

Day Day Day Day Day Day Day

 fresh RBC to perpetuate the asexual life cycle. At the same time,
1 2 3 4 5 6 14
a large amount of toxins and parasite products are also released
and cause the activation of the innate immunity, the release of
Density of +++ + - - - - -
inflammatory mediators and the symptoms associated with the
Plasmodiu malaria attack, such as fever. After 24–32 hours, when young
m parasites mature from the ring to the trophozoite stage, IRBC
adhere to endothelial cells in the microcirculation of various
Haemoglo 10 10,6 7,4 8,3
organs. This phenomenon, termed “sequestration”, is believed to
bin
occur mainly to avoid splenic removal of IRBC. Sequestration
causes microcirculatory obstruction, impaired tissue perfusion
Platelet 150 130 500 850
and inflammatory cells activation and it is linked to the severity
Count 00 00 0 00
of the disease. Cytoadherence is the ability of parasites to adhere

Creatinin 4,16 4,05 4.44 4,16 2 to the vascular endothelium. Mature forms of parasites (asexual
stage and gametocytes) can adhere to the vascular endothelium
Bilirubin 7 9,80 of several organs (lung, heart, brain, lung, liver, and kidney), the
total subcutaneous adipose tissues and the placenta. Rosetting is one
of the forms of cytoadherence of late stages IRBC to non-
Procalcito 24,4 8,96 1,48 parasitized red blood cells and /or platelets. These three
nin 6 pathogenesis of malaria make the severity to malaria. According
to surviving sepsis campaign: international guidelines for
Sofa score 9
management for sepsis and septic shock 2016, sepsis was defined

Table 1. Patient Condition as life-threatening caused by dysregulated host response to

infection11. Severity of organ dysfunction has been assessed with
various scoring systems that quantify abnormalities according to
Discussion clinical findings, laboratory data, or therapeutic interventions.
Severe malaria vivax is defined as one or more of the following
The predominant score in current use is the Sequential Organ
1. impaired consciousness (Glasgow coma scale <11);
Failure Assessment (SOFA) (originally the Sepsis-related Organ
2. Prostration (generalized weakness so that the person is unable
Failure Assessment). A higher SOFA score is associated with an
to sit,stand or walk without assistance);
increased probability of mortality11.
3. Multiple convulsion (more than 2 episodes within 24 hours);
Acidosis (plasma bicarbonate level <15 mmol/L atau venous
plasma lactate > 5mmol/L);
4. Hypoglycemia (plasma glucose < 40mg/dl);
5. Severe malarial anemia ( Hb ≤ 7g/dl or Hematocrit ≤20%);
6. Renal impairment (serum creatinine > 3 mg/dl);
7. Jaundice ( serum bilirubin > 3 mg/dl);
8. Pulmonary edema
9. Significant bleeding ( recurrent or prolonged bleeding from
nose, gums, or venipuncture, hematemesis or melena);
10.Shock ( systolic blood pressure <70 mmHg);
11.Hyperparasitemia (Parasitemia >10 %) with no parasite Figure 2. SOFA score ≥2 means organ dysfunction

density threshold,
Uchil Sudhir, Ravi Kumar Venkatachalaiah et al in their research
This could clinically lead to life-threatening episodes 1,2,3,5,6. In
had a result that Higher SOFA score levels were associated with
this patient, we met the criteria by the malarial anemia,jaundice,
significantly higher serum PCT concentrations (P<0.05)10,
renal impairment, and parasitemia in blood.
Serum PCT proved to be an excellent indicator of sepsis in
Severe malaria could happen to human and it is caused by its
critically ill patients, with sensitivity of 94%.Normally none in
pathogenesis of in human tissues and blood. As the schizonts
the blood stream10. Procalcitonin is a prohormone of calcitonin
rupture, from 4 up to 36 daughter merozoites, depending on the
that is found elevated in any bacterial infection.9 Serum PCT
Plasmodium species, are released into the circulation and invade
levels increase during severe generalized bacterial, parasitic or
fungal infections with systemic manifestation. In severe viral
infections, or inflammatory reactions of non-infectious origin,
serum PCT levels do not increase or only show a moderate
10
increase . PCT cut off point in malaria disease is 10,0 ng/ml with
sensitivity 67%, spesifisity 94%. The higher increase of
procalcitonin were related to fatal outcome 9. According to the
Italian score which is a model to identify patient infected with
extended- spectrum β lactamase (ESBL), 80% of scores 8 or
above were associated with case 12. The carbapenem are still the
first choice of treatment for serious infections with ESBL-
producing E.coli and K. pneumonia but with emergence of
carbapenem=resistant Enterobacteriaceae, the “magic bullet” is
difficult to find 12. There are some drugs which can be used to
treat this bacteria, fosfomycin, colistin tigecycline,
ampicillin/sulbactam,piperacillin-tazobactam 12,13
. According to
second edition WHO guidelines for treatment of malaria, the
dose to treat severe malaria is 2,4mg/Kgbw/IV/IM at 0, 12 hours,
24 hours, then qDay until the could tolerate oral therapy,
complete treatment with 3 days of an ACT (artemisin-based
combination therapies)1.
Conclusion we reported a case of severe
malaria vivax with sepsis in 6 days length of stay in Adam
Malik Hospital and patient got discharged. The prognosis
usually depends on early diagnosis and treat-ment.
Consent
Written informed consent for publication of the clinical details
was obtained from the patient.
Disclosure
The authors report no conflicts of interest in this work.
 9. Dennis A, Hesselink Jan-Steven Burgerhart et al.
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