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Jurnal Indonesia Sosial Teknologi, Vol. 5, No. 6, June 2024 2827

A case report: Maternal complications from severe dengue.

What can happen?

Reny Faristin Putri Arifin

, Wildan Firmansyah

RSUD dr. Soedono Provinsi Jawa Timur, Indonesia

Email: [email protected]

, [email protected]

*Correspondence

ABSTRACT

Keywords: Pregnancy,

DHF, Pulmonary Edema.

Dengue fever (DHF) is an acute infectious disease caused by

dengue virus. Thrombocytopenia results from viral

suppression in the bone marrow, and platelet destruction

occurs. Damaged platelets worsen plasma leakage. When the

amount of filtration fluid exceeds the ability and fluid

trapped in the interstitium eventually enters the alveoli, there

is an increase in alveolar capillaries, resulting in pulmonary

edema. The patient was referred with complaints of fever for

5 days, dizziness (+), shortness of breath (+), nausea (+), and

vomiting (+). Laboratory examination showed platelets 109

x 103/µL, positive Ig G DHF Immuno Serology, and thorax

X-ray with pulmonary edema. Cesarean section and IUD

insertion were performed. During and after surgery, there

were no complications.

Introduction

Dengue viruses (DENVs) form dengue complex in the genus Flavivirus, family

Flaviviridae, and consist of four antigenically related but distinct DENV serotypes

(DENV-1, DENV-2, DENV-2, DENV-3, and DENV-4). These DENVs can cause a

spectrum of illnesses ranging from asymptomatic dengue infection to dengue fever (DF)

to dengue hemorrhagic fever (DHF) to dengue shock syndrome (DSS). It is estimated that

close to 3.6 billion are at risk, with 390 million infections, of which 96 million are

symptomatic. Among the 96 million symptomatic cases, 2 million end in severe forms of

infections, that is, DHF and DSS, and around 21,000 fatal cases occur annually around

the world. Most of these infections occur in developing and underdeveloped countries

where the surveillance network for infectious diseases is not robust, which means there

is a possibility of gross underreporting of dengue (Iskandar, 2022). In this chapter, we

will discuss the evolution of the virus and its vector, the epidemiology of dengue, the

molecular and genomic structure of DENV, their pathogenesis, the immune response of

the host to the infection, laboratory diagnosis, management, and recent developments in

dengue drug and vaccine development (Thergarajan & Sekaran, 2023).

Dengue is endemic to the Southeastern geographical area of Asia (SEA) and spreads

through the mosquito vector Aedes aegypti (Organization, 1997). Globally, the incidence

of dengue increased from 30,668,000 in 1990 to 56,879,000 in 2019 (Murugesan &

Reny Faristin Putri Arifin, Wildan Firmansyah

Jurnal Indonesia Sosial Teknologi, Vol. 5, No. 6, June 2024 2828

Manoharan, 2020). In SEA alone, there were 7,700,000 cases of dengue in 2019 (Tian et

al., 2022).

It was reported that dengue is the most common cause of fever during pregnancy

(46%) in Vientiane, Laos (Chansamouth et al., 2016). In 2015, 82,000 patients in Vietnam

had dengue infection nqw /i25 deaths. The mortality rate for severe dengue fever is 0.8–

2.5%, and pregnancy should be recognized as a coexisting risk factor for severe infection.

However, the maternal and fetal outcomes remain not fully understood. The first systemic

review could not determine whether maternal dengue infection is a risk for adverse effects

because there were few comparative studies (Pouliot et al., 2010). Recently, the first

systematic review on outcomes of neonates born to mothers with dengue fever was

reported, and it demonstrated that preterm birth and low birthweight were reported to be

the most common adverse pregnancy outcomes; however, dengue fever was not

significantly associated with these adverse outcomes, suggesting that symptomatic

dengue fever may indicate risk (Paixão, Teixeira, Maria da Conceição, & Rodrigues,

2016).

The picture of DHF cases in 2023 in Madiun City has affected 144 people, with 1

case of death. The dengue morbidity rate in 2023 was 80.75/100,000 population, and the

dengue mortality rate in 2023 was 0.69%. And the DHF mortality rate in 2023 was 0.69%.

Data for 2024 up to 16 February 2024 show that 66 cases of DHF have been reported, 1

case of death, a morbidity rate of 36.89/100,000 population, and a mortality rate of 1.52%

(Astuti, Dwiningwarni, Atmojo, Masfufa, & Yanesty, 2023).

Case report of Mrs. E, 26 years old, referral from a private hospital, gravida 3, the

first child aged 8 years, abortion 1x. With complaints of fever for 5 days, accompanied

by dizziness (+), headache (+), weakness (+), nausea (+), vomiting (+) 3 times today, and

shortness (-). Mucus comes out of the birth canal. Bleeding complaints such as nosebleeds

or bleeding gums are denied. Complaints of red spots on the skin are denied (Amanda,

Wiratmo, & Utami, 2023). Complaints of tightness - tightness and feeling of fluid seeping

from the birth canal are denied. Paien is 37-38 weeks pregnant from HPHT. Blood

pressure 105/72, pulse 115 times/minute, respiratory rate 20 times/minute, temperature

36.5 degrees Celsius, SpO2 100%. Physical examination found anemis in the conjunctiva.

From the obstetric examination, Leopold I inspection palpable soft, non-bouncy, podium

fundus height of 30 cm; Leopold II palpable flat part on the right side of the mother;

Leopold III palpable round, hard, bouncy part; Leopold IV Not yet entered the upper

pelvic door (PAP), Fetal movement: present, DJJ: 134 x/min, His: (-), VT: Opening 0/10

cm; 0% eff. The results of the reactive NST reading category 1. Ultrasound examination

of a single live baby, head position, estimated fetal weight of 2900 grams. Laboratory

examination results of Hemoglobin 9.3 x 103, Platelets 136 x 103.

Method

The method used is a case report.

A case report: Maternal complications from severe dengue. What can happen?

Jurnal Indonesia Sosial Teknologi, Vol. 5, No. 6, June 2024 2829

Results and Discussion

Dengue hemorrhagic fever is a dengue virus infection with four serotypes: Den-1,

Den-2, Den-3, and Den-4. It is characterized by a sudden fever of 2-7 days, which can be

accompanied by joint pain, retroorbital pain, heartburn, nausea, and vomiting. Bleeding,

thrombocytopenia, and evidence of fluid permeation into the interstitial are also present.

The exact mechanism of the pathophysiology and pathogenesis of dengue

hemorrhagic fever is still unknown, but most adhere to the "secondary heterologous

infection hypothesis", which says that dengue fever can occur if a person after the first

dengue infection gets reinfected with a different type of dengue virus for a certain period

which is estimated to be between 6 months and 5 years.

As a result of a second infection by a different type of dengue virus in a patient with

low levels of anti-dengue antibodies, the anamnestic antibody response that will be caught

in a few days results in the proliferation and transformation of immune lymphocytes by

producing high-titer anti-dengue IgG antibodies. Dengue virus replication occurs as a

result of the presence of a large number of viruses. All of these things will form an

antibody-antigen complex, further activating the complement system. The release of C3a

and C5a due to the activating of C3 and C5 causes increased permeability of the blood

vessel wall and the seepage of plasma through the endothelium of the blood vessel wall.

In people with severe shock, plasma volume can be reduced to more than 30% and lasts

24-48 hours.

Shocks that are not adequately treated can cause tissue anoxia, metabolic acidosis,

and death. Thrombocytopenia is a hematological disorder found in most dengue patients.

The platelet value decreases during fever and reaches its lowest value during shock. The

number of thrombocytes rapidly increases during convalescence, and average values are

usually reached by the 10th day after the onset of the disease.

The endothelium has a vital function, namely maintaining vascular tone, preventing

blood clots and cell migration, producing chemoattractants, and maintaining the

permeability of blood vessels. This function is needed to maintain the blood supply to the

body's organs. In order to function correctly, endothelial cells must remain stable. The

links between cells composed of protein molecules maintain the stability of vascular

endothelial cells. The links between endothelial cells that play the most role are tight

junctions and adherens junctions. The links between endothelial cells form a narrow gap

between endothelial (paracellular pathways). They can only be passed through small

molecules < 2 nm in diameter, such as water, urea, glucose, electrolytes, etc. However, if

the gap widens, the gap between the endothelium can pass through larger molecules and

blood cells (plasma leakage).

In dengue, there is a plasma leak. The release of interleukin (IL)-1, IL-6, tumor

necrosis factor-alpha (TNF-α), histamine, bradykinin, anaphylaxis C3a and C5a, vascular

endothelial growth factor (VEGF), activation of complements, thrombin, and antibodies

during infection can cause activation and contraction of capillary endothelial cell filament

actin. The contraction that occurs makes the link proteins between endothelial cells (tight

Reny Faristin Putri Arifin, Wildan Firmansyah

Jurnal Indonesia Sosial Teknologi, Vol. 5, No. 6, June 2024 2830

junction and adherens junction) enter the cell, making the gap between cells widen and

subsequently causing plasma leakage.

Non-cardiac pulmonary edema is an abnormal or excessive accumulation of fluid

in the interstitial and alveolar spaces of the lungs due to increased microvascular

permeability. Pulmonary edema occurs when the capillary alveoli membrane filtration

rate increases beyond the capacity of lymphatic duct flow.

Under normal circumstances, the mechanisms that maintain the pulmonary alveoli

remain in a fluid-free state by feeding are regulated by the anatomy and physiology of the

lungs themselves, namely the balance of capillary pressure and osmotic pressure of

plasma fluid, as well as the state of permeability of the capillary wall that remains normal.

In general, pulmonary edema occurs due to an increase in pulmonary microvessels

due to an increase in pulmonary veins, generally due to mitral stenosis and left ventricle

decompensation, known as cardiopulmonary edema. Another cause of pulmonary edema

is an increase in capillary alveoli, caused by toxic substances from inside and outside the

lungs due to inhalation of toxic gases. In this state, there is a buildup of protein and fluid

in the pulmonary intertidal without an increase in microvascular, known as non-cardiac

pulmonary edema.

Management of DHF with pulmonary edema in pregnancy

Spreading dengue to the ovaries by its endemic vector can increase the incidence

of dengue hemorrhagic fever. The increase in the number of cases also occurred due to

overcrowding of residents, movement from one place without reporting, poor

environmental sanitation, travel in endemic areas, and ineffective vector eradication

(Organization, 1997). WHO divides the clinical manifestations of dengue hemorrhagic

fever by degrees one to four, according to the manifestations caused.

Acute pulmonary edema is a significant cause of morbidity and mortality in

pregnant and recently pregnant women (Wilkinson, 2011). It is characterized by sudden

onset breathlessness, may be accompanied by agitation, and is often the clinically severe

manifestation of various pathophysiological processes. The Scottish Confidential Audit

of Severe Maternal Morbidity, one of the most extensive maternal morbidity audits,

reported that acute pulmonary edema was the fourth most common form of maternal

morbidity (Wilkinson, 2011). It is also frequently the reason for intensive care admission

(Pollock, 2010) and may occur during the antenatal, intrapartum, or postpartum periods.

Estimated rates of acute pulmonary edema in pregnancy vary from 0.08% to 0.5%

(Dunne, 2008; Altman, 2008). The wide ranges reported are due to the poor reporting of

maternal morbidity and the lack of minimal reporting datasets of key outcomes in

pregnancy and the postpartum period (Tornton, 2011).

Iatrogenic causes remain an essential factor for acute pulmonary edema without

hypertension. The management of preterm labor with the use of tocolytic agents such as

adrenoceptor antagonists (terbutaline and salbutamol) has been associated with acute

pulmonary edema. Important mechanisms in this setting include effects on capillary

permeability, reduced myocardial contractility, and fluid administration.

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Jurnal Indonesia Sosial Teknologi, Vol. 5, No. 6, June 2024 2831

Britain and Ireland during tocolytic therapy and the concurrent use of steroid

medication. Newer single agents such as nifedipine are associated with less acute

pulmonary edema (level 1++ evidence). Magnesium sulfate and corticosteroids have both

been implicated as precipitators of acute pulmonary edema in pregnant or postpartum

women. Women in whom magnesium sulfate infusions are administered for fetal

neuroprotection in preterm labor (level 1++ evidence) need to be carefully monitored and

their fluid balance meticulously recorded.

Non-cardiac pulmonary edema is an abnormal or excessive accumulation of fluid

in the interstitial and alveolar spaces of the lungs due to increased microvascular

permeability. Pulmonary edema occurs when the capillary alveoli membrane filtration

rate increases beyond the capacity of lymphatic duct flow.

Under normal circumstances, the mechanisms that maintain the pulmonary alveoli

in a fluid-free state by feeding are regulated by the anatomy and physiology of the lungs

themselves, namely the balance of capillary pressure and osmotic pressure of plasma

fluid, as well as the normal state of permeability of the capillary wall.

Inhaling toxic gases in this state can cause toxic substances to build up inside and

outside the lungs. This buildup of proteins and fluids in the intertidal lungs without an

increase in microvascular blood flow is known as non-cardiac pulmonary edema.

The administration of diuretics aims to reduce the pre-load that becomes a burden

on the ventricles. In situations where hypotension occurs with low pulmonary capillary

wedge pressure requiring fluid resuscitation to increase blood pressure and tissue

perfusion, if there is no response to inotropic administration, it may be considered.

The triggering factors of non-cardiac pulmonary edema must be identified and

managed optimally. Causes of pulmonary edema with normal microvascular pressure

include inhalation of toxic gases (Nitrogen dioxide, CO, Sulfur dioxide, etc.), gastric fluid

aspiration, and pulmonary edema due to altitude. Pulmonary edema should be treated in

the intensive care unit to monitor and evaluate blood gas analysis, fluid balance, blood

pressure, and radiological picture. Specific treatment refers to the underlying cause of

>40,000 cases of pulmonary edema unless obstetric or termination measures cannot be

avoided in the next six hours.

Attention if urine output is minimal, persistent vomiting, lethargy, weak pulse, slow

filling of capillaries >2 seconds, liver enlargement >2cm, mucosal hemorrhage (epistaxis,

gum bleeding, petechiae, and vaginal bleeding and increased hematocrit >20% from the

baseline line), these symptoms are DHF with warning signs (Group B). Check your vital

signs every hour to know exactly how much urine you will output each hour. (urine target

0.5ml/kg/hour).

Intensive fluid resuscitation is carried out with normal fluid saline bolus 5-7

cc/kg/hour within 1-2 hours; if the situation improves, continue to administer 3-

5ml/Kg/hour in 2-4 hours, gradually reducing to 2-3ml/Kg/hour in 2 to 4 hours. If the

situation improves, stop fluid therapy at 48 hours. Evaluate urine output and pulse

pressure and avoid induction of labor or surgical planning in this phase.3 DHF with shock

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Jurnal Indonesia Sosial Teknologi, Vol. 5, No. 6, June 2024 2832

on admission is categorized in group C. Patients in this category require Intensive Unit

Care (ICU).

Conclusion

Dengue infection is significant in pregnancy. Viral infection can affect the

incidence of morbidity and mortality rates in femtometers. Case recognition to establish

the correct diagnosis of fluid therapy administration is not delayed. DHF in pregnant

women can cause preterm birth, intrauterine fetal death, placental abruption, pulmonary

edema, and miscarriage in early pregnancy. Childbirth is performed by cesarean section

due to the presence of pulmonary edema to evaluate, and pregnancy is highly dependent

on obstetric indications as well as the choice of termination method. It is not

recommended to perform labor induction or surgery planning in the critical phase because

it will cause heavy bleeding. Platelet administration is also not recommended to be done

routinely without any accompanying indications. The administration of PRC is prepared

and can be given immediately if bleeding occurs after termination. The administration

does not wait for the loss of blood volume to reach 500 cc, which will make the hematocrit

drop to the lowest level. Postoperative care is carried out in the ICU room due to the

presence of pulmonary edema that requires observation.

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