Dengue fever in pregnant women: two case reports

Full Text

INTRODUCTION

According to the World Health Organization, approximately 3.9 billion people living in 128 countries face the risk of contracting dengue fever. Its annual incidence is approximately 390 million cases. A substantial increase in dengue fever incidence is associated with urbanization, climate change, and active migration and tourism flows [1, 2].

Dengue fever is a zoonotic, vector-borne infectious disease endemic to countries in Africa, the Americas, Southeast Asia, the Western Pacific, and the Eastern Mediterranean. The main vectors of the disease pathogen are mosquitoes Aedes aegypti and A. albopictus. In the Russian Federation, this infection is imported. A total of 200 disease cases were identified from 2021 to 2023, of which 48% (96 cases) were imported from Thailand. Additionally, dengue fever was recorded in patients returning from Egypt, the Central African Republic, India, Nepal, Bangladesh, Sri Lanka, Indonesia, Vietnam, the United Arab Emirates, Saudi Arabia, Turkey, Cuba, and the Dominican Republic [3].

The causative agent of dengue fever is an RNA-containing virus belonging to the Flaviviridae family and Flavivirus genus. Four serotypes of the dengue virus are distinguished (DENV1, DENV2, DENV3, and DENV4). In most cases, infection occurs through vector transmission; however, transmission is possible through blood transfusion, organ transplantation, or even after a needle-stick injury with an infected needle [4]. There is also evidence of possible vertical transmission of the infection from mother to child, though the probability of this transmission mechanism is considered quite low. Foreign publications report that an infected pregnant woman can transmit the dengue virus to the fetus when fever occurs within 10 days before delivery [5].

Classic dengue fever, hemorrhagic dengue fever, and dengue shock syndrome are distinguished. Classical dengue fever has a favorable course and is associated with primary infection. Currently, cases of hemorrhagic dengue fever during primary infection are described, with their development attributable to specific pathogen serotypes, particularly serotype 2 (DENV2), genetic characteristics, and female sex [2, 6–8]. Virus replication occurs in regional lymph nodes and vascular endothelial cells. Viremia is accompanied by:

• intoxication syndrome
• increased vascular permeability
• hypovolemia
• organ damage.

The accumulation of virus-neutralizing antibodies in the blood leads to viral elimination and recovery. After the disease, lifelong type-specific immunity develops. Recurrent infections are associated with exposure to a different viral serotype, triggering antibody-dependent enhancement (ADE) of infection. Interaction between pre-existing antibodies from primary infection, new dengue virus serotypes, and Fc receptors on monocyte and macrophage membranes facilitates pathogen cell entry, active replication, high-level viremia, suppression of antiviral immunity, and increased chemokine and cytokine production. A systemic inflammatory response develops, characterized by significant vascular disturbances, increased vascular permeability, reduced circulating blood volume, and hemorrhagic syndrome [8–10].

Typical clinical symptoms of dengue fever include:

• elevated body temperature
• headache
• myalgia
• arthralgia
• maculopapular rash.

Warning signs indicate progression to severe disease. These signs include abdominal pain, persistent vomiting, diarrhea, reduced urine output, lethargy, bleeding, and thrombocytopenia with hemoconcentration [8, 9, 11].

Diagnosis is established using polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) to detect serum IgM/IgG antibodies and NS1 antigen [11, 12].

Pregnancy is characterized by immunosuppressive adaptations, potentially worsening acute infectious disease severity. Russian and international literature reports increased preeclampsia risk during acute systemic infections [13, 14].

To expand clinical experience in diagnosing and managing pregnant dengue patients, we present two cases of women returning from international travel.

CASE DESCRIPTION 1

Patient Information

Patient K., 30 years old, was brought by the emergency medical team on January 26, 2023 (day 7 of illness and day 2 of rash) to the admission department of the maternity hospital at Infectious Clinical Hospital No. 2 of the Moscow City Health Department with a referral diagnosis: fever of unknown origin. Early pregnancy.

Anamnesis Morbi

According to the patient, she became acutely ill on January 20 when she noted an increase in body temperature to 39 °C and up to 38 °C in subsequent days. She sought medical care at a hospital in Pattaya City. Symptomatic therapy was prescribed (antipyretic medications, increased fluid intake). She returned to Moscow on January 22. During persistent fever, she experienced daily loose stools without abnormal inclusions once per day. Body temperature returned to normal on January 24. However, the next day, itchy pinpoint rash elements appeared on the palms, along with dry mouth and generalized weakness. Subsequently, on January 26, the patient reported worsening weakness and spread of the rash over her entire body. The disease developed for the first time.

Epidemiologic History

The patient had been traveling in Southeast Asia for the past two months. From December 27, 2023, to January 22, 2023, she was in Thailand (Pattaya City), from where she flew to Hong Kong (January 8–12, 2023). She stayed in a well-appointed hotel, ate at restaurants and cafes, drank bottled water, brushed her teeth with boiled water, and swam in the sea. She did not contact infectious patients. Additionally, the patient denied contact with animals, birds, or rodents. However, she reported multiple mosquito bites.

Diagnostic Assessments

On examination, the patient’s condition was of moderate severity. Body temperature: 36.7 °C. Focal neurological and meningeal signs were absent. A fine punctate maculopapular rash was noted on the skin of the trunk, upper and lower extremities. The mucous membrane of the posterior pharyngeal wall and palatine arches was hyperemic. The lips were dry. The tongue was coated with white plaque. On lung auscultation, vesicular breathing was heard; no wheezes were present. Respiratory rate (RR) was 18 per minute, SpO₂ 98%. Heart sounds were clear and rhythmic. Heart rate (HR) was 80 per minute. Blood pressure (BP) was 114/74 mm Hg. The abdomen is soft and nontender on palpation. The liver and spleen were not enlarged. No abnormal changes in the genitourinary system were noted. Urine output was not reduced. Stool was formed without abnormal admixtures.

Laboratory tests revealed thrombocytopenia (122 × 10⁹/L) in the complete blood count, and elevated alanine aminotransferase (ALT up to 63.9 U/L), aspartate aminotransferase (AST up to 81.2 U/L), and lactate dehydrogenase (up to 385.0 U/L; reference range 0–248.0) in the biochemical blood analysis. No abnormal changes were detected in the coagulogram or urinalysis.

External obstetric examination, cervical examination, and vaginal examination showed no abnormal changes. The antenatal and postnatal venous thromboembolic risk assessment score was 0 (low risk).

Pelvic ultrasound (transvaginal) on January 26: the uterus is positioned normally in the pelvis. A gestational sac is visualized in the uterine cavity (midportion). The mean sac diameter is 6 mm, consistent with 5 weeks’ gestation. The embryo and yolk sac are not visualized. Chorion: annular. The closed cervical length is 36 mm. The ovaries are unremarkable. No free fluid is visualized in the pelvis. Conclusion: pregnancy of uncertain viability.

Diagnosis

Given the epidemiological history (stay in an endemic region, insect bites), acute onset of the disease, intoxication syndrome, exanthema, and laboratory findings, dengue fever was suspected. The diagnosis was confirmed by PCR: dengue virus type 1 RNA was detected in blood and urine.

Diagnosis: classic dengue fever, uncomplicated. Pregnancy of uncertain viability.

Interventions

In the hospital, the patient received infusion therapy with Sterofundin Isotonic^® (potassium chloride + calcium chloride + magnesium chloride + sodium acetate + sodium chloride + malic acid, B. Braun Melsungen AG, Germany). It was administered as an intravenous infusion at a dose of 500 mL a day. Additionally, diosmectite was prescribed at a dose of 3 sachets per day. For a body temperature above 38 °C, paracetamol 500 mg was administered orally. With treatment, the patient’s condition improved, the rash elements regressed, and laboratory parameters returned to normal.

Follow-Up and Outcomes

The patient was discharged on January 29 (on day 10 of illness) in satisfactory condition under the supervision of an obstetrician-gynecologist and an infectious disease specialist. Subsequently, she was followed up at the maternity welfare center regarding the pregnancy, which ended in natural childbirth at 40 weeks. A full-term healthy child was born.

Case Description 2

Patient Information

Patient U., 34 years old, was admitted to the admission department of the maternity hospital at Infectious Clinical Hospital No. 2 of the Moscow City Health Department on June 19, 2023 (day 11 of illness and day 2 of rash) with a referral diagnosis: fever of unknown origin. Pregnancy: 18 weeks and 4 days.

Anamnesis Morbi

The illness began acutely on June 9, when the patient noted a temperature rise to 37.7 °C, accompanied by nausea, a single episode of vomiting, and loose stools up to 10–15 times per day without abnormal impurities. She self-treated by taking Enterosgel^® (polymethylsiloxane polyhydrate, PHARMASIL LLC, Russia) and Regidron^® (dextrose + potassium chloride + sodium chloride + sodium citrate, Valenta Pharm JSC, Russia). From June 11 to 13, she noted improvement in her well-being, though with persistent weakness and headache. On June 13, she visited the Kommunarka Perinatal Center, where an ultrasound examination of the fetus was performed, revealing no abnormalities. The following day, the patient reported increased headache and weakness, onset of eye pain, as well as a rise in body temperature to 37.5 °C and abdominal bloating. She did not seek medical care and continued self-treatment [taking Enterosgel^® (polymethylsiloxane polyhydrate, PHARMASIL LLC, Russia)]. The patient reported that on June 18, her weakness intensified, body temperature rose to 37.8 °C, and a bright red rash appeared on the skin of the trunk and extremities without pruritus.

Epidemiologic History

The patient was in Thailand (Phuket Сity, Samui Island) from May 26, 2023 to June 10, 2023 with her husband, who had similar clinical symptoms. The patient denied contact infections. Medical procedures were performed during the examination at the maternity welfare center. The patient stayed in a well-appointed hotel and swam in the sea. She ate at the hotel and restaurants. She reported mosquito bites. She had no prior history of dengue fever.

Diagnostic Assessments

On examination: the condition was of moderate severity. Body temperature 37.2 °C. The skin of the trunk and extremities showed elements of an abundant, fine, bright red rash, with areas of confluence. Additionally, the rash was denser on the posterior surface of the upper extremities, thighs, and buttocks. The rash was non-pruritic. The oropharyngeal mucosa was hyperemic; tonsils were not enlarged, and there were no plaques. Peripheral lymph nodes were not enlarged. Vesicular breath sounds in the lungs; no wheezing; respiratory rate 18 per minute, SpO₂ 98%. Heart sounds were clear and rhythmic; heart rate was 92 per minute; blood pressure was 108/65 mm Hg. The tongue was dry with a white coating. The abdomen was enlarged due to pregnancy, nontender on palpation in all areas. Stool was formed without abnormal admixtures. Urination was not impaired, painless. Meningeal signs were negative. Focal neurological symptoms were absent.

The patient was examined by an obstetrician-gynecologist: the abdomen enlarged due to the pregnant uterus, corresponding to 18 weeks of gestation. The shape of the abdomen was ovoid. Singleton pregnancy. She did not feel fetal movements. Fetal heart rhythm was regular. The uterus was soft, non-tender on palpation. Mucous discharge. No pelvic deformities were detected on vaginal examination.

On transabdominal ultrasound of the fetus and placenta: one live fetus in cephalic presentation. Heart rate 142 per minute, regular rhythm. Gestation: 18–19 weeks.

The antenatal and postnatal venous thromboembolic risk assessment score was 0 (low risk).

Laboratory tests also showed increased ALT and AST activity to 42.2 U/L and 52.9 U/L, respectively. In turn, the complete blood count, urinalysis, and coagulogram were normal. Platelet and leukocyte counts were 232 and 4.9 × 10^.9/L, respectively.

Diagnosis

Based on clinical and anamnestic data as well as epidemiological history, dengue fever was suspected. The diagnosis was confirmed by PCR: dengue virus type 1 RNA was detected in blood and urine. Based on this, the diagnosis was established: classic dengue fever, uncomplicated. Pregnancy: 18 weeks and 5 days.

Interventions

In the department, the patient received infusion therapy with Sterofundin Isotonic^® (potassium chloride + calcium chloride + magnesium chloride + sodium acetate + sodium chloride + malic acid, B. Braun Melsungen AG, Germany). It was administered as an intravenous infusion at a dose of 500 mL a day. Additionally, dioctahedral smectite was prescribed at a daily dose of 3 sachets. For a body temperature above 38 °C, paracetamol 500 mg was administered orally.

Follow-Up and Outcomes

The patient was discharged on June 23, on day 15 of the disease, in satisfactory condition under the supervision of a local obstetrician-gynecologist and infectious disease specialist at her place of residence.

The pregnancy ended with operative birth delivery due to obstetric indications at 40 weeks. A healthy full-term child was born.

DISCUSSION

The presented clinical cases describe the course of dengue fever during primary infection in pregnant women. The first patient experienced the disease during the first trimester, and the second during the second trimester. Dengue fever in them was uncomplicated and resulted in recovery. Laboratory diagnosis was performed using PCR to detect viral RNA in blood and urine.

Analysis of the patients’ blood laboratory parameters revealed elevated ALT and AST activity in both cases, whereas total bilirubin, albumin, and γ-glutamyltransferase levels were within reference ranges. Thrombocytopenia was recorded in only one patient. No abnormal changes were observed in the coagulogram of any patient. The significance of thrombocytopenia in pregnant women infected with dengue fever should be emphasized, as a platelet count below 80 × 10⁹/L may indicate a risk of hemorrhagic syndrome and severe vascular disorders [15].

Infection during early pregnancy is not associated with fetal malformations or long-term consequences but may result in miscarriage during the first trimester [15, 16]. According to foreign studies, the risk of severe dengue fever is higher in pregnant women than in non-pregnant women. The maternal mortality rate among women with hemorrhagic dengue fever varies across countries, from 6.6% to 15.9% in Sri Lanka and India, respectively [15–18]. Moreover, Paixao et al. [19] noted an increased risk of preeclampsia in dengue fever.

Preterm birth and low birth weight are the most common complications in severe dengue fever in pregnant women. The main causes of these complications are considered to be severe vascular disorders and inflammatory changes in the placenta, leading to progressive placental insufficiency and fetal hypoxia [20]. These data highlight the need for careful attention to the issue of imported infections not only by infectious disease physicians but also by other professionals, including obstetricians-gynecologists.

CONCLUSION

Since traveling to Southeast Asian countries is popular among Russian citizens, the importance of vigilance against imported tropical infections, especially in pregnant women, is increasing. Timely diagnosis of dengue fever and dynamic clinical and laboratory monitoring of the mother and fetus can prevent complications and adverse disease outcomes. In turn, counseling pregnant women before traveling to endemic regions with an assessment of risk factors for contracting tropical diseases and an explanation of prevention principles will help prevent potential illnesses.

ADDITIONAL INFORMATION

Author contributions: T. V. Kharlamova: resources search and analysis, writing—original draft, writing—review & editing; I. V. Barysheva: resources search and analysis, writing—original draft, writing—review & editing; D. M. Munina: investigation, writing—review & editing; A. V. Eremeeva: writing—original draft, writing—review & editing; A. D. Bogoyavlenskaya: resources search and analysis. All the authors approved the version of the manuscript to be published and agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Ethics approval: Not applicable.

Consent for publication: The authors did not obtain patient consent to publish health-related information from the hospitalization period. The reason was the inability to contact the patients: phone numbers listed in the medical records were not answered, no email addresses were provided at admission, and no contact information for the patients’ relatives was available. All data presented are anonymized, and no photographs are published.

Funding sources: No funding.

Disclosure of interests: The authors have no relationships, activities, or interests for the last three years related to for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality: No previously published material (text, images, or data) was used in this work.

Data availability statement: The editorial policy regarding data sharing does not apply to this work.

Generative AI: No generative artificial intelligence technologies were used to prepare this article.

Provenance and peer-review: This paper was submitted unsolicited and reviewed following the standard procedure. The peer review process involved two members of the editorial board.

About the authors

Tatiana V. Kharlamova

Peoples’ Friendship University of Russia

Author for correspondence.
Email: kharlamova_tv@pfur.ru
ORCID iD: 0000-0003-4261-3000
SPIN-code: 2102-1234

MD, Cand. Sci. (Medicine)

Russian Federation, 6 Miklukho-Maklay st, Moscow, 117198

Irina V. Barysheva

Peoples’ Friendship University of Russia

Email: barysheva-iv@pfur.ru
ORCID iD: 0000-0002-3543-9086
SPIN-code: 7381-8660

MD

Russian Federation, Moscow

Darya M. Munina

Peoples’ Friendship University of Russia; Infectious Clinical Hospital No. 2

Email: popova_d@pfur.ru
ORCID iD: 0000-0002-4056-9192
SPIN-code: 6196-2291

MD

Moscow; Moscow

Anna V. Eremeeva

Peoples’ Friendship University of Russia

Email: eremeeva_av@pfur.ru
ORCID iD: 0000-0002-3628-5242
SPIN-code: 7503-9649

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow

Anastasiya D. Bogoyavlenskaya

Peoples’ Friendship University of Russia

Email: 1032203881@pfur.ru
ORCID iD: 0009-0000-3444-4804
SPIN-code: 8446-7403
Russian Federation, Moscow

References

Supplementary files