Chikungunya Virus (CHIKV) Infection and Pregnancy Outcome:
Dr. Kalika Mathur, Ph.D
Background: Chikungunya is a viral disease caused by the chikungunya virus (CHIKV). CHIKV belongs to the genus alphavirus and is transmitted by the bite of infected Aedes aegypti and A. albopictus mosquitoes. Mosquitoes of Aedes spp primarily breed in domestic and peri-domestic environments and aggressively bite during daytime.
The name chikungunya is derived from the Makonde word “kungunyala” (language spoken by an ethnic group in southeast Tanzania) meaning “that which bends up,” referring to the severe joint pain and stooped posture in infected patients. The disease was first identified in Tanzania in 1953 and has since spread to 94 countries worldwide, including India. Chikungunya is a re-emerging disease and is one of the major public health problems in India. In 2006, India witnessed a major CHIKV outbreak with nearly 1.39 million people with fever/suspected cases in 15 states [Krishnamoorthy et al. 2009].
Despite the global impact of CHIKV infections, data for its impact on pregnancy and new-borns is scarce. However, some studies have reported maternal to fetal transmission of CHIKV infection. Women can get infected with CHIKV during different stages of pregnancy, which can then adversely affect the course of pregnancy, resulting in infection of the fetus and newborn. There is no concrete evidence that links CHIKV infection with complications during pregnancy, but reports suggest that CHIKV infection especially before 16 weeks of gestation can potentially result in fetal death. In women with CHIKV infection during the third trimester, reports suggest an increased risk of long-term sequelae and sepsis, increasing the possibility of intensive care unit treatment and complications in neonates [Vouga et al. 2019].
The incidence of symptomatic neonatal CHIKV infection accounts for nearly 15.5% among infections in mothers during gestation. While the reported risk is 0% for antepartum/peripartum maternal infections, it is 50% for intrapartum maternal infections [Contopoulos-Ioannidis et al. 2018]. Fetal loss due to CHIKV infection in mothers has been reported in only three cases so far [Gerardin et al. 2008]. Furthermore, cesarean section delivery is not known to be protective [Vouga et al. 2019].
Symptoms: Chikungunya is a self-limiting febrile disease. The symptoms include sudden onset of fever, headache, chills, joint pain, vomiting, and rashes. The most pronounced symptom is joint pain, which in some patients can persist for several months to years.
Most newborns are asymptomatic at birth; however, symptoms can appear at 3–5 days after delivery.
These include fever, joint swelling, rashes, and elevated levels of liver enzymes [Vouga et al. 2019].
Diagnosis: CHIKV infection can be confirmed by reverse transcription-polymerase chain reaction (RT-PCR), CHIKV-specific IgM detection, or IgG seroconversion. Early CHIKV infection (days 2–5) can only be identified by means of molecular assays such as PCR, since CHIKV-specific antibodies are undetectable during this time. Later stages of infection (days > 5, up to 18 months in some cases) can be confirmed by CHIKV-specific IgM based assays such as ELISA. Since cross-reactions with other alphaviruses have also been reported, CDC recommends Plaque Reduction Neutralization Tests (PRNT) assays for confirming positive or inconclusive test results [Johnson et al. 2016].
As CHIKV infection can also be transferred from infected mothers to infants, infants should be continuously monitored for IgG and IgM levels within the initial 3–4 weeks after birth. Serological monitoring in such cases, especially in symptomatic infants, can minimize the risk of long term neurodevelopmental outcomes [Contopoulos-Ioannidis et al. 2018].
Treatment: Presently, there is no specific treatment for chikungunya, and the treatment is based on symptoms. Also, neither vaccines nor antiviral drugs are available for the same. To prevent adverse effects during pregnancy such as miscarriage, fetal demise, possible neurodevelopmental complications in pre-term neonates or other adverse effects due to fever, antipyretics and analgesics are recommended for the treatment of chikungunya in pregnant women [Gérardin et al. 2016].
Prevention: The best preventative strategy is to avoid mosquito bites. As Aedes mosquitoes breed in domestic and peri-domestic containers, maintaining cleanliness can eliminate vector breeding.
Pregnant women from non-endemic regions should avoid traveling to places with an active CHIKV epidemic. Use of mosquito repellents for pregnant travellers such as insect-repellents registered by the Environmental Protection Agency (EPA) which include diethyl-m-toluamide (DEET), picaridin, lemon eucalyptus oil or para-menthane-diol (PMD) and IR3535 (ethyl butylacetylaminopropionate) are hihly recommended. Besides permethrin-treated clothing and gear are also recommended [Vouga et al. 2019].
Furthermore, clinical manifestations of CHIKV infection should be continuously monitored during pregnancy. In the case of fever physicians should immediately consider the possibility of CHIKV infection. Importantly, pregnant travelers should also be cautious of other mosquito-borne diseases such as Dengue, Zika, and Malaria. While routine laboratory testing for CHIKV is not required before traveling, pregnant women should be tested later if symptoms appear.
Dr. Kalika Mathur, Ph.D, (Vector-Borne Diseases), International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
June 15, 2020
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