To the Editor:
Zika virus (ZIKV), a member of the family Flaviviridae, genus Flavivirus, was first
isolated from the blood of a sentinel rhesus monkey from the Zika Forest of Uganda
in 1948 (
1
). Since that time, serologic studies and virus isolations have demonstrated that
the virus has a wide geographic distribution, including eastern and western Africa;
the Indian subcontinent; Southeast Asia; and most recently, Micronesia (
2
–
5
). The virus is transmitted primarily through the bite of infected mosquitoes and
most likely is maintained in a zoonotic cycle involving nonhuman primates (
1
), although recent evidence suggests the possibility of occasional sexual transmission
in humans (
4
). Few case reports have described the clinical characteristics of ZIKV infection
in humans. Most reports describe a self-limiting febrile illness that could easily
be mistaken for another arboviral infection, such as dengue or chikungunya fever.
We report a confirmed case of ZIKV infection in Cambodia.
Since 2006, the US Naval Medical Research Unit No. 2 (NAMRU-2) has conducted surveillance
for acute fever to determine causes of the infection among patients who seek health
care at local clinics in Cambodia. Patients were enrolled by the health clinic physician
after they gave informed consent in accordance with an institutional review board
protocol approved by NAMRU-2 and the National Ethics Committee for Human Research
of Cambodia. At enrollment, the physician administered a questionnaire and collected
specimens (blood and throat swabs). All items were transported to the NAMRU-2 laboratory
in Phnom Penh, where testing was conducted for a variety of viral, bacterial, and
parasitic pathogens. In August 2010, a blood specimen was collected from a 3-year-old
boy at a health clinic in Kampong Speu Province, Cambodia. The child’s reported clinical
symptoms included 4 days of fever and sore throat and cough and a headache for 3 days.
A maculopapular rash was not observed, and the boy was not hospitalized. The clinic
staff conducted a follow-up interview and reported that the patient recovered fully.
ZIKV infection was confirmed in this patient by using PCR, sequencing, and serology
and through virus isolation. ELISA for chikungunya and dengue virus IgM and IgG antibodies
on acute- and convalescent-phase serum was negative. A universal flavivirus real-time
PCR screen that targets the nonstructural (NS) 5 gene (
6
) determined that the patient’s serum was positive for flavivirus RNA, but subsequent
species-specific PCR ruled out 2 other flaviviruses that are highly endemic to the
region (dengue and Japanese encephalitis viruses) (
7
–
9
). This result was the first nondengue, non–Japanese encephalitis virus flavivirus
detected after samples from ≈10,000 enrolled patients were tested. Nucleic acid sequencing
of the amplicon isolated by gel purification produced a 100-bp fragment with 100%
sequence identity to ZIKV (nucleotide position 8,969 of the NS5 gene of the isolate
GenBank accession no. EU545988). ZIKV infection subsequently was serologically confirmed
by hemagglutination-inhibition tests on paired serum samples. The patient’s acute-phase
sample was negative, but a convalescent-phase sample gave a positive reaction with
ZIKV antigen to a serum dilution of 1:320 and was negative to antigens for the 4 dengue
serotypes and yellow fever and West Nile viruses. These results demonstrate that the
patient had a clear monotypic flavivirus immune response with seroconversion against
ZIKV, indicating a recent primary infection.
The most common signs and symptoms reported in confirmed ZIKV infections are fever,
headache, malaise, maculopapular rash, fatigue or myalgia, and arthritis and arthralgia
(Table). In addition to fever and headache, the patient in this study had a sore throat
and cough. Because of the patient’s age, additional information about symptoms was
difficult to obtain.
Table
Reported or observed clinical signs and symptoms in persons with Zika virus infection,
1962–2010
Sign or symptom
Country, year of infection origin,* no. (%) patients
Uganda, 1962, n = 1
Laboratory acquired, 1973, n = 1
Indonesia,
1977–1978, n = 7
Micronesia, 2007, n = 28
Senegal/United States, 2009, n = 3
Cambodia, 2010, n = 1
Fever
1 (100)
1 (100)
7 (100)
20 (65)
1 (100)
Headache
1 (100)
14 (45)
3 (100)
1 (100)
Malaise
1 (100)
5 (71)
3 (100)
Maculopapular rash
1 (100)
28 (100)
3 (100)
Fatigue or myalgia
1 (100)
1 (100)
1 (14)
14 (45)
1 (33)
Arthritis and arthralgia
1 (14)
20 (65)
3 (100)
Chills
1 (100)
2 (29)
2 (67)
Dizziness
5 (71)
Joint swelling or edema
6 (19)
2 (67)
Stomachache
6 (86)
Retro-orbital pain
1 (100)
12 (39)
Conjunctivitis
1 (14)
17 (55)
1 (33)
Anorexia
4 (57)
Photophobia
1 (33)
Vomiting
1 (14)
3 (10)
Diarrhea
3 (43)
Constipation
3 (43)
Sore throat
1 (100)
Cough
1 (100)
Aphthous ulcer
2 (67)
Hypotension
2 (29)
Hematuria
1 (14)
Prostatitis
1 (33)
Hematospermia
1 (33)
Sweating
1 (100)
Lightheadedness
1 (33)
*References: Uganda (
2
), laboratory-acquired (
10
), Indonesia (
5
), Micronesia (
9
), Senegal/United States (
4
). Blank cells indicate no reported information.
The clinical characteristics exhibited by this case-patient are similar to those of
shown in a small cluster of ZIKV infections described in Indonesia during 1977–1978
in which maculopapular rash was not observed (
5
). Maculopapular rash was reported as a common sign in case-patients from the recent
Yap Island outbreak (
3
), as well as in case reports from Uganda (
2
), Senegal, and the United States (
4
), A case report of laboratory-acquired ZIKV infection also noted the lack of maculopapular
rash (
10
).
The clinical features of ZIKV infection are similar to those of dengue virus and chikungunya
virus infections, and both arboviruses are found in Southeast Asia. In this region,
laboratory-based confirmation is essential. The extent of ZIKV infections in Cambodia
is unknown; further studies are needed to clarify the prevalence and geographic distribution
of ZIKV infection in the country.