Literature review

An 18-year interval between a dengue virus type 1 outbreak in 1977–1979 and a dengue
virus type 2 outbreak in 1997 in Santiago de Cuba, Cuba, provided a unique opportunity
to evaluate risk factors for dengue disease. All patients with symptomatic dengue,
including 205 cases of dengue hemorrhagic fever and 12 deaths, were adults born before
the dengue virus type 1 epidemic, and nearly all (98%) experienced secondary dengue
virus infections. In contrast, almost all of those who seroconverted without illness (97%)
experienced primary dengue virus infection. This provides epidemiologic support for the
immune enhancement theory of dengue pathogenesis. The Cuban experience suggests
that immune enhancement can be seen even 20 years after the primary dengue virus
infection. It also supports the contention that primary infections with dengue virus type 2
(and dengue virus type 4) are largely subclinical. These observations have implications
for dengue vaccine development based on live-attenuated viruses (david,2000).

This paper is essentially a mathematical treatment of the epidemiology of dengue with a

view to control. The paper begins with two important mathematical insights central to the
development of mathematical epidemiology: the mass action principal - the course of an
epidemic is dependent on the rate of contact between susceptible hosts and infectious
vectors, and threshold theory - the introduction of a few infectious individuals into a
community of susceptible individuals will not give rise to an outbreak unless the density
of vectors exceeds a certain critical level. These insights lie at the heart of two
mathematical, mechanistic, and weather-driven models (CIMSiM and DENSiM) used to
elucidate the non-linear relationships influencing the dengue system. Transmission
thresholds in terms of Ae. aegypti pupae per person are discussed in the context of dengue
and control. A method, the pupal demographic survey, is described whereby the
productivities of various classes of water-holding container can be measured, permitting
the development of targeted control strategies that have estimates of endpoints in terms of
transmission thresholds, e.g. Ae. aegypti pupae per person.

Next, the role of weather is discussed noting that daily, seasonal, and interannual
variability in temperature, atmospheric moisture, and rainfall all influence the dengue
system in a variety of ways. Whether a particular aspect of weather can exert a
controlling influence depends on the state of the system. Several cities are contrasted in
terms of rainfall being or not being a driver of the dynamics of Ae. aegypti and dengue.
Atmospheric moisture is shown under rare conditions to adversely influence egg and
adult survival, and transmission dynamics. Under the heading of temperature, the
influence of temperature-driven variation on the extrinsic incubation period and
gonotrophic cycle length is discussed and examples are given where these two
temperature-driven variables are responsible for much of the interannual variability in
transmission. Finally, the influence of weather anomalies associated with El
Niño/Southern Oscillation (ENSO) is discussed. The section concludes with a discussion
of the possible use and potential of early warning systems (EWS) for dengue control.
The section on lags between factors favouring transmission and cases presents examples
of how increasingly high initial values of R0 in the months preceding an epidemic can
result in substantially more infections in the subsequent epidemic phase when conditions
may have actually moderated and R0 values are lower. This phenomenon produces a lag
(temporal autocorrelation) between conditions promoting transmission and the
subsequent realization in the epidemic when the number of infections is high.

The final section, viral factors, investigates the role that virus titre and variation in
viraemic periods play in transmission dynamics. Also covered is the often
underappreciated role that stochastic events play in the dengue system. The section on co-
circulation of multiple serotypes includes the following topics: 1) spatial and temporal
variation in serotype abundance; 2) the founder or stochastic effect; 3) the influence of
herd immunity on serotype abundance; 4) the interaction of different serotypes through
the mechanism of heterologous immunity; and 5) the potential influence of antibody-
dependent enhancement on the dynamics and persistence of multiple serotypes of virus.
(Dana and Roberto,2007)lit6

A case of vertical transmission of dengue infection in the perinatal period is reported. The
mother, a term pregnancy, had acute dengue the day before admission. The infant was
born at term and developed fever on the fifth day of life which lasted for 5 days. No
bleeding or plasma leakage was detected during the course of fever in infant or mother. A
liver function test showed elevated SGOT and SGPT in the infant. The infant developed a
convalescent rash on day 5 of the fever. The diagnosis of secondary dengue hemorrhagic
fever in the mother was confirmed by serology and pri- mary dengue infection in the
infant was confirmed by serology and serotyped as dengue type 2 by PCR. The clinical
course and management of mothers and infants with perinatal dengue infection are
reviewed(Carlous,2008).

To assess the impact of dengue infection during pregnancy on birth outcomes, we

conducted a systematic review of 30 published studies (19 case reports, 9 case series, and
2 comparison studies). Studies were identified by searching computerized databases
using dengue and dengue hemorrhagic fever, cross-referenced with pregnancy, preterm
birth or delivery, low birth weight, small-for-gestational age, spontaneous abortion, pre-
eclampsia, eclampsia, or fetal death as search terms. The case reports examined showed
high rates of cesarean deliveries (44.0%) and pre-eclampsia (12.0%) among women with
dengue infection during pregnancy, while the case series showed elevated rates of
preterm birth (16.1%) and cesarean delivery (20.4%). One comparative study found an
increase in low birth weight among infants born to women with dengue infections during
pregnancy, compared with infants born to noninfected women. Vertical transmission was
described in 64.0% and 12.6% of women in case reports and case series (respectively), as
well as in one comparative study. The authors conclude that there is a risk of vertical
transmission, but whether maternal dengue infection is a significant risk factor for
adverse pregnancy outcomes is inconclusive. More comparative studies are needed.
TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING
OBJECTIVES: After completion of this educational activity, the participant should be
better able to assess symptoms of dengue fever and locations where dengue fever occurs,
describe possible perinatal complications of maternal dengue fever, and identify the
limitations of available literature describing dengue fever in pregnancy(pouliot etal,2010)

Obstet Gynecol Surv. 2010 Feb;65(2):107-18.

Am J Epidemiol 2000;152:800–3.