Transmissibility and potential range of ZIKV
Transmission of ZIKV in a population is a function of local ecology, the natural history of ZIKV, and the population’s susceptibility to infection. The suitability of the local environment for ZIKV transmission and the effect of ZIKV’s natural history are captured by the basic reproductive number R0, the number of secondary infections expected from a single case in a population with no preexisting immunity (e.g., French Polynesia before 2013). R0 is a function of both disease and setting and will vary between locales based on the local environment, human behavior, vector abundance, and, potentially, interactions with other viruses. The combined effect of these factors and susceptibility will be captured by the reproductive number R, which is related to R0 by the equation R = R0 × S, where S is the proportion of the population susceptible to ZIKV. This value, combined with the generation time (the time separating two consecutive infections in a chain of transmission), tells us the speed at which ZIKV will spread in a population. As we consider how to assess the range and effects of ZIKV, we rely both on previous experience with ZIKV and related viruses and on an assessment of factors likely to influence R and R0.
The size of an outbreak after an introduction will depend on
R (
R0 in a ZIKV-naive population) (
99), with small, self-limiting outbreaks becoming more likely as
R approaches one, and increasing epidemics with larger
Rs. Hence, ZIKV can successfully spread to a new region if
R > 1, which requires, among other factors, sufficient density of the vector population. ZIKV has been isolated from multiple
Aedes genus mosquitoes (
23–
26,
38), including
A. albopictus and
A. aegypti, which have a large global range (
Fig. 2B) (
100). Although ZIKV has been occasionally isolated from or experimentally passed to other genera, including
Culex species, there is no current evidence that they contribute substantially to its spread (
22,
23,
101). It is unclear whether all areas across the range of these mosquitoes are at risk for ZIKV epidemics. Dengue, a virus that is also transmitted by
Aedes mosquitoes, has caused epidemics throughout the Americas (
Fig. 2C) but has not achieved sustained transmission in the continental United States, despite widespread vector presence (
100,
102,
103). The reasons for this may include not only climate but also differences in built environments and social factors (
104), all of which are likely to affect ZIKV transmission.
Several groups have attempted to map ZIKV’s potential global range based on currently available data. These maps have been constructed around combinations of environmental, vector abundance, and socioeconomic factors (
105–
109). There is wide agreement that much of the world’s tropical and subtropical regions are at risk for ZIKV spread, including major portions of the Americas, Africa, Southeast Asia, and the Indian subcontinent, as well as many Pacific islands and Northern Australia. These maps differ notably in the extent of risk projected in the southeastern United States and inland areas of South America and Africa, with Carlson and colleagues suggesting a more limited range (
107), particularly in the continental United States, than Messina
et al. and Samy
et al. (
108,
109). These maps are important attempts to refine estimates of ZIKV’s global range beyond those based solely on the distribution of dengue or
Aedes mosquitoes but, as noted by the authors, are based on limited evidence and should be refined as we learn more about ZIKV. These analyses are, arguably, best interpreted as an assessment of the risk of initial postinvasion ZIKV epidemics, not its long-term persistence. Whether ZIKV will in fact spread throughout these areas is uncertain; similar viruses have failed to spread to or take hold in areas theoretically at risk (e.g., yellow fever in Southeast Asia) (
110).
R0 in ZIKV outbreaks in Yap Island and French Polynesia was estimated to be between 1.8 and 5.8 (
111–
113), corresponding to 73.2 to 99.9% of the at-risk population becoming infected in an uncontrolled outbreak, based on classic epidemic theory (
4) [although the true relationship between
R0 and final attack rates for ZIKV will be somewhat more complex (
99)]. Serosurveys in French Polynesia suggest that 66% of the population was infected (
46), which is somewhat lower but not inconsistent with these projections. Preliminary estimates of
R0 from Colombia vary by location and range from 1.4 to 6.6 (
114,
115). These are similar to
R0 estimates presented by Ferguson
et al. for 13 countries in the Americas (
116) and recent estimates of
R0 for Rio de Janeiro (
117). These values are consistent with
R0 estimates for dengue in similar settings. Of note, all of these are from settings with recently observed endogenous transmission of ZIKV, and
R0 will vary widely across settings and is likely to be far lower near the limits and outside of ZIKV’s range.
ZIKV’s potential for endemic circulation
After the initial, postinvasion epidemic of ZIKV, the virus may either go extinct locally or be maintained through endemic human spread or sylvatic transmission (
Fig. 1). Early age-stratified serosurveys in Africa and Asia offer some insight into past transmission patterns of ZIKV in these regions and ZIKV’s past dynamics (
Fig. 4). Serosurveys in Nigeria, the Central African Republic, and Malaysia are consistent with ongoing ZIKV transmission, common spillover infections from a sylvatic reservoir, or frequent reintroductions from other regions over multiple decades (
13,
16,
118). However, these results must be interpreted with caution owing to cross-reactivity with other flaviviruses in serologic tests (
22). Up-to-date, age-stratified serosurveys, broadly covering regions where ZIKV has previously been detected, would tell us much about the virus’s ability to persist.
More recent evidence of sustained transmission comes from Thailand, where seven samples collected in independent outbreak investigations tested positive for ZIKV infection (
43). The broad geographic spread of these cases is consistent with endemic transmission throughout Thailand. Furthermore, occasional but consistent serologic and virologic evidence of ZIKV transmission in humans and mosquitoes from across Africa, India, and Southeast Asia spanning more than 60 years suggests that ZIKV has been persistently present throughout these regions (
22) (
Fig. 1A). Phylogenetic evidence further supports this supposition, because the African and Asian lineages divided in the 1940s and remain distinct up until the present day (
22,
26) (
Fig. 5).
The evidence supports ZIKV’s ability to persist regionally, but it is unclear whether the human population alone can maintain ZIKV endemically. After an initial postinvasion epidemic, the time until there is a risk of additional epidemics will be driven by the replenishment of susceptibles through births and waning immunity [the latter seems unlikely based on evidence that other flaviviruses provide lifelong immunity to the infecting strain (
22)]. For ZIKV to persist in the human population over this period, the population must be large enough to support low levels of transmission between epidemics (
4).
However, all countries with evidence of persistent ZIKV transmission have a plausible sylvatic cycle. Patterns of ZIKV isolations in a study of samples from multiple hosts in Senegal spanning 50 years support episodic transmission across species (
9); phylogenetic evidence indicates ZIKV passes frequently between nonhuman primates and humans in Africa (
26); and numerous studies in Africa and Asia show serologic evidence for ZIKV infection in nonhuman primates (
1,
18,
22,
33,
119). Some areas, where there has been serological evidence of long periods of consistent risk of ZIKV infection, are near areas where serological evidence suggests that human populations are largely ZIKV free (e.g., Nigeria versus Kenya) (
120,
121)—a pattern more consistent with spillover infections from a sylvatic reservoir than of endemic transmission in humans.
In light of this evidence, it is plausible that the persistence of ZIKV in Africa and Asia may depend on the presence of a sustainable sylvatic cycle. However, it is unclear if the primate population in the Americas could support sylvatic transmission (
122) or if such a cycle is necessary for ZIKV to remain endemic. Nonhuman primates are present throughout South and Central America, and ZIKV has recently been isolated from two species in the Ceará State of Brazil (
123), suggesting at least the possibility for sustained sylvatic transmission in the region. Further characterization of ZIKV ecology in Asia and Africa and monitoring of the developing situation in the Americas is needed to assess the long-term risk from ZIKV in newly affected regions.
Because the most severe outcomes of ZIKV infection are associated with pregnancy, the risk from endemic ZIKV will depend on the age distribution of those infected. Serosurveys indicating ongoing ZIKV circulation (
Fig. 4, A to C) support average ages of infection of 17 (Nigeria, 1952), 29 (Central African Republic, 1979) and 30 years (Malaysia 1953 to 1954) (
13,
16,
118). Likewise,
R0 estimates from the literature are consistent with average ages of infection ranging between 10 and 38 years in the setting of endemic human-to-human transmission (although human-to-human transmission should not be necessarily assumed in the settings covered in
Fig. 4, A to C). These ages suggest that in endemic settings, risk of ZIKV infection may be considerable during childbearing years. Importantly, this information could potentially be used to estimate the expected rate of microcephaly and other birth defects in regions where ZIKV becomes endemic.
RE: Global threat from Zika virus. Consider Ivermectin to reduce the transmission of Zika and other diseases by mosquitoes.
Global threat from Zika virus. Consider Ivermectin to reduce the transmission of Zika and other diseases by mosquitoes.
The impressive analysis of Justin Lessler et. al (Science 14 July 2016) motivates us to investigate every reasonable way to reduce the impact of Zika. The Nobel Prize winner antiparasitary medicine Ivermectin has achieved the reduction of about a third of transmissions of malaria in Africa thanks to its ectoparasitizide effect that kills the mosquitoes after they bite the patients.
It has the potential to reduce the enormous impact of Zika, Chikungunya, Dengue and Malaria in Latin America and elsewhere if administered to the appropriate affected patients and family circle, a regular dose daily for four days, with minimal costs and minimal side effects. I propose this dosage since Aedes requires higher dose than Anopheles.
This can be done together with the other known methods to reduce the propagation of mosquitos and the transmission of these diseases.
Given the serious complications of Zika and the actual epidemic in Nicaragua, since the Zika test are not done rapidly, we start treatment based on the clinical manifestations in a pragmatically way, after ruling out Dengue or Chikungunya, to alleviate the symptoms and try to reduce the risk of posterior complications like Guillain Barré.
I treat the symptoms with Cox 2 NSAIDs that have no effects in platelets, or paracetamol, antihistamines and antileukotriens, to improve not only the symptoms, but also trying to avoid an overreaction of the immune system and reduce the risk of neurologic complications.
For intense pruritus that do not response to this treatment, I use Pregabalin with excellent results. I warn against the so popular use of steroids in the acute phase, to avoid any interference with the development of immunity.
I propose that committed researcher and the responsible authorities at the WHO/PAHO analyze the possibilities of success for this strategy.
Prof. Enrique Sánchez-Delgado, MD
Internal Medicine-Clinical Pharmacology and Therapeutics
Hospital Metropolitano Vivian Pellas, Managua