Dengue, the most frequent vector-borne viral disease in the world, constitutes a public health problem in tropical and subtropical countries [1
]. In its 2008 and 2009 reports to the World Health Organization, Mexico reported 31,154 and 55,363 confirmed dengue cases (24.42 cases per 100,000 inhabitants), with 24 and 96 fatality cases, respectively.
Dengue affects the productivity of countries significantly, and generates losses that are as important as those caused by tuberculosis, Chagas, leishmaniasis, hepatitis and malaria, among others [2
]. For instance, the total cost of the Cuban epidemic in 1997 ascended to 10,251,539 USD, taking into account the money invested in vector control and patient care [6
]. Moreover, the direct economic impact of the disease is compounded by the disability-adjusted life years (DALYs) [2
]. For example, in Puerto Rico, from 1984 to 1994, dengue caused an average of 658 DALYs per million inhabitants per year, with a maximum of 2,153 DALYs per million inhabitants estimated for 1994. The greatest burden of disease was attributed to dengue fever [4
It has been established that Dengue virus (DENV) transmission involves a man-vector-virus pathway, but the characteristics and dynamics of the related factors have not been fully determined [7
]. Firstly Aedes aegypti
and secondly Aedes albopictus
mosquitoes have been found to be the leading dengue vectors in the world. However, the virus has also been isolated from species such as Ae. albifasciatus
and Ae. polinensis
The dengue endemic/epidemic cycle is maintained by the vector through mosquito-man- mosquito transmission. On contracting the virus, mosquitoes remain infected and asymptomatic for the remainder of their lives. Human beings are both the definitive host and the reservoir of the virus. A female mosquito feeds on a number of humans during the day. Once it has bitten an infected individual, it incubates the virus for a period of 7-14 days, and then starts to infect healthy individuals through its bite. In humans, DENV incubation extends over a period of 3 to 14 (7 on average) days. The actual infectious stage, or time span during which the diseased person spreads the infection to a vector, commences one to two days before the onset of symptoms, at which time high levels of viremia appear and continue to develop throughout a febrile cycle of 2 to 10 days [9
The DENV infection spectrum covers symptomatic cases (dengue fever, dengue hemorrhagic fever, dengue shock syndrome and death), as well as asymptomatic cases, which, in most studies, represent over half of total infections [10
]. It has been proposed that the high frequency of asymptomatic cases may be contributing to the maintenance of human transmission despite the reduced number of vectors during inter-epidemic periods [24
]. Likewise, as the level of viremia required to produce clinical manifestations is currently unknown [25
] and asymptomatic viremic cases of dengue have been reported [14
], the asymptomatic cases may constitute a determinant of persistent dengue transmission. Being at least as frequent as the symptomatic cases, and not having been combated by preventive measures of any sort, these may well be a source of vector infection, and could thus be generating a significant impact on the spread of dengue among different populations.
Given the absence of a DENV-specific vaccine or antiviral treatment, health services have focused their prevention efforts on vector control. Government vector control programs offer a number of partially successful examples. For instance, in 1965, a PAHO campaign against urban yellow fever (consisting of DDT and malathion spraying) eradicated Ae. aegypti
from America and, collaterally, attenuated dengue. However, the program was discontinued in the early 1970s and America has been reinfested with Aedes
. A second partially successful example occurred in Singapore in 1973, when a government program based on entomological surveillance, larval breeding-site reduction, education and the enforcement of legislation to control Ae. aegypti
and Ae. albopictus
, slashed the House Index (HI) from 50% to 2% and curbed dengue prevalence. Notwithstanding, at 15 years, dengue incidence has intensified, without, however, hoisting the HI [27
Cuba provides yet another example of success: subsequent to its 1981 epidemic, the Cuban government conducted a vector eradication campaign where both vector and dengue were eliminated from the island for 15 years. After 1997, however, despite a stable 1% HI, the virus resurged in certain localities, probably due to a drop in herd immunity and transmission by international travelers. In the two aforementioned cases, government programs have achieved long-term dengue control as a result of the countries' political will and geographic conditions.
At the government level, vector control measures have concentrated on peridomestic dengue areas. For instance, the Mexican National Health Standard obligates the state health services to execute larval control and dejunking campaigns permanently, as well as nebulization and fumigation procedures during peak transmission periods, targeting the domiciles and peridomestic vicinities of dengue cases detected through epidemiological surveillance. Nevertheless, the results have fallen short of expectations.
In this regard, a literature review of Esu E, et al [28
] was conducted to evaluate the effectiveness of peridomestic space fumigation for reducing dengue transmission and yielded no conclusive evidence of reduction through this measure: only one of the 15 studies reviewed reported an impact on the disease (a reduction of case incidence during the four weeks subsequent to the intervention). In this instance, however, the application of insecticides was coupled with anti-breeding campaigns. While 13 studies reported initial cuts in the entomological indices, most cases achieved only an ephemeral impact. As a result, the authors of the review sustain that a reduction in entomological indices does not necessarily imply a reduction in transmission, due to the presence of additional factors relating, for instance, to herd immunity, population density, circulating serotype and a number of other environmental variables [28
]. Further potential factors include a rise in extra-domiciliar transmission, changes in vector surveillance policies and migratory movements [27
Moreover, as regards vector density and its relation to dengue, a study in Thailand reported a negative correlation between the Breteau Index and dengue incidence [24
]. Another study in Brazil revealed not only that the peak case incidence period was not preceded by a rise in vectors in the locality, but also that mosquito density was low when the occurrence of cases was the highest, thus suggesting that infection took place outside the case domiciles (schools, workplaces, etc.) [29
]. Other transmission-related factors have been contemplated, such as: age, low educational and income levels, the number of occupants per room, houses -not apartments- as dwellings, study and work sites outside the home, and subject movement patterns [23
Regarding intra and peridomestic transmission, a study in Thailand reported that only 13 out of 180 families with subjects hospitalized for dengue presented more than one hospitalized case in their households [33
]. Another study in Puerto Rico evaluating the occurrence of infection with a four-month follow up found that out of the 189 sample households (with two or more persons residing with an incident case) 95 presented at least one infected individual during follow up, and only 50 of these indicated two or more infected individuals [23
So far, three studies reported in the literature have evaluated infection in the vicinity of pediatric index cases (through cluster sampling). The first, conducted in Indonesia with a 14 day follow up, included persons living with and neighbors residing within a 10-meter radius of the cases. The results indicated a recent-infection rate of 24.5% (192/785 cases, 17 of which consisted of post-enrollment infections). The index case serotype was analyzed and compared to that of the infected individuals in the surrounding areas: it proved identical in four out of the seven clusters studied, but different in three [26
]. The second study, conducted in Thailand with a 15-day follow up, sampled children aged six to 15 years residing within a 100-meter radius of the index cases' dwellings. Twelve positive clusters (with an index case) and 22 negative clusters (with no index case) were analyzed, yielding an incidence rate of 12.4% in the first and 0% in the second (with an attributable risk of 10.4% and a CI of 95% 1-19.8%) [13
Thirdly, a recent study conducted in Nicaragua with a 14-day follow up reported infection in 2.4% (10/414) of the subjects in the 18 positive clusters (composed of individuals aged two and older residing with or within a 50-meter radius of the confirmed dengue index cases) and 2.5% (2/81) of the subjects in the four negative clusters (composed of persons residing with and neighbors of dengue-negative febrile cases) studied. Additionally, the viral sequences of three index cases and four contacts were analyzed, with the sequence of only one contact diverging from that of its index case [10
In sum, the relationship among the dengue transmission pattern, the incidence of the disease and the density of Ae. aegypti is still unclear. Vector-control programs targeting the peridomestic vicinities of cases have not achieved the desired results, and the causes are unknown. They may include inadequate insecticide application, vector resistance to the insecticides applied, non-continuity of the measures implemented and the fact that transmission is not occurring -or is occurring less than expected- within the peridomestic areas.
Hence, identifying the relationship between exposure to a dengue case in its peridomestic vicinities and the frequency of new infections would help to shed light on the dengue-transmission pattern in endemic urban areas. Additionally, the results of this study would both contribute to improve control activities with the purpose of achieving a greater impact on the burden imposed by dengue, and help to give the resources destined for vector control a more efficient use. This is particularly critical in the dengue-endemic areas where budgets for interventions of this type are restricted.