Beyond efficacy in water containers: Temephos and household entomological indices in six studies between 2005 and 2013 in Managua, Nicaragua
- Jorge ArosteguíEmail author,
- Josefina Coloma,
- Carlos Hernández-Alvarez,
- Harold Suazo-Laguna,
- Angel Balmaseda,
- Eva Harris,
- Neil Andersson and
- Robert J Ledogar
© The Author(s). 2017
Published: 30 May 2017
A cluster-randomized controlled trial of community mobilisation for dengue prevention in Mexico and Nicaragua reported, as a secondary finding, a higher risk of dengue virus infection in households where inspectors found temephos in water containers. Data from control sites in the preceding pilot study and the Nicaragua trial arm provided six time points (2005, 2006, 2007 and 2011, 2012, 2013) to examine potentially protective effects of temephos on entomological indices under every day conditions of the national vector control programme.
Three household entomological indicators for Aedes aegypti breeding were Household Index, Households with pupae, and Pupae per Person. The primary exposure indicator at the six time points was temephos identified physically during the entomological inspection. A stricter criterion for exposure at four time points included households reporting temephos application during the last 30 days and temephos found on inspection. Using generalized linear mixed modelling with cluster as a random effect and temephos as a potential fixed effect, at each time point we examined possible determinants of lower entomological indicators.
Between 2005 and 2013, temephos exposure was not significantly associated with a reduction in any of the three entomological indices, whether or not the exposure indicator included timing of temephos application. In six of 18 multivariate models at the six time points, temephos exposure was associated with higher entomological indices; in these models, we could exclude any protective effect of temephos with 95% confidence.
Our failure to demonstrate a significant protective association between temephos and entomological indices might be explained by several factors. These include ecological adaptability of the vector, resistance of Aedes to the pesticide, operational deficiencies of vector control programme, or a decrease in preventive actions by households resulting from a false sense of protection fostered by the centralized government programme using chemical agents. Whatever the explanation, the implication is that temephos affords less protection under routine field conditions than expected from its efficacy under experimental conditions.
Over the last two decades, Aedes aegypti mosquito control in many countries has relied on household visits by centrally-run vector programmes to eliminate immature vector forms by placing the organophosphate larvicide temephos in clean household water containers. In some places, ultra-low volume pesticide spraying complements temephos placement to control the adult mosquito. In a strategy laid out 20 years ago and followed since then to intensify the “war against Aedes aegypti” , temephos placement in household water stores was “the fundamental operation of the attack phase” of the programme. The World Health Organization promotes integrated vector management  and there are reports of successful experiences of community involvement [3, 4, 5, 6], yet community participation in dengue control is mostly still secondary to chemical-based control strategies run by centralized vector control programmes.
The Nicaraguan government has made substantial efforts to control the Aedes aegypti vector of dengue virus and to mitigate the impact of dengue epidemics. As in nearly all other countries in tropical and subtropical regions of the world, however, the Aedes aegypti mosquito that carries dengue and other arboviruses of medical relevance, continues to gain ground. After two decades of temephos use in the country, a recent paediatric cohort study in Nicaragua found an incidence rate of 16.1 cases and 90.2 dengue virus infections per 1000 person-years in children aged 2–14 years of age . Complicating the public health picture are multiple viral strains, the increasing severity of clinical cases, and the increasing costs incurred by governments and communities due to dengue infection.
The well-documented temephos resistance [8, 9, 10, 11, 12, 13, 14, 15] combined with recent explosive epidemics of zika and chikungunya across Latin America suggest the vector is out of control, fuelling concern about reliance on temephos in dengue prevention. This has spurred a search for sustainable alternatives to pesticide-based vector control, through biological approaches [16, 17], community self-management [3, 4] or evidence-based communication strategies .
A (2004–2008) pilot study in Managua, Nicaragua, in coordination with the Centro Nacional de Diagnóstico y Referencia (CNDR) of the Nicaraguan Ministry of Health, CIET International, the University of California at Berkeley, and the Sustainable Sciences Institute, established the feasibility and acceptability of a pesticide free approach [18, 19]. The intervention engaged communities in dengue vector control activities through dialogue centred on local evidence and their own experience. Impact assessment found a high level of acceptability and feasibility, improvement of entomological indices, and reduced risk of dengue infection in children, indicated by the level of anti-dengue virus antibodies in saliva before and after the dengue season.
Based on this experience, a multi-centred cluster-randomized controlled trial (2010–2013) tested the added value of community engagement in Managua, Nicaragua, and the Mexican state of Guerrero . The official vector control programmes continued in both intervention and control neighbourhoods. The trial demonstrated a decrease in recent dengue virus infection risk, fewer self-reported cases of dengue illness and a reduction in entomological indices .
This secondary analysis of data from control (non-intervention) neighbourhoods in the Nicaraguan feasibility study and Nicaraguan arm of the trial assessed the impact on household entomological indicators of temephos application by the National Vector Control Programme. The dengue control programme of the Ministry of Health carries out 4–6 cycles of temephos abatement annually in all municipalities of Managua, but the coverage and actual periodicity of application varies year to year due to multiple local factors. In addition, the government programme conducts spatial fumigation and educational activities about elimination of Aedes reproduction sites.
The Camino Verde trial, a pragmatic parallel group cluster randomised controlled trial, involved a random sample of communities in Managua, the capital of Nicaragua, and three coastal regions in Guerrero State in the south of Mexico . A total of 60 clusters in Nicaragua and 90 in Mexico included 85,182 residents in 18,838 households. The community mobilisation protocol began with community discussion of baseline results. Each intervention cluster adapted the basic intervention — chemical-free prevention of mosquito reproduction — to its own circumstances. All clusters continued the government-run dengue control programme. Primary outcomes per protocol were self-reported dengue cases, serological evidence of recent dengue virus infection in children, and conventional entomological indices.
Six measurement points
Data came from this three linked cross-sectional studies in this trial (2011, 2012 and 2013), and another three during the pilot study (2005, 2006 and 2007). Two of the six measurements points were in the dry season (2011 and 2013) and four during the rainy season (2005, 2006, 2007, 2012). During these entomological surveys, qualified government personnel collected, classified and counted Aedes aegypti larvae and pupae from households.
Inspections and analysis of specimens
Twelve-person field teams conducted the household interviews and entomological inspections. Entomological inspections used the standard protocols of the national programme for inspecting, collecting, transporting, identifying, counting and classifying immature Aedes aegypti specimens. Inspectors checked every water container using the appropriate instruments (net, pipette, bowl, magnifying glass, flashlight) to find larvae or pupae. They classified containers as: barrels or large tanks, buckets, washtubs, flowerpot plates, flowerpots, tyres, containers for non-storage use (bowls, water fountains, etc.), and items that had no clear household use (calaches). The government entomologists verified and classified the collected specimens of larvae and pupae. A container was considered positive when it contained one or more immature forms of Aedes aegypti in any stage, confirmed by the government entomologists. A household was considered positive when it had one or more positive containers.
Exposure to temephos
At six measurement points, the temephos exposure indicator came from the observation of temephos in inspected water containers. This served for the principal analysis. In a supplementary analysis at four measurement points (2006, 2007, 2012 and 2013), exposure to temephos came from two variables: i) temephos identified at the time of the entomological inspection in at least one container in the household (yes/no), and ii) the report in the household questionnaire of the last temephos application within 30 days of the interview (data binomialised at 30 days). We excluded from the analysis households unable to respond about the timing of the temephos application visits — 10 in 2006 (<1%), 15 in 2007 (<1%), 361 in 2012 (9%) and 403 in 2013 (10%).
We derived three entomological indicators of the presence of immature forms of the Aedes aegypti mosquito: The number of larvae- or pupae-positive households per 100 inspected households (Household Index), the households where pupae were found (Households Positive for Pupae (HPP) and the number of pupae per person (PPP).
The principal analysis of the main trial used cluster as the unit in an intention to treat analysis ; the unit of analysis of this secondary analysis was the household because exposure to temephos was not uniform within the clusters. Bivariate and then multivariate analysis evaluated impact on each entomological index, for each exposure measure in the context of other factors that might affect the outcome, derived from household responses to an administered questionnaire.