Monthly biological larviciding associated with a tenfold decrease in larval density in fish farming ponds and reduced community-wide malaria incidence in northwestern Brazil

Abstract

Background: Larvicides are typically applied to fixed and findable mosquito breeding sites, such as fish farming ponds used in commercial aquaculture, to kill immature forms and thereby reduce the size of adult malaria vector populations. However, there is little evidence suggesting that larviciding may suppress community-wide malaria transmission outside Africa. Here, we tested whether the biological larvicide VectoMax FG applied at monthly intervals to fish farming ponds can reduce malaria incidence in Amazonian Brazil.

Methods: This study was carried out in Vila Assis Brasil (VAB; population 1700), a peri-urban malaria hotspot in northwestern Brazil with a baseline annual parasite incidence of 553 malaria cases per 1000 inhabitants. The intervention consisted of monthly treatments with 20 kg/ha of VectoMax FG of all water-filled fish ponds in VAB (n ranging between 167 and 170) with a surface area between 20 and 8000 m², using knapsack power mistblowers. We used single-group interrupted time-series analysis to compare monthly larval density measurements in fish ponds during a 14-month pre-intervention period (September 2017-October 2018), with measurements made during November 2018-October 2019 and shortly after the 12-month intervention (November 2019). We used interrupted time-series analysis with a comparison group to contrast the malaria incidence trends in VAB and nearby nonintervention localities before and during the intervention.

Results: Average larval densities decreased tenfold in treated fish farming ponds, from 0.467 (95% confidence interval [CI], 0.444-0.490) anopheline larvae per dip pre-intervention (September 2017-October 2018) to 0.046 (95% CI, 0.041-0.051) larvae per dip during (November 2018-October 2019) and shortly after the intervention (November 2019). Average malaria incidence rates decreased by 0.08 (95% CI, 0.04-0.11) cases per 100 person-months (P < 0.0001) during the intervention in VAB and remained nearly unchanged in comparison localities. We estimate that the intervention averted 24.5 (95% CI, 6.2-42.8) malaria cases in VAB between January and December 2019.

Conclusions: Regular larviciding is associated with a dramatic decrease in larval density and a modest but significant decrease in community-wide malaria incidence. Larviciding may provide a valuable complementary vector control strategy in commercial aquaculture settings across the Amazon.

Keywords: Amazon; Anopheles; Biological larvicides; Fish farming; Malaria.

Fig. 1

Study site (Vila Assis Brasil; VAB) in northwestern Brazil and the location of individual fish farming ponds that were treated with biological larvicides (red dots). The inset shows a map of Brazil, with Acre State highlighted in dark gray and the municipality of Cruzeiro do Sul (where VAB is situated) in red

Fig. 2

Monitoring of anopheline larval density in fish farming ponds of Vila Assis Brasil (VAB), northwestern Brazil, from September 2017 through November 2019. Monthly averages of larvae per dip are shown for early instar (L1 and L2; dark green) and late instar larvae (L3 and L4; light green) collected in fish farming ponds in VAB (number of ponds ranging between 127 and 165 before the intervention and between 167 and 170 during and shortly after the intervention). Vertical arrows indicate the timing of larvicide treatment (from October 2018 through April 2019 and from June 2019 through October 2019). Larval density measurements were carried out 21 days after each larvicide application during the intervention. The light blue area chart indicates the monthly rainfall (mm)

Fig. 3

Interrupted time-series regression analysis of average monthly larval densities in Vila Assis Brasil before (September 2017–October 2018), during (November 2018–October 2019), and shortly after larviciding (November 2019). The solid line shows the trend based on least-squares linear regression fitted to empirical data (black dots) adjusted for a time-dependent variable (rainfall estimates 15 days prior to larval sampling) and for autocorrelation of residuals over time. The dashed vertical line indicates the time of the first larvicide application. No larvicide treatment was applied in May 2019 (see the main text for details)

Fig. 4

Malaria incidence and prevalence in Vila Assis Brasil (intervention site) and nearby larvicide-untreated localities in northwestern Brazil. The monthly incidence of microscopy-confirmed clinical malaria (P. vivax and P. falciparum infections combined) in Vila Assis Brasil (VAB) and comparison localities between September 2017 and December 2019 is shown as gray (VAB) and black lines (seven comparison localities in the municipality of Cruzeiro do Sul). Prevalence rates measured by microscopy and PCR in VAB before (September 2018) and during (March 2019 and September 2019) the intervention are indicated by red and green diamonds, respectively. Vertical arrows indicate the timing of larvicide treatment, and the light blue area chart indicates the monthly rainfall (mm)

Fig. 5

Interrupted time-series regression analysis of malaria incidence in Vila Assis Brasil (black dots and solid lines) and comparison localities (open dots and dashed lines) before and after the larviciding intervention. The least-squares linear regression model fitted to empirical data (dots) is adjusted for autocorrelation of residuals over time. The vertical dashed line separates pre- and post-intervention incidence measurements. The intervention started in November 2018, but we include only incidence estimates obtained from January 2019 in the “post-intervention period,” as we expect a 2-month delay in the effect of larval density reduction on malaria transmission (see “Methods”)