A noninferiority cluster randomised evaluation of a broflanilide indoor residual spraying insecticide, VECTRON T500, for malaria vector control in Tanzania

Categories: Disease & Virus

April 29, 2025

The number of houses per study cluster ranged between 100 and 200 houses. In most study clusters, houses with walls made of mud were predominant, i.e. 80.75% (95% CI: 75.0–86.5%) in the Fludora^® Fusion and 77.6% (95% CI: 65.2–90.0%) VECTRON™ T500 arms. Coverage of ITNs in study clusters were 85.0% (95% CI: 73.2–96.9%) and 90.8% (95% CI: 81.1–100%) in the Fludora^® Fusion and VECTRON™ T500 arms, respectively.

Between February-March 2021, a total of 844 houses were sprayed in the intervention arm and 916 houses in the reference arm. The community accepted the intervention and did not report adverse effects.

Residual bioefficacy

A total of 12 monthly rounds of in situ wall cone bioassays with pyrethroid-susceptible and pyrethroid-resistant strain mosquitoes were conducted. In most cone bioassays conducted, both VECTRON™ T500 and Fludora^® Fusion induced over 90% mortality of susceptible An. gambiae s.s. Kisumu strain and resistant An. gambiae s.s. Muleba-Kis strain mosquitoes on both concrete and mud walls up to 12 months after spraying (Fig. 1). With both VECTRON™ T500 and Fludora^® Fusion, relatively higher mortalities were recorded on concrete walls than on mud walls. The residual efficacy for both interventions 12 months post spraying remained above 80% for both concrete and mud walls (Fig. 1).

Vector bionomics and insecticide resistance monitoring

The insecticide susceptibility testing results indicated that An. gambiae s.l. from Muheza was resistant to deltamethrin (mortality rates < 90%) (Supplementary Fig. 1).

A total of 7,127 mosquitoes were collected from the 16 study clusters during the baseline period between January 2021 and the second week of February 2021. Of these 3,262 (46%) were morphologically identified as non-malaria vectors (Culex species) and 3865 were Anopheles mosquitoes. Of the Anopheles mosquitoes, 2357 (32%) and 1488 (21%) were morphologically identified as An. gambiae s.l. and An. funestus s.l., respectively. The other 41 specimens (1%) were identified as other Anophelines.

A sequence of 12 rounds of monthly CDC light trapping was carried out in 5 randomly selected houses per cluster. Proportionally, species of the Culex genus were most abundant, followed by An. gambiae s.l. and then An. funestus s.l. (Fig. 2). The density of An. gambiae s.l. was considerably higher than An. funestus s.l. As expected from its biology, An. funestus s.l. was a late season vector due to its proclivity for breeding in more permanent bodies of water compared to An. gambiae s.l. which, if predominantly An. gambiae s.s. would prefer temporary breeding sites. Both An. gambiae s.l and An. funestus recorded a declining trend in abundance post intervention (Fig. 3). All species declined significantly from the baseline survey to the first month post survey (P = 0.001). With all surveys, the number of Anopheline mosquitoes collected from the VECTRON™ T500 arm were not significantly different to those collected from the Fludora^® Fusion arm (Table 1). The prolonged impact of both IRS products over one year is illustrated in Fig. 4.

For the pre-intervention period, the results showed that the average number of indoor Anopheline mosquitoes collected per house per night in Fludora^® Fusion clusters was 17.4, (95% CI: 0.9–33.9), while the average number of indoor Anopheline mosquitoes collected in VECTRON™ T500 clusters was 15.4 (95% CI: 0.5–30.3). The difference between the two arms pre-intervention was not significant (Table 1). Post-intervention, the results showed that the average number of indoor Anopheline mosquitoes collected per house per night decreased: in Fludora^® Fusion clusters it was 1.6 (95% CI: 0.2–3.0), while the average number of indoor Anopheline mosquitoes collected post-intervention in VECTRON ^TM T500 clusters was 1.5 (95% CI: 0.03–2.9). The difference in vector density between VECTRON™ T500 arm and Fludora^® Fusion arm post intervention was not significant (Table 1).

Table 1 Anopheline mosquito density pre and post intervention in the VECTRON™ T500 and Fludora^® Fusion trial arms.

The mean geometric village level density of indoor Anopheline mosquitoes collected per house per night in the Fludora^® Fusion treated clusters was 2.87 while the mean geometric village level density of indoor Anopheline mosquitoes collected in the VECTRON™ T500 treated clusters was 2.32. The total Anopheles density ratio was 0.77 (95% CI: 0.45–1.29), after adjustment for baseline density, month of catch, percentage of houses with ITNs and percentage of houses plastered with mud (Table 2). The mosquito density ratios according to taxon are shown in Table 2.

Table 2 Overall mosquito densities in each trial arm and ratio between trial arms.

The species identification assays revealed that the majority of Anopheline samples were An. gambiae s.s., being between 60% and 67% in both trial arms before and after spraying (Table 3). The species composition of samples assayed before and after spraying are highlighted in Table 3.

Table 3 Species composition of anopheline mosquitoes from the VECTRON™ T500 and Fludora^® fusion trial arms pre- and post-intervention.

The mean village level P. falciparum sporozoite rates in the VECTRON™ T500 and Fludora^® Fusion trial arms were 0.39% and 1.04%, respectively (Table 4). The difference, adjusted for baseline measure, month of catch, percent of houses with ITNs and percent of houses with mud plastered walls, was 0.84% (95% CI: −1.24–2.93%). The mean village level EIR in the VECTRON™ T500 and Fludora^® Fusion trial arms were 3.18 and 15.44, respectively (Table 4). The difference adjusted for baseline measure, month of catch, percent of houses with ITNs and percent of mud plastered houses was 15.61 (95% CI: −11.56–42.79).

Table 4 Sporozoite and entomological inoculation rates in each trial arm.

A total of 1,341 An. gambiae s.s. and An. arabiensis were analysed for the kdr mutation L1014S. Of these, 812 and 529 were collected at baseline and after IRS, respectively. Molecular analysis for kdr in An. gambiae s.s. and An. arabiensis samples showed a significant difference in the frequency of homozygous resistant (RR), heterozygous resistant (RS), and homozygous susceptible (SS) after IRS compared to the baseline in the Fludora^® Fusion arm (X² = 27.77; P < 0.001; Table 5). Similarly, in the VECTRON™ T500 arm, there was a significant difference in the frequency of RR, RS and SS after IRS compared to baseline (X² = 14.39; P = 0.001; Table 5). The frequency of RR, RS and SS pre- and post-intervention for each species are shown in Supplementary Tables 1 and 2.

Table 5 Kdr (L1014S) target site mutation frequency before and after IRS in each arm.

Adverse effects and acceptability

Participants in all groups reported that the spray exercise was organized in such a way that it did not interfere with any of their routine household activities. It was reported that before the spray team arrived at a consented house, one person visited the targeted houses a few hours prior to the spray team to remind house owners about house preparations for spraying. According to participants, the reminder also gave them the opportunity to shift some of the in-house activities such as cooking to outside the house. This served to minimise the interference of the spraying on household activities.

“There is someone who passed earlier to check if the properties in the house have been arranged properly, then later on the sprayer came for the spraying, therefore, they found us we have already taken out all properties…….” (Male, p6, Muungano).

Another female participant added that;

“The activities indeed were neither stopped nor affected, for us who resides in the house since there were early pass of the information, hence making all issues such as preparing of children food was conducted earlier before the arrival of the team at the house…….” (Female, p4, Misozwe).

All group discussants in intervention and reference clusters expressed a preference for village residents to serve as spray operators. They noted that, having known the sprayers for years, it would not be likely for them to disclose household secrets, as the community shares living conditions. Consequently, revealing another household’s secrets would be regarded the same as revealing their own. In addition, discussants highlighted that the spraying activity provided income for their children and youths, which contributed to the village development. Finally, some participants mentioned that using sprayers from within the village enhanced security, as their behaviour was known and trusted, unlike that of strangers.

“I think the inside village sprayers should continue since they already knew our life in the house, it is easy for them to keep our secrets….”(Female, p5, Misozwe).

All group discussants reported initially having great interest and high expectations for the spray exercise, believing that the intervention could completely eliminate mosquitoes and malaria in the village. In all the intervention clusters, group discussants reported a tremendous decline in mosquito density, similar to group discussants from the Fludora^® Fusion clusters, where discussants noted that mosquitoes disappeared in the first three weeks after spraying. They continued by adding that after the first three weeks of the spray, mosquitoes returned into the houses. Opinions varied on why mosquitoes returned; some discussants believed it was due to standing water and bushes which surround their houses. In one male group from the intervention cluster, it was suggested that the product which was sprayed in their village was fake, since they did not observe any changes in the mosquito abundance.

“Since we were told that there would be no mosquitoes we expected to see no mosquitoes indeed, and frankly speaking at first there were no mosquitoes at all, but in the coming days say after three weeks the mosquitoes returned back….” (Male, p6, Mtindiro).

All discussants showed interest in having their entire house sprayed. In some clusters, house owners decided which room should be sprayed or given priority, but in other clusters the sprayers were the one who made these decisions. For the clusters where homeowners chose, the whole house was sprayed. However, in other clusters in which the sprayers decided, some of the preferred rooms were not sprayed. A few discussants, especially in the female groups, commented that toilets/bathrooms and kitchen should not be left unsprayed to ensure comprehensive protection from mosquito bites, especially as the bathrooms were marked as areas with a lot of resting mosquitoes.

“I also prefer the spray to be sprayed even in the toilets and bathrooms as well as other surrounding places, because if you go in the toilets mosquitoes can bite you there, because there are so many mosquitoes there, they can miss you in the seating room but they will get you in the toilets….”(Female, p8, Misozwe).

Most did not experience or hear of any adverse events after the spray campaign. A few women in the intervention arm reported having experienced an increased heartbeat, unpleasant smells and skin itching. Minor reactions were noted by others which included physical fatigue, burning face sensation, dry throat and dizziness. Some discussants admitted entering their houses before the recommended waiting period after spraying, accidentally coming into contact with the chemicals, or sleeping on wet sprayed beds. These mild reactions typically lasted only a few hours and claimed were alleviated by washing with water and drinking milk. No medical attention was required for these adverse events.

“I passed near the window during the spraying and I was accidentally sprayed on the face, at that time I felt normal but later on I started feeling face itching, hence I decided to wash by water but after few minutes of washing the face my throat became dried and started feeling some fire burning in the stomach….” (Female, p6, Mtindiro).

“…….there after we were told to wait outside the house for two hours, but after they left I decided to go inside and take some of my two oranges, I picked them washed and peel, after peeling I ate them, after eating them I started feeling dizzy and loss of bodily strength….” (Female, p9, Misozwe).

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