This study highlighted high resistance intensity to alpha cypermethrin and moderate resistance to deltamethrin and permethrin in An. funestus s.l. from Chikwawa. Anopheles funestus s.l. exposed to deltamethrin indicated confirmed resistance at 1X DC, and when assayed at 2.5X DC and 5X DC, the mortality was less than 98%. Susceptibility was only restored when a 10X dose was used, hence the classification as moderate intensity . Similar results were observed for permethrin with the only difference being that mortality at 1X DC was 92.5% indicating possible resistance, which was confirmed when higher doses were used at 2.5X and 5X DC with mortalities ranging from 90-98%. Susceptibility was also restored at 10X DC as with deltamethrin, indicating moderate resistance. Mortality to alpha-cypermethrin was less than 90% at 1X DC and 2.5X DC, while it fell in the range 90-98% at 5X and 10X DC, indicative of high intensity of resistance to this pyrethroid.
In addition to resistance against all the three pyrethroids, low mortality (33.8%, n=93) of An. funestus to the carbamate bendiocarb was also observed. However, intensity assays were not carried out in this study and this warrants further investigations. Previous studies in southern Malawi reported that An. funestus mortality to bendiocarb dropped from 60% in 2009 to 30.1% in 2014, before a further decrease to 19% in 2015 . Unlike previous studies which reported moderate resistance or variable responses to DDT in the An. funestus population [12, 15], complete susceptibility to DDT (mortality 98.9%, n=103) was observed in the current study. The current study also corroborates previous observations of full susceptibility to organophosphates with observed mortality of 100% (n=103) to pirimiphos-methyl [10-13, 15].
This study used wild-caught female Anopheles funestus group mosquitoes of unknown age and did not rear any specimens in the laboratory or insectary for the insecticide susceptibility tests. One limitation of using wild mosquitoes was the fact they could have been exposed to various field conditions including varying degrees of insecticide doses (e.g. on nets, wall surfaces or in agricultural fields), therefore potentially running the risk of over-estimating resistance in the given mosquito population . However, the given scenario more closely represents the actual conditions that any given intervention would encounter in the field, in addition to the fact that wild-collected specimen are also the epidemiologically relevant cohort of vectors . Another limitation of the current study was that we could not test many insecticides at all doses due to low sample numbers. However, even given the low numbers, the study was still able to document the problem and its severity. Advanced molecular or biochemical tests for resistance mechanisms were not done as these were previously described in the study area by Riveron et al. .
The Malawi National Malaria Control Program (NMCP) recently adopted an Integrated Vector Control Strategy (IVCS) 2020-2024 and the Insecticide Resistance Management Plan (IRMP) 2019-2022 which currently form the core of the malaria control program in the country. For vector control, universal coverage of all at-risk populations with insecticide-treated nets is the main approach together with complementary indoor residual spraying in selected districts. ITNs are distributed via mass campaigns every three years and through routine distribution in clinics to pregnant mothers and children under the age of five while IRS is implemented yearly in four districts [10, 28]. However, the implementation of IRS over the years has not been consistent in all the selected districts due to logistical and financial constraints and the rise in pyrethroid resistance. The rise of pyrethroid resistance prompted the development of the strategic plan for monitoring and managing resistance (the IRMP) to counter the potential detrimental impact of resistance [10, 29]. The current study demonstrates the importance of the IRMP to safeguard progress in malaria control.
Recently, the NMCP scaled down the IRS spraying to only one district (Nkhotakota) and switched to pirimiphos-methyl for two consecutive spray rounds, spaced one year apart but the program has bounced back to four districts for IRS. The insecticides of choice in the new IRS strategy include pirimiphos-methyl (organophosphate), clothianidin (neonicotinoid) and a formulation that combines clothianidin and deltamethrin, while the upscaling of IRS to more districts is also affected by high costs of the recommended alternative insecticides [10, 13].
Although DDT is still effective against local mosquitoes and is recommended in the current vector control strategy, the potential use of this insecticide is hampered by concerns surrounding its use [30-33]. In 2006, the WHO made a call for the use of DDT for vector control and provided clear and strict guidelines which it adopted from the Stockholm Convention, stipulating how countries can incorporate DDT for malaria control while strongly mitigating against any potential risks. In fact, following the 2006 WHO recommendation for the use of DDT in highly endemic settings, Malawi announced that it would pilot a DDT IRS program [32, 34]. Evidence shows that countries that continue both timely and correct use of DDT for IRS can reduce malaria transmission by up to 90% . When South Africa reintroduced DDT spraying in 2000, they reduced the number of malaria cases and deaths drastically, managed to keep levels under control and by 2012, set the goal to eliminate the disease entirely [36, 37]. The number of countries in Africa adopting DDT spraying for malaria control has risen, and since 2005, it includes Malawi’s eastern and southern neighbour Mozambique, where An. funestus is a key vector too .
However, it has been argued that because Malawi is a largely agricultural economy, the benefits of using DDT for the fight against malaria may be outweighed by the potential detrimental effects on the agricultural industry and the economy at large . This debate is also common in other African countries and some studies have even suggested that the potential benefits of DDT use for malaria vector control would be in the same order of magnitude as its detrimental effects on infant mortality . Compounds such as clothianidin and deltamethrin/clothianidin combinations thus offer a good option for the rotation strategy with organophosphates for the IRS program. The current vector control strategy also recommends PBO-nets and combination ITNs for areas with high levels of pyrethroid resistance [10, 29]. The present study supports and highlights the critical importance of this strategy as resistance intensity data add predictive value for making informed insecticide choices, to prevent compromised transmission control [26, 27, 41].
Clearly, a vector control strategy such as IRS that incorporates DDT and pirimiphos-methyl or other organophosphates may be a preferred means to managing the current situation of resistance. This would serve as an interim solution as novel compounds are being developed or await registration and WHO approval and recommendation. Also, strategies that incorporate insecticides with new generation modes of action, or those that do not involve the use of insecticides at all, should complement ongoing interventions to avoid further risks that resistance may pose to the control program. These findings also highlight the importance of making new generation ITNs (such as PBO-Nets) readily and widely accessible to communities as they have demonstrated to have greater entomological and epidemiological impact than standard LLINs in settings of high insecticide resistance . Such a multi-pronged approach will aid the country as it transitions towards elimination.
In this study, Anopheles funestus s.s. was found to be the most abundant species, as also previously observed [11, 12]. Anopheles parensis and An. rivulorum were detected in this study and continuous surveillance and monitoring of these species needs to be incorporated as a routine, as these two species have been shown elsewhere to be contributing to transmission and also found biting humans indoors [42, 43]. Very few An. gambiae s.l. were collected (n=13) in this study and no further investigations were done.