Combating Resistance to Insecticides: Alternative Approaches in Sustaining the Relevance of Vector Control Strategies—A Policy Brief

Summary

Resistance to insecticides by malaria vectors is an emerging threat in malaria-endemic countries that threatens gains so far achieved in control of the epidemic. The effectiveness of vector control strategies are largely dependent on the potency of the chemicals used. Evidence from the analysis of data from the insecticide resistance database, managed by the Uganda National Malaria Control Program, suggests resistance to pyrethroid chemicals; and partial or total resistance to carbamates. The recommendation of the World Health Organization is to use only chemicals in the pyrethroid class in the impregnation of mosquito nets. Resistance to pyrethroids therefore may compromise the effectiveness of this strategy for malaria control.

Uganda registered dramatic reduction in the malaria burden between 2000 and 2015. There has however, been a reversal in the trend in recent years, with malaria cases rising above the 2015 levels. Consequently, there has been a massive scale-up of vector control strategies. A second mosquito net distribution campaign targeting all households in the country was conducted in 2017, following the first campaign which was implemented in 2013/4. This was envisaged to achieve a target mosquito net coverage of 85%, and consequently further reduce the prevalence of malaria in the country. Indoor Residual Spraying (IRS) has also been implemented in high burden districts in Northern and Eastern Uganda.

The role of insecticide resistance in the reversal of gains in malaria control in Uganda has not been widely explored, yet can- not be dismissed. In order to curtail, the further spread of insecticide resistance, we suggest the roll out of mosquito nets treated with insecticides enhanced with Piperonyl Butoxide (PBO), a synthetic synergist. Organic alternatives to pyrethroids like pyre- thrum, which has been demonstrated to be effective, may also be considered.

Background

Malaria remains the leading cause of mortality and morbidity in the world. In 2015, it was reported that some 214 million cases of malaria had occurred globally, with over 440,000 deaths. The World Health Organization reports that sub- Saharan Africa bears a disproportionate burden of this disease, with 90% of childhood deaths due to malaria occurring in this region (2,3). Over the last decade, however, significant progress has been made in the fight against malaria. The African Leaders Malaria Alliance (ALMA), a platform that brings together leaders in the continent, recently recognized five African countries which decreased malaria prevalence by over 50% from the year 2000 to 2015 (1). Despite these efforts in malaria reduction, there has been an increase in malaria cases in recent years (4). This increase may have been due to a number of factors, including insecticide resistance.

This relative success has been achieved through the application of two major vector control strategies, namely Indoor Residual Spraying (IRS) and the use of Insecticide Treated mosquito nets (ITNs). The application of IRS, and the use of ITNs are the mainstay of vector control in most malaria- endemic countries (5). In Uganda, IRS has a long history dating back to the 1950s. However, in recent years, it has mostly been used in 25 districts in Northern and Eastern Uganda. In these districts, IRS has been used in combination with ITNs, which are widely available countrywide (3).

Uganda has just completed the second universal coverage campaign (UCC) for ITNs (Ministry of Health, Uganda). The first one was implemented in 2013/4 (6). In these campaigns, all households in the country are targeted for mosquito net distribution. The target is for a universal coverage of 85% nationwide. Mosquito nets are also given out routinely in health facilities to pregnant women attending antenatal care (ANC) and to children during EPI vaccination. Mosquito nets are also made available through the private sector, where anyone who can afford can buy for themselves. The UCC and routinely provided mosquito nets are free of charge. Both IRS and ITNs are insecticide- based strategies; meaning that they are as effective as the chemicals employed in their implementation.

Currently, the World Health Organization (WHO) recommends only pyrethroids for use in the impregnation of mosquito nets (7). However, four classes of chemicals are approved for use in IRS, including pyrethroids, organophosphates, carbamates and organochlorines (8). Currently, the coverage of IRS in Uganda is limited to less than 20% of the entire country; ITNs on the other hand have been distributed widely, with coverage rates of over 75% (3,9).

Extent Of The Problem

Recent evidence abounds on the extent of insecticide resistance in Uganda. Analysis of data from the Uganda national insecticide resistance database showed that the malaria vector has developed significant resistance to chemicals in the pyrethroid and organochlorine classes. We analyzed insecticide resistance data from five sentinel sites collected from 2011 We used the WHO criteria of classifying resistance, which states thus; less than 90% mortality rates within a specified period indicated resistance. Malaria vector mortality rates greater than 90% but less than 97% suggested partial or possible resistance.

Mortality rates greater than 97% indicated vector susceptibility to the insecticide. In Apac, Hoima, Tororo, Wakiso and Kanungu Districts, anopheline mosquitoes were resistant, or partially resistant to both permethrin and deltamethrin. Both these chemicals belong to the pyrethroid class. There was evidence of resistance to more chemicals in the pyrethroid class. In these districts, resistance to Dichloro-diphenyl trichloroethane (DDT), an organochlorine, was also demonstrated. Moderate resistance was also demonstrated to bendiocarb, a carbamate. There was resistance to propoxur, another carbamate, in Wakiso and Tororo Districts. Only the organophosphates were potent against malaria vectors in all sentinel sites selected.

Vector control strategies have made a vital contribution in reducing the malaria epidemic to current levels. The effectiveness of IRS has been widely documented; however, it is expensive and therefore less widely used, except in high transmission areas for the rapid reduction of the prevalence of malaria. Various studies have also demonstrated the effectiveness of mosquito nets in reducing childhood morbidity and mortality. With the current UCC coverage rates, the ITN is the most available malaria control intervention. However, the emergence of resistance to insecticides used in the impregnation of ITNs means that mosquito nets can no longer be relied upon to protect its users against malaria.

Policy Critique

Presently, the WHO Pesticide Evaluation Scheme (WHOPES) recommends three LLINs for public sector procurement; namely, Olyset Net^®, PermaNet^®, and Interceptor^®. These LLINs are all impregnated with varying concentrations of pyrethroid chemicals. The Olyset Net^® has 2% permethrin, while PermaNet^® is impregnated with deltamethrin. Interceptor^® on the other hand has alpha-cypermethrin, another chemical in the pyrethroid class (10). Mosquito nets provide a physical barrier, limiting access by mosquito vectors and thus providing protection to the human being from malaria. Pyrethroid insecticides further have an excitorepellant effect providing protection against malaria to the individual. Often, these chemicals kill mosquito vectors that come in contact with them. The emergence of insecticide resistance therefore calls for the need for creative alternatives to enhance protection against malaria using mosquito nets. Though the use of pyrethroids is not as common in indoor residual spraying (IRS), this demonstrated resistance com- promises pyrethroids as the chemical of choice.

Policy Alternatives

Piperonyl Butoxide (PBO) is a synthetic synergist that helps to enhance the performance of LLINs by increasing the susceptibility of malaria vectors to pyrethroid chemicals (11). The mode of action of PBO, among others, is inhibiting the activity of enzymes in mosquitoes, and the incorporation of the synergist has been demonstrated to restore the efficacy of pyrethroids where there is widespread pyrethroid resistance (12).

Bendiocarb, against which resistance by malaria vectors has been demonstrated in Tororo and Wakiso Districts may not be effective when used for IRS in these districts. Pirimiphos methyl, an organophosphate, may be used as an alternative. In the last round of IRS in the fourteen Northern and Eastern Uganda districts, pirimiphos methyl was indeed used. The WHO recommends rotation of insecticides as one of strategies to delay or manage resistance by malaria vectors (7). These strategies need to be incorporated in the Ministry of Health policy documents to clearly guide procurement and choice of insecticides for IRS.

Policy Recommendations

In view of the above, it is recommended that the mosquito nets encouraged for use should be those impregnated with pyrethroids enhanced with PBOs. Currently, there is a mix of mosquito nets with different chemicals used. With the private sector largely unregulated, there is a real danger of non-ITNs offered for sale to Ugandans. According to the Malaria Indica- tor Survey conducted in 2014, there was a similar number of people with any type of mosquito net as there were with ITNs, including LLIN (13).

Alternatives to pyrethroids may be considered for use in mosquito nets. Organic compounds like pyrethrum have been demonstrated to work as well as pyrethroids. Pilot studies have suggested that it is an alternative to pyrethroids with considerable advantages, including lower resistance ratios, repellency, good knock down effect and blood-feeding inhibition against pyrethroid resistant mosquito vectors (14).

Conclusion

The universal coverage campaign for mosquito nets and other channels of distribution have made the vector control intervention more available for use. A significant contributor to the successes in malaria control in Uganda, it is now threatened by the emergence of insecticide resistance by malaria vectors. Incorporation of PBO-enhanced mosquito nets shall restore the relevance of ITNs in vector control. Pyrethrum may yet be another alternative to pyrethroids with lasting results. Lastly, the strategies outlined by WHO in the global plan for insecticide resistance management to delay or manage resistance need to be incorporated in our vector control policies.

References

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