1.0 Description of the article
The paper will review an article published in the emerging infectious diseases journal on “Reduced Efficacy of Insecticide-Treated Nets (ITN) and Indoor Residual Spraying (IRS) for Malaria Control in Pyrethroid Resistance Area, Benin”. The study compared the effectiveness of pyrethroid insecticides used in ITN and IRS in two villages, Ladji and Malanville. In most of the malaria-endemic African countries, including Benin, ITN and IRS are the principal methods used in preventing malaria through vector control. In the two vector control methods, pyrethroid has been the preferred insecticides in the last decade due to the environmental safety of pyrethroids. As a result of the widespread use of the pyrethroid based insecticides, the malaria vector (Anopheles gambiae) has developed and maintained resistance to pyrethroids. In West Africa, pyrethroid resistance has been attributed to the pyrethroid knockdown resistance gene (kdr) which has become widespread in An. gambiae. N’Guessan, et al., (2007) sought to establish whether the spread of the kdr undermines the efficacy of the ITN and IRS programs in two villages in Benin. Consequently, the study evaluated how resistance to pyrethroids affects the fight against malaria.
1.1 Study site, design and data collection
The study was carried out in two villages near Cotonous, Benin’s capital. The two villages were chosen due to their high mosquito population and hence high malaria prevalence. Ladji is one of the villages in Benin that experiences floods during the rainy seasons while Malanville does not experience floods has the paddy rice fields which are flooded with artificial irrigation water. The flooding and the irrigation of rice fields in Ladji and Malanville respectively, make the villages very good breeding grounds for mosquito. Ladji village mostly has a population of An. gambiae with high kdr frequency and the Culex quinquefasciatus (a mosquito strain that does not transmit malaria but is a nuisance), both resistant to pyrethroids with the former being resistant to DDT as well. On the other hand, in Malanville village An. gambiae is susceptible to pyrethroids such as lambdacyalothrin and deltathrin (a synthetic insecticide based on the pyrethrin structure) due to the absence of the kdr gene.
The study was conducted using 4 experimental huts in each of the villages (one hut for the control, one for IRS, one for ITN and one with deliberately holed ITN-each with 80 holes). The effectiveness Pyrethroid treated nets and residual spray treatments were evaluated against respective untreated controls. The experimental huts were specifically designed, in a manner to limit mass exodus of mosquitoes and thus enable the researchers to account for almost all mosquitoes accessing the huts. In addition, there was a veranda trap to trap any exiting the huts. Formulations of lambdacyhalothrin (a pyrethroid) were used to treat the nets, the walls and the ceilings of the huts.
The Centre de Recherche Entomologique de Cotonou (CREC), that owns the huts and participated in the study, employed eight men (sleepers) to sleep in the huts at night and pick mosquitoes from the huts at dawn. The eight men gave their informed consent to take part in the study beforehand and they were given chemoprophylaxis to protect them from malaria. The study commenced a week after insecticide treatment and after establishing mosquitoes were evenly attracted to the huts. The study was conducted for fifty nights (about eight weeks) at each of the two sites, during which period the sleepers were rotated between the huts. The rotation of the sleepers was to correct for the probability of differential in attractiveness to mosquitoes. The mosquitoes collected by the sleepers were identified (by their strains) and labeled as live or dead and unfed or blood-fed. Male mosquitoes were not scored, as they do not feed on blood neither do they transmit malaria.
The effect of the treatment on mosquitoes was compared to the controls based on: the percentage of the collected dead mosquitoes, deterrence, induced exophily, blood-feeding inhibition and the mortality. The formula below was used to calculate the insecticidal effects:
Overall insecticidal effect (%) = 100 (Kt – Ku)/(Tu – Ku)
Where
Kt = number of dead mosquitoes in treated huts
Ku = number of dead mosquitoes in untreated huts
Tu = the total number of mosquitoes collected from the control hut.
1.2 Main results
The study established that there was a major reduction of the efficacy of pyrethroids in areas with pyrethroid resistant An. gambiae (represented by the Ladji village). There was no statistically significant difference in the reduction of efficacy between ITN and IRS, with 22% of the mosquitoes dying in the IRS hut and 19% dying in the ITN hut. On the other hand, in the areas with pyrethroid susceptible mosquito (Malanville), 72% of the mosquitoes that entered the IRS hut died while 98% that entered the ITN. This implies that lambdacyhalothrin is effective in controlling the pyrethroid resistant strains of mosquito. In addition, the results from the trials in Malanville imply that ITNs were more effective than IRS, with regard to killing pyrethroid-susceptible mosquito strains.
Another major finding of the study was that despite the reduction in the efficacy of pyrethroid- treated nets and surfaces to control pyrethroid-resistant mosquito, the pyrethroid treatment partially deterred the entry of mosquito. As such, pyrethroid treatment offered little (45%-50%) protection against pyrethroid-resistant mosquito strains by reducing the population of mosquitoes that entered the huts. However, most of the mosquitoes that entered the huts went on to blood-feed; this was established in deliberately holed ITN, which did not inhibit blood feeding. On the other hand, of the susceptible mosquitoes that entered the huts with holed ITNs, only 4% fed on blood indicating the uncompromised efficacy of pyrethroids in controlling the susceptible strains.
In the context of the spreading pyrethroid resistance, the researchers recommended another phase of evaluation involving a whole community. The researchers also recommended the use of long-lasting insecticide nets (LLIN) in areas with the susceptible mosquito strains and the development of other insecticides (of classes other than pyrethroids) to supplement or replace pyrethroids in ITNs and IRS. However, N’Guessan, et al., (2007), warned that the government’s proposal to upscale the distribution of LLIN would lead to an increase in the population of the pyrethroid resistant strain. Indeed, a recent study established that in three years after the National malaria control program (NMCP) up scaled the distribution of LLINs in the no-flood zones, the frequency of kdr increased, partly due to this strategy. As such, other studies have recommended other strategies to control the malaria vector such as use of other classes of insecticides such as Chlorfenapyr, which was found to be very effective in IRS. Another strategy that has been recommended is the combination of chlorfenapyr IRS with LLINs. Such a combination would curb the spread of the resistance strain as chlorfenapyr IRS would control the pyrethroid-resistant mosquito strains while LLIN would inhibit blood feeding and thus offer double protection.
2.0 Ethical consideration
Since the infamous Tuskegee syphilis study (1930s-1970s), the principles of ethics in research have emerged as key components of any research involving human (and even animal) subjects. At the heart of the ethical principles is the protection of the subjects/participants rights, integrity and safety. According to a brochure on research ethics from the National institutes of Health, there are seven broad ethics principles that researchers must consider which form the basis of ethical evaluation. These principles are social value, fair subject selection, scientific validity, favorable risk-benefit ration, informed consent, independent review and respect for enrolled subjects.
On the social and economic value front, it is unethical and a waste of resources to subject participants to risk if the outcome of the research outcome will not help to improve the socioeconomic (including health in this case) wellbeing of the community. In other words, research should not be conducted just for the sake of scientific knowledge or to further the donors or the researchers’ interests at the expense of the participants and the community at large. In medical/public health, research the social value of a study is based on three aspects. It must generate results that improve disease management (through better disease diagnosis, treatment and prevention), produce information that increases knowledge of the subject being studied and guides further future research on the subject. Thirdly, the research findings ought to be shared with other scholars and the public. Based on these three aspects, the research by N’Guessan, et al., (2007) had social value.
First and foremost, in the context of the emerging and ever increasing resistance An.gambiae to pyrethroids, it is necessary to keep evaluating the efficacy of pyrethroids in ITNs and IRS which are the cornerstones of malaria prevention in Benin. Failure to do so would lead to the government and the private spending billions to buy pyrethroids for the NMCP only to discover that the insecticides are not accomplishing the intended purpose. This would be a loss of economic resources that could be utilized for other vital functions. In addition, the findings of this research recommended the use of LLIN and the development of other classes of insecticides for ITNs and IRS as a way to mitigate the reducing efficacy of pyrethroids and hence improve the control of pyrethroid-resistant mosquito which would intern improve the malaria prevention/control strategies. However, the scholars warned of the negative consequences of the proposed up scaling of LLIN which was to be confirmed by other studies.
Secondly, the information generated from this study (which according to the authors was phase 2 of an earlier study) formed a foundation for phase 3 of evaluating the efficacy of pyrethroids in the face of increasing frequency of the kdr gene in An.gambiae. On the third aspect of social value, the scholars shared their findings by publishing the study in the Emerging infectious diseases journal. The researchers together with the journal managers went further and made the article free on the internet so that anyone can access the findings.
On the principle of scientific validity, any research must follow scientific methods and produce results that will and value to the available body of knowledge. In other words, the study should just be a duplication of another research and neither should it be carried out haphazardly. This particular research revealed relevant knowledge on the reduction of efficacy of pyrethroids as well as the resistance mechanism. From the result, discussed earlier, the study revealed that the use of pyrethroids offered very little protection (mainly due to the deterrent effect) in area with high population of pyrethroid-resistant mosquitoes. On the other hand, pyrethroids offers significant protection against the susceptible mosquitoes and ITNs offer more personal protection than IRS in the pyrethroid-susceptible areas. These findings are obviously useful in determining where the use of pyrethroids in IRS and ITNs can be continued. In addition, the study follow a systematic scientific method which is indicated by the presence of a hypothesis (that there is reduced efficacy in ITNs and IRS for malaria control in the pyrethroid-resistant areas), controls (untreated hut), controlled variables (the trials were conducted in the natural mosquito environment but under controlled conditions). Another important ethical principle in research is subject selection.
With regard to subject selection, eight men employed by CREC participated in the study for the purposes of collecting mosquitoes in the morning and providing blood meal overnight. Since the article does not give information on the inclusion and exclusion criteria, it is difficult to establish whether the subjects were selected fairly. However, they were treated with respect, to the extent they were given chemoprophylaxis which minimized the risk of getting infected with malaria. The issue of paying research participants has always been an ethical dilemma because of the potential to be an inducement (which is unethical) to participate in the study. It is particularly unethical when the researchers use money to exploit the economically challenged people to participate in a risky study. Paying participants can also compromise the principle of informed consent, particularly where the participants are poor. Never the less, the current guidelines allow the researchers to compensate the subject for the time spent and the inconveniences resulting from the participation in the study. Additionally, compensating the participants is a way of respecting them (by respecting hence compensating their time) and their rights. The researchers have not revealed any information about the subjects in the article and thus have respected the subjects’ confidentiality. Therefore, the researchers cannot be judged to have acted out of ethical practice because they paid the sleepers. In addition, there is no indication whatsoever, that the subjects were exploited, coerced or even treated unfairly during the research period. If anything, the provision of chemoprophylaxis reduced the risk of the study by protecting the subjects from malaria. This is in line with the principle of favorable risk-benefit ratio, which dictates that for a research study to be ethical the benefits must outweigh the risk. Lastly, the article expressly states that informed consent was sought beforehand, which is another important ethical principle.
Finally yet importantly, the study adhered to the principle of independent review. The ethical committee (IRB) of the London School of Hygiene and Tropical Medicine (LSHTM) and Benin National Ethics committee reviewed the proposed study and gave the researcher a green light to carry out the research. The Gates Malaria Partnership (GMP) funded the study and LSHTM is part of this partnership. As such, if LSHTM were the only institution that reviewed the study then issues of conflict of interest would arise and thus the review by the Benin National Ethics Committee (which is independent from the funding institution) gave the study ethical legitimacy. In addition, the Gates Malaria Partnership comprises the Melinda and Gates foundation and group of institutions of higher education in Europe and Africa, the funding had no strings attached. In other words, the funding organization had no conflict of interest.
2.1 The IRB process
As earlier mentioned, two different ethical committees ethically reviewed the researchers’ proposal. The review by LSHTM’s ethics committee not only represented a review by the funding organization but by the host institution most of the researchers. LSHTM has a comprehensive process and procedure of giving ethical approval to any research conducted by the staff or students, whether it is conducted in the institution or outside the institution. In addition, the host country gave ethical approval to carry out the research, as LSHTM requires that studies conducted outside the country to get approval from the National Ethical Committee of the host nation. GMP also has a training committee that ensures that the researchers have the relevant training (including ethical training) hence, although it is not expressly mentioned in the article, it can be deduced that the scholars received the relevant training to participate in ethical research. The research did not however, address any issues of health inequalities.
3.0 Recommendations
The article reviewed most of the ethics principles stipulated by the National Institutes of Health. However, there is always room for improvement. First, it is important for the researcher to declare any conflict of interest, which was not the case in the article. There is also need to have a good inclusion and exclusion criteria that can help identify suitable subjects. Another way to improve ethical consideration is to have a representative of the community where the research will be carried out in the ethical committee. Such representation would protect the interests and the rights of the community. For instance, in the article in question, the National Ethical committee approved the article and it is not clear if the committee was represented.
References
Emanuel, E., Abdoler, E., & Stunkel, L. (2009). Research ethics:How to Treat People who Participate in Research. Retrieved May &, 2013, from National institutes of health clinical center Department of Bioethics: http://www.bioethics.nih.gov/education/FNIH_BioethicsBrochure_WEB.PDF
LSHTM. (2010, January). Ethics committee statement of policy and principles. Retrieved May 8, 2013, from http://doctoralschool.ioe.ac.uk/files/lshtm-ethic-policy.pdf
N’Guessan, R., Corbel, V., Akogbéto, M., & Rowland, M. (2007). Reduced Efficacy of Insecticide-Treated Nets and Indoor Residual Spraying for Malaria Control in Pyrethroid Resistance Area, Benin. Emerging Infectious Disease , 13 (2), 199–206.
N'Guessan, R., Boko, P., Odjo, A., Knols, B., Akogbeto, M., & Rowland, M. (2009). Control of pyrethroid-resistant Anopheles gambiae and Culex quinquefasciatus mosquitoes with chlorfenapyr in Benin. Trop Med Int Health , 14 (4), 389-395.
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