Thursday August 18 2011
The mosquitoes developed resistance to the insecticide contained within bed nets
The Daily Telegraph reported today that “insecticide-treated bed nets, whose use is being widely promoted in Africa to combat malaria, may be linked to local resurgence of the disease”. The newspaper said that a study of a village in Senegal indicates that mosquitoes develop resistance to the insect-killing chemical that coats the nets.
This research study investigated malaria attack rates in 504 inhabitants of the village before and after the introduction of insecticide treated bed nets, between 2007 and 2010. The study was well-conducted. The villagers were contacted every day to monitor fever or other malaria symptoms, and they were assessed as to how they used the nets. The researchers also caught mosquitoes and tested their sensitivity to the insecticide on the bed nets. They also tested for any gene mutations that would make the mosquitoes more resistant to the insecticide.
The study found that for the first two years after introducing the nets, the number of new cases of malaria decreased by more than five fold. However, after 27 to 30 months the rates increased to nearly their original rate. The proportion of mosquitos that were resistant to the insecticide had also increased.
The researchers suggest that the rebound in malaria incidence was partly due to the mosquitoes acquiring resistance. But they also speculate that people lost their protective immunity (as they had less exposure to the malaria parasite), and so they were more likely to have a malaria attack when they bitten. This second theory was not tested in this research.
This important research indicates that using insecticide treated nets alone may not be effective in eliminating malaria in the long term. However, this study has some limitations in that it is a small study in only one village in Africa. Other systematic reviews (see links below) have concluded that bed nets can reduce deaths in children by one fifth and episodes of malaria by half. Further research is needed to find an effective strategy that takes into account the ability of mosquitos to acquire resistance to insecticide relatively quickly and to report long-term outcomes from randomised trials.
Where did the story come from?
The study was carried out by researchers from the Research Unit on Emerging Infections and Tropical Diseases, Senegal, the University of Marseille, and the Pasteur Institutes in France, Senegal and Madagascar. Funding was provided by the Institut de Recherche pour le Développement and the Pasteur Institute of Dakar. The study was published in the (peer-reviewed) medical journal The Lancet.
This research was accurately reported by the newspapers, although none reported the extent of current research in the area, which includes a Cochrane systematic review of the use of mosquito nets to prevent malaria.
What kind of research was this?
This was a longitudinal cohort study which followed the inhabitants of Dielmo village, Senegal, for two periods before and after the introduction of bed mosquito nets between January 2007 and December 2010 to see whether malaria prevention and treatment policies were effective in this area.
This is an ongoing study. Since 1990 the population of Dielmo, a Sengalese village, has been part of a long-term study looking at malaria and its carrier, the mosquito. Daily monitoring of fever has taken place, and monthly captures of mosquitoes for analysis have been carried out.
In 2006, the Senegalese Ministry of Health introduced a treatment for uncomplicated malaria attacks called ACT (artemisinin-based combination therapy) following World Health Organisation recommendations. Prior to 2006 (the introduction of this therapy) other treatments were used. As well as ACT, all villagers were offered long-lasting insecticide (deltametrin) - treated nets in 2008. The researchers examined malaria morbidity (the number of people who carried the malaria parasite but had no symptoms) and mosquito populations between 2007 and 2010 to see whether the newer policies were working.
Dielmo is in the Sudan-savannah region of central Senegal. It lies on the marshy bank of a small stream. Mosquitoes breed all year round and there was an average of 258 infected bites per person per year during 1990 to 2006.
What did the research involve?
Between 1990 and 2010, the inhabitants of Dielmo were monitored to identify all episodes of fever. The villagers received routine blood tests to see if they were carrying the malaria parasite. The present study focused on data from 2007 to 2010. In 2008, all villagers were offered mosquito nets with long-acting insecticide.
The precise location of each villager’s house was recorded alongside details of family ties and occupation. The villagers were visited daily (six days a week) to note their presence or absence in the village. Body temperature was measured three times a week in children under five years old, and in older children and adults if they had suspected fever. In cases of fever or other symptoms, a finger prick test was carried out and the blood tested for the presence of malaria parasites. Four times a year the villager’s mosquito nets were inspected to assess their condition and to ask whether the villagers used them.
Every month, the researchers took note of the type of mosquito that landed on humans and collected them. They assessed how sensitive each type of mosquito was to the insecticide on the mosquito nets and also exposed mosquitos to the nets to see the mosquito death rate up to 24 hours later.
The researchers used clinical data on malaria attacks to determine the incidence (new case) rates, the potential exposure and the number of people who had asymptomatic malaria. They compared these rates to those during the 18 months before the introduction of the nets and the 30 months subsequent to this time. They also collected data on malaria prevalence (the total number of people with malaria at any one time) at the end of the rainy season in October 2007, 2008, 2009 and 2010.
What were the basic results?
The study cohort at the start of the study was 405 people aged from 60 days to 96 years, including 301 permanent residents of the village (defined by at least 272 days residence in Dielmo in 2007). By the time this study was carried out in December 2010 there were 468 people aged between two days and 100 years. Overall, between January 2007 and December 2010, 504 villagers were followed for a total of 17,858 person-months (the sum of the different follow-up times for the total population).
In total, 464 malaria cases were caused by one type of malaria parasite called P falciparum. Four cases were caused by other types. Before the distribution of the mosquito nets there were an average of 5.45 attacks per 100 person-months (as measured proportionately between January 2007 and July 2008). After the distribution of the nets the incidence dropped to 0.4 attacks per 100 person-months (as measured between August 2008 and August 2010). However, 27 to 30 months after the introduction of the nets (September to December, 2010) the incidence increased to 4.57 attacks per 100 person-months.
The rebound in malaria attacks occurred in children/adolescents aged 10 to 14 years and adults. A higher proportion of the malaria attacks in 2010 (63%) were in this group, compared to 33% in 2007 and 2008.
Ownership of nets was 98% in 2008, 83% in 2009 and 79% in 2010. Bed nets were used regularly by 79% of people in 2008, 60% in 2009 and 61% in 2010. The proportion of nets in a good state (i.e. no holes or only one hole) in 2010 was 93%.
The average malaria prevalence was 16.3% in 2007, 4.8% in 2008, 5.1% in 2009 and 2.7% in 2010.
Thirty-seven per cent of mosquitoes were resistant to deltamethrin (the insecticide on the nets) in 2010. The proportion of mosquitos that contained a gene mutation allowing resistance to this type of insecticide (a pyrethroid) increased from 8% in 2007 to 48% in 2010.
How did the researchers interpret the results?
The researchers said that increasing resistance to the insecticide deltamethrin and increasing susceptibility of older children and adults caused a rebound in malaria morbidity and a shift in the age of people affected. The researchers said, “strategies to address the problem of insecticide resistance and to mitigate its effects must be urgently defined and implemented”.
They speculated that one reason for the age shift and increase in incidence of attacks in 2010 could be a decrease in protective immunity. They said that “it is generally agreed that the persistence of clinical immunity acquired during early childhood is dependent on sustained exposure and that immunity decreased when exposure to malaria is discontinued”.
This was an important study that looked at resistance of mosquitoes to insecticide-treated bed nets, and the number of new cases of malaria attacks over time in a small village in Senegal. Although the prevention strategy lowered the number of attacks at first, the rebound in cases that was attributed in part to mosquitoes becoming resistant to the insecticide used on the nets. This indicates that future strategies involving nets would need to take this into account.
The researchers postulated that a decrease in protective immunity (in response to subclinical exposure to the malaria parasite) may also have contributed to the rebound. But this was not directly tested in this study.
There are a number of points to note about this report, some of which the authors mention.
- Previous research (including several controlled trials reported in a Cochrane review) looked at the effectiveness of these nets in the short term (1–2 years). These trials were carried out before the introduction of newer drugs (such as the ACTs used in this study) and when chloroquine was still the main treatment for malaria. As such, this suggests that longer-term controlled trials of the treatments in current use are needed.
- The observed increase in pyrethroid resistance and increasing rates of malaria may have several causes. Although this longitudinal study provides a convincing argument that bed nets with insecticides such as deltamethrin may be associated with rebound of malaria, ideally a controlled trial over a longer period would be carried out that would confirm the researchers theory.
The newspapers rightly highlighted that this study was relatively short and that data was collected from one village, therefore it may not reflect the whole of Africa. It is likely that further follow-up work will address what is the best bed net strategy, and will take into account the fact that resistance can spread quickly in the mosquito community. Further research into protective immunity is also needed.