Part of the reason might be that important windows for atopic sensitization such as prenatal exposures were not captured in the study. The number of cases of allergic sensitization to dogs, cats, and ragweed were small among the study children , resulting in compromised statistical power. The low number of dog and cat allergies might have been due to the high dog ownership and medium cat ownership in the study population : living in proximity to animals is associated with lower sensitization to allergens among children. No significant differences in allergic sensitization or symptoms were found between children in group 1 and group 2, among whom chimney stoves were installed around birth and around 18 months old, respectively. This might have been due to the gradual deterioration of chimney stoves during the 2-year gap between the RESPIRE and CRECER studies, during which group 1 might have been exposed to higher HAP than group 2 because of the older stoves. Another reason might be insufficient exposure reduction, which was also found in a previous analysis of the RESPIRE study: a larger reduction in mean CO exposure was associated with reduction in pneumonia risks, but the moderate difference in group mean CO levels between groups 1 and 2 was not enough to yield a statistically significant difference in pneumonia risk between the groups. The high percentages of reported allergic symptoms and high prevalence of cockroach sensitization among the children in this study is contrary to the “hygiene hypothesis” or “microbial deprivation hypothesis” that early life exposure to microorganisms shapes the Th1 , Th2, and regulatory T cell responses and alters immune response patterns.

For instance,grow rack greenhouse children exposed to enteric pathogens have higher resistance to allergic sensitization compared to those living in pathogen-free environments. While the study population was exposed to abundant microorganisms, it is possible that exposure to HAP prenatally, in early life, or even in reduced amounts after the stove upgrade intervention, could promote a shift toward Th2 responses and thus increase risk for atopy. Previous studies have demonstrated that exposure to PM2.5 may increase the risk of asthma via airway inflammation, increase in oxidative stress, changes in immune signaling, and subsequent disruptions of airway epithelial cells and mucosal barrier function. Studies on rhesus monkeys have also found that co-exposure to a pollutant that causes oxidative stress, ozone, and allergen altered airway structural development and increased risk of an asthma-like phenotype. Another consideration is that the increased wheezing and rhinitis symptoms reported by their mothers among children exposed to higher HAP could also be due to the direct irritating effects of biomass smoke to the upper and lower airway epithelium rather than an underlying allergic mechanism. During study design, we hypothesized that group 3 index study children would have the highest cumulative biomass smoke exposure because they were provided the upgraded chimney stoves the latest, thus were exposed to higher levels of biomass smoke for the longest period of time. We also expected groups 2 and 3 to have comparable levels of biomass smoke exposure during the RESPIRE study period because both groups did not have upgraded chimney stoves at this time. While assessing cumulative CO exposure for the index study children, we used the group 3 proxy infant siblings’ personal CO exposure during CRECER as a proxy for group 3 index study children’s personal CO exposure during the RESPIRE study period when the personal CO exposures of groups 1 and 2 were measured. This allowed us to account for the missing early life personal CO information due to the late recruitment of the group 3 households.

This approximation assumes that newborn children raised in the same household by the same parent will have similar activity patterns and thus similar levels of CO exposure. However, several sources of uncertainty may compromise the accuracy of this proxy measure. Firstly, secular differences between RESPIRE and CRECER , such as different biomass fuels used, different CO diffusion tube batches, as well as the potential changes in household cooking conditions and ventilation, were not accounted for. Secondly, group 3 proxy infant siblings’ CO exposures were measured less frequently , compared to groups 1 and 2 index study children’s early life CO exposures , resulting in potential differential exposure mis-classification. These uncertainties might be the reasons that the estimated CO exposure during the RESPIRE study period is much lower for group 3 compared to group 2 , and the subsequent lower cumulative CO exposure for group 3 compared to group 2 , which was different from our original hypothesis. If group 3 CO exposures were indeed underestimated, it would have caused a downward bias of our secondary analysis results because of the high number of cases in group 3, and the true associations would be higher than reported. This is the first cohort study that looked at SPT prevalence in a rural population of a low-income country. The strengths of this study include the quality of the SPTs, which was supported by positive and negative controls and multiple rounds of field worker training, and use of extensive questionnaires on household information, building structure, animal allergen exposures and SES to allow adequate control of potential confounding variables. The partial randomized controlled trial design between groups 1 and 2 further reduced the possibility of residual confounding. The estimation of cumulative CO exposure was based on repeated personal measurements, which was of higher accuracy than commonly used ambient or static household air pollution monitors.

An important limitation of the study was the self-reporting of allergic symptoms. Since the stove upgrade intervention could not be blinded, the mothers’ responses to questionnaires may have been subject to an upward response bias. In addition, the missing exposure information and stove deterioration during the 2-year gap between the RESPIRE and CRECER studies may have led to exposure mis-classifications. The cumulative CO exposure estimation was also less accurate for group 3 because of the use of infant siblings as proxy for the early life exposure of the older children in this group, as well as the less frequent exposure monitoring during CRECER compared to RESPIRE, potentially resulting in differential exposure mis-classification in the secondary analysis.Historically, malaria in the western Kenya highlands has existed. Since the late 1980s, epidemic to hyperendemic malaria has evolved in the western Kenya highlands because of severe public health problems associated with high morbidity and mortality. Prior to the 1990s, malaria was managed by chemotherapy. However, following the resistance of Plasmodium falciparum to chloroquine and sulfadoxine-pyrimethamine, the country shifted to the use of artemisinin-based combination therapy. Insecticide-treated bed nets and other vector control strategies gained favour based on large-scale randomized control trials. Initial trials with ITNs indicated promising protection and a reduction in morbidity and mortality. However, the affected populations could not afford the ITNs in early 2000. The Kenya Government policy on subsidized ITNs and targeting vulnerable populations increased the number of people who had ITNs in their households but the overall effect on malaria transmission was low. By 2011, the government rolled out the universal bed net programme where every two persons in a household were provided with a free ITN. It was expected that ownership and usage of 80% of ITNs would have a high epidemiological impact on malaria transmission. This programme has faced numerous challenges, among them insecticide resistance, non-compliant human behaviour,grow rack systems changes in biting habits of the vector, changes in species composition, and vector density. It has been shown that Anopheles gambiae has developed resistance to pyrethroids in western Kenya. Biting behaviour has seen a small but significant increase in early biting of malaria vectors in the western Kenya lowlands. The proportion of Anopheles arabienis has progressively increased in the western Kenya highlands. Although high ownership of ITNs has been reported in western Kenya, the usage has not been as high. Consequently, this has led to high transmission of the malaria parasite in the population with low usage. This study was carried out to determine the impact of ITNs on indoor vector densities and biting behaviour in western Kenya.This study was carried out to assess the impact of ITNs on indoor vector densities and biting behaviour in western Kenya as the use of ITNs has been shown to be effective in reducing mortality and malaria transmission in the past.

Before the mass distribution of ITNs in 2011, bed net ownership in western Kenya was reported to be below 80% and parasite resurgence had been seen in areas of western Kenya. This was attributed to vector resistance to pyrethroids and the inefficacy of bed nets because of the low ownership. Afterwards, the Roll Back Malaria Partnership raised coverage of ITNs to ≥80% through the free mass distribution of long-lasting insecticidal nets /ITN campaigns, which were carried out in various parts of Africa. The current policy for vector control in Kenya includes the use of LLINs and limited use of IRS where the government-marketed, subsidized bed nets in 2002, 2006 to vulnerable groups until 2011 when there was a universal distribution policy was implemented with every two persons in a household receiving a free bed net. In this study, high bed net ownership of >80% in all six sites was confirmed. The high bed net ownership has a community effect where people without nets are protected by the area-wide effects of ITNs nearby. Anopheles gambiae indoor resting densities over the last decade have decreased tenfold in Iguhu, sixfold in Marani and fourfold in Kombewa, while densities of An. funestus have decreased threefold in Iguhu and sixfold in Kombewa.

However in Marani, over the decade densities of An. funestus have increased threefold compared to a study by Ndenga et al.. Likewise, sporozoite rates of An. gambiae have declined fourfold in Iguhu and Kombewa while they have increased fourfold in Marani. Anopheles funestus sporozite rates remained constant in Kombewa, while in the other sites there were no confirmed infectious An. funestus. Anopheles funestus is seen as one of the most abundant vectors in Kombewa, which has been reported previously. The species is re-emerging in Marani where it was the most abundant species, as shown in the results. Anopheles funestus breeds in permanent habitats towards the end of the wet season and is known to require vegetation and shade and the larval habitats are found mainly in swamps and pastures. Anopheles funestus takes 3 weeks to mature, which is longer than An. gambiae maturation period. Other studies conducted in western Kenya lowland region have reported that An. funestus is re-emerging, which is suspected to be as a result of pyrethroid resistance after a long-term implementation of ITNs. Previous studies in the sugar-belt region of Miwani reported the ratio of An. arabiensis to be higher than that of An. gambiae s.s., especially during the dry season. The use of ITNs has had a great impact on densities, species and sporozoite rates. The proportion of An. arabiensis is increasing in the highlands, a factor that could have malaria transmission implications as An. arabiensis is a less efficient vector than An. gambiae, as An. arabiensis is zoophilic. Githeko et al. found that malaria vectors fed during the late part of the night with peaks at 05.00 h. In this study, An. gambiae caught after midnight was blood fed, while fed An. funestus were caught throughout the night both indoors and outdoors. It is likely that blood-fed An. funestus may have been avoiding resting. This observation supports exophilic behaviour in An. funestus, a phenomenon that requires further investigation. In regard to human and mosquito activity, data from this study suggests that there is a risk of transmission at dusk and at dawn. Data collected during the study did not support continuous outdoor transmission since the majority of humans were indoors between 21.00 and 05.00 h. The use of LLINs has been reported to change the feeding and resting behaviour of mosquitoes. The study reports similar findings that there was high host seeking activity of the vectors at around 18.00 and 20.00 that led to earlier feeding in An. gambiae populations. This could be as a result of the use of ITNs. Anopheles funestus showed no change in feeding habits as the results show that they bite throughout the night both indoors and outdoors. This poses a great risk of malaria transmission throughout the night despite high bed net coverage.