This study characterized risk factors for malarial anemia in an urban setting surrounded by an area of high endemicity in western Kenya. The observed age range of cases was consistent with that observed for severe malaria outcomes in other highly endemic areas, as was the failure to observe any CM among admissions to KDH during the study period.8
Although the latter may be caused by difficulty in diagnosing CM,53,54
the age profile for cases of malarial anemia was more like that observed in rural settings than in typically lower-transmission urban contexts. We found that regular overnight travel to rural areas was a strong risk factor after adjusting for other factors in the multivariate analysis, which suggested that frequent exposure to infected mosquitoes during rural travel significantly increased risk among urban residents. Although prior residence in a rural area did not meet the Bonferroni criteria for inclusion in the multivariate model, it was a risk factor in bivariate analysis. This finding may further substantiate the idea that chronic rural exposure contributes to incidence of malarial anemia, such that children from high-exposure rural areas experience higher risk even after migrating to cities, although this was difficult to evaluate in our study. In bivariate analysis, we did not find an effect for increasing length of time spent in rural areas. However, this finding may reflect recall difficulty in accurately reporting duration of travel or monthly or seasonal variations in travel patterns.
The current data do not enable us to establish a causal link between exposure during rural travel and acute presentation with malarial anemia. Investigating such a link would have required details of recent trips (often multiple trips per household) with respect to timing, location, and participation by individual household members, adding considerable complexity to the survey process for interviewers and respondents. However, there was a significant correlation between reporting typical travel to rural areas and spending at least one night outside Kisumu in the previous month. This link needs to be explored in more detail.
Two-thirds of cases occurred in households where the child did not typically travel to rural areas, indicating some level of intra-urban transmission. The magnitude of this is unclear for various reasons: for example, some children for whom regular travel was not reported might nevertheless have spent a recent night in a rural area. Further research is needed to clarify the roles of travel, rural exposure, chronic and acute infection, and intra-urban transmission in determining severe malaria risk in sub-Saharan African urban settings.
The effects of bed net ownership, mosquito coil use, and house construction were all in the expected direction, but not statistically significant. Bed nets or ITNs have been found not to reduce SMA in some contexts,10,12,15
although it is generally accepted that they reduce Plasmodium
infection and mortality. In urban Kisumu, increased risk of malarial anemia may have resulted if a significant fraction of exposure subsequently occurred during travel when nets were not being used. Mosquito coils were found to be preventive in bivariate analysis, but had a non-significant effect after multivariate adjustment. Good house construction, as characterized in this study, normally is considered to be another barrier to transmission, and was similarly related to malarial anemia in bivariate analysis, but non-significant in the multivariate model. As with nets, good house construction would not have prevented increased exposure during travel.
Household size was found to represent a risk factor in the final model. However, this result is potentially an artifact of the different sampling schemes for cases and controls. To the extent that household size is associated with other risk factors, this finding could bias results in either direction. Although we were unable to include interaction terms in the final model, the inclusion of household size should have controlled for this effect. Moreover, we did not observe inordinately high correlations between household size and other variables in the data.
The overall effect of level of urbanization on malarial anemia risk was non-significant, although some individual variables comprising this index (e.g., distance to the hospital, population density, source of water, and NDVI) were significantly associated with disease in bivariate analysis. These relationships were in the directions expected, except that higher NDVI, indicating more nearby vegetation, was associated with lower risk for malarial anemia. This unexpected relationship may possibly have resulted from the low NDVIs that are found in peri-urban zones (where residents are most likely to travel to rural areas), or from higher socioeconomic levels that enable greater access to malaria prevention in highly urban zones where houses have gardens. The unexpected association with NDVI may explain why the urbanization index was not a significant predictor. Inclusion of interaction terms in a larger dataset would help clarify these relationships.
The limited sample size reduced the statistical power of this study to identify some risk factors. Nonetheless, the strict requirements for inclusion in the final model, the consistent direction and magnitude of observed relationships in comparison with bivariate results, and the robustness of the model to deletion of outliers and exclusion of specific variables indicate that it represents a solid and conservative compromise. A larger study over a longer period of time is needed to further explore the multifactorial nature of risk for severe malaria outcomes. We failed to recruit »40% of cases meeting our case definition at KDH, but differences between identified and missed cases were minimal and should not have biased the analysis. Captured cases were generally sicker than those that were missed, indicating that our results may only be applicable to more severe cases. The reasons why cases were missed are not clear. However, missed cases tended to cluster near the beginning and end of the study period and during times when caseload was high, indicating that failure to capture may have resulted from some combination of an inability to handle the caseload with interviewer inexperience or fatigue. We were also unable to evaluate the effects of caregiver characteristics because of the different methods for recruitment of cases and controls.
These results imply that different prevention and control strategies may be necessary for the large and growing group of urban residents, many of whom frequently travel to rural areas. Traditional prevention strategies may be ineffective for urban families who use bed nets at home but fail to do so when traveling. In particular, travel histories and their impact on severe malaria need to be more carefully described in sub-Saharan Africa because studies have so far been limited on this count. At the same time, the presentation of these cases within urban areas and the limited timeframe within which some may experience exposure (i.e., during travel to rural areas) present opportunities for effective and efficient prevention that are often unavailable in remote areas where access to health facilities is limited and exposure is protracted. A better understanding of the link between travel and severe malaria could have direct practical benefits for public heath by helping to direct the allocation of resources among and within cities, effectively targeting and focusing education and intervention programs, and producing clear and informed policies for urban public health. Likewise, a clearer picture is needed of risk factors for severe malaria for those urban residents who do not travel. A major component of this research should focus on describing the urban environment and delineating the specific elements of urbanization that may increase risk. Such efforts should produce a better understanding of urban malaria risk factors, thus enabling effective targeting of control strategies to those at greatest risk of severe malaria.