Background
Measuring malaria burden in a population is a challenge in most developing countries [
1,
2]. Routine hospital data, reported through the health management information system (HMIS), provide a proxy for measuring the incidence of severe malaria and for crudely measuring morbidity rates [
3,
4]. Describing trends and patterns of such data could assist in monitoring and planning resource needs in a health system [
5]. In particular, explaining geographical variation in such outcomes is important to identify communities at high risk, to assist in designing appropriate interventions, or lead to further investigations to identify important risk factors.
Use of spatial analysis is increasingly being applied in epidemiological research in recent years [
6], and examples of applications in malaria are expanding [
5,
7,
8]. Availability of geo-referenced health data, advances in statistical methodology and developments in geographical information system (GIS) are the reasons for such increased trends [
6]. Despite growing applications of spatial methodology in malaria research, and regardless of several studies using hospital data to explore the burden of malaria [
9‐
12], fewer studies have analysed spatial variation of hospitalization and in-hospital mortality rates [
5,
13].
Because malaria transmission intensity varies geographically, the distribution of hospital cases and subsequent mortality rates may exhibit systematic spatial variation [
14]. Thus spatial analysis may shed light on geographical variations in hospitalization and mortality rates. The main objective of this study was to apply a spatial modelling framework, as a case study, to describe malaria hospitalization and in-hospital deaths using paediatric hospital data from Zomba district in southern Malawi. Two types of spatial models were used. In the first analysis, Poisson models were fitted to analyse rates of hospitalization and in-hospital mortality, adjusted for age and sex, which can be interpreted as population-based cohort studies. In the second, individual-based observations were used and a logistic regression model was applied to assess individual covariates influencing in-hospital mortality.
Discussion
This study provides evidence of the magnitude and spatial variation of malaria hospitalisation and in-hospital mortality in Zomba, Malawi. In all models, the risk of hospitalisation and in-hospital deaths were highest in areas outside of the district centre (where the district hospital is located). Distant areas with low hospitalisation rates suggest problems of access, which does translate into high mortality rate (Figure
1). However, this is not the case with the southern part of the district. The low risk observed in this area may be explained by availability of relatively better service in the area. The area has three health facilities, two health centres and one rural hospital with resident ambulatory services which may assist promptly with referrals to the district hospital.
The residual spatial heterogeneity (Figures
1 and
5), suggests that unobserved factors not captured by the covariate in the models may contribute to the geographical disparities in the two outcomes. It remains a matter of conjecture to identify such factors, and it is possible that determinants of malaria transmission which are spatially correlated, for example, mosquito breeding sites and habitats may influence the pattern of malaria incidence. This may partly explain the high risk of mortality observed in areas along the Likangala river flowing in the south-east direction, Chikanda township and Lake Chirwa swamps on the eastern side of the district. Moreover, such areas practice irrigated rice agriculture and this system has been associated with increased malaria transmission [
24].
Another possible explanation of varied clinical outcomes may be the socio-economic discrepancies in the district. For instance, people from remote or rural areas are relatively poor compared to those at the centre of the district, and these are at increased risk of malaria infection and death because they are not able to pay for effective malaria drugs nor afford transport to a health facility that can treat malaria [
25,
26]. Rurality is, therefore, one of the factors worth considering in future research. Medical services are often concentrated around trading centres. The further the village is from the trading centre, the more disadvantaged the households are in terms of getting early health care.
Health seeking behaviour plays a critical role in accessing prompt and effective care. Because this was not directly observed, we suggest that this may also explain some of the spatial variation in hospitalisation rates (Figure
1). Home based care or traditional medicines are the first sources of care in most communities [
27,
28], because of traditional beliefs, difficulties in accessing and unavailability of formal health services [
27]. Only when the initial remedies have failed, health centres are the next step [
29]. Using a national wide representative survey data, the authors are currently investigating spatial patterns of sources of treatment, including health facility care, for malaria among care-givers of children who had the disease. This may provide some interesting answers on factors affecting health seeking behaviour at community level.
In the 2-year review, the overall case fatality rate of 7.6% was lower than the national rate of 18% [
17]. This may be explained by the relatively high altitude location of Zomba, which may lead to low malaria risk. Indeed, recent statistics show that districts at high altitude had relatively low malaria-attributable admissions and mortality compared to other districts in the country [
18]. Despite the lower rate, malaria was among the leading causes of death, similar to what was noted in other districts in the country [
18], and elsewhere in Africa [
10]. Selected reviews on proportional malaria mortality rates in Africa [
9,
10,
12], suggest that Zomba district experienced comparatively low malaria risk between 2002–2003.
The results indicated that risk of malaria hospitalization decreased with increasing age, with those under the age of 1 years at highest risk than subsequent ages (Figure
2 and Tables
1,
2,
3). CFR decreased with age, again infants being the most vulnerable. Overall, under-five children were at high risk, and confirms previous findings in sub-Saharan Africa [
30‐
33]. Children are vulnerable to malaria from about 4 months of age because of waned maternal immunity, and, in highly endemic areas during the peak transmission season, approximately 70% of one-year-olds have malaria parasites in their blood [
32,
33]. The increase in CFR for those aged 6–14 years, although these are supposed to be protected through acquired immunity, may reflect some aspects of health seeking behaviour, and emphasize the need for prompt and effective management of malaria for all children including those aged over five years even if such cases may not frequently occur in the general population [
9,
32].
The study showed that patients within 5 km of hospital were less likely to die in hospital than those beyond 5 km, and does reflect the fact that nearness to the hospital improved early access to care [
13,
34], thus reduced the risk of in-hospital mortality. It was also observed that referral children were at higher risk of dying in hospital, even after adjusting for distance. This seems to suggest that delayed effective treatment (in the process of being transferred to the district hospital) increased the severity of the disease. This could be because most referring health facilities may often be faced with stock-out of effective drugs or may not have prompt access to ambulatory support when needed [
20]. Possibilities of interaction between referral and distance might be likely, although this was not significant when included in the model, indicating that referral was independently associated with malaria CFR and not simply due to confounding with distance. This suggests inadequate care being available at primary facilities, regardless of whether they are distant from the hospital or not. It is also possible that referring hospitals are referring the more severe cases which are expected to have a higher case facility rate. Further research is warranted to investigate the timing and availability of pre-referral drugs, and other health facility characteristics that may lead to delayed referral, and suggest ways of improving the referral system in the district. This challenge is similar to other districts in the country [
20], and more familiar in most sub-Saharan countries [
4].
With regard to the length of hospital stay, it was found that the pattern of hospital deaths was significantly associated with the length of hospital stay. The findings indicated that the sickest patients had a short length of stay terminating in death, with highest risk of dying in hospital the same day of admission. The high CFR on day 1 can be attributed to severe or complicated cases. Indeed in some settings, biomedical care is sought when the condition is near fatal [
25,
29]. However, as days of stay increased the risk diminished, only to increase again at day 7. This suggests that by and large the care that is provided in the hospital is effective and saves lives, while the increase in risk from day 7 may be a factor of secondary infection although data was not available to investigate this further.
Malaria transmission is more intense in the wet season, yet the results showed that the risk was lower in the wet than the dry season. The likely reason for this is that there were more cases in the wet season (Figure
3), hence the denominator was higher. The huge volume of malaria-related admissions is explained by the increased malaria transmission intensity during the wet season [
5,
11,
12].
These analyses depended on data collected from routine hospital registers. One major shortcoming of using such data is that they only represent those patients who visited the clinics or hospital. As demonstrated in other studies [
27,
28], and elsewhere in Africa for example in Tanzania [
29], most malaria treatments occur outside the formal curative care, and only do so if the illness is perceived to be near fatal. Hence, the true district pattern of hospitalisation and in-hospital mortality may be distorted and underestimated compared to similar tropical setting like Zomba district. For an improved spatial analysis, it would be appropriate to include exact village locations, as opposed to aggregating cases to wards as was done in this study. However, geo-referencing villages would require extra resources as geo-locations are not readily available. Moreover, if such an exercise is undertaken it would be necessary to apply a unique location code that distinguishes locations with similar names which was found to be a challenge in this study.
This study provides evidence that hospital admissions and mortality rates for malaria among Malawian children are high, and that they vary in space. This analysis, accordingly, is the first of its kind and its advantage over other methods is that the impact of location on the two health outcomes was accounted for. These geographical disparities in malaria risk may largely be explained by determinants of malaria transmission, health services availability and accessibility, and health seeking behaviour. Although treatment was not significantly associated with CFR, improved prognosis increased with length of hospital stay indicating that appropriate care when available can save lives. The increased mortality risk for those referred from primary facilities signifies lack of adequate care provided by the primary health care system, but may also be a factor of referring facilities were referring more severe cases, which are expected to have a higher case fatality rate or that patients present later to the hospital if they have been referred. Improved case management at primary facilities by ensuring adequate stocks of effective drugs, combined with home or community interventions, for example, educating the community in management of malaria including training of shopkeepers in the appropriate choice and dose of antimalarial drugs for the treatment of childhood fevers is therefore a high priority [
26], and strategies to interrupt malaria transmission through, for instance, indoor residual spraying and insecticide treated nets, are essential to reduce malaria mortality.
Authors' contributions
LNK conceptualized, analysed and drafted the manuscript. IK and BLS participated in the conception, and critical review of the manuscript.