The age patterns of severe malaria syndromes in sub-Saharan Africa across a range of transmission intensities and seasonality settings

Malaria Journal The age patterns of severe malaria syndromes in sub-Saharan Africa across a range of transmission intensities and seasonality settings Arantxa Roca-Feltrer 0 Ilona Carneiro 0 Lucy Smith 0 Joanna RM Armstrong Schellenberg 0 Brian Greenwood 0 David Schellenberg 0 0 Department of Disease Control, Faculty of Infectious & Tropical Disease, London School of Hygiene & Tropical Medicine , Keppel Street, London WC1E 7HT , UK Background: A greater understanding of the relationship between transmission intensity, seasonality and the agepattern of malaria is needed to guide appropriate targeting of malaria interventions in different epidemiological settings. Methods: A systematic literature review identified studies which reported the age of paediatric hospital admissions with cerebral malaria (CM), severe malarial anaemia (SMA), or respiratory distress (RD). Study sites were categorized into a 3 2 matrix of Plasmodium falciparum transmission intensity and seasonality. Probability distributions were fitted by maximum likelihood methods, and best fitting models were used to estimate median ages and to represent graphically the age-pattern of each outcome for each transmission category in the matrix. Results: A shift in the burden of CM towards younger age groups was seen with increasing intensity of transmission, but this was not the case for SMA or RD. Sites with 'no marked seasonality' showed more evidence of skewed age-patterns compared to areas of 'marked seasonality' for all three severe malaria syndromes. Conclusions: Although the peak age of CM will increase as transmission intensity decreases in Africa, more than 75% of all paediatric hospital admissions of severe malaria are likely to remain in under five year olds in most epidemiological settings. - Background The relationship between the age-pattern of severe malaria and transmission intensity has been studied widely. Several studies conducted in the 1990s reported a peak shift phenomenon - the peak incidence of hospital admissions with severe malaria occurring at a younger age in areas of high transmission intensity compared to areas of lower transmission intensity [1-5] and this finding has been confirmed by a recent pooled analysis [6]. Severe malaria can present clinically in several different ways. The syndromes encountered most frequently in African children are severe malaria anaemia (SMA), cerebral malaria (CM) or respiratory distress (RD)[1]. Previous studies of the age pattern of individual severe malaria syndromes and its relationship to transmission intensity have shown a shift in the peak of admissions with SMA or CM [7,8] toward younger ages with increasing transmission intensity, but this has not been apparent for RD[8]. In addition, it has been shown that the mean age of hospital admissions with SMA is always lower than that of admissions with CM, regardless of transmission intensity. As a result, it is widely believed that SMA will dominate the clinical picture in areas of high transmission, whilst CM should become relatively more important in areas with a lower transmission intensity [9]. However, not all studies have observed such a relationship: in Ifakara, Tanzania an area which previously had intense malaria transmission, a similar incidence of hospital admissions with CM or SMA was reported in under-five year olds [10]. There are likely to be several reasons for the inconsistencies observed between studies, including a lack of standardized definitions of transmission intensity, difficulty in allocating patients to specific clinical syndromes, the use of different age groupings and age ranges across studies, and the small number of studies between which comparisons can be made. Although there has been an attempt to overcome these limitations by looking at this relationship across a wider range of transmission intensities and using standard clinical definitions [11], it still remains unclear whether the peak shift phenomenon occurs for all severe malaria syndromes. To date, no studies have included the role of malaria seasonality in the analysis of the relationship between the age-pattern of severe malaria syndromes and transmission intensity. This paper presents a pooled analysis of existing data that describes the age-pattern of severe malaria syndromes across a wide range of transmission intensities and seasonality settings in sub-Saharan Africa. The methodology used overcomes the difficulty of combining studies that report different age-groupings and ageranges. This has enabled inclusion of data from a variety of transmission settings, including data from studies conducted outside established research sites. Methods Literature review To identify relevant data on the age-pattern of severe malaria syndromes, a series of systematic literature reviews were undertaken between 2005 and 2006 which are reported in more detail elsewhere[6]. PubMed and CAB Abstracts (BIDS) electronic databases were searched using the following terms: malaria (with a major focus on epidemiology, complications, mortality, prevention and control, and transmission) OR Plasmodium falciparum OR Plasmodium vivax AND morbidity (incidence or prevalence) OR fever OR severe malaria or cerebral malaria OR neurological OR an (a)emia. In addition, searches of the WHO library (WHOLIS)[12], and the grey literature (SIGLE) database [13] were undertaken. References were also identified by conducting key author searches and checking crossreferences from the bibliographies of relevant papers. Additional data sources, such as the Severe Malaria in African Children (SMAC) clinical trials network, were also contacted to obtain information on individual hospital admissions. Only studies from countries endemic for P. falciparum and reporting age-breakdown data of hospital admissions with the main severe malaria syndromes in children up to 15 years were included. CM, SMA and RD definitions varied between studies and did not necessarily fulfill WHO definitions [14-16] as authors tended to adapt WHO definitions according to the local epidemiology. However, all severe malaria cases included in these analyses were parasitologically confirmed for P. falciparum. In addition, impaired consciousness or unrousable coma were necessary for inclusion as a CM case, all SMA cases included had either Hb 5.0 g/ dL or a PCV 15%, and all RD cases had acidosis or deep breathing. Categorizing studies into a matrix of transmission intensity and seasonality Currently, the preferred measure for assessing malaria endemicity is the annualized entomological inoculation rate (EIR) defined as the number of malaria infective bites per person per year. However, as measuring EIR is resource-intensive, EIR data across sub-Saharan Africa is scarce. Beier et al [17] reported a linear relationship between malaria prevalence and the logarithm of the annual EIR, justifying the use of parasite prevalence as a marker of transmission intensity in areas wh (...truncated)