Economic and Resource Use Associated With Management of Malaria in Children Aged <5 Years in Sub-Saharan Africa: A Systematic Literature Review.

Background. Malaria is a major health, economic, and social burden in sub-Saharan Africa. Purpose. The objective is to help understanding the economic impact of malaria and informing estimates of the potential economic impact of malaria prevention. To achieve this, we conducted a systematic review of published information on health system costs, health care resource use, and household costs for the management of malaria episodes in children aged <5 years in sub-Saharan Africa. Data Sources and Study Selection. We conducted searches in Medline, EMBASE, and Cochrane Library for studies reporting data on economic cost or resource use associated with management of malaria in children aged <5 years in sub-Saharan Africa. Searches were limited to articles published in English or French between January 1, 2006, and September 1, 2016. Conference abstracts from 2014 to 2016 were hand-searched. Data Extraction and Data Synthesis. We identified 1846 publications, of which 17 met the selection criteria. The studies covered nine countries: The Democratic Republic of Congo, Ghana, Kenya, Malawi, Mozambique, Nigeria, Tanzania, Uganda, and Zambia. All costs were standardized to 2016 US dollars (US$). Seven studies estimated the costs of a malaria episode to health systems, and 10 publications plus one abstract reported household costs. The cost to the health system was US$1.94 to US$31.53 for outpatient malaria cases to US$20 to US$136 for inpatient cases. Families bear a large share of the burden through out-of-pocket payments of medical care and lost income due to time off work. Limitations. Data were missing for many countries and few comparisons could be made. Conclusions. Severe malaria is associated with much higher costs than uncomplicated malaria, and families bear a large share of the cost burden.

The Plasmodium alveolin IMC1a is stabilised by its terminal cysteine motifs and facilitates sporozoite morphogenesis and infectivity in a dose-dependent manner.

Apicomplexan parasites possess a unique cortical cytoskeleton structure composed of intermediate filaments. Its building blocks are provided by a conserved family of proteins named alveolins. The core alveolin structure is made up of tandem repeat sequences, thought to be responsible for the filamentous properties of these proteins. A subset of alveolins also possess conserved motifs composed of three closely spaced cysteine residues situated near the ends of the polypeptides. The roles of these cysteine motifs and their contribution to alveolin function remains poorly understood. The sporozoite-expressed IMC1a is unique within the Plasmodium alveolin family in having conserved cysteine motifs at both termini. Using transgenic Plasmodium berghei parasites, we show in this structure-function analysis that mutagenesis of the amino- or carboxy-terminal cysteine motif causes marked reductions in IMC1a protein levels in the parasite, which are accompanied by partial losses of sporozoite shape and infectivity. Our findings give new insight into alveolin function, identifying a dose-dependent effect of alveolin depletion on sporozoite size and infectivity, and vital roles of the terminal cysteine motifs in maintaining alveolin stability in the parasite.