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infectious and non-infectious co-morbidities that may be either alternative
causes of death or the major underlying cause of death. It is notable that in
the 2012 Manaus autopsy series, at least four of 17 (23.5%) vivax-associated
deaths were attributable to alternative causes ( Lacerda et al., 2012 ), includ-
ing yellow fever and meningitis ( Lacerda et al., 2012 ). This proportion is
identical to the 23% of P. falciparum -associated deaths in Malawi attribut-
able to alternative non-falciparum causes ( Taylor et al., 2004 ). A further
41% of the Manaus vivax malaria autopsy series had major underlying co-
morbidities contributing to death ( Lacerda et al., 2012 ) (Section 7.4 ). This
has long been recognized in the malaria literature. In 1925, James noted that
in southern England, untreated vivax malaria in those who were 'enfeebled
from any cause, not infrequently results fatally' ( James, 1925 ; Hutchinson
and Lindsay, 2006 ). Attributable fractions for severe and fatal disease have
been calculated for falciparum malaria ( Bejon et al., 2007 ) but not yet for
vivax malaria ( Anstey and Price, 2007 ).
7.1. Young Children
In co-endemic areas, morbidity from P. vivax , including both uncompli-
cated and severe disease, generally occurs at a younger age compared to
P. falciparum ( Tjitra et al., 2008 ; Kochar et al., 2010 ; Michon et al., 2007 ; Lin
et al., 2010 ). Children under 5 years of age are at greatest risk of anaemia
from P. vivax , especially severe vivax anaemia ( Tjitra et al., 2008 ; Alexandre
et al., 2010 ; Kochar et al., 2010 ; Lanca et al., 2012 ; Poespoprodjo et al., 2009 ;
Genton et al., 2008 ; Douglas et al., 2012). The risk in the first year of life
is particularly striking. In Indonesian Papua, more infants under 1 year of
age are hospitalised with vivax malaria than falciparum malaria ( Tjitra et al.,
2008 ; Poespoprodjo et al., 2009 ); these patients having a significantly greater
risk of severe anaemia than those hospitalised with falciparum malaria (odds
ratio 2.4) ( Tjitra et al., 2008 ). The risk to infants starts in utero , P. vivax infec-
tion during pregnancy being associated with congenital malaria ( Poespo-
prodjo et al., 2011 ) and a greater risk of clinical disease and severe anaemia
in the neonatal period ( Lanca et al., 2012 ; Poespoprodjo et al., 2009 ).
7.2. Malnutrition
Malnutrition is a clear risk factor for both severe disease and mortality in
falciparum malaria ( Berkley et al., 2009 ) and is also likely to contribute
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