BACKGROUND: Primaquine is a key drug for malaria elimination. In addition to 
being the only drug active against the dormant relapsing forms of Plasmodium 
vivax, primaquine is the sole effective treatment of infectious P. falciparum 
gametocytes, and may interrupt transmission and help contain the spread of 
artemisinin resistance. However, primaquine can trigger haemolysis in patients 
with a deficiency in glucose-6-phosphate dehydrogenase (G6PDd). Poor information 
is available about the distribution of individuals at risk of primaquine-induced 
haemolysis. We present a continuous evidence-based prevalence map of G6PDd and 
estimates of affected populations, together with a national index of relative 
haemolytic risk.
METHODS AND FINDINGS: Representative community surveys of phenotypic G6PDd 
prevalence were identified for 1,734 spatially unique sites. These surveys 
formed the evidence-base for a Bayesian geostatistical model adapted to the 
gene's X-linked inheritance, which predicted a G6PDd allele frequency map across 
malaria endemic countries (MECs) and generated population-weighted estimates of 
affected populations. Highest median prevalence (peaking at 32.5%) was predicted 
across sub-Saharan Africa and the Arabian Peninsula. Although G6PDd prevalence 
was generally lower across central and southeast Asia, rarely exceeding 20%, the 
majority of G6PDd individuals (67.5% median estimate) were from Asian countries. 
We estimated a G6PDd allele frequency of 8.0% (interquartile range: 7.4-8.8) 
across MECs, and 5.3% (4.4-6.7) within malaria-eliminating countries. The 
reliability of the map is contingent on the underlying data informing the model; 
population heterogeneity can only be represented by the available surveys, and 
important weaknesses exist in the map across data-sparse regions. Uncertainty 
metrics are used to quantify some aspects of these limitations in the map. 
Finally, we assembled a database of G6PDd variant occurrences to inform a 
national-level index of relative G6PDd haemolytic risk. Asian countries, where 
variants were most severe, had the highest relative risks from G6PDd.
CONCLUSIONS: G6PDd is widespread and spatially heterogeneous across most MECs 
where primaquine would be valuable for malaria control and elimination. The maps 
and population estimates presented here reflect potential risk of 
primaquine-associated harm. In the absence of non-toxic alternatives to 
primaquine, these results represent additional evidence to help inform safe use 
of this valuable, yet dangerous, component of the malaria-elimination toolkit. 
Please see later in the article for the Editors' Summary.