Plasmodium vivax is an important cause of malaria, associated with a significant public health burden. Whilst enhanced malaria-control activities have successfully reduced the incidence of Plasmodium falciparum malaria in many areas, there has been a consistent increase in the proportion of malaria due to P. vivax in regions where both parasites coexist. This article reviews the epidemiology and biology of P. vivax, how the parasite differs from P. falciparum, and the key features that render it more difficult to control and eliminate. Since transmission of the parasite is driven largely by relapses from dormant liver stages, its timely elimination will require widespread access to safe and effective radical cure. Extent and Burden of Plasmodium vivaxOf the five Plasmodium species that cause human malaria, Plasmodium vivax is the most geographically widespread. The parasite is capable of surviving quiescent for prolonged periods when conditions are not conducive to its ongoing transmission. A century ago P. vivax was prevalent in almost all countries; even though the vivax endemic world has shrunk considerably, over four billion people remain at risk of infection [1]. In 2017, transmission was reported from 49 countries across Central and South America, the Horn of Africa, Asia, and the Pacific islands (Figure 1). In almost two-thirds of coendemic countries P. vivax is the predominant species of malaria (Figure 2), the proportion of malaria attributable to the parasite being greatest in areas where the prevalence of malaria is low (Figure 3) [2,3].Until recently the global burden of P. vivax malaria was derived from estimates of P. falciparum, the most prevalent species causing human malaria. However, a growing awareness of the public health importance of P. vivax has led to the strengthening of surveillance systems and better reporting practices of all of the Plasmodium species. The World Health Organization (WHO) first included P. vivax case estimates in its World Malaria Report (WMR) in 2013, documenting between 11.9 and 22 million P. vivax clinical cases per year [4]. Recent estimates, incorporating national surveillance data, prevalence surveys, and geospatial mapping, have revised the global burden to between 13.7 and 15 million cases in 2017 [1]. An estimated 82% (11.7 million cases) of the global vivax burden comes from four high-burden countries: India, Pakistan, Ethiopia, and Sudan.In sub-Saharan Africa, where the burden of malaria is overwhelmingly attributable to P. falciparum (Figure 1), the low prevalence of P. vivax is attributed to a high proportion of the population having a Duffy-negative blood group. The Duffy antigen is an important molecule for the erythrocytic invasion of P. vivax, and the lack of the receptor on red blood cells reduces the risk of infection [5]. However, a recent review of clinical and vector data has shown that P. vivax is present across almost all malaria-endemic regions of Africa [6].Biological Differences between P. falciparum and P. vivaxThe control and elimination of ...

Introduction-The risk of diabetes mellitus is increasing worldwide, and is particularly high in Indigenous Australians. Complicated foot infection is one of the most common sequelae of diabetes. We describe the incidence and associations of Indigenous and non-Indigenous inpatients with diabetic foot infections at Royal Darwin Hospital.Methods-All adult Royal Darwin Hospital inpatients with diabetic foot infections were enrolled prospectively from September 2012 to November 2013. Incidence, demographics, microbiology, management and clinical outcomes were analysed by Indigenous status, and association with methicillin resistant Staphylococcus aureus and Pseudomonas aeruginosa.Results-There were 245 separate hospital admissions in 177 patients with an incidence of 79 admissions per 100,000 person years. Patients occupied a mean of 19.4 hospital beds each day. Compared to the non-Indigenous population, Indigenous patients had a greater incidence of admission (Rate Ratio (RR) = 5.1, [95%CI = 3.8, 7.0]), were younger (mean difference of 11.1 years; p < 0.001), and more likely to undergo major and minor amputations (RR = 4.1 [95%CI = 1.6, 10.7], and 6.2 [95%CI = 3.5, 11.1] respectively). Non-multiresistant methicillin resistant S. Conclusions-This study highlights a rising burden of diabetic foot infections in the Top End of Australia, with a four-fold increase in bed days since 2002 and an overrepresentation in the Indigenous population. Europe PMC Funders Group

SummaryBackgroundChloroquine remains the mainstay of treatment for Plasmodium vivax malaria despite increasing reports of treatment failure. We did a systematic review and meta-analysis to investigate the effect of chloroquine dose and the addition of primaquine on the risk of recurrent vivax malaria across different settings.MethodsA systematic review done in MEDLINE, Web of Science, Embase, and Cochrane Database of Systematic Reviews identified P vivax clinical trials published between Jan 1, 2000, and March 22, 2017. Principal investigators were invited to share individual patient data, which were pooled using standardised methods. Cox regression analyses with random effects for study site were used to investigate the roles of chloroquine dose and primaquine use on rate of recurrence between day 7 and day 42 (primary outcome). The review protocol is registered in PROSPERO, number CRD42016053310.FindingsOf 134 identified chloroquine studies, 37 studies (from 17 countries) and 5240 patients were included. 2990 patients were treated with chloroquine alone, of whom 1041 (34·8%) received a dose below the target 25 mg/kg. The risk of recurrence was 32·4% (95% CI 29·8–35·1) by day 42. After controlling for confounders, a 5 mg/kg higher chloroquine dose reduced the rate of recurrence overall (adjusted hazard ratio [AHR] 0·82, 95% CI 0·69–0·97; p=0·021) and in children younger than 5 years (0·59, 0·41–0·86; p=0·0058). Adding primaquine reduced the risk of recurrence to 4·9% (95% CI 3·1–7·7) by day 42, which is lower than with chloroquine alone (AHR 0·10, 0·05–0·17; p<0·0001).InterpretationChloroquine is commonly under-dosed in the treatment of vivax malaria. Increasing the recommended dose to 30 mg/kg in children younger than 5 years could reduce substantially the risk of early recurrence when primaquine is not given. Radical cure with primaquine was highly effective in preventing early recurrence and may also improve blood schizontocidal efficacy against chloroquine-resistant P vivax.FundingWellcome Trust, Australian National Health and Medical Research Council, and Bill & Melinda Gates Foundation.