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. 2015 Mar 20:13:57.
doi: 10.1186/s12916-015-0302-y.

Characterization of Plasmodium vivax-associated admissions to reference hospitals in Brazil and India

André M Siqueira  1   2   3 , Marcus V G Lacerda  4   5   6 , Belisa M L Magalhães  7   8 , Maria P G Mourão  9   10 , Gisely C Melo  11   12 , Márcia A A Alexandre  13   14 , Maria G C Alecrim  15   16 , Dhanpat Kochar  17 , Sanjay Kochar  18 , Abhishek Kochar  17 , Kailash Nayak  19 , Hernando del Portillo  20   21 , Caterina Guinovart  22   23 , Pedro Alonso  24   25 , Quique Bassat  26   27
Affiliations

Characterization of Plasmodium vivax-associated admissions to reference hospitals in Brazil and India

André M Siqueira et al. BMC Med. .

Abstract

Background: The benign character formerly attributed to Plasmodium vivax infection has been dismantled by the increasing number of reports of severe disease associated with infection with this parasite, prompting the need for more thorough and comprehensive characterization of the spectrum of resulting clinical complications. Endemic areas exhibit wide variations regarding severe disease frequency. This study, conducted simultaneously in Brazil and India, constitutes, to our knowledge, the first multisite study focused on clinical characterization of P. vivax severe disease.

Methods: Patients admitted with P. vivax mono-infection at reference centers in Manaus (Amazon - Brazil) and Bikaner (Rajasthan - India), where P. vivax predominates, were submitted to standard thorough clinical and laboratory evaluations in order to characterize clinical manifestations and identify concurrent co-morbidities.

Results: In total, 778 patients (88.0% above 12 years old) were hospitalized at clinical discretion with PCR-confirmed P. vivax mono-infection (316 in Manaus and 462 in Bikaner), of which 197 (25.3%) presented at least one severity criterion as defined by the World Health Organization (2010). Hyperlactatemia, respiratory distress, hypoglycemia, and disseminated intravascular coagulation were more frequent in Manaus. Noteworthy, pregnancy status was associated as a risk factor for severe disease (OR = 2.03; 95% CI = 1.2-3.4; P = 0.007). The overall case fatality rate was 0.3/1,000 cases in Manaus and 6.1/1,000 cases in Bikaner, with all deaths occurring among patients fulfilling at least one severity criterion. Within this subgroup, case fatality rates increased respectively to 7.5% in Manaus and 4.4% in Bikaner.

Conclusion: P. vivax-associated severity is not negligible, and although lethality observed for complicated cases was similar, the overall fatality rate was about 20-fold higher in India compared to Brazil, highlighting the variability observed in different settings. Our observations highlight that pregnant women and patients with co-morbidities need special attention when infected by this parasite due to higher risk of complications.

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Figures

Figure 1
Figure 1
Epidemiological profile of the two studied sites: P. vivax 2010 annual parasite index in Brazil (A) and India (B) (reproduced from the Malaria Atlas Project [8]); malaria transmission scenarios in the rainforest, Manaus, Brazil (C) and in the desert, Bikaner, India (D); reference tertiary care center façades in Manaus (E) and Bikaner (F).
Figure 2
Figure 2
Number of diagnosed, hospitalized, severe, and deceased patients with P. vivax malaria, during the study period in Manaus (A) and Bikaner (B).
Figure 3
Figure 3
ROC curves depicting the discriminatory performance of peripheral parasitemia before the use of antimalarials (A) (AUC = 0.538; 95% CI = 0.421-0.657; P  > 0.05); and serum total bilirubin (B) (AUC = 0.743; 95% CI = 0.611-0.875; P  < 0.001) for differentiating P. vivax -associated three or more criteria of severity. AUC: area under the curve; green line: reference.
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