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

Abstract

BackgroundThe 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.MethodsPatients 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.ResultsIn 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.ConclusionP. 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0302-y) contains supplementary material, which is available to authorized users.

Characteristics of Travel-Related Severe Plasmodium vivax and Plasmodium falciparum Malaria in Individuals Hospitalized at a Tertiary Referral Center in Lima, Peru

“…The severity of malaria in Amazonia is less than in Africa, as a recent comparison of patients from India and Brazil showed. 3 In this study, differences in presentation, such as hyperlactatemia, respiratory distress, hypoglycemia, and disseminated intravascular coagulopathy were more frequently reported in Brazilian cases, although the overall fatality rate was 20-fold higher in India. 3 Several comorbidities, socioeconomic differences, health-care access, and infrastructure were some of the factors that could influence the outcome between these two populations.…”

“…1 The clinical spectrum of symptomatic malaria in endemic areas ranges from mild to severe, lethal disease. 2,3 It is important to recognize severe malaria (SM) because it is associated with high mortality. Criteria for SM include high levels of parasitemia and/or major signs of organ dysfunction, but their prevalence in malaria cases varies from region to region and between children and adults.…”

“…[4][5][6][7] In 2014, the WHO and partners updated the 1990, 2000, and 2010 clinical classifications of SM [5][6][7] to include three groups with a gradation of severity. 4 SM includes various clinical presentations, particularly, hypoglycemia, lactic acidosis, respiratory distress, severe thrombocytopenia (< 50,000/mm 3 ), jaundice, neurological dysfunction (coma, seizure), and multiple organ failure. 6,7 Most clinicians traditionally consider Plasmodium falciparum to be the parasite species responsible for SM.…”

The immunological balance between host and parasite in malaria

“…However, in approximately 1% of the infected patients, mostly non-immune residents, travelers and primigravidae, this balance is disrupted and severe disease ensues. Severe complications are most common with P. falciparum, but also with P. vivax and P. knowlesi, severe disease with a possible lethal outcome is increasingly reported (Barber et al 2013;Bhattacharjee et al 2013;Siqueira et al 2015).…”

Could Plasmodium vivax malaria trigger malnutrition? Revisiting the Bradford Hill criteria to assess a causal relationship between two neglected problems

“…7) Coherence. The benign characteristics formerly attributed to P. vivax infection have been largely dismissed by an increasing number of reports of severe vivax malaria, prompting the need for more thorough and comprehensive characterization of the sequelae resulting from complications (22) . P. vivax-associated undernutrition, therefore, seems coherent with current knowledge regarding the virulence of this parasite, increasing the likelihood of a causal effect.…”