Clinical impact of vivax malaria: A collection review.

BACKGROUND: Plasmodium vivax infects an estimated 7 million people every year. Previously, vivax malaria was perceived as a benign condition, particularly when compared to falciparum malaria. Reports of the severe clinical impacts of vivax malaria have been increasing over the last decade. METHODS AND FINDINGS: We describe the main clinical impacts of vivax malaria, incorporating a rapid systematic review of severe disease with meta-analysis of data from studies with clearly defined denominators, stratified by hospitalization status. Severe anemia is a serious consequence of relapsing infections in children in endemic areas, in whom vivax malaria causes increased morbidity and mortality and impaired school performance. P. vivax infection in pregnancy is associated with maternal anemia, prematurity, fetal loss, and low birth weight. More than 11,658 patients with severe vivax malaria have been reported since 1929, with 15,954 manifestations of severe malaria, of which only 7,157 (45%) conformed to the World Health Organization (WHO) diagnostic criteria. Out of 423 articles, 311 (74%) were published since 2010. In a random-effects meta-analysis of 85 studies, 68 of which were in hospitalized patients with vivax malaria, we estimated the proportion of patients with WHO-defined severe disease as 0.7% [95% confidence interval (CI) 0.19% to 2.57%] in all patients with vivax malaria and 7.11% [95% CI 4.30% to 11.55%] in hospitalized patients. We estimated the mortality from vivax malaria as 0.01% [95% CI 0.00% to 0.07%] in all patients and 0.56% [95% CI 0.35% to 0.92%] in hospital settings. WHO-defined cerebral, respiratory, and renal severe complications were generally estimated to occur in fewer than 0.5% patients in all included studies. Limitations of this review include the observational nature and small size of most of the studies of severe vivax malaria, high heterogeneity of included studies which were predominantly in hospitalized patients (who were therefore more likely to be severely unwell), and high risk of bias including small study effects. CONCLUSIONS: Young children and pregnant women are particularly vulnerable to adverse clinical impacts of vivax malaria, and preventing infections and relapse in this groups is a priority. Substantial evidence of severe presentations of vivax malaria has accrued over the last 10 years, but reporting is inconsistent. There are major knowledge gaps, for example, limited understanding of the underlying pathophysiology and the reason for the heterogenous geographical distribution of reported complications. An adapted case definition of severe vivax malaria would facilitate surveillance and future research to better understand this condition.

Vivax malaria in pregnancy and lactation: a long way to health equity.

BACKGROUND: The Sustainable Development Goals (SDG) call for increased gender equity and reduction in malaria-related mortality and morbidity. Plasmodium vivax infections in pregnancy are associated with maternal anaemia and increased adverse perinatal outcomes. Providing radical cure for women with 8-aminoquinolines (e.g., primaquine) is hindered by gender-specific complexities. CASE PRESENTATION: A symptomatic episode of vivax malaria at 18 weeks of gestation in a primigravid woman was associated with maternal anaemia, a recurrent asymptomatic P. vivax episode, severe intra-uterine growth restriction with no other identifiable cause and induction to reduce the risk of stillbirth. At 5 months postpartum a qualitative glucose-6-phosphate dehydrogenase (G6PD) point-of-care test was normal and radical cure with primaquine was prescribed to the mother. A 33% fractional decrease in haematocrit on day 7 of primaquine led to further testing which showed intermediate phenotypic G6PD activity; the G6PD genotype could not be identified. Her infant daughter was well throughout maternal treatment and found to be heterozygous for Mahidol variant. CONCLUSION: Adverse effects of vivax malaria in pregnancy, ineligibility of radical cure for pregnant and postpartum women, and difficulties in diagnosing intermediate levels of G6PD activity multiplied morbidity in this woman. Steps towards meeting the SDG include prevention of malaria in pregnancy, reducing unnecessary exclusion of women from radical cure, and accessible quantitative G6PD screening in P. vivax-endemic settings.

Early and late mortality after malaria in young children in Papua, Indonesia.

BACKGROUND: In southern Papua, Indonesia, malaria is highly prevalent in young children and is a significant cause of morbidity and early mortality. The association between malaria and delayed mortality is unknown. METHODS: Routinely-collected hospital surveillance data from southern Papua, Indonesia, were used to assess the risk of recurrent malaria and mortality within 12 months of an initial presentation with malaria in all children younger than 5 years old attending the local hospital. Analysis was primarily by Kaplan Meier and Cox regression methods. RESULTS: In total 15,716 children presenting with malaria between April 2004 and December 2013 were included in the analysis; 6184 (39.3%) with Plasmodium falciparum, 7499 (47.7%) with P. vivax, 203 (1.3%) with P. malariae, 3 with P. ovale and 1827 (11.6%) with mixed infections. Within 1 year, 48.4% (7620/15,716) of children represented a total of 16,957 times with malaria (range 1 to 11 episodes), with the incidence of malaria being greater in patients initially presenting with P. vivax infection (1334 [95%CI 1307-1361] per 1000 patient years) compared to those with P. falciparum infection (920 [896-944]). In total 266 (1.7%) children died within 1 year of their initial presentation, 129 (48.5%) within 30 days and 137 (51.5%) between 31 and 365 days. There was no significant difference in the mortality risk in patients infected with P. vivax versus P. falciparum either before 30 days (Hazard Ratio (HR) 1.02 [0.69,1.49]) or between 31 and 365 days (HR = 1.30 [0.90,1.88]). Children who died had a greater incidence of malaria, 2280 [95%CI 1946-2671] per 1000 patient years preceding their death, compared to 1141 [95%CI 1124-1158] per 1000 patient years in those surviving. CONCLUSIONS: Children under-5 years old with P. vivax malaria, are at significant risk of multiple representations with malaria and of dying within 1 year of their initial presentation. Preventing recurrent malaria must be a public health priority in this vulnerable population.

Therapeutic efficacy of chloroquine for treatment of Plasmodium vivax malaria cases in Guragae zone southern Central Ethiopia.

BACKGROUND: Malaria continues to be a public health problem and important cause of morbidity and mortality in Ethiopia. Due to continuous interventions to combat malaria in endemic regions, a decline in malaria related deaths and morbidity has been registered. These gains, however, are threatened with the emergency of antimalarial drugs resistant strains of plasmodium parasites. This study aimed to determine therapeutic efficacy of chloroquine for treatment of Plasmodium vivax malaria cases in Guragae zone, southern central Ethiopia. METHODS: A one arm prospective study with recurrence of parasitaemia and clinical conditions of patients were evaluated on days 0, 1, 2, 3, 7, 14, and 28. Patients with Plasmodium vivax malaria mono infection and eligible for study inclusion criteria were recruited. SPSS-21 used for data analysis and management. Kaplan-Meier survival probability analysis was estimated. Mean geometric parasitaemia and average haemoglobin concentration were calculated. RESULTS: Among 87 total recruited subjects, 81 of them completed the 28 days follow up. More than half of (57.5%) the study participants had a history of fever and 42.5% of them had fever at the time of enrollment. The mean body temperature on day of recruitment was 38.2 °C and 36.8 °C on day 28. Geometric mean parasitaemia calculated on day of enrollment was 2270 parasites/µl of blood. Recurrence of parasitaemia was registered from two subjects during entire follow up. The mean haemoglobin concentration of study participants on day of enrolment was 11.8 g/ dl and 13.8 g/dl on day 28. CONCLUSION: This study registered a high chloroquine efficacy rate among the study participants. Therefore, chloroquine remains efficacious for the treatment of Plasmodium vivax malaria in the study area. However, there is a need to monitor chloroquine resistance by employing molecular tools for better evaluation of treatment outcome.

Malaria Severity in Mangaluru City in the Southwestern Coastal Region of India.

Dakshina Kannada district in the Southwestern region of Karnataka state, India, including Mangaluru city is endemic to malaria. About 80% of malaria infections in Mangaluru and its surrounding areas are caused by Plasmodium vivax and the remainder is due to Plasmodium falciparum. Malaria-associated clinical complications significantly occur in this region. Here, we report the pathological conditions of 41 cases of fatal severe malaria, admitted to the district government hospital in Mangaluru city during January 2013 through December 2016. The results of clinical, hematological, and biochemical analyses showed that most of these severe malaria cases were associated with thrombocytopenia, anemia, metabolic acidosis, acute respiratory distress, and single or multi-organ dysfunction involving liver, kidney, and brain. Of the 41 fatal malaria cases, 24, 10, and seven patients had P. vivax, P. falciparum, and P. vivax and P. falciparum mixed infections, respectively. These data suggest that besides P. falciparum that is known to extensively cause severe and fatal malaria illnesses, P. vivax causes fatal illnesses substantially in this region, an observation that is consistent with recent findings in other regions.

Malaria-Associated Mortality in Australian and British Prisoners of War on the Thai-Burma Railway 1943-1944.

During the building of the Thai-Burma railway in 1943 Australian and British prisoners of war died at high rates from tropical infections and nutritional deficiencies. Mortality records from "F" Force (n = 7,000) showed nearly half (44%) of the soldiers perished in a single year, yet only 4% of these deaths were primarily attributed to malaria, with another 7% where malaria was listed as a major contributing cause. Case fatality rates were < 1%, with nearly all soldiers chronically infected with Plasmodium vivax > Plasmodium falciparum. Separate labor camp point prevalence malaria rates by microscopy ranged from 28% to 69% (median 54%) despite intermittent quinine suppression. During complex public health emergencies, malaria mortality may be disguised by its combination with other common infections and nutritional deficiencies.

Malaria epidemiology and interventions in Ethiopia from 2001 to 2016.

BACKGROUND: Ethiopia is one of the African countries where Plasmodium falciparum and P. vivax co-exist. Monitoring and evaluation of current malaria transmission status is an important component of malaria control as it is a measure of the success of ongoing interventions and guides the planning of future control and elimination efforts. MAIN TEXT: We evaluated changes in malaria control policy in Ethiopia, and reviewed dynamics of country-wide confirmed and clinical malaria cases by Plasmodium species and reported deaths for all ages and less than five years from 2001 to 2016. Districts level annual parasite incidence was analysed to characterize the malaria transmission stratification as implemented by the Ministry of Health. We found that Ethiopia has experienced major changes from 2003 to 2005 and subsequent adjustment in malaria diagnosis, treatment and vector control policy. Malaria interventions have been intensified represented by the increased insecticide treated net (ITN) and indoor residual spraying (IRS) coverage, improved health services and improved malaria diagnosis. However, countrywide ITN and IRS coverages were low, with 64% ITN coverage in 2016 and IRS coverage of 92.5% in 2016 and only implemented in epidemic-prone areas of > 2500 m elevation. Clinical malaria incidence rate dropped from an average of 43.1 cases per 1000 population annually between 2001 and 2010 to 29.0 cases per 1000 population annually between 2011 and 2016. Malaria deaths decreased from 2.1 deaths per 100 000 people annually between 2001 and 2010 to 1.1 deaths per 100 000 people annually between 2011 to 2016. There was shrinkage in the malaria transmission map and high transmission is limited mainly to the western international border area. Proportion of P. falciparum malaria remained nearly unchanged from 2000 to 2016 indicating further efforts are needed to suppress transmission. CONCLUSIONS: Malaria morbidity and mortality have been significantly reduced in Ethiopia since 2001, however, malaria case incidence is still high, and there were major gaps between ITN ownership and compliance in malarious areas. Additional efforts are needed to target the high transmission area of western Ethiopia to sustain the achievements made to date.

Insecticide-treated nets for preventing malaria.

BACKGROUND: A previous version of this Cochrane Review identified that insecticide-treated nets (ITNs) are effective at reducing child mortality, parasite prevalence, and uncomplicated and severe malaria episodes. Insecticide-treated nets have since become a core intervention for malaria control and have contributed greatly to the dramatic decline in disease incidence and malaria-related deaths seen since the turn of the millennium. However, this time period has also seen a rise in resistance to pyrethroids (the insecticide used in ITNs), raising questions over whether the evidence from trials conducted before resistance became widespread can be applied to estimate the impact of ITNs on malaria transmission today. OBJECTIVES: The primary objective of this review was to assess the impact of ITNs on mortality and malaria morbidity, incorporating any evidence published since the previous update into new and existing analyses, and assessing the certainty of the resulting evidence using GRADE. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) published in the Cochrane Library, MEDLINE, Embase, LILACS, the World Health Organization (WHO) International Clinical Trials Registry Platform, ClinicalTrials.gov, and the ISRCTN registry for new trials published since 2004 and up to 18 April 2018. SELECTION CRITERIA: We included individual randomized controlled trials (RCTs) and cluster RCTs comparing bed nets or curtains treated with a synthetic pyrethroid insecticide at a minimum target impregnation dose recommended by the WHO with no nets or untreated nets. DATA COLLECTION AND ANALYSIS: One review author assessed the identified trials for eligibility and risk of bias, and extracted data. We compared intervention and control data using risk ratios (RRs), rate ratios, and mean differences, and presented all results with their associated 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach. We drew on evidence from a meta-analysis of entomological outcomes stratified by insecticide resistance from 2014 to inform the GRADE assessments. MAIN RESULTS: Our updated search identified three new trials. A total of 23 trials met the inclusion criteria, enrolling more than 275,793 adults and children. The included studies were conducted between 1987 and 2001.ITN versus no netsInsecticide-treated nets reduce child mortality from all causes by 17% compared to no nets (rate ratio 0.83, 95% CI 0.77 to 0.89; 5 trials, 200,833 participants, high-certainty evidence). This corresponds to a saving of 5.6 lives (95% CI 3.6 to 7.6) each year for every 1000 children protected with ITNs. Insecticide-treated nets also reduce the incidence of uncomplicated episodes of Plasmodium falciparum malaria by almost a half (rate ratio 0.55, 95% CI 0.48 to 0.64; 5 trials, 35,551 participants, high-certainty evidence) and probably reduce the incidence of uncomplicated episodes of Plasmodium vivax malaria (risk ratio (RR) 0.61, 95% CI 0.48 to 0.77; 2 trials, 10,967 participants, moderate-certainty evidence).Insecticide-treated nets were also shown to reduce the prevalence of P falciparum malaria by 17% compared to no nets (RR 0.83, 95% CI 0.71 to 0.98; 6 trials, 18,809 participants, high-certainty evidence) but may have little or no effect on the prevalence of P vivax malaria (RR 1.00, 95% CI 0.75 to 1.34; 2 trials, 10,967 participants, low-certainty evidence). A 44% reduction in the incidence of severe malaria episodes was seen in the ITN group (rate ratio 0.56, 95% CI 0.38 to 0.82; 2 trials, 31,173 participants, high-certainty evidence), as well as an increase in mean haemoglobin (expressed as mean packed cell volume) compared to the no-net group (mean difference 1.29, 95% CI 0.42 to 2.16; 5 trials, 11,489 participants, high-certainty evidence).ITN versus untreated netsInsecticide-treated nets probably reduce child mortality from all causes by a third compared to untreated nets (rate ratio 0.67, 95% CI 0.36 to 1.23; 2 trials, 25,389 participants, moderate-certainty evidence). This corresponds to a saving of 3.5 lives (95% CI -2.4 to 6.8) each year for every 1000 children protected with ITNs. Insecticide-treated nets also reduce the incidence of uncomplicated P falciparum malaria episodes (rate ratio 0.58, 95% CI 0.44 to 0.78; 5 trials, 2036 participants, high-certainty evidence) and may also reduce the incidence of uncomplicated P vixax malaria episodes (rate ratio 0.73, 95% CI 0.51 to 1.05; 3 trials, 1535 participants, low-certainty evidence).Use of an ITN probably reduces P falciparum prevalence by one-tenth in comparison to use of untreated nets (RR 0.91, 95% CI 0.78 to 1.05; 3 trials, 2,259 participants, moderate-certainty evidence). However, based on the current evidence it is unclear whether or not ITNs impact on P vivax prevalence (1 trial, 350 participants, very low certainty evidence) or mean packed cell volume (2 trials, 1,909 participants, low certainty evidence). AUTHORS' CONCLUSIONS: Although there is some evidence that insecticide resistance frequency has some effects on mosquito mortality, it is unclear how quantitatively important this is. It appeared insufficient to downgrade the strong evidence of benefit on mortality and malaria illness from the trials conducted earlier.

Mortality in Malaria: Intensive Care (MIMIC).

Background: While global incidence of malaria has fallen in last decade, it continues to be an important cause of mortality and morbidity in acutely ill febrile patients. Many patients with complicated malaria require ICU care. In past it was believed that vivax is a benign form of malaria, but now all complications of malaria are reported in vivax. . Aims and Objectives: 1. To find out proportion of patients with plasmodium vivax and plasmodium falciparum malaria requiring treatment in Medical ICU. 2. To compare clinical profile and severity of illness in these patients. 3. To study treatment received including organ support requirement in these patients and compare outcome in patients with vivax and falciparum malaria. Results: During study period total 932 patients were diagnosed as confirmed malaria (601 vivax, 240 falciparum and 91 mixed) and 107 (vivax 74, falciparum 20, mixed 13) required ICU admission. Common symptoms observed apart from fever were, oliguria (48), dyspnea(41), bleeding (29), hemoptysis (15) and petechial rash (13). Mean BUN and creatinine and PT INR of falciparum/mixed malaria patients was significantly higher and HCO3 and pH significantly lower than vivax patients. But PaO2/FiO2 of vivax patient was significantly lower as compared falciparum/mixed patients. There was no significant difference between two groups with regards to requirement of supportive treatment like inotropes (11/70 vs 5/30, p=0.858), mechanical ventilation (28/70 vs 7/30, p=0.17), platelet transfusion (24/70 vs 9/30, p=0.853) and renal replacement therapy (5/70 vs 3/30 p=0.936). Out of 100 patients, 21 patients expired. Mortality in mixed malaria group (4/12, 33.3%) and vivax group ( 16/70, 22.9%) was more as compared to falciparum group (1/18, 5.6%, < 0.05). Conclusions: Incidence of Plasmodium vivax malaria is higher compared to falciparum malaria in hospitalized patients and higher percentage of these need ICU care. Most common complications of malaria are thrombocytopenia followed by renal failure, hepatic dysfunction, ARDS, shock and cerebral dysfunction respectively. Mortality was higher in vivax and mixed malaria compared to falciparum. Higher SOFA score (Sequential organ failure assessment score), lower GCS score (Glasgow coma scale), hypotension, ARDS and metabolic acidosis are predictors of mortality.

Distinct inflammatory profile underlies pathological increases in creatinine levels associated with Plasmodium vivax malaria clinical severity.

BACKGROUND: Although Plasmodium vivax infection is a frequent cause of malaria worldwide, severe presentations have been more regularly described only in recent years. In this setting, despite clinical descriptions of multi-organ involvement, data associating it with kidney dysfunction are relatively scarce. Here, renal dysfunction is retrospectively analyzed in a large cohort of vivax malaria patients with an attempt to dissect its association with disease severity and mortality, and to determine the role of inflammation in its progression. METHODS: A retrospective analysis of a databank containing 572 individuals from the Brazilian Amazon, including 179 patients with P. vivax monoinfection (161 symptomatic malaria, 12 severe non-lethal malaria, and 6 severe lethal disease) and 165 healthy controls, was performed. Data on levels of cytokines, chemokines, C-reactive protein (CRP), fibrinogen, creatinine, hepatic enzymes, bilirubin levels, free heme, and haptoglobin were analyzed to depict and compare profiles from patients per creatinine levels. RESULTS: Elevated creatinine levels were found predominantly in women. Vivax malaria severity was highly associated with abnormal creatinine increases, and nonsurvivors presented the highest values of serum creatinine. Indication of kidney dysfunction was not associated with parasitemia levels. IFN-γ/IL-10 ratio and CRP values marked the immune biosignature of vivax malaria patients, and could distinguish subjects with elevated creatinine levels who did not survive from those who did. Patients with elevated serum creatinine or severe vivax malaria displayed indication of cholestasis. Biomarkers of hemolysis did not follow increases in serum creatinine. CONCLUSION: These findings reinforce the hypothesis that renal dysfunction is a key component in P. vivax malaria associated with clinical severity and mortality, possibly through intense inflammation and immune imbalance. Our study argues for systematic evaluation of kidney function as part of the clinical assessment in vivax malaria patients, and warrants additional studies in experimental models for further mechanism investigations.

Severe thrombocytopaenia in patients with vivax malaria compared to falciparum malaria: a systematic review and meta-analysis.

BACKGROUND: Plasmodium vivax is the most geographically widespread species among human malaria parasites. Immunopathological studies have shown that platelets are an important component of the host innate immune response against malaria infections. The objectives of this study were to quantify thrombocytopaenia in P. vivax malaria patients and to determine the associated risks of severe thrombocytopaenia in patients with vivax malaria compared to patients with P. falciparum malaria. MAIN BODY: A systematic review and meta-analysis of the available literature on thrombocytopaenia in P. vivax malaria patients was undertaken. Relevant studies in health-related electronic databases were identified and reviewed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Fifty-eight observational studies (n = 29 664) were included in the current review. Severe thrombocytopaenia (< 50 000/mm3) to very severe thrombocytopaenia (< 20 000/mm3) was observed in 10.1% of patients with P. vivax infection. A meta-analysis of 11 observational studies showed an equal risk of developing severe/very severe thrombocytopaenia between the patients with P. vivax malaria and those with P. falciparum malaria (OR: 1.98, 95% CI: 0.92-4.25). This indicates that thrombocytopaenia is as equally a common manifestation in P. vivax and P. falciparum malaria patients. One study showed a higher risk of developing very severe thrombocytopaenia in children with severe P. vivax malaria than with severe P. falciparum malaria (OR: 2.80, 95% CI: 1.48-5.29). However, a pooled analysis of two studies showed an equal risk among adult severe cases (OR: 1.19, 95% CI: 0.51-2.77). This indicates that the risk of developing thrombocytopaenia in P. vivax malaria can vary with immune status in both children and adults. One study reported higher levels of urea and serum bilirubin in patients with P. vivax malaria and severe thrombocytopaenia compared with patients mild thrombocytopaenia or no thrombocytopaenia, (P < 0.001 in all comparisons). A pooled analysis of two other studies showed a similar proportion of bleeding episodes with thrombocytopaenia in severe P. vivax patients and severe P. falciparum patients (P = 0.09). This implied that both P. vivax and P. falciparum infections could present with bleeding episodes, if there had been a change in platelet counts in the infected patients. A pooled analysis of another two studies showed an equal risk of mortality with severe thrombocytopaenia in both P. vivax and P. falciparum malaria patients (OR: 1.16, 95% CI: 0.30-4.60). However, due to the low number of studies with small sample sizes within the subset of studies that provided clinically relevant information, our confidence in the estimates is limited. CONCLUSION: The current review has provided some evidence of the clinical relevance of severe thrombocytopaenia in P. vivax malaria. To substantiate these findings, there is a need for well designed, large-scale, prospective studies among patients infected with P. vivax. These should include patients from different countries and epidemiological settings with various age and gender groups represented.

Prime-boost vaccination with recombinant protein and adenovirus-vector expressing Plasmodium vivax circumsporozoite protein (CSP) partially protects mice against Pb/Pv sporozoite challenge.

Vaccine development against Plasmodium vivax malaria lags behind that for Plasmodium falciparum. To narrow this gap, we administered recombinant antigens based on P. vivax circumsporozoite protein (CSP) to mice. We expressed in Pichia pastoris two chimeric proteins by merging the three central repeat regions of different CSP alleles (VK210, VK247, and P. vivax-like). The first construct (yPvCSP-AllFL) contained the fused repeat regions flanked by N- and C-terminal regions. The second construct (yPvCSP-AllCT) contained the fused repeat regions and the C-terminal domain, plus RI region. Mice were vaccinated with three doses of yPvCSP in adjuvants Poly (I:C) or Montanide ISA720. We also used replication-defective adenovirus vectors expressing CSP of human serotype 5 (AdHu5) and chimpanzee serotype 68 (AdC68) for priming mice which were subsequently boosted twice with yPvCSP proteins in Poly (I:C) adjuvant. Regardless of the regime used, immunized mice generated high IgG titres specific to all CSP alleles. After challenge with P. berghei ANKA transgenic parasites expressing Pb/PvVK210 or Pb/PvVK247 sporozoites, significant time delays for parasitemia were observed in all vaccinated mice. These vaccine formulations should be clinically tried for their potential as protective universal vaccine against P. vivax malaria.

Respiratory Complications of Plasmodium vivax Malaria: Systematic Review and Meta-Analysis.

Malaria, a major global public health problem, is mainly caused by Plasmodium falciparum and Plasmodium vivax, and is responsible for nearly half a million deaths annually. Although P. vivax malaria was not believed to cause severe disease, recent robust studies have proved otherwise. However, the clinical spectrum and pathogenesis of severe vivax malaria and, especially, its respiratory complications remain poorly understood. A systematic search for articles reporting respiratory complications associated with vivax malaria was performed in Lilacs, Cochrane, Scielo, Web of Science, and Medline databases irrespective of publication date. Prevalence of acute respiratory distress syndrome (ARDS) and associated mortality among vivax patients were calculated from cross-sectional and longitudinal studies, whereas factors associated with mortality were calculated from data pooled from case reports and series of cases. A total of 101 studies were included (49 cross-sectional or longitudinal and 52 case reports or series of cases). Prevalence of ARDS was 2.8% and 2.2% in children and adults, respectively, with nearly 50% mortality. Moreover, female sex (P = 0.013), having any comorbidity (P = 0.036), lower body temperature (P = 0.032), lower hemoglobin (P = 0.043), and oxygen saturation (P = 0.053) values were significantly associated with mortality. Plasmodium vivax malaria respiratory complications included ARDS and were associated with high mortality. Demographics and clinical characteristics upon presentation to hospital were associated with mortality among patients with respiratory complications in vivax malaria. This study reaffirms the evidence of severe and fatal complications of P. vivax malaria and its associated respiratory complications.

Morbidity and mortality associated with Plasmodium vivax and Plasmodium falciparum infection in a tertiary care kidney hospital.

Malaria is a disease of tropical regions and both types of plasmodia, i.e. Plasmodium falciparum and Plasmodium vivax, cause significant morbidity and mortality. P. vivax was thought to be benign and cause less morbidity and mortality. Many reports showed the devastating effect of vivax malaria too. We compared the clinical symptoms, laboratory markers, treatment and outcome of both the plasmodia. This is a retrospective analysis of 95 patients admitted to The Kidney Center, Karachi in a duration of 15 years (1997-2012); 45 patients with falciparum malaria and 50 patients with vivax malaria, and compared the clinical presentation, laboratory workup, treatment and outcome in both groups. The two groups constitute a mixed population of diabetes, chronic kidney disease (CKD) and hemodialysis patients. Both plasmodia have an equal clinical impact in terms of fever and rigors, anorexia, nausea, feeling of dyspnea, change in the mental status, changes in the urine color, diarrhea, volume depletion and pedal edema. However, patients with falciparum had significantly more vomiting (P = 0.02), oliguria (P = 0.003) and jaundice (P = 0.003). Laboratory parameters also showed a severe impact of falciparum, as there was more severe anemia and kidney and liver dysfunction. More patients were treated with dialysis and blood transfusion in the falciparum group. The outcome in the two groups was not significantly different in terms of death and days of hospitalization. Falciparum malaria has a higher clinical impact than the vivax malaria, but vivax is not as benign as it was once thought to be. It also has devastating effects on vulnerable populations like patients with CKD and diabetes.

Malaria-associated morbidity during the rainy season in Saharan and Sahelian zones in Mauritania.

Reliable epidemiological data based on laboratory-confirmed cases are scarce in Mauritania. A large majority of reported malaria cases are based on presumptive clinical diagnosis. The present study was conducted to establish a reliable database on malaria morbidity among febrile paediatric and adult patients consulting spontaneously at public health facilities in Nouakchott, situated in the Saharan zone, and in Hodh Elgharbi region in the Sahelian zone in south-east Mauritania during the peak transmission periods. Giemsa-stained thin and thick films were examined under the microscope, and the parasite density was determined according to the procedures recommended by the World Health Organization. Microscopy results were confirmed by rapid diagnostic test for malaria. A total of 1161 febrile patients (498 in Nouakchott and 663 in Hodh Elgharbi region) were enrolled during two successive peak transmission periods in 2009 and 2010. In Nouakchott, 253 (50.8%) febrile patients had positive smears (83% Plasmodium vivax monoinfections and 17% Plasmodium falciparum monoinfections). In Hodh Elgharbi, 378 of 663 patients (57.0%) were smear-positive, mostly due to P. falciparum monoinfections (96.6%). Unlike in Nouakchott, mixed P. falciparum-P. vivax infections, as well as P. vivax, P. ovale, and P. malariae monoinfections, were also observed at a very low prevalence in southern Mauritania. In Nouakchott, malaria occurred more frequently (P<0.05) with higher slide positivity rates (42-53%) among children aged >5 years old and adults than in young children aged <5 years old in both 2009 and 2010. In Hodh Elgharbi, high slide positivity rates (60.9-86.2%) were observed in all age groups in 2010, and there was no significant trend (P>0.05) in relation with age groups. The present study confirmed the predominance of P. falciparum in southern Mauritania reported in previous studies. The presence of P. vivax in Nouakchott is a new epidemiological reality that requires an urgent adoption of novel strategies for parasitological and vector control to combat urban malaria. Moreover, the present study provides evidence-based data on malaria burden in two regions in Mauritania that may serve as a springboard to establish and develop a national surveillance system of malaria epidemiology.

Mortality attributable to Plasmodium vivax malaria: a clinical audit from Papua, Indonesia.

BACKGROUND: Plasmodium vivax causes almost half of all malaria cases in Asia and is recognised as a significant cause of morbidity. In recent years it has been associated with severe and fatal disease. The extent to which P. vivax contributes to death is not known. METHODS: To define the epidemiology of mortality attributable to vivax malaria in southern Papua, Indonesia, a retrospective clinical records-based audit was conducted of all deaths in patients with vivax malaria at a tertiary referral hospital. RESULTS: Between January 2004 and September 2009, hospital surveillance identified 3,495 inpatients with P. vivax monoinfection and 65 (1.9%) patients who subsequently died. Charts for 54 of these 65 patients could be reviewed, 40 (74%) of whom had pure P. vivax infections on cross-checking. Using pre-defined conservative criteria, vivax malaria was the primary cause of death in 6 cases, a major contributor in 17 cases and a minor contributor in a further 13 cases. Extreme anaemia was the most common primary cause of death. Malnutrition, sepsis with respiratory and gastrointestinal manifestations, and chronic diseases were the commonest attributed causes of death for patients in the latter two categories. There were an estimated 293,763 cases of pure P. vivax infection in the community during the study period giving an overall minimum case fatality of 0.12 per 1,000 infections. The corresponding case fatality in hospitalised patients was 10.3 per 1,000 infections. CONCLUSIONS: Although uncommonly directly fatal, vivax malaria is an important indirect cause of death in southern Papua in patients with malnutrition, sepsis syndrome and chronic diseases, including HIV infection.

A prospective study on adult patients of severe malaria caused by Plasmodium falciparum, Plasmodium vivax and mixed infection from Bikaner, northwest India.

BACKGROUND & OBJECTIVES: Description of severe vivax malaria and mixed species infection requires good clinical study. The present study was undertaken to evalute the characteristics of severe malaria patients in Bikaner, northwest India. METHODS: This prospective study included 539 admitted adult patients of severe malaria (Plasmodium falciparum 274, P. vivax 221, and mixed infection of Pv + Pf 44). The diagnosis was confirmed by polymerase chain reaction. The categorization of severe malaria was done strictly as per WHO criteria. RESULTS: The distribution of severe manifestation was similar in severe vivax, falciparum and mixed infections except more cases of thrombocytopenia in P. vivax (p=0.030) and in mixed infection (p=0.004). The risk of developing severe malaria was greatest in patients of mixed infection [53.01% (44/83)] in comparison to Plasmodium falciparum malaria [49.37% (274/555), RR= 1.135; p=0.616] and P. vivax malaria [45.38% (221/ 487), RR = 1.299, p=0.243]. Hepatic dysfunction was the commonest pernicious syndrome [P. falciparum 50% (137/274), P. vivax 43.89% (97/221), and mixed infections 54.55% (24/44)]. Multiorgan dysfunction was present in 40.26% (217/539) patients, the risk was greatest in mixed infection [90.90% (40/44)] in comparison to P. falciparum monoinfection [37.59% (103/274), RR = 12.238; p=0.0001] or P. vivax monoinfection [33.48% (74/ 221), RR = 13.25; p=0.0001]. The risk of mortality in severe malaria was 6.31% (34/539) in which mixed infection had greater risk [9.09% (4/44)] in comparison to P. falciparum [7.30% (20/274); OR = 1.270 (CI 0.347-4.217); p=0.757] or P. vivax [4.52% (10/221); 0R 2.110 (CI 0.527-7.826); p=0.260]. INTERPRETATION & CONCLUSION: Severe vivax or falciparum malaria had almost similar features and prognosis including mortality. Risk of developing severe malaria, multiorgan dysfunction and mortality was more in patients of mixed infection in comparison to P. falciparum or P. vivax monoinfection. A multicentric study on larger number of patients requires further confirmation.

Is Plasmodium vivax malaria a severe malaria?: a systematic review and meta-analysis.

BACKGROUND: Plasmodium vivax is one of the major species of malaria infecting humans. Although emphasis on P. falciparum is appropriate, the burden of vivax malaria should be given due attention. This study aimed to synthesize the evidence on severe malaria in P. vivax infection compared with that in P. falciparum infection. METHODS/PRINCIPAL FINDINGS: We searched relevant studies in electronic databases. The main outcomes required for inclusion in the review were mortality, severe malaria (SM) and severe anaemia (SA). The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Overall, 26 studies were included. The main meta-analysis was restricted to the high quality studies. Eight studies (n = 27490) compared the incidence of SM between P. vivax infection and P. falciparum mono-infection; a comparable incidence was found in infants (OR: 0.45, 95% CI:0.04-5.68, I2:98%), under 5 year age group (OR: 2.06, 95% CI: 0.83-5.1, I2:83%), the 5-15 year-age group (OR: 0.6, 95% CI: 0.31-1.16, I2:81%) and adults (OR: 0.83, 95% CI: 0.67-1.03, I2:25%). Six studies reported the incidences of SA in P. vivax infection and P. falciparum mono-infection; a comparable incidence of SA was found among infants (OR: 3.47, 95%:0.64-18.94, I2: 92%), the 5-15 year-age group (OR:0.71, 95% CI: 0.06-8.57, I2:82%). This was significantly lower in adults (OR:0.75, 95% CI: 0.62-0.92, I2:0%). Five studies (n = 71079) compared the mortality rate between vivax malaria and falciparum malaria. A lower rate of mortality was found in infants with vivax malaria (OR:0.61, 95% CI:0.5-0.76, I2:0%), while this was comparable in the 5-15 year- age group (OR: 0.43, 95% CI:0.06-2.91, I2:84%) and the children of unspecified-age group (OR: 0.77, 95% CI:0.59-1.01, I2:0%). CONCLUSION: Overall, the present analysis identified that the incidence of SM in patients infected with P. vivax was considerable, indicating that P. vivax is a major cause of SM. Awareness of the clinical manifestations of vivax malaria should prompt early detection. Subsequent treatment and monitoring of complications can be life-saving.