Clinical Profile and Treatment Outcomes of Patients with Malaria Complicated by Acute Kidney Injury.

As Odisha is an endemic region for malaria with many acute kidney injury (AKI) cases, this study evaluated the clinical profile and treatment outcomes of patients with malaria complicated by AKI. This prospective observational study was conducted between December 2015 and September 2017. Detailed histories and clinical examinations were recorded. On admission, tests for routine hematology, plasma glucose, liver function, renal function, serum electrolytes, thick smears, thin smears, and malarial parasites were performed. Of the 958 AKI malarial patients admitted, 202 (82.6 % males) were included in the study, with a mean age of 38.37 years. In total, 86.14%, 3.46%, and 10.39% of patients had Plasmodium falciparum, Plasmodium vivax, and mixed malaria, respectively. Headache and decreased urination (83.66% each) were the most common symptoms after fever (100%). Anuria and oliguria were reported in 5.95% and 67.82% of patients, respectively, whereas 26.23% reported a urine output of >400 mL/24 h. All patients had raised serum creatinine and urea levels, and >60% had anemia, proteinuria, and/or hyponatremia. Multiple organ dysfunction syndrome was observed in 62.87% of patients. Acute tubular necrosis was seen in 60% of renal biopsy specimens (n = 15). Of the 75.75% of patients requiring dialysis, 82.12% and 17.88% of patients required hemodialysis and peritoneal dialysis, respectively, during which 11 patients died. AKI, a serious complication of P. falciparum or P. vivax malaria, is a life-threatening condition. Fever, anemia, oligo/anuria, hepatic involvement, cerebral malaria, high serum creatinine and urea, and disseminated intravascular coagulation were the main predictors of mortality in our study.

Differential impact of malaria control interventions on P. falciparum and P. vivax infections in young Papua New Guinean children.

INTRODUCTION: As malaria transmission declines, understanding the differential impact of intensified control on Plasmodium falciparum relative to Plasmodium vivax and identifying key drivers of ongoing transmission is essential to guide future interventions. METHODS: Three longitudinal child cohorts were conducted in Papua New Guinea before (2006/2007), during (2008) and after scale-up of control interventions (2013). In each cohort, children aged 1-5 years were actively monitored for infection and illness. Incidence of malaria episodes, molecular force of blood-stage infections (molFOB) and population-averaged prevalence of infections were compared across the cohorts to investigate the impact of intensified control in young children and the key risk factors for malaria infection and illness in 2013. RESULTS: Between 2006 and 2008, P. falciparum infection prevalence, molFOB, and clinical malaria episodes reduced by 47%, 59% and 69%, respectively, and a further 49%, 29% and 75% from 2008 to 2013 (prevalence 41.6% to 22.1% to 11.2%; molFOB: 3.4 to 1.4 to 1.0 clones/child/year; clinical episodes incidence rate (IR) 2.6 to 0.8 to IR 0.2 episodes/child/year). P. vivax clinical episodes declined at rates comparable to P. falciparum between 2006, 2008 and 2013 (IR 2.5 to 1.1 to 0.2), while P. vivax molFOB (2006, 9.8; 2008, 12.1) and prevalence (2006, 59.6%; 2008, 65.0%) remained high in 2008. However, in 2013, P. vivax molFOB (1.2) and prevalence (19.7%) had also substantially declined. In 2013, 89% of P. falciparum and 93% of P. vivax infections were asymptomatic, 62% and 47%, respectively, were sub-microscopic. Area of residence was the major determinant of malaria infection and illness. CONCLUSION: Intensified vector control and routine case management had a differential impact on rates of P. falciparum and P. vivax infections but not clinical malaria episodes in young children. This suggests comparable reductions in new mosquito-derived infections but a delayed impact on P. vivax relapsing infections due to a previously acquired reservoir of hypnozoites. This demonstrates the need to strengthen implementation of P. vivax radical cure to maximise impact of control in co-endemic areas. The high heterogeneity of malaria in 2013 highlights the importance of surveillance and targeted interventions to accelerate towards elimination.

Malaria Vaccines: Recent Advances and New Horizons.

The development of highly effective and durable vaccines against the human malaria parasites Plasmodium falciparum and P. vivax remains a key priority. Decades of endeavor have taught that achieving this goal will be challenging; however, recent innovation in malaria vaccine research and a diverse pipeline of novel vaccine candidates for clinical assessment provides optimism. With first-generation pre-erythrocytic vaccines aiming for licensure in the coming years, it is important to reflect on how next-generation approaches can improve on their success. Here we review the latest vaccine approaches that seek to prevent malaria infection, disease, and transmission and highlight some of the major underlying immunological and molecular mechanisms of protection. The synthesis of rational antigen selection, immunogen design, and immunization strategies to induce quantitatively and qualitatively improved immune effector mechanisms offers promise for achieving sustained high-level protection.

Malaria cases in Switzerland from 2005 to 2015 and recent rise of imported Plasmodium vivax malaria.

Reporting cases of malaria to the Federal Office of Public Health has been mandatory in Switzerland since 1974. We analysed notifications of imported confirmed malaria cases between 2005 and 2015 in Switzerland or Liechtenstein. Data for previously visited countries, nationality and reason for travelling were analysed. In contrast with the impressive drop of malaria cases reported worldwide since 2000, we found that the number of malaria cases imported yearly in Switzerland doubled in 2014 and 2015 compared to the average for the preceding decade. Since 2014, Plasmodium vivax infection represented 36% of all diagnosed malaria cases in Switzerland, compared to 11% in the decade leading to 2013. Most of the vivax malaria patients originated from the Horn of Africa, especially from Eritrea. This rise in cases was a consequence not only of an increase in the number of Eritrean refugees, but also their vivax malaria incidence rate, which jumped from 1-3‰ previously to 12‰ in 2014. This is a trend that is not matched by national statistics in Eritrea. An unreported increased incidence in the country of origin (Eritrea) might be the cause of the rise of Pv cases imported into Switzerland, but infections are also likely to occur along the harsh and long migration journey. This epidemiology highlights the need to register and use primaquine for the treatment of latent-phase P. vivax malaria in Switzerland, a medicine currently neither marketed nor systematically reimbursed. Moreover, general practitioners should be aware of this specific epidemiological situation in order to avoid misdiagnosis of febrile Eritreans even months after they reach Switzerland.

Malaria: An Update.

India is endemic for malaria with unstable transmission inhibiting the development of immunity and predisposing all age groups to the disease. Children under five are the greatest sufferers with maximum mortality. P. falciparum and P. vivax cause majority of cases. Fever is the cardinal symptom, though no set of signs and symptoms reliably distinguishes malaria from other causes of fever. In all suspected cases parasitological diagnosis should be confirmed before starting the treatment. Microscopy of blood smears is the gold standard for diagnosis. Rapid diagnostic tests are to be used where microscopy results are not available within 24 h. In complicated malaria and high risk patients like HIV, treatment can be commenced before confirmation, though all efforts to establish the diagnosis should be made. Chloroquine is used for uncomplicated vivax malaria while artemisinin based combination therapy (ACTs) is used for uncomplicated falciparum malaria. For complicated malaria, IV artesunate is the drug of choice irrespective of the Plasmodium species. It is important to follow recommendations diligently to decrease morbidity and mortality due to malaria and to avoid the problem of drug resistance. The gains of the past decade should be scaled up to make malaria elimination and eradication a reality.

P. vivax Malaria presenting as Thrombotic Microangiopathy.

INTRODUCTION: Acute kidney injury (AKI) is reported to occur in patients with falciparum malaria but not uncommon with vivax malaria. AKI, anemia, thrombocytopenia and jaundice is a recurrent finding in severe malaria and can mimic as thrombotic microangiopathy (TMA). Relationship of malaria with TMA is unclear till date however evidences suggest their association. METHODS & MATERIAL: We reviewed our electronic database to evaluate relationship of malaria with TMA, of cases of malaria, jaundice and AKI. RESULTS: 4 patients found to have P. vivax malaria and histopathologically confirmed TMA. All had fever, oliguria, jaundice at presentation. The time between onset of symptoms and admission ranged from 7 to 14 days. All had parasitemia at presentation so were treated with Artesuanate. Hemodialysis and Plasmapheresis was done in all patients. On follow-up all patients recovered and asymptomatic urinary abnormality persisting in one patient. CONCLUSION: High index of suspicion should be kept for TMA in a patient who has nonrecovering AKI with persistent anemia and thrombocytopenia even after clinical and laboratory evidences of recovery from malaria, as response to plasmapheresis seems excellent in this subset of malarial AKI. There could be a pathogenetic link between P.vivax and TMA though yet to be confirmed in larger studies.

Plasmodium vivax: causa de malária grave / Plasmodium vivax: a cause of severe malaria

O presente estudo é um relato de caso de malária por Plasmodium vivax em paciente internado no Hospital Universitário de Mato Grosso do Sul. O objetivo do trabalho foi ressaltar a existência de casos de malária grave provocada por esta espécie do protozoário, visto que a epidemiologia envolvendo P. vivax e suas complicações clínicas severas não é grande, e os relatos não são frequentes na literatura. A doença foi caracterizada por febre contínua, icterícia, hemorragia alveolar e insuficiência renal aguda, sendo que o paciente evoluiu com insuficiência renal, pneumonia associada à ventilação mecânica e meningite bacteriana durante período de internação, com boa resposta ao tratamento.A importância do caso relatado reside na constatação de que a intervenção rápida, mesmo na forma grave da doença, promove a recuperação satisfatória do indivíduo acometido por essa patologia.

This study is a case report of Plasmodium vivax malaria in a patient admitted to the University Hospital of Mato Grosso do Sul. The aim of the work was to highlight the existence of cases of severe malaria caused by this species of the parasite, as the epidemiology involving P. vivax and severe clinical complications is not wide, and the reports are not frequent in the literature. The disease was characterized by continuous fever, jaundice,alveolar hemorrhage and acute renal failure, with the patient developing renal failure, ventilator-associated pneumonia, and bacterial meningitis during hospital stay, with good response to treatment. The importance of the case lies in the realization that rapid intervention, even in the severe form of the disease, promotes safe recovery of the individual affected by this disease

Comparison of Three Screening Test Kits for G6PD Enzyme Deficiency: Implications for Its Use in the Radical Cure of Vivax Malaria in Remote and Resource-Poor Areas in the Philippines.

OBJECTIVE: We evaluated a battery of Glucose-6-Phosphate Dehydrogenase diagnostic point-of-care tests (PoC) to assess the most suitable product in terms of performance and operational characteristics for remote areas. METHODS: Samples were collected in Puerto Princesa City, Palawan, Philippines and tested for G6PD deficiency with a fluorescent spot test (FST; Procedure 203, Trinity Biotech, Ireland), the semiquantitative WST8/1-methoxy PMS (WST; Dojindo, Japan) and the Carestart G6PD Rapid Diagnostic Test (CSG; AccessBio, USA). Results were compared to spectrophotometry (Procedure 345, Trinity Biotech, Ireland). Sensitivity and specificity were calculated for each test with cut-off activities of 10%, 20%, 30% and 60% of the adjusted male median. RESULTS: The adjusted male median was 270.5 IU/10(12) RBC. FST and WST were tested on 621 capillary blood samples, the CSG was tested on venous and capillary blood on 302 samples. At 30% G6PD activity, sensitivity for the FST was between 87.7% (95%CI: 76.8% to 93.9%) and 96.5% (95%CI: 87.9% to 99.5%) depending on definition of intermediate results; the WST was 84.2% (95%CI: 72.1% to 92.5%); and the CSG was between 68.8% (95%CI: 41.3% to 89.0%) and 93.8% (95%CI: 69.8% to 99.8%) when the test was performed on capillary or venous blood respectively. Sensitivity of FST and CSG (tested with venous blood) were comparable (p>0.05). The analysis of venous blood samples by the CSG yielded significantly higher results than FST and CSG performed on capillary blood (p<0.05). Sensitivity of the CSG varied depending on source of blood used (p<0.05). CONCLUSION: The operational characteristics of the CSG were superior to all other test formats. Performance and operational characteristics of the CSG performed on venous blood suggest the test to be a good alternative to the FST.

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.

Imported malaria is stable from Africa but declining from Asia.

INTRODUCTION: In this study, we describe patients with imported malaria seen at the Department of Infectious Diseases (DID), Hvidovre Hospital, Denmark. Our aim was to address possible risk factors for contracting malaria and risk factors for developing complicated malaria. MATERIAL AND METHODS: We searched patient databases for all cases of malaria seen at the DID from 1994 to 2012. Various parameters were registered. RESULTS: A total of 320 cases were identified. We found a significant 3.39 % decrease in the incidence of cases per year (p = 0.0008). Plasmodium falciparum infection was predominant (n = 217) followed by P. vivax infection (n = 76). 37% of all cases were Africans visiting relatives and friends (VRF). A total of 12 patients had one or more re-lapses of their P. vivax infection. In all, 53 (17%) cases were defined as severe malaria. 36% (n = 112) reported using some type of chemoprophylaxis. 14% (n = 26) of patients traveling to Africa in 1999-2012 reported taking chemoprophylaxis as recommended in the current guidelines. Complicated malaria was significantly associated with failure to take any chemoprophylaxis (p = 0.0317, χ(2)-test). CONCLUSION: Imported malaria is decreasing at the DID. The patients who carry the highest risk of imported malaria are ethnic Africans who travel as VRF without using chemoprophylaxis. Recrudescence from P. vivax malaria is a substantial risk. Complicated malaria is associated with failure to take any chemoprophylaxis. It is important that travelers receive expedient advice on the use of efficient chemoprophylaxis to bring down the number of imported malaria cases. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Epidemiological and clinical characteristics of imported malaria in the United Arab Emirates.

BACKGROUND: The United Arab Emirates (UAE) was certified by the World Health Organization to be free of endemic malaria transmission in 2007. There continued to be, however, a substantial number of imported malaria cases. METHODS: A retrospective laboratory and chart review was performed to describe the epidemiological, clinical, and laboratory characteristics of imported malaria in Dubai, UAE. Laboratory records were reviewed at the largest public hospital in Dubai to identify cases of peripheral blood smear-positive malaria from January 1, 2008 to December 31, 2010. Predefined demographic, clinical, and laboratory information was extracted from the electronic medical record system. RESULTS: A total of 629 cases of malaria were identified including 493, 122, and 14 cases of Plasmodium vivax, Plasmodium falciparum, and mixed P. vivax/P. falciparum infections, respectively. Of these, 567 (90.1%) cases were either from India or Pakistan and 7% from sub-Saharan Africa. There were no cases among the local Emirati population. There were 162 hospitalizations, including 8 requiring intensive care support and 1 death. More than 10% of P. vivax infections required hospitalization. The interval between arrival in the UAE and diagnosis was 3 months or longer for 25% of P. vivax cases. CONCLUSIONS: Imported malaria remains an important cause of morbidity in the UAE. Clinicians need to be aware that P. vivax is not benign and can cause severe disease and that malaria cases may present to health facilities several months after arrival from malaria-endemic regions.

Risk factors and outcomes stratified by severity of acute kidney injury in malaria.

Severe acute kidney injury (AKI) is known to have prognostic value for in-hospital outcomes in malaria. However, little is known about the association of AKI of lesser severity with malarial risk factors and outcomes--and such a gap is becoming increasingly relevant with the upsurge in the incidence of AKI due to Plasmodium falciparum malaria and Plasmodium vivax malaria over the last decade. We aimed to identify risk factors of AKI in malaria and assessed in-hospital outcomes stratified by severity of AKI. We performed an observational study of 1,191 hospitalized malaria patients enrolled between 2007 and 2011 in a tertiary care academic center in India. Patients were categorized based on peak serum creatinine into one of three groups: no AKI (<1.6 mg/dL), mild AKI (1.6-3.0 mg/dL), and severe AKI (>3 mg/dL). Plasmodium vivax was the predominant species (61.41%), followed by Plasmodium falciparum (36.41%) and mixed infections with both the species (2.18%). Mild and severe AKI were detected in 12% and 5.6% of patients, respectively. Mild AKI due to Plasmodium vivax (49%) and Plasmodium falciparum (48.5%) was distributed relatively equally within the sample population; however, cases of severe AKI due to Plasmodium falciparum (80%) and Plasmodium vivax (13%) was significantly different (P<0.001). On history and physical examination, risk factors for AKI were age, absence of fever, higher heart rate, lower diastolic blood pressure, icterus, and hepatomegaly. The only laboratory parameter associated with risk of AKI on multivariate analysis was direct bilirubin. Patients with mild and severe AKI had greater organ complications, supportive requirements, longer duration of hospital stay and in-hospital mortality in a dose-dependent relationship, than patients with no AKI. Mild AKI is associated with significant (P<0.05) morbidity compared to no AKI, and future studies should assess strategies for early diagnosis of AKI and prevent AKI progression.

A case of vivax malaria complicated by adult respiratory distress syndrome and successful management with extracorporeal membrane oxygenation.

Complicated malaria is mainly caused by Plasmodium falciparum, but, increasingly, Plasmodium vivax is also being reported as a cause. Since the reemergence of indigenous vivax malaria in 1993, cases of severe malaria have been steadily reported in Korea. Herein, we report a case of vivax malaria complicated by adult respiratory distress syndrome (ARDS) that was successfully managed with extracorporeal membrane oxygenation (ECMO). A 59-year-old man presented at our hospital with fever and abdominal pain, which had persisted for 10 days. On admission, the patient had impaired consciousness, shock, hypoxia and haziness in both lungs, jaundice, thrombocytopenia and disseminated intravascular coagulation, metabolic acidosis, and acute kidney injury. A peripheral blood smear and a rapid diagnostic test verified P. vivax mono-infection. Ten hours after admission, hypoxia became more severe, despite providing maximal ventilatory support. The administration of antimalarial agents, ECMO, and continuous venovenous hemofiltration resulted in an improvement of his vital signs and laboratory findings. He was discharged from the hospital 7 weeks later, without any sequelae.

Plasmodium vivax malaria presenting as acute respiratory distress syndrome: a case report.

Severe pulmonary involvement in malaria has been frequently reported in cases of Plasmodium falciparum infection but rarely in vivax malaria. We look at a case of a 38-year-old man living in a malaria endemic area who presented with acute respiratory distress syndrome (ARDS) caused by P. vivax. DNA polymerase chain reaction (PCR) confirmed that it was not a mixed infection. After specific antimalarial therapy and intensive supportive care, the patient was discharged from the hospital. This case illustrates that P. vivax-induced ARDS is not uncommon and should be readily recognized by the treating physicians. A confirmatory test with PCR is required in order to exclude P. falciparum co-infection.

Acute renal failure associated with malaria in children.

Acute renal failure is one of the serious complications of malaria with untoward consequences including increased risk of mortality. This study was conducted to evaluate the incidence, clinical features, course, outcome, and predictors of mortality of acute renal failure (ARF) in children with malaria in the pediatric general wards and intensive care unit of our medical center from 1 January 2009 to 31 December 2009. Data of all children from 1 month to 12 years of age with confirmed malaria either on peripheral smear and/or OptiMal test were reviewed. Those suffering from ARF were selected for further study. Twelve (eight Plasmodium falciparum; three Plasmodium vivax, and one mixed infection) out of 227 (5%) cases of confirmed malaria had ARF. In addition to ARF, most of the patients had at least one other manifestation of severe malaria. Nine (75%) patients recovered completely, while 3 (25%) died. Presence of associated cerebral malaria, hyperbilirubinemia, and disseminated intravascular coagulopathy (DIC) was a poor prognostic factor and predictor of mortality. In conclusion, ARF can complicate both P. falciparum and P. vivax malaria. Malarial ARF as an isolated complication has a good prognosis. The presence of multiorgan involvement and delayed diagnosis increases morbidity and mortality.

Modeling Plasmodium vivax: relapses, treatment, seasonality, and G6PD deficiency.

Plasmodium vivax (P. vivax) is one of the most important human malaria species that is geographically widely endemic and causes social and economic burden globally. However, its consequences have long been neglected and underestimated as it has been mistakenly considered a benign and inconsequential malaria species as compared to Plasmodium falciparum. One of the important differences between P. falciparum and P. vivax is the formation of P. vivax latent-stage parasites (hypnozoites) that can cause relapses after a course of treatment. In this work, mathematical modeling is employed to investigate how patterns of incubation periods and relapses of P. vivax, variation in treatment, and seasonal abundance of mosquitoes influence the number of humans infected with P. vivax and the mean age at infection of humans in tropical and temperate regions. The model predicts that: (i) the number of humans infected with P. vivax may increase when an incubation period of parasites in humans and a latent period of hypnozoites decrease; (ii) without primaquine, the only licensed drug to prevent relapses, P. vivax may be highly prevalent; (iii) the mean age at infection of humans may increase when a latent period of hypnozoites increases; (iv) the number of infectious humans may peak at a few months before the middle of each dry season and the number of hypnozoite carriers may peak at nearly the middle of each dry season. In addition, glucose-6-phosphate-dehydrogenase (G6PD) deficiency, which is the most common enzyme defect in humans that may provide some protection against P. vivax infection and severity, is taken into account to study its impact on the number of humans infected with P. vivax. Modeling results indicate that the increased number of infected humans may result from a combination of a larger proportion of humans with G6PD deficiency in the population, a lesser protection of G6PD deficiency to P. vivax infection, and a shorter latent period of hypnozoites.