Plasmodium vivax malaria, one of the types of this protozoal disease, is considered to be a global health problem, as it causes up to 390 million clinically apparent infections every year on several continents [1]. P. vivax, transferred by the Anopheles family of mosquitoes to the human host, primarily causes infection in South East Asia and the Central/South America, whereas only a few African countries (Madagascar, Sudan) are the site of P. vivax malaria infection [1] [2] [3]. The pathogenesis of malaria lies in the ability of the protozoa to cause red blood cell (RBC) destruction and a severe inflammatory reaction. Similarly to other types of malaria, the clinical presentation is comprised of chills, myalgia, and high fever, but the 48 hour-cyclic appearance (tertian fever) is a highly specific finding for P. vivax and P. ovale [4]. Additional findings include malaise, abdominal pain, gastrointestinal irritation (nausea, vomiting, diarrhea), jaundice, hepatosplenomegaly, anemia, and a cough [5] [6] [7] Although P. vivax was until recently interpreted as a milder form of malaria, studies have confirmed the increasing presence of prostration, respiratory insufficiency, persistent vomiting and hyperpyrexia in patients suffering from this type of malaria [8]. The incubation period may be quite long, as certain forms of P. vivax inhabit the human liver and remain dormant for a significant period of time (week, months or even years might pass before the onset of symptoms or relapse) [7]. The relapsing and remitting course of the disease, as well as its challenging therapy (but also a delayed diagnosis), are major issues when treating these patients, and requires a comprehensive approach.

• Fever

  An infant developed intermittent fever 20 days after delivery. [ncbi.nlm.nih.gov]

• Chills

  A 37-year-old Ethiopian male presented with a 4-month history of chills, chronic diarrhea and weight loss. He was diagnosed with P. vivax malaria, advanced HIV infection and Isospora belli enteritis. [ncbi.nlm.nih.gov]

  Despite exhibiting low parasite biomass in infected people due to parasite’s specificity to infect only reticulocytes, P. vivax infection triggers higher inflammatory responses and exacerbated clinical symptoms than P. falciparum, such as fever and chills [jvbd.org]

  periodic episodes of fever with chills and rigors, are accompanied by a transient but massive rise in serum TNF levels. [cordis.europa.eu]

• Rigor

  […] the differential diagnosis for febrile patients with a history of travel to malarious areas, health-care providers also should consider malaria as a possible cause of fever among patients who have not traveled but are experiencing alternating fevers, rigors [ncbi.nlm.nih.gov]

  periodic episodes of fever with chills and rigors, are accompanied by a transient but massive rise in serum TNF levels. [cordis.europa.eu]

  A 62-year-old female presented in the emergency department with complaints of fever for the last 4 days which was intermittent in nature and was associated with chills and rigor. On examination, she was febrile with an oral temperature of 104 F. [ijccm.org]

  Case Report A 35 years old male, non diabetic, non hypertensive was admitted following fever for two days with chills, rigor and associated non productive cough and breathing difficulty for two days. [pubs.sciepub.com]

  CASE REPORT A previously healthy 23 year old male, presented to the emergency with chief complaints of high grade fever with chills and rigors but no rash for the last 3 days. [pancreas.imedpub.com]

• Intermittent Fever

  An infant developed intermittent fever 20 days after delivery. [ncbi.nlm.nih.gov]

  On the fourth day of admission, she had intermittent fever, developed dyspnoea and chest radiograph showed bilateral interstitial infiltration. [casereports.bmj.com]

  Case presentation A 22-day-old female infant delivered from a Pakistani mother was referred to the Department of Neonatology and Neonatal Intensive Care, Spedali Civili, Brescia, for intermittent fever of one week duration with picks above 39 C . [malariajournal.biomedcentral.com]

  Hippocrates was apparently the first to distinguish the intermittent fever of malaria from the continual fever of other infectious diseases. Malaria was long known to be associated with swamps. [microbewiki.kenyon.edu]

  According to historical accounts, intermittent fever conditions with the hallmarks of severe malaria—thus likely associated to P. falciparum— spread to India about 3,000 y ago and reached Greece maybe 500 y later. [pnas.org]

• Gangrene

  As far as we are aware, this is the first report of peripheral gangrene associated with P. vivax malaria. [ncbi.nlm.nih.gov]

  Symmetrical peripheral gangrene in severe Plasmodium vivax malaria. Indian J Crit Care Med 2017;21:245-6 How to cite this URL: Kumar P, Tansir G, Gupta H, Dixit J. Symmetrical peripheral gangrene in severe Plasmodium vivax malaria. [ijccm.org]

• Cough

  There was no history of cough, pain abdomen, vomiting, or burning micturition. There was no history of any addiction. Patient first consulted at a clinic and was prescribed paracetamol tablet. [atmph.org]

  Case Report A 35 years old male, non diabetic, non hypertensive was admitted following fever for two days with chills, rigor and associated non productive cough and breathing difficulty for two days. [pubs.sciepub.com]

  Additional findings include malaise, abdominal pain, gastrointestinal irritation (nausea, vomiting, diarrhea), jaundice, hepatosplenomegaly, anemia, and a cough Although P. vivax was until recently interpreted as a milder form of malaria, studies have [symptoma.com]

  There was no history of cough, breathlessness, pain abdomen, vomiting, altered sensorium or burning micturition. There was no history of any addiction or previous hospitalization. [pancreas.imedpub.com]

  Other symptoms may include cough and abdominal pain; occasionally, there may be associated respiratory distress or diarrhea. [journals.lww.com]

• Vomiting

  A nine year old boy presented with high grade fever accompanied by projectile vomiting and abnormal behavior later he developed seizures, shock, and unconsciousness. P. vivax monoinfection was diagnosed based on peripheral smears and PCR. [ncbi.nlm.nih.gov]

  Results The majority of the patients presented with high-grade fever accompanied by projectile vomiting and abnormal behaviour, seizures, shock and unconsciousness. [rcpe.ac.uk]

• Nausea

  Thirteen cases (29.5%) complained of abdominal pain, and 15 cases (34.1%) had gastrointestinal symptoms such as nausea, vomiting, and diarrhea. [kjim.org]

  Additional findings include malaise, abdominal pain, gastrointestinal irritation (nausea, vomiting, diarrhea), jaundice, hepatosplenomegaly, anemia, and a cough Although P. vivax was until recently interpreted as a milder form of malaria, studies have [symptoma.com]

  […] other & to walls of capillaries; depriving tissues of O2; spleen enlarges Located in endemic regions of Africa & s.e. asia Mosquito bite, mother to fetus, transfusion, shared needles, organ transplant None to sever: fever, chills, sweats, headache, nausea [quizlet.com]

  Patient 2 A 24-year old male, born in Pakistan and living in France since 2010, was admitted on 15th of August 2016 to the emergency unit of our hospital for fever, abdominal pain, headache, myalgia, and nausea. [malariajournal.biomedcentral.com]

  Case presentation A 30-year-old woman presented with intermittent, high-grade fever with chills for 5 days prior to admission associated with headache, myalgia and nausea. [casereports.bmj.com]

• Abdominal Pain

  Physicians should suspect and investigate for this rare complication if a patient with malaria complains of left upper quadrant abdominal pain, pleuritic left lower chest pain and/or enlarging tender splenomegaly during the course of malaria infection [ncbi.nlm.nih.gov]

  Three months later, 48 h after the symptoms onset, the patient came back again for fever (38.5 C), headache, arthralgia, myalgia, abdominal pain and subsequently, vomiting and diarrhoea. [malariajournal.biomedcentral.com]

  Thirteen cases (29.5%) complained of abdominal pain, and 15 cases (34.1%) had gastrointestinal symptoms such as nausea, vomiting, and diarrhea. [kjim.org]

  pain, headache and muscle aches and pains Patients with P. vivax or P. ovale infection may have relapses after many months or years Diagnosis Growing trophozoites of P. vivax have irregular shapes and are termed ameboid Identification of malarial parasites [pathologyoutlines.com]

  Additional findings include malaise, abdominal pain, gastrointestinal irritation (nausea, vomiting, diarrhea), jaundice, hepatosplenomegaly, anemia, and a cough Although P. vivax was until recently interpreted as a milder form of malaria, studies have [symptoma.com]

• Chronic Diarrhea

  A 37-year-old Ethiopian male presented with a 4-month history of chills, chronic diarrhea and weight loss. He was diagnosed with P. vivax malaria, advanced HIV infection and Isospora belli enteritis. [ncbi.nlm.nih.gov]

• Jaundice

  Severe P. vivax malaria with cholestatic jaundice in neonates is an uncommon condition that should be included in the differential diagnosis of infants displaying hemolytic anemia, thrombocytopenia, cholestatic jaundice, and hepatosplenomegaly in malaria-endemic [ncbi.nlm.nih.gov]

• Tachycardia

  Patients present with abdominal pain, fever, tachycardia, prostration and rapidly developing anemia and hypotension. Some of these manifestations are seen in malaria itself and therefore splenic rupture can be easily missed. [malariasite.com]

• Vertigo

  Gogtay 1999 reported that nausea and skin rash were mild and infrequent; and Villalobos 2000 reported frequent, mild, transient headache, vertigo, abdominal pain, and nausea. The other trials reported that primaquine regimens were well‐tolerated. [cochranelibrary.com]

The diagnosis of P. vivax malaria must be made early on, as 10-20% of patients are estimated to suffer from a severe form of illness, for whom mortality rates range between 5-15% [3]. The ability of the physician to recognize signs and symptoms of malaria is vital. Patients should be asked about recent travel (possibly to endemic areas) and whether the symptoms appear in a specific fashion (tertian fever). After a detailed physical examination, which may detect hepatosplenomegaly and jaundice, laboratory studies are the next step. A complete blood count (CBC) will virtually always reveal anemia, and thrombocytopenia up to a certain extent [4] [7], while a complete biochemical workup is recommended. To confirm the diagnosis of malaria and determine the specific subtype, several tests have been described in the literature, such as peripheral blood smear examination, microscopy, rapid diagnostic testing and polymerase chain reaction (PCR) [7] [9]. Although microscopic techniques and blood smear examinations lack sensitivity, they are a superior method for the detection of Plasmodium species, but these sophisticated tests are rarely available in areas affected by malaria [9]. Thus, rapid diagnostic tests (RDTs), which are able to detect malarial antigen in blood and cost less are easily performed in this setting [9].

• Erythrocytes Decreased

  CONCLUSIONS: These findings revealed that vivax-infected patients with anaemia have increased levels of IgG auto-antibodies against nRBCs and that their deposition on the surface of non-infected erythrocytes decreases their deformability, which, in turn [ncbi.nlm.nih.gov]

SLCO1A2 and SLCO1B1 gene treatment over time interactions were associated with gametocytemia clearance rate (p FDR 0.018 and p FDR 0.024). ABCB1, ABCC4 and SLCO1B3 were not associated with treatment response. [ncbi.nlm.nih.gov]

[…] malaria has a good prognosis and causes significantly fewer complications than falciparum malaria. [ncbi.nlm.nih.gov]

As compared with complicated falciparum malaria with ARDS, the prognosis is relatively better in ARDS in patients with complicated vivax malaria. [4], [5], [6], [7] Gastrointestinal hemorrhage as a complication of P. vivax malaria again is extremely rare [atmph.org]

This perhaps explains in part the good prognosis with the tertian form of intermittency. [cmr.asm.org]

Parasite density has been identified as a sign of bad prognosis 8. In this study, there was no statistical relation between the level of parasitemia and the severity of clinical manifestations. [scielo.br]

Manning L, Laman M, Law I, Bona C, Aipit S, et al. (2011) Features and prognosis of severe malaria caused by Plasmodium falciparum, Plasmodium vivax and mixed Plasmodium species in Papua New Guinean children. PLoS One 6: e29203. [journals.plos.org]

We found the data supported a role for P. vivax in the etiology of undernutrition in endemic areas. Thus, the application of modern causal inference tools, in future studies, may be useful in determining causation. [ncbi.nlm.nih.gov]

[…] clinically by fever, anemia and splenomegaly and is caused by apicomplexan parasites of the genus Plasmodium P. vivax infections occur in both tropical and temperate zones, between 45 N and 40 S ( WHO: Malaria [Accessed 10 January 2018] ) Pathophysiology / etiology [pathologyoutlines.com]

The pursuit proved fruitless, and when Garnham in 1930 definitively failed to induce malaria in subjects infected only with gametocytes, the way was finally cleared for new ideas about the etiology of relapse. [vivaxmalaria.com]

The epidemiology of P. vivax varies substantially within India, including multiple relapse phenotypes with varying latencies between primary infection and relapse. [ncbi.nlm.nih.gov]

Chapter 2 examines geographic variation in the epidemiology of P. vivax, especially the timing of incubation periods and of relapses, by origin of the parasites. [arxiv.org]

Plasmodium vivax-associated ARDS is a clinically recognisable condition whose underlying pathophysiology is likely to reflect processes that are independent of parasite sequestration in the pulmonary microvasculature. [ncbi.nlm.nih.gov]

REVIEW ARTICLE Year : 2018 Volume : 55 Issue : 1 Page : 1-8 Epidemiology, drug resistance, and pathophysiology of Plasmodium vivax malaria 1 Department of Biochemistry, K.S. [jvbd.org]

Thus, to reduce the overall burden of morbidity and mortality of malaria a clinician needs to be vigilant and acquainted even with the rarest of rare pathophysiological aspects of various complications of malaria. [atmph.org]

Pathophysiology of cerebral malaria: role of host cells in the modulation of cytoadhesion. Ann N Y Acad Sci 2003 ; 992: 30 – 38. Google Scholar Crossref Medline ISI 9. [journals.sagepub.com]

This case highlights the importance of preventing malaria cases among nonimmune or semi-immune individuals traveling to P vivax-endemic areas. [ncbi.nlm.nih.gov]

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