Hidden Biomass of Intact Malaria Parasites in the Human Spleen

Kho, Steven; Qotrunnada, Labibah; Leonardo, Leo; Andries, Benediktus; Wardani, Putu A. I.; Fricot, Aurélie; Henry, B.; Hardy, David; Margyaningsih, Nur Ita; Apriyanti, Dwi; Puspitasari, Agatha M.; Prayoga, Pak; Trianty, Leily; Kenangalem, Enny; Safeukui, Innocent; Portillo, Hernando A. del; Fernández-Becerra, Carmen; Meibalan, Elamaran; Marti, Matthias; Price, Ric N.; Woodberry, Tonia; Ndour, Papa Alioune; Russell, Bruce; Yeo, Tsin Wen; Minigo, Gabriela; Noviyanti, Rintis; Poespoprodjo, Jeanne Rini; Siregar, Nurjati C.; Buffet, Pierre; Anstey, Nicholas M.

doi:10.1056/nejmc2023884

Cited by 88 publications

(89 citation statements)

References 6 publications

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“…Repetitive bouts of malaria induce an abnormal immune response resulting in massive hyperreactive malarial splenomegaly (43). In addition, a large biomass of red cells infected with viable young and mature parasites accumulates in the spleen in asymptomatic persons chronically infected with malaria (44).…”

Section: I) Infectionsmentioning

confidence: 99%

Splenomegaly in Children and Adolescents

Suttorp

Classen²

2021

Front. Pediatr.

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In contrast to other lymphoid tissues making up the immune system, the spleen as its biggest organ is directly linked into the blood circulation. Beside its main task to filter out microorganism, proteins, and overaged or pathologically altered blood cells, also humoral and cellular immune responses are initiated in this organ. The spleen is not palpable during a physical examination in most but not all healthy patients. A correct diagnosis of splenomegaly in children and adolescents must take into account age-dependent size reference values. Ultrasound examination is nowadays used to measure the spleen size and to judge on reasons for morphological alterations in associated with an increase in organ size. An enormous amount of possible causes has to be put in consideration if splenomegaly is diagnosed. Among these are infectious agents, hematologic disorders, infiltrative diseases, hyperplasia of the white pulp, congestion, and changes in the composition and structure of the white pulp by immunologically mediated diseases. This review attempts to discuss a comprehensive list of differential diagnoses to be considered clinically in children and young adolescents.

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Section: I) Infectionsmentioning

confidence: 99%

Splenomegaly in Children and Adolescents

Suttorp

Classen²

2021

Front. Pediatr.

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“…Splenic tropism is the highest in P. vivax infections with more than 98% of asexual-stage parasites. This may suggest that chronic malaria could be due to the infection of the spleen, instead of blood infection solely [ 90 , 91 ]. Infected erythrocytes deformability can also be observed in P. ovale and P. cynomolgi infections [ 87 ].…”

Section: Characteristics and Pathology Associated With Individual Zoonotic Plasmodium Speciesmentioning

confidence: 99%

Zoonotic Malaria: Non-Laverania Plasmodium Biology and Invasion Mechanisms

et al. 2021

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Malaria, which is caused by Plasmodium parasites through Anopheles mosquito transmission, remains one of the most life-threatening diseases affecting hundreds of millions of people worldwide every year. Plasmodium vivax, which accounts for the majority of cases of recurring malaria caused by the Plasmodium (non-Laverania) subgenus, is an ancient and continuing zoonosis originating from monkey hosts probably outside Africa. The emergence of other zoonotic malarias (P. knowlesi, P. cynomolgi, and P. simium) further highlights the seriousness of the disease. The severity of this epidemic disease is dependent on many factors, including the parasite characteristics, host-parasite interactions, and the pathology of the infection. Successful infection depends on the ability of the parasite to invade the host; however, little is known about the parasite invasion biology and mechanisms. The lack of this information adds to the challenges to malaria control and elimination, hence enhancing the potential for continuation of this zoonosis. Here, we review the literature describing the characteristics, distribution, and genome details of the parasites, as well as host specificity, host-parasite interactions, and parasite pathology. This information will provide the basis of a greater understanding of the epidemiology and pathogenesis of malaria to support future development of strategies for the control and prevention of this zoonotic infection.

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“…Semi-immune hosts suppress parasitaemia to below conventionally detectable levels (i.e., sub-patent) and acute illness rarely occurs. Recent work suggests that much of the biomass of asexual trophozoites and schizonts of P. vivax occur in the extravascular spaces of marrow, spleen, and liver (Siquiera et al, 2012;Malleret et al, 2015;Obaldia et al, 2018;Fernandez-Becerra et al, 2020;Kho et al, 2021).…”

Section: States Of Infectionmentioning

confidence: 99%

“…Though not yet demonstrated, it is plausible that this relatively inaccessible compartment may both contribute to acute illness (Lacerda et al, 2012) and sometimes be clinically silent (Siquiera et al, 2012;Kho et al, 2021). In either case, extravascular sub-patency almost certainly places infected red blood cells back into the vascular sinuses and peripheral circulation, be those patent or sub-patent.…”

Section: States Of Infectionmentioning

confidence: 99%

Basic Research of Plasmodium vivax Biology Enabling Its Management as a Clinical and Public Health Problem

Baird

2021

Front. Cell. Infect. Microbiol.

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The emerging understanding of Plasmodium vivax as an infection seated in extravascular spaces of its human host carries fundamentally important implications for its management as a complex clinical and public health problem. This progress begins to reverse decades of neglected research borne of the false dogma of P. vivax as an intrinsically benign and inconsequential parasite. This Review provides real world context for the on-going laboratory explorations of the molecular and cellular events in the life of this parasite. Chemotherapies against the latent reservoir impose extraordinarily complex and difficult problems of science and medicine, but great strides in studies of the biology of hepatic P. vivax promise solutions. Fundamental assumptions regarding the interpretation of parasitaemia in epidemiology, clinical medicine, and public health are being revisited and reassessed in light of new studies of P. vivax cellular/molecular biology and pathogenesis. By examining these long overlooked complexities of P. vivax malaria, we open multiple new avenues to vaccination, chemoprevention, countermeasures against transmission, epidemiology, diagnosis, chemotherapy, and clinical management. This Review expresses how clarity of vision of biology and pathogenesis may rationally and radically transform the multiple means by which we may combat this insidiously harmful infection.

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Hidden Biomass of Intact Malaria Parasites in the Human Spleen

Cited by 88 publications

References 6 publications

Splenomegaly in Children and Adolescents

Splenomegaly in Children and Adolescents

Zoonotic Malaria: Non-Laverania Plasmodium Biology and Invasion Mechanisms

Basic Research of Plasmodium vivax Biology Enabling Its Management as a Clinical and Public Health Problem

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