The differences of parasitemia and lungs size in malaria-associated acute respiratory distress syndrome (MA-ARDS) and non-MA-ARDS in mice infected with Plasmodium berghei ANKA

Eka Noviya Fuzianingsih, Cyuzuzo Callixte, Marselaonety La’lang, Dinda Eka Putri, Heny Arwati, Lucia Tri Suwanti


Malaria-associated acute respiratory distress syndrome (MA-ARDS) is characterized by extensive infiltration of leukocytes, microhemorrhages, vasogenic edema, changes in lung color, and a significant increase in the weight of the lung. This study was aimed to find out the differences in parasitemia and lung size in MA-ARDSand non-MA-ARDSin mice infected with Plasmodium berghei ANKA. Sixteen male BALB/c mice were infected with P. berghei ANKA, and daily parasitemia was observed on Giemsa-stained tail blood smears. Mice were sacrificed when parasitemia reached ±20%. Simultaneously eight uninfected mice were used as negative control (NEG). The statistical analysis was done using Kruskal Wallis, Mann Whitney U tests, and Spearman correlation test. The results showed that there were significant differences in parasitemia (p=0.001), weight (p=0.001), and lung length (p=0.021) between the MA-ARDS and non-MA-ARDS groups. Comparison of NEG and MA-ARDS resulted in a significant difference in lung size (p=0.05). When non-MA-ARDScompared with NEG groups, it showed a significant difference in lung width (p=0.001). However, there was no significant difference in lung weight and length (p>0.05). Spearman correlation test showed that there was a strong correlation between parasitemia with weight (p=0.000), length (p=0.001), and lung width (p=0.017). The findings indicated that parasitemia played a role in the development of MA-ARDS in mice infected with P. berghei ANKA and influenced the size of the lung.



Malaria, MA-ARDS, parasitemia, lung weight, lung length, lung width

Full Text:



Aisiku, IP., Yamal, JM., Doshi, P., Benoit, JS., Gopinath, S., Goodman, JC., & Robertson, CS. (2016). Plasma cytokines IL-6, IL-8, and IL-10 are associated with the development of acute respiratory distress syndrome in patients with severe traumatic brain injury. Critical Care. 20(288): 1-10.

Arwati, H., Yotopranoto, S., Rohmah, EA., & Syafruddin, D. (2018). Submicroscopic malaria cases play role in local transmission in Trenggalek district, East Java Province, Indonesia. Malaria Journal. 17(2): 1-6.

Avrina, R., Risniati, Y., Siswantoro, H., Hasugian, AR., Tjitra, E., dan Delima. (2011). Hubungan Kepadatan Parasit dengan Manifestasi Klinis pada Malaria Plasmodium falciparum dan Plasmodium vivax. Media Litbang Kesehatan. 21 (3): 119-126.

CDC. (2021). Malaria Spotlight. Retrived June 26, 2021, from CDC website:

Deroost, K., Tyberghein, A., Lays, N., Noppen, S., Schwarzer, E., Vanstreels, E., Komuta, M., Prato, M., Lin J.W., Pamplona, A., Janse, C. J., Arese, P., Roskams, T., Daelemans, D., Opdenakker, G., and Van den Steen, PE. (2013). Hemozoin Induced Lung Inflammation and Correlates with Malaria-Associated Acute Respiratory Distress Sydndrome. American Journal of Respiratory cell and molecular biology. 48(5): 589-600.

Dimi, B., Arlin, A., and Alim, A. (2020). Prevalensi Malaria Berdasarkan Karakteristik Sosio Demografi. Jurnal Ilmiah Kesehatan. 19(1): 4-9.

Epiphanio, S., Campos, MC., Pamplona, A., Carapau, D., Pena, AC, Ataide, R., Monteiro, CAA, Fe´lix, N., Costa-Silva, N., Marinho, CRF., Dias, S., & Mota, MM.. (2010). VEGF Promotes Malaria-Associated Acute Lung Injury in Mice. Plos Pathogens. 6(5): 1-10.

Gachot, B., Wolff, M., Nissack, G., Veber, B., and Vachon, F. (1995). Acute lung injury complicating imported Plasmodium falciparum malaria. Chest. 108(3): 746–749.

Gonzales, JN., Lucas, R., and Verin, AD. (2015). The Acute Respiratory Distress Syndrome: Mechanisms and Perspective Therapeutic Approaches. Austin J Vasc Med. 2(1): 1-3.

Jindal, SK., Aggarwal, AN., and Gupta, D. (2002). Adult respiratory distress syndrome in the tropics. Clin Chest Med. 23(2): 445–455. sdfe/pdf/download/eid/1-s2.0-S0272523101000090/first-page-pdf.

Kementerian Kesehatan RI. (2018). Situasi Terkini Perkembangan Program Pengendalian Malaria Di Indonesia. Retrieved June 21, 2021, from Kementrian Kesehatan RI website:

Laboratory Identification of Prasitemia of Public Health Concern. (2020). Determination of Parasitemia. Retrieved March 12, 2021, from Laboratory Identification of Parasitemia of Public Health Concern website: benchaids/malaria/parasitemia_and_lifecycle.pdf.

Matthay, MA., Zemans, RL., Zimmerman, GA., Arabi, YM, Beitle, JR., Mercat, A., Herridge, M., Randolph, AG., and Calfee, CS. (2019). Acute Respiratory Distress Syndrome. Nature Republic Health Emergency Collection. 5(18): 1-22.

Melo, MFV., and Bates, JHT. (2019). Pleural Effusion in Acute Respiratory Distress Syndrome: Water, Water, Everywhere, Nor Any Drop to Drain. Crit Care Med. 41(4): 1133-1134.

Moura, GC., Barcelos, D., Epiphanioand, S., and Ortolan, LS. (2017). Physiopathology of Malaria-Associated Acute Respiratory Distress Syndrome. Journal of Infectious Diseases and Preventive Medicine 5(4): 1-5.

Regaller, M., and Richter, T.(2010). Acute lung injury and acute respiratory distress syndrome. J Emerg Trauma shock. 3(1): 43–51. pmc/articles/PMC2823143/.

Soniran, OT., Idowu, OA., Ajayi, OL., and Olubi, IC. (2012). Comparative Study on the Effects of Chloroquine and Artesunate on Histopathological Damages Caused by Plasmodium berghei in Four Vital Organs of Infected Albino Mice. Malaria Research and Treatment. Article ID 960758. Retrieved from:

Van den Steen, PE., Deroost, K., Deckers, K., Van Herck, E., Sofie S., and Opdenakker, G. (2013). Phatogenesis of Malaria-Associated Acute Respiratory Distress Syndrome. Trends Parasitol. 29 (7): 346-358.

Vandermosten, L., Pham, TT., Possemiers, H., Knoops, S., Herck, EV., Deckers, J., Franke-Fayard, B., Lamb, TJ., Janse, CJ, Opdenakker, G., and Van den Steen, PE.. (2018). Experimental malaria-associated acute respiratory distress syndrome is dependent on the parasite-host combination and coincides with normocyte invasion. Malaria Journal. 17(102): 1-17.

WHO. (2019). Joint Malaria Programme Review reveals Indonesia is on track for malaria elimination. Retrieved June 22, 2021, from WHO website: