Mixed Infection of Vivax and Falciparum Malaria with Severe Manifestations of Malaria at the General Hospital of the Christian University of Indonesia: A Case Report

Malaria is still a health problem in Indonesia. The number of malaria cases according to the 2018 RISKESDAS reached 8076 cases, and the highest number was obtained from Papua province with 3,334 cases. Multiple infection malaria in Indonesia according to RISKESDAS 2018, has a rate of 0.01% of the total cases, namely Plasmodium Falciparum malaria and Plasmodium non Falciparum malaria. A 47 year old man was referred from the clinic with complaints of high fever preceded by chills 10 days before being admitted to the hospital. Accompanied by shortness of breath, unable to get off the treatment bed due to feeling very weak, nauseous, sick and having a bulging stomach. Physical examination revealed a pale conjunctiva, ronkhi in the lower field of the right lung, dim percussion in the basal of the left lung, hepatomegaly, splenomegaly, shifting dullness. ring form vivax, on chest X-ray found a left pleural effusion. It is known that the patient previously lived in Papua from September 2018 to May 2019. During treatment, the patient was given artesunate injection therapy, dihydroartemisin + piperaquine and primaquin for seven days of treatment. At the end of the treatment, another chest X-ray was performed and re-examination of the peripheral blood smear, no more pleural effusions were found and no parasites were found on re-examination of the peripheral blood smear. Mixed infection of vivax and falciparum malaria, is a rare case that may occur in endemic areas where both plasmodium can be found. The prevalence in Indonesia according to RISKESDAS is only about 0.01% of all malaria cases in Indonesia.


Introduction
Malaria is still one of the health problems in Indonesia. The number of malaria cases according to RISKESDAS 2018 reached 8076 cases, and the highest number obtained from papua province as many as 3,334 cases (Ministry of Health, 2013). The number of malaria cases according to the Indonesian Health Profile 2017 from the Ministry of Health states, reaching 59.00 per 1000 inhabitants in Papua and 0.99 per 1000 inhabitants nationally. The population in Papua reaches 3,265,202 people with 192,648 people who are positive for malaria in Papua. Malaria infection doubles in Indonesia according to RISKESDAS 2018, has a figure of 0.01% of the total cases, namely malaria Plasmodium Falciparum and malaria Plasmodium non Falciparum (Ministry of Health, 2013).
Malaria is characterized by a pattern of intermittent fever, accompanied by symptoms such as chills, pallor, headache, no appetite, nausea, vomiting, muscle pain and weakness, to a form of Since June 2, 2019, the patient experienced a sudden high fever, accompanied by complaints of pain throughout the joints and chills and sweating profusely, these complaints were felt every day until the patient was hospitalized. Nausea, vomiting and heartburn were felt by the patient on the seventh day before being admitted to the hospital. Complaints of shortness of breath were felt since one day before being admitted to the hospital.
From the auto history, information was obtained that the patient had been working in Papua, Eastern Indonesia since September 2018 and had just returned to Jakarta two weeks before being admitted to the hospital. Before the patient worked in Papua, while in Papua and two weeks after returning from Papua, the patient did not take malaria prophylaxis.
The patient then came to UKI General Hospital on June 11, 2019, the course of the disease on the ninth day, the patient's blood pressure at the emergency room 130 / 80mmHg, pulse rate 88x per minute, respiratory rate 28x per minute, temperature 38.5C and oxygen saturation 93 %. The patient's complaints while in the ER are fever, shortness of breath that is not affected by a change in position, breath does not wheeze, no cough with phlegm and complains of pain in the gut, nausea and vomiting 1x contents of water and food, pain is also felt in the upper right abdomen and upper left stomach. Defecation and urination were not found abnormal, no appetite and looked lethargic. From the physical examination of the chest, there was dim percussion in the left lung, abdominal examination found 2-finger hepatomegaly under the arch of the ribs, flat surface, sharp edges, supple consistency, positive tenderness, Schuffner II splenomegaly, 110cm abdominal circumference, others within normal limits. Initial laboratory examination results from the SOS Medika International Clinic obtained the following results, Hemoglobin 10.7g/dL, Erythrocyte 3.620.000/uL, Leukocytes 5.160/uL, Hematocrit 31.1%, Platelets 79,000/uL, MCV 85.9 fl, MCH 29.6 pg, MCHC 34.4g/dL. The results of the leukocyte count were as follows, basophils 0.8%, eosinophils 0.4%, neutrophils 85.2%, lymphocytes 7.4%, monocytes 6.2%, SGOT 34 IU/L, SGPT 23 IU/L, Ureum 16mg/dL, creatinine 0.81mg/dL, urea-to-creatinine ratio 19.75, blood sugar check at 104mg/dL, sodium 133 mmol/L, potassium 3.2 mmol/L, Chloride 105 mmol/L, C reactive protein 82 mg/L, malaria blood smear obtained Ring form P .falciparum 244/200 WBC, Ring form P. vivax 208/200 WBC, Trophozoid P. falciparum 12/200 WBC, Trophozoid P.vivax 60/200 WBC. The malaria rapid test showed the following positive P. falciparum and positive P. vivax results. Total bilirubin 2.6 mg/dL, direct bilirubin 1.6 mg/dL, indirect bilirubin 1.0 mg/dL. Blood gas analysis obtained the following results, blood pH 7,473, PCO2 24.7mmHg, PO2 92.5mmHg, oxygen saturation 97.3%, Base excess -4.2 mmol/L, HCO3 18.3 mmol/L, TCO2 19.0 mmol/L, The seventh day of treatment, complaints of breathlessness, nausea, vomiting and abdominal pain were no longer felt by the patient, oxygen saturation was measured at 99% without nasal cannula, and using pulse oximetry. Physical examination of the thoracic and abdomen within normal limits, with routine blood results as follows Hb 10g / dL, Leukocytes 5800 / uL, Ht 27.8%, platelets 363,000 / uL, blood sugar at 83mg / dL, examination of thick and thin blood smears, with the result that no plasmodium was found in various stages, the patient then went for outpatient treatment with Primaquin 40mg 1x1 tablet therapy continued until the fourteenth day.

Results and Discussion
Severe malaria according to the 2015 WHO criteria, is the discovery of asexual stage Plasmodium falciparum or Plasmodium vivax with one or more clinical manifestations, namely, decreased consciousness (GCS <11), muscle weakness, recurrent seizures of more than 2 episodes in 24 hours, respiratory distress, pulmonary edema (O2 saturation <92%, respiratory rate> 30x / minute), circulatory failure or shock, jaundice (bilirubin> 3mg / dL, parasite density> 100,000 in falciparum), hemoglobinuria, abnormal spontaneous bleeding (World Health Organization, 2015) . Respiratory disorders such as ARDS or ALI, are complications that often occur in the context of severe malaria infection, but rarely receive special attention. In particular, ARDS has been reported in 5% -25% of adults with severe falciparum malaria and 1-10% of patients with severe P. vivax infection. The associated mortality rate can reach up to 20% in developed countries (Agarwal et al., 2007).
From the history, physical examination and analysis of blood gases, as well as thick and thin malaria blood smears, it was found that the patient had multiple infections with P. vivax and P. falciparum malaria with severe clinical manifestations. Characterized by the presence of respiratory distress, muscle weakness, and the discovery of the second asexual malaria stage of plasmodium. It is likely that the patient got the infection from Papua province, where the patient worked from September 2018 to May 2019.
In our case, the incidence of ARDS may reflect the presence of inflammatory cytokines in the absence of infected erythrocytes. Emerging evidence suggests that even after treatment, free parasitic antigens can persist, which can provide a stimulus for ongoing inflammation (Koh, 2014;Finlay et al., 2014).
From this case, there was no evidence that the patient's lung condition was caused by community pneumonia so that it could be concluded that this acute lung condition was a complication of severe malaria that occurred in the patient, this is contrary to the theory that mixed infection between P. vivax malaria and P. falciparum rarely gets severe clinical forms (Mohapatra et al., 2012). Most cases of mixed-infected malaria are not found to be severe infections because P. vivax infection has a protective effect against the severe form of falciparum malaria. The management of mixed malaria infection uses a combined vivax and falciparum regimen with artesunate for severe malaria. This patient was treated with an artesunate injection and a combined vivax and falciparum therapeutic regimen, as signs of severe malaria were respiratory distress and muscle weakness. Mixed infection of vivax and falciparum malaria is a rare case with a small prevalence in Indonesia, and is generally not found in the form of severe malaria. Treatment with the right regimen and as early as possible is an important step to prevent the progression of severe malaria.