Abstract
Purpose:
The purpose of this study is to examine the prevalence, clinical spectrum, prognostic factors, and outcome of multi-organ dysfunction syndrome (MODS) in patients with malaria.
Materials and Methods:
One hundred and twenty-four patients with malaria, diagnosed by a positive peripheral blood film and rapid malaria test, were studied for MODS using the sequential organ failure assessment (SOFA) score. The severity of malaria was assessed by the WHO criteria.
Results:
Severe malaria was present in 54 (43.54%) patients. MODS was detected in 108 (87.09%) patients with malaria (Plasmodium falciparum - 57 [85.07%], Plasmodium vivax - 46 [88.46%] and mixed P. falciparum and P. vivax malaria - 5 [100%] cases). SOFA scores of MODS-and non-MODS-patients differed significantly (P < 0.001). No significant association was seen between MODS and type of malaria (P = 0.894). Mortality among malaria patients with MODS was 5.55% (6/108) (P. falciparum 8.77% [5/57] and P. vivax 2.17% [1/46]). The outcome of MODS was associated significantly with the severity of the SOFA score at admission (P = 0.011) but not with the type of malaria, malaria parasite index, and the number of organs involved (P > 0.05 each). The SOFA score at admission correlated significantly with the duration of hospitalization (P < 0.0001).
Conclusions:
MODS occurs with high frequency in malaria and is not dependent on the type of malaria. The outcome of MODS and recovery time depends on the severity of MODS. The SOFA score is useful in detecting MODS and ascertaining its severity and prognosis in malaria.
Keywords: Malaria, multi-organ dysfunction syndrome, sequential organ failure assessment score
INTRODUCTION
Malaria is a major public health problem and led to an estimated 405,000 deaths worldwide in 2018. Most malaria cases were seen in the African Region (213 million or 93%), followed by the South-East Asian Region (3.4%).[1] In India, malaria cases have consistently declined from 2.08 million in 2001 to about 4 lakhs in 2018.[2] Infection with malaria parasites may result in a wide variety of symptoms, ranging from absent or very mild symptoms to severe disease and even death.[3] There is an increasing trend for multiple organ dysfunctions attributed to Plasmodium falciparum as well as Plasmodium vivax.[4,5,6,7]
Cerebral malaria, renal dysfunction, severe anemia, acute respiratory distress syndrome (ARDS), shock, hemoglobinuria, thrombocytopenia, hypoglycemia, and multiple organ involvement are the major reported complications of this infection in India[8,9] as well as in other countries.[10]
The WHO criteria[11] are the standard criteria used for defining the severity of malaria. However, various other scores and criteria have been used to identify patients with severe malaria and/or to predict mortality in severe malaria like the Acute Physiology and Chronic Health Evaluation system score,[12] coma acidosis malaria (CAM) score,[13] malaria prognostic index (MPI),[14] “adapted AQ criteria,”[15] Malaria Severity Assessment (MSA) score,[16] Multiple Organ Dysfunction Score,[17] Malaria Severity Score[18] and Glasgow coma scale, Creatinine, Respiratory rate, Bilirubin, and Systolic blood pressure score.[19]
Most of these models suffered from the disadvantage that evidence is lacking on their generalizability due to a lack of external validation.[20] The MPI score has the disadvantage that the determination of its variables (all except the Glasgow coma scale) requires expertise and quality assurance, which generally is lacking in places of severe malaria.[14] The MSA score was not applicable at the time of hospitalization and had uncertainty regarding its generalizability to other settings. The CAM score was pertinent for adults in a low-transmission setting in Asia and is not validated for severe malaria in children in high-transmission settings.[13]
The Sepsis-related Organ Failure Assessment (SOFA) score was originally developed as an attempt to objectively and quantitatively describe the degree of organ dysfunction over time and to evaluate morbidity in intensive care unit (ICU) septic patients, and later applied to the whole ICU population, including nonseptic patients, and the acronym “SOFA” was taken to refer to Sequential Organ Failure Assessment. Severe malaria is a multi-organ disease, which requires ICU-type supportive treatment. The SOFA score can be used for evaluating the degree of organ failure over time in patients with malaria. It may show the true prevalence of multi-organ dysfunction syndrome (MODS) in malaria, which otherwise may be underestimated by not taking into account the physiologic dysfunction of the organ. However, there is a dearth of studies applying the SOFA score for the assessment of MODS in malaria. We studied the prevalence, clinical spectrum, prognostic factors, and outcome of MODS, using the SOFA score for the assessment of MODS in patients with malaria.
MATERIALS AND METHODS
This observational cross-sectional study was conducted in the Department of Medicine, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India from July 2015 to June 2018. The ethical clearance for the research work was obtained from the ethics committee of the institute, in compliance with the ethical standards of the Declaration of Helsinki. Written informed and free consent was obtained from the patients or their relatives before including the patients in the study.
Inclusion criteria
All patients >18 years of age with a diagnosis of malaria were included in the study.
Exclusion criteria
Conditions other than malaria, which could lead to MODS, such as pancreatitis, dengue, leptospirosis, enteric fever, scrub typhus, and acute viral hepatitis, were excluded from this study.
Study protocol
All cases of fever suspected of suffering from malaria were investigated for malaria. Malaria was suspected in any patient with a history of fever or temperature >37.5°C and no other obvious cause.[21] The diagnosis of malaria was based on the detection of asexual forms of P. vivax and P. falciparum from Giemsa stained peripheral blood smear and a positive rapid malaria test (RMT).
Patients were managed in the high-dependency unit (HDU) or in the ICU (reserved for the severely ill) where the facilities for recording SOFA scores were available.
Investigations
The investigations done were complete hemogram, erythrocyte sedimentation rate, reticulocyte count, complete urinalysis, peripheral blood smear for the malarial parasite, RMT-a rapid immuno-chromatographic test using monoclonal anti-histidine rich protein-2 (anti-HRP-2) (P. falciparum specific) and monoclonal anti-parasite lactate dehydrogenase (anti-pLDH) (P. vivax specific) antibodies coated on the test lines (QDx Malaria P. vivax/P. falciparum Malaria card test, Piramal, Navi Mumbai, India), malaria parasite index, liver function tests, renal function tests, serum glucose-6-phosphate dehydrogenase (G6PD), chest X-ray, electrocardiogram, and fundus examination.
Other special tests such as arterial blood gas analysis, activated partial thromboplastin time, serum fibrinogen, serum fibrin degradation products, D-dimer test, ultrasonographic examination of the abdomen, Widal test, dengue serology, viral markers such as antibodies to hepatitis A virus, hepatitis C virus and hepatitis E virus, hepatitis B surface antigen, blood and urine cultures, and sensitivity test, cerebrospinal fluid examination, echocardiography, and computed tomography scan of the brain were done wherever required.
MODS was assessed using the SOFA score and was considered when patients had the involvement of ≥2 organs and a SOFA score of ≥2.[22]
Treatment
All patients having malaria with MODS received artesunate 2.4 mg/kg intravenous (iv), which was repeated at 12 h and 24 h, and then once daily for 7 days along with doxycycline 100 mg orally twice daily for 14 days. In the event of a lack of parasitological or clinical response to artesunate, patients were administered quinine 20 mg salt/kg body weight through i. v. infusion, followed by 10 mg/kg body weight every 8 h for 7 days.[23]
Broad-spectrum antibiotics were given initially until the bacterial infection was excluded. Blood products were transfused wherever required, along with iv fluids and other supportive measures. All patients having P. vivax malaria/mixed P. vivax and P. falciparum malaria received primaquine 0.25 mg base/kg body weight once daily for 14 days on recovery, after excluding G6PD deficiency for radical cure.
Patients having only P. falciparum malaria received a single dose of primaquine 0.75 mg base/kg body weight for the gametocidal effect.
Clinical and parasitological response to anti-malarial treatment was assessed in the patients. Temperature recording was done every 4 h until resolution of fever and every 8 h thereafter. Assessment of the parasitic index was done on days 0, 1, 2, 4, 7, 14, and 21. Other laboratory parameters were also assessed at regular intervals.
The SOFA score was calculated on the day of admission, the 3rd day, and the day of discharge. The severity of malaria was also determined by taking into consideration the significant derangement of the function of an organ system as per the WHO criteria for severe malaria.[11]
Patients were also studied for prognostic factors for MODS in malaria patients.
Definitions
Fever clearance time was defined as the time taken by the body temperature to fall below 37.5°C and remain below this level for >48 h.[24]
Parasite clearance time was defined as the time for the asexual parasite malaria count to fall below detectable levels after drug administration.[23]
MODS was defined by the simultaneous presence of physiologic dysfunction and/or failure of two or more organs.[25]
Statistical analysis
All data were analyzed with SPSS statistics version 23.0 (IBM Corporation, Armonk, New York, United States). The data were expressed as a mean ± standard deviation for continuous variables and as a frequency or percentage for categorical variables. Chi-square test or Fisher's exact test was used for the statistical comparison of qualitative variables and for determining the association between various variables. Student's t-test was used for the comparison of parametric variables of two groups. Pearson product-moment correlation coefficient was used to assess the correlation between various variables. A value of P < 0.05 was taken as statistically significant.
RESULTS
Of the 145 patients that tested positive for malaria, 21 patients had co-infection with dengue fever, scrub typhus, acute viral hepatitis or enteric fever, and were excluded from the study. Of the remaining 124 patients, 67 (54.03%) patients had P. falciparum malaria, 52 (41.93%) P. vivax malaria, and 5 (4.03%) mixed P. vivax and P. falciparum malaria. Severe malaria as per the WHO criteria was present in 43.54% (54/124) and nonsevere malaria was present in 56.45% (70/124) patients. MODS was seen in 108 patients (87.09%) as per the SOFA score at admission. MODS was present in 100.00% (54/54) patients with severe malaria and 77.14% (54/70) with nonsevere malaria. As per the SOFA score, MODS was seen in 85.07% (57/67) patients with P. falciparum malaria, 88.46% (46/52) with P. vivax malaria, and 100% (5/5) with mixed P. vivax and P. falciparum malaria. No significant association was seen between MODS and the type of malaria (P = 0.894).
The mean age of patients having malaria with MODS was 38.86 ± 16.83 years (age range 19–79 years). Male: female ratio was 1.29:1. Sixty-three (58.33%) patients having malaria with MODS belonged to rural areas and 45 (41.66%) to urban areas. P. falciparum mono-infection prevalence was the highest (57/108, 52.77%) followed by P. vivax, (46/108, 42.59%), and the least was mixed infection (5/108, 4.62%). A previous history of malaria infection was present in 8.33% (9/108) patients of malaria with MODS. P. vivax mono-infection on this admission was seen in 55.55% (5/9) of previously infected patients and the rest had P. falciparum mono-infection. The mean SOFA score at admission was 7.39 ± 3.87 among all malaria patients. There was a significant difference between SOFA scores of malaria patients with MODS (8.18 ± 3.87) and patients without MODS (2 ± 3.99) (P = 0.0001).
The difference between the prevalence of MODS among patients with a previous history (100%, 9/9) and those without a previous history of malaria (86.98%, 99/115), was statistically insignificant (P = 0.809). The difference between SOFA scores on admission (11.44 ± 3.96) among patients with a history and those without any previous history of malaria infection (7.89 ± 3.89) was statistically significant (P = 0.010).
The clinical spectrum of all malaria patients and malaria patients with MODS as per the SOFA score is shown in Table 1. The most common symptom among MODS patients was fever and the mean duration of fever was 7.01 ± 5.02 days. Among patients having MODS, severe malaria manifestations seen were hyperbilirubinemia (45.37%), hemoglobinuria (30.55%), acidosis/acidemia (22.22%) and acute kidney injury (17.59%). Thrombocytopenia (platelet count <150,000/cumm) was seen in 97.22% (105/108) patients.
Table 1.
Clinical spectrum of malaria patients with multi-organ dysfunction syndrome (n=108)
| Number of all malaria patients (%)/Mean±SD | Number of malaria patients with MODS (%)/Mean±SD | |
|---|---|---|
| Symptoms | ||
| Fever | 121 (97.58) | 105 (97.22) |
| Chills | 109 (87.90) | 94 (87.03) |
| Bodyache | 34 (27.41) | 27 (25.0) |
| Headache | 29 (23.38) | 26 (24.07) |
| Jaundice | 47 (37.90) | 47 (43.51) |
| Vomiting | 45 (36.29) | 41 (37.96) |
| Bleeding manifestations (hematuria/bleeding from nose/bleeding gums) | 25 (20.16) | 22 (20.37) |
| Abdominal pain | 25 (20.16) | 24 (22.22) |
| Loose stools | 7 (5.64) | 6 (5.55) |
| Shortness of breath | 16 (12.90) | 15 (13.88) |
| Altered sensorium | 6 (4.83) | 6 (5.55) |
| Decreased urine output | 14 (11.29) | 14 (12.96) |
| Signs/examination findings | ||
| MAP (mmHg) | 78.22±16.69 | 77.35±15.02 |
| Tachycardia | 58 (46.77) | 48 (44.44) |
| Hepatomegaly | 58 (46.77) | 54 (50.0) |
| Pallor | 56 (45.16) | 52 (48.14) |
| Icterus | 51 (41.12) | 51 (47.22) |
| Splenomegaly | 48 (38.70) | 45 (41.66) |
| Pedal edema | 41 (33.06) | 40 (37.03) |
| Hepato-splenomegaly | 32 (25.80) | 32 (29.62) |
| Rashes on body (purpura/ecchymosis/petechiae) | 28 (22.58) | 25 (23.14) |
| Crepitations in chest | 18 (14.51) | 17 (15.74) |
| Subconjunctival hemorrhage | 10 (8.06) | 10 (9.25) |
| Neurological deficit | 6 (4.83) | 4 (3.70) |
| Lymphadenopathy | 3 (2.41) | 2 (1.85) |
| Laboratory findings | ||
| Hemoglobin (g/dL) | 10.05±2.65 | 10.01±2.65 |
| Red cell count (million/cumm) | 3.41±1.00 | 3.39±1.00 |
| TLC (/cumm) | 7353.85±4116.66 | 7297.01±4116.66 |
| Platelet count (thousand/cumm) | 49.43±53.30 | 41.05±53.30 |
| Reticulocyte count (%) | 1.26±2.03 | 1.30±2.07 |
| Erythrocyte sedimentation rate (mm in 1st h) | 44.33±22.65 | 43.15±22.43 |
| Malaria parasite index on admission (%) | 1.22±1.58 | 1.30±1.58 |
| Serum creatinine (mg/dL) | 2.04±2.50 | 2.21±2.52 |
| Serum total bilirubin (mg/dL) | 4.26±5.75 | 4.77±5.51 |
| Serum alanine aminotransferase (U/L) | 46.14±45.25 | 47.20±29.74 |
| Serum aspartate aminotransferase (U/L) | 67.75±79.85 | 69.95±47.60 |
| Serum alkaline phosphatase (U/L) | 121.74±110.6 | 117.90±112.0 |
| Serum albumin (g/dL) | 2.43±0.55 | 2.38±0.55 |
| Serum lactate dehydrogenase (U/L) | 532.83±331.71 | 547.37±335.84 |
MAP: Mean arterial pressure, SD: Standard deviation, MODS: Multi-organ dysfunction syndrome, TLC: Total leucocyte count
Treatment parameters with malaria patients with MODS are shown in Table 2. The mortality observed in MODS patients as per the SOFA score was 5.55% (6/108). Out of the nonsurvivors, 66.66% (4/6) patients had received artesunate and doxycycline, and 33.33% (2/6) patients had received quinine in addition to artesunate and doxycycline. Mortality occurred due to ARDS (33.33%, 2/6), cerebral malaria (33.33%, 2/6), cardiogenic shock (16.66%, 1/6), and disseminated intravascular coagulation (DIC) (16.66%, 1/6).
Table 2.
Treatment parameters in malaria patients with multi-organ dysfunction syndrome (n=108)
| Parameter | Number of MODS patients (%) |
|---|---|
| Conservative management | |
| Artesunte + doxycycline | 99 (91.66) |
| Artesunate + doxycycline + quinine | 9 (8.34) |
| Fever clearance time (days) | |
| 1-3 | 94 (95.38) |
| 4-7 | 5 (4.62) |
| >7 | 0 |
| Number of dialysis sessions | |
| <5 | 14 (12.96) |
| >5 | 4 (3.70) |
| Outcome | |
| Recovered | 102 (94.44) |
| Expired | 6 (5.56) |
| Duration of hospitalization of patients who died (days) | |
| 1-3 | 4 (66.67) |
| 4-6 | 0 |
| >6 | 2 (33.33) |
MODS: Multi-organ dysfunction syndrome
The mean fever clearance time among MODS-survivors was 1.54 ± 1.14 days. The mean duration of hospitalization of MODS-survivors was 5.63 ± 2.79 days, and that of MODS-nonsurvivors was 4.66 ± 2.87 days.
The complications observed among malaria patients with and without MODS are shown in Table 3. The prevalence of jaundice (P = 0.001), thrombocytopenia (P < 0.001), and proteinuria (P = 0.005) was significantly higher in MODS patients, while no significant differences were seen regarding the prevalence rates of other complications (P > 0.05 each).
Table 3.
Complications among malaria patients with (n=108) and without multi-organ dysfunction syndrome (n=16)
| Parameter | Total number of malaria patients (%) | Number of MODS patients (%) | Number of non-MODS patients (%) | P |
|---|---|---|---|---|
| Jaundice | 49 (39.51) | 49 (45.37) | 0 | 0.001 |
| Shock (MAP <70 mmHg) | 26 (20.96) | 25 (23.14) | 1 (6.25) | 0.188 |
| Impaired consciousness | 15 (12.09) | 15 (13.88) | 0 | 0.214 |
| Cerebral malaria | 4 (3.22) | 4 (3.70) | 0 | 1 |
| ARDS (PaO2/FiO2 <200) | 11 (8.87) | 11 (10.18) | 0 | 0.356 |
| Ventilatory support | 7 (5.64) | 7 (6.41) | 0 | 0.593 |
| DIC | 11 (8.87) | 11 (10.18) | 0 | 0.356 |
| Severe anemia (hemoglobin <5 g/dL) | 5 (4.03) | 4 (3.70) | 1 (6.25) | 1 |
| Leucocytosis (TLC >11 thousand/cumm) | 21 (16.93) | 18 (16.66) | 3 (18.75) | 1 |
| Leucopenia (TLC <4 thousand/cumm) | 19 (15.32) | 18 (16.66) | 1 (6.25) | 0.462 |
| Thrombocytopenia (platelet count <150 thousand/cumm) | 116 (93.54) | 105 (97.22) | 11 (68.75) | <0.001 |
| Hypoglycemia (RBS <40 mg/dL) | 5 (4.03) | 5 (4.62) | 0 | 0.619 |
| Acute kidney injury (serum creatinine >3mg/dL) | 19 (15.32) | 19 (17.59) | 0 | 0.128 |
| Hypokalemia (serum potassium <3.5 mmol/L) | 16 (12.90) | 15 (13.88) | 1 (6.25) | 0.479 |
| Hyperkalemia (serum potassium >5 mmol/L) | 12 (9.67) | 12 (11.11) | 0 | 0.224 |
| Hyponatremia (serum sodium <136 mmol/L) | 57 (45.96) | 52 (48.14) | 5 (31.25) | 0.319 |
| Hypernatremia (serum sodium >146 mmol/L) | 1 (0.8) | 1 (0.9) | 0 | 1 |
| Proteinuria | 67 (54.03) | 64 (59.25) | 3 (18.75) | 0.005 |
MAP: Mean arterial pressure, ARDS: Acute respiratory distress syndrome, PaO2/FiO2: Partial pressure of arterial oxygen/fraction of inspired oxygen ratio, DIC: Disseminated intravascular coagulation, TLC: Total leucocyte count, RBS: Random blood sugar, MODS: Multi-organ dysfunction syndrome
Table 4 shows the various prognostic markers among patients of malaria with MODS. There was no significant age difference seen among the survivors and nonsurvivors of MODS patients (P = 0.457). No significant difference was seen between the nonsurvivors and survivors of malaria with MODS regarding the duration of illness before establishing the diagnosis and starting anti-malarial treatment (P = 0.741).
Table 4.
Prognostic factors in malaria patients with multi-organ dysfunction syndromea
| Parameter | Number of malaria patients with MODS (n=108) | P | |
|---|---|---|---|
| Survivors (n=102) | Nonsurvivors (n=6) | ||
| Age (years) | 38.56±16.83 | 43.83±16.99 | 0.457 |
| Durations of illness before initiating antimalarial treatment (days) | 6.81±5.02 | 7.5±3.71 | 0.741 |
| Hemoglobin (g/dL) | 9.97±2.65 | 10.62±2.46 | 0.559 |
| TLC (/cumm) | 7108.90±4116.66 | 10,485±4418.96 | 0.054 |
| Platelet count (thousand/cumm) | 37.37±53.30 | 103.58±51.98 | <0.001 |
| Random blood glucose (mg/dL) | 130.13±71.79 | 128.67±77.42 | 0.961 |
| Serum total bilirubin (mg/dL) | 4.82±5.51 | 3.92±5.17 | 0.697 |
| Serum alanine aminotransferase (U/L) | 47.33±29.74 | 45±31.18 | 0.852 |
| Serum aspartate aminotransferase (U/L) | 70.67±47.60 | 57.67±49.33 | 0.517 |
| Blood urea nitrogen (mg/dL) | 43.15±37.72 | 44.05±40.34 | 0.955 |
| Serum creatinine (mg/dL) | 2.18±2.52 | 2.67±2.70 | 0.645 |
| Serum sodium (mmol/L) | 135.08±9.79 | 137.78±10.75 | 0.514 |
| Serum potassium (mmol/L) | 4.16±0.68 | 3.73±0.73 | 0.136 |
| Serum bicarbonate (mmol/L) | 18.91±4.93 | 18.52±5.35 | 0.851 |
| SOFA score on admission | 7.98±3.87 | 11.67±3.88 | 0.025 |
| SOFA score on day 3* | 5.34±3.18 | 11.67±3.88 | <0.001 |
| SOFA score on discharge/expiry* | 2.61±2.04 | 12±3 | <0.001 |
aData are mean±SD. SOFA score: Sequential organ failure assessment score, *SOFA score on day 3 and at discharge/expiry was calculated for 105 MODS patients (102 MODS-survivors and 3 MODS-nonsurvivors). SD: Standard deviation, MODS: Multi-organ dysfunction syndrome, TLC: Total leucocyte count
The SOFA score at admission was significantly higher among MODS-nonsurvivors than MODS-survivors (P = 0.025). Platelet counts were significantly lower among MODS-survivors than MODS-nonsurvivors (P < 0.001).
There was a significant positive correlation between the SOFA score at admission and the length of stay in the hospital among patients with malaria (r = 0.638, P < 0.0001).
The outcome of MODS patients did not show a significant association with the type of malaria (P = 0.418) and malaria parasite index (P = 0.502). No significant association was seen between the number of organs involved and the outcome of the disease in MODS patients as per the SOFA score (P = 0.339). A significant association was seen between the severity of the SOFA score and the outcome of MODS (P = 0.011) [Table 5].
Table 5.
Association between parameters affecting multi-organ dysfunction syndrome and its outcome
| Variable | Outcome of MODS | P | |
|---|---|---|---|
| Survivors, n (%) | Nonsurvivors, n (%) | ||
| Type of malaria | |||
| P. falciparum | 52 (50.98) | 5 (83.33) | 0.418 |
| P. vivax | 45 (44.11) | 1 (16.66) | |
| P. falciparum + P. vivax | 5 (4.90) | 0 | |
| Malaria parasite index (%) | |||
| 0.1-1 | 44 (43.13) | 4 (66.66) | 0.502 |
| 1.1-5 | 55 (53.92) | 2 (33.34) | |
| >5 | 3 (2.94) | 0 | |
| Number of organs involved | |||
| 2-4 | 76 (64.40) | 3 (50) | 0.339 |
| 5-6 | 26 (22.03) | 3 (50) | |
| >6 | 0 | 0 | |
| Severity of SOFA score | |||
| Mild (2-8) | 65 (63.72) | 1 (16.66) | 0.011 |
| Moderate (9-15) | 36 (35.29) | 4 (66.66) | |
| Severe (16-24) | 1 (1.96) | 1 (16.66) | |
MODS: Multi-organ dysfunction syndrome, SOFA score: Sequential organ failure assessment score, P. falciparum: Plasmodium falciparum, P. vivax: Plasmodium vivax
DISCUSSION
We studied 124 patients proven to have malaria by the RMT and peripheral blood smear. Among these, 108 patients had MODS as per the SOFA score.
Kashinkunti and Alevoor[26] conducted a study in Karnataka and found the prevalence of P. falciparum malaria to be the highest (50%), followed by P. vivax (40%), and mixed-species infection (10%). In another study conducted by Balpande et al.[27] in Madhya Pradesh, the prevalence of P. vivax malaria was the highest among all (95.1%), followed by P. falciparum malaria (4.8%). The study showed the highest prevalence of P. falciparum species (52.7%), followed by P. vivax (42.59%) and mixed-species infection (4.62%) among malaria patients with MODS. Thus, the study was in agreement with that conducted by Kashinkunti and Alevoor[26] showing that there exists a geographical pattern of distribution of different types of malaria species. However, MODS observed in patients with malaria was not significantly associated with the type of malaria, which implies a change in the benign behavior of P. vivax malaria, leading to a rise in prevalence of MODS in patients with P. vivax mono-infection and an almost similar frequency of MODS in P. vivax as well as P. falciparum mono-infections.
The mean duration of fever, in our study, was 7.01 ± 5.02 days. It was in agreement with that observed by Chowta and Chowta[28] as 6.25 days. Other predominant symptoms were jaundice (37.90%), nausea/vomiting (36.29%), body aches (27.41%), headache (23.38%), rashes (22.58%), bleeding manifestations in the form of hematuria, epistaxis and gum bleed (20.16%), abdominal pain (20.16%), shortness of breath (12.90%), decreased urine output (11.29%), loose stools (5.64%), and altered sensorium (4.83%). These symptoms are comparable with those observed by Chowta and Chowta,[28] who found the incidence of vomiting, headache, and altered sensorium to be 37.36%, 33.6%, and 4.21%, respectively. Our findings are also in agreement with those of Galande et al.,[29] who reported a similar pattern of the prevalence of symptoms of abdominal pain (14%), loose stools (8%), altered sensorium (4%), and decreased urine output (9%) in malaria patients in Maharashtra, India. These different types of manifestations signify the potential of the malaria parasite to affect any organ of the body.
The prevalence of severe malaria as per the WHO criteria was 43.54% (54/124), while the prevalence of MODS as per the SOFA score was 87.09% (108/124). Sarkar et al.[30] studied 900 patients and found severe malaria in 22.22% (200/900) patients, according to the WHO criteria for severe malaria. Two or more complications/MODS were observed in 46% (92/200) patients. A higher prevalence rate of severe malaria in our study may be due to differences in the type of malaria or geographical region. However, the almost twice higher rate of the occurrence of MODS in our study is because we considered both the failure of an organ system and physiologic dysfunction to identify MODS. Moreover, Sarkar et al.[30] had included only P. vivax mono-infection patients in their study, while we selected every patient of malaria irrespective of the type.
Jaundice was the most common manifestation of severe malaria in our study, whereas, in another study[31] in 1994, it was cerebral malaria, which points toward the changing trend of clinical presentation of malaria.
When we applied the SOFA score to evaluate the malaria patients, we found the mean SOFA score among all the patients to be 7.39 ± 3.87. The SOFA score was significantly higher among malaria patients with MODS than those without MODS (P = 0.0001). Sahu et al.[32] studied 301 patients and found the mean SOFA score at admission among all malaria patients to be higher than this, i.e., 10.44 ± 4.26. The difference could be because they studied only severe P. falciparum malaria cases, while we studied all malaria patients. In this study, the mean SOFA score on admission among MODS nonsurvivors (11.67 ± 3.88) was significantly higher than in MODS survivors (7.98 ± 3.87) (P = 0.025), which is in accordance with the results of a study by Krishna et al.,[33] who observed the mean SOFA score among nonsurvivors (16.4 ± 2.4) to be significantly higher than among survivors (11.4 ± 3). Our findings are supported by those of Kute et al.,[34] who found a significant association between a SOFA score ≥12 and the outcome of the disease. We found no significant association between the number of organs involved and the outcome of the disease among MODS patients, evaluated based on the SOFA score (P = 0.339), but a significant association was seen between the severity of the SOFA score and the outcome of the disease (P = 0.011), implying that it is the severity which matters and not the number of organs involved. A positive correlation between the SOFA score at admission and the length of stay in the hospital in our study supports this conjecture.
In a study conducted by Chowta and Chowta,[28] no mortality was observed in malaria patients, whereas, in the study conducted by Sarkar et al.,[30] 4.44% (40/900) mortality was observed. The study is comparable to the latter study, as in our study, 4.84% (6/124) patients succumbed to malaria. All the nonsurvivors had MODS as per the SOFA score. We observed 7.47% (5/67) mortality in the P. falciparum group of mono-infection patients and 1.93% (1/52) in the P. vivax group. No mortality was observed in the mixed-species group. Limaye et al.[35] observed a similar prevalence of mortality rates in their study. However, there was no significant association between the type of malaria and the outcome of the disease in our study (P = 0.418), which implies that P. vivax malaria is also becoming similar to P. falciparum malaria regarding the mortality associated with the disease.
A meta-analysis of studies involving 29,664 malaria patients suggested that thrombocytopenia was equally common in both P. vivax and P. falciparum malaria. It further found that there was a similar proportion of bleeding episodes and an equal risk of mortality with severe thrombocytopenia in both P. vivax and P. falciparum malaria.[36] In our study, though thrombocytopenia was significantly more common in malaria patients with MODS than in those without MODS (P < 0.001), it did not contribute to mortality, as the mean platelet count was observed to be significantly lower among MODS-survivors than MODS-nonsurvivors (P < 0.001). While the maximum mortality occurred due to ARDS (33.33%, 2/6) and cerebral malaria (33.33%, 2/6), mortality was also observed due to cardiogenic shock (16.66%, 1/6) and DIC (16.66%, 1/6). All nonsurvivors had MODS as per the SOFA score. Krishna et al.[33] too found ARDS and CNS involvement to be the highest among nonsurvivors. In this study, there was no significant difference between MODS survivors and MODS nonsurvivors regarding the mean age (P = 0.457) and the duration of illness before starting anti-malarial treatment (P = 0.741).
MODS was detected in a sizeable number of cases since we took into account the simultaneous presence of physiologic dysfunction and/or failure of two or more organs. The presence of MODS in 56.45% (70/124) patients having nonsevere malaria as per the WHO criteria implies that the true prevalence of MODS may not be determined if we consider MODS only in patients having severe malaria as per the WHO criteria. As such, the SOFA score can be useful in ascertaining the presence of MODS in patients with nonsevere malaria as well as in patients with severe malaria, where it can objectively and quantitatively reveal the degree of organ dysfunction over time and evaluate morbidity, particularly in patients in the HDU or ICU.
CONCLUSIONS
MODS is a common occurrence in malaria, as assessed by the SOFA score. MODS has no significant association with the type of malaria. Hematological, renal, hepatic, pulmonary, and cerebral involvements occur commonly in different combinations in MODS.
The SOFA score is useful in assessing the presence, severity, course, and prognosis of MODS in patients with malaria admitted in the HDU or ICU. The outcome of MODS and the time required for recovery from illness are dependent on the severity of MODS.
Financial support and sponsorship
Intramural funding by Swami Rama Himalayan University, Dehradun, Uttarakhand, India.
Conflicts of interest
There are no conflicts of interest.
Acknowledgments
We would like to thank Dr. Madhurima Kaushik for carefully checking the manuscript.
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