Tropical Parasitology

ORIGINAL ARTICLE
Year
: 2018  |  Volume : 8  |  Issue : 2  |  Page : 83--87

Correlation of hepatorenal dysfunction in pediatric malaria


Niranjan Nagaraj1, Pramod Kumar Berwal1, Anusha Srinivas2, Prem Prakash1, MS Ramesh1, Ayush Berwal1,  
1 Department of Paediatrics, SP Medical College, Bikaner, Rajasthan, India
2 Department of Paediatrics, Navodaya Medical College, Raichur, Karnataka, India

Correspondence Address:
Dr Niranjan Nagaraj
PG Boys Hostel, Room No. 68, Bikaner, Rajasthan
India

Abstract

Background: Malaria is the most prevalent infectious diseases in the world. This study aims to assess the correlation of hepatorenal dysfunction in malaria patients in pediatric age group. Materials and Methodology: This study was conducted on patients of malaria admitted in the Department of Paediatrics, PBM hospital, Bikaner (Rajasthan), during resurgence of various outbreaks of malaria in the year 2011 and 2012. The diagnosis of malaria was confirmed by examination of thick and thin smear/optimal test; malarial hepatic and renal patients were included in the study. Results: The mean age of patients with hepatic and/or renal dysfunction in malaria was 5–10 years and preponderance of males. Association between hepatic and renal dysfunction was significant as 9 (40.9%) in 22 patients with serum bilirubin >3 mg/dl had renal failure in Plasmodium falciparum (PF) and 5 (71.43%) out of 7 patients in mixed (Plasmodium vivax [PV] and PF) patients. This association was not significant in PV as 6 (10.52%) out of 57 patient with serum bilirubin >3 mg/dl had renal failure. Conclusion: The specific reason for presenting our observation is to develop awareness regarding the early complications of malaria and to prevent them prompt action can be taken.



How to cite this article:
Nagaraj N, Berwal PK, Srinivas A, Prakash P, Ramesh M S, Berwal A. Correlation of hepatorenal dysfunction in pediatric malaria.Trop Parasitol 2018;8:83-87


How to cite this URL:
Nagaraj N, Berwal PK, Srinivas A, Prakash P, Ramesh M S, Berwal A. Correlation of hepatorenal dysfunction in pediatric malaria. Trop Parasitol [serial online] 2018 [cited 2019 Jun 24 ];8:83-87
Available from: http://www.tropicalparasitology.org/text.asp?2018/8/2/83/248676


Full Text



 Introduction



About 100 countries in the world are affected with malaria; more than 2.4 million populations are at risk.[1] Malaria is a major cause of death in the Indian subcontinent with 95.5% population at risk.[2] In 1995, 2.8 million positive cases were reported, of which 1.09 million were due to Plasmodium falciparum (PF) species and 1061 cases died[2] during year 2009. There were 1.56 million cases of malaria in 2009, of which 86 million were PF and 0.72 million of Plasmodium vivax (PV) malaria. Malaria has been a serious concern in northeast due to weather and topographic conditions. These states contribute to 8.5%–11% of total malaria cases and 13%–15% of total mortality due to malaria.[3]

Acute renal failure (ARF) is one of the important manifestations of severe falciparum malaria, although it can also occur with PV.[4] The overall prevalence of renal failure in malaria is reported to be varying from 1% to 60%.[5] There is increase in ARF due to malaria from 6.66% in 1995 to 27% in 1998.[4] PF and PV malaria was responsible for ARF in 80.9% and 11.7% patients, respectively.[6] Multiple etiological factors contribute to the development of ARF in malaria such as volume depletion (51%), intravascular hemolysis (39%), heavy parasitemia (36%), cholestatic jaundice (33%), hypotension, sepsis, and disseminated intravascular coagulation.[6]

Jaundice is one of the common manifestations of severe malaria. Incidence varies from 10% to 45% in different reports and more common in adults than in children. Over a decade ago, cerebral malaria was a common manifestation of severe malaria whereas today the correlation of hepatic dysfunction and renal failure is more common.[7] The presence of jaundice in malaria indicates more severe illness with a higher rate of complication. Reports in 2009 showed that 8.8% of total malaria cases and 4.1% of total falciparum cases were reported from Rajasthan.[8] Desert area of Rajasthan including Bikaner district has been hyperendemic for malaria with certain pockets of existence of PF with a spurt in developmental activities in this area over the past decade. Global climatic change, increased irrigation due to Indira Gandhi nahar project, migration of population from eastern part of India, massive deployment of armed forces, and unprecedented rains in 2007 have caused a marked change in epidemiological and clinical profile of malaria in this region. Hence, this study was conducted.

 Materials and Methodology



This study was conducted on patients with malaria admitted in the Department of Paediatrics, PBM Hospital, Bikaner (Rajasthan), during resurgence of various outbreaks of malaria in the year 2011 and 2012. The study criteria include that patients admitted in pediatric wards of P.B.M Hospital with a clinical diagnosis of malaria were selected. The diagnosis of malaria was confirmed by either (1) peripheral blood film-thick and thin smear examination or (2) optimal test (RDT). Patients positive for malaria parasite with malarial hepatorenal dysfunction at presentation were included in the study. Malarial hepatic and renal dysfunction is defined as patients having derangements in either the liver or renal function tests or both at the time of presentations as per the WHO 2010. The study excludes infection causing multiorgan dysfunction such as enteric fever, brucellosis, leptospirosis, hepatitis A, B, C, and E, dengue, patients with past history of systemic illness which affect renal and liver function tests (RFT and LFT), patients on medication likely to affect LFT and RFT, and unwilling patients. The other investigations were done during the study in every patient who was suffering from malaria. All patients were treated as per the WHO guideline; all collected data were tabulated and statically analyzed using SPSS software (SPSS 20.0.1 and Graph Pad Prism version 5).

 Results



The mean age of patients with hepatic and/or renal dysfunction in malaria was 5–10 years as children of these groups are more mobile. There was preponderance of males as male: female ratio observed (2:1) and spectrum of symptoms include fever in 100%, followed by jaundice in 90%, hypotension in 43%, altered sensorium in 40% patients, bleeding manifestations in 31%, renal failure in 30%, severe anemia in 17%, and pulmonary edema in 14% patients. Serum bilirubin was present more than 10 mg% in 8% of patients with malarial hepatic and/or renal dysfunction, and predominantly conjugated hyperbilirubinemia was present in the majority of patients. Association between serum bilirubin level and development of renal failure was significant as 8 (100%) out of 8 patients with serum bilirubin >10 mg/dl had renal failure. Incidence of renal failure in malaria patients with hepatic dysfunction was found to be 22.2% (20 out of 90). Oliguric renal failure which was found to carry poor prognosis was present in 13 (43.33%) patients with malarial renal dysfunction who had renal failure and 17 (56.67%) had nonoliguric renal failure which carried a good prognosis. Mortality was significant in patients with combined hepatic and renal dysfunction and all mortalities were belonging to this group. Multiorgan failure was the major cause of death in 80% followed by septicemia with pulmonary edema and adult respiratory distress syndrome (ARDS) in 20% of the patients. Association between hepatic and renal dysfunction was significant as 9 (40.9%) in 22 patients with serum bilirubin >3 mg/dl had renal failure in PF and 5 (71.43%) out of 7 patients in mixed (PV and PF) patients. This association was not significant in PV as 6 (10.52%) out of 57 patients with serum bilirubin >3 mg/dl had renal failure.

 Discussion



Desert area of Rajasthan including Bikaner district has been hypoendemic for malaria with certain pockets of existence of PF. With a spurt in activities in this area over the past decade, global climatic changes, increased irrigation activities due to Indira Gandhi Canal Project, increased influx of laborers from the eastern part of the country, massive deployment of armed forces, and unprecedented rains have caused a marked change in epidemiological and clinical profile of malaria in this region over the past many years, jaundice and acute renal failure are increasingly being noticed in patients of malaria. Although hepatorenal dysfunction has invariably been reported in PF malaria, its association with PV malaria is also being noticed. Annual report[9] of Government of India reported that 38.6% of all cases from different parts of the country were due to PF.

Our study reveals that 31% of total cases were from Bikaner tehsil and 15% of cases were complicated and referred from Kolayat tehsil in Bikaner district which are the main pockets of existence of malaria, followed by 8% cases from Nokha and 4% from Chhatargarh [Table 1]. Nearly 64% of the total cases were of PV, 24% cases were due to PF, and 12% were due to mixed infection with PV. In India, about 70% of the infections are reported to be due to PV. Almost 25%–30% due to PFand 4%–8% due to mixed infection.[9] The lower incidence of 0–5 years may be due to maternal immunity in infants and more care and attention given by parents to the young children. Higher incidence among age group 5–10 years may be because of more mobility and unawareness about preventive aspects of disease. Our study shows that, out of the 100 patients, 65 patients were males and 35 were females. Mehta et al.[10] have reported male: female ratio of 2.04, and in our study also, this ratio was same. Over the past one decade, clinical manifestations of malaria have undergone a significant change in this region. Kochar et al.[11] reported that major manifestations were cerebral malaria (25.75%), serum anemia (5.83%), renal failure, jaundice (11.47%), and multiorgan dysfunction (9.59%). Our study (conducted in 2011–2012) revealed that jaundice was present in 90%, cerebral 40%, renal failure in 30%, multiorgan dysfunction in 23%, and serum anemia was 17%. Thus, prevalence of cerebral malaria, serum anemia, jaundice, renal failure, and multiorgan dysfunction has significantly increased in the past two decades. This could be attributed to change in the environment due to various causes as discussed possibility of changes in the antigenic and pathogenic characteristics of the parasite to be ruled out.{Table 1}

Our study shows that 76 out of 100 patients with malarial hepatic and renal dysfunction having moderate anemia with hemoglobin levels between 5 and 10 and only 17 had serum anemia having hemoglobin below 5 g/dl. In one study, a total of 136 (43.72%) of malaria patients were having below 8 g/dl. Our study reveals that 10 (33.33%) patients of renal failure had leukocytosis (total leukocyte count >11,000/cu mm) and 3 (10%) had leukopenia, suggesting some superimposed infection or endotoxemia.

In this study on 100 patients of malaria with hepatic and/or renal dysfunction, [Table 2] shows that level of total serum bilirubin was in the range of 0.3–22.3 mg%, increased serum bilirubin was observed in 90% cases out of them 8% have serum bilirubin of >10 mg%. Maximum value of serum bilirubin observed was 22.3 mg%. Kochar et al.[12] studied 86 patients of malarial hepatitis, of which 29 cases had serum bilirubin level of >10 mg%. Maximum value of serum bilirubin was 48.2. These findings favor our observation in patients of malaria with jaundice. Kochar et al. (2003) also found predominantly conjugated hyperbilirubinemia in their malarial hepatitis patients. These findings are suggesting that besides hemolysis cholestasis and hepatocellular injury are important factors causing malarial hepatitis with predominantly conjugated hyperbilirubinemia. Shah et al. observed that jaundice in PF malaria is not because of hepatitis but maybe because of suppression of bilirubin excretion and they named it “Malarial hepatopathy.”{Table 2}

In this study, we observed that many patients of malaria with jaundice had a significant higher level of aspartate transaminase (AST) and alanine transaminase (ALT). Lowest AST level on starting study in patients of malaria with jaundice was 2.1 IU/L, whereas highest level was 5.32 IU/L. ALT level range between 22 and 488 lU/L. Chawla et al.[13] observed similar findings having AST and ALT level in the range of 100–300 lU/L. In this study, we observed that patients of malarial hepatic and/or renal dysfunction had increased serum alkaline phosphatase with their increased serum bilirubin level. The range of serum alkaline phosphatase in patients of malaria with jaundice was 60–280 lU/L. In our study 80% patients had >110 lU/L. Mishra et al[14] shows that increased serum Bilirubin, AST, ALT, and serum alkaline phosphatase were also increased in 30% of total complicated falciparum malaria patients.

The overall prevalence of renal failure in PF is reported to vary from 1% to 60%.[15] Tran[16] reported that approximately 50% of patients of malaria had biochemical evidence of renal involvement (serum creatinine >2 mg/dl), but only 30% fulfilled the WHO criteria of acute renal failure. In our study, acute renal failure was present in 30% of the cases of malaria who were admitted in the hospital with hepatic or renal dysfunction. In our study, we found that 11 (36.7%) of the cases having renal failure were due to PF, 13 (43.3%) were due to PV, and 6 (20%) cases had a mixed infection. Our study reveals that, in 24 (100%) cases of PF patients, 13 patients had liver dysfunction, 2 patients had renal dysfunction and 9 patients had combined liver and renal dysfunction [Table 3]. In 12 cases of Mixed (PV/PF) patients, 6 patients had liver dysfunction, 1 patients had renal dysfunction and 5 patients had combined liver and renal dysfunction. These findings were statistically significant (P = 0.018). Kumar et al.[17] reported that PF was responsible for 80.9 cases of renal failure in malaria whereas PV was responsible for 11.7%.{Table 3}

This study shows that all thirty cases who had renal dysfunction also had hyperkalemia (100%), hyponatremia found in 21 (70%), and hypematremia in 9 (30%) cases with only hepatic dysfunction had hypokalemia in 8 out of 70 (11.2%) and hyponatremia in 9 (12.8%) cases. Acute renal failure in malaria is usually oliguric or anuric, but urine output may be normal or increased. In our study, table shows the out of 30 patients of renal failure, only 13 (43.3%) were oliguric or anuric whereas 17 (56.7%) were having normal urine output. Stone et al.[18] in contrast reported oliguric renal failure in 36 out of 42 (85.71%) patients and only 6 (14.28%) were nonoliguric. This study supports our observations. Probably, etiopathogenesis of acute failure (ARF) was multifactorial. Our study shows that 92 (95.8%) out of 95 survived patients recovered within 10 days of malarial hepatorenal dysfunction, whereas only 3 (3.2%) had symptoms for more than 10 days after hospitalization and 5 were expired during treatment. Stone et al.[18] also found that average duration of symptoms after admission was 8 days. Our study shows out of 100 patients who presented with hepatic dysfunction, 5 patients died, all who died had serum bilirubin >10 mg%. All expired patients had both hepatic and renal dysfunction. Hence, mortality was more ([62.5%] 5/8) in combined hepatic and renal dysfunction having serum bilirubin level >10 mg. The overall mortality in our study of patients with malarial hepatic and/or renal dysfunction was 5%. In the present study, multiorgan involvement and pulmonary edema were found to be common of death. SitprijaV et al.[19] in their study of 163 malarial patients found that the major mortalities were multiorgan dysfunction in 12 (57, 14%), pulmonary edema in 6, ARDS in 2 (9.52%), and 1 patient died of massive upper gastrointestinal bleeding supports our study.

Hepatic and renal dysfunction in patients of malaria is usually associated with poor prognosis, severe anemia, hypotension, and bleeding manifestations' electrolyte in balance and increased mortality. Most common cause of mortality is multiorgan dysfunction. Our study reveals that 20 out of 100 had combined hepatic and renal dysfunction and 70 had hepatic and 10 had renal dysfunction alone. PF commonly associated with multiorgan failure as compared to PV. In 24 PF patients, 9 (37.5%) Patients had combined hepatic and renalfailure. It presents with isolated hepatic or renal dysfunction out of 64 patients, 58 (90.62%) had either hepatic or renal dysfunction and only 6 patients (9.38%) had combined hepatic and renal dysfunction. Our study reveals the incidence of renal dysfunction higher in patients with increased serum bilirubin level. As all 8% of cases had serum bilirubin >10 mg% also had renal dysfunction, whereas only 12 (15%) out of 82 cases had renal dysfunction with serum bilirubin level 3–10.

 Conclusion



In spite of high prevalence of hepatorenal dysfunction in malaria, it is not reported earlier due to lack of awareness among health-care providers as lack of rapid and sensitive diagnostic facilities. The specific reason for presenting our observation is to develop awareness regarding the early complications of malaria and to prevent them prompt action can be taken. Early diagnosis of ARF and intervention in participants who have hepatic dysfunction in malaria can save many lives. In the light of our study, further studies can commend with larger sample size to see the association of hepatic and renal dysfunction in India.

Limitations of study

Our study does not reflect the true prevalence of PF and PV malaria in the community as most of our patients were from Bikaner and others were serious and complicated cases referred from primary health centers situated in rural areas with semi-developed medical facilities.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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