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Complications and mortality patterns due to Plasmodium falciparum malaria in hospitalized adults and children, Rourkela, Orissa, India
T R A N S A C T I O N S O F T H E R O Y A L S O C I E T Y OF T R O P I C A L M E D I C I N E A N D H Y G I E N E (2003) 97, 6 9 - 7 0
Complications and mortality patterns due to Plasmodium falciparum malaria in hospitalized adults and children, Rourkela, Orissa, India Sanjib Mohanty, Saroj K. Mishra, Sudhansu S. Pati, Jayakrushna Pattnaik and Bhabani S. Das General Hospital, Rourkela 769005, Orissa, India
Ispat
Abstract Of 1857 Plasmodiumfalciparum malaria patients hospitalized from 1995 to 1998, 608 had severe malaria and 83 died. Acute renal failure, jaundice and respiratory distress were common in adults whereas children frequently had severe anaemia. Cerebral malaria occurred equally in adults and children but recovery from coma was quicker in children. Multiple complications caused high mortality in adults.
Keywords" malaria, Plasmodiumfalciparum, epidemiology, clinical study, India Introduction The severity and clinical presentation of Plasmodium falciparum malaria depend on the age of the patient, intensity of transmission and development of immunity. In high transmission areas like sub-Saharan Africa children bear the brunt of the disease, with high mortality. In areas of seasonal and low transmission, mortality rates increase with age. However, this phenomenon is not uniform and documentation of the clinical spectrum of malaria from different geographical areas is required. Traditional malariometric indices mostly focus on parasitaemia. Community-based studies of the clinical features would be an ideal way to study the disease, but as they are almost impossible in developing countries hospital-based studies could provide a viable alternative. Nearly 40% of P. falciparum malaria cases and 50% of the related deaths in India occur in Orissa, but there is a paucity of clinical data. We undertook this study to analyse the clinical pattems of P. falciparum malaria in adults and children in Orissa, India.
Subjects and Methods The study was carried out at Ispat General Hospital (IGH), a 700-bed referral hospital in Rourkela, Sundergarh district of Orissa, India. The area includes undulating uplands, intersected by forested hills, rocky streams, rivers, paddy fields and springs, having a subhumid to savannah type climate with an annual rainfall of 200 cm. Malaria transmission occurs throughout the year but peaks during September to December, immediately after the rains. Admission criteria included: (i) patients with features of severe malaria (WHO, 1990)--cerebral malaria (unrousable coma), severe anaemia (haemoglobin < 5 g/dL), renal failure (serum creatinine > 3 mg/dL), adult respiratory distress syndrome, hypoglycaemia (glucose < 40 mg/dL), circulatory collapse or shock, disseminated intravascular coagulation (DIC), repeated generalized convulsions, acidosis (pH < 7.25), macroscopic haemoglobinuria, hyperparasitaemia (> 5% erythrocytes infected by parasites), or jaundice (bilirubin > 3 mg/dL); and (ii) malaria patients unable to retain or not responding to oral antimalarials. All the patients were symptomatic and had malaria. Pregnant women were excluded from the study.
Results From 1995 to 1998, 1857 patients were admitted to I G H with confirmed P. falciparum malaria; 427 (23%) were children aged < 15 years). Nearly all of the study patients (98%) were febrile throughout their illness and other presenting complaints were vomiting (51%), headache (31%) and diarrhoea (14.5%), which were Address for correspondence: Dr Saroj K. Mishra, Senior Deputy Director (M&HS), Ispat General Hospital, F-139, Sector-19, Rourkela 769005, Orissa, India; e-mail mami@ vsnl.com or [email protected]
observed in equal frequency in both adults and children. Hepatomegaly and splenomegaly occurred more frequently in children (57% vs. 42% and 76% vs. 61%, respectively). The duration of illness before hospitalization was similar ( m e d i a n - 4 d, range 1-30 d). The complications observed in 608 patients who had features of severe malaria are shown in the Table. Cerebral malaria was observed equally in both adults and children (P = 0.313). Median time to recovery from coma was faster in children (24 [range 6-120] h) than in adults (44 [range 4-192] h) and deaths in children were significantly less common. Seizures and severe anaemia were common in children. Multiple complications were more common in adults: cerebral malaria with jaundice was seen in 108 adults and 11 children. Cerebral malaria with acute renal failure occurred in 61 adults but only one child, an 11-year-old boy who also had severe anaemia; he recovered without dialysis. Eighty-three patients died, of whom 90% were adults. Cerebral malaria was the cause of death in all the children, two had associated severe anaemia and one had jaundice. However, five adults without cerebral malaria died: an 18-year-old male with jaundice, hypoglycaemia and acute renal failure; a 27-year-old male with severe anaemia, DIC and gastrointestinal bleeding; a 47-year-old male with severe anaemia; and two males aged 65 years and 41 years with respiratory distress. Mortality from cerebral malaria increased from 7% to 33% when associated with multiple complications. Adults had a higher mortality rate due to the presence of multiple complications (relative risk = 2.8, 95% confidence interval 1.36-5.76).
Discussion In areas of intense transmission, severe anaemia occurs more often in children resulting in death, while adults rarely suffer from the disease. In low transmission areas like Myanmar, adults suffer from cerebral malaria while children are vulnerable to severe anaemia, but not to cerebral malaria. (Greenwood et al., 1987; Molyneux et al., 1989; Brewster & Greenwood, 1993; Marsh et al., 1995; Ejov et al., 1999). The present study showed that children were equally vulnerable to cerebral malaria. However, they had a faster recovery time from coma and low mortality. Though the incidence of severe anaemia was high in children in our study, it was not in itself a cause of death, possibly due to prompt and adequate blood transfusion (Mishra et al., 1999). Jaundice was common in adults, but it did not correlate with the severity of anaemia, hence there might be a component of hepatic dysfunction (Mishra et al., 1992). Since our previous study (Das et al., 1988), quinine has been infused with dextrose or dextrose saline and so hypoglycaemia is encountered infrequently. Acute renal failure is rare amongst children in both high and low transmission areas and our study confirmed this observation.
S. MOHANTY ETAL.
70
Table. Complications observed in hospitalized Plasmodiumfalciparum patients, Rourkela, India, 1995-98
Complication"
Total (n = 608) n (%)
Cerebral malaria Convulsions Acute renal failure Severe anaemia Jaundice Hypoglycaemia Respiratory distress Death
314 107 85 124 269 19 45 83
(52) (18) (14) (20) (44) (3) (7) (14)
Children (n = 156) n (%) 86 58 1 57 21 5 4 8
(55) (37) (1) (37) (13) (3) (3) (5)
Adults (n = 452) pb
n (% )
228 49 84 67 248 14 41 75
(50) (11) (19) (15) (55) (3) (9) (17)
< < < <
NS 0.0001 0.0001 0.0001 0.0001 NS 0.007 0.0003
aFor criteria of different complications see WHO (1990) and text. bX2 test; NS, not significant.
Acknowledgements We are grateful to Prof. B. M. Greenwood, Dr D. N. Mohapatra, (Director, IGH), Dr V. P. Sharma, and Dr S. Pattanayak for their interest. S. K. M. expresses his sincere thanks to the Wellcome Trust for a travel grant to attend and present part of this work at the Oxford-2000 meeting held at the University of Oxford, UK, 18-22 September 2000.
References Brewster, D. & Greenwood, B. M. (1993). Seasonal variation of paediatric diseases in The Gambia, West Africa. Annals of TropicalPaediatrics, 13, 133-146. Das, B. S., Satpathy, S. K., Mohanty, D., Mohanty, S., Mishra, S. K., Satpathy, P. C., Pamaik, J. K. & Bose, T. K. (1988). Hypoglycaemia in severe falciparum malaria. Trans-
actions of the Royal Society of Tropical Medicine and Hygiene, 82, 197-201. Ejov, M. N., Tun, T., Aung, S., Lwin, S. & Sein, K. (1999). Hospital-based study of severe malaria and associated deaths in Myanmar. Bulletin of the World Health Organization, 77, 310-314. Greenwood, B. M., Bradley, A. K., Greenwood, A. M., Byass, P., Jammeh, K., Marsh, K., Tulloch, S., Oldfield, F. S. ]~. & Hayes, R. (1987), Mortality and morbidity from malaria among children in a rural area of The Gambia, West Africa.
Book Review Cestode Zoonoses: Echinococcosis and Cysticercosis. An Emergent and Global Problem. Nato Science Series, Series 1: Life and Behavioural Sciences, Volume 341. P. Craig & Z. Pawlowski (editors). A m sterdam: IOS Press, 2002. xiii + 395 pp. Price 4100 (about £60.00). I S B N 1-58603-220-8. I S S N 15667693. This book has arisen from presentations at an Advanced Research Workshop in Poznafl, Poland in September 2000, that brought together 59 experts from 28 countries with the aim of reviewing and updating a wide range of topics covering the increasingly recognized public health problems associated with h u m a n and animal infection with Taenia solium, Echinococeus granulosus and E. multilocularis. T h e r e were four sessions: disease status, re-emergence and spread; tools and methods for diagnosis; transmission and epidemiology, wildlife ecology and transmission of Echinocoecus; and approaches to control. Each section of the book contains a series of papers based on presentations. Collectively, this publication is an extremely valuable
Transactions of the Royal Society of Tropical Medicine and Hygiene, 81, 478-486. Marsh, K., Forster, D., Waruiru, C., Mwangi, I., Winstanley, M., Marsh, V., Newton, C., Winstanley, P., Warn, P., Peshu, N., Pasvol, G. & Snow, R. (1995). Indicators of life threatening malaria in African children. New England Journal of Medicine, 332, 1399-1404. Mishra, S. K., Mohanty, S., Das, B. S., Pamaik, J. K., Satpathy, S. K., Mohanty, D. & Bose, T. K. (1992). Hepatic changes in P. falciparum malaria. Indian Journal of Malariology, 29,167-171. Mishra S. K., Satpathy, S. K. & Mohanty, S. (1999). Survey of malaria treatment and deaths. Bulletin of the World Health Organization, 77, 1020. Molyneux, M. E., Taylor, T. E., Wirima, J. J. & Borgstein, A. (1989). Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Quarterlyffournal of Medicine, 71, 441-459. WHO (1990). Severe and complicated malaria, 2nd edition.
Transactions of the Royal Society of Tropical Medicine and Hygiene, 84, supplement 2. Received 3 May 2002; revised 19 August 2002; accepted for publication 21 August 2002
addition to the literature, as the papers identify the current status of different areas of research, supported by summaries of results. References are often comprehensive and key gaps in knowledge are routinely identified. This approach, together with the basic background information m a n y of the papers include, means that all those interested in this area, no matter how inexperienced, can gain benefit. T h e first session particularly identifies some of the problems in the quality of data currently available and a key message is the need for further carefully controlled and, where possible, coordinated studies. T h o s e readers who use the publication extensively will have to c o m e to terms with the fact that it will win few prizes for publication quality, littered as some parts are with grammatical and editorial errors. Nonetheless, this should not detract from its usefulness as an important resource.
Ian Marshall Department of Parasitology Liverpool School of Tropical Medicine Pembroke Place Liverpool L3 5QA, UK
Complications and mortality patterns due to Plasmodium falciparum malaria in hospitalized adults and children, Rourkela, Orissa, India Sanjib Mohanty, Saroj K. Mishra, Sudhansu S. Pati, Jayakrushna Pattnaik and Bhabani S. Das General Hospital, Rourkela 769005, Orissa, India
Ispat
Abstract Of 1857 Plasmodiumfalciparum malaria patients hospitalized from 1995 to 1998, 608 had severe malaria and 83 died. Acute renal failure, jaundice and respiratory distress were common in adults whereas children frequently had severe anaemia. Cerebral malaria occurred equally in adults and children but recovery from coma was quicker in children. Multiple complications caused high mortality in adults.
Keywords" malaria, Plasmodiumfalciparum, epidemiology, clinical study, India Introduction The severity and clinical presentation of Plasmodium falciparum malaria depend on the age of the patient, intensity of transmission and development of immunity. In high transmission areas like sub-Saharan Africa children bear the brunt of the disease, with high mortality. In areas of seasonal and low transmission, mortality rates increase with age. However, this phenomenon is not uniform and documentation of the clinical spectrum of malaria from different geographical areas is required. Traditional malariometric indices mostly focus on parasitaemia. Community-based studies of the clinical features would be an ideal way to study the disease, but as they are almost impossible in developing countries hospital-based studies could provide a viable alternative. Nearly 40% of P. falciparum malaria cases and 50% of the related deaths in India occur in Orissa, but there is a paucity of clinical data. We undertook this study to analyse the clinical pattems of P. falciparum malaria in adults and children in Orissa, India.
Subjects and Methods The study was carried out at Ispat General Hospital (IGH), a 700-bed referral hospital in Rourkela, Sundergarh district of Orissa, India. The area includes undulating uplands, intersected by forested hills, rocky streams, rivers, paddy fields and springs, having a subhumid to savannah type climate with an annual rainfall of 200 cm. Malaria transmission occurs throughout the year but peaks during September to December, immediately after the rains. Admission criteria included: (i) patients with features of severe malaria (WHO, 1990)--cerebral malaria (unrousable coma), severe anaemia (haemoglobin < 5 g/dL), renal failure (serum creatinine > 3 mg/dL), adult respiratory distress syndrome, hypoglycaemia (glucose < 40 mg/dL), circulatory collapse or shock, disseminated intravascular coagulation (DIC), repeated generalized convulsions, acidosis (pH < 7.25), macroscopic haemoglobinuria, hyperparasitaemia (> 5% erythrocytes infected by parasites), or jaundice (bilirubin > 3 mg/dL); and (ii) malaria patients unable to retain or not responding to oral antimalarials. All the patients were symptomatic and had malaria. Pregnant women were excluded from the study.
Results From 1995 to 1998, 1857 patients were admitted to I G H with confirmed P. falciparum malaria; 427 (23%) were children aged < 15 years). Nearly all of the study patients (98%) were febrile throughout their illness and other presenting complaints were vomiting (51%), headache (31%) and diarrhoea (14.5%), which were Address for correspondence: Dr Saroj K. Mishra, Senior Deputy Director (M&HS), Ispat General Hospital, F-139, Sector-19, Rourkela 769005, Orissa, India; e-mail mami@ vsnl.com or [email protected]
observed in equal frequency in both adults and children. Hepatomegaly and splenomegaly occurred more frequently in children (57% vs. 42% and 76% vs. 61%, respectively). The duration of illness before hospitalization was similar ( m e d i a n - 4 d, range 1-30 d). The complications observed in 608 patients who had features of severe malaria are shown in the Table. Cerebral malaria was observed equally in both adults and children (P = 0.313). Median time to recovery from coma was faster in children (24 [range 6-120] h) than in adults (44 [range 4-192] h) and deaths in children were significantly less common. Seizures and severe anaemia were common in children. Multiple complications were more common in adults: cerebral malaria with jaundice was seen in 108 adults and 11 children. Cerebral malaria with acute renal failure occurred in 61 adults but only one child, an 11-year-old boy who also had severe anaemia; he recovered without dialysis. Eighty-three patients died, of whom 90% were adults. Cerebral malaria was the cause of death in all the children, two had associated severe anaemia and one had jaundice. However, five adults without cerebral malaria died: an 18-year-old male with jaundice, hypoglycaemia and acute renal failure; a 27-year-old male with severe anaemia, DIC and gastrointestinal bleeding; a 47-year-old male with severe anaemia; and two males aged 65 years and 41 years with respiratory distress. Mortality from cerebral malaria increased from 7% to 33% when associated with multiple complications. Adults had a higher mortality rate due to the presence of multiple complications (relative risk = 2.8, 95% confidence interval 1.36-5.76).
Discussion In areas of intense transmission, severe anaemia occurs more often in children resulting in death, while adults rarely suffer from the disease. In low transmission areas like Myanmar, adults suffer from cerebral malaria while children are vulnerable to severe anaemia, but not to cerebral malaria. (Greenwood et al., 1987; Molyneux et al., 1989; Brewster & Greenwood, 1993; Marsh et al., 1995; Ejov et al., 1999). The present study showed that children were equally vulnerable to cerebral malaria. However, they had a faster recovery time from coma and low mortality. Though the incidence of severe anaemia was high in children in our study, it was not in itself a cause of death, possibly due to prompt and adequate blood transfusion (Mishra et al., 1999). Jaundice was common in adults, but it did not correlate with the severity of anaemia, hence there might be a component of hepatic dysfunction (Mishra et al., 1992). Since our previous study (Das et al., 1988), quinine has been infused with dextrose or dextrose saline and so hypoglycaemia is encountered infrequently. Acute renal failure is rare amongst children in both high and low transmission areas and our study confirmed this observation.
S. MOHANTY ETAL.
70
Table. Complications observed in hospitalized Plasmodiumfalciparum patients, Rourkela, India, 1995-98
Complication"
Total (n = 608) n (%)
Cerebral malaria Convulsions Acute renal failure Severe anaemia Jaundice Hypoglycaemia Respiratory distress Death
314 107 85 124 269 19 45 83
(52) (18) (14) (20) (44) (3) (7) (14)
Children (n = 156) n (%) 86 58 1 57 21 5 4 8
(55) (37) (1) (37) (13) (3) (3) (5)
Adults (n = 452) pb
n (% )
228 49 84 67 248 14 41 75
(50) (11) (19) (15) (55) (3) (9) (17)
< < < <
NS 0.0001 0.0001 0.0001 0.0001 NS 0.007 0.0003
aFor criteria of different complications see WHO (1990) and text. bX2 test; NS, not significant.
Acknowledgements We are grateful to Prof. B. M. Greenwood, Dr D. N. Mohapatra, (Director, IGH), Dr V. P. Sharma, and Dr S. Pattanayak for their interest. S. K. M. expresses his sincere thanks to the Wellcome Trust for a travel grant to attend and present part of this work at the Oxford-2000 meeting held at the University of Oxford, UK, 18-22 September 2000.
References Brewster, D. & Greenwood, B. M. (1993). Seasonal variation of paediatric diseases in The Gambia, West Africa. Annals of TropicalPaediatrics, 13, 133-146. Das, B. S., Satpathy, S. K., Mohanty, D., Mohanty, S., Mishra, S. K., Satpathy, P. C., Pamaik, J. K. & Bose, T. K. (1988). Hypoglycaemia in severe falciparum malaria. Trans-
actions of the Royal Society of Tropical Medicine and Hygiene, 82, 197-201. Ejov, M. N., Tun, T., Aung, S., Lwin, S. & Sein, K. (1999). Hospital-based study of severe malaria and associated deaths in Myanmar. Bulletin of the World Health Organization, 77, 310-314. Greenwood, B. M., Bradley, A. K., Greenwood, A. M., Byass, P., Jammeh, K., Marsh, K., Tulloch, S., Oldfield, F. S. ]~. & Hayes, R. (1987), Mortality and morbidity from malaria among children in a rural area of The Gambia, West Africa.
Book Review Cestode Zoonoses: Echinococcosis and Cysticercosis. An Emergent and Global Problem. Nato Science Series, Series 1: Life and Behavioural Sciences, Volume 341. P. Craig & Z. Pawlowski (editors). A m sterdam: IOS Press, 2002. xiii + 395 pp. Price 4100 (about £60.00). I S B N 1-58603-220-8. I S S N 15667693. This book has arisen from presentations at an Advanced Research Workshop in Poznafl, Poland in September 2000, that brought together 59 experts from 28 countries with the aim of reviewing and updating a wide range of topics covering the increasingly recognized public health problems associated with h u m a n and animal infection with Taenia solium, Echinococeus granulosus and E. multilocularis. T h e r e were four sessions: disease status, re-emergence and spread; tools and methods for diagnosis; transmission and epidemiology, wildlife ecology and transmission of Echinocoecus; and approaches to control. Each section of the book contains a series of papers based on presentations. Collectively, this publication is an extremely valuable
Transactions of the Royal Society of Tropical Medicine and Hygiene, 81, 478-486. Marsh, K., Forster, D., Waruiru, C., Mwangi, I., Winstanley, M., Marsh, V., Newton, C., Winstanley, P., Warn, P., Peshu, N., Pasvol, G. & Snow, R. (1995). Indicators of life threatening malaria in African children. New England Journal of Medicine, 332, 1399-1404. Mishra, S. K., Mohanty, S., Das, B. S., Pamaik, J. K., Satpathy, S. K., Mohanty, D. & Bose, T. K. (1992). Hepatic changes in P. falciparum malaria. Indian Journal of Malariology, 29,167-171. Mishra S. K., Satpathy, S. K. & Mohanty, S. (1999). Survey of malaria treatment and deaths. Bulletin of the World Health Organization, 77, 1020. Molyneux, M. E., Taylor, T. E., Wirima, J. J. & Borgstein, A. (1989). Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Quarterlyffournal of Medicine, 71, 441-459. WHO (1990). Severe and complicated malaria, 2nd edition.
Transactions of the Royal Society of Tropical Medicine and Hygiene, 84, supplement 2. Received 3 May 2002; revised 19 August 2002; accepted for publication 21 August 2002
addition to the literature, as the papers identify the current status of different areas of research, supported by summaries of results. References are often comprehensive and key gaps in knowledge are routinely identified. This approach, together with the basic background information m a n y of the papers include, means that all those interested in this area, no matter how inexperienced, can gain benefit. T h e first session particularly identifies some of the problems in the quality of data currently available and a key message is the need for further carefully controlled and, where possible, coordinated studies. T h o s e readers who use the publication extensively will have to c o m e to terms with the fact that it will win few prizes for publication quality, littered as some parts are with grammatical and editorial errors. Nonetheless, this should not detract from its usefulness as an important resource.
Ian Marshall Department of Parasitology Liverpool School of Tropical Medicine Pembroke Place Liverpool L3 5QA, UK