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Published in: Malaria Journal 1/2020

Open Access 01-12-2020 | Malaria | Research

Defining symptoms of malaria in India in an era of asymptomatic infections

Authors: Anna Maria van Eijk, Asad S. Mannan, Steven A. Sullivan, Jane M. Carlton

Published in: Malaria Journal | Issue 1/2020

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Abstract

Background

Malaria is a major public health problem in India. Data from surveys totaling 3031 participants at three sites revealed a high proportion of asymptomatic infections, complicating diagnosis. The aim of this study was to identify differences in complaints and symptoms between sites, and factors associated with asymptomatic Plasmodium infections.

Methods

Published data from community-based cross-sectional studies conducted between 2012 and 2015 in Nadiad (Gujarat), Chennai (Tamil Nadu), and Rourkela (Odisha) as part of the Center for the Study of Complex Malaria in India were analysed. Complaints and symptoms were systematically recorded, and Plasmodium infections confirmed using microscopy, rapid diagnostic tests (RDTs), and polymerase chain reaction (PCR). Multivariate analyses were conducted to determine the association between general symptoms and age, season, or gender, and factors associated with asymptomatic Plasmodium infections were assessed.

Results

Complaints of any illness were lowest in Chennai (17.7%), 30.6% in Rourkela and 42.7% in Nadiad. Complaints were more often reported for children; gender differences were noted in Rourkela only. In Nadiad, 7.0% of 796 participants were positive for malaria by PCR (32% Plasmodium falciparum); 78.6% had a history of fever or documented fever, 14.3% had other symptoms, and 7.1% were “truly asymptomatic”. For Chennai this was 29.2%, 4.2% and 66.7% respectively, with a malaria prevalence of 2.6% by PCR of 928 participants (29% P. falciparum). In Rourkela, with 7.7% of 1307 participants positive for malaria by PCR (82% P. falciparum), the percentages were 35.6%, 24.8% and 39.6%, respectively. In Rourkela, asymptomatic infections were associated with young age and male gender (microscopy or RDT), and with rainy season (PCR). In the same site, participants with Plasmodium vivax were more likely to be asymptomatic (11/18 or 61.1%) than persons with P. falciparum mono-infections (27/78 or 34.6%); gametocytes for P. falciparum were evenly distributed between symptomatic and asymptomatic infections (2/53 vs. 2/49, respectively). The addition of the symptoms “headache”, “aches” and “chills” to fever improved the case-definition of symptomatic malaria.

Conclusion

There were considerable differences in complaints at the three sites in India. Malaria and asymptomatic infections differ by region, indicating that malaria elimination will require localized approaches.
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Literature
1.
go back to reference National Vector Borne Disease Control Programme, Directorate general of Health Services, Ministry of Health and Family Welfare. Malaria, magnitude of the problem. 2018. https://nvbdcp.gov.in. Accessed 22 Jan 2019. National Vector Borne Disease Control Programme, Directorate general of Health Services, Ministry of Health and Family Welfare. Malaria, magnitude of the problem. 2018. https://​nvbdcp.​gov.​in. Accessed 22 Jan 2019.
3.
go back to reference Das A, Anvikar AR, Cator LJ, Dhiman RC, Eapen A, Mishra N, et al. Malaria in India: the center for the study of complex malaria in India. Acta Trop. 2012;121:267–73.CrossRef Das A, Anvikar AR, Cator LJ, Dhiman RC, Eapen A, Mishra N, et al. Malaria in India: the center for the study of complex malaria in India. Acta Trop. 2012;121:267–73.CrossRef
4.
go back to reference Dash AP, Valecha N, Anvikar AR, Kumar A. Malaria in India: challenges and opportunities. J Biosci. 2008;33:583–92.CrossRef Dash AP, Valecha N, Anvikar AR, Kumar A. Malaria in India: challenges and opportunities. J Biosci. 2008;33:583–92.CrossRef
5.
go back to reference Directorate of National Vector Borne Disease Control Programme, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India. National framework for malaria elimination in India 2016–2030. New Delhi, India, 2016. https://apps.who.int/iris/handle/10665/246096. Accessed 22 Jan 2019. Directorate of National Vector Borne Disease Control Programme, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India. National framework for malaria elimination in India 2016–2030. New Delhi, India, 2016. https://​apps.​who.​int/​iris/​handle/​10665/​246096. Accessed 22 Jan 2019.
6.
go back to reference Chandramohan D, Carneiro I, Kavishwar A, Brugha R, Desai V, Greenwood B. A clinical algorithm for the diagnosis of malaria: results of an evaluation in an area of low endemicity. Trop Med Int Health. 2001;6:505–10.CrossRef Chandramohan D, Carneiro I, Kavishwar A, Brugha R, Desai V, Greenwood B. A clinical algorithm for the diagnosis of malaria: results of an evaluation in an area of low endemicity. Trop Med Int Health. 2001;6:505–10.CrossRef
7.
go back to reference Ndyomugyenyi R, Magnussen P, Clarke S. Diagnosis and treatment of malaria in peripheral health facilities in Uganda: findings from an area of low transmission in south-western Uganda. Malar J. 2007;6:39.CrossRef Ndyomugyenyi R, Magnussen P, Clarke S. Diagnosis and treatment of malaria in peripheral health facilities in Uganda: findings from an area of low transmission in south-western Uganda. Malar J. 2007;6:39.CrossRef
8.
go back to reference Chandramohan D, Jaffar S, Greenwood B. Use of clinical algorithms for diagnosing malaria. Trop Med Int Health. 2002;7:45–52.CrossRef Chandramohan D, Jaffar S, Greenwood B. Use of clinical algorithms for diagnosing malaria. Trop Med Int Health. 2002;7:45–52.CrossRef
9.
go back to reference Savargaonkar D, Sinha S, Srivastava B, Nagpal BN, Sinha A, Shamim A, et al. An epidemiological study of dengue and its coinfections in Delhi. Int J Infect Dis. 2018;74:41–6.CrossRef Savargaonkar D, Sinha S, Srivastava B, Nagpal BN, Sinha A, Shamim A, et al. An epidemiological study of dengue and its coinfections in Delhi. Int J Infect Dis. 2018;74:41–6.CrossRef
10.
go back to reference Dass R, Barman H, Duwarah SG, Deka NM, Jain P, Choudhury V. Unusual presentations of malaria in children: an experience from a tertiary care center in North East India. Indian J Pediatr. 2010;77:655–60.CrossRef Dass R, Barman H, Duwarah SG, Deka NM, Jain P, Choudhury V. Unusual presentations of malaria in children: an experience from a tertiary care center in North East India. Indian J Pediatr. 2010;77:655–60.CrossRef
11.
go back to reference Rao PN, van Eijk AM, Choubey S, Ali SZ, Dash A, Barla P, et al. Dengue, chikungunya, and scrub typhus are important etiologies of non-malarial febrile illness in Rourkela, Odisha, India. BMC Infect Dis. 2019;19:572.CrossRef Rao PN, van Eijk AM, Choubey S, Ali SZ, Dash A, Barla P, et al. Dengue, chikungunya, and scrub typhus are important etiologies of non-malarial febrile illness in Rourkela, Odisha, India. BMC Infect Dis. 2019;19:572.CrossRef
12.
go back to reference Okell LC, Ghani AC, Lyons E, Drakeley CJ. Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. J Infect Dis. 2009;200:1509–17.CrossRef Okell LC, Ghani AC, Lyons E, Drakeley CJ. Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. J Infect Dis. 2009;200:1509–17.CrossRef
13.
go back to reference Okell LC, Bousema T, Griffin JT, Ouedraogo AL, Ghani AC, Drakeley CJ. Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat Commun. 2012;3:1237.CrossRef Okell LC, Bousema T, Griffin JT, Ouedraogo AL, Ghani AC, Drakeley CJ. Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat Commun. 2012;3:1237.CrossRef
14.
go back to reference Bousema T, Okell L, Felger I, Drakeley C. Asymptomatic malaria infections: detectability, transmissibility and public health relevance. Nat Rev Microbiol. 2014;12:833–40.CrossRef Bousema T, Okell L, Felger I, Drakeley C. Asymptomatic malaria infections: detectability, transmissibility and public health relevance. Nat Rev Microbiol. 2014;12:833–40.CrossRef
15.
go back to reference de Mast Q, Brouwers J, Syafruddin D, Bousema T, Baidjoe AY, de Groot PG, et al. Is asymptomatic malaria really asymptomatic? Hematological, vascular and inflammatory effects of asymptomatic malaria parasitemia. J Infect. 2015;71:587–96.CrossRef de Mast Q, Brouwers J, Syafruddin D, Bousema T, Baidjoe AY, de Groot PG, et al. Is asymptomatic malaria really asymptomatic? Hematological, vascular and inflammatory effects of asymptomatic malaria parasitemia. J Infect. 2015;71:587–96.CrossRef
16.
go back to reference Chen I, Clarke SE, Gosling R, Hamainza B, Killeen G, Magill A, et al. “Asymptomatic” malaria: a chronic and debilitating infection that should be treated. PLoS Med. 2016;13:e1001942.CrossRef Chen I, Clarke SE, Gosling R, Hamainza B, Killeen G, Magill A, et al. “Asymptomatic” malaria: a chronic and debilitating infection that should be treated. PLoS Med. 2016;13:e1001942.CrossRef
17.
go back to reference Kauhl B, Pilot E, Rao R, Gruebner O, Schweikart J, Krafft T. Estimating the spatial distribution of acute undifferentiated fever (AUF) and associated risk factors using emergency call data in India. A symptom-based approach for public health surveillance. Health Place. 2015;31:111–9.CrossRef Kauhl B, Pilot E, Rao R, Gruebner O, Schweikart J, Krafft T. Estimating the spatial distribution of acute undifferentiated fever (AUF) and associated risk factors using emergency call data in India. A symptom-based approach for public health surveillance. Health Place. 2015;31:111–9.CrossRef
18.
go back to reference van Eijk AM, Sutton PL, Ramanathapuram L, Sullivan SA, Kanagaraj D, Priya GSL, et al. The burden of submicroscopic and asymptomatic malaria in India revealed from epidemiology studies at three varied transmission sites in India. Sci Rep. 2019;9:17095.CrossRef van Eijk AM, Sutton PL, Ramanathapuram L, Sullivan SA, Kanagaraj D, Priya GSL, et al. The burden of submicroscopic and asymptomatic malaria in India revealed from epidemiology studies at three varied transmission sites in India. Sci Rep. 2019;9:17095.CrossRef
19.
go back to reference van Eijk AM, Ramanathapuram L, Sutton PL, Peddy N, Choubey S, Mohanty S, et al. The use of mosquito repellents at three sites in India with declining malaria transmission: surveys in the community and clinic. Parasit Vectors. 2016;9:418.CrossRef van Eijk AM, Ramanathapuram L, Sutton PL, Peddy N, Choubey S, Mohanty S, et al. The use of mosquito repellents at three sites in India with declining malaria transmission: surveys in the community and clinic. Parasit Vectors. 2016;9:418.CrossRef
20.
go back to reference Attri SD, Tyagi A. Climate profile of India. New Delhi: India Meterological Department, Ministry of Earth Sciences; 2010. Attri SD, Tyagi A. Climate profile of India. New Delhi: India Meterological Department, Ministry of Earth Sciences; 2010.
21.
go back to reference Anvikar AR, Arora U, Sonal GS, Mishra N, Shahi B, Savargaonkar D, et al. Antimalarial drug policy in India: past, present & future. Indian J Med Res. 2014;139:205–15.PubMedPubMedCentral Anvikar AR, Arora U, Sonal GS, Mishra N, Shahi B, Savargaonkar D, et al. Antimalarial drug policy in India: past, present & future. Indian J Med Res. 2014;139:205–15.PubMedPubMedCentral
22.
go back to reference Rubio JM, Benito A, Berzosa PJ, Roche J, Puente S, Subirats M, et al. Usefulness of seminested multiplex PCR in surveillance of imported malaria in Spain. J Clin Microbiol. 1999;37:3260–4.CrossRef Rubio JM, Benito A, Berzosa PJ, Roche J, Puente S, Subirats M, et al. Usefulness of seminested multiplex PCR in surveillance of imported malaria in Spain. J Clin Microbiol. 1999;37:3260–4.CrossRef
23.
go back to reference Rubio JM, Benito A, Roche J, Berzosa PJ, Garcia ML, Mico M, et al. Semi-nested, multiplex polymerase chain reaction for detection of human malaria parasites and evidence of Plasmodium vivax infection in Equatorial Guinea. Am J Trop Med Hyg. 1999;60:183–7.CrossRef Rubio JM, Benito A, Roche J, Berzosa PJ, Garcia ML, Mico M, et al. Semi-nested, multiplex polymerase chain reaction for detection of human malaria parasites and evidence of Plasmodium vivax infection in Equatorial Guinea. Am J Trop Med Hyg. 1999;60:183–7.CrossRef
24.
go back to reference Arnold F, Parasuraman S, Arokiasamy P, Kothari M. Nutrition in India. National Family Health Survey (NFHS-3) India 2005–06. Mumbai: International Institute for Population Sciences, ICF Macro; 2009. Arnold F, Parasuraman S, Arokiasamy P, Kothari M. Nutrition in India. National Family Health Survey (NFHS-3) India 2005–06. Mumbai: International Institute for Population Sciences, ICF Macro; 2009.
25.
go back to reference Cummings P. Methods for estimating adjusted risk ratios. Stata J. 2009;9:175–96.CrossRef Cummings P. Methods for estimating adjusted risk ratios. Stata J. 2009;9:175–96.CrossRef
26.
go back to reference Suswardany DL, Sibbritt DW, Supardi S, Chang S, Adams J. A critical review of traditional medicine and traditional healer use for malaria and among people in malaria-endemic areas: contemporary research in low to middle-income Asia-Pacific countries. Malar J. 2015;14:98.CrossRef Suswardany DL, Sibbritt DW, Supardi S, Chang S, Adams J. A critical review of traditional medicine and traditional healer use for malaria and among people in malaria-endemic areas: contemporary research in low to middle-income Asia-Pacific countries. Malar J. 2015;14:98.CrossRef
27.
go back to reference Lillie PJ, Duncan CJ, Sheehy SH, Meyer J, O’Hara GA, Gilbert SC, et al. Distinguishing malaria and influenza: early clinical features in controlled human experimental infection studies. Travel Med Infect Dis. 2012;10:192–6.CrossRef Lillie PJ, Duncan CJ, Sheehy SH, Meyer J, O’Hara GA, Gilbert SC, et al. Distinguishing malaria and influenza: early clinical features in controlled human experimental infection studies. Travel Med Infect Dis. 2012;10:192–6.CrossRef
28.
go back to reference Nguyen TN, von Seidlein L, Nguyen TV, Truong PN, Hung SD, Pham HT, et al. The persistence and oscillations of submicroscopic Plasmodium falciparum and Plasmodium vivax infections over time in Vietnam: an open cohort study. Lancet Infect Dis. 2018;18:565–72.CrossRef Nguyen TN, von Seidlein L, Nguyen TV, Truong PN, Hung SD, Pham HT, et al. The persistence and oscillations of submicroscopic Plasmodium falciparum and Plasmodium vivax infections over time in Vietnam: an open cohort study. Lancet Infect Dis. 2018;18:565–72.CrossRef
29.
go back to reference Baum E, Sattabongkot J, Sirichaisinthop J, Kiattibutr K, Jain A, Taghavian O, et al. Common asymptomatic and submicroscopic malaria infections in Western Thailand revealed in longitudinal molecular and serological studies: a challenge to malaria elimination. Malar J. 2016;15:333.CrossRef Baum E, Sattabongkot J, Sirichaisinthop J, Kiattibutr K, Jain A, Taghavian O, et al. Common asymptomatic and submicroscopic malaria infections in Western Thailand revealed in longitudinal molecular and serological studies: a challenge to malaria elimination. Malar J. 2016;15:333.CrossRef
30.
go back to reference Galatas B, Bassat Q, Mayor A. Malaria parasites in the asymptomatic: looking for the hay in the haystack. Trends Parasitol. 2016;32:296–308.CrossRef Galatas B, Bassat Q, Mayor A. Malaria parasites in the asymptomatic: looking for the hay in the haystack. Trends Parasitol. 2016;32:296–308.CrossRef
31.
go back to reference Pradhan A, Anasuya A, Pradhan MM, Ak K, Kar P, Sahoo KC, et al. Trends in malaria in Odisha, India-an analysis of the 2003–2013 time-series data from the National Vector Borne Disease Control Program. PLoS ONE. 2016;11:e0149126.CrossRef Pradhan A, Anasuya A, Pradhan MM, Ak K, Kar P, Sahoo KC, et al. Trends in malaria in Odisha, India-an analysis of the 2003–2013 time-series data from the National Vector Borne Disease Control Program. PLoS ONE. 2016;11:e0149126.CrossRef
32.
go back to reference Kumar DS, Andimuthu R, Rajan R, Venkatesan MS. Spatial trend, environmental and socioeconomic factors associated with malaria prevalence in Chennai. Malar J. 2014;13:14.CrossRef Kumar DS, Andimuthu R, Rajan R, Venkatesan MS. Spatial trend, environmental and socioeconomic factors associated with malaria prevalence in Chennai. Malar J. 2014;13:14.CrossRef
33.
go back to reference Lindblade KA, Steinhardt L, Samuels A, Kachur SP, Slutsker L. The silent threat: asymptomatic parasitemia and malaria transmission. Expert Rev Anti Infect Ther. 2013;11:623–39.CrossRef Lindblade KA, Steinhardt L, Samuels A, Kachur SP, Slutsker L. The silent threat: asymptomatic parasitemia and malaria transmission. Expert Rev Anti Infect Ther. 2013;11:623–39.CrossRef
34.
go back to reference Babiker HA, Gadalla AA, Ranford-Cartwright LC. The role of asymptomatic P. falciparum parasitaemia in the evolution of antimalarial drug resistance in areas of seasonal transmission. Drug Resist Update. 2013;16:1–9.CrossRef Babiker HA, Gadalla AA, Ranford-Cartwright LC. The role of asymptomatic P. falciparum parasitaemia in the evolution of antimalarial drug resistance in areas of seasonal transmission. Drug Resist Update. 2013;16:1–9.CrossRef
35.
go back to reference Gray KA, Dowd S, Bain L, Bobogare A, Wini L, Shanks GD, et al. Population genetics of Plasmodium falciparum and Plasmodium vivax and asymptomatic malaria in Temotu Province, Solomon Islands. Malar J. 2013;12:429.CrossRef Gray KA, Dowd S, Bain L, Bobogare A, Wini L, Shanks GD, et al. Population genetics of Plasmodium falciparum and Plasmodium vivax and asymptomatic malaria in Temotu Province, Solomon Islands. Malar J. 2013;12:429.CrossRef
36.
go back to reference Tanner M, Greenwood B, Whitty CJ, Ansah EK, Price RN, Dondorp AM, et al. Malaria eradication and elimination: views on how to translate a vision into reality. BMC Med. 2015;13:167.CrossRef Tanner M, Greenwood B, Whitty CJ, Ansah EK, Price RN, Dondorp AM, et al. Malaria eradication and elimination: views on how to translate a vision into reality. BMC Med. 2015;13:167.CrossRef
37.
go back to reference Eldh M, Hammar U, Arnot D, Beck HP, Garcia A, Liljander A, et al. Multiplicity of asymptomatic Plasmodium falciparum infections and risk of clinical malaria: a systematic review and pooled analysis of individual participant data. J Infect Dis. 2020;221:775–85.CrossRef Eldh M, Hammar U, Arnot D, Beck HP, Garcia A, Liljander A, et al. Multiplicity of asymptomatic Plasmodium falciparum infections and risk of clinical malaria: a systematic review and pooled analysis of individual participant data. J Infect Dis. 2020;221:775–85.CrossRef
38.
go back to reference van Eijk AM, Ramanathapuram L, Sutton PL, Kanagaraj D, Sri Lakshmi Priya G, Ravishankaran S, et al. What is the value of reactive case detection in malaria control? A case-study in India and a systematic review. Malar J. 2016;15:67.CrossRef van Eijk AM, Ramanathapuram L, Sutton PL, Kanagaraj D, Sri Lakshmi Priya G, Ravishankaran S, et al. What is the value of reactive case detection in malaria control? A case-study in India and a systematic review. Malar J. 2016;15:67.CrossRef
Metadata
Title
Defining symptoms of malaria in India in an era of asymptomatic infections
Authors
Anna Maria van Eijk
Asad S. Mannan
Steven A. Sullivan
Jane M. Carlton
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2020
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-020-03310-9

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