A report on incidence of COVID-19 among febrile patients attending a malaria clinic.

CONTEXT: Screening for malaria and coronavirus disease (COVID-19) in all patients with acute febrile illness is necessary in malaria-endemic areas to reduce malaria-related mortality and to prevent the transmission of COVID-19 by isolation. AIMS: A pilot study was undertaken to determine the incidence of SARS-CoV-2 infection among febrile patients attending a malaria clinic. SUBJECTS AND METHODS: All patients were tested for malaria parasite by examining thick and thin blood smears as well as by rapid malaria antigen tests. COVID-19 was detected by rapid antigen test and reverse transcriptase-polymerase chain reaction in patients agreeing to undergo the test.
RESULTS: Out of 262 patients examined, 66 (25.19%) were positive for Plasmodium vivax, 45 (17.17%) for Plasmodium falciparum (Pf) with a slide positivity rate of 42.40%, and Pf% of 40.50%. Only 29 patients consented for COVID-19 testing along with malaria; of them, 3 (10.34%) were positive for COVID-19 alone and 2 (6.89%) were positive for both COVID-19 and P. vivax with an incidence of 17.24%. A maximum number of patients (196) did not examine for COVID-19 as they did not agree to do the test.
CONCLUSION: Diagnosis of COVID-19 among three patients (10.34%) is significant both in terms of identification of cases and to isolate them for preventing transmission in the community. Detection of COVID-19 along with malaria is equally important for their proper management. Copyright:

INTRODUCTION

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is now pandemic throughout the world. This has imposed an additional burden to the health-care delivery system and emerged as a global challenge for management of other prevailing infectious and communicable diseases including tuberculosis, malaria, and AIDS.[1] About 50% of the world population is at risk of both malaria and COVID-19.[23] In 2019, a total of 338,494 cases and 77 deaths due to malaria have been reported from India.[4] Malaria endemic countries are facing the daunting task of diagnosis of these diseases and differentiation from COVID-19 disease. COVID-19 shows some symptoms similar to that of malaria (fever, headache, difficulty in breathing, and body ache).[2] COVID-19-positive individuals may be symptomatic or asymptomatic but transmitting the infections to their close contacts.[56] Although the nature of fever varies from disease to disease, it is very difficult to differentiate clinically at the time of initial clinical evaluation. Hence, proper diagnosis of malaria and COVID-19 is of utmost importance to reduce mortality. Hence, there is a need to differentiate between malaria and COVID-19 among acute febrile patients in malaria-endemic countries like India where malaria is seasonal and most prevalent during June to November due to high humidity and warm environment.[7] The situation is complicated by COVID-19 infection this year. Public health experts are of the view that COVID-19 will peak during August–December that coincides with high malaria transmission season.[8] A pilot study was undertaken to determine the incidence of COVID-19 infection among the acute febrile patients attending the Malaria Clinic attached with Calcutta School of Tropical Medicine, India.

SUBJECTS AND METHODS

The present study was conducted from August 29 to September 12, 2020. The Malaria Clinic of the School of Tropical Medicine is engaged in the diagnosis and treatment of malaria routinely and draws patients from surrounding areas. All febrile patients attending the clinic were examined clinically and Giemsa-stained thick and thin blood smears were checked microscopically for malaria parasite, in addition to rapid malaria antigen testing using a dual-antigen test kit for malaria supplied by the National Vector Borne Disease Control Programme (NVBDCP). All clinic attendees were counseled and advised for COVID-19 testing along with malaria, but only a few of them (29) agreed to do so. Both nasopharyngeal and oropharyngeal swabs were taken. Nasopharyngeal swab samples were examined for SARS-CoV-2 antigen using rapid antigen test (RAT) (Standard Q COVID-19 Ag test kit made by SD Biosensor Healthcare Pvt. Ltd., India) as per manufacturer's instruction. As per guidelines formulated by the Indian Council of Medical Research (ICMR),[9] those positives by RAT were declared as COVID-19 positive. Samples negative by RAT were tested by reverse transcriptase–polymerase chain reaction (RT-PCR) for detection of SARS-CoV-2 viral RNA by targeting E_Sarbeco gene and HKUORF1bnsp genes (ICMR, NIV, Pune).[10] Both RAT and RT-PCR for detection of COVID-19 infection were done at the Microbiology Department of the Calcutta School of Tropical Medicine.

Malaria patients were treated according to diagnosed parasite species: chloroquine (CQ) plus primaquine (PQ) for Plasmodium vivax and artesunate (AS) plus sulfadoxine-pyrimethamine (SP) with PQ for Plasmodium falciparum (Pf) were prescribed as per NVBDCP guideline of India. COVID-19 patients were referred to a nearby dedicated COVID hospital for their appropriate inpatient management or home isolation.

Ethical aspects

This was an observational study. The data presented in this manuscript were generated from routine service to the patients. No clinical or therapeutic data of any patients are included in this manuscript. Verbal informed consent was obtained from all febrile patients attended for diagnosis of malaria before the interview and requested for COVID-19 testing. Those, who consented, were tested for COVID-19 along with malaria. The appropriate permission for publication of the data was obtained from the head of the institute.

RESULTS

During the study period, a total of 262 patients attended the malaria clinic. All of them were examined for malaria, but only 29 (11.06%) consented for COVID-19 testing. Out of the 233 patients examined only for malaria, P. vivax was detected in 61 and Pf in 42 patients with a slide positivity rate (SPR) of 44.20% and Pf% of 40.80%. Among 29 patients tested for both malaria and COVID-19, P. vivax was detected in 5 and Pf in 3 patients. Three were positive for COVID-19 alone and two patients were coinfected with COVID-19 and P. vivax with an incidence of 17.24%. The overall SPR for malaria was 42.40% with Pf% of 40.50% [Table 1]. The COVID-19 patients were referred to COVID-19 hospital immediately for proper management. Both the coinfected cases opted for home isolation with appropriate advice by the health authority along with CQ and PQ in prescribed dose. The most important aspect was that the total attendance of the malaria clinic was dropped to one-third in respect to the same period of the previous year [Table 2].

Table 1

Febrile patients attending the Malaria Clinic of School of Tropical Medicine for diagnosis of malaria during the study period and the observed pattern of malaria and COVID-19 infection (n=262)

	Plasmodium vivax	Pf	SPR (%)	Pf (%)	COVID-19	COVID-19+malaria
Patients examined for malaria parasite only (n=233), n (%)	61 (26.18)	42 (18.02)	44.20	40.80	ND	ND
Patients examined for malaria parasite and COVID-19 (n=29), n (%)	5 (17.24)	3 (10.34)	27.60	37.50	3 (10.34)	2 (6.89)
Total, n (%)	66 (25.19)	45 (17.17)	42.40	40.50

SPR: Slide positivity rate, Pf: Plasmodium falciparum

Table 2

The decline in attendance of acute febrile patients (from March to August) during 2019 and 2020 at the malaria clinic

Months	2019					2020
	Total examined	Plasmodium vivax	Pf	Total positive	SPR (%)	Total examined	Plasmodium vivax	Pf	Total positive	SPR (%)
March	574	35	0	35	6.10	443	9	2	11	2.48
April	486	63	20	83	17.08	254	9	0	9	3.54
May	954	106	4	110	11.53	57	5	0	5	8.77
June	581	65	0	65	11.19	97	28	0	28	28.87
July	730	127	1	128	17.53	317	82	13	95	29.97
August	696	99	7	106	15.23	350	100	31	131	37.43

SPR: Slide positivity rate, Pf: Plasmodium falciparum

DISCUSSION

Detection of SARS-CoV-2 infection either alone or along with malaria among acutely ill febrile patients attending for malaria diagnosis is alarming from the public health perspective. In the present study, nearly 90% of patients attending the malaria clinic did not agree to take the COVID-19 test. This high refusal rate denotes that a significant proportion of patients with acute febrile illness are not being tested for COVID-19 diagnosis. The reason may be lack of awareness or fear of getting infected from COVID-19 testing laboratory or stigmatization with COVID-19 diagnosis. It is possible that some of them might be carrying the virus and staying with their family without self-isolation. Similarly, a large proportion of patients attending for COVID-19 diagnosis are not being examined for malaria during the pandemic. The COVID-19 patients might also be infected with malaria. Fever is common to both malaria and COVID-19 infection.[11] In this pilot study, two patients had coinfection of COVID-19 and P. vivax malaria. Unless looked for specifically, one of the infections may remain undiagnosed. At present, negative febrile patients tested for COVID-19 or malaria alone are advised to back home. In fact, some of the malaria negative cases have COVID-19 infection, as observed in the present study. Such cases have the potential to transmit up to 3.58 susceptible individuals.[12] On the other hand, untreated malaria cases remained as a source of transmission and deaths globally.[31314]

Although the modes of transmission of the diseases are different, such undiagnosed cases will play an important role in transmitting the diseases in the community.[313] The presence of undiagnosed coinfection will worsen the clinical outcome as well.

Of note, patient attendance to the malaria clinic has declined sharply this year as compared to previous years [Table 2]. This indicates that some of the febrile patients are not attending for malaria diagnosis and treatment. Such cases might pose serious community transmission.[13]

Coinfection of P. vivax malaria and COVID-19 was first reported from Qatar.[15] There are few more such coinfection reports from Delhi and Mumbai, India.[161718]

Rapid diagnostic kits for malaria diagnosis and antimalarial drugs are readily available at each point of care including remote peripheral sites. This should also be made available in all COVID-19 hospitals and care facilities. An enhanced sensitization of the clinicians about COVID-19 and malaria coinfections and their management will reduce mortality by proper treatment with effective antimalarial drugs through appropriate referrals.[19] Management of COVID-19 infection will obviously be as per current country and state guidelines.[20]

Coinfection with malaria may also modify the clinical features of COVID-19. Malaria can induce a cytokine storm and pro-coagulant state similar to that seen in severe COVID-19. Consequently, coinfections with Plasmodium spp. and SARS-CoV-2 could result in substantially worse outcomes than mono-infections with either pathogen, and could shift the age pattern of severe COVID-19 to younger age groups.[21]

India is having a policy of using hydroxychloroquine as primary chemoprophylaxis against COVID-19 infection among health-care workers as well as other frontline workers and asymptomatic, direct-contact family members. Hydroxychloroquine is also used for the treatment of mild patients with comorbidity and moderate cases of COVID-19 in India.[22] Hence, it is expected to be equally effective against P. vivax coinfection as P. vivax in India is sensitive to it.[22] Hence, Artemisinin combination therapy (ACT) (AS + SP) should be used for coinfection of COVID-19 with Pf coinfection.

Coinfection of COVID-19 with other viral and bacterial diseases like dengue, chikungunya, leptospirosis, enteric fever is also been reported.[23] Such cases should be screened at the same point of testing, particularly in endemic areas.

CONCLUSIONS

A significant proportion of the febrile patients were unwilling for COVID-19 testing which requires urgent addressal through public health education. The seasonal outbreak of dengue, chikungunya, leptospirosis, and enteric fever during monsoon should also be considered in all COVID-19 patients for appropriate antimicrobial therapy and better clinical outcome. Hence, urgent research is needed in studying the impact of seasonal common infectious diseases on the natural history, clinical presentation, and mortality among COVID-19 patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.