Syndemic Challenges of Malaria and COVID-19 and Reported Coinfection of Both: Experience from a Tertiary Care Center

INTRODUCTION

Globally there were 229 million cases of malaria in 2019 according to the WHO Malaria Report 2020. India achieved the largest absolute reductions in the WHO South-East Asian regions, from 20 million cases in 2000 to 5.6 million cases in 2019. Tamil Nadu reported 2,088 cases in 2019 and 891 cases in 2020 of which Chennai constitutes 69.5% and 81.7%, respectively.¹ The coronavirus disease-2019 (COVID-19) pandemic has disrupted the essential malaria services (Fig. 1). Early messaging targeted at reducing coronavirus transmission advised the public to stay at home if they had fever, potentially disrupting treatment seeking for febrile diseases like malaria. There are five species of plasmodium that cause human infection—falciparum, vivax, ovale, malariae, and knowlesi. Plasmodium falciparum accumulates in the blood spaces of the placenta. This placental parasite escapes the immune system. The parasite expresses a surface ligand called VAR2CSA which sticks to the placental receptor chondroitin sulfate A.² The infiltration of immune cells into intervillous space and the production of inflammatory cytokines in response to infection is said to be the reason for the adverse birth outcomes and maternal anemia. This placental sequestration does not occur in other malarial species. Plasmodium falciparum infection in pregnancy causes greater morbidity and mortality. But nowadays vivax is not less potential in causing severe disease. The treatment protocols differ depending on the endemicity and resistance to the antimalarials.

Here we report 10 cases of malaria in pregnancy at a tertiary care center in Chennai with different clinical features, perinatal outcomes, management, and the follow-up of these patients.

MATERIALS AND METHODS

Ten patients admitted in the Government RSRM Lying in Hospital, Chennai, between September 2020 and July 2021 with diagnosis of malaria in pregnancy were described. All these cases acquired infection during their antenatal period. Seven cases in their second trimester and three cases reported in the third trimester.

Detailed history taking was done. All patients were from endemic areas of Chennai. The presenting complaints and other significant history related to malaria were recorded. Physical examination done after obtaining consent from all the patients. Complete blood count, renal function and liver function tests, ultrasound abdomen and pelvis, fever investigations (peripheral smear for Mp, Mf, dengue IgM, WIDAL, IgM leptospirosis, IgM scrubs typhus), and COVID RT-PCR were done. The diagnosis of malaria in all these patients was confirmed by peripheral smear and Quantitative Buffy Coat (QBC) test. Quantitative Buffy Coat can detect as little as one parasite as they contain DNA that takes up the acridine orange stain and appear as bright specks of light among the non-fluorescent RBCs.

RESULTS

We identified 10 cases of malaria in antenatal women admitted at our hospital during the COVID-19 pandemic. Six patients were primigravida and four second gravida; three affected in the second trimester (Fig. 2; one patient at 24–26 weeks; two patients at 26–28 weeks); and seven in the third trimester (two patients at 28–30 weeks; two at 32–34 weeks; two at 34–36 weeks, and one at 36–38 weeks; Fig. 3). All these patients were admitted with complaint of fever. Added symptoms were myalgia, vomiting, and breathlessness, and one patient presented with high colored urine (Fig. 4). All were from malaria endemic areas. One patient had overt diabetes mellitus and gestational hypertension. Others had no significant comorbidities.

All 10 patients had anemia and thrombocytopenia; 1 with elevated urea, creatinine and bilirubin levels; splenomegaly in 5 cases. Peripheral smear showed mycoplasma pneumoniae (MP) positive ring forms of P. falciparum in two patients and trophozoites of Plasmodium vivax in eight (Figs 5 and 6); and three were detected by QBC. One case affected with falciparum infection was serology positive for Scrub typhus; two with RT-PCR positive for COVID and one with RT-PCR negative COVID infection with CT score 2/25 involving 8% of the lung.

One patient had severe P. vivax infection with anemia Hb 8.2 gm/dL and thrombocytopenia with platelet count 21,000 (Table 1); elevated urea value 73 mg/dL; creatinine 2.4 mg/dL; total bilirubin 7.5; direct bilirubin 4.8; indirect bilirubin 2.7; and massive splenomegaly of up to 20 cm with gall bladder wall edema and mild ascites. She was at 25 weeks of gestation.

Ultrasound revealed normal liquor status in six patients, two had oligohydramnios and two had polyhdramnios. Ultrasonography or sonography (USG) parameters were corresponding to the period of gestation in all these cases (Fig. 7).

All these patients were started on chloroquine course initially. Six patients responded well to the chloroquine treatment. Only four patients required artemisinin-based combination therapy—Inj. Artesunate. Three patients affected with COVID infection were treated with ACT. Seven patients required blood transfusion and one with severe vivax infection required platelet transfusion. Primaquine was given for 14 days for all patients infected with P. vivax infection after their lactation period (Fig. 8).

The average length of stay in hospital for all these patients was 10 days. They were on regular follow-up and all of them delivered at tertiary care centers. Two patients had spontaneous expulsion—one with severe vivax infection and the other with malaria and COVID coinfection. One patient had preterm delivery at 35 weeks 5 days with baby weight 2.4 kg and other seven delivered at term with all birth weights more than 2.5 kg (Fig. 9).

Postpartum hemorrhage (PPH) and disseminated intravascular coagulation (DIC) was observed in one case, treated with blood and blood products transfusion.

DISCUSSION

There are only limited studies regarding the malaria and COVID coinfection and the challenges faced in managing infectious disease during the pandemic. Once the COVID pandemic control measures started, the outpatient services got limited and people’s movement to the healthcare facility has drastically came down. Outpatients seen during the pandemic in our center declined to 30%.³ Routine antenatal visits were also limited as people were worried about acquiring the infection. Many healthcare professionals were infected with COVID, and outpatient department (OPD) was suspended in many centers. There were overlapping symptoms for malaria and COVID like fever, myalgia, vomiting, and respiratory symptoms.⁴ All these factors were the reason for difficulties in identifying other infectious diseases that had similar presentation like COVID and also for implementing endemic disease control measures like insecticide-treated nets distribution and chemoprophylaxis.⁵ For mild symptoms, patients were advised home isolation in many countries. This can lead to undiagnosed and untreated malarial infection that can be endangering to life. Patients identified with COVID were not tested for malaria infection and this may lead to under-treatment of cases.

Two contradictory statements have been put forth regarding malaria and COVID. Malaria and COVID coinfection may lead to severe manifestations and poor prognosis due to excessive proinflammatory response. Other study suggests that there might be a protective effect of malaria on worsening COVID-19 infection.² COVID infection was found relatively low in malaria endemic Sub Saharan African countries.⁶ This might be attributed to the immunomodulation caused by previous malaria exposure and the use of antimalarials like chloroquine and artemisinin which is found to be effective against SARS-CoV-1 and SARS-CoV-2 in vitro.

Hemolysis and microthrombi formation is common to both infections. This can lead to anemia, thrombocytopenia, jaundice, pulmonary edema and acute respiratory distress syndrome (ARDS), and acute renal failure. Placenta microthrombi can lead to pre-eclampsia, oligohydramnios, and fetal growth restriction. Fetal complications include preterm births, low birth weight, and intrauterine demise.³

In this study, cases with malaria and COVID-19 coinfection were treated with intravenous Inj. artesunate to fasten clearance of parasite and it yielded good results. The management of coinfection was difficult during the initial pandemic situation as there was no proper protocol for the usage of drugs and many were under trial. Steroids and heparin being the first-line drugs in treating COVID-19 are considered double-edged sword in treating patients with malaria coinfection.

CONCLUSION

It is the need of the hour to sensitize healthcare professionals to extend malaria testing services as they screen for COVID-19. Owing to the similarity of symptoms between malaria and COVID-19, clinicians may tend to misdiagnose/mistreat a malaria infection as COVID-19 and vive versa or the coinfection. Pregnant patients with acute febrile illness should be screened for other infectious diseases along with COVID RT-PCR, thereby reducing maternal and fetal morbidity and mortality. Artemesinin has been found to be effective in malaria and COVID coinfection. Efforts should be taken to extend malaria prevention measures and elimination campaigns mainly targeting the vulnerable pregnant population.

ORCID

Nivedita S https://orcid.org/0000-0003-4846-1140

Monisha Mohan https://orcid.org/0000-0002-1586-8705

REFERENCES

1. WHO. WHO World Malaria Report 2020. Malaria report. 2020.

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