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Table of Contents
CASE REPORT
Year : 2022  |  Volume : 59  |  Issue : 1  |  Page : 105-107

Molecular characterization of the severe falciparum malaria with typhoid co-infection: A case report


1 Cell Biology Laboratory and Malaria Parasite Bank, ICMR-National Institute of Malaria Research, New Delhi, India
2 Department of Microbiology, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India
3 Department of Pediatric, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India
4 Department of Biotechnology, Kumaun University, Nainital, Uttarakhand, India

Date of Submission17-Aug-2020
Date of Acceptance04-Aug-2021
Date of Web Publication07-Jun-2022

Correspondence Address:
Vineeta Singh
Cell Biology Laboratory and Malaria Parasite Bank, ICMR-National Institute of Malaria Research, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-9062.331416

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  Abstract 

Malaria and typhoid co-infections can be a serious public health issue in tropical countries leading to incorrect diagnosis due to overlapping clinical presentations of malaria and typhoid and hence, causing a delay in implementing the appropriate treatment regimen for these concurrent infections. This study reports a case of six-year-old female child co-infected with severe malaria (Plasmodium falciparum) and typhoid (Salmonella typhi) diagnosed by rapid malaria antigen test (RMAT) and blood culture respectively. Further, analysis of the chloroquine resistance gene Pfcrt for the falciparum demonstrated the presence of K76T mutant allele in pfcrt gene with high IC50 (150nM) for chloroquine (CQ) drug. The present case highlights the significance of timely identification and treatment of co-infections and also provides information about the circulating P. falciparum clinical strains.

Keywords: coinfections; falciparum malaria; typhoid; drug resistance; hematological and molecular markers.


How to cite this article:
Chaudhry S, Arya A, Matlani M, Meena SS, Pande V, Singh V. Molecular characterization of the severe falciparum malaria with typhoid co-infection: A case report. J Vector Borne Dis 2022;59:105-7

How to cite this URL:
Chaudhry S, Arya A, Matlani M, Meena SS, Pande V, Singh V. Molecular characterization of the severe falciparum malaria with typhoid co-infection: A case report. J Vector Borne Dis [serial online] 2022 [cited 2022 Jun 25];59:105-7. Available from: https://www.jvbd.org/text.asp?2022/59/1/105/331416


  Introduction Top


Malaria and typhoid fever still remain diseases of major public health importance in the tropical countries including India resulting in huge economic burden[1]. Individuals in areas endemic for both these diseases are at substantial risk of contracting both these diseases, either concurrently or one acute infection superimposed on a chronic one though causative agent for these two diseases and their mode of transmission are totally different[2]. Malaria is a common infectious disease estimated to have caused 228 million cases in 2018 while Salmonella typhi is most commonly reported from Southeast Asian countries with a prevalence of around 377/ 100,000 population in India[3],[4]. Such concurrent infections with similar clinical symptoms make the correct diagnosis and management of the patient a daunting task for the clinicians.

The case of ‘typhomalaria’ was first reported by a US army surgeon in the war soldiers having clinical features of typhoid with periodic chills and rigors[5]. The authors report here the clinical complications and follow-up of a six-year-old child admitted in hospital with concurrent typhomalaria infection.

A six-year-old female child was hospitalized to Pediatrics Emergency in a government hospital in Delhi in September 2020, with high grade fever for last seven days but no associated chills and rigors with fever, progressive pallor for the last five days and bluish spots over the whole body for the past two days. In detailed history she had fever without any symptoms of jaundice, vomiting or hematuria and these was no history of previous hospitalization. On physical examination, the child was lethargic, febrile (102°F), with cold extremities, prolonged capillary refilling time (>3), low blood pressure (80/60mm Hg), breathing difficulty (36 breaths/minutes with retraction), tachycardia (110bpm) with severe pallorness and body pain (paroxysms). She had tiny purple, red or brownish spots (petechiae) on the skin. Hepatosplenomegaly was observed on her abdomen examination. Cardiovascular findings and respiratory examination were within range during systemic examination except for the hemic murmur. The central nervous system examination showed she had altered sensorium without meningial signs or focal deficit. In view of the malaria season which is during May-October in Delhi, initial diagnosis was made as complicated clinical malaria and empirical anti-malarial therapy as well as symptomatic treatment was started. Blood sample were sent for investigations like hemogram, liver-kidney function test, coagulation profile (PT/APTT/INR), rapid malarial antigen test, peripheral smear for malaria parasite, serology for typhoid and rickettsial infection, blood culture etc. Two ml blood sample was collected in EDTA vial for culture and 200μl blood was spotted on filter paper for molecular analysis of P. falciparum.

Microbiological investigations revealed positive blood culture for S. typhi and rapid malaria antigen test (RMAT) was positive for P. falciparum. The child’s shock condition improved in 24 hours with increased dose of inotropes and blood transfusion however, the fever still persisted. Hematological investigations sent on day one revealed pancytopenia with severe anemia [Table 1]. Platelet count declined on day two and three (37,000 and 49,000/μl respectively) which indicated severe thrombocytopenia [Figure 1]A. On day three of admission, ceftriaxone was added in view of persistent fever and blood culture positivity. With artesunate combination therapy, ceftriax-one, intravenous fluids, blood transfusion and ionotropes the child showed improvement with decreased fever and gradual increase in appetite on day five of hospital stay. On day six the platelet count and other hematological investigations became normal with 8.1 gm/dl haemoglobin, indicating that anemia had been corrected and on seventh day she was discharged on oral hematinics [Figure 1]A,[Figure 1]B,[Figure 1]C.
Figure 1: The trends of various haematological parameters during the hospital stay of the patient. A. Graph presents trends of MCV, PLT and PDW after six days of follow up, B. Graph represent RBC, WBC and HG during the same duration, C. Shows the tendencies of MCHC, HCT, MCH, RDWsd, RDWcv and MPV. *HG, haemoglobin; MCV, mean corpuscular volume; WBC, white blood cell; RBC, red blood cell; PLT, platelet count; PCT, plateletcrit; PDW, platelet distribution width; MCH, mean corpuscular hemoglobin; HCT, hematocrit; MCHC, mean corpuscular hemoglobin concentration; RDWsd, red cell distribution width; MPV, mean platelet volume; RDWcv.

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Table 1: Laboratory investigations of typhomalaria patient

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The malaria sample took around 28 days of continuous culture to adapt in the culture. By schizont maturation inhibition (SMI) assay the IC50 value for artemisnin (ART) and CQ was 1.93nM and 150nM respectively[6]. The sample was a single clone falciparum infection by locus analysis of merozoite surface genes viz pfmsp1 and 2 on day zero and also after its adaptation in culture. The molecular analysis of the drug resistance genes in the patient sample revealed mutation in pfcrt gene at K76T position associated with CQR but no mutations were observed in pfmdr-1 and pfk13 genes on comparison with the reference sequence 3D7 (GenBank ID: for pfcrt PF3D7_0709000, pfk13 NC_004331.3 and pfmdr1 PF3D7_0523000) [Figure 2].
Figure 2: Sequence analysis of pfcrt, pfmdr1 and pfk13 genes in the clinical sample and their alignment with 3D7 reference strain. The coloured sequences represent mutation at the K76T in pfcrt gene and no mutation were found in other two genes viz (pfmdr-1 and pfk13).
#3D7, 3D7reference strain; $ P_F, patient forward sequence; & P_R, patient reverse sequence.


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  Discussion Top


This case was diagnosed as typhoid malaria co-infection along with severe anemia, pancytopenia and the malarial parasitemia was >1.5% thus classifying it as severe falciparum malaria[7]. Both these diseases are associated with poor sanitation, bad hygiene and several epidemiological factors leading to typhoid malaria co-infection[2]. There are few reports of malaria and typhoid co-infections however, there are hardly any reported studies on co-infection of severe falciparum malaria and enteric fever. The in vitro IC50 value for CQ was 150nM along with the presence of K76T mutation in the pfcrt gene which is associated with CQR attributing to the disease severity of falciparum malaria[8]. The thrombocytopenia platelet (PLT) count and platelet indices like mean platelet volume (MPV), platelet distribution width (PDW) in this sample were studied to understand the association of hematological parameters, most importantly platelet parameters in severe malaria patient. The higher PDW is attributed to the early release of platelets probably as a response mechanism in the patient with platelets below the normal range during the disease[9]. These parameters can be useful as a marker to demonstrate the clinical severity of malaria in infected patients.

Persistent fever despite adequate treatment should be an important indication for clinicians to explore the possibility of co-infections[10]. Further studies should be undertaken to assess the risk factors of malaria and typhoid co-infections in different transmission seasons and settings. Development of better diagnostic tools for both these infections in tropical countries are needed for early management of diseases and hence reduced disease burden.



 
  References Top

1.
Uneke CJ. Concurrent malaria and typhoid fever in the tropics: the diagnostic challenges and public health implications. J Vector Borne Dis 2008; 45(2): 133–142.  Back to cited text no. 1
    
2.
Odikamnoro OO, Ikeh IM, Okoh FN, et al. incidence of malaria/typhoid co-infection among adult population in unwana community, afikpo north local government area, ebonyi state, southeastern nigeria. Afr J Infect Dis 2017; 12(1): 33–38.  Back to cited text no. 2
    
3.
World malaria report 2019. Available from https://www.who.int/ publications-detail/world-malaria-report-2019. (Accessed on March 25, 2020)  Back to cited text no. 3
    
4.
John J, Van Aart CJC, Grassly NC. The Burden of Typhoid and Paratyphoid in India: Systematic Review and Meta-analysis. PLoS Negl Trop Dis 2016; 10(4).  Back to cited text no. 4
    
5.
Jakubowski R, Steed LL, Dorman SE, Marculescu C. A Case of Malaria Predisposing to Salmonella Bacteremia in a Returning Traveler from Nigeria. Case Reports in Infectious Diseases.  Back to cited text no. 5
    
6.
Petersen. World Health Organization. Organisation Mondiale de la Sante. Commun Dent Oral Epidemiol 2003; 31(6): 471–471.  Back to cited text no. 6
    
7.
Health I, Malaria RB. Severe malaria. Trop Med Int Health 2014; 19(1): 7–131.  Back to cited text no. 7
    
8.
Antony HA, Das S, Parija SC, Padhi S. Sequence analysis of pfcrt and pfmdr1 genes and its association with chloroquine resistance in Southeast Indian Plasmodium falciparum isolates. Genom Data 2016; 8: 85–90.  Back to cited text no. 8
    
9.
Saravu K, Docherla M, Vasudev A, Shastry BA. Thrombocytopenia in vivax and falciparum malaria: an observational study of 131 patients in Karnataka, India. Annals of Tropical Medicine & Parasitology 2011; 105(8): 593–598.  Back to cited text no. 9
    
10.
Keong BCM, Sulaiman W. Typhoid and Malaria Co-Infection – An Interesting Finding in the Investigation of a Tropical Fever. Malays J Med Sci 2006; 13(1): 74–75.  Back to cited text no. 10
    


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