IDCases 20 (2020) e00717

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IDCases
journal homepage: www.elsevier.com/locate/idcr

Case report

Typhoid and paratyphoid fever co-infection in children from an urban

slum of Delhi
Ankita Dutta, Deepak More* , Ananya Tupaki-Sreepurna, Bireshwar Sinha, Nidhi Goyal,
Temsunaro Rongsen-Chandola
Centre for Health Research and Development Society for Applied Studies (CHRD-SAS), New Delhi, India

A R T I C L E I N F O A B S T R A C T

Article history: We report two cases of co-infection with Salmonella Typhi and Salmonella Paratyphi A identified by blood
Received 9 January 2020 culture and confirmed by serotyping from an ongoing fever surveillance cohort in an urban slum in New
Received in revised form 7 February 2020 Delhi. Co-infections such as these have important implications on diagnosis, treatment options including
Accepted 7 February 2020
choice of antimicrobial(s), disease outcome and strategy for prevention.
© 2020 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://
Keywords: creativecommons.org/licenses/by-nc-nd/4.0/).
Salmonella Typhi
Salmonella Paratyphi A
Co-infection
Community-Acquired

Introduction child presented to the pediatric study fever clinic at Hakeem Abdul
Hameed Centenary Hospital (HAHCH) with three days of fever
Enteric fever, including typhoid and paratyphoid fevers, is a associated with nausea, headache, sore throat, cough and
food and waterborne disease, known to be endemic in Indian abdominal pain. There was no history of rash, diarrhea, joint
settings. It is primarily transmitted through the fecal-oral route pains or blood in stools. On examination, an oral temperature of
and is associated with poor water quality, sanitation and hygiene 98.0 F was noted. There was no contact with someone in the family
[1–3]. Typhoid is caused by Salmonella enterica serotype Typhi, with known tuberculosis and no travel history in the two weeks
whereas paratyphoid fever is caused by Salmonella enterica before the onset of illness. The child was previously vaccinated
serotypes Paratyphi A, B or C. These organisms are human adapted with a polysaccharide typhoid vaccine from a public health facility
pathogens having no animal reservoir, except S. Paratyphi C [1–3]. in March 2013 at two years of age, as documented in the
Co-infection with S. Typhi and S. Paratyphi A is known but has immunization card. One day prior to presentation to the pediatric
not been reported often [3,4]. The authors report two cases of study fever clinic, the child was prescribed with antipyretics and
Salmonella Typhi and Paratyphi A co-infection in a child from a amoxicillin (375 mg/kg) by a local practitioner. A provisional
community-based cohort in an urban slum of New Delhi where diagnosis of upper respiratory tract infection was made, and the
6000 children are being followed-up for 24 months or till they antibacterial was continued for five days. Despite the medication
reach 15 years of age. This cohort is part of a multicentric study to provided, there were persisting fever spikes and the child re-
estimate the age-specific burden of culture-confirmed typhoid visited the clinic on the sixth day of fever onset with complaints of
fever in the community in children aged 6 months to <15 years persisting high-grade fever. On examination, a temperature of
across India [5]. 104.2 F was recorded and the child was suspected to have typhoid
fever. Blood specimen of 5 mL was aseptically drawn into the Peds
Case report Plus bottle and sent to the study laboratory (Clinical and Research
Laboratories-Society for Applied Studies, New Delhi) for blood
The first case was a boy aged 8 years 5 months, belonging to a culture to investigate typhoid fever.
Hindu-nuclear family in Block B, Sangam Vihar, Delhi, residing in a Blood culture specimen was received in the Lab within two
pucca house with no overcrowding and a separate kitchen. The hours of collection and was processed into the Bactec Fx40 (Becton
Dickinson, United States) which beeped positive within 24 h of
incubation. Gram stained smear (K001, Hi-Media Laboratories,
* Corresponding author. India) showed long and slender Gram-negative bacilli. Sub-culture
E-mail address: [email protected] (D. More). was done on MacConkey Agar, Sheep Blood Agar and Nutrient Agar

https://doi.org/10.1016/j.idcr.2020.e00717
2214-2509/© 2020 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
2 A. Dutta et al. / IDCases 20 (2020) e00717

plates (Pre-Prepared media plates, Hi-Media Laboratories, India) Serotype Identification- Larger colonies showed visible agglu-
and incubated in the microbiological incubator overnight at 37  C. tination with ‘O9’ and ‘d’ antisera (procured from CRI, Kasauli,
Colony morphology on MacConkey plate was small, moist, Himachal Pradesh) by slide agglutination method and were
medium to large, non-lactose fermenting, further subjected to confirmed to be Salmonella Typhi. Smaller colonies showed visible
oxidase test resulting negative. Hanging drop motility showing agglutination with ‘O2’ and ‘a’ antisera (procured from CRI, Kasauli)
actively motile bacilli under 40x immersion lens. Biochemical tests by slide agglutination method and were confirmed to be Salmonella
were performed from the growth plate and results were noted Paratyphi A.
after 18 24 h of incubation in the TSI (Triple Sugar Iron) agar Antibiotic susceptibility testing was performed for both the
which showed both gas and speck of H2S. Suspecting a possible colonies separately, by Kirby-Bauer disc diffusion method. Both
contamination, the biochemical tests were repeated and a fresh organisms showed similar antibiograms with intermediate suscep-
sub-culture was done. Repeat biochemical tests (two times) tibility to ciprofloxacin, resistance to pefloxacin and susceptibility to
showed the same results. ampicillin, azithromycin, chloramphenicol and cotrimoxazole
A fresh sub-culture on the MacConkey agar plate from the blood (Figs. 2 and 3). Based on the lab findings, the child was diagnosed
culture bottle was done to relook at growth for a single or multiple to be infected with both SalmonellaTyphi and Salmonella Paratyphi A.
colony types. We identified two distinct colonies; pure cultures of Based on the culture results, the child was treated with the
both the colonies were isolated and processed (Fig. 1). combination therapy of azithromycin (20 mg/kg) and cefixime (10
Biochemical Identification- (A) Small, round colonies yielded mg/kg) for five days as per the advice of the pediatrician at our
alkaline/acid reaction with gas and no H2S, did not decarboxylate study fever clinic. The child recovered after five days of treatment
lysine (Fig. 3) and (B) Large, moist, irregular colonies yielded without any complications. The total duration of the episode was
alkaline/acid reaction with speck of H2S and no gas, decarboxylated 14 days. Repeated episodes of fever were observed in the child
lysine (Fig. 2). Both the organisms were oxidase negative, motile, during the total follow-up period at 8 yr 10 m 23d, 8 yr 10 m 29d
did not utilise citrate, indole negative and mannitol fermentative. and 9 yr 1 m 11d ages. These fever episodes lasted for 11, 6 and 4
days, respectively. Blood culture revealed no growth in the episode
that lasted for 11 days and the family did not agree for blood testing
for the subsequent two episodes. All episodes subsided without
any sequelae.
The child belonged to a four-membered family with highest
education up to senior secondary level and monthly income of INR
6000/-. The younger sibling of the index child, a four-year-old
female, also had an episode of culture-confirmed typhoid fever in
six months after episode in the index case and was treated with
cefpodoxime for four days and azithromycin for eight days. Child
recovered without any hospitalization and further complications.
There was no history of fever among the other family members.
A similar case of co-infection was reported in a girl aged four
years, belonging to low socio-economic Hindu joint family in
January 2020 from the same cohort. The child presented on the
third day of fever with sore throat, cough, and abdominal pain. On
physical examination in the pediatric study clinic, the child was
found to be febrile with an oral temperature of 102.4 F and a
provisional diagnosis of URTI was made. The child was prescribed
antipyretics and azithromycin syrup 5 mL for five days, blood
Fig. 1. Blood culture growth on MacConkey Agar showing non-lactose fermenting culture was performed. Blood culture showed Gram-negative
colonies with two different morphologies – small round (A) and large irregular (B). bacilli. Sub-culture on MacConkey agar showed two types of

Fig. 2. Results of disc diffusion susceptibility testing (left) and biochemical reactions (right) of Salmonella enterica serovar Typhi.
 A. Dutta et al. / IDCases 20 (2020) e00717 3

Fig. 3. Results of disc diffusion susceptibility testing (left) and biochemical reactions (right) of Salmonella enterica serovar Paratyphi A.

colonies superimposed. A repeat sub-culture showed a pure Mixed infections with S. Typhi and S. Paratyphi have also been
culture of small, moist, regular edged non-lactose fermenting and previously reported from hospital settings in India [10–13]. This
large, moist, irregular edged non-lactose fermenting colonies. co-infection may be more common than suspected and is often
Biochemical identification and serotyping were performed for both missed due to indistinguishable clinical features [14,15].
colony types and identified to be as Salmonella Paratyphi A and In a case of dual infection, both strains could have the same
Salmonella Typhi respectively. susceptibility profiles [10] or may differ in their antibiograms
The child was admitted to the Pediatric Intensive Care Unit [11,12]. The strains isolated in the reported cases had the same
(PICU) on the eighth day of illness due to persisting fever and antibiotic sensitivities. In our ongoing cohort, the cases of co-
complaints of two episodes of loose stools along with infection seem to be more severe in terms of duration of illness
vomiting. The child was treated with IV ceftriaxone 700 mg (14–17 days) as compared to infections with single organisms
for 10 days. The final diagnosis was complicated enteric fever (median duration 9 days) and therefore require prolonged care [1].
with shock and moderate iron deficiency anemia. The child was The severity of fever was also higher in these cases (102–104 F).
further prescribed Syp Tonoferon (80 mg/5mL) for three Vigilant observation during lab testing is critical for diagnosis.
months and Syp Beevon 5 mL for 15 days for anemia During conventional processing of a clinical Salmonella isolate,
management and recovered without any further complica- presence of trace elements of hydrogen sulphide and gas should
tions. Hospitalization duration was for 11 days; total duration alert the microbiologist to the possibility of a co-infection.. Further
of episode was 17 days. No other family members were incubation of the culture plates could show two types of colonies
diagnosed with enteric fever during the study period. (e.g. large and small). Going beyond blood cultures, novel
We captured household WASH practices in both the cases. In multiplex PCR protocols can be useful for diagnosis of enteric
the first case, the main source of drinking water was piped water fever infections [16].
from Delhi Jal board and that in the second case was tube well WHO recommends programmatic use of typhoid vaccines to
water. Neither of the two households practiced any further control typhoid fever, especially in countries with high burden of
treatment of water before drinking. Both used a pit latrine with the disease and antimicrobial resistance [17]. New prevention
slab which was not shared with other households. The frequency of strategies targeting both Typhi and Paratyphi together may be
buying ready-to-eat food from street vendors was around once a helpful in South Asia where co-infections are common. Polyvalent
month and once a week in the first and second household, vaccines that protect against S. Typhi as well as S. Paratyphi A may
respectively. be of greater relevance in these settings. Vaccines using Vi antigen
as principal agent lacks ability to elicit cross protection against
paratyphoid A. The approved typhoid vaccines (Vi Polysaccharide
Discussion and live oral Ty21a) do not seem to be efficacious against
S. Paratyphi A infection [18,19]. Increasing mixed infections with
Salmonella Typhi and Salmonella Paratyphi A co-infection is not S.Typhi and S.Paratyphi A,may necessitate development of novel
uncommon and has implications on clinical management. While control strategies [18].
similar treatment strategies may work for both organisms,
serotypes with different antibiograms can pose challenge to Acknowledgement
successful treatment in areas where multi drug-resistant strains
are common. In India, the extensively drug-resistant H58 We would like to extend our special thanks to Dr. Gagandeep
haplotype of S. Typhi has been reported, harboring a promiscuous Kang (SEFI Principal Investigator), Dr. Jacob John (Co-Principal
plasmid conferring resistance to fluoroquinolones and third Investigator at Christian Medical College, Vellore), Dr. Shanta Dutta
generation cephalosporins [6]. Multidrug-resistant Salmonella (Co-Principal Investigator at National Institute of Cholera and
Paratyphi A harboring IncHI1 plasmids like those found in serovar Enteric Diseases, Kolkata), Dr. Ashish Bavdekar (Co-Principal
Typhi have also been reported [7]. Such co-infections are likely to Investigator at KEM Hospital Research Centre, Pune) and other
cause severe illness and may require hospitalization. study team members. We also would like to express our gratitude
Infections caused by S. Paratyphi A have been increasing, to the study participants for their participation in the study. The
particularly in Asia [1,8]. In a study by Pratap et al., 2014 [9] work was funded by a grant from the Bill and Melinda Gates
occurrence of co-infection with S. Paratyphi A was seen in >40% of foundation (Grant Number OPP1159351) through Christian
the typhoid cases and chronic typhoid carriers by nested PCR. Medical College, Vellore.
4 A. Dutta et al. / IDCases 20 (2020) e00717

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