A case series on common cold to severe bronchiolitis and pneumonia in children following human metapneumovirus infection in Sri Lanka
Jayaweera et al. BMC Res Notes
A case series on common cold to severe bronchiolitis and pneumonia in children following human metapneumovirus infection in Sri Lanka
J. A. A. S. Jayaweera 0 2
F. Noordeen 2
S. Kothalaweala 2
F. N. N. Pitchai 2
M. L. M. Rayes 1
0 Department of Microbiology, Faculty of Medical and Allied Sciences, Rajarata University of Sri Lanka , Anuradhapura , Sri Lanka
1 Department of Pediatrics, Faculty of Medical and Allied Sciences, Rajarata University of Sri Lanka , Anuradhapura , Sri Lanka
2 Department of Microbiology, Faculty of Medicine, University of Peradeniya , Peradeniya , Sri Lanka
Objectives: The prevalence of hMPV infections in Sri Lanka has not been reported and here we report a case series of hMPV infection in children less than 5 years. Patients with ARTI were included from Teaching Hospital, Anuradhapura from March 2013 to August 2014. Indirect fluorescence assay was performed on nasopharyngeal aspirates for the identification of respiratory viruses [respiratory syncytial virus (RSV), parainfluenza virus 1, 2 and 3, influenza A and B and hMPV]. Moreover, reverse transcriptase-polymerase chain reaction was done to further confirm the hMPV infection. Results: In this case series, hMPV infection showed a range of respiratory symptoms from common cold to life threatening lower respiratory tract infections with varying severity. In some cases, the clinical presentation of hMPV infection was similar to the ARTI caused by RSV. hMPV co-infections with of RSV have also been seen in some cases of ARTI. A child delivered through cesarean section and birth order > 3 has an Odds ratio of 3.5 and 4.3 (95% CI) for developing co-infection with RSV compared to hMPV mono-infections. Lack of diagnostic facilities to identify the viral aetiology has contributed to the use of antibiotics indicating the need for establishing viral diagnostic facilities in the country.
Human metapneumovirus; Acute respiratory tract infections; Children; Sri Lanka
Acute respiratory tract infection (ARTI) is one of the
most common illnesses of childhood. ARTIs range from
common cold, a mild self-limiting catarrhal syndrome to
life threatening lower respiratory tract infection. Viruses
account for most ARTIs and associated respiratory
]. The most frequently reported viruses in
newborns and children under 5 years with ARTI are
respiratory syncytial virus (RSV), parainfluenza virus types
1, 2, 3, adenovirus, influenza virus types A, B, corona
virus, Coxsackievirus, other enteroviruses, human boca
virus and human metapneumovirus (hMPV) .
The hMPV, is the first member of a new genus
Metapneumovirus of the Paramyxoviridae family that infects
]. The RSV belongs to a separate genus
within the Paramyxoviridae family . hMPV was first
isolated in 2001 in the Netherlands [
]. hMPV has been
recently identified in nasopharyngeal aspirates (NPA)
of children and adults with ARTI in various parts of the
]. In temperate zones, hMPV infections
peak in late winter and spring months but slightly later
to the RSV peak in most studies [
]. We do not know the
prevalence of hMPV in tropical countries and it might be
due to lack of diagnostic facilities to detect respiratory
viruses in these countries.
The clinical syndrome in the children infected with
hMPV ranges from mild respiratory disease to severe
bronchiolitis and pneumonia [
]. The children with
severe disease require hospitalization [
with RSV and hMPV causes severe disease compared to
RSV or hMPV mono-infections [
]. The risk factors
for acquisition of viral ARTI is being studied in depth but
the details of the viral co-infection have not being fully
explored. Conversely, the prevalence of hMPV infection
in Sri Lanka was not known and there are no published
reports on the presence of hMPV in the country. Here
we report a case series of hMPV infection in children less
than 5 years of age in Sri Lanka.
The present study was conducted as a case series in which
patients admitted with ARTI (age 1 to ≤ 60 months)
were included from the Paediatric Professorial Unit,
Teaching Hospital, Anuradhapura from March 2013 to
August 2014. The informed consent was obtained from
all parents or guardians prior to taking information and
collecting nasopharyngeal aspirate (NPA) for viral
diagnosis. Indirect immunofluorescence assay was performed
using the DAKO IMAGEN™ UK (United Kingdom) as a
screening test followed by a direct immunofluorescence
assay (DFA) for specific identification of eight viruses
(RSV, parainfluenza virus 1, 2 and 3, influenza A and B
and hMPV) [
]. Stained slides were examined under
UV-epi fluorescence microscope (Leids, Germany) and
intracellular nuclear and/or cytoplasmic granular apple
green fluorescence emitting cells were considered as
virus positive (Fig. 1). Test was employed under
standard conditions while having simultaneous run of positive
and negative controls provided by manufacturer. Reverse
transcriptase-polymerase chain reaction (RT-PCR) of
hMPV was done to further confirm the hMPV infection.
A nested PCR was performed with L7 (5′-CACCCCAGT
CTTTCTTGAAA-3′) from 11,471 to 11,490 positions in
the detection of hMPV .
Data on clinical signs and symptoms, demography and
risk factors for acquiring ARTI were collected using an
investigator administered questionnaire by
interviewing the parent or guardian (Additional file 1).
Multivariable analyses were performed using a step wise logistic
regression analysis to assess the risk factors for the
development of RSV and RSV/hMPV co-infection. The risk
factors included in the study were age at hospitalization,
duration of the disease, gender of the child, ethnicity,
weight for the given age (as a measure of acute
malnutrition), height for the given age (as a measure of chronic
malnutrition) and Hb%, gestational age to assess the
maturity of the mother, mode of delivery and presence
of concurrent medical conditions (congenital heart
disease (CHD), chronic lung disease (CLD), asthma, cystic
fibrosis, immunodeficiencies and epilepsy) and genetic
disorders like Down’s syndrome-trisomy 21,
neuromuscular disorders and pre-existing respiratory tract
morbidity, parental passive smoking (father or any other family
member regularly smoking cigarettes in the vicinity of
the child), having house hold pets, presence of indoor
(cooking using firewood) and outdoor air pollution
(construction activities in the vicinity of the child),
overcrowding (living area of the child is < 24 m2 and living > 2
people in that area [
]), day care attendance (child
regularly attending to daycare), parent/guardian’s educational
level (< grade 8, up to advanced level and graduates),
experience of the caregiver (first child or having cared
for > 1 child) and parent/guardian’s occupation. For the
risk factor analysis, stepwise logistic regression and when
appropriate chi-squired test was also used. Odds ratio
was calculated and variables with a p value of < 0.05 and
multivariate odds ratios with 95% confident interval (CI)
s that did not include 1.0 were considered as significant.
Statistical analysis was done using SAS software, Version
During the study period, 418 patients with ARTI were
tested and 14 (0.03%) were diagnosed having hMPV
infection. Six children had co-infection with RSV. hMPV
infected patients were detected on two peaks, the first
peak occurred in April 2013 and 2014 and the second
peak occurred between December 2013 and January
Of the 14 hMPV infected children, nine were males
(0.66%). Twelve children were from rural areas and 3
were from semi-urban areas. Mean age of the hMPV
infected children was 18 months (6–36 months). Nine
patients had fever as the presenting complaint; 4 children
had only rales and 3 had only wheezing as the
presenting complaint. One patient had watery diarrhoea but his
stool culture was negative for bacterial pathogens causing
Three cases were diagnosed having exacerbation of
bronchiolitis following hMPV infection. One child had
severe bronchiolitis associated with RSV/hMPV
coinfection. One child had bilateral lower lobar
pneumonia and severe bronchiolitis following hMPV infection;
another child had right lower lobe pneumonia and severe
bronchiolitis following RSV/hMPV co-infection. These
children were admitted to intensive care unit and later
discharged with follow-ups by paediatric clinic for the
management of bronchiolitis. Two children had
infective exacerbation of asthma with hMPV infection and
the other had RSV/hMPV co-infection. Two patients had
common cold following hMPV infection and one had
common cold with RSV/hMPV co-infection. The disease
spectrum and severity following hMPV and RSV/hMPV
co-infection are described in Table 1.
Risk factor assessment for hMPV infection vs. RSV/
hMPV co-infection showed that the children delivered
through lower segmental cesarean section (LSCS) had an
odds ratio of 3.5 (95% CI 3.5, 2.2–4.8) and birth order > 3
had an odds ratio of 4.3 (95% CI 4.3, 3.2–5.6) for
developing RSV/hMPV co-infection compared to hMPV
monoinfection. The duration of illness and the average hospital
stay did not differ significantly in either hMPV or RSV/
hMPV co-infection (Table 2).
Viruses account for most of the respiratory tract
infections in childhood [
1, 12, 14
]. Viral infections of the
respiratory tract are often treated with antibiotics due to the
absence of viral diagnostics to identify the viral aetiology.
Both were treated
IEA infective exacerbation of asthma, ICU intensive care unit
Thus, a proper diagnosis is crucial prior to initiating
antibiotic treatment for bacterial ARTI or pneumonia [
In developing countries, a lack of availability of
diagnostic facilities contributes to the use of antibiotics and thus
to development of antimicrobial resistance [
imaging studies and blood cell differential count may give
a clue on the type of infective agent. However, in atypical
pneumonias, getting an educated guess about the
bacterial and viral causes are difficult. Hence, routine viral
laboratory diagnosis is crucial and implementation of such
facilities is highly warranted.
RSV is the most common respiratory viral pathogen
causing hospitalization of thousands of children each
]. Many of the affected children do not require
hospitalization and some with severe respiratory disease
are hospitalized or even managed in the intensive care
unit (ICU). The children requiring ICU admission are
typically young infants and those with co-morbidities.
These children can be severely ill and require
intubation and mechanical ventilation but most of the children
recover and a very few succumb to the disease. Currently
we are seeing the emergence of respiratory pathogens
either due to change in antigenicity in influenza viruses
or emergence and introduction of newly emerging viral
pathogens like hMPV [
In this case series, hMPV infection showed a disease
spectrum similar to that seen during RSV infection,
common cold to life threatening pneumonia. Children
delivered through LSCS appear to have less resistance to
] and in our study also, children delivered
through LSCS had a high risk of developing hMPV/RSV
co-infection. A child with a birth order > 3 had a high risk
of getting hMPV/RSV co-infection and this might be due
to lack of care to subsequent children in bigger families.
LSCS lower segment caesarian section
* p < 0.05 was considered as significant
** Only one hMPV infected child and no children with RSV/hMPV co-infection were available for comparison
In a few cases, even without co- morbidities, children
experienced severe hMPV infection needing ICU care. In
many cases, RSV/hMPV co-infection resulted in similar
disease spectrum to that of RSV infection.
Specific aetiological diagnosis of childhood ARTI is not
performed routinely in Sri Lanka. But if it is done
routinely it will invariably guide the clinicians on the use of
antibiotics including antivirals. This case series indicates
the importance of establishing laboratory diagnosis for
viral ARTI. Furthermore, hMPV is a potential pathogen
that needs to be tested in children with ARTI. A detailed
epidemiological study is in progress to elucidate the
prevalence and seasonality of childhood ARTI caused by a
wider range of respiratory viruses including hMPV in Sri
In this study, we have focused on inward patients only.
Therefore, we may have missed a significant number of
outpatients, who would have had milder form of hMPV
Additional file 1. Questionnaire of the respiratory study. Questionnaire
was used to gather demography and clinical manifestations in study
ARTI: acute respiratory tract infection; RSV: respiratory syncytial virus; hMPV:
human metapeumovirus; NPA: nasopharyngeal aspirates; UK: United
Kingdom; RT-PCR: reverse transcriptase-polymerase chain reaction; CHD:
congenital heart disease; CLD: chronic lung disease; ICU: intensive care unit.
MLMR involved in the medical management of the patients. JAASJ, FN, SK,
FNNP involved in designing and acquisition, analysis of data and writing up
the paper. FN critically read and corrected English in the final version. All
authors read and approved the final manuscript.
The authors thank Mr. AMSB Abeykoon, Department of Microbiology, Faculty
of Medicine, University of Peradeniya for the technical assistance.
The laboratory work was conducted at Department of Microbiology,
Faculty of Medicine, University of Peradeniya, Sri Lanka.
There authors declare that they have no competing interests.
Availability of data and materials
We have not shared the patients’ clinic records as they contain personal
Consent for publication
Ethics approval and consent to participation
The ethical approval was obtained from the Ethical Review Committee of the
Faculty of Medicine, University of Peradeniya, Sri Lanka. An informed written
consent was obtained from the parents/guardians of the study participants.
University Grants Commission (UGC/2012/JAAS Jayaweera) and University of
Peradeniya (RG/AF/2013/38/M—Prof F Noordeen).
Springer Nature remains neutral with regard to jurisdictional claims in
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