Sains Malaysiana 50(2)(2021): 437-447

http://dx.doi.org/10.17576/jsm-2021-5002-15

Determinants of Pertussis among Young Children in Selangor, Malaysia

(Penentuan Pertusis dalam Kalangan Kanak-kanak di Selangor, Malaysia)

J ULIANA M ANSOR, H ALIM I SMAIL* & N ORIAH I SMAIL

ABSTRACT
The resurgence of pertussis infection worldwide, including Malaysia, is alarming. Young children have the highest
reported pertussis incidence and death rates. However, little is known of the risk factors of pertussis in Malaysia. In this
study, we aimed to determine the risk factors of pertussis infection among children. We conducted a case-control study
involving 143 children aged ≤2 years from Selangor, Malaysia. The children were identified from eNotifikasi, a web-
based notification site, from 1 January to 31 December, 2018. Information on clinical presentation and risk factors
were collected during investigation of the case by the district health office. Multivariate analysis showed that the odds
for pertussis were higher among children aged <3 months (adjusted odds ratio (aOR) 5.54; 95% confidence interval
(CI); 1.835, 16.710) and among children who had not received their vaccination according to age (aOR 5.641; 95% CI;
1.845, 17.245). The mean duration of cough among the cases was 10.22 days (SD 8.964); that of the controls was 6.47
days (SD 7.098). Paroxysmal cough (93.6%) was the predominant symptom among the cases. A total of 42.6% of
cases were aged <2 months, whilst most of the controls were aged >5 months (40.4%). Up to 42.6% of cases and 68.7%
of controls were immunised according to their age. Therefore, it is important to ensure that children are vaccinated
once they have attained the appropriate age.
Keywords: Children; DTaP; factors; immunization; pertussis

ABSTRAK
Kemunculan semula jangkitan pertusis atau batuk kokol di seluruh dunia, termasuk Malaysia, adalah membimbangkan.
Kanak-kanak merupakan kumpulan dengan kadar insiden dan kematian tertinggi direkodkan. Walau bagaimanapun,
maklumat risiko jangkitan tersebut amat sedikit di Malaysia. Oleh itu, kajian ini dijalankan bagi menentukan faktor
risiko jangkitan pertusis dalam kalangan kanak-kanak. Kajian kes kawalan dijalankan melibatkan 143 kanak-kanak
berusia ≤2 tahun. Subjek dikenal pasti melalui sistem eNotifikasi dari 1 Januari sehingga 31 Disember, 2018. Maklumat
berkaitan dengan tanda-tanda klinikal dan faktor risiko diperoleh semasa siasatan kes oleh pejabat kesihatan daerah.
Analisis multivariat mendapati bahawa risiko penjangkitan pertusis adalah tinggi pada bayi berusia <3 bulan (aOR
5.54; 95% CI; 1.835,16.710) dan kanak-kanak yang tidak menerima vaksinasi seperti dijadualkan (aOR 5.641; 95%
CI; 1.845,17.245). Purata jangka masa batuk dalam kalangan kes adalah 10.22 hari (SD 8.964); purata jangka masa
batuk dalam kalangan kawalan adalah 6.47 hari (SD 7.098). Batuk paroksisma (93.6%) merupakan gejala utama pada
kes. Sejumlah 42.6% kes berusia <2 bulan, manakala majoriti kumpulan kawalan berusia >5 bulan (40.4%). Sebanyak
42.6% kes dan 68.7% kawalan telah diberi vaksin mengikut jadual. Kesimpulannya, adalah penting bagi kanak-kanak
diimunisasi mengikut jadual yang telah ditetapkan.
Kata kunci: DtaP; faktor; imunisasi; kanak-kanak; pertusis

I NTRODUCTION preventive method against vaccine-preventable diseases

Children and young infants, especially those aged ≤2 (VPD) (WHO 2018a, 2015). Pertussis is a VPD and is an
years, are vulnerable to infectious disease (Edwards acute infection caused by the Gram-negative bacteria
2014; Esposito & Principi 2016). Many countries have (WHO 2017a) Bordetella pertussis, which is transmitted
introduced immunisation schedules for children as a person-to-person through direct contact with the airway
438

secretions of an infected person or indirectly by touching the risk factors associated with pertussis infection
a contaminated surface (WHO 2017a). To date, humans are among children in Selangor and to describe the clinical
the only known reservoir for B. pertussis (Tiwari 2005). presentation of the cases.
However, a recent study in naïve baboons noted that the
species can be infected with B. pertussis (Warfel et al. M ATERIALS AND M ETHODS
2016), and entirely airborne transmission of the bacteria
can occur (Warfel et al. 2012). Pertussis tends to occur STUDY SETTING
in younger infants and cause a severe life-threatening According to Malaysia’ Act 342 ( LOM 2006), all
condition (Edwards 2014; Esposito & Principi 2016). suspected pertussis cases must be notified to the nearest
In 2014, there were an estimated 24.1 million cases district health office. All notified cases are captured in
globally in children aged <5 years, including 5.1 million the real-time, web-based notification system, eNotifikasi.
cases among infants (WHO 2018a; Yeung et al. 2017). Any suspected case with suggestive clinical features of
The incidence rate of pertussis in Malaysia also shows pertussis infection diagnosed by health facilities must
an increasing trend, from 0.2/100,000 population to be notified to the nearest district health office (DHO). A
1.0/100,000 population, over the past twenty years (MOH confirmatory laboratory test, either by PCR or culture,
2017). However, it is believed that the true incidence must proceed together with the notification. A positive
of pertussis is notably higher than the data captured test is classified as a confirmed case. In Malaysia, PCR
by reporting and surveillance systems due to incorrect is mainly used for laboratory confirmation of pertussis,
diagnosis, under-reporting and low consultation, especially as it yields results quickly (DCD 2010). Subsequently,
among adolescents and adults with mild symptoms the DHO investigates each notified case using a Pertussis
(Esposito & Principi 2016). In Malaysia, pertussis is a Investigation Form. Here, we conducted a case–control
mandatory notifiable disease and is monitored under a study using the data captured in the form in Selangor,
surveillance system (WHO 2018b). Besides, the increasing Malaysia from 1 January, 2018 to 31 December, 2018.
prevalence of pertussis infection increases the healthcare
burden (Koh et al. 2016; Van Hoek et al. 2014). For SAMPLE SIZE
pertussis cases, the estimated overall loss of quality of The minimum sample size calculated using PS: Power
life is 0.097 quality-adjusted life years (QALYs) (Van and Sample Size Calculation (Dupont & Plummer 2009)
Hoek et al. 2014). In 2012, the medical-related cost in based on multiple risk factors (Curtis et al. 2017; Deeks et
Malaysia was around 2% of the average monthly wage al. 1999; Glanz et al. 2013), with a confidence interval (CI)
(Koh et al. 2016). of 95% and power of 80%, was 150 (50 cases and 100
Multiple international studies have shown a number controls), allowing for a 20% missing data rate.
of risk factors linked to pertussis infection, such as
waning immunity against pertussis in the community SAMPLE SELECTION
(Cherry 2012), infection transmission from asymptomatic
individuals (Althouse & Scarpino 2015) and vaccine Stratified random sampling was performed (Figure 1).
refusal or delay (Glanz et al. 2013). However, research Initially, a list of positive and negative cases was obtained
from the eNotifikasi system. Both lists were stratified
on this issue in Malaysia is very scarce. Furthermore,
into all nine districts in Selangor based on the addresses.
the increasing trend of the anti-vaccine movement adds
Then, a proportion of positive cases was selected from
to the underlying problem of vaccine defaulters, thus
each district based on the total number of cases required
contributing to the resurgence of pertussis. Unpublished
using the simple random technique by SPSS software
data by the Ministry of Health Malaysia (MOH) shows
(IBM 2013). Cases were defined as children aged ≤2 years
that the number of vaccine refusal cases increased from
with laboratory-confirmed pertussis. For every case, we
600 in 2013 to 1600 in 2016 (Faridah 2017). Although included two controls from the same district. Controls
the vaccination rate in Malaysia has always been high were captured from the list of discarded (negative)
(WHO 2018a; 2018b), there remain pockets of vaccine cases using the simple random technique. Children were
refusal in many communities. This poses a threat to the excluded if the DHO had been unable to investigate them
local population, as the risk for VPD outbreak, including and if the child had died during the investigation. The
pertussis is high (Phadke et al. 2016; Smith 2017). Thus, same applied to the control, with the additional exclusion
the main aim of the present study was to determine criterion of no sample obtained.
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FIGURE 1. The sampling protocol for the study

INSTRUMENTS version 22 ( SPSS 22) ( IBM 2013). Categorical data

The form includes demographic data, signs and symptoms, are expressed as frequencies (n) and percentage (%);
complications, immunisation status, breastfeeding continuous data are expressed as the mean and standard
status, suspected sources of infection, and laboratory deviation (SD). Bivariable comparison of risk factors
results. Information on clinical signs and symptoms between the cases and controls was calculated using
and complications related to pertussis was obtained for simple logistic regression; the multivariable test using
both groups. The risk covariates were divided into two stepwise logistic regression was performed to assess the
groups: The individual’s covariates: age (0-1 months, 2 impact of several factors on the likelihood of pertussis
months, 3-4 months, ≥5 months), sex (male/female), race infection and for obtaining important risk factors
(Malay/Chinese/Indian/Other), immunisation status (age- of pertussis infection. The odds ratio (OR) for each
appropriate immunisation: dose 1 at 2 months, dose 2 at independent variable in the model was estimated
3 months, dose 3 at 5 months, booster dose at 18 months; using a logistic regression coefficient. A p-value < 0.05
those with age-appropriate immunisation were classified was used as the level of significance. Interaction and
as yes; those aged <2 months were classified as unqualified multicollinearity were checked.
for immunisation) and number of doses (0/1/2/3/4),
breastfeeding status (breastfeeding/mixed feeding/ ETHICAL APPROVAL
formula milk feeding); Their contacts’ covariates: Source
This research was approved by the National Medical
of infection (household/other/unknown) and symptom
Research Registry of Malaysia (NMRR ID: NMRR-19-
status (symptomatic/asymptomatic). In Malaysia, pertussis
534-46053) and the Research Ethics Committee (REC) of
immunisation is administered through the Diphtheria-
Universiti Kebangsaan Malaysia (Ref no.: UKM PPI.800-
Tetanus-acellular Pertussis (DTaP) vaccine, with primary
1/1/5/JEP-2019-405).
doses given at 2, 3 and 5 months, and a booster dose at
18 months. The presence of any type of complication was
classified as yes. RESULTS
Out of 1085 notifications, a total of 256 laboratory-
confirmed cases were recorded in Selangor from 1
STATISTICAL ANALYSIS
January, 2018, until 31 December, 2018, of which 253
All data collected and extracted were analysed using cases (98.8%) were children. Of these, 241 (95%) were ≤2
the software Statistical Package for the Social Sciences years old. A final 146 children were enrolled in the study:
440

47 pertussis cases and 97 negative controls. The mean age suspected source, with no or unknown contact with an ill
of the cases was 3.9 months (SD 4.4) months; 51.1% were person. Most of the children were born at term and were
female (Table 1). The majority of cases were Malaysian breastfed solely or were on mixed feeding. Regarding
citizens (97.9%) and were Malay (91.5%). Only 42.6% clinical presentation, the mean days of cough before
of cases had received immunisation according to age; cases received treatment was 10.2 days; only 30% of
68.7% of the control group had been immunised up-to- cases had a history of prolonged cough for >14 days. The
age. Around 55.3% of the cases had never have received top three common symptoms the cases experienced were
any DTaP vaccine previously; in contrast, the control paroxysmal cough (93.6%), fever (57.4%) and post-tussive
group had a lower portion of unimmunised children, i.e. vomiting (51.1%); the most common complication was
29.3%. Regarding the source of infection, 51.1% of the pneumonia (21.3%) (Figures 2 & 3).
cases and 53.5% of the controls were unsure of the

TABLE 1. Descriptive analysis showing the characteristics of the children

Case n (%) Total

Control
Socio-demographics
Citizenship Malaysian 46 (97.9) 97 (98.0) 143 (97.9)
Non-Malaysian 1 (2.1) 2 (2.0) 3 (2.1)
Age (months) Mean (SD) 3.94 (4.37) 4.93 (4.01)

9(((4.3706) ((4.0090)
0–1 9 (19.1) 15 (15.2) 24 (16.4)
2 20 (42.6) 18 (18.2) 38 (26.0)
3–4 7 (14.9) 26 (26.3) 33 (22.6)
≥5 11 (23.4) 40 (40.4) 51 (34.9)
Race Malay 43 (91.5) 93 (93.9) 136 (93.2)
Chinese 1 (2.1) 0 (0) 1 (0.7)
Indian 2 (4.3) 2 (2) 4 (2.7)
Other 1 (2.1) 4 (4) 5 (3.4)
Sex Male 23 (48.9) 56 (56.6) 79 (54.1)
Female 24 (51.1) 43 (43.4) 67 (45.9)
Clinical presentation: Days of cough before seeking 10.22 (8.96) 6.97 (7.10)

treatment, mean (SD)

Presence of complications: Yes 11 (23.4) 37 (37.4) 48 (32.9)

Immunisation
Age-appropriate Yes 20 (42.6) 68 (68.7) 88 (60.3)

immunisation Unqualified 15 (31.9) 23 (23.2) 38 (26.0)

No 12 (25.5) 8 (8.1) 20 (13.7)
DTaP dose 1 12 (25.5) 16 (16.2) 28 (19.2)
2 3 (6.4) 22 (22.2) 25 (17.1)
3 6 (12.8) 31 (31.3) 37 (25.3)
4 0 1 (1) 1 (0.7)
0 26 (55.3) 29 (29.3) 55 (37.7)
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Source and contact

Suspected source of Household 20 (42.6) 29 (29.3) 49 (33.6)

infection Unknown 24 (51.1) 53 (53.5) 77 (52.7)

Other 3 (6.4) 17 (17.2) 20 (13.7)

Contact health status Symptomatic (Yes) 19 (40.4) 36 (36.4) 55 (37.7)

Asymptomatic (No/unknown) 28 (59.6) 63 (63.6) 91 (62.3)

Relationship of Household 16 (34) 25 (25.3) 41 (28.1)

symptomatic contact Other 5 (10.6) 14 (14.1) 19 (13.0)

Not relevant 26 (55.3) 60 (60.6) 86 (58.9)
to case

Birth and feeding

Gestation Term 40 (85.1) 84 (84.8) 124 (84.9)
Preterm 7 (14.9) 15 (15.2) 22 (15.1)
Feeding status Breastfeeding only 24 (51.1) 38 (38.4) 62 (42.5)
Formula milk 3 (6.4) 19 (19.2) 22 (15.1)
Mixed feeding 20 (42.6) 42 (42.4) 62 (15.1)

Distribution of clinical presentation among cases and controls, n = 47

100
90
Number of people (%)

80
70
60
50
40
30
20
10
0
congestion
Fever

Posttussive

Inspiratory

Cyanosis

Apnea
Paroxysmal

Prolonged
vomiting

whoop

Facial
cough

cough

FIGURE 2. The distribution of clinical presentation among the cases and controls

Distribution of complications among cases and controls, n = 47

25
Number of people (%)

20

15

10

0
Pneumonia Seizure ICU admission Intubation Encephalopathy

FIGURE 3. The distribution of complications among the cases and controls

442

In the bivariable analysis, only the risk factors were 5.1 more likely to develop pertussis than those who had
analysed. We did not analyse the clinical presentation been immunised accordingly (p = 0.002). Children who
and complications further. The analysis showed three had received two (p = 0.019) and three doses (p = 0.021)
significant factors: Age group, immunisation status and were 1.5-2 times less likely to be infected compared to
DTaP vaccine dosage received (Table 2). Infants aged those who did not receive any vaccination. The more
2 months had 4.04 greater odds of being infected DTaP dosages received, the less likely the child would
compared to those aged ≥3 months (p = 0.003). Children be infected.
who had not been immunised according to their age were

TABLE 2. Association of risk factors with pertussis infection

Variables Crude OR 95% CI χ2 (df)a p-valuea

Citizenship Malaysian 0.95 0.08, 10.73 0.01 (1) 0.966

Non-Malaysian 1.00
Race Malay 0.69 0.19, 2.59 0.29 (1) 0.590
Non-Malay 1.00

Sex Male 0.74 0.37, 1.48 0.75 (1) 0.388

Female 1.00

Age, months 11.85 (3) 0.008

0–1 2.18 0.75, 6.31 2.07 (1)b 0.150b

2 4.04 1.61, 10.16 8.80 (1)b 0.003b

3–4 0.98 0.34, 2.85 0.002 (1)b 0.969b

≥5 1.00

Complications Yes 0.51 0.23, 1.13 2.92 (1) 0.088

No 1.00

Age-appropriate 11.23 (2) 0.004

immunisation Yes 1.00

Unqualified 2.22 0.98, 5.03 3.63 (1)b 0.057b

No 5.10 1.83, 14.20 9.72 (1)b 0.002b

DTaP dose 17.99 (4) 0.001

1 0.84 0.33, 2.09 0.15 (1)b 0.70b

2 0.15 0.04, 0.57 7.85 (1)b 0.019b

3 0.22 0.08, 0.60 8.65 (1)b 0.021b

4 <0.01 <0.01 <0.01 (1)b 1.000b

0 1.00

Suspected source of 4.74 (2) 0.093

infection Household 3.91 1.01, 15.12 3.90 (1)b 0.048b

Unknown 2.57 0.69, 9.59 1.96 (1)b 0.161b

Other 1.00
 443

Contacts’ health status Yes 1.19 0.58, 2.42 0.22 (1) 0.637

(Symptomatic) No/unknown 1.00

Relationship of 1.31 (2) 0.519

symptomatic contact Household 1.48 0.68, 3.22 0.97 (1)b 0.33b

to case Other 0.82 0.27, 2.53 0.12 (1)b 0.735b
Not relevant 1.00

Gestation Term 1.00

Preterm 1.02 0.39, 2.70 0.01 (1) 0.968

Feeding status 5.21 (2) 0.074

Breastfeeding 1.00

Formula milk 0.25 0.07, 0.94 4.23 (1)b 0.040b

Mixed feeding 0.75 0.36, 1.58 0.56 (1)b 0.453b

Likelihood ratio test, bWald test, df, Degree of freedom

a

Multivariable analysis was performed using all present. Infants aged <3 months had 5.5 times greater
variables that were significant in the bivariable analysis. odds of being infected compared to those aged ≥5
The final backward stepwise model containing both months. Meanwhile, children who had never received
predictors was statistically significant (χ2 (6, n = 146) any vaccination against pertussis had 5.6 times higher
= 22.013, p = 0.001). The model correctly classified odds of infection than those who had been immunised
71.2% of cases. Neither interaction nor collinearity was according to schedule (Table 3).

TABLE 3. Multivariable analysis of pertussis risk factors

Variable Crude OR Adjustedb OR χ2 (df)a p-valuea

(95% CI) (95% CI)
Age, months 0–1 2.18 4.04 (0.72, 22.64) 2.51 (1)b 0.113b
2 4.04 5.54 (1.84, 16.71) 9.23 (1)b 0.002b

3–4 0.98 1.31 (0.42, 4.11) 0.21 (1)b 0.646b

≥5 1.00 1.00

Age-appropriate Yes 1.00 1.00

immunisation Unqualified 2.217 0.90 (0.23; 3.45) 0.03 (1)b 0.873b

No 5.10 5.64 (1.845, 17.245) 9.208 (1)b 0.002b

a
Likelihood ratio test, bWald test, df, Degree of freedom
444

DISCUSSION Immunisation Campaign, the provision of immunisation

Our results indicate that young infants are vulnerable to kits to clinics as education material, training healthcare
pertussis infection. This finding is consistent with that of workers as vaccine advocates, forums and seminars with
other studies (Masseria et al. 2017; Winter et al. 2015). multiagency collaboration, and promotion through social
Another study in Malaysia reported similar findings, where media and mass media (Faridah 2017).
the majority of positive PCR results were from children Multiple studies have shown that adult and maternal
aged <3 months (Ting et al. 2013). Due to the immunisation vaccination of Tdap (Tetanus, diphtheria, acellular
schedule, there is a window of vulnerability for pertussis pertussis) given during pregnancy is effective for
infection in infants aged <2 months. Younger infants are preventing pertussis in new-borns, at least until the child
more vulnerable to infection because their immunity has has received their vaccination (Curtis et al. 2017; Forsyth
not fully matured. Besides, immunity against infection is et al. 2015), as breastfeeding does not confer protection
not long-lasting, even in people who have previously been against pertussis (Pandolfi et al. 2017). Besides that,
infected or immunized, thus rendering young infants a few studies have shown the role of households or
more vulnerable (Cherry 2016). If a deduction were to mothers as a risk factor for infection (Hughes et al. 2017;
be made based on age group, it would be that the first Winter & Harriman 2018). The Advisory Committee
dose of DTaP does not confer protection against pertussis on Immunisation Practices (ACIP) recommends a
infection, while the second and third doses do, as shown Tdap booster for adults with no previous immunization
in the bivariate analysis. Radke et al. (2017) reported a and a dose of Tdap at 27-36 weeks of gestation during
similar finding, where vaccine effectiveness increased with each pregnancy for women regardless of the previous
the number of doses received, at least until the primary dose vaccination (Liang et al. 2018). Nevertheless, we found
had been completed. However, we observed that although that contact status and relationship were not significant.
the children might not have received a complete primary However, there might be a role for introducing adult or
dose of DTaP vaccine, receiving vaccination according maternal Tdap vaccination to curb pertussis among young
to their age means that the children would be protected infants in Malaysia, as there is evidence of elevated risk of
compared to children who have missed their vaccination. pertussis among younger infants. Tdap vaccination would
This is supported by Glanz et al. (2013), McNamara et increase the population’s herd immunity and protect
al. (2017) and Radke et al. (2017). younger infants from contracting the infection.
The effectiveness of the acellular pertussis vaccine Here, the mean duration of cough among the cases
in protecting children according to the number of doses was shorter than the conventional clinical criteria for
received has been demonstrated (Radke et al. 2017). pertussis, which is 14 days (CDC 2014; WHO 2017b).
However, no formal efficacy study has addressed the However, in recent years, international organizations
effect of incomplete primary dose or a single dose (WHO have made an exception for prolonged cough as the
2017a). The difference recorded in the present study was clinical criteria, especially among children aged <1 year.
because 39.7% of the children had not received their The Centers for Disease Control and Prevention (CDC)
immunization, although one-third of them had attained has stated that the presence of apnoea (with or without
the appropriate age for vaccination. There might be similar cyanosis) in infants, paroxysmal cough, inspiratory whoop
findings in other states in Malaysia, especially those with or post-tussive vomiting with cough of any duration
similar demographic and socioeconomic distribution are clinical criteria for pertussis (CDC 2014). A study
to Selangor. Through the Malaysia National Health and conducted among infants with critical pertussis in a tertiary
Morbidity Survey 2016, Lim et al. (2017) noted that the healthcare centre in Malaysia noted a mean duration of
vaccination coverage of DTaP among participants aged cough of 1 week (Lin et al. 2016). Meanwhile, a study
0-59 months was 89.0-89.8% for the three doses. in North-West Malaysia found that cyanosis was the
In the present study, we found a higher rate of 18.5% only symptom associated with pertussis (Salwana et al.
non-vaccinated children among those who qualified 2017), a similar finding to ours. In contrast, a systematic
for the vaccine. Although the rate appears sufficient review by Ebell et al. (2017) noted greater susceptibility to
for herd immunity level, we should bear in mind that whooping cough (41%) and post-tussive vomiting (56%),
immunity against pertussis is not long-lasting. Hence, whilst children were four times more likely than adults
this will increase the pool of non-immune people over to present with whooping cough. However, the overall
time. In comparison with regional and global vaccination presentation is the most accurate predictor, rather than
coverage, which is 85-94% for DTaP1 and DTaP3 (WHO individual signs or symptoms (Moore et al. 2017). The
2019a, 2019b, 2018c), our findings indicate slightly lower authors also noted that vaccinated children tend to lack
coverage in Malaysia. The MOH has made continual efforts the typical signs and symptoms of pertussis, explaining
to ensure high vaccine coverage, such as the National the low rate of clinical suspicion among them compared to
 445

unvaccinated children. A meta-analysis noted that apnoea in Selangor and the Selangor State Health Department for
and cyanosis were both moderately specific and sensitive their cooperation during this study. This research received
in infants, while post-tussive vomiting was less helpful as a a PPUKM Fundamental Grant from the Universiti
clinical diagnostic criterion (Moore et al. 2017). Regarding Kebangsaan Malaysia Health Centre.
complications, most of the cases developed pneumonia.
A study in Peru has reported similar findings (Del Valle- REFERENCES
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