Tetanus in Southern Vietnam: Current Situation
Am. J. Trop. Med. Hyg.
Tetanus in Southern Vietnam: Current Situation
Duong Bich Thuy 0 1 2 3 4
James I. Campbell 0 1 2 4
Tran Tan Thanh 1 2 4
Cao Thu Thuy 1 2 4
Huynh Thi Loan 2 3 4
Nguyen Van Hao 2 3 4
Yen Lam Minh 1 2 4
Le Van Tan 0 1 2 4
Maciej F. Boni 0 1 2 4
C. Louise Thwaites 0 1 2 4
0 Centre for Tropical Medicine and Global Health, University of Oxford , Oxford , United Kingdom
1 Oxford University Clinical Research Unit , Ho Chi Minh City , Vietnam
2 Clinical Research Unit, Hospital for Tropical Diseases , 764 Vo Van Kiet, Ho Chi Minh City , Vietnam
3 Hospital for Tropical Diseases , Ho Chi Minh City , Vietnam
4 Authors' addresses: Duong Bich Thuy, Tran Tan Thanh, Cao Thu Thuy , Yen Lam Minh, Le Van Tan, and Maciej F. Boni , Oxford Uni- versity Clinical Research Unit , Ho Chi Minh City , Vietnam
In Vietnam, there are no accurate data on tetanus incidence to allow assessment of disease burden or vaccination program efficacy. We analyzed age structure of 786 tetanus cases admitted to a tertiary referral center in Vietnam for three separate years during an 18-year period to examine the impact of tetanus prevention programs, namely the Expanded Program on Immunization (EPI) and the Maternal and Neonatal Tetanus (MNT) initiative. Most cases were born before the initiation of EPI. Median age increased from 33 (interquartile range: 20-52) in 1994, to 46 (32-63) in 2012 (P < 0.001). Birth-year distribution was unchanged, indicating the same birth cohorts presented with tetanus in 1994, 2003, and 2012. Enzyme-linked immunosorbent assay measurements in 90 men and 90 women covered by MNT but not EPI showed 73.3% (95% confidence interval [CI]: 62.9-82.1%) of women had anti-tetanus antibody compared with 24.4% (95% CI: 15.9-34.7%) of men, indicating continued tetanus vulnerability in older men in Vietnam.
cases from the whole of southern Vietnam. Over recent
years, admissions of tetanus have remained high, with over
200 cases annually; similar to figures reported 20 years
ago.11 In view of the lack of accurate published data on
incidence of tetanus in LMICs and to estimate the impact
of the EPI and MNT programs in Vietnam, we carried out a
study examining patient demographics over an 18-year
period and measured anti-tetanus antibodies in a
population sample old enough to have been born prior to the
institution of the EPI program but young enough to have
reached child-bearing age after the initiation of MNT
initiative in 1991.
This study was approved by the Scientific and Ethics
Committee of HTD. Demographic data for all cases of
tetanus admitted to HTD between January 1 and December 31
for years 1994, 2003, and 2012 were collected. Although
accurate data collection began in 1993,11 data were only
available for 9 months in that year and to have a complete
year for analysis, 1994 was chosen. Recently in 2012
complete data were available and the year 2003 was selected
as it was the midpoint between 1994 and 2012. Data from
years 1994 and 2003 were collected prospectively onto
special case record forms and stored in an electronic
database. Data for 2012 were retrieved from the hospital
database. No data were available on neonatal patients in 1994,
therefore, cases occurring in infants < 1 year old were
excluded from all years. Both data sources distinguished
between patients discharged alive and those discharged
home against medical advice and felt likely to die by
attending staff. These latter events were classified as “deaths.”
To ascertain the degree of tetanus protection in the
population most at risk of tetanus, anti-tetanus antibodies were
measured in a random sample of 90 men and 90 women
born between 30 and 45 years (birth years 1984 or older)
using specimens from long-term general population serum
collection that has been ongoing in Ho Chi Minh City since
2009.12 Although EPI was initiated in Vietnam in 1981,
coverage in 1984 was still only 5%.2,13 Thus, individuals in this
cohort were selected as they were unlikely to be vaccinated
under the EPI program, but should have been covered by
the MNT initiative. Antibodies were measured using
nonquantitative enzyme-linked immunosorbent assay (ELISA) as
Records were retrieved from a total of 790 patients with
tetanus ≥ 1 year old. Four cases from the year 2003 were
excluded due to insufficient data, leaving a total of 786 cases
for analysis. Mortality rates fell during the study from 91/322
(28.3%) in 1994, to 20/245 (8.2%) in 2003 and 17/219 (7.8%)
in 2012. This coincided increased availability of mechanical
ventilation between 2000 and 2002.11
Male:female ratios were 1:2.12, 1:2.22, and 1:3.4 for the
years 1994, 2003, and 2012, respectively. Median (interquartile
range [IQR]) age of patients increased over the study period
from 33 (20–52) in 1994, to 35 (22–54) in 2003 and 46 (32–63)
in 2012 (P < 0.001; one-way analysis of variance [ANOVA]).
When the 2012 admissions were analyzed according to
gender, a particularly marked reduction was noted in women
born before 1981: 5/50 (10%) admissions were female in
2012 compared with 15/76 (19.7%) in 2003 and 22/103
(21.3%) in 1994.
The distribution of birth year for patient admissions is
shown in Figure 1. The majority of cases (75%) were born
before 1981. After correction for multiple comparisons,
there was no statistical support for the birth year
distribution changing by year of admission (one-way ANOVA,
Kruskal–Wallis test). Even if a larger sample size had made
these associations significant, the median birth year (1967,
across all patients) did not change by more than 1 year
when stratifying the data by year of admission. Median birth
year for males was 1970 and for females was 1952. In other
words, the same birth cohorts (mainly, pre-EPI cohorts)
were being admitted for tetanus infection over an 18-year
period despite the entire population aging by 18 years
during this time.
ELISA results are shown in Figure 2. Of women born before
1985, 73.3% (95% confidence interval [CI]: 62.9–82.1%) had
detectable anti-tetanus antibody compared with 24.4% (95%
CI: 15.9–34.7%) of men.
We report that significant numbers of tetanus cases
continue to occur in southern Vietnam. Although there are
relatively robust methods of recording cases of neonatal tetanus,
FIGURE 1. Birth year of tetanus admissions (≥ 1 year of age) admitted to the Hospital for Tropical Diseases by year. Effect of admission year
on birth year was tested with a one-way analysis of variance (ANOVA) and a Kruskal–Wallis (KW) test. The birth cohorts that represent tetanus
admissions do not appear to be changing over an 18-year period.
TETANUS IN SOUTHERN VIETNAM
FIGURE 2. Anti-tetanus antibody protection in 90 males and 90 females from a bank of general-population serum samples for Ho Chi Minh
City. Individuals are grouped into 4-year age bands. Confidence intervals are plotted with the exact binomial method.
in many countries, the reporting of tetanus in other age
groups remains inaccurate with significant underreporting.1,15
In 2012, the WHO reported a total of 186 cases in Vietnam
as a whole, 33 cases fewer than admitted to our hospital
alone.16 Improved surveillance has been a crucial element in
the success of the MNT initiative and if extended to all
tetanus cases, it would provide evidence of the need for wider
vaccination programs, and enable more accurate evaluation
of their success.17,18
Consistently high tetanus vaccination coverage has been
reported in Vietnam (range approximately 90–99% since
1994 for EPI and 89–93% for MNT2), and our data suggest
this appears to be having a significant impact. The majority
of cases still occur in individuals born before 1981.
Antibody measurements showed a large difference between
men and women born before the EPI program achieved
widespread coverage. In 2012, only 5/50 of female
admissions (10%) were born after 1981 compared with 47/219
(21%) of male admissions suggesting there continues to be
an extra benefit of the MNT initiative.
Our study is limited in that we were not able to ascertain
the number of tetanus cases that did not present to our
hospital and may have been treated in private facilities,
provincial hospitals, or may not have attended
healthcare facilities. It is likely that, as facilities for care have
improved over the 18-year study period, an increased
proportion of tetanus cases are being cared for in other
hospitals and we have underestimated the true regional
incidence. We also only examined disease impact from a
health-care perspective but the continuing occurrence of
tetanus has other consequences. The median hospital
cost of patients in our study was 521 U.S. dollars (IQR:
190–1,799) mostly paid directly by patient’s relatives.
When compared with a construction worker’s average
monthly salary of 215 U.S. dollars, this represents an
additional financial and social burden.19
Nevertheless, although a significant number of cases of
tetanus continue to occur in southern Vietnam, there is
evidence of the efficacy of prevention programs, particularly in
women. Improved understanding of how this is occurring
and which individuals remain at risk would improve the
design of vaccination catch-up programs and help reduce
the burden of this entirely preventable disease.
Received June 13, 2016. Accepted for publication September 9, 2016.
Published online November 7, 2016.
Financial support: This work was funded by Wellcome Trust grants
089276/B/09/7 and 098511/Z/12/Z.
This is an open-access article distributed under the terms of the
Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the
original author and source are credited.
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