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Current Drug Therapy, 2023, 18, 205-210

SYSTEMATIC REVIEW ARTICLE
ISSN: 1574-8855
eISSN: 2212-3903

Yellow Fever Vaccination in Hemodialysis Patients: A Systematic Review

Emery Ciana Figueiredo Vidal1,2, Glaucia Luciano da Veiga2, Marcelo Rodrigues Bacci2,*, Eglidia
Carla Figueiredo Vidal1,2, Beatriz da Costa Aguiar Alves2, Thaís Gascón2 and Fernando Luiz Affonso
Fonseca2

1
Universidade Regional do Cariri (URCA), Ceará, Brazil; 2Clinical Analysis Laboratory, Centro Universitário ABC,
Santo Andre, Brasil

Abstract: Introduction: Yellow fever is an infectious disease endemic to Africa, and Central and
ARTICLE HISTORY
Received: April 19, 2022
Revised: November 29, 2022
Accepted: November 30, 2022
DOI:
10.2174/1574885518666230123160533
South America with a significant impact on public health, causing outbreaks and epidemics. Clinical
manifestations can vary from asymptomatic to more severe and lethal disease outcomes. The primary
prevention of yellow fever occurs through the vaccination of individuals, which confers immunity for
life. Patients with chronic kidney disease, especially those undergoing dialysis, have low vaccination
and seroconversion rates. As mentioned above, this research aimed to perform a systematic review of
the yellow fever vaccination protocol in hemodialysis patients.
Methods: A systematic review on vaccination against yellow fever in hemodialysis patients using da-
tabases, PubMed and Biblioteca Virtual em Saúde (BVS), was performed. For data collection, combi-
nations were made using the following descriptors: protocols, vaccination, yellow fever, kidney dialy-
sis, chronic kidney failure, chronic kidney disease, and group risk included in the title and abstract de-
scription. Articles with no subject related to the search were excluded and also if they were duplicated.
Results: In this review, 90 scientific articles were identified in both databases. After applying exclu-
sion criteria, a total of 3 articles were selected.
Conclusion: We recommend carefully assessing the risk-benefit and contraindications for the patient,
emphasizing the risk groups. There is an evident lack of studies on the subject, and there is a need to
broaden investigations related toimmunization for patients on dialysis. The review is registered in the
PROSPERO system with the number 323550.

Keywords: Hemodialysis, chronic kidney disease, vaccine, vaccination, yellow fever, infectious disease.
Current Drug Therapy

1. INTRODUCTION These outbreaks are induced by the existence of a high

Yellow fever (YF) is an immune acute, viral infectious
disease whose causative agent is the Flavivirus of the family
Flaviviridae. Mosquitoes of the Culicidae family transmit
the disease with their bites, with Aedes aegypti being the
primary vector for urban YF transmission and Haemagogus
the primary vector for wild YF.
YF is an endemic disease found in the tropical areas of
Africa, Central America, and South America. In Brazil,
since 2000, the endemic cloud has increased from the
Northern and Central areas to the Southeastern and Southern
regions. In the extra-Amazon area, epidemic periods occur,
characterizing the resurgence of the virus in the country,
with the most significant number of cases occurring be-
tween December and May.
*Address correspondence to this author at the Clinical Analysis Laboratory,
Centro Universitário ABC, Santo Andre, Brasil;
E-mail: mrbacci@yahoo.com
density of vectors and primary hosts, susceptible individu-
als, and low vaccination coverages [1-3].
It is estimated that 200,000 cases occur annually, result-
ing in over 30 thousand deaths, with 90% of them in Africa.
Since 2016, Brazil has experienced one of the most signifi-
cant outbreaks of wild-type YF in its history, occurring in
states of the Southeastern region. 448 cases and 144 deaths
were confirmed from this year to 2017 [4].
The clinical spectrum of YF pathology ranges from
asymptomatic cases to severe and lethal ones. In
mild/moderate forms (20 to 60% of cases), treatment is
symptomatic; in severe forms (20 to 40% of cases), renal
and hepatic failure may occur, of which 20 to 50% of cases
may be fatal [1, 5].
The measures for the prevention and control of yellow
fever consist of vaccinating at-risk people and populations
and vector control in the transmission areas to reduce the
infection rates [1, 6].

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206 Current Drug Therapy, 2023, Vol. 18, No. 3
Yellow fever vaccination (YFV) is the most critical and
influential measure for preventing and controlling the dis-
ease. The World Health Organization (WHO) recommended
that the vaccine contains sub-strains of the 17D or 17DD
virus. It is considered highly immunogenic, immunizing
above 95% of adults and 90% of children less than two
years of age one week after application [1, 6].
The WHO recommends vaccination for all individuals
over nine months of age who are residents or travelers to
areas with vaccination recommendations (ACRV) and coun-
tries at risk for the disease. Since 2018, Brazil has become a
YFV recommendation area. The vaccine is also indicated
for health care professionals [7-10]. The YFV is not rec-
ommended for children under six months of age, people
over 60 years of age, pregnant women, nursing mothers,
individuals with a history of proven anaphylaxis to chicken
eggs and their derivatives, in addition to bovine gelatin, and
also in patients with severe immunosuppression, organ
transplant patients, patients with thymus diseases and pa-
tients with systemic lupus erythematosus [3, 10, 11].
According to Pileggi et al., the YFV is highly immuno-
genic, with the potential risk of inducing a severe adverse
event following vaccination (AEFV). However, the majority
of symptoms are mild. More rarely, a severe adverse event
(SAE) may occur, characterized by hospitalization. The neu-
rotropic disease is also associated with the YFV, which can
cause hypersensitive reactions and neurological manifesta-
tions (encephalitis, meningitis, Guillain-Barré syndrome)
[3].
In 2013, the WHO recommended one dose of YFV suf-
ficient for permanent protection instead of the previous 10-
year booster dose. In 2014, the International Health Regula-
tions were amended, extending the validity of the Interna-
tional Certificate of vaccination against YF from 10 years to
the whole lifespan of the vaccine [12]. These recommenda-
tions were implemented in Brazil as of April 2017 [13].
Chronic kidney disease (CKD) is a significant public
health problem that advances silently, slowly, and with a
progressive reduction of the glomerular filtration rate. In
late advanced disease, there is the possibility of initiation of
renal replacement therapy (RRT): hemodialysis, peritoneal
dialysis, or kidney transplantation. The prevalence of pa-
tients on RRT is approximately 1,500 patients per million
people in Brazil [14, 15].
CKD is also an inflammatory condition closely related to
other diseases responsible for its development, such as arte-
rial hypertension and diabetes. As the glomerular filtration
rate declines, the inflammatory profile increases, vaccina-
tion might be affected, and a particular regimen could be
implemented.
Within this context, the individual with chronic kidney
disease needs to be carefully evaluated for vaccination sta-
tus, including immunity to yellow fever. These are generally
immunosuppressed patients.
For instance, there is a particular regimen for vaccina-
tion against type B hepatitis with four shots instead three as
what the general population receives, so it is reasonable to
ask why there is no guidance regarding YFV for this specif-
ic group.
Vidal et al.
In Brazil, according to the last census conducted by the
Brazilian Society of Nephrology (BSN) in 2018, there were
an estimated 133.464 patients undergoing dialysis, 92.3% of
whom were on conventional hemodialysis. The estimated
prevalence rate of patients on dialysis was 640 patients per
million inhabitants, and the mortality rate was about 19.5%
for the year [16].
As mentioned above, this research aimed to perform a
systematic review of the yellow fever vaccination protocol
in hemodialysis patients in Brazil.
2. METHODS
We performed a systematic review study of an explora-
tory-descriptive character with a quantitative approach. The
following steps of the integrative literature review method
were followed: identification of the problem (the purpose of
the review was clearly defined) and the literature search,
i.e., the evaluation and analysis of the data obtained [17,
18]. The bibliographical survey was carried during the be-
ginning of each database until Nov 30, 2019; inclusion crite-
ria were articles in Portuguese, English, and Spanish, pub-
lished in the databases U.S. National Library of Medicine
National Institute of Health (PubMed) and Biblioteca Virtu-
al em Saúde (BVS), and also on government websites (Min-
istry of Health) and Brazilian Society of Nephrology, which
presented in their discussion considerations about the yellow
fever vaccination protocol in hemodialysis patients.
For data collection, combinations were made using the
following descriptors from Mesh (Medical Subject Head-
ings) and DeCS (Health Sciences Descriptors): protocols,
vaccination, yellow fever, kidney dialysis, chronic kidney
failure, chronic kidney disease and risk group included in
the title and abstract description. All the results found have
been reported in this analysis to avoid bias.
3. RESULTS
In this review, 35 scientific articles were initially identi-
fied in PubMed and 55 in BVS for exploratory reading of
abstracts, totaling 90 articles; of these, 25 were duplicated,
with 65 articles selected for analysis of abstracts and, ac-
cording to the theme, read in full. After the analytical read-
ing of these articles, only 3 were selected as the object of
study, as they presented aspects that answered the guiding
question of this review. The steps of this process are pre-
sented in Table 1.
One document was identified in a search carried out on
the websites of the Brazilian government and the Brazilian
Society of Nephrology. Fig. (1) shows the PRISMA flow
diagram, which shows the articles' choice process.
Three scientific articles and one official document from
the BSN were selected, presenting aspects related to this
review's guiding question.
The table below specifies the articles selected.
Despite being an integrative review, we chose to insert
the recommendation of the Brazilian Nephrology Society to
emphasize the lack of guidance regarding this vital aspect of
immunization for an endemic condition in Brazil.
Yellow Fever Vaccination in Hemodialysis Patients Current Drug Therapy, 2023, Vol. 18, No. 3 207

Table 1. Distribution of bibliographic references obtained in the PubMed and BVS databases, according to selected descriptors.

Database Descriptors Number of Analyzed Duplicated Selected

References Abstracts References References for
Obtained Revision

Protocols AND vaccination AND yellow fever AND renal dialysis 0 0 0 0

PubMed Protocols AND vaccination AND yellow fever 7 7 0 1
Vaccination AND yellow fever AND renal dialysis 6 6 0 2
Vaccination AND yellow fever AND Renal Insufficiency Chronic 0 0 0 0
Vaccination AND yellow fever AND Chronic kidney disease 3 3 1 0
Vaccination AND yellow fever AND Risk Groups 19 19 1 0

- - 35 35 2 3

Protocols AND vaccination AND yellow fever AND renal dialysis 0 0 0 0

BVS Protocols AND vaccination AND yellow fever 13 13 4 0
Vaccination AND yellow fever AND renal dialysis 2 2 1 0
Vaccination AND yellow fever AND Renal Insufficiency Chronic 0 0 0 0
Vaccination AND yellow fever AND Chronic kidney disease 1 1 1 0
Vaccination AND yellow fever AND Risk Groups 39 39 17 0

- - 55 55 23 0

Fig. (1). PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only.
208 Current Drug Therapy, 2023, Vol. 18, No. 3 Vidal et al.

There were no randomized controlled trials found, and 4. DISCUSSION

only one observational study was obtained. Moreover, sys-
Although CKD research has advanced, the lack of he-
tematic reviews and meta-analyses were not found. In the
modialysis patients' immunization is evident. Most studies
cross-sectional study mentioned above, the coverage for
recommend diagnostic vaccination against hepatitis B, in-
YFV in CKD and hemodialysis patients was low. Adverse
reactions might occur, but they did not contraindicate its fluenza, and pneumococcus [18]. According to Table 2, a
specific protocol for YFV for hemodialysis patients has not
administration.
been identified.
Table 2. The analysis of methodological aspects of articles collected in databases on YFV protocol in hemodialysis and CKD
patients.

Article Author, Journal, Year Title Type of Study Main Conclusions

1 Porudominsky R, Gotuzzo, EH Yellow Fever Vaccine and
Rev Panam Salud Publica, 2018 [18] Risk of Developing Serious
Adverse Events: A Systematic
Review
Systematic The safety of the yellow fever vaccine is con-
Review firmed based on data from several vaccination
campaigns and studies. Adverse effects appear
more frequently after an initial dose, mainly in
risk groups. However, this review evaluated
vaccination in risk groups, and most of the
vaccine was considered safe.

2 Lopes RL, Pinto JR, Junior GBS et al.
Rev Inst Med Trop Sao Paulo, 2019
[19]
Kidney Involvement in Yellow
Fever: A Review
Review Yellow fever mortality can be high, even with
intensive treatment, due to multiple organ fail-
ure, including acute kidney injury (AKI). The
pathophysiology of acute kidney injury (AKI)
induced by yellow fever has yet to be fully
understood. This manuscript presents the most
recent scientific evidence of kidney involve-
ment in yellow fever, as AKI plays an essential
role in the mortality rate.
It highlights the importance of immunization.

3 Facincani T, Guimarães, MNC,
Santos, SS
Int J Infect Dis, 2016 [20]
Yellow Fever Vaccination
Status and Safety in Hemodi-
alysis Patients
Author links open overlay
panel Tila Facincani Maia
Nogueira Crown Guimarães
Sigrid de Sousa dos Santos
Cross-sectional Previous vaccination has been verified in 44
patients in the last ten years and 26 patients for
more than ten years, with no adverse effects.
Thirty-six patients had never been vaccinated,
and 24 had an unknown vaccination status. Of
the 86 patients referred for immunization, 45
received the vaccine against yellow fever, with
24.4% showing mild local adverse effects and
4.4% developing a fever. No serious adverse
effects were attributable to the YF vaccine
(anaphylaxis, neurological or viscerotropic
disease).
Yellow fever vaccine coverage among hemodi-
alysis patients is low, and the vaccine appeared
safe in this population with a small sample size.
The yellow fever vaccine was tested in patients
with CKD and was considered safe for this popu-
lation group. It is indicated for patients with
advanced CKD living in endemic regions. No
comparative data show its relative (or absolute)
efficacy compared to the general population.

4 Brazilian Society of Nephrology,
2018 [21]
Statement of the BSN on
Yellow Fever Vaccination in
Patients with CKD.
Newsletter The vaccine should be evaluated with caution,
considering the risk of the area where the pa-
tient lives or will travel, and the situation of
immunodepression in which he finds himself
since viremia after vaccination may cause
transmission in blood transfusion.
The contraindications of the vaccine have been
evaluated.
Vaccination in kidney transplant patients is not
recommended.
Yellow Fever Vaccination in Hemodialysis Patients
The safety aspect of YFV has been confirmed through
many campaigns and studies investigating the serious ad-
verse effects, mainly in risk groups (the vaccine was consid-
ered safe in most of them). First-dose results in elderly pa-
tients were conflicting, justifying, in this way, the contrain-
dication for those over 60 years of age and evidence of the
need to implement the vaccine from 9 months of age rou-
tinely throughout the country [19].
Even with intensive care, mortality from YF remains
high, caused by multiple organ failure, including acute kid-
ney injury (AKI), which accounts for a large portion of the
mortality rate [20].
In a cross-sectional study involving hemodialysis pa-
tients, no serious adverse effects attributable to the YFV
(anaphylaxis, neurological or bowel disease) were observed.
The YFV was tested in patients with CKD and was consid-
ered safe for this population group. Of 86 patients referred
for vaccination, 45 received the vaccine, with 24.4% having
mild adverse effects and 4.4% developing a fever. However,
no comparative data could demonstrate the relative (or abso-
lute) effectiveness compared to the general population [21].
This study has some limitations regarding the available
database to perform the search and few articles analyzing
this theme. All the efforts were made to avoid bias in the
selection.
Due to the increased incidence of YF in Brazil, the BSN
issued a specific recommendation on vaccination for pa-
tients with CKD undergoing dialysis and transplantation. It
emphasizes the individual and cautious evaluation for the
indication of the vaccine at risk of acquiring the disease and
reinforces not to perform it if there is an immunosuppres-
sion situation or transplant [21].
CONCLUSION
In conclusion, there is no specific protocol or recom-
mendation for YFV in patients with CKD, especially those
on hemodialysis. In the current scenario of disease expan-
sion and an increase in hemodialysis patients, YFV may
represent protection for them, and an individual assessment
of it is recommended.
LIST OF ABBREVIATIONS
AKI = Acute Kidney Injury
BSN = Brazilian Society of Nephrology
CKD = Chronic Kidney Disease
RRT = Renal Replacement Therapy
SAE = Severe Adverse Event
WHO = World Health Organization
YF = Yellow Fever
YFV = Yellow Fever Vaccination
CONSENT FOR PUBLICATION
Not applicable.
STANDARD FOR REPORTING
PRISMA guidelines and methodology were followed.
Current Drug Therapy, 2023, Vol. 18, No. 3 209
FUNDING
None.
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or
otherwise.
ACKNOWLEDGEMENTS
Declared none.
SUPPLEMENTARY MATERIAL
PRISMA checklist is available as supplementary material
on the publisher’s website along with the published article.
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