Review Article

A Systematic Review of Yellow Fever Outbreaks

and Public Health Responses in Nigeria

Wilson Chukwukasi Kassy¹, *Casmir Ndubuisi Ochie¹, Anne Chigedu Ndu^1,2,Olanike R Agwu-Umuahi^1,2,� Charles Ntat Ibiok^1,2, Ifeoma Juliet Ogugua^1,2, Onyinye Hope Chime^3,4, Chino= nye Orji^3,4, Sussan Uzoamaka Arinze-Onyia^3,4, = Emmanuel Nwabueze Aguwa^1,2,

Theodora Adaeze Okeke^1,2.

¹Department of Community Medicine, UNTH Ituku-ozalla , Enugu, Nige= ria.²Department of

community Medicine, University of Nigeria Ituku-Ozalla, Enugu, Nigeria.³Department o= f

Community of Medicine, Enugu State University of Science and Technology, College of Medicine,

Park Lane GRA Enugu, Nigeria.⁴Departm= ent of Community of Medicine, Enugu State University

of Science and Technology Teaching Hospital, Park Lane GRA Enugu, Nigeria.

Background: Yellow fever (YF) outbreaks continue to occur in Nigeria with a high mortality rate despite a well-established mode of transmission and the availability of a potent vaccine. This review is aimed at describing the epidemiology, determinants, and public health responses of yellow fever outbreaks in Nige= ria from 1864 to 2020.

Methodology:� The guidelines for the Preferred Report= ing Items for Systematic Review and Meta-Analysis (PRISMA) were used to conduct= the review from November 2020 to April 2021. PubMed database, WHO library databases, and Google Scholar we= re used to search for relevant published materials including original and revi= ewed articles, conference papers and case reports from 1864 to 2020

Results:<= /span> Forty � eight articles and reports were included in the final reviews. Twenty � three outbreaks were described involving 33,830 suspected, presumptive, or confirmed cases of ye= llow fever and 8,355 deaths. The outbreaks occurred in every state of Nigeria including the Federal Capital Territory mostly during the rainy season. Low immunity in the population or low vaccination coverage, poor vector control, rainforest or savanna vegetation, rural�urban migration, and imported virus= by travelers were common determinants noted. Public health responses have been through, centrally coordinated laboratory support, case management, emergen= cy immunization, vector control, and surveillance.��

Conclusion: Yellow fever outbreaks have increased in frequency and geographical spread with associated mortality rates. To stem the tide, mass immunization with 17D vaccines is encouraged, planned urbanization with adequate vector control measures enforced, effective case definition, vector surveillance, and effective awareness campaigns should be emphasized.

Keywords= : Yellow Fever, Outbreaks, Determinants, Public Health Response, Nigeria.=

��<= /o:p>

*Corresp= ondence:� Ochie, Casmir= N Department of Community Medicine, UNTH, Ituku-Ozalla, Enugu, Nigeria.

Email: <= span style=3D'font-size:9.0pt;font-family:"Times New Roman",serif;color:black; mso-themecolor:text1;mso-bidi-font-weight:bold;text-decoration:none;text-un= derline: none'>drcasmirnf@gmail.com

This is an open access journal, and articles are distributed und= er the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creati= ons are licensed under the identical terms.

How to cite this article: Kassy WC, Ochie CN, = Ndu AC, Agwu-Umuahi OR, <= span class=3DSpellE>Ibiok CN, Ogugua IJ, Chime OH, Orji C, Arinze-Onyia SU, Aguwa EN, Okek= e TA. A Systematic Review of Yellow Fever Outbreaks and Public Health Responses in Nigeria. Niger Med J 2023;64(4): 427-447. Accepted: August 29, 2023. Publis= hed: September 21, 2023.

Introduction

Yellow fever= (YF) is an acute viral haemorrhagic disease caused b= y the yellow fever virus, an arbovirus, belonging to the family Flaviviridae and genus Flavivirus.^{1 - 3} Historically, the origin of the disease is uncertain but believed by consensus to have been in Africa 500 years ago wh= ere it has remained endemic and was disseminated to the Americas and other part= s of the world through sailing ships and the slave trade. ^{3 � 5}The colonial expeditions and imper= ial activities of non�immune Europeans and Americans led to the early recorded outbreaks of YF disease in West Africa. ^{4, 6, 7} The earliest recorded yellow fever ou= tbreak in Nigeria was reported in Lagos in 1864, followed by repeated outbreaks in 1894, 1905, 1906, 1925, and 1926, and have continued to the present among t= he indigenous population.^{8 - 10} By the end of the 20^{th<=
/sup>
century, the viral origin of the disease was identified, its means of
spreading, and possible ways of prevention were found. These were evidenced=
by
the works of Carlos Finlay and Walter Reed in the discovery of the disease
urban mosquito vector which set the stage for a successful eradication
programme.^{11, 12} =
As
vector control proved effective and urban epidemics were controlled in the
Americas, the West African yellow fever commission was established in 1925 =
by
the international health division of Rockefeller Foundation in collaboration
with British colonial authorities purely on yellow fever research.6, 7} By 1927, the first isolation of the yellow = fever virus called the Asibi strain from a patient Asibi was achieved followed by the identification of = the rhesus monkey used for the important protection test, a method used to iden= tify individuals exposed to yellow fever and developed immunity.⁷From 1931 to 1937, Max Theiler, successfully used the Asibi= strain and the protection test method propagated on mice using intracerebral injections to produce a vaccine called 17D (Rockefeller) vaccine of the Asibi strain. The combined discoveries of the vector = and safe vaccine implied that the disease and epidemic could be effectively controlled and possibly eradicated.^{6, 7, 11}

<= /o:p>

Yellow fever= is transmitted through a cycle that involves a vector (Mosquito), humans, and monkeys. The cycles are categorized into sylvatic / jungle/forest cycle whi= ch is in the natural or endemic zone. The virus is transmitted or circulated by the wild species of mosquitoes (Aedesafricanus = and furcifer) and arboreal monkeys. The monkeys are resis= tant but if infected, are immune. Man is accidentally infected following a short forest stay leading to sporadic or limited local epidemics causing immune protection of the population. The second cycle is the intermediate / savann= ah cycle which is in the border zone of emergence with settlements near the fo= rest where there are some human activities. The virus is transmitted by monkeys = to humans or humans to humans via mosquitoes. (Aedesluteocephalus, Aedesfurcifer, Aedesmetallicus, Aedesopok, Aedestaylori, Aedesvittatus, and members of the Aedessimpsoni complex), anthropization of the environment through deforestati= on, population growth, and global warming. Lastly is the urban cycle which is t= he epidemic zone characterized by low population immune status or poor immunization coverage, no presence of wild mosquitoes, and circulation of virus. The virus is imported by an infected person from the jungle or savan= na zones and transmitted from human to human transmission through urban mosqui= toes; Aedes aegypti.^{3,=
5, 10}

<= /o:p>

The incubati= on period is 3 � 6 days with a case fatality rate of 20 � 50 % or higher.^{=
2, 3} The symptoms range from mi= ld symptoms (first phase) to severe illness or fatal disease (toxic phase). On= ly about 15% of those infected will be in this phase.� Those with mild symptoms develop sudden= onset of fever, headache, muscle pain, backache, general weakness, red eyes (inje= cted conjunctiva), nausea and vomiting. During this phase, patients quickly reco= ver though they have viraemia, and are infectious to mosquitoes. This is follow= ed by 24 hour period of remission. The second and toxic phase includes high fe= ver, vomiting, epigastric pains, jaundice, hemorrhagic diathesis (hematemesis), = coma, and death. YF virus is usually absent from the blood of patients during the toxic phase, and anti-YF virus antibodies appear.³ Confirmation of yellow is by viral isolation, serology test (Enzyme�Linked Immunosorbent Assay [ELISA], reverse transcription polymerase chain reaction [RT � PCR], Plaque reduction and neutralization test [PRNT]). Serology has the challenges of cross�reaction = with other flaviviruses.^{10, 13}Yellow fever outbreaks are controlled through an effective and timely surveillance system, laboratory capability, routine, and mass immunization, supportive management of cases, environmental and vector control using registered insect repellents for the= outdoors, bed nets, long-sleeved clothing, long pants, and socks are necessary. In 20= 18, the Eliminate Yellow Fever Epidemics (EYE) was launched in Nigeria to elimi= nate yellow fever by 2026. The strategic objectives are to protect at-risk populations, prevent international spread, and contain outbreaks rapidly.9, 10, 14<= /span>

<= /o:p>

Yellow Fever= is endemic in the tropical areas of Africa, Central and South America with more than 90% global burden in Africa. The World Health Organization (WHO) estim= ates the burden of YF in Africa to be at 84,000 � 170,000 severe cases and 29,00= 0 � 60,000 deaths annually.^{1, 14} Nigeria has over the century experienced a series of outbreaks of yellow fever which have been associated with various public health response measures. Despite these public health responses, the current increased frequency of the epidemics is of great con= cern, especially for a disease marked for elimination. This study review will hel= p to understand the current drivers and gaps in public health response measures = for the effective control of the epidemics and possible elimination by 2026 thr= ough EYE. The study is aimed at describing the epidemiology, determinants, and public health responses of yellow fever outbreaks in Nigeria from 1864 � 20= 20.

<= /o:p>

Methodology

The guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were used to conduct a systematic search= of Yellow fever outbreaks in Nigeria. The strategy is detailed in Figure 1.15The search was conducted between November 2020 and April 2021. PubMed database,= WHO library databases, and Google Scholar were used to search for relevant published materials including original and reviewed articles, conference pa= pers, and case reports from 1900 to 2020. Other websites such as the World Health Organization, and Center for Disease Control were searched for outbreaks and were included if they contained information on each reporting year. The main themes considered were Yellow fever outbreaks in Nigeria, the epidemiologic= al profile, the determinants, and the public health responses.

<= /o:p>

Data Abstrac= tion and Synthesis

Data abstraction and synthesis included the following 4 steps: identification, screening, eligibility, and inclusion. Articles were identi= fied using the search strategy described above. Titles and abstracts were then screened to assess their suitability to the study objectives. Then the full texts of the articles were reviewed to determine eligibility for the study. Detailed information relevant to the study was extracted and tabulated according to; outbreak year, time of year (month), states affected, persons affected, laboratory confirmation, mortality or case fatality rates, determining factors, and public health responses. Studies were then categor= ized by epidemiological profile, determinants, and public health response. =

<= /o:p>

Inclusion and Exclusion Criteria

Articles that described Yellow fever outbreak epidemiology, determinants, and public health response were included while outbreaks outs= ide Nigeria and those conducted in animals were excluded.

Results.��= ��

The initial search generated 2950 results. After the removal of 245 duplicates, 2705 articles and reports remaining were screened based on titles and abstracts resulting in the further exclusion of 2417 papers. Con= tent review of the 288 full texts articles and reports led to the exclusion of an additional 240 papers. Finally, 48 full-text articles and reports were incl= uded based on yellow fever outbreaks in Nigeria from 1864 to 2020, epidemiologic= al profiles, determinants, and public health responses. (See Figure 1)

Figure 1: Flow Chart selection of rele= vant documents for review of literature.

Documents identified: 2950<= /p>

Documents Screened: 2705

Documents Eligible: 288

Included for study: 48

Duplicates excluded: 245

Excluded: 2417

Excluded: 240

<= /o:p>

From our review of the literature, the Yellow fever outbreak occurred 23 times f= rom the years 1864 to 2020 under review. About 33,830 cases (suspected, presump= tive, or confirmed) and 8,355 deaths of yellow fever were observed. There were no observed age or sex predilections from the reviewed materials. The highest number of cases and deaths were reported in 1950 � 52, 1986 � 87, 1991, and 2019 while the lowest were from 1864 � 1937. The highest case fatality rate= was 84.1% reported in 1990. (See Table 1 and Figure 2).

<= /o:p>

Table 1. Description of yellow fever outbreaks = in Nigeria 1864-2020

Outbreak y= ear

Season

States

Cases

Deaths

Case fatal= ity rates (%)��

Lab. confirmed� =

References=

1864 � 1900

�------

Lagos

�-----

------

---------

-----

(7) (9) (16)

1905- 1906

�-----

Lagos

�-----

------

--------

------

(17) (9)

1913 � 1914

Jan � Feb & Oct

Lagos, Onitsha

9

1

--------

-------

(18)

1925 � 1926

April � Sept

Lagos

17

7

--------

------

(19) (20)

1934 � 1937

July � Dec

Ogbomosho, Kano

4

------

-------

Lab. Confirmed

(21) (22) (23) (6)

1946

April

Ogbomosho

75

9

< 1%

�Lab. Confirmed

(6)

1950 � 1952

-------

Onitsha

12, 000

500 - 600

�-----

Lab. Confirmed

(6) (24)

1969

Sept-Dec

Benue � Plateau

100,000 (252 hospitalized)

123

40%

Lab. Confirmed

(25)

1970

Aug � Dec

(Okwaga) Benue

786

3

1.6% - 14.4%

Lab. Confirmed

(26)

1976

--------

Akwa � Ibom

------

-------

56%

Isolation & Serology

(27)

1979

Jan � Feb

Bauchi (Azare)

11

None

----

------

(28)

1986

June � July

Benue, Cross river, Anambra, Imo

9800 Benue alone

5600 Benue alone

2.8%

Serology

(29), (30)

1987

April � Dec

Oyo, Niger.

805 + 644 =3D 1449

416 + 149 =3D 565

0.6%

Viral isolation & serology

(31) (32) (30)

1988

----

Potiskum (Yobe)

30

---

------

(33)

1990

Aug � Dec

Borno

102

83

84.1%

Serology

(33)

1991

April � Dec

Delta, Anambra, Kaduna, Kastina& Plateau

2561

661

26%

(34)� (35)�

1992

-------

-----

149

8

5%

(36)

1993

------

------

152

8

5%

(36)

1994

Sept-Dec

Imo, Anambra

1227

415

34%

(37)

2017

July � Dec

Kwara State, Ab= ia, Anambra, Borno, Edo, Enugu, Kano, Katsina, Kogi, Kebbi, Lagos, Nassarawa, Niger, Oyo, Plateau and Zamfara.�

341 suspected cases. 32 confirmed cases

45 among suspected cases while 9 among confirmed cases.�

21.1% in suspected cases and 28.1% in confirmed cases

Serology using IgM ELISA and RT � PCR

(9) (38)

2018

Nov � Dec

Edo State

146 suspected, 42 presumptive, and 32 confirmed cases

26 deaths

18%

IgM and RT � PCR and Plaque Reduction Neutralization Test (PRNT)

(39)� (16)

2019

Jan � Dec

All 36 + FCT

4189 suspected cases.

23 deaths from Bauchi, Katsina and Benue states

12.2% for confirmed cases

207 confirmed by IgM, 197 by RT � PCR.

(40)� (41)

2020

Nov � Dec

Enugu, Delta, Ebonyi, Benue and Bauchi

530 suspected cases, 48 laboratory-confirmed

178 deaths among the suspected

------

RT � PCR and IP Dakar

(42)

<= /o:p>

<= /o:p>

<= /o:p>

<= /o:p>

Figure 2: Time Trend of Yellow Fever Outbreak= s in Nigeria 1864-2020

Between 1864= and 2020, all the states plus the Federal Capital Territory recorded an outbrea= k of yellow fever. Most outbreaks in Nigeria were reported in the southern states while few were in the northern states. Anambra, Lagos, and Benue had the highest recorded outbreaks with 5 � 7 outbreaks of yellow fever. (See table= 2 and figure 3).

Table 2: Frequency of yellow fever outbreaks among states in Nigeria 186= 4-2020.

State

Number

Abia<= /o:p>

2

Adamawa

1

Akwaibom

2

Anambra

7

Bauchi

2

Bayelsa

1

Benue=

5

Borno=

3

Cross Rive= r

2

Delta

3

Ebonyi

2

Edo <= /o:p>

3

Ekiti=

1

Enugu

3

Gombe=

1

Imo <= /o:p>

3

Jigawa

1

Kaduna

2

Kano<= /o:p>

3

Katsina

3

kebbi

2

Kogi<= /o:p>

2

Kwara

2

Lagos

6

Nasarawa

2

Niger

3

Ogun<= /o:p>

1

Ondo<= /o:p>

1

Osun<= /o:p>

3

Oyo <= /o:p>

3

Plateau

4

Rivers

1

Sokoto

1

Taraba

1

Yobe<= /o:p>

2

Zamfara

2

Fct

1

<= /span>

Fig 3. Map showing frequency of yellow fever outbreaks among the states in Nigeria 1864 � 2020.�

Key

<= /span>

States with a total of 5 - 7 outbreaks

<= /span>

States with a total of 3 - 4 outbreaks

<= /span>

States with a total of 1 - 2 outbreaks

From 1864 to 2020, outbreaks occurred every decade except in 2000 to 2010. The seasonality of the outbreaks as reported from reviewed materials showed that most outbreaks happened in the rainy seasons of July to November. (See table 3 and figure 4).

Table 3: Determinants of Yellow fever outbreaks in Nigeria from 1864 � 2020.

Outbreak y= ear

Inference<= span style=3D'mso-spacerun:yes'>�

References=

1864 � 1900

*Non immune European and American expeditions.

*Endemic disease among indigenous population.

*No knowledge of the disease epidemiology (aetiology and transmission).

*presence of few foreign doctors competent to make diagnosis.

(7)

1905 - 1906

*Non immune European and American expeditions.

*Endemic disease among indigenous population.

*earliest awareness and� recorded case of t= he disease

*presence of few foreign doctors competent to make diagnosis.

(7)

1913 � 1914

*Non immune European and American expeditions.

*presence of few foreign doctors competent to make diagnosis.

*Poor sanitary conditions for mosquito � breeding Field

(7)�

1925 � 1926

*Non immune European and American expeditions.

*presence of few foreign doctors competent to make diagnosis.

*Poor sanitary conditions for mosquito bleeding

(20)� (7)�=

1934 - 1937

-------

1946

*Water pots for storage following droughts, dye pits from the dyeing industry ac= ted as a mosquito breeding grounds.� =

*Prior vaccination program were largely to colonial military

(6)

1950 � 1952

*Waning immunity or non � immune population due deforestation / forest disappeara= nce in the densely populated south eastern and south southern Nigeria. <= /o:p>

*some cities are in transitional belt.

*infected travelers entering the northern

Region from the south.

* Unchecked and unplanned urbanization� *trade

*Rural � urban migration�� *low vacci= nation coverage

(6) (24) (43)

1969

*Low immunization coverage to surrounding areas to JOS city.=

*epidemic was preceded by rainfall to aid mosquito breeding

*Rural transmission

*Suspected to be imported from Benue province south of Plateau province. =

*Vector was believed to be Aedesleteocephalus (Wild breeding Stegomyia mosquitos)

*Absence of Aedesaegypti mosquitoes<= /p>

(25)

1970

*Rainfall with breeding sites of mosquitos in the forest

*Rural transmission by wild breeding Stegomyia mosqu= itos

*many species of mosquitoes, A. africanus, A. argenteovent= ralis, A. ingrami, A. simpsoni<= /span>,

(26)

1976

*First reported outbreak in the area. �<= o:p>

*Forest vegetation

(27)

1979

--------

1986

*Aedesafricanus

*Sylvatus transmission

*Savanna and rainforest vegetation

*Rainy season and water collection in cans

*Poor Immunization coverage

(29)

1987

*AedesEgypti breeding in domestic water containers. =

*Urban type transmission following the sylvatic yellow fever in eastern Nigeria = the previous year imported by viraemic travelers.=

(31)

1990

*Non � immune status of the population evidence from affectation of all ages. =

*Sporadic vaccination

*Sylvatic spread from the rural border town of Bama, Gwoza

*water storage habits

(33)

1991

*Aedesaegypti

*Aedesalbopictus

*Aedesafricanus

*Low immunization coverage

(34) (35)

1992 - 1993

*Low immunization coverage < 50%, 1% for Nigeria.

(36)�

1994

*Sylvatic transmission / Exposure.

*Low immunization coverage < 50%, 1% for Nigeria.

(37)�

2017

*low index of suspicion

*poor reporting of cases

*fear of treatment of cases

*low vaccination coverage

*Sylvatic (Aedesafricanus and leut= eocephalus) and Urban (Aedesaegypti) exposures.

*Water collection

*Priorities 1 and 2 high risk areas

(9)

2018

*Low immunity, vaccine coverage < 50%

*Land use practices, cultivation close to dwellings

(39)�

2019

*low index of suspicion of yellow fever among health care workers

*low but improving immunization coverage

*Poor documentation of yellow fever surveillance in many health facilities.

*

(41)�

2020

= ;

= ;

<= /o:p>

The commonest determinants of yellow fever outbreaks in Nigeria as noted from t= he reviewed articles were low immune � population or low vaccination coverage, poor sanitary conditions with available collected water for breeding of mosquitos, wild mosquitos vectors in the rainforest or savanna, rural�urban migration and importation of virus by travelers. (See Tables 3 = and 4).

The common public health response to the outbreaks in Nigeria observed from the= reviewed material was team coordination, laboratory support, case management and emergency immunization, vector control, and surveillance. (See Tables 4 and= 5).

��

Table 4: Summary of determinants of Ye= llow Fever Outbreaks in Nigeria 1864 � 2020.

<= /o:p>

= Year	= �� Determinants
=	= Ignorance	= Low index of suspicion	= Low immunity / Vaccination	= Sanitary condition	= Rainforest or savanna	= Imported travellers	= R � U Migration	= rainfall	= Case reporting	= Farming near dwelling
= 1864 � 1900	�� +	�+	� +	�� -	�+	� ----	�� -----	� ----	�� ----	�-----
= 1905 - 1906	�� +	+	�+��= ��	----	�+	�-------	------	----	--------<= /p>	-------
= 1913 - 1914	�� +	+	�+	�+	�+	� -------	-------	-------	-------	--------<= /p>
= 1925 - 1926	�� +	+	+	+	+	------	--------<= /p>	+	------	-------
= 1934 - 1937	No Info	No Info	No Info <= /p>	No Info	No Info	No Info	No Info	No Info	No Info	No Info
= 1946			�� +	�+	�+			+
= 1950 � 1952			�� +	�+	�+	�+�	�+			� +
= 1969			� +	+	� +	+	�+	�+		� +
= 1970				+	� +			�+		� +
= 1976	�+	�+			� +
= 1979	No info	No Info	No Info <= /p>	No Info	No Info	No Info	No Info	No Info	No Info	No Info
= 1986			�+	�+	+			�+		� +
= 1987				�+		� +		�+
= 1990			�+	�+		� +	�+
= 1991			�+
= 1992 - 1993			�+
= 1994			�+		�+		�+			+
= 2017		� +	�+	�+	�+			�+	�� +
= 2018			�+							+
= 2019		� +	�+						�� +
= 2020	No info	No Info	No Info <= /p>	No Info	No Info	No Info	No Info	No Info	No Info	No Info

<= /o:p>

�� Table 5: Public Health Response to yellow outbreaks in Nigeria 1864 � 2020.

Outbreak y= ears	Inferences= �	References=
1864 � 1900	None	(7)
1905 � 1906	None	(7)
1913 � 1914	British Commission on Yellow fever in 1913. 1^st West African Yellow Fever Commission (Rockefeller Foundati= on) in 1920.�	(7)
1925 � 1926	* 2^nd West African Yellow Fever Commission (Rockefeller Foundati= on) in July 1925 with a laboratory in Yaba. Lagos= . The commission was site of research, not public health intervention Sanitation awareness to clear mosquito breeding containers Field studies for intensive search of the disease in the African population both clinically and entomology for yellow fever eradication.� YF protection test experiment was conducted which identified those expose= d to YF and developed immunity. *Isolation of the Yellow fever virus from Asibi and development of vaccine.	(20) (6) (4) (7)
1934 � 1937	Mass vaccination were initiated from 1939.	[44]
1946	Outbreak management�� Supportive treatment Autopsy�� DDT spraying�� Emptying water pots Restriction of movement in and out of the town Community involvement of school teachers, school records for absenteeism�� ver= bal autopsy Home visitations�� mass vaccinati= on Thirty � four isolated strains of the virus were included in vaccine development= .	[6]
1950 � 1952	�No available Record<= /p>
1969	Attempt at immunization that covered up to 20% of the population of Plateau provi= nce. Response was from virus research laboratory of the university of Ibadan. rapid case finding�� Autopsy�� viral isolation= ELISA test and complement fixation test	(25)
1970	Late response in December when the epidemic was waning House to House survey using verbal autopsy to obtain data on cases and deaths viral isolation�� complement fixation= *75% vaccination coverage using 17D vaccine.	(26)
1976	Viral isolation and serology	(27)
1986	Vaccination containment outbreak and epidemiological assessment. Yellow fever vaccination to be included in Expanded Program= me on Immunization control environmental sanitation	(29)�
1987	*Yellow fever vaccination to be included in Expanded Program= me on Immunization	(31)
1988	No available record
1990	Patient survey, case finding and assessment outbreak investigation and entomology investigation.� Virus Isolation and Serology test. increase vaccination through EPI.	(33)
1994	vaccination by the Local PHC department.�� = Dry weather	(37)
2017	Active case search Rapid yellow fever vaccination coverage assessment Verbal autopsy�� human blood sample collection Entomological Surveillance Risk communication and social mobilization Data management�� Vaccination campaig= ns and mass Surveillance One week training on diagnosis of Yellow fever in Lagos Strengthen Laboratory capacity WHO advised Vaccination and Mosquito control as the primary means for prevent= ion and control.	(9) (38)
2018	Multi � agency, multi � partner incident management system (IMS), National Emergency Operation Centre (EOC) at NCDC Rapid Respond Teams Yellow Fever Surveillance and active case findings Strengthen Laboratory capacity Vaccination campaigns�� *Entomological Surve= y.	(39) (16)
2019	NCDC activated National EOC�� Par= tners Risk communication and community Engagement through social mobilization Prevention and Active case finding. Case management support Vector control � destruction of breeding grounds of mosquitoes. New laboratories.�� Immunization	(40)
2020	National EOC�� partners Prevention and Active case search�� Immuni= zation	(42)

<= /o:p>

Table 5. Public Health Response Summar= y to yellow fever outbreaks in Nigeria from 1864 � 2020

Year	�� Publ= ic Responses
	Coordina � tion<= o:p>	Lab. support	isolation	Case mgt	awareness campaign	Emergency Iz	Mass Iz	Envt& rodent control	Case surveillance	Vector surveillance
1864 � 1900	-----=	------	------	-----=	�-------	�-------	�-----	�� ------	�-------	�--------
1905 � 1906	-----=	------	------	-----=	�-------	�-------	�-----	�� ------	�-------	�--------
1913 � 1914	�� +	------	------	-----=	�-------	�-------	�-----	�� ------	�-------	�--------
1925 � 1926	�� +	�+	= ;	= ;	= ;	= ;	= ;	�� +	�� +	= ;
1934 � 1937	= ;	= ;	= ;	= ;	= ;	= ;	� +	= ;	= ;	= ;
1946	+	+	+	+	�+	= ;	� +	�+	= ;	= ;
1950 � 1952	-----=	------	------	-----=	�-------	�-------	�-----	�� ------	�-------	�--------
1969	+	+	= ;	+	= ;	+	= ;	= ;	+	= ;
1970	�---	+	= ;	= ;	= ;	+	= ;	= ;	+	= ;
1976	= ;	+	= ;	= ;	= ;	= ;	= ;	= ;	= ;	= ;
1979	-----=	------	------	-----=	�-------	�-------	�-----	�� ------	�-------	�--------
1986	= ;	= ;	= ;	= ;	= ;	�+ (EPI)	= ;	�+	= ;	= ;
1987	= ;	= ;	= ;	= ;	= ;	�+ (EPI)�	= ;	= ;	= ;	= ;
1990	= ;	+	= ;	+	= ;	= ;	(EPI)=	= ;	�+	+
1991	= ;	= ;	= ;	= ;	= ;	= ;	= ;	= ;	= ;	= ;
1992 � 1993	= ;	= ;	= ;	= ;	= ;	= ;	= ;	= ;	= ;	= ;
1994	= ;	= ;	= ;	= ;	= ;	+	= ;	= ;	= ;	= ;
2017	+	+	= ;	+	+	+	= ;	= ;	�+	�+
2018	+	+	= ;	+	+	+	= ;	= ;	�+	�+
2019	+	+	= ;	+	+	+	= ;	+	�+	= ;
2020	+	+	= ;	+	= ;	+	= ;	= ;	�+	= ;

<= /o:p>

Outbreak y= ear	Season	States	Cases	Deaths	Case fatal= ity rates (%)��	Lab. confirmed� =	References=
1864 � 1900	�------	Lagos	�-----	------	---------	-----	(7) (9) (16)
1905- 1906	�-----	Lagos	�-----	------	--------	------	(17) (9)
1913 � 1914	Jan � Feb & Oct	Lagos, Onitsha	9	1	--------	-------	(18)
1925 � 1926	April � Sept	Lagos	17	7	--------	------	(19) (20)
1934 � 1937	July � Dec	Ogbomosho, Kano	4	------	-------	Lab. Confirmed	(21) (22) (23) (6)
1946	April	Ogbomosho	75	9	< 1%	�Lab. Confirmed	(6)
1950 � 1952	-------	Onitsha	12, 000	500 - 600	�-----	Lab. Confirmed	(6) (24)
1969	Sept-Dec	Benue � Plateau	100,000 (252 hospitalized)	123	40%	Lab. Confirmed	(25)
1970	Aug � Dec	(Okwaga) Benue	786	3	1.6% - 14.4%	Lab. Confirmed	(26)
1976	--------	Akwa � Ibom	------	-------	56%	Isolation & Serology	(27)
1979	Jan � Feb	Bauchi (Azare)	11	None	----	------	(28)
1986	June � July	Benue, Cross river, Anambra, Imo	9800 Benue alone	5600 Benue alone	2.8%	Serology	(29), (30)
1987	April � Dec	Oyo, Niger.	805 + 644 =3D 1449	416 + 149 =3D 565	0.6%	Viral isolation & serology	(31) (32) (30)
1988	----	Potiskum (Yobe)	30	---	------		(33)
1990	Aug � Dec	Borno	102	83	84.1%	Serology	(33)
1991	April � Dec	Delta, Anambra, Kaduna, Kastina& Plateau	2561	661	26%		(34)� (35)�
1992	-------	-----	149	8	5%		(36)
1993	------	------	152	8	5%		(36)
1994	Sept-Dec	Imo, Anambra	1227	415	34%		(37)
2017	July � Dec	Kwara State, Ab= ia, Anambra, Borno, Edo, Enugu, Kano, Katsina, Kogi, Kebbi, Lagos, Nassarawa, Niger, Oyo, Plateau and Zamfara.�	341 suspected cases. 32 confirmed cases	45 among suspected cases while 9 among confirmed cases.�	21.1% in suspected cases and 28.1% in confirmed cases	Serology using IgM ELISA and RT � PCR	(9) (38)
2018	Nov � Dec	Edo State	146 suspected, 42 presumptive, and 32 confirmed cases	26 deaths	18%	IgM and RT � PCR and Plaque Reduction Neutralization Test (PRNT)	(39)� (16)
2019	Jan � Dec	All 36 + FCT	4189 suspected cases.	23 deaths from Bauchi, Katsina and Benue states	12.2% for confirmed cases	207 confirmed by IgM, 197 by RT � PCR.	(40)� (41)
2020	Nov � Dec	Enugu, Delta, Ebonyi, Benue and Bauchi	530 suspected cases, 48 laboratory-confirmed	178 deaths among the suspected	------	RT � PCR and IP Dakar	(42)

State	Number
Abia<= /o:p>	2
Adamawa	1
Akwaibom	2
Anambra	7
Bauchi	2
Bayelsa	1
Benue=	5
Borno=	3
Cross Rive= r	2
Delta	3
Ebonyi	2
Edo <= /o:p>	3
Ekiti=	1
Enugu	3
Gombe=	1
Imo <= /o:p>	3
Jigawa	1
Kaduna	2
Kano<= /o:p>	3
Katsina	3
kebbi	2
Kogi<= /o:p>	2
Kwara	2
Lagos	6
Nasarawa	2
Niger	3
Ogun<= /o:p>	1
Ondo<= /o:p>	1
Osun<= /o:p>	3
Oyo <= /o:p>	3
Plateau	4
Rivers	1
Sokoto	1
Taraba	1
Yobe<= /o:p>	2
Zamfara	2
Fct	1

	<= /span>	States with a total of 5 - 7 outbreaks

	<= /span>	States with a total of 3 - 4 outbreaks

	<= /span>	States with a total of 1 - 2 outbreaks

Outbreak y= ear	Inference<= span style=3D'mso-spacerun:yes'>�	References=
1864 � 1900	Non immune European and American expeditions. Endemic disease among indigenous population. No knowledge of the disease epidemiology (aetiology and transmission). presence of few foreign doctors competent to make diagnosis.	(7)
1905 - 1906	Non immune European and American expeditions. Endemic disease among indigenous population. earliest awareness and� recorded case of t= he disease presence of few foreign doctors competent to make diagnosis.	(7)
1913 � 1914	Non immune European and American expeditions. presence of few foreign doctors competent to make diagnosis. *Poor sanitary conditions for mosquito � breeding Field	(7)�
1925 � 1926	Non immune European and American expeditions. presence of few foreign doctors competent to make diagnosis. *Poor sanitary conditions for mosquito bleeding	(20)� (7)�=
1934 - 1937	-------
1946	Water pots for storage following droughts, dye pits from the dyeing industry ac= ted as a mosquito breeding grounds.� = Prior vaccination program were largely to colonial military	(6)
1950 � 1952	Waning immunity or non � immune population due deforestation / forest disappeara= nce in the densely populated south eastern and south southern Nigeria. <= /o:p> some cities are in transitional belt. infected travelers entering the northern Region from the south. Unchecked and unplanned urbanization� trade Rural � urban migration�� *low vacci= nation coverage	(6) (24) (43)
1969	Low immunization coverage to surrounding areas to JOS city.= epidemic was preceded by rainfall to aid mosquito breeding Rural transmission Suspected to be imported from Benue province south of Plateau province. = Vector was believed to be Aedesleteocephalus (Wild breeding Stegomyia mosquitos) Absence of Aedesaegypti mosquitoes<= /p>	(25)
1970	Rainfall with breeding sites of mosquitos in the forest Rural transmission by wild breeding Stegomyia mosqu= itos *many species of mosquitoes, A. africanus, A. argenteovent= ralis, A. ingrami, A. simpsoni<= /span>,	(26)
1976	First reported outbreak in the area. �<= o:p> Forest vegetation	(27)
1979	--------
1986	Aedesafricanus Sylvatus transmission Savanna and rainforest vegetation Rainy season and water collection in cans *Poor Immunization coverage	(29)
1987	AedesEgypti breeding in domestic water containers. = Urban type transmission following the sylvatic yellow fever in eastern Nigeria = the previous year imported by viraemic travelers.=	(31)
1990	Non � immune status of the population evidence from affectation of all ages. = Sporadic vaccination Sylvatic spread from the rural border town of Bama, Gwoza water storage habits	(33)
1991	Aedesaegypti Aedesalbopictus Aedesafricanus Low immunization coverage	(34) (35)
1992 - 1993	*Low immunization coverage < 50%, 1% for Nigeria.	(36)�
1994	Sylvatic transmission / Exposure. Low immunization coverage < 50%, 1% for Nigeria.	(37)�
2017	low index of suspicion poor reporting of cases fear of treatment of cases low vaccination coverage Sylvatic (Aedesafricanus and leut= eocephalus) and Urban (Aedesaegypti) exposures. Water collection *Priorities 1 and 2 high risk areas	(9)
2018	Low immunity, vaccine coverage < 50% Land use practices, cultivation close to dwellings	(39)�
2019	low index of suspicion of yellow fever among health care workers low but improving immunization coverage Poor documentation of yellow fever surveillance in many health facilities.	(41)�
2020	= ;	= ;