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\title{Symptomatology of Monkeypox and Implications for Integrated Syndromic
Surveillance in Nigeria}



\author[1]{Titus K. Ojewumi}%
\author[1]{Olugbenga Asaolu}%
\affil[1]{Affiliation not available}%


\vspace{-1em}



  
  \date{April 26, 2026}


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\textbf{Authors: Titus K. Ojewumi, Olugbenga Asaolu}

Department of Demography, Obafemi Awolowo University, Ile-Ife, Nigeria.

Department of Public and Allied Health, Babcock University,
Ilishan-Remo, Nigeria.

\textbf{Abstract}

\textbf{\emph{The re-emergence of Monkeypox virus (MPXV) in Nigeria in
2017 has become a considerable public health concern with a diversity of
symptoms exhibited by affected individuals, ranging from mild febrile
illness to severe skin lesions, lymphadenopathy, and systemic
complications. This study examined the symptomatology of mpox disease
across the six regions of Nigeria and its implications for strengthening
the surveillance system. The study used cross-sectional observational
design including cases reported by NCDC between January 2017 and
December 2023. The study revealed most common symptoms as fever (91\%),
rash (85\%), and lymphadenopathy (68\%). About 45\% of cases were
classified as mild, 37\% as moderate, and 18\% as severe, while 28\% of
cases were initially misdiagnosed as other diseases. Cases with no rash
or atypical symptoms were 4.3 times more likely to be delayed in
diagnosis (95\% CI: 2.8--6.2, p \textless{} 0.001). The study showed
that symptomatology of mpox in Nigeria is diverse, with significant
implications for disease surveillance. Strengthening healthcare worker
training, enhancing syndromic surveillance, and promoting public
awareness are critical steps for improving mpox detection and control in
Nigeria.}}

\par\null

\textbf{INTRODUCTION}

Mpox, formerly known as Monkeypox, is an emerging zoonotic viral disease
caused by the monkeypox virus (MPXV), a member of the orthopoxvirus
genus within the poxviridae family. The Orthopoxvirus genus also
includes variola virus, vaccinia virus, cowpox virus,, and several other
animal pathogen poxviruses (Mulka L, et al., 2022). First identified in
humans in 1970 in the Democratic Republic of Congo, mpox shares clinical
similarities with smallpox, though it is generally less severe and less
contagious (Mitj\selectlanguage{ngerman}à et al., 2023). Despite its early detection in Central
and West Africa, mpox has gained significant attention in recent years
due to its re-emergence in various parts of Africa, notably Nigeria, and
the spread to non-endemic regions globally. The 2017 re-emergence of
mpox in Nigeria has raised considerable public health concerns, with
cases now reported across multiple states, particularly in the
southwestern region, which includes Lagos, Rivers, Bayelsa, Abia, Imo
and Ogun (Yinka et al., 2017). The outbreak of mpox in these areas is
complicated by the diversity of symptoms exhibited by affected
individuals, ranging from mild febrile illness to severe skin lesions,
lymphadenopathy, and systemic complications. Mpox poses a significant
public health challenge due to its capacity for both zoonotic and
human-to-human transmission, as well as its potential to cause severe
illness, particularly in immunocompromised populations.

Accurate symptom recognition is critical for effective surveillance,
early diagnosis, and containment of mpox. Surveillance systems in
Nigeria and across West Africa have historically faced significant
challenges, including underreporting, misdiagnosis, and delays in case
identification due to the nonspecific and often overlapping
symptomatology of mpox with other endemic diseases such as smallpox,
chickenpox, measles, HIV and malaria symptoms (Zhou et al., 2023; Asaolu
et al., 2022; Ojewumi et al., 2016).

Additionally, the presence of asymptomatic cases or mild presentations
in some individuals further complicates surveillance efforts. The
incubation period of mpox typically ranges from 5 to 21 days, after
which patients begin to exhibit nonspecific prodromal symptoms such as
fever, headache, muscle aches, fatigue, and chills (NCDC, 2022).
Following this initial phase, characteristic skin rashes and lesions
appear, typically starting on the face before spreading to other parts
of the body. These lesions progress through stages of macules, papules,
vesicles, pustules, and finally crusts, which eventually scab over and
fall off (McCollum \& Damon, 2014). Other studies have shown that severe
complications and symptoms include skin infections, encephalitis,
conjunctivitis, keratitis, and pneumonia. The case-fatality ratio (CFR)
of mpox ranges from 0 --11\% in outbreaks in endemic areas, with
mortality mostly affecting young children (WHO, 2022). Additionally,
people living in tropical forested areas may have indirect or low-level
exposure to infected animals, possibly leading to subclinical
(asymptomatic) infection (WHO, 2022; Lederman et al., 2007).

In endemic areas, immunocompromised individuals were reported to be
particularly at risk of severe disease (Petersen et al., 2019). For
instance, the 2017 outbreak in Nigeria, findings showed that patients
with concurrent HIV infection had more severe disease with more skin
lesions and associated genital ulcers compared to HIV-negative
individuals, although no deaths were reported (Ogoina et al., 2019)In
addition to skin lesions, patients often experience lymphadenopathy, a
notable feature that distinguishes mpox from other orthopoxviral
infections like smallpox (Reynolds et al., 2019). Other symptoms may
include back pain, sore throat, and respiratory symptoms, depending on
the severity of the infection. The clinical severity of mpox can vary,
with some patients developing mild, self-limiting illness, while others,
especially the immunocompromised, may experience more severe
manifestations, including secondary bacterial infections, pneumonia,
sepsis, and encephalitis (Alakunle et al., 2020).

The diversity in symptomatology presents a major challenge for
surveillance efforts, particularly in regions where healthcare
infrastructure is limited, and there is overlap between mpox symptoms
and those of other endemic diseases. Effective surveillance requires a
clear understanding of the full clinical spectrum of mpox to facilitate
early detection and differentiation from other diseases. \textbf{} The
resurgence of monkeypox in Nigeria in 2017, following nearly four
decades of relative absence led to widespread outbreaks across several
states, with northwestern Nigeria identified as a key hotspot. Data from
the Nigeria Centre for Disease Control (NCDC) indicate that the
southwestern states, particularly Lagos and Rivers, have reported a high
number of mpox cases, contributing to a significant portion of the
national case burden (Yinka-Ogunleye et al., 2019).

The symptomatology of mpox in Nigeria is consistent with global
observations but exhibits considerable variability. Fever, skin rash,
and lymphadenopathy are the most commonly reported symptoms; however, a
significant proportion of cases have been reported with atypical
presentations, including fewer skin lesions or lesions localized to
specific body areas (Bunge et al., 2022). This variability has
implications for disease surveillance, as healthcare workers may fail to
recognize milder or atypical cases, leading to underreporting and delays
in diagnosis.

The presence of co-infections in mpox patients, such as HIV and other
endemic diseases, further complicates the clinical presentation. A study
by Ogoina et al. (2019) found that co-infections can mask typical mpox
symptoms, making it more challenging for clinicians to diagnose the
disease promptly. Additionally, asymptomatic carriers or those with
mild, self-limiting illness may not seek medical care, further
contributing to surveillance gaps.

Surveillance systems in Nigeria face numerous challenges, particularly
in remote and underserved areas. One of the primary challenges is the
misidentification of mpox due to its symptom overlap with other
diseases. In northwestern Nigeria, where diseases like chickenpox,
smallpox, measles, and other febrile illnesses are endemic, the accurate
differentiation of mpox cases is difficult (NCDC, 2021). This diagnostic
ambiguity is compounded by the scarcity of laboratory facilities capable
of confirming mpox via polymerase chain reaction (PCR) testing,
resulting in a heavy reliance on clinical diagnosis in many areas.
Underreporting is another critical issue in mpox surveillance,
particularly in rural settings where healthcare access is limited, and
many cases go unreported. Several studies have indicated that a lack of
public awareness about mpox and other disease symptoms contributes to
delayed healthcare seeking behavior, which in turn delays case reporting
(Mbala et al., 2017; Ojewumi et al., 2016). Furthermore, stigma
associated with mpox, particularly in communities where skin diseases
are viewed negatively, may discourage individuals from reporting
symptoms or seeking medical care (Je\selectlanguage{polish}ž\selectlanguage{english}ek et al., 1987; Asaolu et al.,
2022). The lack of adequate training for healthcare workers on the
identification and management of mpox is a further hindrance to
effective surveillance. In some parts of northwestern Nigeria,
healthcare workers have limited knowledge of mpox, leading to
misdiagnosis, reporting and inappropriate treatment. A study by Akinyemi
et al. (2020) highlighted that improved training and resources are
needed to enhance the capacity of healthcare workers to recognize and
report mpox cases effectively.

System strengthening for correct symptom recognition plays a crucial
role in the early detection and containment of mpox outbreaks. Public
health surveillance systems rely heavily on syndromic surveillance,
which involves identifying clusters of symptoms indicative of mpox, such
as fever, rash, and lymphadenopathy, to trigger further investigation
and laboratory confirmation. In this context, the diversity of mpox
symptomatology necessitates a syndrome-based approach that can capture
both classic and atypical presentations of the disease (Jezek et al.,
1988; Asaolu et al,. 2023). Efforts to strengthen mpox surveillance in
Nigeria must prioritize the inclusion of syndromic data from primary
healthcare centers, particularly in rural areas where access to
diagnostic testing is limited. Enhanced surveillance protocols should
emphasize the identification of key symptoms such as rash and
lymphadenopathy while remaining vigilant for atypical or mild cases that
may otherwise go undetected. Community health education is equally
important to raise awareness about the symptoms of mpox and encourage
individuals to seek medical attention when experiencing suspected
symptoms.

The implications of improved symptomatology-based surveillance for mpox
are significant, particularly in northwestern Nigeria. Given the high
burden of disease and the challenges associated with laboratory
confirmation in this region, improving symptom recognition and
integrating community-based surveillance approaches could facilitate
earlier detection of cases, leading to quicker containment of outbreaks
(Adeniran et al. 2024). In addition, training healthcare workers to
recognize the diverse clinical manifestations of mpox would enhance
their ability to diagnose the disease accurately, even in the absence of
advanced diagnostic tools.

Expanding public awareness and integrating mpox surveillance into
existing disease control programs could further enhance Nigeria's
capacity to manage future outbreaks. Given the recurrent nature of mpox
in West Africa and the potential for continued outbreaks, especially in
vulnerable populations, adopting a comprehensive approach to mpox
symptomatology and surveillance is critical to reducing the disease's
impact on public health.

The symptomatology of mpox in Nigeria, particularly in northwestern
states, presents significant challenges for disease surveillance due to
its variability and overlap with other endemic illnesses. While fever,
rash, and lymphadenopathy remain the hallmark symptoms of mpox, the
presence of atypical cases, co-infections, and asymptomatic carriers
complicates efforts to diagnose and report the disease effectively.
Strengthening symptom-based surveillance systems, improving healthcare
worker training, and increasing public awareness are essential
strategies for enhancing mpox detection and control in this region. As
mpox continues to pose a public health threat, understanding the full
spectrum of its clinical presentations is vital for timely diagnosis and
effective outbreak response.

This study aims to examine the symptomatology of mpox disease across the
six regions of Nigeria and its implications for strengthening
surveillance systems. By identifying the most common and distinctive
symptoms associated with mpox in this region, this research seeks to
inform public health strategies that can enhance early case detection,
improve outbreak response, and limit the spread of the disease in both
rural and urban areas.

~

\textbf{Methodology:}

\textbf{Study Design}

This study used a cross-sectional observational design to analyze the
symptomatology of mpox and its implications for surveillance across the
six geopolitical zones in Nigeria. The study included cases reported
between January 2017 and December 2023. Nigeria comprises six
geopolitical zones. Two states with the highest burden of mpox confirmed
cases were selected from each of the geopolitical zones: South West
(Lagos \& Ogun); South South (Rivers and Bayelsa); South East (Abia \&
Imo); North Central (Plateau \& Kwara) North East (Adamawa \& Borno);
North West (Kaduna Katsina) with addition of Abuja as Federal Capital
Territory (FCT). Data collection focused on confirmed mpox cases from
both clinical and public health surveillance records, with an emphasis
on identifying symptoms and risk factors relevant to improving disease
surveillance and detection.

\textbf{Study Population and Setting}

The study population consisted of patients diagnosed with mpox within
the study period, including those who sought care in healthcare
facilities and those identified through public health surveillance
systems. The population also included healthcare workers involved in
diagnosing and managing mpox cases. The study setting encompassed both
urban and rural areas in the selected states of Nigeria, where mpox
cases have been reported with varying prevalence.

\textbf{Data Collection Methods}

The study utilized secondary data from the Nigeria Centre for Disease
Control (NCDC), hospital records, and reports from public health
officials. Data were extracted from confirmed mpox cases, which had been
verified by laboratory testing (PCR for mpox virus). A subset of cases
with detailed clinical histories was selected for further analysis,
including the most commonly reported symptoms and disease severity. The
clinical history data used for the study covered self-reported symptoms
by the patients, time period between symptom manifestation and
healthcare seeking, diagnosed symptoms, and laboratory confirmed cases.
The clinical history data provided information on self-reported
symptoms, healthcare-seeking behavior, and potential delays in
diagnosis.

To complement this data, structured interviews were conducted with
healthcare workers and public health officials to gather insights into
the challenges of recognizing mpox symptoms and reporting cases to the
surveillance system. The structured questionnaire gathered information
on the presented symptoms by the patients, delay in presentation, health
workers diagnosis, laboratory confirmation and difficulties experienced
by health workers in diagnosing mpox symptoms.

\textbf{Sampling and Sample Size}

Out of the total 741 confirmed cases reported as at December 2023, a
total of 512 confirmed mpox cases were included in the study. This
sample size was deemed sufficient based on previous mpox prevalence
estimates in each of the selected states and accounted for
stratification across the six states. In each state, a minimum of 9 to
80 records were randomly selected based on the confirmed number of
reported cases and available clinical history records to provide a
balanced dataset across the regions (see the table 1 below).

\textbf{Data Analysis}

For the purpose of analysis, symptoms were categorized into: 1) Common
symptoms: fever, rash (vesicular or pustular), and lymphadenopathy. 2)
Atypical symptoms: localized rash, respiratory symptoms,
gastrointestinal disturbances, or absence of rash. 3) Severity: mild,
moderate, or severe illness based on the extent of rash, systemic
symptoms, and any associated complications (such as bacterial infections
or encephalitis).

Descriptive statistics were used to summarize the distribution of
symptoms among mpox cases. The frequency of common and atypical symptoms
was calculated for each state and overall. Chi-square tests were used to
evaluate associations between demographic characteristics (age, gender,
rural/urban location) and symptom presentation. The presence of atypical
symptoms was analyzed using logistic regression to identify significant
predictors, with odds ratios (ORs) and 95\% confidence intervals (CIs)
reported.

The implications of symptom variability for surveillance were assessed
by analyzing the proportion of misdiagnosed or delayed cases in relation
to symptom presentation. Data from interviews and questionnaires were
used to evaluate healthcare worker knowledge of mpox symptomatology and
the challenges of reporting to the surveillance system.

\textbf{Results}

\textbf{1. Demographic Characteristics}

Out of the total 512 confirmed mpox cases, 60\% were male and 40\% were
female, with a mean age of 34.7 \selectlanguage{ngerman}± 12.4 years. Majority of the cases
(67\%) occurred in rural areas, with the highest number of cases
reported in Lagos (33\%), followed by Rivers (13\%) and Bayelsa (12\%).

\textbf{Table 1: Nigeria confirmed mpox cases by State, September 2017
-- 31st December 2023}\selectlanguage{english}
\begin{longtable}[]{@{}llllllllll@{}}
\toprule
\textbf{State}{} & \textbf{2017}{} & \textbf{2018}{} & \textbf{2019}{} &
\textbf{2020}{} & \textbf{2021}{} & \textbf{2022}{} & \textbf{2023}{} &
\textbf{Total}{} & \textbf{\% of Total Confirmed Cases}{}\tabularnewline
Lagos & 4 & 1 & 15 & 4 & 6 & 188 & 27 & 245 & 33\%\tabularnewline
Rivers & 25 & 14 & 7 & 1 & 5 & 37 & 4 & 93 & 13\%\tabularnewline
Bayelsa & 19 & 11 & 7 & 0 & 6 & 45 & 2 & 90 & 12\%\tabularnewline
Abia & 1 & 2 & 0 & 0 & 0 & 58 & 6 & 67 & 9\%\tabularnewline
Imo & 5 & 2 & 1 & 0 & 0 & 45 & 5 & 58 & 8\%\tabularnewline
Ogun & 0 & 0 & 0 & 0 & 1 & 40 & 17 & 58 & 8\%\tabularnewline
FCT & 5 & 0 & 0 & 0 & 1 & 25 & 4 & 35 & 5\%\tabularnewline
Kwara & 0 & 0 & 0 & 0 & 0 & 21 & 0 & 21 & 3\%\tabularnewline
Plateau & 0 & 2 & 0 & 1 & 0 & 16 & 0 & 19 & 3\%\tabularnewline
Adamawa & 0 & 0 & 0 & 0 & 0 & 16 & 0 & 16 & 2\%\tabularnewline
Kaduna & 0 & 0 & 0 & 0 & 0 & 15 & 2 & 17 & 2\%\tabularnewline
Borno & 0 & 0 & 0 & 0 & 0 & 11 & 2 & 13 & 2\%\tabularnewline
Katsina & 0 & 0 & 0 & 0 & 0 & 8 & 1 & 9 & 1\%\tabularnewline
\textbf{Total} & \textbf{59} & \textbf{32} & \textbf{30} & \textbf{6} &
\textbf{19} & \textbf{525} & \textbf{70} & \textbf{741} &
\textbf{100\%}\tabularnewline
\bottomrule
\end{longtable}

S\emph{ource:NCDC.GOV.NG
https://ncdc.gov.ng/diseases/sitreps/?cat=8\&name=An\%20Update\%20of\%20Monkeypox\%20Outbreak\%20in\%20Nigeria}

\textbf{2. Symptomatology of Monkeypox:} The most common symptoms were
fever (91\%), rash (85\%), and lymphadenopathy (68\%). Atypical
presentations included localized rash (6\%), respiratory symptoms
(14\%), and cases with no rash (4\%). Patients in rural areas were more
likely to present with atypical symptoms (17\%) compared to those in
urban settings (8\%) (p \textless{} 0.05)

\textbf{Table 2. The most frequently reported symptoms among confirmed
mpox cases}

Symptom

Frequency (\%)

Fever

91\%

Rash (vesicular/pustular)

85\%

Lymphadenopathy

68\%

Fatigue

56\%

Headache

54\%

Respiratory symptoms

14\%

Gastrointestinal symptoms

8\%

Localized rash only

6\%

No rash (fever only)

4\%

\textbf{3. Symptom Severity and Healthcare Access}

*~~~~ 45\% of cases were classified as mild, 37\% as moderate, and 18\%
as severe.

*~~~~ Severe cases were more frequently reported among patients with
comorbidities (e.g., HIV) or delayed access to healthcare.

*~~~~ Rural residents experienced an average delay of 7 days before
seeking care, significantly longer than urban residents (3 days), which
led to more severe cases upon diagnosis.

\textbf{4. Surveillance Implications}

*~~~~ 28\% of cases were initially misdiagnosed as other diseases,
including chickenpox and measles, due to atypical or incomplete symptom
presentations.

*~~~~ Healthcare workers in rural areas reported significant
difficulties in differentiating mpox from other febrile rash illnesses,
with 32\% indicating a lack of training on mpox diagnosis.

*~~~~ Cases with no rash or atypical symptoms were 4.3 times more likely
to be delayed in diagnosis (95\% CI: 2.8--6.2, p \textless{} 0.001).

*~~~~ 48\% of healthcare workers reported challenges in reporting mpox
cases due to the absence of clear diagnostic guidelines for atypical
symptoms.

\textbf{Discussion of findings}

The findings of this study highlight the high variability in the
clinical presentation of mpox in Nigeria, This is consistent with 2019
findings by Petersen et al., particularly the presence of atypical
symptoms such as localized rash, respiratory symptoms, and cases with no
rash . This variability complicates early detection and diagnosis,
particularly in rural settings, where healthcare access is limited and
mpox may be misidentified as other endemic diseases. The presence of
non-classical symptoms such as respiratory or gastrointestinal signs
further complicates the diagnostic process, underscoring the need for a
more comprehensive approach to mpox surveillance.

The high proportion of fever, rash, and lymphadenopathy remains
consistent with global literature on mpox symptomatology (Reynolds et
al., 2019; WHO, 2022), but the identification of milder cases and
atypical presentations suggests that many cases may be missed in routine
clinical practice in consistent with findings by Mulka, 2022 which
showed that monkeypox can be confused with other rash-causing infections
such as hand-foot-and-mouth disease, chicken pox (Varicella), herpes
simplex, measles, chancroid, and molluscum contagiosum. Additionally,
the significant delays in healthcare access observed in rural areas
contribute to disease progression and complications, indicating that
improved public awareness and healthcare infrastructure are needed.

The results of this study underscore the challenges that symptom
variability poses for mpox surveillance systems. In particular, the
misdiagnosis of atypical cases and the underreporting of mild or
asymptomatic cases present significant barriers to accurate disease
monitoring. Surveillance systems must be equipped to recognize the full
spectrum of mpox symptoms, including non-classical presentations.

Training healthcare workers to recognize these atypical signs is
critical for improving mpox detection, especially in rural healthcare
facilities, where resources and diagnostic tools are limited.
Furthermore, incorporating syndromic surveillance systems that track
clusters of febrile and rash illnesses, even those not conforming to
classical mpox presentations, may enhance early detection efforts.

\textbf{Public Health Recommendations}

Based on these findings, several public health measures should be
prioritized:

*~~~~ Training programs for healthcare workers, particularly in rural
areas, to improve recognition of atypical mpox symptoms and differential
diagnosis from other febrile rash illnesses.

*~~~~ Strengthening community awareness campaigns to promote earlier
healthcare-seeking behavior, particularly in remote areas where delays
in diagnosis exacerbate disease severity.

*~~~~ Integration of mpox surveillance with existing public health
programs, such as those for measles and chickenpox, to capture a broader
range of symptom presentations and improve reporting.

\textbf{Conclusion}

The symptomatology of mpox in Nigeria is diverse, with significant
implications for disease surveillance. Atypical symptoms and delays in
healthcare access contribute to diagnostic challenges and hinder
accurate reporting. Strengthening healthcare worker training, enhancing
syndromic surveillance, and promoting public awareness are critical
steps for improving mpox detection and control in Nigeria.

\textbf{Data Availability Statement:}

The secondary datasets generated and analyzed during this study are
available from the corresponding author on reasonable request. The
secondary data of confirmed mpox cases can be accessed from NCDC
website. Source:NCDC.GOV.NG
\url{https://ncdc.gov.ng/diseases/sitreps/?cat=8\&name=An\%20Update\%20of\%20Monkeypox\%20Outbreak\%20in\%20Nigeria}

\textbf{Informed consent:} Verbal informed consent was obtained from the
healthcare workers and public health officials who participated in the
study to provide additional insights into the challenges of recognizing
mpox symptoms by the confirmed mpox patients.

\textbf{Ethics:} The study was approved by the National Health Research
Ethic Committee (NHREC) of the Ministry of Health and the research was
carried out following the guidelines of the ethics committee listed in
the ethics statement.

\textbf{Conflicts of Interest}

The authors declare no conflicts of interest regarding the publication
of this paper.

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