Clinical and Epidemiological Findings from Enhanced Monkeypox Surveillance in Tshuapa Province, Democratic Republic of the Congo During 2011-2015 ...
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
The Journal of Infectious Diseases
Major Article
Clinical and Epidemiological Findings from Enhanced
Monkeypox Surveillance in Tshuapa Province, Democratic
Republic of the Congo During 2011–2015
Erin R. Whitehouse,1,2,a, Jesse Bonwitt,2,a Christine M. Hughes,2 Robert Shongo Lushima,3 Toutou Likafi,4 Beatrice Nguete,4 Joelle Kabamba,5
Benjamin Monroe,2 Jeffrey B. Doty,2 Yoshinori Nakazawa,2 Inger Damon,2 Jean Malekani,6 Whitni Davidson,2 Kimberly Wilkins,2 Yu Li,2 Kay W. Radford,7
D. Scott Schmid,7 Elisabeth Pukuta,8 Elisabeth Muyamuna,8 Stomy Karhemere,8 Jean-Jacques Muyembe Tamfum,8 Emile Wemakoy Okitolonda,4,b
Andrea M. McCollum,2 and Mary G. Reynolds2
Downloaded from https://academic.oup.com/jid/article/223/11/1870/6174433 by guest on 09 September 2021
1
Epidemic Intelligence Service, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA, 2Division of High Consequence Pathogens and Pathology, US Centers for Disease Control
and Prevention, Atlanta, Georgia, USA, 3Ministère de la Santé Publique, Kinshasa, Democratic Republic of the Congo, 4Ecole de Santé Publique de Kinshasa, Kinshasa, Democratic Republic of
the Congo, 5US Centers for Disease Control and Prevention, Kinshasa, Democratic Republic of the Congo, 6Faculty of Science, University of Kinshasa, Kinshasa, Democratic Republic of the Congo,
7
Division of Viral Diseases, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA, and 8Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo
(See the Editorial Commentary by Heymann and Simpson, on pages 1839–41.)
Background. Monkeypox is a poorly described emerging zoonosis endemic to Central and Western Africa.
Methods. Using surveillance data from Tshuapa Province, Democratic Republic of the Congo during 2011–2015, we evaluated
differences in incidence, exposures, and clinical presentation of polymerase chain reaction–confirmed cases by sex and age.
Results. We report 1057 confirmed cases. The average annual incidence was 14.1 per 100 000 (95% confidence interval, 13.3–15.0).
The incidence was higher in male patients (incidence rate ratio comparing males to females, 1.21; 95% confidence interval, 1.07–1.37), ex-
cept among those 20–29 years old (0.70; .51–.95). Females aged 20–29 years also reported a high frequency of exposures (26.2%) to people
with monkeypox-like symptoms.The highest incidence was among 10–19-year-old males, the cohort reporting the highest proportion of
animal exposures (37.5%). The incidence was lower among those presumed to have received smallpox vaccination than among those pre-
sumed unvaccinated. No differences were observed by age group in lesion count or lesion severity score.
Conclusions. Monkeypox incidence was twice that reported during 1980–1985, an increase possibly linked to declining im-
munity provided by smallpox vaccination. The high proportion of cases attributed to human exposures suggests changing exposure
patterns. Cases were distributed across age and sex, suggesting frequent exposures that follow sociocultural norms.
Keywords. Monkeypox; Monkeypox virus; Surveillance; Democratic Republic of the Congo; Orthopoxvirus.
Monkeypox virus (MPXV) presents a cautionary tale of path- including elephant shrews and rodents, are thought to be in-
ogen emergence evidenced by increasing incidence in Central volved in the natural history of the virus [7]. Recent emergence
Africa [1], geographic expansion and increasing recognition is attributed to altered environmental drivers, strengthened dis-
in West Africa [2], and rising numbers of exportation events ease surveillance and disease recognition [8], and waning im-
throughout the world [3]. MPXV is a DNA virus of the genus munity conferred by childhood vaccination against smallpox
Orthopoxvirus and counts variola virus (the causative agent [9, 10] , a disease declared eradicated by the World Health
of smallpox) as a close relative. In endemic settings, MPXV is Organization in 1980 [11].
introduced into communities by zoonotic transmission [2], MPXV differs from other zoonotic orthopoxviruses by its
rather than by sustained human-to-human transmission [4–6]. ability to cause disseminated skin lesions in immune-competent
Although the reservoir host remains elusive, small mammals, hosts, relatively severe systemic signs and symptoms, and a fa-
tality rate of up to 11% in unvaccinated individuals [1, 12].
Monkeypox is characterized by a rash that progresses from
macular, papular, vesicular, and pustular lesions to crusts in a
Received 20 November 2020; editorial decision 1 February 2021; accepted 15 March 2021;
published online March 16, 2021. centrifugal distribution. Respiratory and gastrointestinal signs
are common, with more serious cases involving ocular le-
a
E. R. W. and J. B. contributed equally to this work.
b
E. W. O. died on October 29, 2019 prior to publication.
Correspondence: Jesse Bonwitt, Poxvirus and Rabies Branch, Centers for Disease Control sions, bronchopneumonia, encephalitis, and septicemia [12].
and Prevention, 1600 Clifton Rd NE, MS H24-12, Atlanta, GA 30329 (lyn5@cdc.gov). Monkeypox can be confused with chickenpox, a viral infec-
The Journal of Infectious Diseases® 2021;223:1870–8 tion caused by varicella-zoster virus (VZV). In endemic set-
Published by Oxford University Press for the Infectious Diseases Society of America 2021.
This work is written by (a) US Government employee(s) and is in the public domain in the US. tings, clinical diagnosis is complicated by MPXV and VZV
DOI: 10.1093/infdis/jiab133 coinfection [13].
1870 • jid 2021:223 (1 June) • Whitehouse et alThe Democratic Republic of Congo (DRC) reports the highest Healthcare workers alert surveillance officers of patients
annual number of monkeypox cases worldwide, with about who meet the suspected case definition. Investigations
5000 suspected cases in 2019 alone [14]. Using data obtained consist of administering a monkeypox-specific case in-
from enhanced monkeypox surveillance during 2011–2015 in vestigation form and collecting ≥2 lesion samples (on
Tshuapa Province, DRC, we sought to evaluate differences in rare occasions, blood is collected from patients with re-
cumulative incidence, exposure histories, and clinical presenta- solved symptoms). The case investigation form ascertains
tion of laboratory-confirmed monkeypox cases by sex and age skin lesion characteristics, general symptoms and signs,
groups. We hypothesized differences across age and sex based and exposure history (contact with animals or individuals
on previous findings [12, 15–17]. with monkeypox-like symptoms in the 3 weeks preceding
symptom onset).
METHODS
Surveillance Structure Case Definitions
Monkeypox is a notifiable disease in the DRC. Since 2010, the A suspected monkeypox case was defined as an individual with
Downloaded from https://academic.oup.com/jid/article/223/11/1870/6174433 by guest on 09 September 2021
Ministry of Health, Kinshasa School of Public Health, the Institut a vesicular or pustular rash with deep-seated, firm pustules, and
National de Recherche Biomédicale (INRB), and the US Centers ≥1 of the following symptoms: fever preceding the eruption,
for Disease Control and Prevention (CDC) have provided tech- lymphadenopathy (inguinal, axillary, or cervical), or pustules
nical and financial support for enhanced monkeypox surveil- or crusts on the palms of the hands or soles of the feet. A con-
lance in Tshuapa Province. Located in northwestern DRC (Figure firmed monkeypox case requires detection of Orthopoxvirus or
1), Tshuapa Province covers approximately 133 000 km2 with an MPXV DNA with real-time polymerase chain reaction (PCR)
estimated population density of 13.8 inhabitants/km2. Its inhab- or isolation of MPXV in culture from ≥1 specimen. A con-
itants live in mostly rural areas and depend primarily on subsist- firmed VZV case requires detection of VZV DNA by real-time
ence farming, fishing, trapping, and hunting for food sources. PCR from ≥1 specimen.
CENTRAL
SOUTH SUD
N AFRICAN
MEROON REPUBLIC
Lingomo UGA
29.7
CONGO
BON
DR CONGO
Befale
9.3
Mompono Djolu
16.4 16.6
Bokungu
Boende
15.5 ANGOLA
8.6
Wema ZAMBIA
Mondombe
7.5 14.2
Busanga
44.6 Legend
Yalifafu
Ikela Kinshasa
Monkoto 4.9
3.0 13.6
Boende
Monkeypox Incidence (per 100 000)
3.0–7.5
7.6–13.6
13.7–16.4
16.5–44.6
0 70 140 280 km
Service layer credits: Esri, HERE, Garmin, (c) OpenStreetMap contributors, and the GIS user
Figure 1. Average cumulative incidence of confirmed monkeypox cases per 100 000 by health zone—Tshuapa Province, 2011–2015. Data were not corrected for reporting
and investigation effort between health zones.
Monkeypox Surveillance in the Democratic Republic of the Congo • jid 2021:223 (1 June) • 1871Laboratory Testing Statistical Analysis
Swab eluates, crust homogenates, or blood from suspected cases Incidence estimates were expressed as cumulative incidences and
were tested at the INRB and the CDC, as described elsewhere 95% confidence intervals (CIs) were estimated using a Poisson
[13, 18]. Briefly, at the INRB, DNA was extracted from swab distribution. Incidence rate ratios were calculated to compare in-
eluates or crust homogenates, using the QIAamp DNA Blood cidences of confirmed cases by age and sex. Comparisons were
Mini Kit (Qiagen). Samples were first tested for Orthopoxvirus calculated using χ2 or Fisher exact for categorical variables and
DNA with real-time PCR assay [19], and if negative, were tested Kruskal-Wallis tests for continuous variables, as continuous vari-
for VZV DNA, also with real-time PCR assay [20]. Duplicate ables were not normally distributed. Differences were considered
samples and extracted DNA were sent for confirmatory testing statistically significant at P < .05 for all tests. All statistical analyses
to the CDC, where DNA was extracted using the Qiagen EZ1 were performed using Stata 14.0 software (StataCorp).
DNA Tissue Kit (Qiagen) [18]; and tested for MPXV [19] and
VZV [20] DNA, using real-time PCR. Ethical Approval
Surveillance was conducted in accordance with Congolese
Downloaded from https://academic.oup.com/jid/article/223/11/1870/6174433 by guest on 09 September 2021
Data set and Treatment of Variables national guidelines. The activity was determined to be
Inclusion Criteria nonresearch by a CDC human subjects advisor.
Analysis of incidence, demographic, clinical, and exposure
characteristics was conducted for patients with confirmed RESULTS
monkeypox, irrespective of VZV status, with rash onset from Study Population
January 2011 to December 2015. During 2011–2015, the province received 3639 suspected mon-
keypox case notifications, 46.8% (n = 1702) of which were
Demographic Variables
investigated. A total of 3608 samples were collected and sub-
Occupation was included for individuals aged ≥16 years, with
mitted for testing from 1694 individuals. Of these samples,
the possibility of ≥1 occupation per person. Age was calculated
2566 (71.1%) were vesicular or pustular swab samples, 1011
using the interval between date of birth and date of investiga-
(28.0%) were crust samples, 30 (0.8%) were blood samples, and
tion (or date of sample collection and then date of rash onset if
1 (0.03%) was a corneal swab sample. In 1494 suspected cases
date of investigation was missing); reported age was used if date
with a known date of investigation, the median time interval
of birth was missing. Because of the difficulty in using vacci-
between rash onset and sample collection was 4 days (inter-
nation scars to determine smallpox vaccination status, individ-
quartile range [IQR], 3–7; range 1–67 days). Of the 1702 inves-
uals born before January 1980 were presumed to have received
tigated cases, 44 were excluded from further analysis because
smallpox vaccination.
of a missing case investigation form (n = 1) or inconclusive
or missing laboratory results (n = 43). Of the remaining 1658
Incidence
cases, 1057 (29.0% of all notifications and 62.1% of all investiga-
To calculate incidence rates, we used population data for Tshuapa
tions) were confirmed as monkeypox; 775 (73.3%) had MPXV
Province from 2015 [21] and applied these to demographic es-
only, 169 (16.0%) were concurrently infected with both MPXV
timates for each health zone (unpublished, Division Provinciale
and VZV, and for 113 (10.7%) specimens were not available for
de la Santé, Tshuapa). Data for 2011–2014 were extrapolated as-
VZV testing at CDC.
suming an annual growth of 3.3%, and the midpoint population
The median age of confirmed case patients was 14.0 years
(2013) was used to calculate average cumulative incidence [22].
(IQR, 6.0–23.9 years; range, 1 month to 79 years). Among
Because population estimates were only available in 5-year age
1054 case patients in whom sex was recorded, 53.7% were
increments, we included all individuals aged ≥35 years as popula-
male (n = 568), and 46.0% female (n = 486). Most confirmed
tion denominators for presumed vaccinated and all agedIncidence humans (Figure 2A), although there was no significant differ-
Confirmed cases of monkeypox were reported in all 12 health ence by age groups (χ 2 = 6.60; P = .25). Seventy-five percent of
zones, ranging from 3.0 to 44.5 per 100 000 (Figure 1). The av- animal exposures among females occurred among those aged
erage incidence for all health zones was 14.1 per 100 000 (95% 5–29 years (Figure 3A). Animal exposures differed significantly
CI, 13.3–15.0) and was significantly higher in males than in by age group among males (χ 2 = 19.68; P = .001). Males aged
females (Table 1). Males aged 5–9 and 10–19 years had the 0–9 years were reported to have had more exposures to symp-
highest incidences of all age and sex categories, followed by tomatic humans than animals, a trend that was reversed be-
females aged 20–29 years. Males aged 0–4 and ≥40 years, and yond 10 years of age (Figure 2B). Among males, the frequency
females aged 20–29 years had significantly higher incidences of animal exposures ranged between 11.4% and 14.2%, except
than their respective sex counterparts (Table 1).The incidence for males aged 10–19 years, who accounted for 37.5% of animal
of confirmed cases among those presumed unvaccinated was exposures (Figure 3A and Supplementary Table 2).
>2.5 times the incidence of monkeypox among those presumed Monkeypox cases with animal exposures had contact with
vaccinated (incidence rate ratio, 2.73; 95% CI, 2.21–3.40). nonhuman primates (68.4%; n = 199), “rats” (typically re-
Downloaded from https://academic.oup.com/jid/article/223/11/1870/6174433 by guest on 09 September 2021
fers to pouched rats of genus Cricetomys spp) (17.5%; n = 51),
Exposure History squirrels (10.3%; n = 30), or other domestic or wild animal
Of 837 confirmed cases with completed exposure history, 309 species (15.2%; n = 44). Males were more likely than females
(36.9%) reported having had contact with ≥1 animal as their to report contact with rats (72.6% vs 27.5%; χ 2 = 5.43; P = .02)
only exposure in the 3 weeks prior to symptom onset, and (Supplementary Table 3), but there were no significant differ-
279 (33.3%) reported contact with ≥1 symptomatic human ences by age group (Supplementary Table 4). Females (58 of 132;
with monkeypox-like symptoms as their only exposure in the 47.2%) were more likely than males (56 of 176; 34.8%) to re-
3 weeks before symptom onset. An additional 109 confirmed port contact with a dead animal purchased for meat (χ 2 = 4.44;
case patients (13.0%) reported contact with both animals and P = .04). There were no significant differences by sex with other
symptomatic humans, and 140 (16.7%) reported no known ex- types of animal-human contact (Supplementary Table 3).
posures; both groups were excluded from further analysis of ex- Of the 279 case patients reporting contact with a sympto-
posure history. matic person, 96.1% (n = 268) reported 1 symptomatic contact,
There were significant differences in exposure type by age 2.9% (n = 8) reported 2 symptomatic contacts, and 1.1% (n = 3)
(within males) and sex among cases with mutually exclusive ex- reported 3 symptomatic contacts. Females (n = 149; 53.4%)
posures. Overall, males (57.1%; n = 176) were more likely than reported more contact than males with symptomatic people
females (42.9%; n = 132) to report animal exposures (χ 2 = 6.53; (n = 130; 46.6%; χ 2 = 6.53; P = .01). There were significant dif-
P = .01). Among females, those aged 5–19 and ≥40 years had ferences in the distribution of people reporting exposures only
higher frequency of exposures to animals than to symptomatic to symptomatic humans between males and females across age
Table 1. Confirmed Monkeypox Cases and Annual Incidence per 100 000 by Age Group, Vaccination Status, and Sex—Tshuapa Province, 2011–2015a
All Patients Male Patients Female Patients
Incidence per Incidence per Incidence per
100 000 100 000 100 000 IRR Comparing Male to Female
Patient Group Cases, No. (95% CI) Cases, No. (95% CI) Cases, No. (95% CI) Patients (95% CI)
Age group, y
0–4 205 15.1 (13.1–17.3) 118 17.3 (14.3–20.7) 86 12.7 (10.1–15.7) 1.36 (1.02–1.82b)
5–9 200 18.1 (15.7–20.8) 104 18.9 (15.4–22.8) 96 17.4 (14.1–21.3) 1.08 (.81–1.44)
10–19 302 17.4 (15.5–19.4) 168 19.3 (16.5–22.5) 133 15.3 (12.8–18.1) 1.26 (1.00–1.60)
20–29 185 15.5 (13.4–17.9) 76 12.7 (10.0–15.9) 108 18.2 (14.9–22.0) 0.70 (.51–.95b)
30–39 100 11.3 (9.2–13.8) 57 13.0 (9.8–16.8) 43 9.7 (7.0–13.0) 1.34 (.89–2.04)
≥40 65 5.4 (4.1–6.8) 45 8.4 (6.1–11.2) 20 3.0 (1.8–4.6) 2.82 (1.63–5.04b)
Total 1057 14.1 (13.3–15.0) 568 15.4 (14.2–16.8) 486 12.8 (11.7–13.9) 1.21 (1.07–1.37b)
c
Unvaccinated 960 16.4 (15.3–17.4) 504 17.1 (15.7–18.7) 453 15.5 (14.1–16.9) 1.11 (.97–1.26)
Vaccinatedc 97 6.0 (4.9–7.3) 64 8.7 (6.7–11.1) 33 3.8 (2.6–5.3) 2.31 (1.49–3.63b)
Abbreviations: CI, confidence interval; IRR, incidence rate ratio.
a
Population and demographic estimates for Tshuapa Province from 2015 [20] were used to estimate annual population size and demographics for 2013, the midpoint population, assuming
an annual growth rate of 3.3% [21].
b
Statistically significant 95% CIs.
c
Because smallpox vaccination was discontinued in 1980, individuals born before January 1980 were presumed to have been vaccinated.
Monkeypox Surveillance in the Democratic Republic of the Congo • jid 2021:223 (1 June) • 1873A B
Human only (n = 149) 6.9% (n = 9)
4.0% (n = 6)
>40 >40 11.4% (n = 20)
6.1% (n = 8) Animal only (n = 132)
6.9% (n = 9)
7.4% (n = 11)
30–39 30–39 11.4% (n = 20) Human only (n = 130)
6.8% (n = 9)
Age Category, y
Age Category, y
9.2% (n = 12) Animal only (n = 176)
26.2% (n = 39)
20–29 20–29 13.1% (n = 23)
20.5% (n = 27)
26.2% (n = 34)
27.5% (n = 41)
10–19 10–19 37.5% (n = 66)
31.1% (n = 41)
22.3% (n = 29)
15.4% (n = 23)
5–9 5–9 14.2% (n = 25)
23.5% (n = 31)
28.5% (n = 37)
19.5% (n = 29)
0–4 0–4
12.1% (n = 16) 12.5% (n = 22)
Downloaded from https://academic.oup.com/jid/article/223/11/1870/6174433 by guest on 09 September 2021
0% 10% 20% 30% 40% 50% 0% 10% 20% 30% 40% 50%
Figure 2. A, Age distribution of female case patients with confirmed monkeypox, by exposure to animals only or symptomatic humans only—Tshuapa Province, 2011–2015
(n = 281; P = .25). B, Age distribution of male case patients with confirmed monkeypox, by exposure to animals only or symptomatic humans only—Tshuapa Province,
2011–2015 (n = 306; P = .001).
groups (χ 2 = 16.19; P = .006) (Figure 3B). Among individuals playing together (6.6%; 18 of 271), and other interactions (6.5%;
aged 10–29 years, females reported significantly more exposures 18 of 276). There were no significant differences in the type of
to symptomatic humans than males (age 10–19 years, 54.7% fe- contact or relationship to the contact by sex (Supplementary
male vs 45.3% male [P = .03]; age 20–29 years: 76.5% female Table 3). Although a higher proportion of females (n = 65;
vs 23.5% male [P = .02]) (Supplementary Table 2). Among fe- 60.2%) reported providing care for symptomatic contacts than
males, exposure to symptomatic humans remained relatively males (n = 43; 39.8%), this difference was not significant (χ 2 =
constant until 29 years of age, in contrast to males, for whom 3.06; P = .08). Across age groups, the proportion of case pa-
human exposures decreased beyond 19 years of age (Figure 3B). tients providing care for symptomatic contacts increased with
Among 264 case patients with complete information on age (Fisher exact P < .001) (Supplementary Table 4).
contact with symptomatic humans, family members were the
most frequently reported contact (90.5%; n = 239), followed by Clinical Characteristics
friends (6.4%; n = 17), and others (3.4%; n = 9). Reported ex- All 1057 confirmed cases reported a cutaneous rash; 8 (.8%)
posure types included shared living space (89.8%; 247 of 275), were deceased at the time of the investigation (complete out-
preparing food together (58.2%; 160 of 275), sharing a bed come data were not collected, and mortality rates could there-
(48.9%; 134 of 274), providing medical care (39.4%; 108 of 274), fore not be calculated). Of 1029 confirmed case patients with
A B
>40 6.1% 11.4% >40 4.0% 6.9%,
(n = 8) (n = 20) (n = 6) (n = 9)
Females (n = 132) Females (n = 149)
Males (n = 176) Males (n = 130)
30–39 6.8% 11.4% 30–39 7.4% 6.9%
(n = 9) (n = 20) (n = 11) (n = 9)
20.5% 26.2% 9.2%
Age Category, y
Age Category, y
20–29 13.1% 20–29
(n = 27) (n = 23) (n = 39) (n = 12)
31.1% 37.5% 27.5% 26.2%,
10–19 10–19
(n = 41) (n = 66) (n = 41) (n = 34)
23.5% 14.2% 15.4% 22.3%
5–9 5–9 (n = 23) (n = 29)
(n = 31) (n = 25)
12.1% 12.5% 19.5% 28.5%,
0–4 0–4 (n = 29) (n = 37)
(n = 16) (n = 22)
Figure 3. A, Age distribution by sex among confirmed monkeypox case patients who self-reported only an exposure to a domestic or wild animal in the 3 weeks before
illness onset—Tshuapa Province, 2011–2015 (n = 308). B, Age distribution by sex among confirmed monkeypox case patients who self-reported only an exposure to a human
with a similar rash illness in the 3 weeks before symptom onset —Tshuapa Province, 2011–2015 (n = 279).
1874 • jid 2021:223 (1 June) • Whitehouse et alcomplete dates, 99.4% (n = 1023) reported a subjective or meas- historical vaccination against smallpox might confer a degree
ured fever before rash onset. The median interval between fever of cross-protection against monkeypox [10, 23]. This is further
and rash onset was 2 days (IQR, 2–3 days; range, 1–34 days; supported by the increase in the median age of case patients
n = 932), and there was no significant difference in this interval as the susceptible population ages, from 4.4 years in the 1980s
between age groups (χ 2 = 3.06; P = .69). Of 1025 confirmed [12, 16], to 11.9 years in Sankuru Provence during 2006–2007
case patients with known lesion distribution, 96.5% (n = 989) [23], 14 years among our cohort, and 29 years in Nigeria during
presented with centrifugal distribution, 3.2% (n = 33) with cen- 2017–2018 [2]. The global ramifications of waning immunity
tripetal distribution, and 0.3% (n = 3) had equal lesion counts against orthopoxviruses are underscored by the recent mon-
on their trunk and extremities. The median lesion count was keypox outbreak in Nigeria [2] and the increasing number of
102 (IQR, 61–177; range, 1–2679; n = 1043). No differences cases reported in West and Central Africa [25].
were observed by age group in lesion count by body site, me- Monkeypox incidence was overall higher in males than in
dian lesion count, or lesion severity score (Table 2). females (Table 1), in keeping with previous studies [12, 23].
Among signs and symptoms reported during the period of Notably, incidence was significantly higher in females aged
Downloaded from https://academic.oup.com/jid/article/223/11/1870/6174433 by guest on 09 September 2021
illness, coughing, lymphadenopathy, dysphagia, headache, 20–29 years than in males, a group that also reported the second
and conjunctivitis differed significantly by age group (Table 2). highest proportion of exposures to symptomatic people (Figure
There was no consistent pattern between frequency of specific 3B). This might be because 20–29-year-old women are of child-
signs and symptoms and age groups. Patients born before 1980 bearing age and possibly most at risk of exposure when caring
(presumed vaccinated) were less likely to report lymphadenop- for sick children [26]. Additional differences in self-reported
athy, buccal ulcers, dysphagia, conjunctivitis, and photophobia exposures by sex and age could be explained by established
but more likely to report headache than patients born after 1980 gender-specific roles [24]. For example, females were more
(Supplementary Table 5). No significant differences in lesion likely to report contact with a dead animal purchased for meat,
count or severity were observed between individuals born be- a behavioral risk factor for exposure to zoonotic pathogens
fore versus after 1980 (Supplementary Table 5). [15]. Similarly, the highest incidence among males was in those
aged 10–19 years (Table 1), the same cohort that accounted for
DISCUSSION
the highest proportion of animal exposures (Figure 3A). This
Incidence in Tshuapa Province during the surveillance period is consistent with prior epidemiological studies from DRC [6,
was more than twice that reported immediately north (Bumba 16], and likely reflects hunting practices in Central [9, 27] and
zone) during 1981–1985 using active surveillance (6.3 cases Western Africa [28], whereby young males are frequently in-
per 100 000) [10]. Although comparing incidence across space volved in hunting small mammals that are possible MPXV res-
and time is inherently perilous owing to diverse and incon- ervoir hosts [7]. Nevertheless, exposures to animals were widely
sistent surveillance and laboratory capacity [8], this doubling distributed across sex and age groups, indicating that potential
between 2 adjacent provinces is noteworthy. This is consistent exposures to zoonotic diseases occur frequently throughout
with an increase in monkeypox incidence at the national level the population, as previously reported in rural settings where
during 2001–2013, which could not be solely attributed to im- people depend on and routinely interact with wild animals [27,
proved disease surveillance [8]. While incidence varied dramat- 28].
ically by health zone, the overall incidence in Tshuapa Province One-third of confirmed case patients reported exposures to
was lower than that reported immediately south (Sankuru symptomatic humans only, indicating that secondary exposures
Province) during 2006–2007 using active surveillance (55.3 among household members are relatively common. These in-
cases per 100 000) [23]. Such differences could be due to sur- cluded frequent and potentially high-risk exposures involving
veillance artifacts but also call for further investigations to ad- communal activities in shared domestic spaces or providing care
dress whether differences or changes in reservoir distribution for ill family members. Studies from the 1980s demonstrated
or density [10, 24], or sociocultural factors that affect animal- that most monkeypox cases were from animal exposures [10,
human interactions and land use could be contributing to the 29], but this study and others suggest that human-to-human
effect [24]. transmission could be a significant driver of infection [30],
The incidence among confirmed case patients was almost especially in households [24]. Although only relatively short
3 times higher among those presumed unvaccinated (16.4 monkeypox transmission chains (≤7) have been described [4,
per 100 000) than among those presumed vaccinated (6.0 per 5, 30], increasing human-to-human transmission may be due to
100 000). The incidence among individuals presumed vac- waning immunity and provide opportunities for evolutionary
cinated was comparable to that in the Bumba zone during adaption that increases secondary transmission [30].
1981–1985 (6.3 per 100 000), a cohort that presumably in- Most of the case patients in this study presented with mon-
cluded people vaccinated against smallpox [10]. These find- keypox before rash (99.4%) and lymphadenopathy (84.7%)
ings strengthen findings of previous studies suggesting that (Table 2), both defining features of monkeypox infection [12].
Monkeypox Surveillance in the Democratic Republic of the Congo • jid 2021:223 (1 June) • 1875Table 2. Clinical Characteristics of Confirmed Monkeypox Cases by Age Category—Tshuapa Province, 2011–2015
Case Patients by Age Group, No. (%)
Characteristic 0–4 y 5–9 y 10–19 y 20–29 y 30–39 y ≥40 y Total P Valuea
Presence of lesions (n = 1057)
Face 202 197 291 184 98 64 1036 .27 (exact)
(98.5) (98.5) (96.4) (99.5) (99.0) (98.5) (98.0)
Trunk 200 196 291 181 97 63 1028 .89 (exact)
(97.6) (98.0) (96.4) (97.8) (97.0) (96.9) (97.3)
Arms 196 194 294 181 98 63 1026 .84 (exact)
(95.6) (97.0) (97.4) (97.8) (98.0) (96.9) (97.1)
Palms 197 190 287 179 95 61 1009 .88 (exact)
(96.1) (95.0) (95.0) (96.8) (95.0) (93.9) (95.5)
Legs 154 142 222 142 76 50 786 .81 (χ 2 = 2.28)
(75.1) (71.0) (73.5) (76.8) (76.0) (76.9) (74.3)
Downloaded from https://academic.oup.com/jid/article/223/11/1870/6174433 by guest on 09 September 2021
Soles 172 168 252 162 80 51 885 .50 (χ 2 = 4.38)
(83.9) (84.0) (83.4) (87.6) (80.0) (78.5) (83.7)
Genitals 64 65 68 56 30 17 300 .15 (χ 2 = 8.20)
(31.2) (32.5) (22.5) (30.3) (30.0) (26.2) (28.4)
Total lesion count, median 93.5 97 106.5 109.5 115.5 115 102 .25 (Kruskal-Wallis
(IQR; range), (n = 1043) (57–152; (59–169; (63.5–184.5; (65.5–192.5; (63–195; (62–168.5; (61–177; χ 2 = 6.63)
5–510) 1–660) 5–2679) 13–929) 18–940) 9–739) 1–2679)
Lesion severity (n = 1043)
Mild (≤25 lesions) 13 10 16 5 1 3 48 .41 (χ 2 = 15.54)
(6.4) (5.0) (5.4) (2.7) (1.0) (4.7) (4.6)
Moderate (26–100 lesions) 101 92 126 77 42 24 462
(50.0) (46.2) (42.6) (41.9) (42.9) (37.5) (44.3)
Severe (101–249 lesions) 65 73 109 78 38 29 392
(32.2) (36.7) (36.8) (42.4) (38.8) (45.3) (37.6)
Exceptional (≥250 lesions) 23 24 45 24 17 8 141
(11.4) (12.1) (15.2) (13.0) (17.4) (12.5) (13.5)
Clinical signs and symptomsb
Vomiting (n = 1010) 49 49 73 37 28 14 250 .74 (χ 2 = 2.72)
(24.9) (25.5) (25.5) (20.9) (29.2) (22.6) (24.8)
Cough (n = 1024) 125 102 172 92 45 25 561 .01c (χ 2 = 14.85)
(62.8) (52.0) (58.3) (51.4) (48.4) (40.3) (54.8)
Lymphadenopathy (n = 1034) 155 170 255 164 80 52 876 .04c (χ 2 = 11.82)
(79.1) (87.2) (85.6) (90.1) (81.6) (80.0) (84.7)
Chills (n = 1027) 157 161 242 161 79 52 852 .13 (χ 2 = 8.52)
(78.9) (82.1) (82.3) (89.4) (85.0) (80.0) (83.0)
Dysphagia (n = 1032) 128 136 226 140 69 37 736 .02c (χ 2 = 13.94)
(66.0) (69.4) (75.3) (76.9) (71.9) (57.8) (71.3)
Buccal ulcers (n = 1018) 103 109 164 114 53 27 570 .06 (χ 2 = 10.66)
(52.8) (56.8) (56.0) (63.7) (56.4) (41.5) (56.0)
Headache (n = 1011) 121 141 242 147 87 55 793The absence of differences in clinical presentation, lesion distri- the relative importance of behavioral risk factors and waning
bution, severity, and count by age groups stand out in our anal- smallpox immunity for incidence. Differences in incidence and
ysis. Historical studies suggest that smallpox vaccination lessened exposure histories by sex and age are complicated by the diver-
the risk of monkeypox infection and illness severity, particularly sity and intensity of animal-human interactions and are best
within 20 years of vaccination [11, 12]; however, these findings elucidated through collaborative epidemiological, anthropolog-
were not confirmed in studies in which vaccination occurred ical, and ecological approaches.
more than 20 years earlier [15]. While our results showed dif-
ferences in symptoms by patient age (Table 2) and vaccination Supplementary Data
status (Supplementary Table 5), there was no clear relationship Supplementary materials are available at The Journal of Infectious
between these variables and frequency of symptoms. This could Diseases online. Consisting of data provided by the authors to
be due to differences in symptoms by age independent of vacci- benefit the reader, the posted materials are not copyedited and
nation status, differences in the durability of the immunological are the sole responsibility of the authors, so questions or com-
response conferred by smallpox vaccination, reporting bias by ments should be addressed to the corresponding author.
Downloaded from https://academic.oup.com/jid/article/223/11/1870/6174433 by guest on 09 September 2021
age group, or collection of data from patients at different time
points in their clinical progression. In addition, 10% of case pa- Notes
tients described in this study were presumed to be vaccinated, Acknowledgments. We are indebted to the surveillance of-
further indicating that vaccine-derived immunity may wane or is ficers of Tshuapa Province and to all the patients featured in
not 100% effective at preventing infection [12, 29]. this study. We are thankful to Brett Petersen for reviewing the
Our study has several limitations. Healthcare-seeking be- manuscript.
haviors and investigations in Tshuapa Province can be im- Financial support. This work was supported by the US
peded by impassible roads, and by limited and competing Centers for Disease Control and Prevention. The findings
public health resources. Fewer than half of suspected mon- and conclusions in this report are those of the authors and do
keypox cases reported to the provincial public health de- not necessarily represent the views of the Centers for Disease
partment were investigated, which likely underestimated the Control and Prevention.
number of confirmed cases, and could have biased our re- Potential conflicts of interest. All authors: No reported
sults. Estimating incidence was further complicated by unre- conflicts. All authors have submitted the ICMJE Form for
liable demographic data. Exposure history was self-reported, Disclosure of Potential Conflicts of Interest. Conflicts that the
which is subject to recall bias, although this might be tem- editors consider relevant to the content of the manuscript have
pered by the short median interval between rash onset and been disclosed.
investigation (4 days). Reported exposures to persons with
monkeypox-like symptoms were not systematically inves- References
tigated and could be due to other illnesses involving rash. 1. McCollum AM, Damon IK. Human monkeypox. Clin
Clinical characteristics might also have been affected by the Infect Dis 2014; 58:260–7.
inclusion of VZV coinfection [18]. Because smallpox vacci- 2. Yinka-Ogunleye A, Aruna O, Dalhat M, et al. Outbreak of
nation status was calculated from age, some individuals are human monkeypox in Nigeria in 2017–18: a clinical and ep-
likely to be misclassified. Additional studies are needed to idemiological report. Lancet Infect Dis 2019; 19:872–9.
determine whether age, independent of vaccination status, 3. Mauldin MR, McCollum AM, Nakazawa Y, Mandra A,
affects MPXV immunity and clinical outcome. Whitehouse ER, Davidson W. Exportation of mon-
In conclusion, based on 5 years of enhanced surveillance in keypox virus from the African continent. J Infect Dis
Tshuapa Province, this data set represents one of the largest co- 2020:1–10.
horts of laboratory-confirmed monkeypox cases. This provides 4. Nolen LD, Osadebe L, Katomba J, et al. Extended human-
uniquely detailed insight into the clinical and epidemiological to-human transmission during a monkeypox outbreak in
features of monkeypox in an endemic setting and identification the Democratic Republic of the Congo. Emerg Infect Dis
of specific risk groups, such as females of childbearing age or 2016; 22:1014–21.
young males who might benefit from targeted interventions. 5. Jezek Z, Arita I, Mutombo M, Dunn C, Nakano JH,
An evaluation of film-based educational activities demon- Szczeniowski M. Four generations of probable per-
strated that it could increase awareness of monkeypox [31] and son-to-person transmission of human monkeypox. Am J
be an effective medium for targeted health education on mon- Epidemiol 1986; 123:1004–12.
keypox. Our findings reveal potential changes in monkeypox 6. Nolen LD, Osadebe L, Katomba J, et al. Introduction of
epidemiology, including the effects of waning immunity to monkeypox into a community and household: risk factors
orthopoxviruses, and increasing proportion of cases attributed and zoonotic reservoirs in the Democratic Republic of the
to human exposures. Continued surveillance could help clarify Congo. Am J Trop Med Hyg 2015; 93:410–5.
Monkeypox Surveillance in the Democratic Republic of the Congo • jid 2021:223 (1 June) • 18777. Doty JB, Malekani JM, Kalemba LN, et al. Assessing mon- West African and Congo Basin strain DNA. J Virol Methods
keypox virus prevalence in small mammals at the human– 2010; 169:223–7.
animal interface in the Democratic Republic of the Congo. 20. Pahud BA, Glaser CA, Dekker CL, Arvin AM, Schmid DS.
Viruses 2017; 9:283. Varicella zoster disease of the central nervous system: epi-
8. Hoff N, Doshi R, Colwell B, et al. Evolution of a disease sur- demiological, clinical, and laboratory features 10 years after
veillance system: an increase in reporting of human mon- the introduction of the varicella vaccine. J Infect Dis 2011;
keypox disease in the Democratic Republic of the Congo, 203:316–23.
2001–2013. Int J Trop Dis Heal 2017; 25:1–10. 21. Institut National de la Statistique. Annuaire Statistique 2015.
9. Rimoin AW, Alfonso VH, Hoff NA, et al. Human ex- https://www.ins.cd/wp-content/uploads/2021/04/Annuaire-
posure to wild animals in the Sankuru Province of the statistique-2015-Web.pdf. Accessed 27 October 2020.
Democratic Republic of the Congo. Ecohealth 2017; 22. Ecole de Santé Publique de l’Université de Kinshasa (ESPK)
14:552–63. and ICF. République Démocratique Du Congo: Evaluation
10. Jezek Z, Grab B, Paluku KM, Szczeniowski MV. Human des Prestations des Services de Soins de Santé (EPSS RDC)
Downloaded from https://academic.oup.com/jid/article/223/11/1870/6174433 by guest on 09 September 2021
monkeypox: disease pattern, incidence and attack rates 2017-2018. https://dhsprogram.com/pubs/pdf/SPA30/
in a rural area of northern Zaire. Trop Geogr Med 1988; SPA30.pdf. Accessed 27 October 2020.
40:73–83. 23. Rimoin AW, Mulembakani PM, Johnston SC, et al. Major
11. Fenner F, Henderson D, Arita I, Jezek Z, Ladnyi I. Smallpox increase in human monkeypox incidence 30 years after smallpox
and its eradication. Geneva, Switzerland: World Health vaccination campaigns cease in the Democratic Republic of
Organization, 1988. Congo. Proc Natl Acad Sci U S A 2010; 107:16262–7.
12. Jezek Z, Szczeniowski M, Paluku KM, Mutombo M. Human 24. Khodakevich L, Szczeniowski M, Nambu-ma-Disu, et al.
monkeypox: clinical features of 282 patients. J Infect Dis Monkeypox virus in relation to the ecological features sur-
1987; 156:293–8. rounding human settlements in Bumba zone, Zaire. Trop
13. Hughes CM, Liu L, Davidson WB, et al. A tale of two vir- Geogr Med 1987; 39:56–63.
uses: coinfections of monkeypox and varicella zoster virus 25. Durski KN, McCollum AM, Nakazawa Y, et al. Emergence
in Democratic Republic of Congo. Am Soc Trop Med Hyg of monkeypox—West and Central Africa, 1970–2017. Morb
2020; 104:604–11.. Mortal Wkly Rep 2018; 67:306–10.
14. World Health Organization Regional Office for Africa. 26. Jezek Z, Grab B, Szczeniowski MV, Paluku KM,
Weekly bulletin on outbreaks and other emergencies. Week Mutombo M. Human monkeypox: secondary attack rates.
53: 23–29 December 2019. https://apps.who.int/iris/bit- Bull World Health Organ 1988; 66:465–70.
stream/handle/10665/331023/OEW07-1016022020.pdf. 27. Narat V, Kampo M, Heyer T, et al. Using physical contact
Accessed 27 October 2020. heterogeneity and frequency to characterize dynamics of
15. Doshi RH, Alfonso VH, Morier D, et al. Monkeypox rash human exposure to nonhuman primate bodily fluids in
severity and animal exposures in the Democratic Republic central Africa. PLoS Negl Trop Dis 2018; 12:1–25.
of the Congo. Ecohealth 2020; 17:64–73. 28. Bonwitt J, Kandeh M, Dawson M, et al. Participation of
16. Jezek Z, Grab B, Szczeniowski M, Paluku KM, Mutombo M. women and children in hunting activities in Sierra Leone
Clinico-epidemiological features of monkeypox patients and implications for control of zoonotic infections. PLoS
with an animal or human source of infection. Bull World Negl Trop Dis 2017; 11:1–21.
Health Organ 1988; 66:459–64. 29. Arita I, Jezek Z, Khodakevich L, Ruti K. Human monkeypox:
17. Reynolds MGG, Yorita KLL, Kuehnert MJJ, et al. Clinical a newly emerged orthopoxvirus zoonosis in the tropical rain
manifestations of human monkeypox influenced by route forests of Africa. Am J Trop Med Hyg 1985; 34:781–9.
of infection. J Infect Dis 2006; 194:773–80. 30. Learned LA, Reynolds MG, Wassa Wassa D, et al. Extended
18. Osadebe L, Hughes CM, Shongo Lushima R, et al. interhuman transmission of monkeypox in a hospital com-
Enhancing case definitions for surveillance of human mon- munity in the Republic of the Congo, 2003. Am J Trop Med
keypox in the Democratic Republic of Congo. PLoS Negl Hyg 2005; 73:428–34.
Trop Dis 2017; 11:1–13. 31. Roess AA, Monroe BP, Kinzoni EA, et al. Assessing the effec-
19. Li Y, Zhao H, Wilkins K, Hughes C, Damon IK. Real-time tiveness of a community intervention for monkeypox preven-
PCR assays for the specific detection of monkeypox virus tion in the Congo basin. PLoS Negl Trop Dis 2011; 5:e1356.
1878 • jid 2021:223 (1 June) • Whitehouse et alYou can also read
