rocky mountain spotted fever in sonora, mexico mountain spotted fever in sonora, mexico gerardo...
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Rocky Mountain spotted fever in Sonora, Mexico
Gerardo Álvarez PhD
Session: Vector-Borne/Zoonotic Disease
Phoenix, Arizona. July 28th 2016
Background
• Sonora, Mexico borders the U.S. state of Arizona
• Population: 2,925,366
• Considered as a well-developed state within Mexico (UN Program,
2012)
• After 5 decades with no cases of RMSF, reemerged early
2000’s (Álvarez G. Salud Publica Mex 2013; 55 (2): 151-52)
• Endemic from 1900-1950. Known as “Fiebre Pinta”
• RMSF incidence coincides with the presence of the tick
Rhipicephalus sanguineus on dogs (Tinoco L. Vet Rec 2009;164:59-61;
Eremeeva ME. J Med Entomol. 2011;48:418–21)
Background
• April 2015, Mexican MOH issued a declaration of
epidemiologic emergency on Rocky Mountain
spotted fever (RMSF)
• Public health concerns in several states, mostly in
northern Mexico
• Significant impact in underserved populations
• Particularly children < 10 years old
Incidence of RMSF by state. Mexico, 2009-2014
States with positive samples
States with documented incidence From 2000
Epi Bulletin DGE/SSA Registered cases 2009-2014: 3978 2009: 3/32 States notified cases 2014: 21/32 States documented cases
3 States with highest incidence 1. Baja California 2. Baja California Sur
3. Sonora (331) 1034 cases in state epi surveillance system http://www.epidemiologia.salud.gob.mx/doctos/
Source: Source: Annual Morbidity Reports, 1984-2014. National Department of Epidemiology. Secretariat of Health
RMSF incidence by State, Mexico, 2014
Incidence/100,000 hab.
>2.5
0.21 – 2.49
0.03 – 0.2
Without notified cases
0.03
0.13
0.16
0.17
0.26
0.26
0.40
0.62
2.56
2.71
2.97
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5
Guanajuato
Quintana Roo
Chihuahua
Sinaloa
Nacional
Morelos
Baja…
Nuevo León
Sonora
Baja California
Coahuila
Cumulative incidence 100,000 hab.
RMSF (A77.0) incidence by State. México, 2014
Source: Source: Annual Morbidity Reports, 1984-2014. National Department of Epidemiology. Secretariat of Health
RMSF Annual incidence. Mexico, 2003-2016
Source: Annual Morbidity Reports, 1984-2014. National Department of Epidemiology. Secretariat of Health * Up to May 31, 2016
9 8 8 3 1 2
948
527 545
677
1032
308 266
64
0
200
400
600
800
1000
1200
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016*
Cas
es
Year of occurrence
RMSF cases by year of occurrence, Mexico 2003-2016*
RMSF Annual incidence. Sonora, 2003-2016*
Source: Sonora Secretariat of Health * Up to July 22, 2016
82 89
42
17
64
156
90
121 115
84
101
168
60
0
20
40
60
80
100
120
140
160
180
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016*
Cas
es
RMSF incidence by year of occurrence. Sonora, 2004-2016*
Cases Incidence trend
RMSF incidence and CFR, Sonora. 2003-2016*
USA CFR <0.5%. Sonora CFR >25%
Source: Sonora Secretariat of Health * Up to July 22, 2016
0.0 0.0 0.0 2.4
5.9 7.8
9.6
17.8
14.0 16.5
22.6
25.7
41.1
37.7
0.0
10.0
20.0
30.0
40.0
50.0
0.0
10.0
20.0
30.0
40.0
50.0
60.0
70.0
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016*
CR
F p
er
10
0
Cas
es
pe
r m
illio
n in
hab
.
RMSF, trend of cumulative incidence and CFR. Sonora, 2003-2016*
CI CFR
Epidemiology
• RMSF in Sonora spreads from the southern to
the northern areas of the state
• 2004-2016: 1200 cases; 211 deaths. CFR =
17.6%
• 497 cases in <19 years old; 108 deaths. 51% of
RMSF total mortality. CFR=22%
• 225 cases in a pediatric hospital; 75 deaths.
CFR=33.3%
50.0
64.3
82.7 82.4 89.4 89.5
94.7 91.0 92.9 90.8
96.4
85.1
73.1
93.8 88.9
50.0
35.7
17.3 17.6 10.6 10.5
5.3 9.0 7.1 9.2
3.6
14.9
26.9
6.3 11.1
< 1 1 - 4 5 - 9 1 0 - 1 4 1 5 - 1 9 2 0 - 2 4 2 5 - 2 9 3 0 - 3 4 3 5 - 3 9 4 0 - 4 4 4 5 - 4 9 5 0 - 5 4 5 5 - 5 9 6 0 - 6 4 > 6 5
Per
cen
tage
Age group
Rocky Mountain spotted fever. Case-fatality ratio by age group. Sonora, Mexico. 2004-2015*
(n=1030)
Nonfatal Fatal
Source: Epidemiological Surveillance System. UIEES/DE/DGSSC/SSP *Up to 10/22/2015
n=4 n=70 n=156 n=142 n=85 n=86 n=75 n=78 n=85 n=65 n=55 n=47 n=26 n=16 n=36
Epidemiology
• RMSF in children from Sonora
• Mostly urban (75% patients live in urban localities)
• Socioenvironmental factors may play a role in the
epidemic 90% live in poverty
• 85% has temporary medical insurance (seguro
popular)
• 90% had a documented history of tick contact
84.7%
15.3%
RMSF cases by medical care insurance. Mexico, 2009-2013
SSA
Other
Epidemiology
• “Where you live makes a
difference to your health,
over and above who you
are” (S.V. Subramanian, 2000)
* 01/01/2004-06/18/2015
100
92.1
85.7
77.8 82.5
69.8
62.3
52.4
99.3
86.4
80.2
41.5
55.8 57.1
10.2
23.8
0
20
40
60
80
100
120
Fever Rash (palms and soles) Headache/Irritability Leukocytosis Thrombocytopenia(<50,000µL)
Hyponatremia (<135meq/L)
Acute kidney injury Severe sepsis
Per
cen
tage
Clinical features of RMSF in hospitalized children. Sonora, Mexico. 2004-2015* (n=225)
Fatal (63) Nonfatal (147)
<0.001
<0.001
<0.001
<0.001
RMSF. Clinical features
RMSF rash may involve palms
and soles. Sign of delay in clinical suspicion
[Buckingham, 2007; Graham, 2011, Alvarez, 2015]
RMSF. Female. 15 years old. 2011
RMSF. Female. 4 years old. 2014
RMSF. Male. 6 years old. 2014
RMSF. Clinical features
Other significant clinical signs include periorbital edema and swelling
of ankles and hands. [Buckingham, 2005; Graham, 2011; SSA-Mexico, 2013]
RMSF. Female 15 years old, 2009
RMSF. Male. 12 years old. 2010
RMSF. Male, 8 years old. 2012
RMSF. Female. 6 years old. 2012
RMSF. Clinical features
RMSF. Male. 4 years old. 2015 RMSF. Male. 17 years old. 2015 RMSF. Female. 7 years old. 2015
“With progression the rash becomes more petechial and individual lesions often enlarge and coalesce to form
ecchymoses” (Paddock, C. In press, 2015)
RMSF. Clinical features
Petechial component is very frequent, 82% of our patients had severe petechiae
RMSF. Female 4 years old. 2014 RMSF. Male 3 years old. 2013
RMSF. Female 16 years old. 2013
RMSF. Clinical features
RMSF. Male 6 years old. 2006
RMSF. Male 1 year old. 2015
RMSF. Clinical features
Predictors of mortality in hospitalized children with Rocky Mountain Spotted Fever, Sonora 2004-2015
Results of logistic multivariate analysis*
Predictor β coefficient Standard
error ORadj
1/ 95% IC
Intercept -2.33 0.28 0.10 (0.02, 0.42)
Delay in specific treatment with doxycycline (> 5th day) [1=Yes] 1.08 0.51 2.95 (1.10, 7.95)*
Acute kidney injury (1=Yes) 2.17 0.48 8.79 (3.46, 22.33)*
Severe sepsis (1=Yes) 1.31 0.48 3.71 (1.44, 9.58)*
Age (1= Less than 10 years old) 1.07 0.57 2.93 (0.97, 8.87)
Hypoproteinemia [<6.4 g/dL] (1=Yes) 0.70 0.92 2.02 (0.33, 12.32)
Ecchymosis (1=Yes) 0.46 0.46 1.58 (0.64, 3.91)
Petechiae (1=Yes) -0.88 0.70 0.42 (0.11, 1.64)
Thrombocytopenia <50,000 μL (1=Yes) 1.08 0.64 2.95 (0.84, 10.35)
* The significance of the final model was assessed by Log Likelihood [-66.36229]. Model R2 = 0.50224.
1/ Adjusted odds ratio accounting for all the variables included in the final model. *Statistically significant
Alvarez et al. Pediatr Infect Dis J 2015; 34: 125-130
Multiple risk factors for RMSF
Social context
Urban planning
Migration
Biological factors
Health system
Global warming
(Suárez, 2006; Süss, 2008; Labruna, 2011)
• Social deprivation (poverty, marginalization) • Risk perception (daily contact with ticks; the role of dogs) • Knowledge of disease (i.e. meaning of fever) • Thoughts on prevention
• Policies, programs and allocated resources • The role of science • Risk communication • Knowledge of disease (clinical signs and
symptoms, and risk factors) • Poor knowledge on prevention (timely
diagnosis, reluctance to treatment, care of medical complications)
• What factors are associated with
morbidity and mortality of people
infected by R. rickettsii in Sonora?
0
20
40
60
80
100
< 30 30 to 49 50 and more
Per
cen
tage
Age of medical provider
Aware of RMSF case-fatality rate, by age of medical provider. Sonora, Mexico. 2015
(n=343)
P = 0.023
Alvarez G et al. Knowledge, attitudes and practices of physicians on Rocky Mountain spotted fever. Sonora, 2015 Manuscript in preparation. Do not cite
• Physicians do know very
little about fatality of RMSF
0
20
40
60
80
100
< 30 30 to 49 50 and more
Per
cen
tage
Age of medical provider
Use of doxicycl ine in chi ldren with RMSF, by age of medical provider. Sonora, México. 2015
(n=343) • 30-40% of physicians are
reluctant to initiate doxycycline
in children
P = 0.013
Alvarez G et al. Knowledge, attitudes and practices of physicians on Rocky Mountain spotted fever. Sonora, 2015 Manuscript in preparation. Do not cite
0
20
40
60
80
100
< 30 30 to 49 50 and more
Pe
rce
nta
ge
Age of medical provider
Treat pat ients wi th RMSF with in recommended t ime f rame. Sonora, Mex ico. 2015
(n=343)
• <50% of physicians initiate
timely specific treatment P < 0.001
Alvarez G et al. Knowledge, attitudes and practices of physicians on Rocky Mountain spotted fever. Sonora, 2015 Manuscript in preparation. Do not cite
31.7
12.7
9.5 9.5 7.9 7.9
20.8
29.9
6.8
10.2
19.0
9.5 6.8
17.9
0
10
20
30
40
50
Acute respiratoryinfection
Gastroenteritis Exanthematous fever Rickettsiosis Fever syndrome Dengue fever Other
Per
cen
tage
Diagnosis at initial presentation for medical care in children with RMSF. Sonora, Mexico, 2004-
2015*
Fatal (63) Nonfatal (147)
* 01/01/2004-06/18/2015 No statistically significant differences were observed
0
5
10
15
20
25
30
No request medicalcare
Hospital/ER Drug store Private physician Health center Two or more
Pe
rce
nta
ge
Community knowledge about RMSF. Sonora, 2015 If you or someone of your family got fever, where
would you go?
P=0.034
Alvarez G et al. Knowledge at community level on Rocky Mountain spotted fever. Sonora, 2015 Manuscript in preparation. Do not cite
• There is a low perception in
community about early
manifestations of RMSF
0
20
40
60
80
Yes Not sure No
Po
rce
nta
je
Community knowledge about RMSF. Sonora, 2015 Have you heard about a disease called RMSF or “rickettsia”?
(n=400)
• In areas highly epidemic, 40% of
those responsible for family
health care do not know about
RMSF
P < 0.001
0
10
20
30
40
50
Do not know Dog collar Two or moreactivities
Avoid dog contact Avoid placesinfested by ticks
Declined Dogs do not live inhome
Pe
rce
nta
ge
Community perception about how to prevent RMSF. Sonora, 2015 (n=400)
• Almost 50% of subjects do not
know how to prevent RMSF
P < 0.001
• Poor knowledge about RMSF in both physicians
and community
• We know very little about diagnosis, treatment,
prevention
• “…I allude to a blindness of reason. We are blind
to reason and behave as blind” (José Saramago,
1995)
Final remarks
1. RMSF is reemerging in Sonora
2. Highly lethal but preventable. Deaths can be
avoided
3. Shows an unacceptable burden in pediatric
population
4. Participation of pharmaceutical industry and
international agencies of health and social welfare
is required
Final question
• Is RMSF in Mexico just a health-related
problem ... or is an ethical neglect?
• It is not only a health problem, it is an
expression of social injustice
• Because it is associated with social
backwardness, does affect individuals and
vulnerable populations and is not addressed as a
priority
Conclusion
• In Mexico, to properly address RMSF
political will and moral commitment is
needed, in addition to technical and
scientific approach
Contact:
Gerardo Alvarez PhD
Department of Medicine and Health Sciences
University of Sonora