Leishmania panamensis transmission in the domestic environment: the results of a prospective epidemiological survey in Santander, Colombia.
ABSTRACT Domestic transmission now appears to be the principal route of Leishmania panamensis infection in deforested regions characterized by the replacement of primary forest by permanent plantations, i,e coffee or cacao crops. This paper presents the results of the disease patterns in a representative population of the Opón focus, in Santander, Colombia.
The principal aims were: 1) to measure the incidence rate in a representative population of the Opón focus; 2) to identify demographic risk factors for infection; 3) to estimate the proportion of infections which cause disease; 4) to estimate the protection against disease from acquired immunity; 5) to estimate the frequency of reactivations, and 6) to estimate the risk of mucosal leishmaniasis.
A 19 month prospective survey of leishmaniasis caused by Leishmania panamensis was carried out amongst 1380 people in a cacao growing region of Santander Department, Colombia. The population was diagnosed clinically and by the Montenegro skin test (at two time points).
The incidence rate was 0.19 infections/person-year, with 31% of infections apparently subclinical. The risk of acquiring cutaneous leishmaniasis decreased with age even in the absence of apparent previous infections. Protective immunity followed both clinical and subclinical infections, persisting for at least 10 years after a primary lesion. Mucocutaneous leishmaniasis was detected in 12% of the population with cutaneous lesions, of which 77% had mild symptoms, and 23% perforated nasal septa. The risk of mucosal leishmaniasis was greatest for males, and for people whose primary cutaneous lesion was on the head.
The average age of infection in Opón, 7.7 years (1/lambda), and the absence of gender as a risk factor is highly indicative of intradomiciliary or peridomiciliary transmission.
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ABSTRACT: Children have a lower response rate to antimonial drugs and higher elimination rate of antimony (Sb) than adults. Oral miltefosine has not been evaluated for pediatric cutaneous leishmaniasis. A randomized, noninferiority clinical trial with masked evaluation was conducted at 3 locations in Colombia where Leishmania panamensis and Leishmania guyanensis predominated. One hundred sixteen children aged 2-12 years with parasitologically confirmed cutaneous leishmaniasis were randomized to directly observed treatment with meglumine antimoniate (20 mg Sb/kg/d for 20 days; intramuscular) (n = 58) or miltefosine (1.8-2.5 mg/kg/d for 28 days; by mouth) (n = 58). Primary outcome was treatment failure at or before week 26 after initiation of treatment. Miltefosine was noninferior if the proportion of treatment failures was ≤15% higher than achieved with meglumine antimoniate (1-sided test, α = .05). Ninety-five percent of children (111/116) completed follow-up evaluation. By intention-to-treat analysis, failure rate was 17.2% (98% confidence interval [CI], 5.7%-28.7%) for miltefosine and 31% (98% CI, 16.9%-45.2%) for meglumine antimoniate. The difference between treatment groups was 13.8%, (98% CI, -4.5% to 32%) (P = .04). Adverse events were mild for both treatments. Miltefosine is noninferior to meglumine antimoniate for treatment of pediatric cutaneous leishmaniasis caused by Leishmania (Viannia) species. Advantages of oral administration and low toxicity favor use of miltefosine in children. NCT00487253.The Journal of Infectious Diseases 02/2012; 205(4):684-92. · 5.85 Impact Factor
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ABSTRACT: Infectious disease incidence is often male-biased. Two main hypotheses have been proposed to explain this observation. The physiological hypothesis (PH) emphasizes differences in sex hormones and genetic architecture, while the behavioral hypothesis (BH) stresses gender-related differences in exposure. Surprisingly, the population-level predictions of these hypotheses are yet to be thoroughly tested in humans. For ten major pathogens, we tested PH and BH predictions about incidence and exposure-prevalence patterns. Compulsory-notification records (Brazil, 2006-2009) were used to estimate age-stratified ♂:♀ incidence rate ratios for the general population and across selected sociological contrasts. Exposure-prevalence odds ratios were derived from 82 published surveys. We estimated summary effect-size measures using random-effects models; our analyses encompass ∼0.5 million cases of disease or exposure. We found that, after puberty, disease incidence is male-biased in cutaneous and visceral leishmaniasis, schistosomiasis, pulmonary tuberculosis, leptospirosis, meningococcal meningitis, and hepatitis A. Severe dengue is female-biased, and no clear pattern is evident for typhoid fever. In leprosy, milder tuberculoid forms are female-biased, whereas more severe lepromatous forms are male-biased. For most diseases, male bias emerges also during infancy, when behavior is unbiased but sex steroid levels transiently rise. Behavioral factors likely modulate male-female differences in some diseases (the leishmaniases, tuberculosis, leptospirosis, or schistosomiasis) and age classes; however, average exposure-prevalence is significantly sex-biased only for Schistosoma and Leptospira. Our results closely match some key PH predictions and contradict some crucial BH predictions, suggesting that gender-specific behavior plays an overall secondary role in generating sex bias. Physiological differences, including the crosstalk between sex hormones and immune effectors, thus emerge as the main candidate drivers of gender differences in infectious disease susceptibility.PLoS ONE 01/2013; 8(4):e62390. · 3.73 Impact Factor
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ABSTRACT: We present a review of current knowledge about mucosal leishmaniasis (ML). Although involvement of mucous membranes is classically admitted in New World leishmaniasis, particularly occurring in infection by Leishmania (L.) braziliensis species complex, ML is also a possible presentation of Old World leishmaniasis, in either L. donovani or L. major species complex infections. Thus, ML has to be considered not only as a Latin American disease but as an Old and New World disease. We describe ML epidemiology, pathogenesis, clinics, diagnosis, and therapy. Considering both its highly disfiguring lesions and its possible lethal outcome, ML should not be underestimated by physicians. Moreover, leishmaniasis is expected to increase its burden in many countries as sandfly vector distribution is widespreading towards non-endemic areas. Finally, the lack of clear understanding of ML pathogenesis and the absence of effective human vaccines strongly claim for more research.BioMed research international. 01/2013; 2013:805108.
Instituto Nacional de Salud (I.N.S.)
ISSN (Versión impresa): 0120-4157
Gerardo Muñoz / Clive R. Davies
LEISHMANIA PANAMENSIS TRANSMISSION IN THE DOMESTIC ENVIRONMENT:
THE RESULTS OF A PROSPECTIVE EPIDEMIOLOGICAL SURVEY IN
Biomédica, octubre, año/vol. 26, número Suplemento 1
Instituto Nacional de Salud (I.N.S.)
Red de Revistas Científicas de América Latina y el Caribe, España y Portugal
Universidad Autónoma del Estado de México
Biomédica 2006;26(Supl.1):131-44LEISHMANIA PANAMENSIS EPIDEMIOLOGY
Leishmania panamensis transmission in
the domestic environment:
the results of a prospective epidemiological survey in
Gerardo Muñoz 1, Clive R. Davies 2
1Departamento de Ciencias Básicas, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga,
2Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London,
Introduction. Domestic transmission now appears to be the principal route of Leishmania
panamensis infection in deforested regions characterized by the replacement of primary forest
by permanent plantations, i,e coffee or cacao crops. This paper presents the results of the
disease patterns in a representative population of the Opón focus, in Santander, Colombia.
Objective. The principal aims were: 1) to measure the incidence rate in a representative
population of the Opón focus; 2) to identify demographic risk factors for infection; 3) to estimate
the proportion of infections which cause disease; 4) to estimate the protection against disease
from acquired immunity; 5) to estimate the frequency of reactivations, and 6) to estimate the risk
of mucosal leishmaniasis.
Material and methods. A 19 month prospective survey of leishmaniasis caused by Leishmania
panamensis was carried out amongst 1380 people in a cacao growing region of Santander
Department, Colombia. The population was diagnosed clinically and by the Montenegro skin
test (at two time points).
Results: The incidence rate was 0.19 infections/person-year, with 31% of infections apparently
subclinical. The risk of acquiring cutaneous leishmaniasis decreased with age even in the
absence of apparent previous infections. Protective immunity followed both clinical and
subclinical infections, persisting for at least 10 years after a primary lesion. Mucocutaneous
leishmaniasis was detected in 12% of the population with cutaneous lesions, of which 77% had
mild symptoms, and 23% perforated nasal septa. The risk of mucosal leishmaniasis was greatest
for males, and for people whose primary cutaneous lesion was on the head.
Conclusion. The average age of infection in Opón, 7.7 years (1/λ), and the absence of gender
as a risk factor is highly indicative of intradomiciliary or peridomiciliary transmission.
Key words: Leishmania, epidemiology, cutaneous leishmaniasis, mucocutaneous
Transmisión de Leishmania panamensis en ambientes domésticos: resultados de un
estudio epidemiológico prospectivo en Santander, Colombia
Introducción. La transmisión doméstica de Leishmania panamensis parece ser la fuente de
infección mas frecuente en regiones deforestadas, caracterizadas por el reemplazo del bosque
primario por plantaciones permanentes como cacao y café. Este papel presenta los resultados
de los patrones de enfermedad en una población representativa del foco del Opón, en
Objetivo. Los objetivos principales fueron: 1) cuantificar la tasa de incidencia en una población
representativa de la población del foco del Opón; 2) identificar los factores de riesgo
demográficos para la infección; 3) estimar la proporción de infecciones que causan enfermedad;
4) estimar la protección contra la enfermedad según la inmunidad adquirida; 5) estimar la
frecuencia de reactivaciones, y 6) estimar el riesgo de leishmaniasis mucosa.
Biomédica 2006;26(Supl.1):131-44MUÑOZ G., DAVIES C.R.
Materiales y métodos: Se llevó a cabo un estudio prospectivo de leishmaniasis causada por
Leishmania panamensis durante 19 meses, entre 1.380 personas habitantes de una región
cacaotera del departamento de Santander, Colombia. La población fue diagnosticada por
clínica y por la prueba de Montenegro (en dos tiempos).
Resultados: La tasa de incidencia fue de 0,19 infecciones/persona-año, 31% de los cuales
tuvieron una infección aparentemente subclínica. El riesgo de adquirir leishmaniasis cutánea
decrece con la edad aún en ausencia de infecciones previas aparentes. Una inmunidad
protectiva subsiguió a las infecciones clínicas y subclínicas, persistiendo por lo menos durante
10 años posterior a una infección primaria. La leishmaniasis mucocutánea se detectó en 12%
de la población con lesiones cutáneas, de las cuales 77% tuvieron síntomas no severos, y
23% perforación del tabique nasal. El riesgo de leishmaniasis mucosa fue más grande para
hombres y para personas cuyas lesiones primarias se localizaron en la cabeza.
Conclusión. El promedio de edad de infección en el Opón, 7,7 años (1/λ), y la ausencia de
factores de riesgo relacionados con el género indican que la transmisión es intra o peri
Palabras clave: Leishmania, epidemiología, leishmaniasis cutánea, leishmaniasis
Leishmania (Viannia) panamensis is responsible
for zoonotic cutaneous leishmaniasis and occa-
sionally mucocutaneous leishmaniasis in eight
countries in Central and South America (1,2). The
total number of human cases caused by L.
panamensis annually is unknown, as i) most cu-
taneous leishmaniasis cases are not reported (3),
ii) L. panamensis is often sympatric with other
Leishmania species responsible for cutaneous
leishmaniasis (e.g. Leishmania braziliensis), and
iii) the Leishmania species responsible for the re-
ported cases are rarely identified.
However, on the basis of those few human isolates
which have been characterized, it appears that
about half of all cutaneous leishmaniasis cases
reported each year within the eight endemic
countries are due to L. panamensis (2). This
percentage varies from less than 1% in Guatemala
to over 90% in Panama and Costa Rica. In
Colombia, about 50% of all cutaneous
leishmaniasis cases reported are due to L.
panamensis; but this represents the greatest
number of reported cases caused by L.
panamensis in any country (an estimated 3,000/
The geographic distribution of L. panamensis co-
incides with the overlapping distribution of the two-
toed sloth Choloepus hoffmanni thought to be the
principal reservoir host, and the sandfly species
Lutzomyia trapidoi and Lutzomyia ylephiletor,
thought to be the principal vectors (4). Hence, the
classical risk factors for human infection, as de-
scribed in Panama (5) and on the Pacific coast of
Colombia (6) involve occupational exposure to in-
fectious sandfly bites when adult male humans
enter the forest.
Indeed, the requirement of forest habitat for the
survival of sloth populations led Herrer and
Christensen to write optimistically in 1976 that the
“increased deforestation activities by new immi-
grants to provide more farm land may soon dis-
rupt the transmission cycle of Leishmania which
will lead to the disappearance of the disease.” In
fact, the history of the last 25 years is that while
the deforestation of endemic areas has continued
unabated, the incidence rate of L. panamensis has
increased steadily. How has this been possible?
Part of the answer lies in the changing patterns of
L. panamensis transmission. Persistently endemic
communities, characterised by a high prevalence
of active lesions in children and apparent domestic
transmission, were occasionally detected in
Panama in the 1970s, e.g. in El Aguacate (7).
However, this epidemiological pattern has only
recently become widespread, with all household
members now apparently at risk of infection in
Gerardo Muñoz M., Departamento de Ciencias Básicas,
Facultad de Salud, Universidad Industrial de Santander,
Carrera 32 Nº 29 - 31, Bucaramanga, Santander, Colombia.
Phone number and fax: (577) 645 5693.
Recibido: 10/08/05; aceptado: 24/02/06
Biomédica 2006;26(Supl.1):131-44 LEISHMANIA PANAMENSIS EPIDEMIOLOGY
many endemic zones of L. panamensis. For ex-
ample, domestic transmission now appears to be
the principal route of L. panamensis infection in
the provinces of Esmeraldas and Pichincha on
the Pacific coast of Ecuador (8), a deforested
region characterized by the replacement of pri-
mary forest by coffee plantations, and by relatively
high densities of Lutzomyia trapidoi and Lutzomyia
gomezi in and around houses. Domestic trans-
mission of L. panamensis is also suspected in
Acosta, Costa Rica, where the presumed sandfly
vectors, L. ylephiletor and L. gomezi, are abun-
dant in the coffee plantations that have replaced
the primary forest (9,10).
Because the course of cutaneous leishmaniasis
infection depends on both the age and immune
status of patients (11,12) the change in L.
panamensis transmission from sylvatic to domes-
tic could also affect the characteristic clinical
symptoms of an exposed population.
This paper describes the results of the first pro-
spective survey to investigate the course of in-
fection in a population apparently exposed to L.
panamensis in the domestic environment (Angulo
and others, unpublished data): the inhabitants of
the Opón focus in Colombia. The principal aims
were (1) to measure the incidence rate in a repre-
sentative population of the Opón focus, (2) to iden-
tify demographic risk factors for infection, (3) to
estimate the proportion of infections which cause
disease, (4) to estimate the protection against dis-
ease from acquired immunity, (5) to estimate the
frequency of reactivations, and (6) to estimate the
risk of mucosal leishmaniasis.
Materials and methods
The study was carried out in 12 villages in the
Opón area, Landázuri municipality (6° 20' N; 73°,
43' W), Santander Department at altitudes ranging
from 400 to 1,200 m above sea level. It is a
mountainous region where the principal economic
activities are silviculture of tropical hard woods
(in the rain forest), cattle ranching, and the cacao
crops. The relative abundance (in percentage) of
the vegetation around houses was estimated by
eye within concentric circles with radiuses from
the house of 50 m, 100 m, 200 m, 300 m, and 800
m, respectively. Most houses adjoin pasture land
(ca. 80%) and/or cacao plantations (ca. 40%), and
are some distance away from the surviving
patches of primary or secondary forest. About 35%
and 85% of houses are within 800m from primary
and secondary forest, respectively.
Study design and population
During the first visit in January, 1995, a scaled
map for each village was completed and all 527
occupied houses recorded. A unique identification
number was allocated to each person in every
household and the Colombian national identity card
was requested in order to verify the date of birth.
If possible, the whole family attended the
interviews in order to minimise recall bias.
Demographic data (age, sex, and date of
immigration, when appropriate) and clinical status
(including age when infected) were recorded, and
a proportion of the population (those giving
consent) were given a Montenegro skin test (April-
All households were visited five times at about
three month intervals following the initial cross-
sectional survey, checking for changes in the
study population (due to immigration, emigration,
birth or death) and looking for new cutaneous or
mucocutaneous leishmaniasis cases.
During the final visit (February-March, 1997) the
study population was given a second Montenegro
skin test an average of 19 months after the first
one using the same batch of antigen as before. In
1995 the Montenegro skin test was applied to
51% of the Opón population (1,380/2,704), of which
55.5% (766) received a second one.
There were no differences by gender between the
group remaining in the project and the emigrants/
refusal group; nevertheless, the former were
slightly older (mean=20.8 years old) than the latter
(mean=18.2 years old) (Kruskal-Wallis H: 7.303,
The great majority of refusals were adults with a
positive result in the first Montehnegro skin test.
Thus, the main possibility of bias due to the re-
fusal would apply to the measurement of recov-
ery rate (r) rather than the measurement of trans-
mission rate. During the prospective study, 163
Biomédica 2006;26(Supl.1):131-44MUÑOZ G., DAVIES C.R.
emigrants, 10 deaths, 126 immigrants and 37 births
were recorded in the study population. Analysis
incorporating age were carried out on a reduced
data set of 1,333 persons, because of missing
data from 47 people.
Past cases of cutaneous leishmaniasis were iden-
tified by characteristic scars, which were detected
using the following criteria: no history of trauma,
duration for more than 2 weeks, central depressed
surface and contours with no sharp angles. Sus-
pected leishmaniasis lesions were defined by the
absence of prior history of trauma and more than
two weeks of evolution. Confirmation of the aeti-
ology of suspected lesions was made by a positive
result from one or more diagnostic tests (13), with
the informed written consent of the patients. These
included: 1) microscopic examination of Giemsa-
stained slides made from dermal scrapings; 2)
PCR using the B1 and B2 primers as described
by de Bruijn (1992) (14), and 3) the in vitro culture
of parasites from aspirates or biopsies in NNN
biphasic medium. The sensitivity of microscopy
diagnosis was 40% for all suspected patients and
60% for the 55 patients with a positive culture,
while the equivalent values for PCR were 43%
All confirmed patients were provided with free treat-
ment (Glucantime®) and followed-up on a monthly
basis. Characterisation of Leishmania isolates was
carried out by IEA in thin-layer starch-gel electro-
phoresis, using 8 isoenzymes (PEPD, NH, MPI,
ME, GPI, PGM, 6PGD, and ES) as described by
Godfrey and Kilgour (1976) (15). All 25 parasites
isolated during the survey were characterised as
L. panamensis; 23 were indistinguishable from the
reference strain MHOM/PA/71/LS94, and two
isolates demonstrated the same variant of PEPD.
After clinical inspection and following the results
of the diagnostic tests, the study population was
classified into two groups: people with scar or
lesions (L+) and people with no history of
leishmaniasis (L-). The upper respiratory tract was
visualised with the help of a nasal speculum,
lantern and a tongue depressor by a trained clini-
cian (16) on the L+ population. Lesions compat-
ible with mucosal leishmaniasis were defined as
septal erosion or perforation; erythema or ulcers
in the septum, turbinate, oral or nasal mucosa. In
order to exclude acute lesions the clinician visited
the same population three times in three consecu-
tive months. Persistent lesions were included as
suspected a mucocutaneous leishmaniasis patient
but biopsy was not taken because there was not
hospital aid in such remote areas.
Montenegro skin tests
The Montenegro skin test was applied (with their
informed written consent) to some or all of the
residents of 331 households following the
technique recommended by the World Health
Organization (17), i.e. using a mixture of L.
panamensis and L. braziliensis at a concentration
of 5x106 ml-1 heat-killed promastigotes for each
species. A pressurised intradermal injector
(Dermo-jet model G, Robbins Instruments, USA)
was used to inject 0.1 ml of leishmanin
intradermally on the external surface of one arm,
and the diameter of induration was measured 48
hours later. The choice of cut-off point, 3 mm,
was made empirically, and the study population
with a Montenegro skin test was classified into
two groups according to their skin test response:
Montenegro negative (M-) and Montenegro posi-
Written informed consent was obtained from every
person or family included in the present study,
following the indications of the Ministerio de Salud
de Colombia (Resolution 008430, 1993). In
addition, approval was requested and obtained
from the ethical committee of the Industrial
University of Santander
The transmission rate was measured using the
results of both the cross-sectional and prospective
studies. The analysis of the cross-sectional data
focused on the comparison of prevalence rates
(active or cumulative; Montenegro skin test re-
sponsiveness or clinical) according to sex and
age. In addition, a simple infection-recovery model
(11) was fitted to the age prevalence curves (i.e.
the proportion that were infected at age “a”) by
maximum likelihood (18). The model assumes that