44 research outputs found
In vivo cytokine profiles in patients with kala-azar. Marked elevation of both interleukin-10 and interferon-gamma
No full textThe immunological mechanisms underlying the susceptibility to disseminated visceral parasitism of mononuclear phagocytes in patients with kala-azar remain undefined. Resistance and susceptibility are correlated with distinct patterns of cytokine production in murine models of disseminated leishmanial dis-ease. To assess lesional cytokine profiles in patients with kala-azar, bone marrow aspirates were analyzed using a quantitative reverse transcriptase PCR technique to amplify specific mRNA sequences of multiple Thl-, Th2-, and/or macrophage-asso-ciated cytokines. Transcript levels of IL-10 as well as IFN-y were significantly elevated in patients with active visceral leish-maniasis; IL-10 levels decreased markedly with resolution of disease. These findings suggest that IL-10, a potent, pleiotro-pic suppressor of all known microbicidal effector functions of macrophages, may contribute to the pathogenesis of kala-azar by inhibiting the cytokine-mediated activation of host macro-phages that is necessary for the control of leishmanial infec-tion. (J. Clin. Invest. 1993.91:1644-1648.) Key words: cyto-kines * leishmaniasis * polymerase chain reaction * human-macrophag
Epidemiology of the Leishmaniases in southwest Saudi Arabia.
No full textVisceral (VL) and cutaneous
leishmaniasis (CL)
are
public health problems
in the
southwest of
Saudi
Arabia. The
causative parasites, the vectors
and the
possible
animal
reservoirs In that area were
all
unknown
before this
study
began.
Because of the size of the
area
and to
achieve
the
different aims of the study,
a
laboratory
was
established
in
Abha City which is in the centre of the
study area,
altitude
approximately 2000 m.
More than 50 isolates from
CL lesions,
17 from VL
patients and 700 human filter
paper
blood
samples
were
collected. Eighty nine
feral dogs
were
captured
In
Kala-azar endemic areas and examined
for
Leishmania. More than
8,000 sandflies collected
from fixed
stations
were examined
and more than 1600 Phlebotomus females
were
dissected.
Forty four human isolates from human CL lesions
were
typed
by the isoenzyme technique which showed that L. tropica is
responsible for CL in both lowlands
(altitude
about
450
-
700 m) and the highlands (altitude
about
2000
m).
Only
one
zymodeme (LON-63) was found in the isolates from the
lowlands but, in the highlands, four
zymodemes
(LON-10, 71,
72 and 73) were found. Zymodemes
LON-10
and
LON-71
were also
Isolated from Phlebotomus sergenti, which
has
been
shown
clearly to be a major vector of L. tropica In the
highlands.
Animal susceptibility experiments showed. that
neither
BALB/c
mice nor the golden hamster were
susceptible to
L. tropica. L. donovani sensu lato zymodeme
LON-42
causes
zoonotic
Infantile Kala-azar in areas
at altitudes of up
to
700m.
Neither the vector nor the reservoir
host
were
identified in
spite of an active search
for them. The limited
sero-epidemiological survey using the
ELISA
procedure
revealed a
high frequency of antibodies in children
in
Al Baha
province, much greater than was previously
believed to
exist.
Feral dogs In this area
were
found to
be
carriers
of
typical L. infantum, NOT the
parasite
found in
man.
The
prevalence rate in dogs was
high (19.3%).
The
dog's
possible
role in the epidemiology
of
Kala-azar in the
study
area
is
discussed.
The entomological studies
revealed that
six
species
of
Phlebotomus exist in the study
area,
with
Ph.
sergenti
as the
dominant species In the highlands
and
Ph.
bergeroti in the
lowlands. Some species such as
Ph.
arabicus
are
limited to
high altitudes (about 2000 m),
and
others such as
Ph. alexandri to low altitudes (up to
700
m).
Ph.
orientalis
was
found mainly in the highlands but
a
few
samples were
collected from the lowlands. Sergentomyi
species were
abundant in all areas. The seasonal
distribution based
on
a
longitudinal study indicated that the
population peak
in
both ecological areas (high and
lowlands)
occurs
in July.
The factors Including the collection
method
and trap
sites
controlling the apparent seasonal
distributions
are
discussed. Statistical
data
on
the total
cases of
CL
and
VL
reported In The Kingdom are
presented and
data from the study area are compared with those from
other
areas
such
as
the Eastern Province (where L.
major
is
dominant) to
give an
overall picture of the leishmaniases throughout the
country
Genetic diversity in the Leishmania donovani complex.
No full textThe Leishmania donovani complex comprises four described species: L.
donovani, L. archibaldi, L. infantum and L. chagasi. L. chagasi is the only New World
species and has been considered similar to L. infantum, although some authors insist
on maintenance of its independent species status. L. donovani has at least two major
epidemiological subgroups whose relationships are poorly understood.
In this thesis, molecular biological techniques were used to investigate the
taxonomy and phylogenetic relationships within the L. donovani complex, with
isoenzyme analysis (lEA) as reference technique. Random amplification of
polymorphic DNA (RAPD) was used to provide anonymous genetic markers which
allowed overall comparisons of genomes. Selected target genes and intergenic
regions were also amplified by the polymerase chain reaction (PCR), namely the
major surface protease (msp or gp63), the mini-exon and the ribosomal internal
transcribed spacer (ITS). PCR products of intergenic regions between msp genes
(ITG/CS and ITG/L), mini-exon and ITS were analysed by restriction fragment length
polymorphism (RFLP). Phylogenies generated from each of the methods were
compared with that of IEA.
L. infantum and L. chagasi were found to be synonymous, whilst L. donovani
was found to be more polymorphic than L. infantum and a fourth possible species in
the complex, L. archibaldi, was not supported. Six genetic groups of strains were
identified in the L. donovani complex, based on all DNA based analyses, which
agreed with IEA typing. Pooled data from RFLP and RAPD analyses generated
robust phylogenies which were congruent with ITG/CS RFLP and msp DNA
sequence based phylogenies, but not with lEA phylogenies. The evolutionary history
of the L. donovani complex is analysed in the light of the present results. The diverse
typing methods were also evaluated and genetic markers suggested, that are
applicable to classification and typing of L. donovani species and strains
Evaluation and treatment of post-renal transplant cytomegalovirus disease in children
No full textCytomegalovirus (CMV) infection typically presents as viremia, a clinical syndrome, or tissue-invasive disease. Identifying risk factors and conducting initial blood investigations, followed by invasive tests when appropriate, are crucial steps to rule out serious tissue-invasive disease. Ganciclovir is the cornerstone of CMV disease treatment, with oral valganciclovir used subsequently based on treatment response. For patients with UL-97 mutant ganciclovir-resistant CMV, foscarnet may be administered, often alongside intravenous immunoglobulin (IVIG), particularly in cases of life-threatening conditions such as CMV pneumonitis. Despite the significance of CMV in this population, there is currently a lack of comprehensive clinical reviews or guidelines specifically addressing the management of post-renal transplant CMV disease in children. This article aims to fill that gap by discussing the various modalities for treating post-renal transplant CMV in children, along with its clinical manifestations and necessary investigations
Silent citizens: state, citizenship and media in the Gulf
No full textThis thesis attempts to unravel the essence of the state in the Gulf Arab countries. The study's main argument is that the Gulf Emirates have been able to manipulate the oil wealth and create what appear to be modern states. The Gulf ruling families were confronted, however, with the dilemma of introducing the kind of civil society that accompanies modernity. They have been able to survive and legitimate their dominion by exploiting religion as the state ideology. Traditional patriarchal norms and cultures have been maintained by the ruling tribes in the Gulf. The issue of citizenship and citizens' rights has rarely been debated in regard to the Gulf. However, this is one of the main problems of the contemporary situation in the Gulf states. This study concentrates on this issue by means of a review of the media. The Gulf media have been utilised to promote the modem patriarchal structure of the state. The main body of the thesis examines the media in relation to two main issues: foreign workers in the Gulf and Gulf women. The final chapter of the thesis, however, exposes the fact that Gulf journalists themselves have no rights and that at times of crisis the tenuous autonomy they enjoy withers. A major crisis occurred very recently to reinforce this argument. The Iraqi invasion of Kuwait on 2 August 1990 and the deployment of foreign troops in the Gulf created a further complication for the Gulf ruling families. They were forced to allow foreign - mainly American and British journalists- to cover the war, but they compelled national reporters to use material which was filtered through the foreign press
Studies on coinfections with Schistosoma mansoni and Leischmania
No full textSchistosomiasis and
visceral
leishmaniasis,
each responsible
for
serious
morbidity
and mortality, also
have
overlapping
endemicities
e. g.
in the
Sudan. Both
cause
granulomatous responses
in the liver.
Leishmania
donovani
amastigotes
are
killed
by
Th1 dependent macrophage activation
whereas
schistosome
eggs
induce
Th2
dependent
granulomas which protect
the liver tissue from toxic
products
and
from
Th1
dependent
inflammatory responses.
In
view
of
the
reciprocal
counter-regulation
of
Th1
and
Th2
responses it was
hypothesized that
co-infection
would
lead to
altered
immune
responses
and exacerbation of
disease.
This
was modelled
in the
mouse using
Schistosoma
mansoni
and L. donovani. When C57BL/6
mice were
infected
with
25
cercariae of
S.
mansoni
and
superinfected, 8 weeks
later
with
L.
donovani the
co-infected mice
(CO-INFECT)
suffered
increased morbidity and
mortality and
elevation
of
serum
liver
enzymes,
ALT/AST
(aspartate/alanine aminotransaminase)
compared with
mice given
the
single
infections
(LEISH or SCHISTO). Schistosome
worm
and egg
burdens
and
egg granulomatous
responses were comparable
in
CO-INFECT
and
SCHISTO
mice.
In
contrast,
CO-INFECT
and LEISH mice
showed
comparable
L.
donovani infection (Leishman
Donovan
units
[LDUs]) in both liver
and
spleen at
+2
weeks
but the
CO-INFECT
mice
showed
progressively increased LDU
up
to
+8weeks
post
Leishmania infection
compared to
declining LDUs in the
LEISH
group.
The S. mansoni
infection induced
significant
IL-4
and
IL-10
but
not
IFN-γ
splenocyte and liver lymphocyte
recall responses
to
schistosome
antigens
and
mitogen
whereas the LEISH infection induced
specific
IFN-γ
production
but
not
IL-4 to
Leishmania
antigen (Formalin fixed Leishmania
amastigote
antigen,
FLAA). This IFN-γ
response
was
markedly lower at
+2
and
+8
weeks
post
infection in the
CO-INFECT
mice
but
FLAA-
specific IL- 10 responses were
higher.
Since
B-cells
have been
reported
to
be
a
major source
of IL-10 in S. mansoni
infected
mice, co-infection experiments were carried out
in
μMT
mice which lack B
cells.
Indeed there
was
lower IL-10
production
in the
CO-INFECT
μMT
mice and also a
lower fold increase in
LDU in the liver
of
CO-INFECT
vs.
LEISH
mice
compared with the wild-type
(WT, C57BL/6)
mice.
However, the
μMT
mice were
also
much less susceptible to infection
with
L.
donovani
alone
than the
WT
mice so it is
difficult
to interpret the significance of
these
results.
Administration
of anti-IL-10
receptor
antibody (anti-IL-10R) between weeks
6-8
after super-infection
reduced the
high
L.
donovani LDU
in the CO-INFECT mice
but the
significance
of this
was uncertain since
anti-IL-10R treated
LEISH mice also had lower
LDUs.
Morphologically mature
L.
donovani
granulomas
are associated with
leishmanicidal
activity. Histology and
immuno-histology
showed
an
increasing
proportion
of
morphologically mature granulomas
in the
hepatic
parenchyma
of
LEISH
mice
as the
infection resolved
(i.e.
between
weeks
+2
and
+8)
but in the
CO-INFECT
mice this
proportion did not change. Higher
mean
amastigote numbers
in
L.
donovani
granulomas
in
the parenchyma of
CO-INFECT
mice
suggested
reduced
leishmanicidal
activity.
Throughout the time course
60%
of the foci
of
L.
donovani infection
were seen
in
various
locations within the egg granulomatous
response,
most
commonly
in
a ring
around the
outside of the granulomas
but
occasionally
within
giant cells
in
egg
shells at the
centre
of
the granulomas. Typical hepatic
L.
donovani
granulomas
did
not
form
around such
foci
and
the amastigotes appeared partly contained.
The data suggests that in
LEISH
mice mature
granulomas effectively
kill the
contained amastigotes
limiting
new
infections
so that
by
+8
weeks
the
granulomas are all
mature or fully resolved.
In
contrast
although morphologically normal mature
L.
donovani
granulomas form in the
parenchyma of
CO-INFECT
mice these
show reduced
leishmanicidal activity resulting in spread and establishment
of new
infections. It
is
concluded that raised
Th2
responses
to
S.
mansoni results
in lowered
Leishmania
specific
IFN-γ responses and
raised
levels
of
IL-10,
both
of
which would reduce
Th1
mediated
macrophage activation required
for killing
of
L.
donovani
amastigotes.
The
effects of
IL-10
plus the failure of
Leishmania
granulomas to
develop
around
foci
within the
egg
granulomas suggests very
poor
leishmanicidal
activity
in
such
foci.
The final section
of these
studies was
concerned
with
the
effects of an established
L.
donovani infection on a
S.
mansoni
infection
superimposed
2
weeks
later. At
8
weeks
post
super-infection, there was
no effect on the
schistosome worm or egg
burdens
or the
immunological and pathological
response to the
eggs
i.e. a strong
Th2
response
still
developed. However, lower
L.
donovani
LDUs
were seen
in the
CO-INFECT
mice than in
the LEISH alone and
it is
suggested that the
early
phase of the
schistosome
infection
which
is characterised by Th1
responses may
have
promoted the
protective anti-leishmanial
respons
Financing the Climate Mitigation and Adaptation Measures in Developing Countries
No full textThe threat of climate change requires a rapid transition to a new, low-carbon style of economic development. How will the transition be financed? Most of the global potential for emission reduction is located in developing countries. Achieving this potential, plus adaptation to climate damages, will cost hundreds of billions of dollars per year. Existing climate funding amounts to less than $15 billion annually, mostly through CDM – far less than is needed. A new climate funding agreement could build on the lessons of the Montreal Protocol for reduction of ozone-depleting substances, a successful case of international environmental cooperation.
Safety and efficacy of paromomycin/miltefosine/liposomal amphotericin B combinations for the treatment of post-kala-azar dermal leishmaniasis in Sudan: A phase II, open label, randomized, parallel arm study.
No full textBackgroundTreatment for post-kala-azar dermal leishmaniasis (PKDL) in Sudan is currently recommended only for patients with persistent or severe disease, mainly because of the limitations of current therapies, namely toxicity and long hospitalization. We assessed the safety and efficacy of miltefosine combined with paromomycin and liposomal amphotericin B (LAmB) for the treatment of PKDL in Sudan.Methodology/principal findingsAn open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with persistent (stable or progressive disease for ≥ 6 months) or grade 3 PKDL, aged 6 to ≤ 60 years in Sudan. The median age was 9.0 years (IQR 7.0-10.0y) and 87% of patients were ≤12 years old. Patients were randomly assigned to either daily intra-muscular paromomycin (20mg/kg, 14 days) plus oral miltefosine (allometric dose, 42 days)-PM/MF-or LAmB (total dose of 20mg/kg, administered in four injections in week one) and oral miltefosine (allometric dose, 28 days)-LAmB/MF. The primary endpoint was a definitive cure at 12 months after treatment onset, defined as clinical cure (100% lesion resolution) and no additional PKDL treatment between end of therapy and 12-month follow-up assessment. 104/110 patients completed the trial. Definitive cure at 12 months was achieved in 54/55 (98.2%, 95% CI 90.3-100) and 44/55 (80.0%, 95% CI 70.2-91.9) of patients in the PM/MF and AmB/MF arms, respectively, in the mITT set (all randomized patients receiving at least one dose of treatment; in case of error of treatment allocation, the actual treatment received was used in the analysis). No SAEs or deaths were reported, and most AEs were mild or moderate. At least one adverse drug reaction (ADR) was reported in 13/55 (23.6%) patients in PM/MF arm and 28/55 (50.9%) in LAmB/MF arm, the most frequent being miltefosine-related vomiting and nausea, and LAmB-related hypokalaemia; no ocular or auditory ADRs were reported.Conclusions/significanceThe PM/MF regimen requires shorter hospitalization than the currently recommended 60-90-day treatment, and is safe and highly efficacious, even for patients with moderate and severe PKDL. It can be administered at primary health care facilities, with LAmB/MF as a good alternative. For future VL elimination, we need new, safe oral therapies for all patients with PKDL.Trial registrationClinicalTrials.gov NCT03399955, https://clinicaltrials.gov/study/NCT03399955 ClinicalTrials.gov ClinicalTrials.gov
PKDL lesion distribution grade over time by treatment arm–mITT set.
No full textAmB = liposomal amphotericin B; MF = Miltefosine; mITT = Modified intention-to-treat; PKDL = Post-kala-azar dermal leishmaniasis; PM = Paromomycin. Note: The grade “none” refers to the absence of lesions in the patients, i.e., the patients are cured.</p
Efecto del polvo de roca volcánica y Fe-EDTA sobre las bacterias de los nódulos de las raíces y el crecimiento y rendimiento de plantas de haba
No full textThe experiment was conducted during the 2018 season at the research station of the College of Agriculture and Forestry (University of Mosul, Iraq) to investigate the effect of volcanic rock dust (VRD) (0, 125, 250 g m-2) and the fertilizer chelated Iron Fe-EDTA (0, 100, 200 mg L-1) on the bacteria Rhizobium fabae, and the growth and yield of two broad bean (Vicia faba L.) varieties, Histal and Aquadulce. A randomized complete block design was used with three replicates and least significant difference (LSD) to compare means at a significance level of 0.05. Results showed that VRD 250 g m-2 obtained the highest significant mean for the following traits: leaf area index (LAI), number of branches per plant, leaf contents of chlorophyll and total iron, number of effective bacteria nodules per plant, 100-seed weight, plant yield, and percentage of protein in the seeds. On the other hand, 200 mg L-1 Fe-EDTA obtained the highest significant mean of all the traits for both varieties, except for LAI and number of branches per plant. The application of Fe-EDTA per plant had no significant effect on the leaf content of chlorophyll for both varieties and the percentage of protein in the seeds for variety Aquadulce. The interaction of VRD 250 g m-2 with 200 mg L-1 Fe-EDTA achieved the highest significant average for all the traits, except for plant height.El experimento se llevó a cabo durante la temporada 2018 en la estación de investigación del College of Agriculture and Forestry (Universidad de Mosul, Irak), para investigar el efecto del polvo de rocas volcánicas (PRV) (0, 125, 250 g m-2) y el fertilizante hierro quelado Fe-EDTA (0, 100, 200 mg L-1) sobre la bacteria Rhizobium fabae y el crecimiento y rendimiento de dos variedades de haba (Vicia faba L.), Histal y Aquadulce. Se utilizó un diseño en bloques completos al azar con tres repeticiones y la diferencia mínima significativa (DMS) para hacer una comparación entre las medias a un nivel de significancia de 0.05. Los resultados mostraron que PRV 250 g m-2 obtuvo la media significativa más alta para las siguientes características: índice de área foliar (IAF), número de ramas por planta, contenidos foliares de clorofila y hierro, número de nódulos bacterianos efectivos por planta, peso de 100 semillas, rendimiento de la planta, y porcentaje de proteína en las semillas. Por otra parte, 200 mg L-1 Fe-EDTA obtuvo la media significativa más alta de todas las características para ambas variedades, excepto para el IAF y el número de ramas por planta. La aplicación de Fe-EDTA por planta no tuvo un efecto significativo sobre el contenido foliar de clorofila para ambas variedades ni sobre el porcentaje de proteína en las semillas para la variedad Aquadulce. La interacción del PRV 250 g m-2 con 200 mg L-1 Fe-EDTA logró la media significativa más alta para todas las características, a excepción de la altura de la planta
