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					                                                                                                Final

                      Visceral leishmaniasis: kala-azar

                                                                                         Subedi, P.*

Abstract

Visceral leishmaniasis also known as kala-azar is an infectious disease of
reticuloendothelial system caused by the parasite Leishmania donovani. Bite of infected
Phlebotomus argentipus (sand fly) is responsible for the transmission of the parasite from
one person to another or infected animals to a man. Leishmaniasis remains endemic in
88 countries of the world with an annual incidence of about two million cases. 90% of
these cases are found in Bangladesh, Brazil, India, Nepal and Sudan. People of all ages
are at risk for infection if they live or travel where leishmaniasis is found. Around 5.5
million people living in the affected areas of Nepal i.e. southeastern Terai and borders of
Bihar of India are at high risk of transmission of kala-azar. Case fatality rate of kala-
azar was found to be between 0.23% and 13.6%. The Visceral Leishmaniasis Elimination
Plan of Nepal proposed in 2002 aims at reducing the annual morbidity to less than 1 per
hundred thousand populations at risk by 2015. Integrated vector management, case
treatment should go side by side for an effective prevention of the disease.

Keywords: visceral, leishmaniasis, signs, symptoms, treatment, relative risk

Introduction

Leishmaniasis is a group of protozoal diseases caused by parasites of the genus
Leishmania, and transmitted to man by the bite of infected female Phlebotomine sand fly.
(Park 2009) It is a vector-borne disease. Visceral leishmaniasis also known as Kala-azar
is a tropical infectious disease of reticuloendothelial system caused by amastigote form of
Leishmania donovani. (Joshi, Bajracharya et al. 2006) An infected sand fly consists of
promastigote stage of Leishmania donovani in its salivary gland. When such sand fly
bites a healthy person the promastigote stage is inoculated inside the body of the man.
The promastigote stage further develops into amastigote stage inside man. The
amastigote stage is responsible for the clinical manifestation of kala-azar in man.
Amastigote form is engulfed by macrophages which are then carried by blood stream to
distant organs like spleen, liver and bone marrow. There they cause marked hyperplasia
of reticuloendothelial cells. Mortality is 100% if not treated.(Joshi, Bajracharya et al.
2006) Visceral leishmaniasis can be prevented by protecting yourself from the bite of
sand fly.


*
 Pooja Subedi, University redg no 2009-1-37-0085, BPH, Second semester, 2010, CIST, affiliated to
Pokhara University
According to the World Health Organization (WHO), leishmaniasis remains endemic in
88 countries of the world with an annual incidence of about two million cases. 90% of
these cases are found in Bangladesh, Brazil, India, Nepal and Sudan.(Adhikari,
Supakankunti et al. 2010) The problem has thus become of global importance. The
overall prevalence of leishmaniasis is 13 million cases with an estimated population of
350 million at risk. World wide there is an increasing number of cases and a more
widespread geographical distribution, the disease being reported from previously non-
endemic areas. (Park 2009)

Methodology

Literature search and review

To prepare this paper first of all literatures related to visceral leishmaniasis were searched
for review. To retrieve literatures Pub Med library was used. The endnote software was
used to retrieve literatures and save the references as it is easy in endnote to create library
and cite while we write. Literature search in Pub Med was made on 17th September,
2010.

In the first phase of literature search the key word 'leishmaniasis' was searched in any
field. To decrease the number of literatures again the keyword 'leishmaniasis' was
searched in title. Again the keyword ' leishmaniasis ' in title and 'visceral' in any field was
searched. This also resulted in large number of articles. Again the keywords
'leishmaniasis' and 'visceral' in title and 'symptoms' in any field was searched. To narrow
down the search field again the keyword 'treatment' was added to the search option and
searched in any field. This also led to a large number of references so above keywords
and next keyword 'relative risk' was added and searched in any field. This decreased the
number of articles displayed to 1 which was saved to the endnote library.

In next stage of literature review, the keyword 'leishmaniasis' and 'visceral' in title and
only 'relative risk' in any field was searched. The search displayed 12 papers. These
references were also saved in the endnote library.

Again next stage of literature review was performed. The keyword 'leishmaniasis' and
'visceral' in title and 'treatment' in any field was searched. This search generated 12
papers. These references were also saved in the endnote library.

To get more number of references another phase of literature search was also performed.
In this phase the keyword 'Leishmaniasis' and 'visceral' in title and 'signs' in any field was
searched. This search led to 6 references which were also saved in the endnote library.
Then all the references obtained were searched for full text. Among the 31 references
saved in endnote library, full text articles of only 5 references were found and their pdf
versions were downloaded for review.
And for more articles advanced search was done in the Google. 3 documents which were
related to the diphtheria were downloaded and references of those documents were
created in end note library.

Again the articles published in journals of Kathmandu University, that were related to
visceral leishmaniasis were searched and downloaded from the website www.kumj.com.
3 articles were downloaded from this site. The references of the articles downloaded from
Google and journal of Kathmandu University were created in the endnote library. A
reference of Park's Textbook of Preventive and Social Medicine was also created in
endnote library as information mentioned in that book was also used while preparing this
paper.

A total of 38 references and 12 articles were found. Among the 12 articles, 5 articles were
ignored after their study as their contents were not appropriate for this paper and
information in some article were not relatively different from the used articles.

Findings

First of all leishmaniasis was searched in any field which showed 16434 articles. The
result was cancelled and leishmaniasis was searched as a title which gave 8369 articles.
The result was also ignored. Then visceral keyword was added to search in any field
which showed 3847 results. It was also cancelled and visceral keyword was searched in
title with leishmaniasis as title which gave 2835 results. To reduce those results the
keyword symptoms was searched in any field which gave 1559 results. The search field
was further more narrowed down adding the key word treatment in any field giving 758
results. Again the keyword relative risk was added which gave only one article which
was copied to the end note library. Using the keywords leishmaniasis, visceral and
relative risk 12 articles were retrieved. The key word leishmaniasis, visceral, in title and
'signs' in any field search gave 6 results which were also copied to the end note library.
Again the keyword 'leishmaniasis' and 'visceral' in title and 'treatment' in any field was
searched. This search generated 12 papers.

Using the key words leishmaniasis, visceral, sign, symptom, treatment, relative risk, I got
38 references out of which I got full versions of 12 references. Based on those 12 articles
following findings are derived.

Kala-azar is a parasitic disease caused by the amastigote form of Leishmania donovani.
(Joshi, Bajracharya et al. 2006) Leishmaniasis is transmitted from one person to another
by the bite of Phlebotomine sand flies. Sand flies become infected by biting an infected
animal (for example, a rodent or dog) or person. Sand flies bite actively during the
twilight, evening and night. Leishmaniasis is found rarely transmitted form a pregnant
mother to her baby. Leishmaniasis also can be spread by blood transfusions or
contaminated needle. (CDC 2010; Medicinenet 2010)

The incubation period of Leishmania donovani in man is usually 2-4 months.(Joshi,
Bajracharya et al. 2006)
People living in houses made up of mud, living to proximity to ponds, and people living
in polluted environment or unhygienic places have more chances of transmission of the
disease.(Schenkel, Rijal et al. 2006) Raring domestic animals around the houses may also
increase the risk of transmission of Kala-azar. People of all ages are at risk for infection if
they live or travel where leishmaniasis is found. (CDC 2010) Males are affected twice as
often as females. (Park 2009) The risk is highest from dusk to dawn because this is when
sand flies generally are the most active. Examples of people who may have an increased
risk for infection include adventure travelers, farmers, forestry, fishers, ecotourists, Peace
Corps volunteers, missionaries, soldiers, ornithologists (people who study birds), and
other people who do research (or are active) outdoors at night/twilight. (CDC 2010)

Kala-azar is mostly confined to the plains; it does not occur in altitudes over 2000 feet
(600 meters). There is high prevalence of kala-azar during and after rains. This disease is
generally confined to rural areas, where conditions for breeding of sandflies readily exists
compared to the urban areas. (Park 2009)

The common sign and symptom of visceral leishmaniasis are fever (CDC 2010;
newyorktimes 2010), weight loss, (CDC 2010; newyorktimes 2010)an enlarged spleen
and liver (typically, the spleen is bigger than the liver) (CDC 2010) and some abnormal
blood tests like low blood counts, including a low red blood cell count (anemia), low
white blood cell count, and low platelet count. (CDC 2010) Double peak of temperatures
in 24 hours is considered highly suggestive of kala-azar. (Joshi, Bajracharya et al. 2006)
Belly area (abdominal) discomfort (newyorktimes 2010), night sweats (newyorktimes
2010), and thinning hair (newyorktimes 2010) are also the symptoms of kala-azar.
Fatigue, weakness, and appetite loss are commonly seen during kala-azar infection.
(newyorktimes 2010) Patient may develop intercurrent infections of respiratory and
gastrointestinal systems. (Joshi, Bajracharya et al. 2006) A large number of patients
develop darkening of skin especially on face, hand, and upper torso. (Joshi, Bajracharya
et al. 2006) This is why the disease is known as kala-azar.

For the treatment of kala-azar Sodium antimony gluconate is used as a First line durg and
Amphoterecin B is used as a Second line drug. (Joshi, Banjara et al. 2006) Three weeks
course of intravenous Amphotericin-B is being used by National Program of Nepal for
Kala-azar as the first choice drug.(Joshi, Bajracharya et al. 2006)

Vaccination against kala-azar is not yet discovered. Even though vaccination would be
available it would not be proved cost effective. (Joshi, Banjara et al. 2006)

Visceral leishmaniasis can be prevented by protecting yourself from the bite of sand fly.
It can be possible by removing stagnant water from around the houses, filling the cracked
house wall, wearing protective long sleeved clothes, using bed nets, spraying insecticides
around the houses where sand fly can breed.
Discussion

It is one of the major public health threats in the Terai (lowlands) in southeast Nepal and
the bordering districts of the Indian state of Bihar.(Joshi, Banjara et al. 2006; Schenkel,
Rijal et al. 2006) The first officially recorded case of visceral leishmaniasis in Nepal was
in 1980. (Joshi, Banjara et al. 2006; Schenkel, Rijal et al. 2006) Since then, there has
been a steady increase in the reported cases, and presently 12 districts are identified to be
endemic with more than 5.5 million people estimated to be at risk of the disease
(Schenkel, Rijal et al. 2006)

Around 5.5 million people living in those affected areas are at high risk of transmission
of kala-azar. Case fatality rate of kala-azar was found to be between 0.23% and 13.6%.
(Joshi, Banjara et al. 2006) From 1980 to 1989, the incidence rate per 100,000 person-
year remained below 10 but it has been increasing since then steadily and in last few
years it has been reported to be 43-55 per 100,000 person-year. (Schenkel, Rijal et al.
2006) Lack of surveillance, cross-border migration from Bihar, inadequate treatment of
cases and an increasing vector density are contributing to an increasing burden of
infection and disease. (Schenkel, Rijal et al. 2006)

Karl Schenkel et all found a positive correlation between holding small animals and
protection of human beings from the infection. It may probably be because sandflies are
attracted by fowl more than by humans and therefore their owners could be protected
from bite of sandfly and hence from the transmission of the parasite.(Schenkel, Rijal et
al. 2006) The same study found no relation between raring domestic animals around the
house and transmission of leishmania. Kala-azar is found to be highly prevalent in
poorest communities. (Adhikari, Supakankunti et al. 2010) Elimination of kala-azar is
directly related to poverty alleviation because if poverty incidence is reduced by 10%, it
will lead to reduction of kala-azar incidence by 16%. (Adhikari, Supakankunti et al.
2010)

Kala-azar elimination programme has been identified as priority programme in India,
Nepal and Bangladesh and committed to eliminate it by 2015 from the region. For this a
high level of political commitment a Memorandum of Understanding (MoU) calling for
the elimination of Visceral Leishmaniasis through intercooperation was signed. (Joshi,
Banjara et al. 2006) The Visceral Leishmaniasis Elimination Plan of Nepal proposed in
2002 aims at reducing the annual morbidity to less than 1 per hundred thousand
population at risk by 2015.(Joshi, Banjara et al. 2006) To achieve this goal surveillance
of disease and vector and communication behavioral impacts and operational research
should be important component of elimination programme. Only focal IRS is inadequate
to prevent transmission of leishmania so it should be carried along with integrated vector
management and training to village health workers and female community health
volunteers to early screen cases. (Joshi, Banjara et al. 2006)
Conclusion and Recommendation

From this study it is concluded that Nepal especially southeastern parts of Nepal is at
high risk of visceral leishmaniasis. Leishmaniasis is a serious disease and has 100%
mortality in untreated cases. Leishmaniasis, when diagnosed and treated in an early stage
before any complication arises, does not harm the health of a person seriously. So, it is
urgent to implement appropriate preventive programmes in those areas of Nepal.

So, it is necessary to implement programmes that help in early diagnosis and treatment of
leishmaniasis especially in those parts of Nepal with high burden of disease. Since open
migration of people from the endemic areas of Bihar of India to Nepal is seen as a major
reason behind the increased incidence of leishmaniasis in recent years, migration from
those areas should be checked and the affected people should be quarantined. To fulfill
the goal of Nepal to eliminate kala-azar by 2015 adequate research in the disease and
vectors prevalent in the endemic areas should be done and the interventions applied under
this goal should be monitored. As socioeconomic condition of the people was also seen
as a determinant of incidence of kala-azar, not only case treatment is adequate to
eliminate the disease but a holistic approach of disease prevention is required. Integrated
vector management, case treatment should go side by side for an effective prevention of
the disease.

References

Adhikari, S. R., S. Supakankunti, et al. (2010). "Kala-azar in Nepal: Estimating the
        effects of socioeconomic factors in disease incidence." Kathmandu University
        Medical Journal 8(29): 73-79.
CDC. (2010, September 22, 2008 ). "Leishmania Infection." Retrieved 21 September,
        2010,                                                                          from
        http://www.cdc.gov/ncidod/dpd/parasites/leishmania/factsht_leishmania.htm.
Joshi, A. B., M. R. Banjara, et al. (2006). "Elimination of visceral leishmaniasis in Nepal:
        pipe-dreams and possibilities." Kathmandu University Medical Journal 4(16):
        488-496.
Joshi, S., B. L. Bajracharya, et al. (2006). "Kala-azar (Visceral Leishmaniasis) from
        Khotang." Kathmandu University Medical Journal 2(14): 232-234.
Medicinenet. (2010). "What is leishmaniasis?" Retrieved 21 September, 2010, from
        http://www.medicinenet.com/leishmaniasis/index.htm.
newyorktimes. (2010). "Leishmaniasis."            Retrieved 21 september, 2010, from
        http://health.nytimes.com/health/guides/disease/leishmaniasis/overview.html.
Park, K. (2009). Park's Textbook of Preventive and Social Medicine, M/s Banarsidas
        Bhanot
Schenkel, K., S. Rijal, et al. (2006). "Visceral leishmaniasis in southeastern Nepal: a
        cross-sectional survey on Leishmania donovani infection and its risk factors."
        Trop Med Int Health 11(12): 1792-9.

				
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