Visceral leishmaniasis

Leishmanioses are widespread in 88 countries of the tropical and subtropical zone, including regions of the Mediterranean Sea basin of Southern Europe. Actually, approximately 350 million of people live in Leishmania endemic areas and about 12 million of individuals are infected. Visceral leishmaniosis (kala-azar disease, tropical splenomegaly) is caused by at least 3 species of Leishmania protozoa: L. donovani, L. infantum and L. chagasi. The incidence of the disease is estimated at 500,000 new cases annually. The infection is transmitted by Phlebotomus or Lutzomyia mosquitos bites, in which intestines forms invasive to humans are developed. Leishmania spp. have a predilection to the reticulo-histiocytary system cells, leading to their proliferation and disruption, and after spreading to the circulation they invade spleen, liver and bone marrow. Visceral leishmaniosis should be suspected in travelers returning from tropical and subtropical areas with signs of splenomegaly and twice temperature spikes in a day. We reported a case of the kala-azar disease in the 22 year-old Polish patient seasonally working in Italy. The clinical picture was expressed by two daily pikes of fever proceeded by chills, excessive sweat, hepatosplenomegaly, lymphadenopathy, general weakness, abdominal pain and nausea. The Leishmania infection was complicated by candidiosis. Laboratory tests showed anaemia, thrombocytopenia, leucopenia, hypergammaglobulinaemia and a suppression of immunological cellular response. The diagnosis was confirmed by a presence of amastigota forms in macrophages of the bone marrow aspirate and a detection of specific antibodies to L. infantum by Westernblotting. The patient was successfully treated with Glucantime.     

Visceral leishmaniasis in Africa

2 large epidemics of visceral leishmaniasis are presently occurring in Bihar State, India and in southern Sudan where it had not previously been a problem. Civil war which in turn led to sizable malnutrition and migration of many people and animals contributed greatly to the present epidemic. In southern Sudan, 30,000-40,000 people have already died. Villages have lost 30=65% of their population to visceral leishmaniasis, 4-40% carry the parasites, and 30-40% are immune to it. The epidemic is extending to the north. Other endemic areas in Africa include Kenya, many western and central African countries, and all the countries in northern Africa. Animal hosts include rats, genets, several cats, jackals, and dogs. The protozoan parasites Leishmania species are becoming more and more resistant to drugs which exacerbates these epidemics. The treatments include pentavalent antimonials, aminosidine, pentamidine, amphotericin B, liposomal amphotericin B, and sodium stibogluconate. The sandfly vector in India is beginning to exhibit resistance to DDT, but this is not yet a problem in Africa, however. The sandfly transmits promastigotes into the skin where an inflammatory factor in the sandfly saliva strengthens infectivity. They then infect phagocytic cells, especially macrophages, which essentially suppresses immunity. There they transform into amastigotes. Even though the body has very high levels of antileishmanial antibodies, the macrophages cannot eliminate the intracellular amastigotes. The parasites invade the spleen, liver, bone marrow, and lymph nodes--the macrophage-rich organs--which causes clinical symptoms. Some of these clinical symptoms include fever, wasting, splenomegaly, bone marrow failure, and lower than normal amounts of all cellular elements of blood. In HIV-positive Europeans who have lived in or visited endemic areas, visceral leishmaniasis has become an opportunistic infection. Their atypical features make it important to look for the parasites in tissues to diagnose it.     

Visceral leishmaniasis in southern Sudan

Reports made by Médecins Sans Frontières in Khartoum on an outbreak of visceral leishmaniasis among displaced people from the western Upper Nile prompted an investigation at Ler Hospital, the second largest in the region. In a 10 d period during April 1989, 100 persons with visceral leishmaniasis were identified. Of these, 82% were men; 67% were aged 20 to 39 years. Except for the absence of ulcerated skin lesions, the clinical features corresponded to those traditionally described in the Sudan. A cross-sectional serological survey was conducted in Kuernyang (400 inhabitants), 40 km north of Ler. The anti-Leishmania antibody prevalence was 18.2%, being higher among those older than 15 years, and higher among adult women (28%) than among men (18%). The overall prevalence of splenomegaly was 16.4%. 33% of seropositive cases presented with splenomegaly, compared with 11.6% of those who were seronegative. Three serological surveys conducted on the eastern side of the Nile showed no seropositive cases. However, 2 autochthonous cases were clinically diagnosed and confirmed by serological assays. The war conflicts and population movements appear to be the main cause of this large outbreak that may have killed thousands of tribespeople in southern Sudan. There is a risk of the disease spreading into other areas with devastating consequences for the population, should energetic measures not be immediately taken.     

3. Visceral leishmaniasis

From the early 1900s, visceral leishmaniasis (VL; kala-azar) has been among the most important health problems in Sudan, particularly in the main endemic area in the eastern and central regions. Several major epidemics have occurred, the most recent—in Western Upper Nile province in southern Sudan, detected in 1988 — claiming over 100000 lives. The disease spread to other areas that were previously not known to be endemic for VL. A major upsurge in the number of cases was noted in the endemic area. These events triggered renewed interest in the disease. Epidemiological and entomological studies confirmed Phlebotomus orientalis as the vector in several parts of the country, typically associated with Acacia seyal and Balanites aegyptiaca vegetation. Infection rates with Leishmania were high, but subject to seasonal variation, as were the numbers of sand flies. Parasites isolated from humans and sand flies belonged to three zymodemes (MON-18, MON-30 and MON-82), which all belong to the L. donovani sensu lato cluster. Transmission dynamics have not been elucidated fully; heavy transmission in relatively scarcely populated areas such as Dinder national park suggested zoonotic transmission whereas the large numbers of patients with post kala-azar dermal leishmaniasis (PKDL) in heavily affected villages may indicate a human reservoir and anthroponotic transmission. Clinical presentation in adults and in children did not differ significantly, except that children were more anaemic. Fever, weight loss, hepato-splenomegaly and lymphadenopathy were the most common findings. PKDL was much more common than expected (56% of patients with VL developed PKDL), but other post-VL manifestations were also found affecting the eyes (uveitis, conjunctivitis, blepharitis), nasal and/or oral mucosa. Evaluation of diagnostic methods showed that parasitological diagnosis should still be the mainstay in diagnosis, with sensitivities for lymph node, bone marrow and spleen aspirates of 58%, 70% and 96%, respectively. Simple, cheap serological tests are needed. The direct agglutination test (DAT) had a sensitivity of 72%, specificity of 94%, positive predictive value of 78% and negative predictive value of 92%. As with other serological tests, the DAT cannot distinguish between active disease, subclinical infection or past infection. The introduction of freeze-dried antigen and control sera greatly improved the practicality and accuracy of the DAT in the field. An enzyme-linked immunosorbent assay using recombinant K39 antigen had higher sensitivity than DAT (93%). The polymerase chain reaction using peripheral blood gave a sensitivity of 70–93% and was more sensitive than microscopy of lymph node or bone marrow aspirates in patients with suspected VL. The leishmanin skin test (LST) was typically negative during active VL and converted to positive in c. 80% of patients 6 months after treatment. Immunological studies showed that both Th1 and Th2 cell responses could be demonstrated in lymph nodes from VL patients as evidenced by the presence of messenger ribonucleic acid for interleukin (IL)-10, interferon γ and IL-2. Treatment of peripheral blood mononuclear cells from VL patients with IL-12 was found to drive the immune response toward a Th1 type response with the production of interferon γ, indicating a potential therapeutic role for IL-12. VL responded well to treatment with sodium stibogluconate, which is still the first line drug at a dose of 20 mg/kg intravenously or intramuscularly per day for 15–30 d. Side effects and resistance were rare. Liposomal amphotericin B was effective, with few side effects. Control measures have not been implemented. Based on observations that VL does not occur in individuals who have a positive LST, probably because of previous cutaneous leishmaniasis, a vaccine containing heat-killed L. major promastigotes is currently undergoing a phase III trial.     

Visceral leishmaniasis in eastern Africa--current status

Visceral leishmaniasis (VL) is among the most neglected of the tropical diseases, afflicting the poorest of the poor. In eastern Africa, VL causes at least 4000 deaths annually, a loss of approximately 385,000 disability-adjusted life years. Due to the chronicity of underlying causes, it is likely that the caseload will increase in the foreseeable future. While efforts should be pursued to develop novel case management and prevention tools, several effective interventions already exist but are rarely deployed. Funds are needed now to procure commodities and strengthen health systems, so that effective VL control can be delivered to populations at risk.     

Leishmaniasis in Sudan. Visceral leishmaniasis

From the early 1900s, visceral leishmaniasis (VL; kala-azar) has been among the most important health problems in Sudan, particularly in the main endemic area in the eastern and central regions. Several major epidemics have occurred, the most recent--in Western Upper Nile province in southern Sudan, detected in 1988--claiming over 100,000 lives. The disease spread to other areas that were previously not known to be endemic for VL. A major upsurge in the number of cases was noted in the endemic area. These events triggered renewed interest in the disease. Epidemiological and entomological studies confirmed Phlebotomus orientalis as the vector in several parts of the country, typically associated with Acacia seyal and Balanites aegyptiaca vegetation. Infection rates with Leishmania were high, but subject to seasonal variation, as were the numbers of sand flies. Parasites isolated from humans and sand flies belonged to three zymodemes (MON-18, MON-30 and MON-82), which all belong to the L. donovani sensu lato cluster. Transmission dynamics have not been elucidated fully; heavy transmission in relatively scarcely populated areas such as Dinder national park suggested zoonotic transmission whereas the large numbers of patients with post kala-azar dermal leishmaniasis (PKDL) in heavily affected villages may indicate a human reservoir and anthroponotic transmission. Clinical presentation in adults and in children did not differ significantly, except that children were more anaemic. Fever, weight loss, hepato-splenomegaly and lymphadenopathy were the most common findings. PKDL was much more common than expected (56% of patients with VL developed PKDL), but other post-VL manifestations were also found affecting the eyes (uveitis, conjunctivitis, blepharitis), nasal and/or oral mucosa. Evaluation of diagnostic methods showed that parasitological diagnosis should still be the mainstay in diagnosis, with sensitivities for lymph node, bone marrow and spleen aspirates of 58%, 70% and 96%, respectively. Simple, cheap serological tests are needed. The direct agglutination test (DAT) had a sensitivity of 72%, specificity of 94%, positive predictive value of 78% and negative predictive value of 92%. As with other serological tests, the DAT cannot distinguish between active disease, subclinical infection or past infection. The introduction of freeze-dried antigen and control sera greatly improved the practicality and accuracy of the DAT in the field. An enzyme-linked immunosorbent assay using recombinant K39 antigen had higher sensitivity than DAT (93%). The polymerase chain reaction using peripheral blood gave a sensitivity of 70-93% and was more sensitive than microscopy of lymph node or bone marrow aspirates in patients with suspected VL. The leishmanin skin test (LST) was typically negative during active VL and converted to positive in c. 80% of patients 6 months after treatment. Immunological studies showed that both Th1 and Th2 cell responses could be demonstrated in lymph nodes from VL patients as evidenced by the presence of messenger ribonucleic acid for interleukin (IL)-10, interferon gamma and IL-2. Treatment of peripheral blood mononuclear cells from VL patients with IL-12 was found to drive the immune response toward a Th1 type response with the production of interferon gamma, indicating a potential therapeutic role for IL-12. VL responded well to treatment with sodium stibogluconate, which is still the first line drug at a dose of 20 mg/kg intravenously or intramuscularly per day for 15-30 d. Side effects and resistance were rare. Liposomal amphotericin B was effective, with few side effects. Control measures have not been implemented. Based on observations that VL does not occur in individuals who have a positive LST, probably because of previous cutaneous leishmaniasis, a vaccine containing heat-killed L. major promastigotes is currently undergoing a phase III trial.     

Visceral leishmaniasis treatment, Italy

First-line drug treatment was recorded in 573 immunocompetent patients with visceral leishmaniasis in Italy. In the past 12 years, the proportion of antimonial treatments decreased from 100% to 2.8%, while the proportion of amphotericin B treatments increased from 0% to 97.2%. The countrywide change in therapy is a response to both disease reemergence and increasing antimonial failure.     

Visceral leishmaniasis in immunocompetent children: diagnostic and epidemiologic value of peripheral leishmania blood culture

Utilisation of new diagnosis means and particularly non invasive oues in visceral leishmaniasis can be very valuable for the biologist, the clinician as well as the patient. In this, detection of leishmania in peripheral blood, well know for VIH patients, has been applied to 37 immunocompetent tunisan children suffering from kala azar that has been shown through direct examination of bone marrow. Observed results show that culture on NNN peripheral blood medium was positive in 25 cases (67.57%). On the other side, detection of leishmania through concomitant culture of blood and marrow bone for 24 children with visceral leishmaniasis match the results in 75% of the cases. Detection of leishmania by mean of blood culture for immunocompetent children is a diagnosis mean of visceral leishmaniasis and has also an epidemiologic utility by isoenzymatic characterization of isolated leishmania strains.     

Visceral leishmaniasis control: a public health perspective

Visceral leishmaniasis (VL), also known as kala-azar, is a vector-borne disease caused by a protozoan of the Leishmania donovani complex. A phlebotomine sandfly transmits the parasite from person to person or via an animal reservoir. VL is a severe, debilitating disease, characterized by prolonged fever, splenomegaly, hypergammaglobulinaemia and pancytopenia. Patients become gradually ill over a period of a few months, and nearly always die if untreated. Case-fatality ratios are high even in treated patients. Worldwide an estimated 500,000 VL cases occur each year. This study reviews clinical, epidemiological and public health aspects of the disease and shows how critical adequate case detection is for the success of VL control. Examination of the issue of VL diagnosis with respect to the global challenges in VL control leads to the observation that a sound diagnostic-therapeutic algorithm for the health services in endemic areas is badly needed. Serological tests could be an alternative to parasitological diagnosis and the direct agglutination test (DAT) was found to fulfil many criteria for a 'field test', including cost effectiveness. Although research needs on vaccine and better drugs continue to be high on the agenda, a VL test-treatment strategy based on currently available highly sensitive serological tests, such as the DAT, should be introduced in the health services in endemic areas.     

Visceral leishmaniasis and its control in Bangladesh

Visceral leishmaniasis, which is also known as kala-azar, reappeared in Bangladesh during the 1980s, approximately 7-8 years after large-scale use of DDT had been abandoned by the malaria eradication programme in the country. Pabna, Mymensingh and Rajshahi were the regions most affected with kala-azar. The article presents a historical review and information about the present status of leishmaniasis in Bangladesh together with control strategies and a proposed plan of operation.     

Visceral leishmaniasis: consequences to women in a Bangladeshi community

Visceral leishmaniasis (VL) or kala-azar (KA) affects the rural poor, causing significant morbidity and mortality. We examined the epidemiological and social impact of KA in an affected village in Bangladesh. A population-based survey of the village residents showed a case fatality rate of 14.7% among females and 5.3% among males. Before initiation of the study, female patients were ill longer than males before they received treatment. Future work needs to focus on understanding the implications of KA on women and to develop sustainable strategies for appropriate and timely access to treatment.