Showing papers on "Visceral leishmaniasis published in 1990"

Opportunistic infections in AIDS in developed and developing countries.

Abstract: The acquired immune deficiency syndrome (AIDS) is fundamentally the same disease in all parts of the world, but the prevalence of microorganisms in an environment governs the patterns of disease arising from reactivated latent infections, invading pathogens and opportunistic infections. AIDS in Africa has certain characteristic presentations. Enteropathic AIDS is most common: Cryptosporidium and Isospora belli are identified in up to 60% of patients, but it is uncertain whether they are the causes of diarrhoea. Pneumocystis carinii pneumonia is rare. Tuberculosis, both pulmonary and extrapulmonary, is the supreme complicating infection. Herpes zoster is frequently the first clinical presentation, and has a 95% positive predictive value for HIV positivity. Measles may be more frequent in infants born to HIV-infected mothers, and appears to be worse in HIV-infected children. There is accelerated progress of both diseases in patients infected by HIV and Mycobacterium leprae. Salmonellosis is frequent. There is no direct interaction between malaria and HIV, but, by being a potent cause of anaemia, malaria enhances transmission of HIV to children through blood transfusion. HIV-positive subjects are liable to new or reactivated visceral leishmaniasis with dissemination to unusual sites. Cerebral toxoplasmosis is common. There are no apparent interactions between HIV and helminths, although there is one report of hyperinfection with Strongyloides stercoralis. Cryptococcal meningitis has high frequency. Infections with Histoplasma encapsulatum are common in tropical America, but there has been no increase of frequency of H. duboisii in Africa since the advent of AIDS.

Treatment of visceral leishmaniasis with pentavalent antimony and interferon gamma.

Abstract: Acute visceral leishmaniasis is associated with an antigen-specific immunosuppression of mononuclear cells as evidenced by defective in vitro production of interferon gamma. We evaluated treatment with recombinant human interferon gamma in combination with conventional pentavalent antimony therapy in patients with visceral leishmaniasis. Six of eight patients with visceral leishmaniasis (mean duration, 17 months) that had been unresponsive to multiple courses of pentavalent antimony responded to treatment with recombinant human interferon gamma (100 to 400 micrograms per square meter of body-surface area per day) in addition to pentavalent antimony (20 mg per kilogram of body weight per day) for 10 to 40 days. The other two patients improved initially but then relapsed and required treatment with amphotericin B. Eight of nine additional patients with previously untreated severe visceral leishmaniasis were also successfully treated with the combination of interferon gamma and pentavalent antimony. The 14 patients who responded to this regimen had marked improvement in symptoms and in measures of anemia and leukopenia, as well as weight gain, a decrease in spleen size, and an absence or reduction of leishmanias in splenic aspirates. These patients had no recurrence of illness after a mean (+/- SE) follow-up of 8 +/- 1 months. Fever was the only major side effect of interferon gamma. We conclude that the combination of interferon gamma and pentavalent antimony is effective in treating seriously ill patients with refractory or previously untreated visceral leishmaniasis.

Treatment of visceral leishmaniasis in Kenya by aminosidine alone or combined with sodium stibogluconate

Abstract: The treatment of leishmaniasis, as currently conducted in Kenya with sodium stibogluconate, is unsatisfactory as it is expensive, resistance and relapses may occur, and major adverse effects have been reported. Recently, aminosidine (paromomycin) sulphate has shown good antileishmanial activity on its own as well as synergism with pentavalent antimony, administered concurrently. The present study was designed to assess the effectiveness of parenteral aminosidine, alone or combined with sodium stibogluconate, in visceral leishmaniasis, compared to treatment by stibogluconate alone. 53 patients were allocated to the 3 therapeutic regimes. The presenting signs and symptoms of leishmaniasis were those commonly seen in the visceral form of the disease, particularly in Kenya. At termination, clinical cures were achieved in all 53 patients with no difference between treatment groups. Spleen aspirates revealed the best parasitological results in patients receiving the combined treatment, with only 13% failures (partial cures+relapses), as opposed to 21% failures with aminosidine alone and 45% with stibogluconate alone. Treatment with aminosidine alone was the cheapest and safest regime.

Visceral leishmaniasis in HIV infection and AIDS: clinical features and response to therapy.

Abstract: The development of visceral leishmaniasis with atypical features in an AIDS patient, and the recent flurry of reports of visceral leishmaniasis in HIV-infected individuals prompted the review of its manifestations in the 47 reported cases. Splenomegaly, which is almost always a feature of visceral leishmaniasis in the immunocompetent host, was absent in eight. Antibodies to Leishmania donovani , which are present in approximately 95 per cent of immunocompetent patients with visceral leishmaniasis, were absent in 29 of 45 (66 per cent) of HIV-infected patients tested. Nine HIV-positive patients with visceral leishmaniasis did not exhibit a primary clinical response to therapy with antimonials and of those who did show a response, relapse occurred in 13, at a mean 4.5 months after stopping therapy. Seventeen patients are known to have died often in association with respiratory disease; Leishmania was seen in one bronchial lavage specimen and in lung tissue in one post-mortem performed. In order to improve the prognosis of visceral leishmaniasis in HIV-infected patients diagnosis will have to be made earlier, taking account of the atypical features, and treatment will need to be improved, both initially and perhaps also by the use of long-term maintenance therapy.

Identification and characterisation of a Leishmania donovani antigen belonging to the 70-kDa heat-shock protein family.

Abstract: A Leishmania donovani promastigote cDNA library was screened with serum obtained from a patient infected with visceral leishmaniasis. Sequence analysis of a clone obtained from this library revealed that the 600-bp insert corresponded to the carboxy-terminal region of an antigen related to the 70-kDa heat-shock protein family. The full-length sequence of the corresponding gene (1959 nucleotides) was determined after isolation of genomic clones. Genes encoding the antigen are present on a single chromosome as a series of approximately twelve 3.7-kb direct tandem repeats. The antigen can be identified as a 70-kDa heat-shock cognate protein by virtue of its molecular mass, sequence and constitutive expression during heat shock. It is expressed at all stages of the parasite life-cycle. Antibodies against the λgt11 fusion protein were detected in more than 50% of serum samples obtained from patients with visceral leishmaniasis, but were not detected in sera from patients with cutaneous leishmaniasis or Chagas' disease.

Lutzomyia evansi, an alternate vector of Leishmania chagasi in a Colombian focus of visceral leishmaniasis.

Abstract: brigipulpis was abseni. In addition tu the laiicr sprcics, the authors corisidercd Lu. ezluilsi iu be B puiaiivr vrcior of VL in ihis lwiiliry. In Custa Rica, 2El.liUON el d. (I 984) also observed the association of Lu. cuutrsi wiih Lu. lorigipulp¡s i i i an endemic focus of the disease. ¡hing rxploraiory visi18 IO ihr aburiginal rcscrvr of Sari Andres de Soiavcnio (SAS), Dcparilnelit of Ctirdoba, Coloinbia, preliminary cnioiiiological studies wert uridcriakcii io ideniify the ariihru opliilic ptilrbotoinincs of ihis area, in which $L aiid culaiictus Irishnianiasis are endemic. J'rcvíous sancflly collecriuns revealed 11ia1 Lu. murisi was the predominani species UI different iiines of the year (VELU er d., 1986'). During the prrrcnr work, sandHies were caught between 1800 and 2300 h using Shaiirion iraps and prutccied human bait in huuses and L ~ K pericloiiiiciliary region. In ihc laboratory 329 cryol)rcserved fcmak sandiiirs were ihawed and individually d i ~ ~ c t c d for taxonomic purposes, and to search lor proniasiiyoic infection in thc digrsiive tract. L u . rvurwi was the predominant s p i e s (87%), iblluwtd by Lw. purnezzl (10%) and Lu. ~UNNIC~IS~S (3%). I n one specimen of Lu. mumi lorig promasiigutes wrre found in the hindgut and sioniodeal valve. 'l'lie parasites (fewer than 2W) wcrc suspsnJcd in phiJsphalc-bullkd sahic plus \\\"/o vlv prnicilliiisircpiomycin (Giko) , and inoculaicd intraporiiuiirally io a goldcii hanistcr. Tlie animal was killed alter 3 inuiiihs, debpite ihe'absciicr of clinicul signs o!' VL. Abundant unastigutcs were observed in Giemsastained sincars froin spleen and liver. 'l'rituraies of these organs were hculaicd io Scnckjie's and Sshneidcr's uuliurc inedia, aiid 3 boiir-marrow aq+ raie was inucularrd intrapcri~unrally I O a sccuiirl lianistcr. Duc to subculiuriiig problenis wiih ihr I h r isolate, thc latrcr animal was killcd 1 molillis larcr, a t which lime 110 c h i c d sign of disease was obscrvcd. Aillericas (ZUL.iUbN, 198s; DEANI! &f CKIMAI.DI,

Pre- and post-treatment antibody levels in visceral leishmaniasis.

Abstract: Enzyme-linked immunosorbent assay (ELISA) and the direct agglutination test (DAT) were employed to test sera obtained from a visceral leishmaniasis (VL) endemic area, the Aba-Roba focus in south-west Ethiopia. Thirty sera of untreated VL patients, 37 sera 6–90 months after treatment, 18 sera from endemic controls, 8 sera from non-endemic controls and 23 sera from patients with other diseases (schistosomiasis, tuberculosis, cutaneous leishmaniasis) were tested. Based on ELISA, the percentages negative were found to be 50% up to one year and 89% from 2 to 8 years after treatment. In contrast, these rates based on DAT were 0% in one year and 33% from 1–8 years after treatment. The relevance of persisting antibodies in the kinetics and profile of antibody production during treatment is discussed. The use of ELISA in the evaluation of clinical prognosis and patient follow-up is recommended. Serum from a diffuse cutaneous leishmaniasis patient cross-reacted with the DAT and ELISA for VL.

Canine visceral leishmaniasis in northeast Brazil: assessment of serodiagnostic methods.

Abstract: Domestic dogs are considered to be a major reservoir of Leishmania donovani chagasi in northeast Brazil, and the elimination of infected dogs is an important part of the control program. We assessed 2 serological methods, IFA and ELISA. Of 405 dogs, 8% were positive by IFA obtained from blood collected by drying onto filter paper followed by elution, 17% were positive by IFA performed using sera, and 38% were positive by ELISA on the same sera. Thirty-five dogs, seropositive by 1 or more of the above tests, were killed and touch preparations were made of liver, spleen, and mesenteric lymph nodes. Samples were cultured in enriched NNN media. The ELISA recognized all dogs with proven infection; IFA detected 10 of 12. Eleven dogs were positive by touch preparations and 7 by culture. In addition, kDNA hybridization was undertaken with probes to L. donovani chagasi, L. braziliensis ssp., and L. mexicana amazonensis. Positive results were obtained from tissue in 19 instances, but 10 culture positive specimens were not recognized.

Bacterial Infections in Patients with Visceral Leishmaniasis

Abstract: Bacterial infections are often seen in patients with visceral leishmaniasis. To determine the incidence of such infection and the more common infectious agents, 30 consecutive patients with visceral leishmaniasis were followed throughout hospitalization. There were 24 episodes of bacterial infection in 18 patients (60%). The incidence of bacterial infections in these patients was 22.2/1000 days of admission. The proportion of patients becoming infected by time was significantly greater in the visceral leishmaniasis group than in controls (P less than .01). The skin, respiratory tract, and middle ear were the most common sites of infection, and Pseudomonas aeruginosa and Staphylococcus aureus were the most common agents. Low-grade-virulence bacteria (e.g., Serratia and Providencia species) were also isolated from some cases. Bacterial infections (mainly nosocomial) in patients with visceral leishmaniasis tend to be severe and can cause death. When bacterial infection is suspected in these patients, empiric antibiotic therapy should be started immediately, including coverage for P. aeruginosa and S. aureus, after appropriate diagnostic procedures are taken.

An improved serodiagnostic procedure for visceral leishmaniasis.

Abstract: The enzyme-linked immunosorbent assay (ELISA) is a sensitive and specific serodiagnostic method for leishmaniasis. In this report, we describe how this versatile assay can be improved by the use of protein A or protein G conjugates for the specific detection of Leishmania antibody in the sera of patients with visceral leishmaniasis. In direct comparisons with anti-immunoglobulin conjugate, enzyme-linked protein A gave significantly higher absorbance values for positive sera without a corresponding increase in absorbance values for sera from normal individuals or from patients with other diseases known to cross-react with leishmaniasis. The effect was to increase the distance between positive and negative values, which aided in the interpretation of the results. This also permitted visual distinction between positive sera and negative or weakly reactive sera. The assay was effective using either blood or serum as the source of primary antibody. A further advantage of protein A over anti-Ig conjugate was its ability to detect specific antibody in dog as well as human sera. Finally, we demonstrated the usefulness of the protein A ELISA with a recombinant leishmania antigen, gp63.

Effect of Continuous Administration of Interferon-γ in Experimental Visceral Leishmaniasis

Abstract: In experimental visceral leishmaniasis, intermittently administered interferon-gamma (IFN-gamma) induces antileishmanial activity, which is primarily microbistatic. To determine if the efficacy of IFN-gamma immunotherapy could be enhanced by continuous delivery, Leishmania donovani-infected mice were treated using a subcutaneous osmotic pump. Once-daily intraperitoneal injections of 10(5) or 10(6) units of IFN-gamma inhibited the replication of L. donovani within liver macrophages but overall did not reduce liver parasite burdens. In contrast, a comparable dose of IFN-gamma (2.4 x 10(5) units/day) administered continuously induced an enhanced effect and reduced liver burdens by almost 50%. Although pump delivery did not similarly increase the efficacy of antimony chemotherapy in infected mice, continuous treatment with IFN-gamma plus antimony produced an additive antileishmanial effect. These results suggest that continuous infusions of macrophage-activating lymphokines such as IFN-gamma (used alone or in combination with chemotherapy) may be required to optimize in vivo antimicrobial effects.

Characterization of two proteins from Leishmania donovani and their use for vaccination against visceral leishmaniasis.

Abstract: Two proteins from Leishmania donovani, dp72 and gp70-2, have been previously utilized to specifically serodiagnose patients with visceral leishmaniasis. The proteins were shown by ELISA and Western blotting with monoclonal and polyclonal antibodies to be present in both stages of the parasite. Antibodies to gp70-2 recognize in promastigotes multiple discrete bands of similar m.w. which are common to several isolates of L. donovani. The total amount of Ag and number of bands observed per isolate is not constant. Lectin blots with Con A show gp70-2 to be a glycoprotein. Dp72 shows pronounced microheterogeneity between isolates of L. donovani. The Brazilian isolates examined appear to possess a lower m.w. form (64,000 or 68,000) of this molecule. No reactions were observed with dp72 and lectins in Western blots; and neither tunicamycin, N-glycanase, endoglycosidase H nor F affected the migration of [35S]-methionine-labeled protein on SDS-PAGE. A mAb against dp72 also cross-reacted in Western blots with a 60-kDa protein in Leishmania major, Leishmania aethiopica, and Leishmania tropica. No reaction was observed between the purified promastigote surface protease (gp63) and either monoclonal or polyclonal antibodies produced to dp72 or gp70-2. The ability of the pure proteins to provide protection against a challenge by L. donovani amastigotes was examined. BALB/c mice were immunized with gp70-2 and/or dp72 by using Corynebacterium parvum as an adjuvant. Mice immunized with gp70-2 were not protected; however, mice receiving dp72 showed a 81.1% reduction in the liver parasitemia compared with the adjuvant controls.

The value of a direct agglutination test in the diagnosis of cutaneous and visceral leishmaniasis in Ethiopia.

Abstract: The usefulness and sensitivity of a direct agglutination test (DAT) in the diagnosis of cutaneous leishmaniasis due to Leishmania aethiopica infection has been investigated. Formalin-fixed, trypsin-treated and Coomassie blue-stained Leishmania promastigotes of various origins were used as antigens. L. Major, L. Donovani, L. aethiopica but not L. tropica antigen preparations were able to distinguish sera from individuals infected with Leishmania from sera of uninfected controls, although the titres of sera from patients with localized cutaneous leishmaniasis were low. Comparable results were obtained when the same sera were tested using freshly prepared antigen or antigen stored for 10 months at 4 °C. The assay was also used to monitor improvement of disease status following treatment of diffuse cutaneous leishmaniasis patients, and it was found to correlate well with the changing clinical status of the patients.

In vitro responses to Leishmania antigens by lymphocytes from patients with leishmaniasis or Chagas' disease.

Abstract: T cell responses are correlated with recovery from and resistance to leishmaniasis. Antigens of Leishmania chagasi were evaluated by determining their ability to elicit in vitro proliferation and cytokine production in peripheral blood lymphocytes and in T cell lines and clones from patients with histories of leishmaniasis or Chagas' disease. Antigens tested were selected by their reactivity with patient antibodies. Several of the antigens induced proliferative responses in peripheral blood lymphocytes from patients recovered from visceral or cutaneous leishmaniasis or with chronic Chagas' disease. Two purified glycoproteins, 30 and 42 kD, were consistently among the most effective in eliciting high proliferative responses and IL-2 production. Lymphocytes from a recovered visceral leishmaniasis patient were used to produce T cell lines against either the 30- or 42-kD antigen. Each of the lines responded to both of these antigens as well as to crude leishmania lysate. CD4+ T cell clones specific for either or both of these antigens were also isolated from a visceral leishmaniasis patient. In contrast, rabbit antisera produced against these two antigens were not crossreactive. Both antigens were effective in inducing the production of IFN-gamma from T cell lines from both leishmaniasis and Chagas' disease patients. These studies demonstrate the potential for defining parasite antigens with broad immunostimulatory capabilities.

Regulation of Cell-Mediated Immunity in Leishmaniasis

Abstract: Leishmaniasis is caused by species of the intracellular protozoan parasite belonging to the genus Leishmania. There are three main categories of leishmaniasis: cutaneous leishmaniasis (oriental sore), mucocutaneous leishmaniasis (espundia) and visceral leishmaniasis (kala azar). An incidence rate of 400 000 new cases per year has been reported, and the world wide prevalence of leishmaniasis is estimated to be 12 million cases (MODABBER 1987). Visceral leishmaniasis is fatal if not treated. The last epidemic of leishmaniasis that occurred in India in 1977-1978 caused an estimated 20 000 deaths. Most forms of leishmaniasis are zoonotic, and humans are infected only secondarily. Animal reservoirs of species pathogenic to man include the sloth, dog and rodent. The parasites are transmitted by female sandflies, and the flagellated promastigotes develop in the gut of the sandfly and in cell-free cultures. Transformation into the amastigote stage occurs within the mammalian macrophage. Primary drug treatment is based on antimony compounds, notably the pentavalent antimonials sodium stibogluconate and N-methylglucamine antimonate. These must be given in daily intramuscular doses for several weeks; they entail unpleasant side effects and are not very effective against cutaneous leishmaniasis. The only immunisation strategy against leishmaniasis used so far with any success in man has been restricted to the cutaneous diseases. It is based on convalescent immunity following controlled induction of a lesion with viable L. major (GREENBLATT 1980). The feasibility of vaccination with killed vaccines is currently being evaluated.

Visceral leishmaniasis in Sudan. Clinical features.

Abstract: Kala azar is a disease endemic to the Sudan and a cause of major morbidity and mortality to affected patients when the diagnosis or treatment has been delayed. In this report we described the clinical features of 99 parasite proven patients with visceral leishmaniasis. The Sudanese kala azar patient is young in age (teens to 20's), has marked weight loss despite a continuous, excellent appetite and suffers from insomnia, epistaxis and abdominal pain. Hepatosplenomegaly is universally present. Generalized lymphadenopathy is a prominent feature (72%). The high prevalence of lymphadenopathy has a wide range of implications: for diagnosis, i.e., the use of lymph node aspiration; for response to treatment, i.e., the resolution of lymphadenopathy; and for studies of immunoregulation in this systemic infection.

T-Cell Subsets and T-Cell Antigens in Protective Immunity Against Experimental Leishmaniasis

Abstract: Leishmaniasis is a chronic protozoal infection of man found in South and Central America, Mexico, Africa, Asia, and Europe. The parasite life cycle involves two forms, promastigotes and amastigotes. Promastigotes, found within the sandfly vector, initiate infection by invading macrophages. Once inside macrophages, promastigotes rapidly transform to the nonflagellated amastigote stage, which multiplies intracellularly. Eventually the infected cells rupture, and amastigotes reinvade other macrophages. The ensuing infection can manifest itself in a variety of ways, ranging from healing cutaneous lesions to non-healing cutaneous or visceral infections. This spectral nature is due, in part, to the host’s immunologic response. Thus, although the various species of Leishmania exhibit significant differences, most species appear to be able to produce an inapparent, healing, or nonhealing infection. For example, although the visceral species of Leishmania have long been considered to produce a fatal infection in the absence of drug treatment, it is now known that these parasites may also produce relatively benign cutaneous lesions or completely inapparent infections (BADARO et al. 1986). Similarly, L. braziliensis species often produce a healing cutaneous lesion, although in a small percentage of patients severe mucocutaneous lesions develop.