Summary: To date, most Leishmania and human immunodeficiency virus (HIV) coinfection cases reported to WHO come from Southern Europe. Up to the year 2001, nearly 2,000 cases of coinfection were identified, of which 90% were from Spain, Italy, France, and Portugal. However, these figures are misleading because they do not account for the large proportion of cases in many African and Asian countries that are missed due to a lack of diagnostic facilities and poor reporting systems. Most cases of coinfection in the Americas are reported in Brazil, where the incidence of leishmaniasis has spread in recent years due to overlap with major areas of HIV transmission. In some areas of Africa, the number of coinfection cases has increased dramatically due to social phenomena such as mass migration and wars. In northwest Ethiopia, up to 30% of all visceral leishmaniasis patients are also infected with HIV. In Asia, coinfections are increasingly being reported in India, which also has the highest global burden of leishmaniasis and a high rate of resistance to antimonial drugs. Based on the previous experience of 20 years of coinfection in Europe, this review focuses on the management of Leishmania-HIV-coinfected patients in low-income countries where leishmaniasis is endemic.

https://www.who.int/leishmaniasis/burden/hiv_coinfection/Clinical_Microbiology_Reviews_2008.pdf

The Relationship between Leishmaniasis and AIDS: the Second 10 Years

Over 850 Leishmania-human immunodeficiency virus (HIV) coinfection cases have been recorded, the majority in Europe, where 7 to 17% of HIV-positive individuals with fever have amastigotes, suggesting that Leishmania-infected individuals without symptoms will express symptoms of leishmaniasis if they become immunosuppressed. However, there are indirect reasons and statistical data demonstrating that intravenous drug addiction plays a specific role in Leishmania infantum transmission: an anthroponotic cycle complementary to the zoonotic one has been suggested. Due to anergy in patients with coinfection, L. infantum dermotropic zymodemes are isolated from patient viscera and a higher L. infantum phenotypic variability is seen. Moreover, insect trypanosomatids that are currently considered nonpathogenic have been isolated from coinfected patients. HIV infection and Leishmania infection each induce important analogous immunological changes whose effects are multiplied if they occur concomitantly, such as a Th1-to-Th2 response switch; however, the consequences of the viral infection predominate. In fact, a large proportion of coinfected patients have no detectable anti-Leishmania antibodies. The microorganisms share target cells, and it has been demonstrated in vitro how L. infantum induces the expression of latent HIV-1. Bone marrow culture is the most useful diagnostic technique, but it is invasive. Blood smears and culture are good alternatives. PCR, xenodiagnosis, and circulating-antigen detection are available only in specialized laboratories. The relationship with low levels of CD4+ cells conditions the clinical presentation and evolution of disease. Most patients have visceral leishmaniasis, but asymptomatic, cutaneous, mucocutaneous, diffuse cutaneous, and post-kala-azar dermal leishmaniasis can be produced by L. infantum. The digestive and respiratory tracts are frequently parasitized. The course of coinfection is marked by a high relapse rate. There is a lack of randomized prospective treatment trials; therefore, coinfected patients are treated by conventional regimens. Prophylactic therapy is suggested to be helpful in preventing relapses.

Leishmania and human immunodeficiency virus coinfection: the first 10 years.

Coxiella burnetii is the agent of Q fever, or ``query fever,'' a zoonosis first described in Australia in 1937. Since this first description, knowledge about this pathogen and its associated infections has increased dramatically. We review here all the progress made over the last 20 years on this topic. C. burnetii is classically a strict intracellular, Gram-negative bacterium. However, a major step in the characterization of this pathogen was achieved by the establishment of its axenic culture. C. burnetii infects a wide range of animals, from arthropods to humans. The genetic determinants of virulence are now better known, thanks to the achievement of determining the genome sequences of several strains of this species and comparative genomic analyses. Q fever can be found worldwide, but the epidemiological features of this disease vary according to the geographic area considered, including situations where it is endemic or hyperendemic, and the occurrence of large epidemic outbreaks. In recent years, a major breakthrough in the understanding of the natural history of human infection with C. burnetii was the breaking of the old dichotomy between ``acute'' and ``chronic'' Q fever. The clinical presentation of C. burnetii infection depends on both the virulence of the infecting C. burnetii strain and specific risks factors in the infected patient. Moreover, no persistent infection can exist without a focus of infection. This paradigm change should allow better diagnosis and management of primary infection and long-term complications in patients with C. burnetii infection.

https://hal.archives-ouvertes.fr/hal-01496178/document

From Q Fever to Coxiella burnetii Infection: a Paradigm Change.

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.

Leishmaniasis in Sudan. 3. Visceral leishmaniasis

SUMMARY Although the incidence of Pneumocystis pneumonia (PCP) has decreased since the introduction of combination antiretroviral therapy, it remains an important cause of disease in both HIV-infected and non-HIV-infected immunosuppressed populations. The epidemiology of PCP has shifted over the course of the HIV epidemic both from changes in HIV and PCP treatment and prevention and from changes in critical care medicine. Although less common in non-HIV-infected immunosuppressed patients, PCP is now more frequently seen due to the increasing numbers of organ transplants and development of novel immunotherapies. New diagnostic and treatment modalities are under investigation. The immune response is critical in preventing this disease but also results in lung damage, and future work may offer potential areas for vaccine development or immunomodulatory therapy. Colonization with Pneumocystis is an area of increasing clinical and research interest and may be important in development of lung diseases such as chronic obstructive pulmonary disease. In this review, we discuss current clinical and research topics in the study of Pneumocystis and highlight areas for future research.

Colonization by Pneumocystis jirovecii and Its Role in Disease

Pneumocystis carinii infection in patients with chronic bronchial disease

An easy and quick method for the diagnosis of visceral leishmaniasis in HIV-1-infected individuals.

Objectives: In spite of the high prevalence of Pneumocystis carinii (PC) pneumonia in immunocompromised patients, little is known about the epidemiological characteristics of this infection, and whether the cases of PC pneumonia in immunosuppressed patients are the result of a reactivation of a latent infection or a due to a recent infection is unknown. The aim of this study was to provide information about the epidemiological characteristics of PC pneumonia in a cohort of heart transplant (HT) recipients when compared with the epidemiology of PC infection in a cohort of chronic sputum producers (CSP) representative of the general population of the same geographical area. Methods: We identified all the cases of PC pneumonia in the cohort of 72 subjects who underwent cardiac transplantation at our institution between January 1991 and December 1996 and compared them with the cases of PC infection identified in a non-selected cohort of 34 CSP. This second group was included to obtain an approximation of the frequency of PC carriers in the general population. Identification of PC was accomplished through customary stain techniques and immunofluorescence with monoclonal antibodies. Results: Of the 72 HT recipients four (5.5%) developed PC pneumonia, but one had two episodes. Only one had received primary chemoprophylaxis, but developed PC pneumonia 2 months after discontinuing prophylactic therapy. PC pneumonia episodes were produced 53, 102, 230, 181 and 772 days after the moment of transplant, respectively. PC was identified in two (5.8%) of the 34 CSP. No significant differences were found when the accumulative incidences of PC pneumonia in HT patients and PC infection in CSP were compared (P ¼ 0:7). Conclusions: The frequency of PC pneumonia among HT patients is the same as the frequency of PC infection in the general population. This observation and the long interval between transplantation and the development of PC pneumonia observed in the study support the hypothesis that the occurrence of PC pneumonia in immunocompromised patients might be from a new infection rather than from the reactivation of latent organisms. Therefore, continuous prophylaxis might be indicated in areas with a high prevalence of PC for patients at highest risk. q 2001 Elsevier Science B.V. All rights reserved.

/pdf/pneumocystis-carinii-pneumonia-in-heart-transplant-3597guditp.pdf

Pneumocystis carinii pneumonia in heart transplant recipients.

Following the unexpected finding of antibodies to GBM in a patient with Pneumocystis carinii pneumonia in the absence of kidney abnormalities, the presence of anti-GBM antibodies was analysed in 14 patients with pulmonary P. carinii infection who did not have clinical evidence of autoimmune glomerulonephritis. Patients were divided into three groups: HIV- with P. carinii pneumonia (n = 4), HIV+ with P. carinii pneumonia (n = 5) and HIV- carriers of P. carinii without pneumonia (n = 5). As control groups, HIV- patients with community-acquired non-P. carinii pneumonia (n = 6) and healthy individuals (n = 16) were included. Anti-GBM antibodies, studied with a quantitative enzyme immunoassay (EIA) for anti-alpha3 chain of collagen IV antibodies, were detected in three out of the four HIV-patients with P. carinii pneumonia, but not in any individuals of the other categories. These results suggest that P. carinii alveolar injury or the host response to the organism could affect the basal membrane Goodpasture antigen or a similar antigen, and induces anti-GBM antibody production in HIV- patients, and support the hypothesis that, at least in some cases, Goodpasture's syndrome could be triggered by an alveolar lesion induced by a P. carinii pneumonia.

Presence of glomerular basement membrane (GBM) antibodies in HIV− patients with Pneumocystis carinii pneumonia

Pneumocystis carinii infection is acquired by inhalation and stimulates both humoral and cellular immune responses [2]. Yet, the basic immunobiology and hostparasite relationship in Pneumocystis carinii infection remains poorly understood [3]. The prevailing model for the etiology of Pneumocystis carinii pneumonia (PCP) in adult humans suggests that individuals become infected early in life, and that later episodes of PCP are due to reactivation of latent organisms [2]. Seroepidemiologic studies have shown that environmental exposure to subclinical infection with the organism occurs commonly in the general population but with variations in frequency and epidemiological pattern [4]. The latent organisms are presumed to be acquired in early childhood, because serum antibodies to human Pneumocystis carinii antigens are detected in 85% of subjects by 2 years of age [5]. However, serologic testing cannot distinguish between past and current infections [4].

C. Regordán

Papers

Pneumocystis carinii infection in patients with chronic bronchial disease

An easy and quick method for the diagnosis of visceral leishmaniasis in HIV-1-infected individuals.

Pneumocystis carinii pneumonia in heart transplant recipients.

Presence of glomerular basement membrane (GBM) antibodies in HIV− patients with Pneumocystis carinii pneumonia

Absence of Pneumocystis carinii carriers among patients with cystic fibrosis.