Uptake of the lateral flow urine LAM test in Europe and Central Asia.

INTRODUCTION: Since 2015 (updated in 2019), the WHO has recommended to include the commercial lateral flow urine lipoarabinomannan TB test (LF-LAM), AlereLAM, in the diagnostic toolkit for severely ill people living with HIV.METHODS: To assess the current use and barriers to the implementation of the test, we conducted an electronic survey among national focal points and managers of TB and HIV programmes in the 53 Member States of the WHO European Region and a European network of clinicians working in TB and HIV medicine.RESULTS: In all, 45 individual responses (37 countries) were received from programme managers and focal points and 17 responses (14 countries) from clinicians. Only eight countries reported adopting LF-LAM policies, with only four currently using the AlereLAM (Armenia, Belarus, Ukraine and Uzbekistan). The most commonly reported barriers to implementing the test were the small number of eligible patients (with HIV-TB co-infections), the test not being included in the TB or HIV programme´s mandate and lack of budget allocation.CONCLUSION: Consistent with findings from high TB burden countries in Africa and Asia, the survey demonstrated that uptake of AlereLAM is almost non-existent. Addressing the identified barriers and the intrinsic limitations of the test could help to increase the use of the test.

HIV and syphilis infection among gold and diamond miners--Guyana, 2004.

BACKGROUND: Guyana had an estimated HIVprevalence of 1.5% among pregnant women in 2006 (95% confidence interval [CI] = 1.1-1.9). However, a survey of miners in one mine found a 6.5% HIV prevalence in 2002. To determine whether Guyanese miners are at high risk for HIV infection we conducted a HIV and syphilis prevalence survey of miners in several mines. METHODS: Adult male consenting miners in 45 Guyanese mines were interviewed, counselled, tested for HIV and syphilis with rapid tests and provided onsite test results. The survey was cross-sectional and used a multi-stage cluster sampling design; population estimates were calculated using SUDAAN. RESULTS: Of 651 miners approached, 539 (83%) were interviewed and 509 (78%) tested. The estimated prevalence for HIV was 3.9% (CI = 2.1, 7.1) and for life-time syphilis exposure was 6.4% (CI = 4.5, 9.1). Fifty-four per cent (CI = 41.3, 66.7) of miners had casual sex during the preceding year, of whom 44.4% (CI = 34.3, 55.0) had always used condoms with these partners. CONCLUSION: The estimated HIV prevalence among Guyanese miners was higher than that of the general population. Targeted interventions including condom promotion are recommended to prevent further spread of HIV and other sexually transmitted infections among miners.

Tuberculosis infection control measures at health care facilities offering HIV and tuberculosis services in India: A baseline assessment.

BACKGROUND: Tuberculosis (TB) is one of world's oldest infectious disease and ranks alongside HIV as leading infectious killer. Tuberculosis infection control especially in HIV and TB care facilities has warranted attention after the recent health care-associated outbreaks in South Africa. The aim of this study was to describe the tuberculosis infection control measures implemented by HIV and TB care facilities in five high HIV burden provinces in India. METHODS: Baseline assessment of 30 high burden Antiretroviral centers and TB facilities was conducted during Oct 2015-Dec 2015 by AIC trained staff using a structured format. RESULTS: Thirty HIV and TB care facilities in five high HIV burden provinces were enrolled. Facility infrastructure and airborne infection control practices were highly varied between facilities. TB screening and fast tracking at ART centers is happening at majority of centers however inadequate TB infection control training, poor compliance to administrative and personal protective measures and lack of mechanism for health care workers surveillance need attention. CONCLUSIONS: Local specific TB infection control interventions to be designed and implemented at HIV and TB care facilities including implementation of administrative, environmental and use of personal protective equipment's with the training of staff members. Health care workers surveillance needs to be prioritized considering the rising instances of tuberculosis among Health care workers.

Effect of a killer toxin of Pichia anomala to Pneumocystis. Perspectives in the control of pneumocystosis.

Despite the development of drugs in the prophylaxis of pneumocystosis, Pneumocystis carinii remains a major opportunistic microorganism in immunosuppressed individuals, especially in human immunodeficiency virus-infected patients. Since side effects were frequently observed after administration of trimethoprim-sulfamethoxazole or pentamidine, the drugs which are mainly used in treating human P. carinii pneumonia (PCP), new therapeutic strategies should be developed. Over the last years, the inhibitory effect of a Pichia anomala killer toxin (PaKT), a molecule with a wide spectrum of antimicrobial activity, was characterized on P. carinii. The susceptibility of mouse and rat-derived Pneumocystis to PaKT has been demonstrated by in vitro attachment tests and in vivo infectivity assays. Nevertheless, PaKT is strongly antigenic, toxic and could not be used directly as a therapeutic agent. Then, a new strategy using killer toxin-like anti-idiotypic antibodies (KT-antiIds) mimicking the fungal toxin activity has been developed. Different KT-antiIds were obtained by idiotypic immunization with a monoclonal antibody (mabKT4). This mabKT4 neutralized the killer properties of the PaKT. KT-antiIds were produced by immunization against the variable domain (idiotype) of mAbKT4 (internal image of the killer toxin receptor), or they were obtained directly from vaginal fluid of patients affected by recurrent vaginal candidiosis. In this last case, such natural KT-antiIds were immunopurified by affinity-chromatography with mAbKT4 and their anti-P. carinii activity was then evaluated. Our results showed that both the in vitro attachment of rat-derived parasites and their infectivity to nude rats were inhibited by the KT-antiIds. With regard to KT-antiIds obtained by immunization, the antimicrobial activity of a monoclonal KT-antiIds (mAbK10) has been evaluated by using a PCP experimental nude rat model treated by mAbK10 administered by aerosol. The pneumocystosis extension was significantly reduced in this model. The monoclonal KT-antiIds were effective against P. carinii in reducing parasite proliferation in lungs of nude rats. Further experiments are in progress to study the in vivo anti-P. carinii activity of KT-antiIds by using recombinant single-chain of the variable fragment of KT-antiIds. Yeast killer toxin-like recombinant molecules could provide the basis for a new therapeutic strategy towards the control of pneumocystosis.

Toxic action of ethylene oxide on pulmonary cells (L132) cultured under aerobic conditions.

In environmental health, inhalation is the most prominent route of ethylene oxide (EO) exposure. In the current study, human embryonic pulmonary epithelial cells (L132 cell line) were exposed to EO following a prior adaptation to atmospheric conditions. A comparative study between two EO exposure conditions (0.07 and 0.18 g/m3 gas injections) was carried out after a 1-h incubation. Whereas control cells were exposed to a pure air stream. The EO cytotoxicity was established by electron microscopy and LDH and ATP determinations after 1, 3, 6 and 24 h following the exposure. The ultrastructural examination revealed a remarkable vacuolisation of the exposed cells leading to cell death. In spite of this modification, the number of mitochondria and the content of endoplasmic reticulum increased in the L132 cells. For both exposure concentrations LDH was released into the extracellular milieu. In the presence of the high EO concentration, LDH activity increased with respect to the post-exposure time involving alteration of the membrane and permeability. For low EO exposure, ATP synthesis was significantly increased after 1 h of post-exposure (P < 0.01) and decreased to normal levels after 6 h. For the high EO concentration, however, ATP continually increased with respect to the post-exposure time. This indicates cellular stimulation and suggests the activation of a defense mechanism. This study shows a direct EO cytotoxicity on L132 cells cultured in atmospheric conditions.

The yeast killer phenomenon: a hypothetical way to control Pneumocystis carinii pneumonia.

Pneumocystis carinii is an important agent of pneumonia in immunocompromised individuals, especially in acquired immunodeficiency syndrome AIDS patients P. carinii attaches specifically to type 1 pneumocytes. Although this phenomenon must play a marked role in pneumocystosis pathophysiology, no therapeutic molecules able to inhibit specifically the parasite attachment were found. A killer toxin, secreted by the yeast Pichia anomala, induced a significant decrease in P. carinii in vitro attachment and inhibited the parasite infectivity in SCID mice. Killer toxins cannot be used as systemic antibiotics. However, it was possible to produce antiidiotypic antibodies against a monoclonal antibody specific of the toxin active site. These antilds were shown to mimic the in vitro killer effect for the toxin and were called 'antibiobodies'. The susceptibility of P. carinii to the antimicrobial activity of the killer toxin made it possible to hypothesize that the killer phenomenon could constitute a new way for the treatment and prophylaxis of P. carinii infections.

Evaluation of the consistency of refills for antiretroviral medications in two hospitals in the state of Rio de Janeiro, Brazil.

We conducted a retrospective cohort study using pharmacy records to assess the frequency of delay in picking up antiretroviral (ARV) medication refills from the pharmacy and to identify determinants of delay among HIV-infected patients at two Brazilian hospitals. We selected patients who were on ARV therapy before January 2001 at Nova Iguaçu Hospital (NIPRH) (N = 265) and Evandro Chagas (N=424) Clinical Research Institute. We abstracted medical records and pharmacy data using standardised forms and analysed potential associations between delay in refilling medications and patients' demographic characteristics, type of ARV drug regimen and evolution of HIV disease. Sixty-nine patients (26%) had delays in medication refills >1 month at least once in 2001 at NIPRH compared with 140 (33%) patients at IPEC (p=0.052). No factor was found to be associated with having a delay in medication refill >1 month at NIPRH. At IPEC, delays in medication refill >1 month were associated with a median CD4+ T cell count <200/mm(3) versus >500/mm(3) (adjusted odds ratio (AOR) = 3.8; 95% confidence interval (CI) =1.6-8.9) and with dual protease inhibitor-based ARV regimens versus other regimens (AOR = 4.3; 95% CI = 1.9-9.4). In conclusion, rates of delay in medication refills were similar to rates of adherence to ARV therapy found in other studies in Brazil, suggesting that delay in medication refills could be used as a surrogate for adherence. Analysing ARV medication refills can complement self-reported information on adherence.

Inhibitory effect of a Pichia anomala killer toxin on Pneumocystis carinii infectivity to the SCID mouse.

A Pichia anomala killer toxin has been demonstrated to have a specific inhibitory effect on the in vitro attachment of Pneumocystis carinii. The results presented herein show that this yeast toxin is also effective against P. carinii infectivity in reducing parasite colonization in the lungs of SCID mice. The specificity of this inhibitory effect was controlled using a monoclonal antibody neutralizing the killer properties of the yeast toxin.

Killer toxin secretion through the cell wall of the yeast Pichia anomala.

A secreted killer toxin was detected through the cell wall of Pichia anomala cells by ultrastructural immunodetection with a specific monoclonal antibody (MAb KT4). MAb KT4 was successively detected by colloidal gold labeled streptavidin and biotinylated anti-mouse F(ab')2 antibodies. The antigenic determinants of the toxin were localized throughout the cytoplasm and the cell wall of killer yeast cells. The Lowicryl K4M-immunogold method gave very satisfactory results and showed that the killer toxin was somewhat concentrated in the yeast cell wall layers before being exported into the medium. In agreement with previous reports, the binding of MAb KT4 suggested that the P. anomala killer toxin secretion did not result from a homogeneous diffusion across the yeast cell wall.

Monoclonal yeast killer toxin-like candidacidal anti-idiotypic antibodies.

Rat monoclonal yeast killer toxin (KT)-like immunoglobulin M (IgM) anti-idiotypic antibodies (KT-IdAbs) were produced by idiotypic vaccination with a mouse monoclonal antibody (MAb; MAb KT4) that neutralized a Pichia anomala KT characterized by a wide spectrum of antimicrobial activity. The characteristics of the KT-IdAbs were demonstrated by their capacity to compete with the KT to the idiotype of MAb KT4 and to interact with putative KT cell wall receptors (KTRs) of sensitive Candida albicans cells. The internal-image properties of KT-IdAbs were proven by their killer activity against KT-sensitive yeasts. This lethal effect was abolished by prior adsorption of KT-IdAbs with MAb KT4. These findings stressed the potential importance of antibody-mediated immunoprotection against candidiasis and suggested a feasible experimental approach for producing antimicrobial receptor antibodies without purifying the receptor. KT-IdAbs might represent the basis for producing engineered derivatives with a high potential for effective therapeutic antifungal activity.

Inhibitory effect of human natural yeast killer toxin-like candidacidal antibodies on Pneumocystis carinii.

BACKGROUND: Human natural antibodies have been found that owe their candidacidal action to the mimicry of a yeast killer toxin produced by the yeast Pichia anomala (PaKT). Candidacidal human natural antibodies (KTAb) are elicited by and bind to a KT receptor (PaKTR) present on the cell surface of infectious PaKT-sensitive microorganisms. Because of the recognized susceptibility of Pneumocystis carinii organisms to PaKT upon the occurrence of specific PaKTR, we examined whether human natural KTAb could also bind to and inhibit P. carinii. MATERIALS AND METHODS: Immunoaffinity-purified KTAb from the vaginal fluid of patients affected by candidiasis were tested and compared with PaKT for their ability to inhibit rat-derived P. carinii attachment to epithelial lung cells as well as infectivity to nude rats. Immunofluorescence studies were also performed by biotinylated PaKT in competition with human KTAb to establish their specific binding to PaKTR on the surface of rat-derived and human P. carinii organisms. RESULTS: Human natural candidacidal KTAb exerted a strong, specific inhibitory activity against rat-derived P. carinii organisms that are susceptible to PaKT itself. The antimicrobial activity of human KTAb was abolished by adsorption with a specific PaKT-neutralizing mAb KT4. Immunofluorescence studies of competition with PaKT showed that human KTAb efficiently bind to the specific PaKTR on the surface of rat-derived and human P. carinii organisms. CONCLUSIONS: The results strongly suggest that human KTAb, elicited by a common transphyletic receptor of different pathogenic microorganisms during infection, may play a role in antibody-mediated cross-immunity and, if properly engineered, as functionally equivalent recombinant antibodies they could exert a therapeutic activity against pneumocystosis in vivo.

Transmission of Pneumocystis carinii disease from immunocompetent contacts of infected hosts to susceptible hosts.

Pneumocystis carinii organisms constitute a large group of heterogeneous atypical microscopic fungi that are able to infect immunocompromised mammals by an airborne route and to proliferate in their lungs, inducing Pneumocystis carinii pneumonia. This pneumonia remains a crucial epidemiological challenge, since neither the source of Pneumocystis carinii infection in humans nor the process by which humans become infected has been clearly established. Polymerase chain reaction (PCR) assays have shown that profoundly immunosuppressed patients without pneumocystosis can be subclinically infected with Pneumocystis. Other PCR-based studies have suggested that healthy immunocompetent hosts are not latent carriers of the parasite. However, recent reports have indicated that Pneumocystis carinii can persist for limited periods in the lungs of convalescent rats after recovery from corticosteroid-induced pneumocystosis, and also that immunocompetent mammals can be transiently parasitized by Pneumocystis carinii after close contact with hosts with Pneumocystis carinii pneumonia. Can transiently parasitized hosts be a source of infection for immunosuppressed hosts? In order to investigate this important clinical question, the ability of immunocompetent BALB/c mice, which were carrying subclinical levels of Pneumocystis carinii, to transmit the infection by the airborne route to highly susceptible, uninfected mice with severe combined immunodeficiency was studied. The results indicated that the immunocompetent mice, transiently parasitized by Pneumocystis carinii organisms after close contact with Pneumocystis carinii-infected mice, were able to transmit the infection to Pneumocystis carinii-free mice with severe combined immunodeficiency.

Pneumocystis carinii: an atypical fungal micro-organism.

The purpose of this review is to assist mycologists in having a better understanding of Pneumocystis carinii and the disease that it causes. Now considered to be a fungus, P. carinii is unusual in its life cycle and relationship with the host. P. carinii pneumonia (PCP) pathogenesis, immunology and host defence mechanisms are examined, as well as epidemiological and control strategies. Most pneumocystosis pathophysiological changes result from the parasite's attachment and proliferation in the lungs, resulting in a filling of the alveoli with masses of the micro-organism. Pathological changes include an increase in alveolar capillary membrane permeability and injury to the alveolar epithelium, which may be mediated by the release of degradative enzymes from the pathogen. A host response takes place by hypertrophy, and hyperplasia involving type II epithelial alveolar cells. P carinii interacts with pulmonary surfactants by binding to the hydrophilic proteins A and D, and by modifying their phospholipid composition. Alveolar macrophages and CD4+ T cells play a key role in the host's defence against Pneumocystis. The epidemiology of PCP remains poorly understood. Airborne transmission has been established, but the actual infective form and its source remains unknown. Studies concerning P. carinii genetic diversity have shown that the parasite polymorphism is related, at least partially, to the host species. A strong host-species specificity in P. carinii has been found. From an epidemiological perspective, there appears to be no animal reservoir for the agent of human PCP. Thus, this disease should not be considered to be zoonotic. Although a significant decrease in the incidence of pneumocystosis has been obtained when employing chemoprophylaxis, anti-P. carinii drugs are not completely successful, often inducing deleterious side-effects. For these reasons, new prophylactic and therapeutic strategies need to be developed. One approach could be based on the anti-P. carinii effect of yeast killer toxins and antibiotic anti-idiotypic antibodies.

HIV and syphilis infection among gold and diamond miners - Guyana, 2004 / La Infección por sífilis o VIH entre los mineros de oro y diamante - Guyana, 2004

BACKGROUND: Guyana had an estimated HIV prevalence of 1.5% among pregnant women in 2006 (95% confidence interval [CI] = 1.1-1.9). However, a survey of miners in one mine found a 6.5% HIV prevalence in 2002. To determine whether Guyanese miners are at high risk for HIV infection we conducted a HIV and syphilis prevalence survey of miners in several mines. METHODS: Adult male consenting miners in 45 Guyanese mines were interviewed, counselled, tested for HIV and syphilis with rapid tests and provided onsite test results. The survey was cross-sectional and used a multi-stage cluster sampling design; population estimates were calculated using SUDAAN. RESULTS: Of 651 miners approached, 539 (83%) were interviewed and 509 (78%) tested. The estimated prevalence for HIV was 3.9% (CI = 2.1, 7.1) and for life-time syphilis exposure was 6.4% (CI = 4.5, 9.1). Fifty-four per cent (CI = 41.3, 66.7) of miners had casual sex during the preceding year, of whom 44.4% (CI = 34.3, 55.0) had always used condoms with these partners. CONCLUSION: The estimated HIV prevalence among Guyanese miners was higher than that of the general population. Targeted interventions including condom promotion are recommended to prevent further spread of HIV and other sexually transmitted infections among miners.

ANTECEDENTES: Guyana tenía un estimado de prevalencia de VIH de 1.5% entre las mujeres embarazadas en 2006 (95% intervalo de confianza [CI] =1.1-1.9). Sin embargo, una encuesta realizada a mineros en una mina, reveló una prevalencia de un 65% de VIH en 2002. Para determinar si los mineros guyaneses se hallan en un alto riesgo de infección por VIH, llevamos a cabo un estudio de la prevalencia de sífilis y VIH entre los mineros en varias minas. MÉTODOS: Mineros varones adultos en 45 minas guyaneses, fueron entrevistados previo consentimiento, recibieron aconsejamiento (counselling), y fueron sometidos a pruebas de detección de VIH y sífilis mediante tests rápidos que proveyeron resultados en el sitio. La encuesta fue transversal y usó un diseño de muestreo por conglomerados en etapas múltiples. Los estimados de la población fueron calculados usando SUDAAN. RESULTADOS: De 651 mineros abordados, 539 (83%) fueron entrevistados y a 509 (78%) se les aplicó la prueba. El estimado de la prevalencia de VIH fue 3.9% (CI = 2.1, 7.1) y la de la exposición a la sífilis de por vida fue 6.4% (CI = 4.5, 9.1). Cincuenta y cuatro por ciento (CI = 41.3, 66.7) de los mineros tuvieron sexo casual el año anterior, de los cuales 44.4% (CI = 34.3, 55.0) había usado siempre condones con sus parejas. CONCLUSIÓN: La prevelancia estimada de VIH entre los mineros guyaneses fue más alta que la de la población general. Se recomiendan intervenciones, incluyendo la promoción de condones, dirigidas a prevenir la ulterior difusión del VIH y otras enfermedades de trasmisión sexual entre los mineros.