Isolation unit for multidrug-resistant tuberculosis patients in a low endemic country, a step towards the World Health Organization End TB Strategy.

Tuberculosis (TB) remains a threat to public health and is the second cause of death due to a single infectious agent after HIV/AIDS. The worldwide distribution of TB is heterogeneous. The incidence is decreasing in most high-income regions, but the situation remains worrying in many parts of the world. The emergence of Mycobacterium tuberculosis strains resistant to key agents used in treatment (rifampin and isoniazid) contributes to TB transmission around the world. To achieve TB elimination, both high and low endemic countries must upscale their efforts to decrease disease transmission and improve cure rates. Management of drug-resistant TB is of particular importance. In this paper, we discuss the different models of care of multidrug-resistant TB (MDR-TB), the ethical considerations and the specific constraints present in high income countries. The management model chosen by the Belgian TB specialists in accordance with public health authorities as well as building of a specific MDR/XDR-TB isolation unit are also discussed.

[HIV infection : Reaching a zero risk of transmission]. / Transmission du VIH : Est-ce une fatalité ?

Despite a global reduction in the prevalence of HIV-infection, the HIV-epidemic is far from over. The prevention of HIV-transmission in all its forms (sexual, mother-to-child etc) must therefore remain a pillar in the fight against AIDS, and both potent and accessible prevention strategies are required. In addition to the classical and wellknown methods such as the condom, ant iretroviral therapy represents a potent prevention tool and the residual risk of transmission of correctly treated HIV-positive persons is virtually nihil. Antiretroviral therapy may and should be used in the prevention of HIV-transmission as Treatment as Prevention (TasP), Pre-Exposure Prophylaxis (PrEP), and Post- Exposure Prophylaxis (PEP). However, because of their exorbitant costs, the accessibility of these prevention strategies is limited, particularly for the most vulnerable populations.

Si l'infection par le VIH est globalement en diminution dans le monde, nous n'apercevons pas encore la fin de l'épidémie. Dès lors, nous avons besoin de moyens performants et accessibles pour tous pour diminuer la transmission du virus, essentiellement sexuelle mais aussi via la transmission de la mère à son enfant. En plus des moyens utilisés de façon répandue tel que le préservatif, le traitement antirétroviral représente à ce jour un outil très performant en termes de prévention, à travers la prophylaxie pré-exposition, la prophylaxie postexposition et le traitement de la personne infectée qui voit son risque de transmission virtuellement annulé. Néanmoins, l'accès à ces molécules coûteuses reste difficile pour les populations les plus défavorisées.

Implementation of latent tuberculosis screening in HIV care centres: evaluation in a low tuberculosis incidence setting.

The screening and treatment of latent tuberculosis infection (LTBI) to prevent active tuberculosis (TB) is recommended by the WHO in all HIV-infected patients. The aim of this study was to evaluate its implementation within Belgium's HIV care. A multiple-choice questionnaire was sent to 55 physicians working in the country's AIDS reference centres. Response rate reached 62%. Only 20% screened all their HIV-infected patients for LTBI. Screening methods used and their interpretation vary from one physician to another. The main barriers to the implementation of LTBI screening and treatment, as perceived by the participants, are lack of sensitivity of screening tools, risks associated with polypharmacy and toxicity of treatment. The poor coverage of LTBI screening reported here and the inconsistency in methods used raises concern. However, this was not unexpected as, in low-TB incidence countries, who, when and how to screen for LTBI remains unclear and published guidelines show important disparities. Recently, a targeted approach in which only HIV-infected patients at highest risk of TB are screened has been suggested. Such a strategy would limit unnecessary exposure to LTBI treatment. This methodology was approved by 80% of the participants and could therefore achieve greater coverage. Its clinical validation is still pending.

Long-incubation-time gamma interferon release assays in response to purified protein derivative, ESAT-6, and/or CFP-10 for the diagnosis of Mycobacterium tuberculosis infection in children.

The diagnosis of childhood active tuberculosis (aTB) and latent Mycobacterium tuberculosis (M. tuberculosis) infection (LTBI) remains a challenge, and the replacement of tuberculin skin tests (TST) with commercialized gamma interferon (IFN-γ) release assays (IGRA) is not currently recommended. Two hundred sixty-six children between 1 month and 15 years of age, 214 of whom were at risk of recent M. tuberculosis infection and 51 who were included as controls, were prospectively enrolled in our study. According to the results of a clinical evaluation, TST, chest X ray, and microbiological assessment, each children was classified as noninfected, having LTBI, or having aTB. Long-incubation-time purified protein derivative (PPD), ESAT-6, and CFP-10 IGRA were performed and evaluated for their accuracy in correctly classifying the children. Whereas both TST and PPD IGRA were suboptimal for detecting aTB, combining the CFP-10 IGRA with a TST or with a PPD IGRA allowed us to detect all the children with aTB with a specificity of 96% for children who were positive for the CFP-10 IGRA. Moreover, the combination of the CFP-10 IGRA and PPD IGRA detected 96% of children who were eventually classified as having LTBI, but a strong IFN-γ response to CFP-10 (defined as >500 pg/ml) was highly suggestive of aTB, at least among the children who were <3 years old. The use of long-incubation-time CFP-10 IGRA and PPD IGRA should help clinicians to quickly identify aTB or LTBI in young children.

[Screening for tuberculosis]. / Le dépistage de la tuberculose.

Rapid identification using bacteriological methods and adequate treatment of active tuberculosis cases are the most important objective of any tuberculosis activity but, in order to eliminate the disease, another important component of tuberculosis control is to reduce the vast reservoir of latent tuberculosis infections. Tuberculin skin test and interferon-gamma release assays are designed to identify immune response against mycobacterial antigens. Both tests are accurate to detect latent but not active forms of tuberculosis. Interferon-gamma release assays have higher specificity than tuberculin skin testing in BCG-vaccinated populations particularly if BCG was administered after 1 year of age. Both tests perform poorly to predict risk for progression to active tuberculosis. Screening should therefore be limited to situations with a clear likelihood of transmission after contact, taking account of the infectiousness of the index case and the intensity of exposure, or to those with a great probability of developing tuberculosis: young children and immunocompromised persons.

[Which immunizations for which adults in 2011?]. / Quelles vaccinations pour quels adultes en 2011?

Immunizations are extremely efficient in prevention of diseases with a lethal potential. Healthy adults, pregnant women and patients suffering from chronic diseases may have a different benefit from vaccine available in our country. Numerous health problems need to be addressed during a short consultation, relegating immunization to a position of secondary importance. This paper will address the issue of immunization in special circumstances such as: healthy adults, pregnant women, HIV-infected patients, patients with end-stage renal disease, patients with chronic liver diseases and solid organ transplant candidates and recipients.

[Pulmonary tuberculosis]. / La tuberculose pulmonaire.

Tuberculosis (TB) is a global health problem driven by poverty, HIV infection, etc. In Europe, the problem of multidrug resistance (i.e., resistance to at least rifampin and isoniazid) (MR) develops. The cases come essentially from the former U.S.S.R. In Belgium, the incidence of tuberculosis continues to decline to 9.4/100,000 inhabitants in 2008. The percentage of MR germs is 2.8%. The distribution of cases is not uniform across the country. The incidence is much higher among people recently coming from high prevalence countries than among the Belgian native. The pulmonary forms of TB are more contagious and more common. The clinical signs are frequently non specific. The diagnosis is often mentioned up after performing a chest Xray and must always be confirmed by microbiological examination and culture of several sputum or other respiratory specimens. It is very important to identify the germ, M. tuberculosis complex and to test its sensitivity to anti-TB agents. Standard treatment consists of 4 drugs: isoniazid, rifampin, ethambutol and pyrazinamide for 2 months followed by rifampin and isoniazid for at least 4 additional months. In suspected cases of MR, 5 drugs are prescribed at the outset. Treatment and duration will be adjusted according to the results of susceptibility testing. The potential toxicities of second-line drugs should be well known by the physicians. Compliance of the patient is essential. Screening in the entourage is part of the therapeutic process.

Paradoxical worsening of tuberculosis in a heart-lung transplant recipient.

UNLABELLED: We report on a heart-lung transplant recipient who presented with pulmonary tuberculosis (TB) 2.5 months after transplantation and then developed a paradoxical reaction after 4 months of adequate anti-TB treatment. She eventually recovered with anti-TB and high-dose steroid treatments. METHODS: Using sequential bronchoalveolar lavages, we assessed the inflammatory response in the lung and investigated the alveolar immune response against a Mycobacterium tuberculosis antigen. RESULTS: The paradoxical reaction was characterized by a massive infiltration of the alveolar space by M. tuberculosis antigen-specific CD4(+) T cells and by the presence of a CD4(-)CD8(-) T lymphocyte subpopulation bearing phenotypic markers (CD16(+)/56(+)) classically associated with NK cells. CONCLUSION: This case report illustrates that even solid organ transplant recipients receiving intense triple-drug immune suppression may be able to develop a paradoxical reaction during TB treatment. Transplant physicians should be aware of this phenomenon in order to differentiate it from treatment failure.

Human herpesvirus 8 investigations: a role in the clinical management of Kaposi's sarcoma?

Kaposi's sarcoma (KS) is a vascular tumour associated with infection by human herpesvirus 8 (HHV-8). Most of the recent studies on KS have focused on the epidemiology and molecular biology of HHV-8. However, the contribution of virological investigations into HHV-8 to the clinical management of KS has been poorly evaluated so far. From a diagnostic point of view, HHV-8 currently appears as a useful tool for distinguishing KS from its mimics. Seroconversion to antibodies against HHV-8 may predict the development of KS in susceptible individuals, and reduction of HHV-8 viraemia is associated with therapies effective against KS. Further prospective studies are still required to determine the role of serological or genotypic investigations into HHV-8 in the prevention of KS and in KS response to therapy.

[Medically assisted reproduction in couples carrying the human immunodeficiency virus]. / L'assistance médicale à la procréation chez les couples porteurs du virus de l'immunodéficience humaine.

Today, in developed countries, many HIV-infected people remain in good health thanks to antiviral medication, and a growing number of them want to have children. The benefit of resorting to assisted procreation and the contamination prevention strategies, throughout pregnancy, are summarized as well as the changes in ethical considerations. The balance between the importance of the message of prevention and the benefit for patients of being assisted in their desire for a child, has evolved towards a growing interest for medical intervention in order to avoid the risks of spontaneous conception outside health care structures. We are presenting the medical structure adapted at Erasme hospital and the 38 first requests taken into account by our pluridisciplinary team. This approach, which is coherent from a scientific point of view, respects both the autonomy of people, carrying HIV as well as the essential interest of the child, in being born uninfected, and also has the enormous advantage of allowing access to parenthood without destroying the consistency and coherence of the message of prevention of sexual contamination.

Stimulation of Kaposi's sarcoma cell growth by urine from women in early pregnancy, the current source for clinical-grade human chorionic gonadotropin preparations.

Clinical-grade preparations of human chorionic gonadotropin (hCG) have been shown to be toxic to Kaposi's sarcoma (KS) cells. However, the results of clinical studies using commercial hCG preparations KS remain highly contradictory. More particularly, some hCG preparations could have a paradoxical growth effect on KS. Such discrepant results may be explained by the fact that the anti-KS activity is not associated with hCG itself but with one or more factors that are co-purified with the hormone. We found here that crude urine from first trimester pregnant women, the current source for commercial hCG, had a growth stimulatory effect on KS cells. By contrast, urine from last trimester pregnant women, from non-pregnant young women, from menopausal women and from men exhibited neither a growth stimulatory nor a growth inhibitory effect on KS cells. The amplitude of this pregnancy urine-associated pro-KS activity/hCG unit was higher than that achieved with clinical-grade hCG preparations. Partial co-purification of pregnancy-associated factors during the extraction procedure of commercial hCG from urine may explain the pro-KS activity achieved with some hCG preparations. We, therefore, suggest a cautious use of hCG purified from pregnancy urine for the treatment of KS.

Enhancement of classic Kaposi's sarcoma growth after intralesional injections of desferrioxamine.

We have previously shown that iron may be involved in the pathogenesis of Kaposi's sarcoma (KS) and that the iron chelator desferrioxamine (DFO) inhibits the growth and induces the apoptosis of KS cells in vitro. We treated an 85-year-old man with classic KS with 5 weekly intralesional injections of DFO and observed the opposite effect in vivo. The DFO-treated lesion was characterised by the development of numerous KS papules within the drug diffusion area, whereas no change was noted in untreated or control saline-treated lesions. This suggests that intralesional iron chelators are not indicated in patients with KS.

Treatment of Kaposi's sarcoma with human chorionic gonadotropin.

Clinical-grade preparations of human chorionic gonadotropin (hCG) have been shown to be toxic to Kaposi's sarcoma (KS) cells. However, the mechanism of the anti-KS activity achieved with these preparations remains unclear. The results of clinical studies using commercial hCG preparations in human KS are also highly contradictory. The apparent controversy between different studies may be due to the fact that pro- and anti-KS components are present in varying proportions in different hCG preparations. As certain hCG preparations could not only lack the ability to control KS but also contain some contaminant KS growth factor(s), we suggest a cautious use of crude hCG for the treatment of KS.

High-dose chemotherapy and autologous CD34-positive blood stem cell transplantation for multiple myeloma in an HIV carrier.

The epidemiology and clinical outcome of multiple myeloma in human immunodeficiency virus (HIV)-positive patients is poorly documented. There are uncertainties concerning the optimal management of this rare disorder. We report on the use of myeloablative chemotherapy with autologous stem cell transplantation in an HIV-positive patient with multiple myeloma.

[Gastrointestinal infections in the immunocompromised patient]. / Infections gastro-intestinales chez le patient immunocompromis.

The gastrointestinal tract is frequently involved in immunocompromised hosts. The most common digestive manifestations are dysphagia, odynophagia and diarrhea. These diseases are more frequent in patients with acquired immunodeficiency virus (AIDS).These GI diseases are of several categories: HIV related inflammatory conditions (HIV related enteropathy, idiopathic esophageal ulceration), infections due to germs also commonly present in immunocompetent patients (Salmonellosis, shigellosis,…), opportunistic infections (CMV, Mucormycosis,Cryptosporidium, Mycobacterium, Isospora belli,…).The prevalence, pathogenesis, clinical manifestation, gross pathological findings and microscopic features are discussed for each entity.

[The immunodeficiency treatment unit]. / L'Unité de Traitement des Immunodéficiences.

Physicians of the unit have first taken care of patients with acquired Immunodeficiency in 1981. We have become an independent "Reference Centre" in 1998. The multidisciplinary team follows more than 300 patients on a regular basis. AIDS has been amply publicized, but other immuno-deficiencies have not. Primary immunodeficiencies are "orphan" diseases; they can be as serious, or more severe even, than AIDS. About 60 patients with "PID" are followed by the team. We are involved in research, and have participated in the identification of a mutation of an HIV co receptor that protects against HIV infection. We also studied the pathogenesis of Kaposi's sarcoma, and the immunological basis of adverse reactions to intravenous gammaglobulins.

[NTBR (Not to Be Resuscitated) in 10 questions]. / NTBR en 10 questions.

The term "Not To Be Resuscitated" or "NTBR" is largely used in hospitals in the setting of therapeutic limitations. However, interpretations of this term are sometimes very different. The objective of this article is to define the exact meaning of "NTBR", namely, no resuscitation only in case of cardiac arrest. The rules for therapeutic limitation are also defined.

Immunologic and virologic response after tetanus toxoid booster among HIV-1- and HIV-2-infected Senegalese individuals.

Twelve HIV-1-infected, nine HIV-2-infected patients and eight HIV-negative subjects were given a 40IU booster dose of tetanus toxoid (TT). Blood was collected on days 0, 7 and 30 after immunization. Changes in HIV-1 or HIV-2 RNA load were evaluated by nested PCR. TT-IgG antibody levels were quantified by ELISA. CD4 cell counts as well as activation, memory and maturation markers of T lymphocyte subsets were determined by flow cytometry. The induction of apoptosis was investigated using 7-aminoactinomycin D (AAD) and propidium iodide (PI) staining. Proliferative responses to TT and pokeweed mitogen (PWM) were determined by the level of [(3)H] thymidine incorporation. Seven and 30 days after immunization, there was no detectable increase in HIV-1 or HIV-2 plasma load. There were also no changes in CD4 cell counts, CD69, HLA-DR and memory CD45RO or naive CD45RA antigens. Immunization did not increase the spontaneous apoptosis of peripheral blood mononuclear cells (PBMCs), CD4+ and CD8+ T cells subsets neither in controls nor in HIV-infected patients. Similarly, apoptosis induced in vitro by PWM or by the specific TT recall antigen did not vary during the study period. The proliferative response to PWM and to the TT recall antigen was decreased both in HIV-1- and HIV-2-infected patients compared to HIV-negative controls. Immunization significantly increased the TT-IgG levels in healthy controls and in HIV-infected patients. However, the anti-TT-IgG response, as measured by the fold-increase index between days 0 and 30, was significantly higher in healthy controls than in HIV-1- (P=0.036) and HIV-2-infected patients (P=0.003). In conclusion, we found no deleterious immunologic or virologic effect was detected in healthy HIV-1- and HIV-2-infected individuals after antigenic challenge with a TT booster. However, the response to TT vaccination was lower in HIV-1- and in HIV-2-infected individuals than in healthy HIV-negative controls.