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Detection of Taenia solium antigens and anti-T. solium antibodies in paired serum and cerebrospinal fluid samples from patients with intraparenchymal or extraparenchymal neurocysticercosis
Background. Neurocysticercosis (NCC) is a frequent cause of epilepsy worldwide. Compared with the more common parenchymal brain cysts, extraparenchymal infections are difficult to manage and have a poor prognosis. Serological assays are used to detect circulating Taenia solium antigens or anti-T. solium antibodies in serum or cerebrospinal fluid (CSF) samples. There are no guidelines on whether to use serum or CSF specimens for a particular assay. Methods. We obtained paired serum and CSF samples from 91 patients with NCC (48 had intraparenchymal NCC, and 43 had extraparenchymal NCC) for detection of antibodies, using an enzyme-linked immunotransfer blot (EITB) assay, and antigens, using a monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA). Results. For the intraparenchymal NCC group, the EITB assay yielded more true-positive results for serum samples, and the ELISA yielded slightly more true-positive results for CSF samples than for serum samples, but none of these differences were statistically significant. Most patients with calcified NCC were antibody positive but antigen negative. For extraparenchymal disease, all samples were antibody positive, and all but 2 were antigen positive, with most samples containing high antigen levels. Conclusions. The sensitivity of antibody-detecting EITB assays is not increased through the use of CSF samples rather than serum samples. The antigen-detecting ELISA performed better for CSF samples than for serum samples, but for both specimen types it was less sensitive than the EITB assay. Active and inactive NCC are better differentiated from each other by the antigen-detecting ELISA, for both serum and CSF samples. High antigen levels suggest the presence of subarachnoid NCC
Three-year outcome data of second-line antiretroviral therapy in Ugandan adults: good virological response but high rate of toxicity
OBJECTIVE: To evaluate the safety and virological response to lopinavir/ritonavir containing second-line therapy after failing a first line nonnucleoside reverse transcriptase inhibitor (NNRTI) based regimen. DESIGN: Prospective 36 months cohort study of patients switched to zidovudine/stavudine plus didanosine plus lopinavir/ritonavir capsules as second-line regimen. METHODOLOGY: Structured interview, medical examination, and laboratory assessment performed every 6 months. RESULTS: We enrolled 40 patients; 1 died and 3 were lost to follow-up. Median CD4+ count at baseline was 108 cell/microL, median log viral load was 4.8 copies/mL. Sixteen (40%) patients had baseline genotypic resistant test, 14 (87%) had lamivudine resistance mutations, and all had NNRTIs resistance mutations. At month 36, 82% of the patients achieved viral suppression (<400 copies/ mL) and the median increase in CD4+ count was 214 cell/microL, (interquartile range: 128-295). Twenty-five patients (62%) experienced at least one adverse event. CONCLUSIONS: Our study confirms lopinavir/ ritonavir-based second-line regimen but with a high rate of toxicities
Coping with TB immune reconstitution inflammatory syndrome
The TB immune reconstitution inflammatory syndrome (IRIS) is a relatively frequent complication in HIV–TB-coinfected patients after they start highly active antiretroviral therapy (HAART). There are two forms of TB IRIS: the ‘paradoxical’ type (clinical worsening of a patient on TB treatment) and the ‘unmasking’ type (undiagnosed TB becoming apparent after starting HAART). Their pathogeneses are not fully understood, although, as the name suggests, IRIS following initiation of HAART is accompanied by an increase in immune responses to Mycobacterium tuberculosis. The diagnosis of TB IRIS is mainly clinical; so far there are no laboratory tests able to diagnose or predict TB IRIS. Risk factors for TB IRIS include a low CD4+ lymphocyte count, disseminated TB infection at HAART initiation and a short interval between TB treatment and HAART initiation. TB IRIS complicates the treatment and care for HIV–TB-coinfected patients. In this paper, we discuss some aspects of pathogenesis and options for the treatment and prevention of TB IRIS
Bilan de santé chez le voyageur asymptomatique de retour des tropiques
Travelers to developing countries may be exposed to several infectious pathogens sometimes leading to complications after a long latency period. Screening of asymptomatic returning travelers is only justified in case of specific risks during travel or after a long tropical stay (> 3 months). Based mainly on the history taking of risk patterns, some occult infections have to be looked for: tuberculosis, sexual transmitted infections and some parasitic conditions (schistosomiasis, amebiasis, strongyloidosis,...). Post-travel screening is most effective about 3 months after return, and may be even more beneficial if associated with screening of major western morbidities and preventive counseling for future travels
Variation spatiale du risque pour les porcs de contracter la trypanosomiase dans la zone périurbaine de Kinshasa
Task shifting: the answer to the human resources crisis in Africa?
ABSTRACT: Ever since the 2006 World Health Report advocated increased community participation and the systematic delegation of tasks to less-specialized cadres, there has been a great deal of debate about the expediency, efficacy and modalities of task shifting.The delegation of tasks from one cadre to another, previously often called substitution, is not a new concept. It has been used in many countries and for many decades, either as a response to emergency needs or as a method to provide adequate care at primary and secondary levels, especially in understaffed rural facilities, to enhance quality and reduce costs. However, rapidly increasing care needs generated by the HIV/AIDS epidemic and accelerating human resource crises in many African countries have given the concept and practice of task shifting new prominence and urgency. Furthermore, the question arises as to whether task shifting and increased community participation can be more than a short-term solution to address the HIV/AIDS crisis and can contribute to a revival of the primary health care approach as an answer to health systems crises.In this commentary we argue that, while task shifting holds great promise, any long-term success of task shifting hinges on serious political and financial commitments. We reason that it requires a comprehensive and integrated reconfiguration of health teams, changed scopes of practice and regulatory frameworks and enhanced training infrastructure, as well as availability of reliable medium- to long-term funding, with time frames of 20 to 30 years instead of three to five years. The concept and practice of community participation needs to be revisited.Most importantly, task shifting strategies require leadership from national governments to ensure an enabling regulatory framework; drive the implementation of relevant policies; guide and support training institutions and ensure adequate resources; and harness the support of the multiple stakeholders. With such leadership and a willingness to learn from those with relevant experience (for example, Brazil, Ethiopia, Malawi, Mozambique and Zambia), task shifting can indeed make a vital contribution to building sustainable, cost-effective and equitable health care systems. Without it, task shifting runs the risk of being yet another unsuccessful health sector reform initiative
A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients
BACKGROUND: Human African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic tropical disease. It progresses from the first, haemolymphatic stage to a neurological second stage due to invasion of parasites into the central nervous system (CNS). As treatment depends on the stage of disease, there is a critical need for tools that efficiently discriminate the two stages of HAT. We hypothesized that markers of brain damage discovered by proteomic strategies and inflammation-related proteins could individually or in combination indicate the CNS invasion by the parasite. METHODS: Cerebrospinal fluid (CSF) originated from parasitologically confirmed Trypanosoma brucei gambiense patients. Patients were staged on the basis of CSF white blood cell (WBC) count and presence of parasites in CSF. One hundred samples were analysed: 21 from stage 1 (no trypanosomes in CSF and 5 WBC/microL) patients. The concentration of H-FABP, GSTP-1 and S100beta in CSF was measured by ELISA. The levels of thirteen inflammation-related proteins (IL-1ra, IL-1beta, IL-6, IL-9, IL-10, G-CSF, VEGF, IFN-gamma, TNF-alpha, CCL2, CCL4, CXCL8 and CXCL10) were determined by bead suspension arrays. RESULTS: CXCL10 most accurately distinguished stage 1 and stage 2 patients, with a sensitivity of 84% and specificity of 100%. Rule Induction Like (RIL) analysis defined a panel characterized by CXCL10, CXCL8 and H-FABP that improved the detection of stage 2 patients to 97% sensitivity and 100% specificity. CONCLUSION: This study highlights the value of CXCL10 as a single biomarker for staging T. b. gambiense-infected HAT patients. Further combination of CXCL10 with H-FABP and CXCL8 results in a panel that efficiently rules in stage 2 HAT patients. As these molecules could potentially be markers of other CNS infections and disorders, these results should be validated in a larger multi-centric cohort including other inflammatory diseases such as cerebral malaria and active tuberculosis
Research ethics review in humanitarian contexts: the experience of the independent ethics review board of Médecins Sans Frontières
Safety and efficacy of dihydroartemisinin-piperaquine in falciparum malaria: a prospective multi-centre individual patient data analysis
BACKGROUND: The fixed dose antimalarial combination of dihydroartemisinin-piperaquine (DP) is a promising new artemisinin-based combination therapy (ACT). We present an individual patient data analysis of efficacy and tolerability in acute uncomplicated falciparum malaria, from seven published randomized clinical trials conducted in Africa and South East Asia using a predefined in-vivo protocol. Comparator drugs were mefloquine-artesunate (MAS3) in Thailand, Myanmar, Laos and Cambodia; artemether-lumefantrine in Uganda; and amodiaquine+sulfadoxine-pyrimethamine and artesunate+amodiaquine in Rwanda. METHODS AND FINDINGS: In total 3,547 patients were enrolled: 1,814 patients (32% children under five years) received DP and 1,733 received a comparator antimalarial at 12 different sites and were followed for 28-63 days. There was no significant heterogeneity between trials. DP was well tolerated with 1.7% early vomiting. There were less adverse events with DP in children and adults compared to MAS3 except for diarrhea; ORs (95%CI) 2.74 (2.13 to 3.51) and 3.11 (2.31 to 4.18), respectively. DP treatment resulted in a rapid clearance of fever and parasitaemia. The PCR genotype corrected efficacy at Day 28 of DP assessed by survival analysis was 98.7% (95%CI 97.6-99.8). DP was superior to the comparator drugs in protecting against both P.falciparum recurrence and recrudescence (P = 0.001, weighted by site). There was no difference between DP and MAS3 in treating P. vivax co-infections and in suppressing the first relapse (median interval to P. vivax recurrence: 6 weeks). Children under 5 y were at higher risk of recurrence for both infections. The proportion of patients developing gametocytaemia (P = 0.002, weighted by site) and the subsequent gametocyte carriage rates were higher with DP (11/1000 person gametocyte week, PGW) than MAS3 (6/1000 PGW, P = 0.001, weighted by site). CONCLUSIONS: DP proved a safe, well tolerated, and highly effective treatment of P.falciparum malaria in Asia and Africa, but the effect on gametocyte carriage was inferior to that of MAS3