Constraints in the diagnosis and treatment of Lassa Fever and the effect on mortality in hospitalized children and women with obstetric conditions in a rural district hospital in Sierra Leone.

BACKGROUND: Lassa fever (LF) is an acute viral haemorrhagic infection, endemic in West Africa. Confirmatory diagnosis and treatment (ribavirin) is difficult, expensive, and restricted to specialised hospitals. Among confirmed and suspected LF cases, we report on clinical and laboratory features, timing and administration of ribavirin and the relationship with case fatality. METHODS: We conducted an audit of patient files of suspected LF cases admitted to a pediatric and obstetric referral hospital in rural Sierra Leone (April 2011 to February 2012). RESULTS: There were 84 suspected LF cases; 36 (43%) were laboratory-confirmed cases, of whom only 20 (56%) received ribavirin after a median duration of eight days (IQR 314 days) of hospital admission. Of 16 patients who did not receive ribavirin, 14 (87%) died before ribavirin treatment could be commenced. Starting ribavirin within six days of admission was associated with a case fatality of 29% (2/7), while starting ribavirin later than six days was associated with a case fatality of 50% (6/12). Among the 48 suspected LF cases without laboratory confirmation, there were 21 (44%) deaths. CONCLUSIONS: These findings highlight shortcomings in LF management, including diagnostic and treatment delays. More research and development efforts should be devoted to this 'neglected disease'.

Non-adherence to standard treatment guidelines in a rural paediatric hospital in Sierra Leone.

SETTING: A rural paediatric hospital in Bo, Sierra Leone. OBJECTIVES: To assess the level of adherence to standard treatment guidelines among clinicians prescribing treatment for children admitted with a diagnosis of malaria and/or lower respiratory tract infection (LRTI), and determine the association between (non) adherence and hospital outcomes, given that non-rational use of medicines is a serious global problem. DESIGN: Secondary analysis of routine programme data. RESULTS: Data were collected for 865 children admitted with an entry diagnosis of malaria and 690 children with LRTI during the period January to April 2011; some patients were classified in both categories. Non-adherence to guidelines comprised use of non-standard drug regimens, dosage variations, non-standard frequency of administration and treatment duration. Cumulative non-adherence to guidelines for LRTI cases was 86%. For malaria, this involved 12% of patients. Potentially harmful non-adherence was significantly associated with an unfavourable hospital outcome, both for malaria and for LRTI cases. CONCLUSIONS: Overall non-adherence to standard treatment guidelines by clinicians in a routine hospital setting is very high and influences hospital outcomes. This study advocates for the implementation of routine measures to monitor and improve rational drug use and the quality of clinical care in such hospitals.

Peanut-based ready-to-use therapeutic food: acceptability among malnourished children and community workers in Bangladesh.

OBJECTIVES: To assess the acceptability of a ready-to-use therapeutic food (Plumpy'nut(®) [PPN]) among 1) care givers of malnourished children and 2) community health workers (CHWs) at a nutrition rehabilitation centre in an urban slum in Dhaka, Bangladesh. METHODS: This was a cross-sectional semi-structured questionnaire survey conducted between April and June 2011 as part of a nutritional programme run by Médecins Sans Frontières. The study population included care givers of malnourished children aged 6-59 months who received PPN for at least 3 weeks, and CHWs. RESULTS: Of the 149 care givers (93% female) interviewed, 60% expressed problems with PPN acceptability. Overall, 43% perceived the child's dissatisfaction with the taste, 31% with consistency and 64% attributed side effects to PPN (nausea, vomiting, loose motion, diarrhoea, abdominal distension and pain). It is to be noted that 47% of children needed encouragement or were forced to eat PPN, while 5% completely rejected it after 3 weeks. Of the 29 CHWs interviewed, 48% were dissatisfied with PPN's taste and consistency, and 55% with its smell. However, 91% of the care givers and all CHWs still perceived a therapeutic benefit of PPN for malnourished children. CONCLUSION: Despite a therapeutic benefit, only 4 in 10 care givers perceived PPN as being acceptable as a food product, which is of concern.

Out-of-pocket costs of AIDS care in China: are free antiretroviral drugs enough?

Financial access to HIV care and treatment can be difficult for many people in China, where the government provides free antiretroviral drugs but does not cover the cost of other medically necessary components, such as lab tests and drugs for opportunistic infections. This article estimates out-of-pocket costs for treatment and care that a person living with HIV/AIDS in China might face over the course of one year. Data comes from two treatment projects run by Médecins Sans Frontières in Nanning, Guangxi Province and Xiangfan, Hubei Province. Based on the national treatment guidelines, we estimated costs for seven different patient profiles ranging from WHO Clinical Stages I through IV. We found that patients face significant financial barriers to even qualify for the free ARV program. For those who do, HIV care and treatment can be a catastrophic health expenditure, with cumulative patient contributions ranging from approximately US$200-3939/year in Nanning and US$13-1179/year in Xiangfan, depending on the patient's clinical stage of HIV infection. In Nanning, these expenses translate as up to 340% of an urban resident's annual income or 1200% for rural residents; in Xiangfan, expenses rise to 116% of annual income for city dwellers and 295% in rural areas. While providing ARV drugs free of charge is an important step, the costs of other components of care constitute important financial barriers that may exclude patients from accessing appropriate care. Such barriers can also lead to undesirable outcomes in the future, such as impoverishment of AIDS-affected households, higher ARV drug-resistance rates and greater need for complex, expensive second-line antiretroviral drugs.

Differential effect of vanadate on receptor-mediated endocytosis of the asialoglycoprotein receptor in hepatocytes from normal and diabetic rats.

Insulin-dependent diabetes has been shown to affect several aspects of receptor-mediated endocytosis. Since vanadate, a phosphate analogue, is known to exert insulin-like actions in target tissues, we studied the effects of vanadate on the endocytosis of the asialoglycoprotein receptor (ASGP-R) after its administration either in vivo (oral therapy) and/or in vitro by direct incubation of isolated hepatocytes with vanadate. The surface binding, internalization, and degradation of 3H-asialoorosomucoid (3H-ASOR), a prototype ligand of the ASGP-R, were decreased in diabetic rats by approximately 36.5%, 22.3%, and 12.9%, respectively. These values were normalized in diabetic rats treated by vanadate. Similarly, vanadate treatment normalized the biphasic dissociation of 3H-ASOR/ASGP-R complexes by restoring the rapid dissociation process. In contrast, vanadate treatment did not affect any of these endocytic parameters in normal rats. In vitro experiments were monitored by direct incubation of isolated hepatocytes with 10 mM vanadate. This incubation created an inhibitory effect on the endocytic parameters. In this work, we have demonstrated that vanadate treatment can reverse the alterations induced by diabetes on receptor-mediated endocytosis of the ASGP-R.

[Study of symbiotic, serological and antibiotic resistance characteristics of different Rhizobium cicerii strains]. / Etude des caractéristiques symbiotiques, sérologiques et de résistance aux antibiotiques de différents isolats de Rhizobium cicerii.

The symbiotic performance of 24 isolates of Rhizobium Cicerii, collected from different Tunisien soils, were studied in a growth room and compared to the performance of two international strains (Som and 43). The antibiotic and serologic tests showed a large biogenetic diversity among the different isolates. Three serogroups gathering 18 isolates have been identified. Monchar strain (isolat 12) was shown to be resistant to all the six different antibiotic used. The standard strain 43 produced the greatest number of nodules and the best nitrogen yield in association with "Amdoun" roots, whereas the Menzel bouzelfa isolate brought about the best nitrogen yield in association with "Amdoun" and thus was the most efficient. An interesting result, consisted on the existence of a significant correlation (r = 0.67) between streptomycin resistance of the isolates and their capacity of nodule initiation (infectivity).

Kinetic analysis of epidermal growth factor endocytosis in rat hepatocytes. Effects of diabetes.

In the present study we followed the different steps of epidermal growth factor receptor (EGF-R) endocytosis in freshly isolated rat hepatocytes. Hepatocytes exhibit two classes of surface EGF receptors consisting of approximately 5,000 high-affinity sites (Kd = 15 pM) and 166,000 low-affinity sites (Kd = 670 pM). Binding of labeled EGF to hepatocytes permeabilized by digitonin shows that 75% of the total EGF-R are localized at the cell surface. At 37 degrees C, hepatocytes continuously internalized and degraded EGF in spite of a down-regulation of cell surface receptors. The internalization rate constants measured as a function of a range 125I-EGF concentrations (0.01 - 5 nM) involving various degrees of EGF-R occupancy show superimposable curves. This indicates that the specific internalization rate of EGF-R complex is independent of receptor occupancy. Streptozotocin-induced diabetes reduces the number of low-affinity EGF-R to 50,000 and produces a complete loss of high-affinity sites. The dynamics of 125I-EGF endocytosis show that diabetic hepatocytes fail to down-regulate the surface EGF-R efficiently although the constant rate of internalization is not modified. Decreased down-regulation of EGF-R together with enhanced EGF endocytosis suggest a greater efficiency in EGF-R recycling in diabetic rat hepatocytes.