Epitope mapping and biological function analysis of antibodies produced by immunization of mice with an inactivated Chinese isolate of severe acute respiratory syndrome-associated coronavirus (SARS-CoV)

Inactivated severe acute respiratory syndrome-associated coronavirus (SARS-CoV) has been tested as a candidate vaccine against the re-emergence of SARS. In order to understand the efficacy and safety of this approach, it is important to know the antibody specificities generated with inactivated SARS-CoV. In the current study, a panel of twelve monoclonal antibodies (mAbs) was established by immunizing Balb/c mice with the inactivated BJ01 strain of SARS-CoV isolated from the lung tissue of a SARS-infected Chinese patient. These mAbs could recognize SARS-CoV-infected cells by immunofluorescence analysis (IFA). Seven of them were mapped to the specific segments of recombinant spike (S) protein: six on S1 subunit (aa 12-798) and one on S2 subunit (aa 797-1192). High neutralizing titers against SARS-CoV were detected with two mAbs (1A5 and 2C5) targeting at a subdomain of S protein (aa 310-535), consistent with the previous report that this segment of S protein contains the major neutralizing domain. Some of these S-specific mAbs were able to recognize cleaved products of S protein in SARS-CoV-infected Vero E6 cells. None of the remaining five mAbs could recognize either of the recombinant S, N, M, or E antigens by ELISA. This study demonstrated that the inactivated SARS-CoV was able to preserve the immunogenicity of S protein including its major neutralizing domain. The relative ease with which these mAbs were generated against SARS-CoV virions further supports that subunit vaccination with S constructs may also be able to protect animals and perhaps humans. It is somewhat unexpected that no N-specific mAbs were identified albeit anti-N IgG was easily identified in SARS-CoV-infected patients. The availability of this panel of mAbs also provided potentially useful agents with applications in therapy, diagnosis, and basic research of SARS-CoV.     

Field efficacy of praziquantel oral paste against naturally acquired equine cestodes in Ethiopia

The efficacy of an oral formulation of praziquantel (Equitape, Horse paste, Fort Dodge) in the reduction of cestode egg counts and serum antibody level against Anoplocephala perfoliata was assessed in 44 donkeys under field conditions. The donkeys were confirmed both by faecal examination and serum antibody assessed by an enzyme-linked immunosorbent assay to have natural infection with tapeworms. The donkeys were randomly allocated into treatment (n?=?22) and control (n?=?22) groups. The treatment group was treated with both praziquantel and ivermectin (Ivomec, Merial) at a dose rate of 1 mg/kg and 200 μg/kg, respectively while the control group was treated only with ivermectin. Faecal samples were collected before treatment (day-0) and 2, 6, 8, 12, and 16 weeks post-treatment while blood samples were collected before treatment and 8 and 16 weeks after treatment and analysed. The results of the study demonstrated that praziquantel paste was highly effective in reducing cestode eggs in donkeys and had an efficacy of more than 99 % until week 16 (day?112). No cestode egg reappearance by 16 weeks post-treatment in any animal in the treatment group was observed while donkeys in the control group continued shedding cestode eggs. The immunological assay also showed a significant reduction in serum antibody level against A. perfoliata in treated donkeys compared to the control group (p?=?0.0001). This marked decrease in serum antibody level indicates reduced risk of cestode-associated colic and other gastrointestinal disorders and clinical diseases. No adverse reactions or clinical effects were encountered in any animal within either group throughout the trial period.     

Bioguidage search of active compounds from Waltheria indica L. (Malvaceae) used for asthma and inflammation treatment in Burkina Faso

Waltheria indica is used in traditional pharmacopeia in Burkina Faso for the treatment of asthma and conditions of inflammation. To evaluate its pharmacological properties and isolate the active compounds, a study through a bioguided phytochemical approach was conducted. This search was guided by a two‐level investigation. First, we evaluated the impact of various fractions on the activity of enzymes involved in smooth muscle contraction (PDE4A1α) and inflammatory processes (PLA₂, 5‐LOX). Second, we investigated the inhibitory effect of fractions on isolated rat trachea. The initial hydroalcoholic extract from roots of W. indica (HA), n‐hexane fraction (F₁), dichloromethane fraction (F₂), ethyl acetate fraction (F₃), residuary fraction (F₄) reduced enzyme activity of PDE4A1α (inhibition of 22–42% at 50 μg/mL), 5‐LOX (60–80% at 10 μg/mL), and PLA₂ (42–94% at 100 μg/mL). On isolated rat trachea, only HA, F₃, and fractions obtained from F₃ by chromatography on silica gel column, using dichloromethane/methanol, dose dependently inhibited contraction induced by acetylcholine. IC₅₀ was 1051 μg/mL for HA and comprised between 181 and 477 μg/mL for F₃ and its fractions. The most active fractions were purified and led to the identification of (‐)‐epicatechin. (‐)‐epicatechin from W. indica dose dependently inhibited PLA₂ (IC₅₀ = 154.7 μm ) and 5‐LOX (IC₅₀ = 15.8 μm ). In conclusion, both inhibition of PDE4A1α, 5‐LOX, and PLA₂ activities and rat trachea relaxation by W. indica validate its use in traditional management of asthma and other conditions of inflammation. These effects should be, at least in part, attributed to the presence of (‐)‐epicatechin in roots of W. indica.     

Comparative analysis of urinary schistosomiasis among primary school children and rural farmers in Obollo–Eke,Enugu State,Nigeria: Implications for control

ObjectiveTo determine the prevalence, sex-age related intensity of urinary schistosomiasis and to compare such parameters among rural school children and rural farmers in selected communities in Obollo-Eke located in Southeast, Nigeria.MethodsA cross-sectional survey involving 1 337 school children and farmers was conducted in Obollo-Eke community between September 2006 and July 2007. Demographic data of subjects was collected using a questionnaire prepared for this purpose. Urine samples were collected and examined for haematuria and ova of Schistosoma haematobium (S. haematobium) using Medi-test Combi 9 and sedimentation technique respectively.ResultsThe prevalence of urinary schistosomiasis based on microscopic examination of the urine sediment for the ova of S. haematobium was 17.5% while the prevalence of haematuria was 15.6%. Infection intensity varied from light to heavy. In general, the prevalence was higher among males (20.8%) than females (14.6%; P>0.05) and was slightly higher among primary school children (18.0%; n=762) than farmers (16.9%; n=575; P>0.05). The age-specific prevalence of schistosomiasis among the study subjects ranged from 8.3% to 21.2% in 0-5 years and 11-15 years age groups respectively.ConclusionsHaematuria and mean egg/10 mL urine (r = 0.95; P<0.01) showed that both procedures are reliable for the diagnosis of the disease and can be used to ascertain the prevalence of the disease in any community. The comparative analysis of urinary bilharziasis among primary school children and rural farmers demonstrated that the infection is moderately high in these two risk population groups at Obollo-Eke. A robust intervention strategy is clearly needed.     

A randomized trial of amodiaquine and artesunate alone and in combination for the treatment of uncomplicated falciparum malaria in children from Burkina Faso

Combining artesunate (AR) with existing antimalarial drugs may improve cure rates, delay emergence of resistance and reduce parasite clearance time. In order to investigate the latter, we conducted a randomized clinical trial testing the AR plus amodiaquine (AQ) combination for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso. Children aged 1-15 years were randomly assigned to either AQ (10 mg/kg) or AR (4 mg/kg first day then half dose) or AQ + AR (AQAR) as a single daily dose under supervision for three consecutive days for all groups. Follow-up lasted 28 days. Primary endpoints were parasite and fever clearance time. Eighty-seven children were evaluated: 27 received AQ, 27 AR and 33 AQAR. Using an intention to treat analysis, fever clearance time was similar in the three groups. However, it was significantly faster in the AR (1.21 days; P = 0.02) and AQAR groups (1.19 days; P < 0.01) than in the AQ group (1.46 days) when excluding other concomitant causes of fever. Parasite clearance time was faster in AR (1.13 days; P = 0.008) and AQAR groups (1.13 days; P < 0.01) than in the AQ group (1.6 days). All children cleared their parasites by day 14, including the child with Late Parasitological Failure (LPF) at day 7 after rescue treatment. Only one child (4%) from the AR group and one (4%) from the AQ group presented with asymptomatic parasitaemia at day 7 and day 21, respectively (LPF). Gametocyte carriage was not detectable in any group during follow-up nor was any adverse reaction observed. While resistance to first-line treatment (chloroquine) is already established in the country, AQ and AR used alone or in combination therapy proved highly efficacious in our study. Burkina Faso stands in a very good situation for an internationally recommended switch to AR-containing combination as first-line treatment for uncomplicated malaria. Including AQ in this regimen seems the best option.     

Priority interventions to reduce HIV transmission in sex work settings in sub-Saharan Africa and delivery of these services

Introduction

Virtually no African country provides HIV prevention services in sex work settings with an adequate scale and intensity. Uncertainty remains about the optimal set of interventions and mode of delivery.

Methods

We systematically reviewed studies reporting interventions for reducing HIV transmission among female sex workers in sub-Saharan Africa between January 2000 and July 2011. Medline (PubMed) and non-indexed journals were searched for studies with quantitative study outcomes.

Results

We located 26 studies, including seven randomized trials. Evidence supports implementation of the following interventions to reduce unprotected sex among female sex workers: peer-mediated condom promotion, risk-reduction counselling and skills-building for safer sex. One study found that interventions to counter hazardous alcohol-use lowered unprotected sex. Data also show effectiveness of screening for sexually transmitted infections (STIs) and syndromic STI treatment, but experience with periodic presumptive treatment is limited. HIV testing and counselling is essential for facilitating sex workers’ access to care and antiretroviral treatment (ART), but testing models for sex workers and indeed for ART access are little studied, as are structural interventions, which create conditions conducive for risk reduction. With the exception of Senegal, persistent criminalization of sex work across Africa reduces sex workers’ control over working conditions and impedes their access to health services. It also obstructs health-service provision and legal protection.

Conclusions

There is sufficient evidence of effectiveness of targeted interventions with female sex workers in Africa to inform delivery of services for this population. With improved planning and political will, services – including peer interventions, condom promotion and STI screening – would act at multiple levels to reduce HIV exposure and transmission efficiency among sex workers. Initiatives are required to enhance access to HIV testing and ART for sex workers, using current CD4 thresholds, or possibly earlier for prevention. Services implemented at sufficient scale and intensity also serve as a platform for subsequent community mobilization and sex worker empowerment, and alleviate a major source of incident infection sustaining even generalized HIV epidemics. Ultimately, structural and legal changes that align public health and human rights are needed to ensure that sex workers on the continent are adequately protected from HIV.     

Comparative in vitro activities of aztreonam, ciprofloxacin, norfloxacin, ofloxacin, HR 810 (a new cephalosporin), RU28965 (a new macrolide), and other agents against enteropathogens.

The in vitro activity of drugs currently used in the treatment of diarrhea against 595 enteropathogens from worldwide sources was compared with that of six newly developed antibiotics, ciprofloxacin; norfloxacin; ofloxacin; aztreonam; HR810, an expanded-spectrum cephalosporin; and RU28965, a new macrolide. In contrast with ampicillin and chloramphenicol, trimethoprim-sulfamethoxazole showed an excellent activity against all of the enteropathogens tested, except Campylobacter species. Ciprofloxacin had the highest activity, with an overall 90% MIC of less than or equal to 0.097 micrograms/ml, except for Campylobacter species (0.39 micrograms/ml). Unlike other cephalosporins, HR810 showed a satisfactory activity against Campylobacter species (90% MIC of 3.12 micrograms/ml). RU28965 was three times less active than erythromycin against Campylobacter species.