Proof-of-Principle of Onchocerciasis Elimination with Ivermectin Treatment in Endemic Foci in Africa: Final Results of a Study in Mali and Senegal

Background

Mass treatment with ivermectin controls onchocerciasis as a public health problem, but it was not known if it could also interrupt transmission and eliminate the parasite in endemic foci in Africa where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission, and test whether treatment could be safely stopped. This article reports the results of the final evaluations up to 5 years after the last treatment.

Methodology/Principal Findings

Skin snip surveys were undertaken in 131 villages where 29,753 people were examined and 492,600 blackflies were analyzed for the presence of Onchocerca volvulus larva using a specific DNA probe. There was a declining trend in infection and transmission levels after the last treatment. In two sites the prevalence of microfilaria and vector infectivity rate were zero 3 to 4 years after the last treatment. In the third site, where infection levels were comparatively high before stopping treatment, there was also a consistent decline in infection and transmission to very low levels 3 to 5 years after stopping treatment. All infection and transmission indicators were below postulated thresholds for elimination.

Conclusion/Significance

The study has established the proof of principle that onchocerciasis elimination with ivermectin treatment is feasible in at least some endemic foci in Africa. The study results have been instrumental for the current evolution from onchocerciasis control to elimination in Africa.     

Integrated Real-Time PCR for Detection and Monitoring of Legionella pneumophila in Water Systems

We evaluated a ready-to-use real-time quantitative Legionella pneumophila PCR assay system by testing 136 hot-water-system samples collected from 55 sites as well as 49 cooling tower samples collected from 20 different sites, in parallel with the standard culture method. The PCR assay was reproducible and suitable for routine quantification of L. pneumophila. An acceptable correlation between PCR and culture results was obtained for sanitary hot-water samples but not for cooling tower samples. We also monitored the same L. pneumophila-contaminated cooling tower for 13 months by analyzing 104 serial samples. The culture and PCR results were extremely variable over time, but the curves were similar. The differences between the PCR and culture results did not change over time and were not affected by regular biocide treatment. This ready-to-use PCR assay for L. pneumophila quantification could permit more timely disinfection of cooling towers.     

Modelling the Abundances of Two Major Culicoides (Diptera: Ceratopogonidae) Species in the Niayes Area of Senegal

In Senegal, considerable mortality in the equine population and hence major economic losses were caused by the African horse sickness (AHS) epizootic in 2007. Culicoides oxystoma and Culicoides imicola, known or suspected of being vectors of bluetongue and AHS viruses are two predominant species in the vicinity of horses and are present all year-round in Niayes area, Senegal. The aim of this study was to better understand the environmental and climatic drivers of the dynamics of these two species. Culicoides collections were obtained using OVI (Onderstepoort Veterinary Institute) light traps at each of the 5 sites for three nights of consecutive collection per month over one year. Cross Correlation Map analysis was performed to determine the time-lags for which environmental variables and abundance data were the most correlated. C. oxystoma and C. imicola count data were highly variable and overdispersed. Despite modelling large Culicoides counts (over 220,000 Culicoides captured in 354 night-traps), using on-site climate measures, overdispersion persisted in Poisson, negative binomial, Poisson regression mixed-effect with random effect at the site of capture models. The only model able to take into account overdispersion was the Poisson regression mixed-effect model with nested random effects at the site and date of capture levels. According to this model, meteorological variables that contribute to explaining the dynamics of C. oxystoma and C. imicola abundances were: mean temperature and relative humidity of the capture day, mean humidity between 21 and 19 days prior a capture event, density of ruminants, percentage cover of water bodies within a 2 km radius and interaction between temperature and humidity for C. oxystoma; mean rainfall and NDVI of the capture day and percentage cover of water bodies for C. imicola. Other variables such as soil moisture, wind speed, degree days, land cover or landscape metrics could be tested to improve the models. Further work should also assess whether other trapping methods such as host-baited traps help reduce overdispersion.     

Effects of aerobic exercise on the torque-velocity relationship in cycling

The kinetics of the torque-velocity (T-ω) relationship after aerobic exercise was studied to assess the effect of fatigue on the contractile properties of muscle. A group of 13 subjects exercised until fatigued on a cycle ergometer, at an intensity which corresponded to 60% of their maximal aerobic power for 50 min (MAP60%); ten subjects exercised until fatigued at 80% of their maximal aerobic power for 15 min (MAP80%). Of the subjects 7 exercised at both intensities with at least a 1-week interval between sessions. Pedalling rate was set at 60 rpm. The T-ω relationship was determined from the velocity data collected during all-out sprints against a 19 N · m braking torque on the same ergometer, according to a method proposed previously. Maximal theoretical velocity (ω₀) and maximal theoretical torque (T ₀) were estimated by extrapolation of the linear T-ω relationship. Maximal power (P _max) was calculated from the values of T ₀ and ω₀ (P _max = 0.25 ω₀ T ₀). The T-ω relationships were determined before, immediately after and 5 and 10 min after the aerobic exercise. The kinetics of ω₀, T ₀ and P _max was assumed to express the effects of fatigue on the muscle contractile properties (maximal shortening velocity, maximal muscle strength and maximal power). Immediately after exercise at MAP60% a 7.8% decrease in T ₀ and 8.8% decrease in P _max was seen while the decrease in ω₀ was nonsignificant, which suggested that P _max decreased in the main because of a loss in maximal muscle strength. In contrast, MAP80% induced a 8.1% decrease in ω₀ and 12.8% decrease in P _max while the decrease in T ₀ was nonsignificant, which suggested that the main cause of the decrease in P _max was probably a slowing of maximal shortening velocity. The short recovery time of the T-ω relationship suggests that the causes of the decrease of torque and velocity are processes which recover rapidly. Accepted: 25 November 1996     

Seroprevalence of Pertussis in Senegal: A Prospective Study

Background

Pertussis, also known as whooping cough, is a vaccine-preventable respiratory disease caused by Bordetella pertussis infection, against which Senegalese children are immunized with the diphtheria-tetanus-whole cell pertussis vaccine (DTwP). Seroepidemiology of pertussis has been widely described in industrialized countries, but rare are the studies referring to it in developing countries.

Methods

We conducted a longitudinal survey in Northern Senegal to investigate the epidemiology of B. pertussis by evaluating the IgG antibody (Ab) response against pertussis toxin (PT). A cohort of 410 children aged 1 to 9 from five villages in the Middle Senegal River Valley were followed-up for 18 months. During that period, five visits were made to assess the immunological status of the children.

Principal Findings

PT-specific IgG responses were significantly different according to age. Until the age of 3, there was a decrease in the Ab response, which then increased in the older groups. Assessment of IgG antibodies to PT (IgG-PT) suggested evidence of recent exposures to the pathogen. Surprisingly, in one of the five villages the average Ab response to PT was very low at all ages during the first 6 months of the study. At the third visit, IgG-PT concentrations peaked to very high levels, to slightly decline at the end of the survey. This indicates an outbreak of B. pertussis, whereas in the other villages a pertussis endemic profile could be observed.

Conclusions

Pertussis is endemic in Northern Senegal despite the introduction of vaccination. The circulation of the bacteria seems to differ between geographic locations and over time. A more complete understanding of the epidemiology of pertussis and its environmental determinants could provide information to adapt vaccination programs.     

Quantification of dimethyl-ifosfamide and its N-deschloropropylated metabolites in mouse plasma by liquid chromatography-tandem mass spectrometry

Among antitumor oxazaphosphorine drugs, the prodrug ifosfamide (IFO) and its analogs require metabolic activation by specific liver cytochrome P450 (CYP) enzymes to become therapeutically active. New 7,9-dimethyl-ifosfamide analogs have shown greater cytotoxic activity than IFO, whereas side-chain oxidation still occurred leading to monochloroacetone after N-dechloropropylation. A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed and validated for the simultaneous quantitation of the prodrug 7S,9S-dimethyl-ifosfamide (diMeIFO) and its two inactive metabolites, N(2)- and N(3)-deschloropropyl-dimethylifosfamide (N(2)-DCP-diMeIFO and N(3)-DCP-diMeIFO) in mouse plasma. After protein precipitation with methanol, the analytes were separated by isocratic reversed-phase chromatography with (methanol/ammonium formate pH 5.5, 60:40, v/v) and detected by tandem mass spectrometry using multiple reaction monitoring of transitions ions m/z 289→168 for diMeIFO, m/z 213→168 for N(2)-DCP-diMeIFO, m/z 213→92 for N(3)-DCP-diMeIFO and m/z 261→154 for IFO (internal standard). The calibration curves were linear over the concentration range of 20-10,000ng/mL for the three analytes. Mean extraction recoveries from mouse plasma were 99, 96, 99 and 100% for diMeIFO, N(2)-DCP-diMeIFO, N(3)-DCP-diMeIFO and IFO, respectively. The lower limit of quantitation for diMeIFO and its metabolites was 20 ng/mL in 50 μL plasma. The method was accurate with calculated bias from -5.8 to 4.0% for diMeIFO, from -1.1 to 10.6% for N(2)-DCP-diMeIFO and from -6.9 to 9.8% for N(3)-DCP-diMeIFO, and precise with coefficients of variation lower than 6.8%, 7.8% and 14.3%, respectively. The assay was successfully applied to a preliminary pharmacokinetic study of diMeIFO and of its metabolites in mice.