Morbidity, mortality and long-term sequelae of West Nile virus disease in Québec.

We aimed to describe the clinical characteristics of West Nile patients reported in Québec in 2012 and 2013 and to document physical, mental and functional status 24 months after symptom onset according to illness severity. The cases were recruited by a public health professional. Data were collected from public health files, medical records and two standardised phone questionnaires: the Short Form-36 and the Instrumental Activities of Daily Living. In all, 92 persons participated in the study (25 had West Nile fever (WNF), 18 had meningitis and 49 had encephalitis). Encephalitis participants were older, had more underlying medical conditions, more neurological symptoms, worse hospital course and higher lethality than meningitis or WNF participants. Nearly half of the surviving hospitalised encephalitis patients required extra support upon discharge. At 24-month follow-up, encephalitis and meningitis patients had a lower score in two domains of the mental component: mental health and social functioning (P = 0.0025 and 0.0297, respectively) compared with the norms based on age- and sex-matched Canadians. Physical status was not affected by West Nile virus (WNV) infection. In addition, 5/36 (15%) of encephalitis, 1/17 (6%) of meningitis and 1/23 (5%) of WNF participants had new functional limitations 24 months after symptom onset. In summary, mental and functional sequelae in encephalitis patients are likely to represent a source of long-term morbidity. Preventive measures should target patients at higher risk of severe illness after WNV infection.

Immunogenicity and feasibility of intradermal vaccination against rabies in Quebec.

OBJECTIVES: Preexposure vaccination against rabies is recommended for some travellers and individuals exposed to the virus through their work. At a cost of at least $150 per intramuscular (IM) dose, few follow this recommendation. In Canada, provided certain conditions are met, the National Advisory Committee on Immunization (NACI) and the Comité d'immunisation du Québec allow a more economical alternative, intradermal vaccine administration (ID) which uses 1/10 the IM dose. The purpose of this study is to assess the feasibility and immunogenicity of intradermal preexposure vaccination. METHODS: Students and employees at the Faculty of Veterinary Medicine received three doses of ImovaxRage™ (Sanofi Pasteur) inactivated, human diploid cell rabies vaccine at days 0, 7 and 21 or 28. An IM or ID booster dose was administered after two years when indicated. OUTCOMES: Among the 159 participants who received three doses, 139 underwent serological testing in the year following vaccination and all achieved protective antibody levels. The antibody level was higher when measured within five weeks of the third dose. When the serological control was performed two years later, 65% of participants had a <0.5 IU/ml titre. Of the 22/30 participants who chose an ID booster, 100% responded and the average antibody titres were multiplied by 11, indicating a strong anamnestic response. DISCUSSION: ID rabies vaccination is immunogenic, economic and could be considered for the booster dose. Protective antibodies decline rapidly after primary immunization by ID, so it would seem prudent to perform a serological control one year later on individuals at high risk of occult occupational exposure. An alternative would be to give these individuals a routine ID booster dose one year after primary vaccination, which would simplify initial treatment and reduce related costs (follow-up, blood sampling, serological tests, etc.). The persistence of protective antibodies after this booster dose should be assessed to determine the need for subsequent serological tests and the ideal interval between tests.

Harvested white-tailed deer as sentinel hosts for early establishing Ixodes scapularis populations and risk from vector-borne zoonoses in southeastern Canada.

Due to recent establishment of the blacklegged tick, Ixodes scapularis Say, in southeastern Canada, tick-borne zoonoses (Lyme disease, human granulocytotropic anaplasmosis, and babesiosis) are of growing concern for public health. Using white-tailed deer (Odocoileus virginianus) culled in southwestern Quebec during 2007-2008, we investigated whether hunter-killed deer could act as sentinels for early establishing tick populations and for tick-borne pathogens. Accounting for environmental characteristics of culling sites, and age and sex of deer, we investigated whether their tick infestation levels could identify locations of known tick populations detected in active surveillance, presumed tick populations detected by passive surveillance, or both. We also used spatial cluster analyses to identify spatial patterns of tick infestation and occurrence of tick-borne zoonoses infection in ticks collected from the deer. Adult ticks were found on 15% of the 583 deer examined. Adult male deer had the greatest number (approximately 90%) of adult ticks. Overall, 3, 15, and 0% of the ticks collected were polymerase chain reaction (PCR)-positive for Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia microti, respectively. Our statistical analyses suggest that sex and age of deer, temperature, precipitation, and an index of tick dispersion by migratory birds were significantly associated with tick infestation levels. Cluster analysis identified significant clusters of deer carrying ticks PCR-positive for A. phagocytophilum, and for deer carrying two or more I. scapularis. Our study suggests that hunter-killed deer may be effective as sentinels for emerging areas of tick-borne anaplasmosis. They may have limited use as sentinels for early emerging I. scapularis tick populations and emerging Lyme disease risk.

Cyclospora cayetanensis: a description of clinical aspects of an outbreak in Quebec, Canada.

Cyclospora cayetanensis is an emerging infectious agent. The aim of this study was to describe an outbreak that occurred in 250 adults exposed to contaminated food, focusing on the duration and relapses of symptoms, complications and evidence of local transmission. This outbreak affected workers who ate in a restaurant in June 2005. Cyclospora sp. was observed in the stools of 20 cases and 122 probable cases were identified. The attack rate was estimated at 89%. Main symptoms were diarrhoea (96%), nausea (88%), fatigue (87%), abdominal cramps (85%), fever (52%) and headaches (45%). Contaminated fresh basil originating from a Mexican farm, used to prepare an uncooked appetizer, was identified as the source. In this non-endemic population of immunocompetent adults, Cyclospora infection presents with watery diarrhoea lasting from 4 to 18 days and fatigue lasting from 11 to 42 days. For a small proportion of affected persons, recovery can be delayed.

Associations between Ixodes scapularis ticks and small mammal hosts in a newly endemic zone in southeastern Canada: implications for Borrelia burgdorferi transmission.

Immature Ixodes scapularis infestation and Borrelia burgdorferi infection of wild small mammals were studied from June to October in 2007 and from May to October in 2008 at 71 study sites in a zone where I. scapularis populations and environmental Lyme disease risk are emerging in southwestern Quebec. Seasonal host-seeking activity of immature I. scapularis was similar to patterns reported previously in Canada and the USA: nymphal activity peaked in spring while larval activity peaked in late summer. Synchronous activity of nymphs with some larvae was observed in late spring, which could favour establishment of B. burgdorferi strains that cause short-lived infections in their hosts. White-footed mice (Peromyscus leucopus), deer mice (P. maniculatus), chipmunks (Tamias striatus), and red squirrels (Tamiasciurus hudsonicus) carried 92.0% of the larvae and 94.2% of the nymphs collected. Adult male white-footed mice carried significantly larger numbers of both larval and nymphal I. scapularis than other species and classes of small mammals (different demographic groups or physiological status: age, sex, sexual activity). We conclude that seasonality and host association were comparable to previous studies in North America, even in the context of a newly endemic pattern of low infection prevalence and low densities of host-seeking and feeding I. scapularis in southwestern Quebec. Our studies suggest that B. burgdorferi transmission cycles are focused on adult male mice (which carried 35% of all feeding ticks collected in the study), so control methods targeting this class of hosts may be particularly effective. However, our study also suggested that habitats containing a diverse host structure may dilute transmission cycles by partitioning of nymphal and larval ticks on different host species.

Cost-effectiveness of a lottery for increasing physicians' responses to a mail survey.

To evaluate the cost-effectiveness of a lottery on physicians' responses to a mail survey, a randomized controlled trial was conducted with a random sample of 1,000 members of the Quebec Federation of General Practitioners in 1997. For the first mailing of this survey, each respondent was randomly assigned to the control or experimental group, which was offered participation in a lottery upon return of the questionnaire. Response rate was 41.2% in the experimental group and 34.8% in the control group, a 6.4% difference (CI95%: 0.6%-12.6%). The additional cost of the lottery was about Can$500, giving an incremental cost of Can$16 per questionnaire returned. In conclusion, a lottery resulted in a small but statistically significant increase in the response rate of physicians to a mail survey. This method may be a cost-effective option when applied to large surveys.

Vaccination practices of Quebec family physicians. Influenza vaccination status and professional practices for influenza vaccination.

OBJECTIVE: To assess influenza vaccination status and influenza vaccination practices of family physicians in Quebec. DESIGN: Mail survey of a random sample of 1000 family physicians. SETTING: Family practices in the province of Quebec. PARTICIPANTS: Of 1000 Quebec family physicians sent questionnaires, 550 responded. After excluding physicians who worked only in institutions, had no patients older than 65 years, or did clinical work less than 20% of the time, 379 respondents were eligible for the study. MAIN OUTCOME MEASURES: Vaccination status of family physicians in 1996 and professional practices based on six clinical and administrative activities pertaining to influenza vaccination. RESULTS: Prevalence of vaccination was 35.5% (95% confidence interval 30.8% to 40.4%) among responding physicians and was higher among those 60 years and older, those with a chronic condition, and those perceiving high peer pressure to get vaccinated. Most respondents frequently assessed the current influenza vaccination status of their patients, risk factors for influenza-related complications, and contraindications to the vaccine. They also frequently provided education about influenza and its vaccine, recommended vaccination, and administered the vaccine. Only a few reported assessing prior influenza vaccinations or recording vaccination status regularly. Finally, vaccinated physicians recommended the vaccine more frequently to their patients than unvaccinated physicians did. CONCLUSION: Promotion programs focusing on peer influence could increase vaccination of family physicians. This could in turn improve vaccination coverage of elderly patients.

Evaluation of the rubella surveillance system in Quebec.

OBJECTIVE: To evaluate the validity of information in the rubella surveillance system in Quebec. DATA AND METHODS: Cases of rubella in the provincial registry of notifiable diseases, "Maladies à declaration obligatoire" (MADO), from 1994 to 1996 were matched with laboratory-identified cases and with cases in a reference file created from all case investigation records of regional departments of public health for the same period. Sensitivity and the proportion of cases in agreement were calculated. RESULTS: Compared with laboratories, the sensitivity of the provincial registry was 56%. Compared with the reference file, global sensitivity (confirmed cases plus clinical cases) was 58% and the positive predictive value was 50%. Of the 356 cases reported to regional public health departments, 65% were classified in the same diagnostic category (confirmed case, clinical case, excluded case) by public health professionals and a group of experts (weighted kappa=0.32). Information on rubella vaccination status was missing in 25% of cases in the MADO file for rubella. CONCLUSIONS: Notification of positive results for immunoglobulin M antibodies and viral cultures should be required of all laboratories. Uniform procedures should be adopted and applied for the validation of cases that are reported to regional departments of public health. In the context of the rarefaction of rubella, any immunoglobulin M-positive result should be interpreted using all available epidemiological information.

Epidemiological evidence for immunity following Trypanosoma brucei gambiense sleeping sickness.

In order to investigate whether protective immunity appears after Trypanosoma brucei gambiense sleeping sickness, we undertook a retrospective cohort study of 3 remote villages in central Zaire (total population 1431), in which 38% of all adults had a past history of human African trypanosomiasis. Among adults previously diagnosed with trypanosomiasis and treated, the risk of a second episode of trypanosomiasis during the 10 years period of observation was only 15% (with a 24 months refractory period) and 30% (without a refractory period) of the risk of a first episode in adults never previously diagnosed. We could not demonstrate a similar difference among children, to some extent because only a few of them were diagnosed for a first time with trypanosomiasis. Our findings suggest that very significant immunity appears after Gambian sleeping sickness, and that developing a vaccine against this subspecies of trypanosomes is biologically plausible.

Risk factors for encephalopathy and mortality during melarsoprol treatment of Trypanosoma brucei gambiense sleeping sickness.

This paper reviews the incidence of, and risk factors for, drug-induced encephalopathy and mortality (from all causes) during treatment with melarsoprol of 1083 patients with Trypanosoma brucei gambiense sleeping sickness in Nioki hospital (Zaire) between 1983 and 1990. Sixty-four patients (5.9%) developed encephalopathy and 62 (5.7%) died: 43 from reactive encephalopathy and 19 from other causes. Univariate and multivariate analyses showed that the administration of prednisolone reduced significantly the incidence of encephalopathy and mortality during treatment, especially in patients with trypanosomes observed in the cerebrospinal fluid (CSF) and/or with a CSF white blood cell (WBC) count of 100 or more per mm3. The risk of encephalopathy was associated more strongly with the CSF WBC count than with the presence of CSF trypanosomes. In the subgroup of patients with a CSF WBC count of 100 or more mm3, changing the melarsoprol regimen to 3 series of 3 injections instead of 3 series of 4 injections halved the mortality rate during treatment. Treatment of patients who do develop reactive encephalopathy with the heavy metal chelator dimercaprol, in addition to intravenous steroids and anticonvulsants, may be harmful. The data suggest that a further reduction of the total dose of melarsoprol may decrease toxicity without jeopardizing efficacy.

Gambiense trypanosomiasis: frequency of, and risk factors for, failure of melarsoprol therapy.

1083 patients with late-stage Trypanosoma brucei gambiense sleeping sickness were treated with melarsoprol in Nioki hospital, Zaire, between 1983 and 1990. Sixty-two (5.7%) died during treatment. Of the 1021 patients who survived the treatment, 63 (6.2%) subsequently relapsed, 58 (92%) of whom were diagnosed within 2 years of melarsoprol treatment. There was no evidence of an increase in the frequency of treatment failures during the study period, and the rate of relapses that we documented is comparable to that reported from Zaire more than 30 years ago. Relapses were more frequent among patients who had trypanosomes seen in the cerebrospinal fluid (CSF) at the time of the initial diagnosis (odds ratio [OR] = 2.76, 95% confidence interval [CI] = 1.65-4.63, P = 0.0001). Male patients had twice as many relapses as females (OR = 2.00, 95% CI = 1.19-3.36, P = 0.009), which was partly explained by males having trypanosomes in the CSF more often than females. There were important geographical variations in the frequency of relapses within the territory of the Nioki rural health zone, suggesting that the circulation of trypanosomes was geographically limited. Prednisolone treatment did not increase the risk of treatment failure, nor did decreasing the total dose of melarsoprol from 12 to 9 injections for patients with > or = 100 white blood cells/mm3 of CSF. Since patients with trypanosomes in the CSF are also those who are at the highest risk of melarsoprol-induced encephalopathy, more aggressive treatment regimens cannot be recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Eflornithine concentrations in serum and cerebrospinal fluid of 63 patients treated for Trypanosoma brucei gambiense sleeping sickness.

Eflornithine (difluoromethylornithine, DFMO) has recently been approved for the treatment of Trypanosoma brucei gambiense trypanosomiasis. Treatment failures have been infrequent but have occurred among patients treated with oral DFMO only, and among children. To investigate the higher frequency of failures observed in young patients, DFMO trough concentrations in serum and cerebrospinal fluid (CSF) were measured at the end of treatment in 13 children and 50 adults who had received 200 mg/kg intravenously every 12 h for 14 d. Mean DFMO concentration in CSF was significantly lower among children aged less than 12 years when compared to older patients (25.1 vs 68.9 nmol/mL, P < 0.001). Mean serum concentration was also lower in children (49.2 vs 87.5 nmol/mL, P = 0.03). Among patients who received DFMO as initial therapy for sleeping sickness, the mean CSF/serum ratio was lower in children (0.41 vs 0.91, P < 0.005). The 3 patients who failed DFMO treatment had CSF trough concentrations around or below 50 nmol/mL. Convulsions and anaemia were associated with higher drug levels and previous therapy with melarsoprol. The lower CSF drug concentrations observed in children could result from higher renal clearance and different CSF pharmacokinetics of DFMO in that age group. To avoid treatment failures, a 6-hourly regimen as well as higher DFMO dosage based on body surface area rather than on weight are recommended for children.

Efficacy and toxicity of eflornithine for treatment of Trypanosoma brucei gambiense sleeping sickness.

The usual first-line treatment for Trypanosoma brucei gambiense sleeping sickness is melarsoprol, but when that fails the outlook has hitherto been grim. The polyamine synthesis inhibitor eflornithine (difluoromethylornithine, DFMO) has emerged as an alternative therapy. 207 patients with late-stage T b gambiense sleeping sickness were treated in rural Zaire with three different regimens of DFMO in an open-trial design. During treatment, trypanosomes disappeared from the CSF of all 87 patients in whom parasites had been seen before DFMO administration, and there was a sharp fall in CSF white cell count from a mean of 186/microliters to 21/microliters. 152 patients have been followed for at least a year after DFMO treatment, and only 13 (9%) have relapsed. Treatment failures were more common in children less than 12 years, among patients treated with oral DFMO only, and among patients who received DFMO as the initial treatment of their recently diagnosed trypanosomiasis. Toxicity was acceptable. Only 4 patients died during or shortly after treatment. Bone marrow suppression resulting in anaemia (43%) or leucopenia (53%) was common but bore little consequence. This open trial shows that DFMO is as active as and possibly less toxic than melarsoprol. For economic and logistic reasons DFMO may not be the first-choice therapy in rural Africa but for the vast majority of patients who relapse after melarsoprol DFMO will be curative.

The impact of human immunodeficiency virus infection on the epidemiology and treatment of Trypanosoma brucei gambiense sleeping sickness in Nioki, Zaire.

To determine if there is an association between human immunodeficiency virus type 1 (HIV-1) infection and Trypanosoma brucei gambiense sleeping sickness, all incident cases of trypanosomiasis and a control group of blood donors presenting to the same rural hospital in Zaire were tested for anti-human immunodeficiency virus type 1 (anti-HIV-1) antibodies. There was no significant difference in the prevalence of HIV-1 infection between the two groups (7 of 220, [3.2%] for the incident cases and 8 of 388 [2.1%] for the blood donors; P = 0.56). Among the three HIV-1 seropositive incident cases of trypanosomiasis treated with difluoromethylornithine, two (67%) relapsed after treatment compared with four of 39 (10%) HIV-1 seronegative incident cases treated with the same drug (P = 0.05). These findings suggest that at the present time, HIV-1 infection is not having a significant impact on the incidence of T. brucei gambiense sleeping sickness in rural Zaire, but the possibility that incident cases of trypanosomiasis concurrently infected with HIV-1 may be at higher risk of treatment failure warrants further investigation.