Christophe Paquet

Chikungunya Disease Outbreak, Reunion Island

During 2005, the monthly CDR remained within expected range of statistical variation. From January through April 2006, respectively, monthly CDRs were 7.1%, 34.4%, 25.2%, and 8.3% higher than expected rates (p 75 years of age.

Treatment of human African trypanosomiasis— present situation and needs for research and development

Human African trypanosomiasis re-emerged in the 1980s. However, little progress has been made in the treatment of this disease over the past decades. The first-line treatment for second-stage cases is melarsoprol, a toxic drug in use since 1949. High therapeutic failure rates have been reported recently in several foci. The alternative, eflornithine, is better tolerated but difficult to administer. A third drug, nifurtimox, is a cheap, orally administered drug not yet fully validated for use in human African trypanosomiasis. No new drugs for second-stage cases are expected in the near future. Because of resistance to and limited number of current treatments, there may soon be no effective drugs available to treat trypanosomiasis patients, especially second-stage cases. Additional research and development efforts must be made for the development of new compounds, including: testing combinations of current trypanocidal drugs, completing the clinical development of nifurtimox and registering it for trypanosomiasis, completing the clinical development of an oral form of eflornithine, pursuing the development of DB 289 and its derivatives, and advancing the pre-clinical development of megazol, eventually engaging firmly in its clinical development. Partners from the public and private sector are already engaged in joint initiatives to maintain the production of current drugs. This network should go further and be responsible for assigning selected teams to urgently needed research projects with funds provided by industry and governments. At the same time, on a long term basis, ambitious research programmes for new compounds must be supported to ensure the sustainable development of new drugs.

Timely detection of meningococcal meningitis epidemics in Africa.

BACKGROUND Epidemics of meningococcal disease in Africa are commonly detected too late to prevent many cases. We assessed weekly meningitis incidence as a tool to detect epidemics in time to implement mass vaccination. METHODS Meningitis incidence for 41 subdistricts in Mali was determined from cases recorded in health centres (1989-98) and from surveillance data (1996-98). For incidence thresholds of 5 to 20 cases per 100000 inhabitants per week, we calculated sensitivity and specificity for detecting epidemics, and determined the time lapse between threshold and epidemic peak. FINDINGS We recorded 9084 meningitis cases. Clinic-based weekly incidence of 5 and 10 cases per 100000 inhabitants detected all meningitis epidemics (sensitivity 100%, 95% CI 93-100), with median threshold-to-peak time of 5 and 3 weeks. Under-reporting reduced sensitivity: only surveillance thresholds of 5 or 7 cases per 100000 inhabitants per week detected all epidemics. Crossing the lower threshold before the 10th calendar week doubled epidemic risk relative to crossing it later (relative risk 2.1, 95% CI 1.4-3.2). At 10 cases per 100000 inhabitants per week, specificity for outbreak prediction was 88%, 95% CI 83-91). For populations under 30000, 3 to 5 cases in one or two weeks predicted epidemics with 85% to 97% specificity. INTERPRETATION Low meningitis thresholds improve timely detection of epidemics. Ten cases per 100000 inhabitants per week in one area confirm epidemic activity in a region, with few false alarms. An alert threshold of 5 cases per 100000 inhabitants per week allows time to investigate, prepare for an epidemic, and initiate mass vaccination where appropriate. For populations under 30000, the alert threshold is two cases in a week. High quality surveillance is essential.

Outbreak of Chikungunya fever in Mayotte, Comoros archipelago, 2005–2006

In 2005-2006, a large outbreak of Chikungunya (CHIK) fever occurred on the western Indian Ocean Islands. In Mayotte, concurrent with an enhanced passive case notification system, we carried out two surveys. A seroprevalence survey designed to document recent CHIK infection was conducted on serum samples collected from pregnant women in October 2005 (n=316) and in March-April 2006 (n=629). A cross-sectional clinical community survey carried out from 2 to 10 May 2006 among 2235 individuals was designed to determine the cumulative incidence of presumptive CHIK fever cases. The seroprevalence of recent infection among pregnant women was 1.6% in October 2005 and rose to 26% in April 2006. The clinical community survey showed that nearly 26% of respondents had experienced presumptive CHIK fever between January and May 2006. Extrapolated to the overall population of Mayotte, these figures lead to an estimated attack rate of 249.5 cases per 1000 population as of early May 2006. Nine patients with the maternofetal form and six subjects with the severe form were recorded. This first emergence of CHIK fever in Mayotte lead to a very large outbreak. Efforts to strengthen surveillance and prevention of arbovirus infection are needed at country and regional levels.

Research in complex humanitarian emergencies: the Médecins Sans Frontières/Epicentre experience

Vincent Brown and colleagues review Epicentres 20 years of experience conducting research during complex humanitarian emergencies.

Measles vaccine effectiveness in standard and early immunization strategies, Niger, 1995

BACKGROUND An Expanded Programme on Immunization was started in late 1987 in Niger, including vaccination against measles with one dose of standard titer Schwarz vaccine given to infants after 9 months of age. During epidemics an early two-dose strategy was implemented (one dose between 6 and 8 months and one dose after 9 months). From January 1, 1995, until May 7, 1995, 13 892 measles cases were reported in Niamey, Niger. METHODS A retrospective cohort study was conducted in a crowded area of Niamey at the end of the outbreak to assess the effectiveness of measles vaccine in standard (after 9 months) and early (before 9 months) immunization strategies under field conditions. RESULTS Highest measles incidence rates were observed among children <1 year of age. Vaccine effectiveness estimates increased with age at vaccination from 78% with a single dose administered at 6 months of age to 95% at 9 months. Vaccine effectiveness with the early two dose strategy was 93%. CONCLUSIONS Immunization with a single dose of standard titer Schwarz vaccine before 9 months of age provided higher clinical protection than expected from seropositivity studies. The early two dose strategy is justified in contexts where measles incidence is high before 9 months of age. Our results raise the issue of lowering the recommended age for measles vaccination in developing countries.

Risk factors for death in hospitalized dysentery patients in Rwanda

Summary To evaluate the management of severe dysentery cases in in‐patient facilities during an epidemic of Shigella dysenteriae type 1 (Sd1), and to identify the factors associated with the risk of death, we conducted a prospective cohort study in 10 Rwandese hospitals between September and December 1994. Data were obtained from 849 cases admitted to hospitals with diarrhoea and visible blood in stools. The proportion of patients with persistent bloody diarrhoea was 51.0% at treatment day 3 and 27.9% at treatment day 5. At discharge, 79.9% had improved or were cured. The case fatality ratio was 13.2%, higher for patients treated with nalidixic acid than for those treated with ciprofloxacin (12.2%vs. 2.2%, RR = 5.80, 95% CI = 0.83–40.72). In a logistic regression model three risk factors were significantly associated with an increased risk of death during hospitalization: severe dehydration on admission (adjusted OR = 2.79, 95% CI = 1.46–5.33), age over 50 (adjusted OR vs. 5–49 age group = 3.22, 95% CI = 1.70–6.11) and prescription of nalidixic acid (adjusted OR vs. ciprofloxacin = 8.66, 95% CI = 1.08–69.67). Those results were consistent with reported high levels of resistance of Sd1 to the commonest antibiotics, including nalidixic acid. Patients belonging to groups with a higher risk of dying should be given special medical attention and supportive care. In areas of high resistance to nalidixic acid, severe cases of dysentery should be treated with fluoroquinolones in order to reduce the mortality associated with these epidemics.

Viroses émergentes en Asie du Sud-Est et dans le Pacifique

The epidemiology of several viral diseases underwent profound changes in South-East Asia and Oceania over the past decades. This was due to several factors, including the geographical distribution of vectors and the viruses they transmit; increasing traveling and trade; increasing ecological and demographic pressure. We reviewed the current state of knowledge based on published sources and available epidemiological data. The review was limited to potentially emerging viruses in Southeast Asia and the Pacific reported in human cases. Dengue, Chikungunya, and Japanese Encephalitis viruses have recurred on a yearly basis with a steady increase in these regions. Ross River and Barmah viruses now appear regularly in Australia, in an increasing number of cases. Nipah virus strikes regularly with limited but deadly epidemics in Southeast Asia. Finally, infections by lyssaviruses, Kunjin, Murray Valley, or Zika viruses were also reviewed.

International Epidemic Intelligence at the Institut de Veille Sanitaire, France

The French Institute for Public Health Surveillance monitors health events of potential international importance occurring worldwide to provide timely warning to French health authorities. We reviewed the nature and place of occurrence of the last 200 events. From an individual country’s perspective, the need for multiple sources is emphasized.

Risk and control of imported cholera in a high-income country

Jane Zuckerman and colleagues rightly conclude that most cases of cholera worldwide are unreported and most cases of imported cholera go undetected. Failure to acknowledge a cholera epidemic may hinder governmental response and control eff orts in epidemic settings. But is the system really ineff ective in controlling imported cholera risks in high-income countries? Since 1973, there have been 135 imported cases of cholera in travellers returning to France. A detailed review of these cases up to 2005 has been published. Two (1·5%) of the 135 patients died. Of 63 patients for whom information on medical management was available, 51 (81%) were admitted to hospital and 12 (19%) were managed in the ambulatory setting. Since Jan 1, 2004, notifi ed cases, co-exposed individuals, family members, and health-care workers who provided care before cholera was suspected have been systematically and actively investigated. Of the nine cases notifi ed since Jan 1, 2004, three were managed in an ambulatory setting and six in the hospital. These six cases were all young children or elderly travellers to India or Pakistan, and their combined total hospital-stay was 81 days (mostly in intensive care) because of cholera treatment or complications. In 2006–07, investigations around two index cases found evidence of Vibrio cholerae O1 infection among other travellers returning to France, all of whom had been exposed to the same infection source. However, in fi ve of the six cases mentioned above, no indications (suggestive symptoms or bacteriological evidence) of secondary cholera were found in family members or among 192 health-care workers who provided direct care before diagnosis was suspected. There are no documented cases of secondary transmission for the 135 returning travellers to France notifi ed to date, and to our knowledge there is no evidence worldwide of secondary transmission of cholera from returning travellers, with the exception of one probable case in the USA. Based on this evidence of the low risk of secondary transmission of V cholerae O1, French health authorities are developing a rationale and step-by-step guide for managing alerts around imported cases to metropolitan France. In recommendations that are updated yearly, French authorities remind travellers of measures to prevent infection by diarrhoea-causing pathogens, including V cholerae O1 or V cholerae O139. Should a traveller become infected, however, the objective is not to avoid importation of V cholerae O1 or O139, since it does not result in secondary transmission when basic prevention methods are observed. Instead, the main aim of the guidelines is to detect and treat severe cases of cholera in people who are likely to die or have severe morbidity. As mentioned by Zuckerman and colleagues, many cases of V cholerae O1 or O139 infection cause few or no symptoms; therefore, detecting all imported cases is not technically feasible. It is not cost eff ective either, since detecting symptom-free cases would not reduce mortality or morbidity. Furthermore, the detection of all imported cases would not avoid secondary cases, which are unlikely to occur because of the current standards of hygiene in high-income countries. Finally, this control measure would be costly in terms of human and fi nancial resources. Recommendations for the control of imported cholera should focus on the prevention of infection and the detection of symptomatic cholera in people exposed to the same source as the index case. Available data show that secondary transmission to people who have not been co-exposed to the initial source is improbable and should not be a cause of undue concern. However, improved coordination between European and other countries undertaking surveillance on imported cholera is needed to help identify undeclared cholera epidemics worldwide, to provide guidance for clinicians advising travellers, and to help document antibiotic-resistant strains.