Sylvain Aldighieri

Zika Virus as a Cause of Neurologic Disorders

As researchers investigate whether and by what mechanisms Zika virus infections could affect the nervous system, there is a key question for public health: How can currently available evidence about causality guide the choice and implementation of interventions?

Global health security and the International Health Regulations

Global nuclear proliferation, bioterrorism, and emerging infections have challenged national capacities to achieve and maintain global security. Over the last century, emerging infectious disease threats resulted in the development of the preliminary versions of the International Health Regulations (IHR) of the World Health Organization (WHO). The current HR(2005) contain major differences compared to earlier versions, including: substantial shifts from containment at the border to containment at the source of the event; shifts from a rather small disease list (smallpox, plague, cholera, and yellow fever) required to be reported, to all public health threats; and shifts from preset measures to tailored responses with more flexibility to deal with the local situations on the ground. The new IHR(2005) call for accountability. They also call for strengthened national capacity for surveillance and control; prevention, alert, and response to international public health emergencies beyond the traditional short list of required reporting; global partnership and collaboration; and human rights, obligations, accountability, and procedures of monitoring. Under these evolved regulations, as well as other measures, such as the Revolving Fund for vaccine procurement of the Pan American Health Organization (PAHO), global health security could be maintained in the response to urban yellow fever in Paraguay in 2008 and the influenza (H1N1) pandemic of 2009-2010.

Zika Virus Infection and Associated Neurologic Disorders in Brazil

Zika virus has spread rapidly throughout the Americas and has been associated with fetal abnormalities and a variety of neurologic disorders. This report updates the epidemiologic findings over the past 2 years.

Leptospirosis Outbreaks in Nicaragua: Identifying Critical Areas and Exploring Drivers for Evidence-Based Planning

Leptospirosis is an epidemic-prone zoonotic disease that occurs worldwide. In Central America, leptospirosis outbreaks have been reported in almost all countries; Nicaragua in particular has faced several outbreaks. The objective of this study was to stratify the risk and identify “critical areas” for leptospirosis outbreaks in Nicaragua, and to perform an exploratory analysis of potential “drivers”. This ecological study includes the entire country (153 municipalities). Cases from 2004 to 2010 were obtained from the country’s health information system, demographic and socioeconomic variables from its Census, and environmental data from external sources. Criteria for risk stratification of leptospirosis were defined. Nicaragua reported 1,980 cases of leptospirosis during this period, with the highest percentage of cases (26.36%) in León, followed by Chinandega (15.35%). Among the 153 municipalities, 48 were considered critical areas, 85 were endemic and 20 silent. Using spatial and statistical analysis, the variable presenting the most evident pattern of association with critical areas defined by top quintile of incidence rate is the percentage of municipal surface occupied by the soil combination of cambisol (over pyroclastic and lava bedrock) and andosol (over a volcanic ashes foundation). Precipitation and percentage of rural population are also associated with critical areas. This methodology and findings could be used for Nicaragua’s Leptospirosis Intersectoral Plan, and to identify possible risk areas in other countries with similar drivers.

Zika Virus Transmission - Region of the Americas, May 15, 2015-December 15, 2016.

Zika virus, a mosquito-borne flavivirus that can cause rash with fever, emerged in the Region of the Americas on Easter Island, Chile, in 2014 and in northeast Brazil in 2015 (1). In response, in May 2015, the Pan American Health Organization (PAHO), which serves as the Regional Office of the Americas for the World Health Organization (WHO), issued recommendations to enhance surveillance for Zika virus. Subsequently, Brazilian investigators reported Guillain-Barré syndrome (GBS), which had been previously recognized among some patients with Zika virus disease, and identified an association between Zika virus infection during pregnancy and congenital microcephaly (2). On February 1, 2016, WHO declared Zika virus-related microcephaly clusters and other neurologic disorders a Public Health Emergency of International Concern.* In March 2016, PAHO developed case definitions and surveillance guidance for Zika virus disease and associated complications (3). Analysis of reports submitted to PAHO by countries in the region or published in national epidemiologic bulletins revealed that Zika virus transmission had extended to 48 countries and territories in the Region of the Americas by late 2016. Reported Zika virus disease cases peaked at different times in different areas during 2016. Because of ongoing transmission and the risk for recurrence of large outbreaks, response efforts, including surveillance for Zika virus disease and its complications, and vector control and other prevention activities, need to be maintained.

Leptospirosis: A Silent Epidemic Disease

This special issue of International Journal of Environmental Research and Public Health is dedicated to leptospirosis, an endemic zoonotic disease that is a cause of many acute undifferentiated fevers, especially in tropical countries. While it can be debated whether leptospirosis is an emerging disease, it is evident that it is becoming an emerging public health problem. It is recognized as a disease of epidemic potential that has a significant health impact in many parts of the world.

Association between microcephaly, Zika virus infection, and other risk factors in Brazil: final report of a case-control study

BACKGROUND A Zika virus epidemic emerged in northeast Brazil in 2015 and was followed by a striking increase in congenital microcephaly cases, triggering a declaration of an international public health emergency. This is the final report of the first case-control study evaluating the potential causes of microcephaly: congenital Zika virus infection, vaccines, and larvicides. The published preliminary report suggested a strong association between microcephaly and congenital Zika virus infection. METHODS We did a case-control study in eight public maternity hospitals in Recife, Brazil. Cases were neonates born with microcephaly, defined as a head circumference of 2 SD below the mean. Two controls without microcephaly were matched to each case by expected date of delivery and area of residence. We tested the serum of cases and controls and the CSF of cases for detection of Zika virus genomes with quantitative RT-PCR and for detection of IgM antibodies with capture-IgM ELISA. We also tested maternal serum with plaque reduction neutralisation assays for Zika and dengue viruses. We estimated matched crude and adjusted odds ratios with exact conditional logistic regression to determine the association between microcephaly and Zika virus infection. FINDINGS We screened neonates born between Jan 15 and Nov 30, 2016, and prospectively recruited 91 cases and 173 controls. In 32 (35%) cases, congenital Zika virus infection was confirmed by laboratory tests and no controls had confirmed Zika virus infections. 69 (83%) of 83 cases with known birthweight were small for gestational age, compared with eight (5%) of 173 controls. The overall matched odds ratio was 73·1 (95% CI 13·0-∞) for microcephaly and Zika virus infection after adjustments. Neither vaccination during pregnancy or use of the larvicide pyriproxyfen was associated with microcephaly. Results of laboratory tests for Zika virus and brain imaging results were available for 79 (87%) cases; within these cases, ten were positive for Zika virus and had cerebral abnormalities, 13 were positive for Zika infection but had no cerebral abnormalities, and 11 were negative for Zika virus but had cerebral abnormalities. INTERPRETATION The association between microcephaly and congenital Zika virus infection was confirmed. We provide evidence of the absence of an effect of other potential factors, such as exposure to pyriproxyfen or vaccines (tetanus, diphtheria, and acellular pertussis, measles and rubella, or measles, mumps, and rubella) during pregnancy, confirming the findings of an ecological study of pyriproxyfen in Pernambuco and previous studies on the safety of Tdap vaccine administration during pregnancy. FUNDING Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations.

Where does human plague still persist in Latin America

Background Plague is an epidemic-prone disease with a potential impact on public health, international trade, and tourism. It may emerge and re-emerge after decades of epidemiological silence. Today, in Latin America, human cases and foci are present in Bolivia, Brazil, Ecuador, and Peru. Aims The objective of this study is to identify where cases of human plague still persist in Latin America and map areas that may be at risk for emergence or re-emergence. This analysis will provide evidence-based information for countries to prioritize areas for intervention. Methods Evidence of the presence of plague was demonstrated using existing official information from WHO, PAHO, and Ministries of Health. A geo-referenced database was created to map the historical presence of plague by country between the first registered case in 1899 and 2012. Areas where plague still persists were mapped at the second level of the political/administrative divisions (counties). Selected demographic, socioeconomic, and environmental variables were described. Results Plague was found to be present for one or more years in 14 out of 25 countries in Latin America (1899–2012). Foci persisted in six countries, two of which have no report of current cases. There is evidence that human cases of plague still persist in 18 counties. Demographic and poverty patterns were observed in 11/18 counties. Four types of biomes are most commonly found. 12/18 have an average altitude higher than 1,300 meters above sea level. Discussion Even though human plague cases are very localized, the risk is present, and unexpected outbreaks could occur. Countries need to make the final push to eliminate plague as a public health problem for the Americas. A further disaggregated risk evaluation is recommended, including identification of foci and possible interactions among areas where plague could emerge or re-emerge. A closer geographical approach and environmental characterization are suggested.

Outbreak of rotavirus gastroenteritis with high mortality, Nicaragua, 2005

OBJECTIVES We investigated a nationwide outbreak of severe rotavirus gastroenteritis in Nicaragua in children under 5 years old, leading to many consultations, hospitalizations, and deaths. We questioned whether a vaccine might have prevented these illnesses and deaths, sought to identify risk factors for death, and developed a clinical profile of children hospitalized with diarrhea. METHODS We conducted a case-control study to determine whether children who died had access to routine immunizations, a proxy predicting access to a rotavirus vaccine. We identified risk factors for death among children who died in the outbreak compared with surviving age-matched controls with diarrhea. We collected stools, clinical data, and immunization data on children hospitalized for diarrhea to test for rotavirus, develop the profile, and forecast future access to a rotavirus vaccine. RESULTS The outbreak from February to April 2005 caused 47 470 consultations and 52 deaths. Approximately 80% of cases and controls and 60% of children hospitalized with diarrhea had access to routine immunizations and would likely have had access to a rotavirus vaccine. With a vaccine efficacy of 85%, up to 51% of severe rotavirus cases and up to 68% of deaths could have been prevented if a rotavirus vaccine were available as part of routine childhood immunizations. Study of 35 case-control pairs indicated that severe illnesses, malnutrition, and care by traditional healers were risk factors for death. Rotavirus was found in 42% of samples from hospitalized children and was associated with severe disease and dehydration. CONCLUSIONS The impact of the seasonal outbreaks of rotavirus disease could be diminished with a rotavirus vaccine, improvements in oral rehydration programs, and training of traditional healers in the proper management of children with acute diarrhea.

Analyzing climate variations at multiple timescales can guide Zika virus response measures.

BackgroundThe emergence of Zika virus (ZIKV) in Latin America and the Caribbean in 2014–2016 occurred during a period of severe drought and unusually high temperatures, conditions that have been associated with the 2015–2016 El Niño event, and/or climate change; however, no quantitative assessment has been made to date. Analysis of related flaviviruses transmitted by the same vectors suggests that ZIKV dynamics are sensitive to climate seasonality and longer-term variability and trends. A better understanding of the climate conditions conducive to the 2014–2016 epidemic may permit the development of climate-informed short and long-term strategies for ZIKV prevention and control.ResultsUsing a novel timescale-decomposition methodology, we demonstrate that the extreme climate anomalies observed in most parts of South America during the current epidemic are not caused exclusively by El Niño or climate change, but by a combination of climate signals acting at multiple timescales. In Brazil, the dry conditions present in 2013–2015 are primarily explained by year-to-year variability superimposed on decadal variability, but with little contribution of long-term trends. In contrast, the warm temperatures of 2014–2015 resulted from the compound effect of climate change, decadal and year-to-year climate variability.ConclusionsZIKV response strategies made in Brazil during the drought concurrent with the 2015-2016 El Niño event, may require revision in light of the likely return of rainfall associated with the borderline La Niña event expected in 2016–2017. Temperatures are likely to remain warm given the importance of long term and decadal scale climate signals.