• The dynamics of measles in sub-Saharan Africa.

      Ferrari, M J; Grais, R; Bharti, N; Conlan, A J K; Bjørnstad, O N; Wolfson, L J; Guerin, P J; Djibo, A; Grenfell, B T; Center for Infectious Disease Dynamics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. mferrari@psu.edu (Macmillan, 2008-02-07)
      Although vaccination has almost eliminated measles in parts of the world, the disease remains a major killer in some high birth rate countries of the Sahel. On the basis of measles dynamics for industrialized countries, high birth rate regions should experience regular annual epidemics. Here, however, we show that measles epidemics in Niger are highly episodic, particularly in the capital Niamey. Models demonstrate that this variability arises from powerful seasonality in transmission-generating high amplitude epidemics-within the chaotic domain of deterministic dynamics. In practice, this leads to frequent stochastic fadeouts, interspersed with irregular, large epidemics. A metapopulation model illustrates how increased vaccine coverage, but still below the local elimination threshold, could lead to increasingly variable major outbreaks in highly seasonally forced contexts. Such erratic dynamics emphasize the importance both of control strategies that address build-up of susceptible individuals and efforts to mitigate the impact of large outbreaks when they occur.
    • Estimates of measles case fatality ratios: a comprehensive review of community-based studies.

      Wolfson, Lara J; Grais, Rebecca F; Luquero, Francisco J; Birmingham, Maureen E; Strebel, Peter M; Health Security and Environment, World Health Organization, Geneva 27, Switzerland. wolfsonl@who.int (2009-02)
      BACKGROUND: Global deaths from measles have decreased notably in past decades, due to both increases in immunization rates and decreases in measles case fatality ratios (CFRs). While some aspects of the reduction in measles mortality can be monitored through increases in immunization coverage, estimating the level of measles deaths (in absolute terms) is problematic, particularly since incidence-based methods of estimation rely on accurate measures of measles CFRs. These ratios vary widely by geographic and epidemiologic context and even within the same community from year-to-year. METHODS: To understand better the variations in CFRs, we reviewed community-based studies published between 1980 and 2008 reporting age-specific measles CFRs. RESULTS: The results of the search consistently document that measles CFRs are highest in unvaccinated children under age 5 years; in outbreaks; the lowest CFRs occur in vaccinated children regardless of setting. The broad range of case and death definitions, study populations and geography highlight the complexities in extrapolating results for global public health planning. CONCLUSIONS: Values for measles CFRs remain imprecise, resulting in continued uncertainty about the actual toll measles exacts.
    • Exploring the Time to Intervene with a Reactive Mass Vaccination Campaign in Measles Epidemics.

      Grais, R; de Radiguès, X; Dubray, C; Fermon, F; Guerin, P J; Epicentre, 8 rue Saint Sabin, Paris, France. rebecca.grais@epicentre.msf.org (2006-08)
      The current WHO policy during measles outbreaks focuses on case management rather than reactive vaccination campaigns in urban areas of resource-poor countries having low vaccine coverage. Vaccination campaigns may be costly, or not timely enough to impact significantly on morbidity and mortality. We explored the time available for intervention during two recent epidemics. Our analysis suggests that the spread of measles in African urban settings may not be as fast as expected. Examining measles epidemic spread in Kinshasa (DRC), and Niamey (Niger) reveals a progression of smaller epidemics. Intervening with a mass campaign or in areas where cases have not yet been reported could slow the epidemic spread. The results of this preliminary analysis illustrate the importance of revisiting outbreak response plans.
    • A long-lasting measles epidemic in Maroua, Cameroon 2008-2009: mass vaccination as response to the epidemic.

      Luquero, Francisco J; Pham-Orsetti, Heloise; Cummings, D A T; Ngaunji, Philippe E; Nimpa, Marcelino; Fermon, Florence; Ngoe, Ndong; Sosler, Stephen; Strebel, Peter; Grais, Rebecca F; et al. (2011-07)
      A measles outbreak occurred in Maroua, Cameroon, from January 2008 to April 2009. In accordance with recent World Health Organization guidelines, an outbreak-response immunization (ORI) was conducted in January 2009. The aim of this study was to investigate the causes of the epidemic in order to guide vaccination strategies.
    • Measles epidemic in the urban community of Niamey: transmission patterns, vaccine efficacy and immunization strategies, Niger, 1990 to 1991.

      Malfait, P; Jataou, I M; Jollet, M C; Margot, A; De Benoist, A C; Moren, A; Epicentre, Paris, France. (1994-01)
      From October 1, 1990, until April 28, 1991, 13,578 cases of measles were reported in the urban community of Niamey, Niger. Vaccine coverages (one dose of Schwarz vaccine given after 9 months) in urban community of Niamey were, respectively, 63% at the age of 12 months and 73% at 24 months before the epidemic. Incidence rates were the highest among children ages 6 to 8 months and 9 to 11 months and 22% of the cases were less than 1 year old. Vaccine efficacy estimates ranged from 86 to 94% according to age groups and the method used (screening method, case control study, retrospective cohort study). The risk of transmission of illness increased with the intensity of contact with a case. Contact with a health facility 7 to 22 days before onset of rash was not a risk factor. Seasonal migrants in Niamey were more likely to develop measles. Recommendations included implementation of an early two dose schedule of measles immunization during the outbreak, vaccination offered at each contact with a health facility, radio and television advertising for measles immunization and distribution of vitamin A to all measles cases.
    • Measles hotspots and epidemiological connectivity

      Bharti, N; Djibo, A; Ferrari, M J; Grais, R F; Tatem, A J; McCabe, C A; Bjornstad, O N; Grenfell, B T; Penn State University, Biology Department and Center for Infectious Disease Dynamics, University Park, PA, USA; Ministry of Health, Niamey, Niger; Epicentre, Paris, France; University of Florida, Emerging Pathogens Institute and Department of Geography, Gainesville, FL, USA; Penn State University, Department of Geography and GeoVISTA Center, University Park, PA, USA; Penn State University, Department of Entomology, University Park, PA, USA; Fogarty International Center, National Institutes of Health, Bethesda, MD, USA (2010-09-25)
      Though largely controlled in developed countries, measles remains a major global public health issue. Regional and local transmission patterns are rooted in human mixing behaviour across spatial scales. Identifying spatial interactions that contribute to recurring epidemics helps define and predict outbreak patterns. Using spatially explicit reported cases from measles outbreaks in Niger, we explored how regional variations in movement and contact patterns relate to patterns of measles incidence. Because we expected to see lower rates of re-introductions in small, compared to large, populations, we measured the population-size corrected proportion of weeks with zero cases across districts to understand relative rates of measles re-introductions. We found that critical elements of spatial disease dynamics in Niger are agricultural seasonality, transnational contact clusters, and roads networks that facilitate host movement and connectivity. These results highlight the need to understand local patterns of seasonality, demographic characteristics, and spatial heterogeneities to inform vaccination policy.
    • Measles outbreaks in the Mozambican refugee camps in Malawi: the continued need for an effective vaccine.

      Porter, J D; Gastellu-Etchegorry, M; Navarre, I; Lungu, G; Moren, A; Epicentre, Paris, France. (Oxford University Press, 1990-12)
      Between November 1988 and January 1989, measles outbreaks occurred in 11 Mozambican refugee camps in Malawi with five camps principally affected. A total of 1214 cases were reported. Despite the reduction of the age of measles vaccination to six months in 1987, attack rates were highest in children aged 6-9 months (10-26%); rates were also high in the 0-5 month age group (3-21%). The case-fatality rate was high among children less than five years old (15-21%). Children were being inappropriately vaccinated, either being vaccinated at less than six months of age (2-29%) or failing to receive a second dose if vaccinated at six months (0-25%). With vaccine coverage between 66-87%, vaccine efficacy in children less than five years old was estimated to be more than 90% in the camps principally affected. Reduction of the age of vaccination leads to logistical problems in vaccine delivery in refugee situations. These outbreaks again indicate the need to improve vaccine coverage with the existing Schwarz vaccine, and also highlight the urgent need for an effective single dose measles vaccine for children less than nine months of age.
    • Measles vaccine effectiveness in standard and early immunization strategies, Niger, 1995.

      Kaninda, A V; Legros, D; Jataou, I M; Malfait, P; Maisonneuve, M; Paquet, C; Moren, A; Epicentre, Paris, France. epimail@epicentre.msf.org (1998-11)
      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.
    • Modelling the first dose of measles vaccination: the role of maternal immunity, demographic factors, and delivery systems.

      Metcalf, C J E; Klepac, P; Ferrari, M; Grais, R F; Djibo, A; Grenfell, B T; Department of Ecology and Evolutionary Biology, Princeton University, NJ 0854, USA. cmetcalf@princeton.edu (Cambridge University Press, 2011-02)
      Measles vaccine efficacy is higher at 12 months than 9 months because of maternal immunity, but delaying vaccination exposes the children most vulnerable to measles mortality to infection. We explored how this trade-off changes as a function of regionally varying epidemiological drivers, e.g. demography, transmission seasonality, and vaccination coverage. High birth rates and low coverage both favour early vaccination, and initiating vaccination at 9-11 months, then switching to 12-14 months can reduce case numbers. Overall however, increasing the age-window of vaccination decreases case numbers relative to vaccinating within a narrow age-window (e.g. 9-11 months). The width of the age-window that minimizes mortality varies as a function of birth rate, vaccination coverage and patterns of access to care. Our results suggest that locally age-targeted strategies, at both national and sub-national scales, tuned to local variation in birth rate, seasonality, and access to care may substantially decrease case numbers and fatalities for routine vaccination.
    • Should outbreak response immunization be recommended for measles outbreaks in middle- and low-income countries? An update.

      Cairns, K Lisa; Perry, Robert T; Ryman, Tove K; Nandy, Robin K; Grais, Rebecca F; Global Immunization Division, US Centers for Disease Control and Prevention, Atlanta, Georgia 30306, USA. kfc4@cdc.gov (2011-07)
      Measles caused mortality in >164,000 children in 2008, with most deaths occurring during outbreaks. Nonetheless, the impact and desirability of conducting measles outbreak response immunization (ORI) in middle- and low-income countries has been controversial. World Health Organization guidelines published in 1999 recommended against ORI in such settings, although recently these guidelines have been reversed for countries with measles mortality reduction goals.
    • Time is of the essence: exploring a measles outbreak response vaccination in Niamey, Niger.

      Grais, R; Conlan, A J K; Ferrari, M J; Djibo, A; Le Menach, A; Bjørnstad, O N; Grenfell, B T; Epicentre, 8 rue Saint Sabin, 75011 Paris, France. rebecca.grais@epicentre.msf.org (The Royal Society Publishing, 2008-01-06)
      The current World Health Organization recommendations for response during measles epidemics focus on case management rather than outbreak response vaccination (ORV) campaigns, which may occur too late to impact morbidity and mortality and have a high cost per case prevented. Here, we explore the potential impact of an ORV campaign conducted during the 2003-2004 measles epidemic in Niamey, Niger. We measured the impact of this intervention and also the potential impact of alternative strategies. Using a unique geographical, epidemiologic and demographic dataset collected during the epidemic, we developed an individual-based simulation model. We estimate that a median of 7.6% [4.9-8.9] of cases were potentially averted as a result of the outbreak response, which vaccinated approximately 57% (84563 of an estimated 148600) of children in the target age range (6-59 months), 23 weeks after the epidemic started. We found that intervening early (up to 60 days after the start of the epidemic) and expanding the age range to all children aged 6 months to 15 years may lead to a much larger (up to 90%) reduction in the number of cases in a West African urban setting like Niamey. Our results suggest that intervening earlier even with lower target coverage (approx. 60%), but a wider age range, may be more effective than intervening later with high coverage (more than 90%) in similar settings. This has important implications for the implementation of reactive vaccination interventions as they can be highly effective if the response is fast with respect to the spread of the epidemic.