Robin Nandy

Laboratory characterization of measles virus infection in previously vaccinated and unvaccinated individuals.

Waning immunity or secondary vaccine failure (SVF) has been anticipated by some as a challenge to global measles elimination efforts. Although such cases are infrequent, measles virus (MeV) infection can occur in vaccinated individuals following intense and/or prolonged exposure to an infected individual and may present as a modified illness that is unrecognizable as measles outside of the context of a measles outbreak. The immunoglobulin M response in previously vaccinated individuals may be nominal or fleeting, and viral replication may be limited. As global elimination proceeds, additional methods for confirming modified measles cases may be needed to understand whether SVF cases contribute to continued measles virus (MeV) transmission. In this report, we describe clinical symptoms and laboratory results for unvaccinated individuals with acute measles and individuals with SVF identified during MeV outbreaks. SVF cases were characterized by the serological parameters of high-avidity antibodies and distinctively high levels of neutralizing antibody. These parameters may represent useful biomarkers for classification of SVF cases that previously could not be confirmed as such using routine laboratory diagnostic techniques.

Measles outbreak in South Africa, 2003-2005.

OBJECTIVES Measles was virtually eliminated in South Africa following control activities in 1996/7. However, from July 2003 to November 2005, 1676 laboratory-confirmed measles cases were reported in South Africa. We investigated the outbreaks cause and the role of HIV. DESIGN We traced laboratory-confirmed case-patients residing in the Johannesburg metropolitan (JBM) and O. R. Tambo districts. We interviewed laboratory--or epidemiologically confirmed case-patients or their caregivers to determine vaccination status and, in JBM, HIV status. We calculated vaccine effectiveness using the screening method. SETTING Household survey in JBM and O. R. Tambo districts. Outcome measures. Vaccine effectiveness, case-fatality rate, and hospitalisations. RESULTS In JBM, 109 case-patients were investigated. Of the 57 case-patients eligible for immunisation, 27 (47.4%) were vaccinated. Fourteen (12.8%) case-patients were HIV infected, 46 (42.2%) were HIV uninfected, and 49 (45.0%) had unknown HIV status. Among children aged 12-59 months, vaccine effectiveness was 85% (95% confidence interval (CI): 63, 94) for all children, 63% for HIV infected, 75% for HIV uninfected, and 96% for children with unknown HIV status. (Confidence intervals were not calculated for sub-groups owing to small sample size.) In O. R. Tambo district, 157 case-patients were investigated. Among the 138 case-patients eligible for immunisation, 41 (29.7%) were vaccinated. Vaccine effectiveness was 89% (95% CI 77, 95). CONCLUSIONS The outbreaks primary cause was failure to vaccinate enough of the population to prevent endemic measles transmission. Although vaccine effectiveness might have been lower in HIV-infected than in uninfected children, population vaccine effectiveness remained high.

Laboratory confirmation of measles in elimination settings: experience from the Republic of the Marshall Islands, 2003

OBJECTIVE To highlight the complications involved in interpreting laboratory tests of measles immunoglobulin M (IgM) for confirmation of infection during a measles outbreak in a highly vaccinated population after conducting a mass immunization campaign as a control measure. METHODS This case study was undertaken in the Republic of the Marshall Islands during a measles outbreak in 2003, when response immunization was conducted. A measles case was defined as fever and rash and one or more of cough, coryza or conjunctivitis. Between 13 July and 7 November 2003, serum samples were obtained from suspected measles cases for serologic testing and nasopharyngeal swabs were taken for viral isolation by reverse transcriptase polymerase chain reaction (RT-PCR). FINDINGS Specimens were collected from 201 suspected measles cases (19% of total): of the ones that satisfied the clinical case definition, 45% were IgM positive (IgM+) and, of these, 24% had received measles vaccination within the previous 45 days (up to 45 days after vaccination an IgM+ result could be due to either vaccination or wild-type measles infection). The proportion of IgM+ results varied with clinical presentation, the timing of specimen collection and vaccination status. Positive results on RT-PCR occurred in specimens from eight IgM-negative and four IgM+ individuals who had recently been vaccinated. CONCLUSION During measles outbreaks, limiting IgM testing to individuals who meet the clinical case definition and have not been recently vaccinated allows for measles to be confirmed while conserving resources.

Measles deaths in Nepal: estimating the national case-fatality ratio

OBJECTIVE To estimate the case-fatality ratio (CFR) for measles in Nepal, determine the role of risk factors, such as political instability, for measles mortality, and compare the use of a nationally representative sample of outbreaks versus routine surveillance or a localized study to establish the national CFR (nCFR). METHODS This was a retrospective study of measles cases and deaths in Nepal. Through two-stage random sampling, we selected 37 districts with selection probability proportional to the number of districts in each region, and then randomly selected within each district one outbreak among all those that had occurred between 1 March and 1 September 2004. Cases were identified by interviewing a member of each and every household and tracing contacts. Bivariate analyses were performed to assess the risk factors for a high CFR and determine the time from rash onset until death. Each factors contribution to the CFR was determined through multivariate logistic regression. From the number of measles cases and deaths found in the study we calculated the total number of measles cases and deaths for all of Nepal during the study period and in 2004. FINDINGS We identified 4657 measles cases and 64 deaths in the study period and area. This yielded a total of about 82 000 cases and 900 deaths for all outbreaks in 2004 and a national CFR of 1.1% (95% confidence interval, CI: 0.5-2.3). CFR ranged from 0.1% in the eastern region to 3.4% in the mid-western region and was highest in politically insecure areas, in the Ganges plains and among cases < 5 years of age. Vitamin A treatment and measles immunization were protective. Most deaths occurred during the first week of illness. CONCLUSION To our knowledge, this is the first CFR study based on a nationally representative sample of measles outbreaks. Routine surveillance and studies of a single outbreak may not yield an accurate nCFR. Increased fatalities associated with political insecurity are a challenge for health-care service delivery. The short period from disease onset to death and reduced mortality from treatment with vitamin A suggest the need for rapid, field-based treatment early in the outbreak.

Mortalidad por sarampión en Nepal: estimación de la tasa de letalidad

Introduction Estimates of measles-related deaths are critical for monitoring progress towards global measles elimination goals and for prioritizing measles control in relation to other public health interventions. However, such estimates vary widely. WHO uses underlying case-fatality ratios (CFRs) to estimate measles-related deaths. (1,2) Studies of measles CFRs have generally been restricted to one or two areas within a country or to specific populations involving fewer than 1000 cases, and they have not evaluated geographic variability or the localized effects of factors such as political insecurity. (3-17) To our knowledge, no nationally representative study of measles CFRs has previously been conducted in a measles-endemic country. Localized CFR estimates in south-east Asia (4,9-11,13,15,16) and globally (3,5-8,12,14,18-20) have varied from less than 1% to 25%, but many studies were conducted before implementation of the Integrated Management of Childhood Illness strategy and recommendations to administer vitamin A to all measles cases. Therefore, many of these studies may not reflect the current situation. No estimates of measles CFRs have previously been published from Nepal, a country characterized by geographic inaccessibility and, for the last decade, by political unrest. Uncertainty about the national case fatality ratio (nCFR) for measles hinders evaluation of the measles control programme, including strategies to reduce measles mortality. This paper describes a study of measles cases and deaths in a nationally representative sample of measles outbreaks. The aim was to estimate the nCFR, establish a baseline for evaluating disease burden, and determine the role of political instability and other risk factors for measles mortality. We used the data to estimate the number of measles cases and deaths that occurred in Nepal in 2004. We also examined the implications of determining the nCFR using a nationally representative sample of outbreaks rather than data from routine surveillance of a localized study. Methods Setting Nepal has a population of 28 million people, of whom 86% live in rural areas, 42% are unemployed and nearly 33% live in poverty. (21,22) The country is administratively divided into 75 districts in five development regions--far-western, mid-western, western, central and eastern. Topography divides Nepal into three ecological zones--the Himalayas in the north bordering China, the Ganges plains in the south bordering India and the Himalayan foothills in-between. These regions and zones vary with respect to economic status, accessibility and health infrastructure, with the western regions being less developed than the central and eastern regions. From 1996 to 2006, a Maoist insurgency led to more than 12 000 deaths and internal displacement of 400 000 rural families, and it destroyed physical infrastructure worth at least US

Case-Fatality Rate during a Measles Outbreak in Eastern Niger in 2003

250 million. (23) Security concerns, lack of infrastructure and mountainous terrain make the delivery of public health services challenging in much of Nepal. Measles is endemic in Nepal; an estimated average of 90 000 cases per year occurred from 1994 to 2002, based on extrapolations from routine surveillance reports. (24) Routine measles vaccination began in three districts in 1979 and was expanded nationwide by 1989; children receive a single dose of measles vaccine at 9 months of age. The most recent Demographic and Health Survey, conducted in 2001, estimated that coverage with one dose of measles vaccine among children aged 12-23 months was approximately 71% overall, with regional variability from 65% to 79%. (25) Routine surveillance system A measles outbreak is defined as more than five cases in a geographic area (i.e. village of urban ward) during a one-week period. Since 1994, Nepals national Health Management Information System has received monthly data on such outbreaks from local heath personnel or other local authorities in 4000 clinics nationwide. …