The efficacy and safety of rotavirus vaccines in countries in Africa and Asia with high child mortality.

Rotavirus remains a leading cause of diarrhoeal morbidity and mortality in young children and rotavirus vaccines are critical for reducing global disease burden. This report addresses the performance of rotavirus vaccines in countries with high child mortality. We performed a sensitivity analysis as part of a systematic review on rotavirus vaccines to inform development of World Health Organization vaccine recommendations. The efficacy of four prequalified vaccines against severe rotavirus gastroenteritis was similar across high mortality settings in Asia and Africa. Within the first year following vaccination, vaccine efficacy for the four vaccines ranged from 48% to 57% while in the second year, efficacy ranged from 29% to 54%. The four vaccines showed no increase in intussusception risk in these settings. All four vaccines appear to prevent significant numbers of severe rotavirus gastroenteritis episodes with no measurable increase in intussusception risk in high mortality settings in Africa and Asia.

Complex interactions between malaria and malnutrition: a systematic literature review.

BACKGROUND: Despite substantial improvement in the control of malaria and decreased prevalence of malnutrition over the past two decades, both conditions remain heavy burdens that cause hundreds of thousands of deaths in children in resource-poor countries every year. Better understanding of the complex interactions between malaria and malnutrition is crucial for optimally targeting interventions where both conditions co-exist. This systematic review aimed to assess the evidence of the interplay between malaria and malnutrition. METHODS: Database searches were conducted in PubMed, Global Health and Cochrane Libraries and articles published in English, French or Spanish between Jan 1980 and Feb 2018 were accessed and screened. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale and the risk of bias across studies was assessed using the GRADE approach. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline were followed. RESULTS: Of 2945 articles screened from databases, a total of 33 articles were identified looking at the association between malnutrition and risk of malaria and/or the impact of malnutrition in antimalarial treatment efficacy. Large methodological heterogeneity of studies precluded conducting meaningful aggregated data meta-analysis. Divergent results were reported on the effect of malnutrition on malaria risk. While no consistent association between risk of malaria and acute malnutrition was found, chronic malnutrition was relatively consistently associated with severity of malaria such as high-density parasitemia and anaemia. Furthermore, there is little information on the effect of malnutrition on therapeutic responses to artemisinin combination therapies (ACTs) and their pharmacokinetic properties in malnourished children in published literature. CONCLUSIONS: The evidence on the effect of malnutrition on malaria risk remains inconclusive. Further analyses using individual patient data could provide an important opportunity to better understand the variability observed in publications by standardising both malaria and nutritional metrics. Our findings highlight the need to improve our understanding of the pharmacodynamics and pharmacokinetics of ACTs in malnourished children. Further clarification on malaria-malnutrition interactions would also serve as a basis for designing future trials and provide an opportunity to optimise antimalarial treatment for this large, vulnerable and neglected population. TRIAL REGISTRATION: PROSPERO CRD42017056934 .

Characteristics of human encounters and social mixing patterns relevant to infectious diseases spread by close contact: a survey in Southwest Uganda.

BACKGROUND: Quantification of human interactions relevant to infectious disease transmission through social contact is central to predict disease dynamics, yet data from low-resource settings remain scarce. METHODS: We undertook a social contact survey in rural Uganda, whereby participants were asked to recall details about the frequency, type, and socio-demographic characteristics of any conversational encounter that lasted for ≥5 min (henceforth defined as 'contacts') during the previous day. An estimate of the number of 'casual contacts' (i.e. < 5 min) was also obtained. RESULTS: In total, 566 individuals were included in the study. On average participants reported having routine contact with 7.2 individuals (range 1-25). Children aged 5-14 years had the highest frequency of contacts and the elderly (≥65 years) the fewest (P < 0.001). A strong age-assortative pattern was seen, particularly outside the household and increasingly so for contacts occurring further away from home. Adults aged 25-64 years tended to travel more often and further than others, and males travelled more frequently than females. CONCLUSION: Our study provides detailed information on contact patterns and their spatial characteristics in an African setting. It therefore fills an important knowledge gap that will help more accurately predict transmission dynamics and the impact of control strategies in such areas.

Strengthening the evidence base for health programming in humanitarian crises.

Given the growing scale and complexity of responses to humanitarian crises, it is important to develop a stronger evidence base for health interventions in such contexts. Humanitarian crises present unique challenges to rigorous and effective research, but there are substantial opportunities for scientific advance. Studies need to focus where the translation of evidence from noncrisis scenarios is not viable and on ethical ways of determining what happens in the absence of an intervention. Robust methodologies suited to crisis settings have to be developed and used to assess interventions with potential for delivery at scale. Strengthening research capacity in the low- to middle-income countries that are vulnerable to crises is also crucial.

Spatial dynamics of meningococcal meningitis in Niger: observed patterns in comparison with measles.

Throughout the African meningitis belt, meningococcal meningitis outbreaks occur only during the dry season. Measles in Niger exhibits similar seasonality, where increased population density during the dry season probably escalates measles transmission. Because meningococcal meningitis and measles are both directly transmitted, we propose that host aggregation also impacts the transmission of meningococcal meningitis. Although climate affects broad meningococcal meningitis seasonality, we focus on the less examined role of human density at a finer spatial scale. By analysing spatial patterns of suspected cases of meningococcal meningitis, we show fewer absences of suspected cases in districts along primary roads, similar to measles fadeouts in the same Nigerien metapopulation. We further show that, following periods during no suspected cases, districts with high reappearance rates of meningococcal meningitis also have high measles reintroduction rates. Despite many biological and epidemiological differences, similar seasonal and spatial patterns emerge from the dynamics of both diseases. This analysis enhances our understanding of spatial patterns and disease transmission and suggests hotspots for infection and potential target areas for meningococcal meningitis surveillance and intervention.

Explaining seasonal fluctuations of measles in Niger using nighttime lights imagery.

Measles epidemics in West Africa cause a significant proportion of vaccine-preventable childhood mortality. Epidemics are strongly seasonal, but the drivers of these fluctuations are poorly understood, which limits the predictability of outbreaks and the dynamic response to immunization. We show that measles seasonality can be explained by spatiotemporal changes in population density, which we measure by quantifying anthropogenic light from satellite imagery. We find that measles transmission and population density are highly correlated for three cities in Niger. With dynamic epidemic models, we demonstrate that measures of population density are essential for predicting epidemic progression at the city level and improving intervention strategies. In addition to epidemiological applications, the ability to measure fine-scale changes in population density has implications for public health, crisis management, and economic development.

Modelling the first dose of measles vaccination: the role of maternal immunity, demographic factors, and delivery systems.

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.

Outbreak response immunisation: The experience of Chad during recurrent measles epidemics in 2005 and 2010.

Despite impressive gains in measles control globally, measles epidemics continue to occur in countries with insufficient vaccination coverage. WHO guidelines now recommend outbreak response immunisation (ORI) for controlling measles outbreaks in certain contexts. The objective of this study was to describe late and early response vaccination activities during two consecutive measles outbreaks that occurred in 2005 and 2010 in N'Djamena, Chad. Using Lot Quality Assurance Sampling, vaccination coverage was estimated to be low before the interventions. Following mass vaccination campaigns, measles cases declined. The timeliness and quality of ORI activities are crucial determinants of success. However, effective outbreak response should be accompanied by strong routine vaccination programmes to ensure sustainable high vaccination coverage.

Measles hotspots and epidemiological connectivity.

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.

Episodic outbreaks bias estimates of age-specific force of infection: a corrected method using measles as an example.

Understanding age-specific differences in infection rates can be important in predicting the magnitude of and mortality in outbreaks and targeting age groups for vaccination programmes. Standard methods to estimate age-specific rates assume that the age-specific force of infection is constant in time. However, this assumption may easily be violated in the face of a highly variable outbreak history, as recently observed for acute immunizing infections like measles, in strongly seasonal settings. Here we investigate the biases that result from ignoring such fluctuations in incidence and present a correction based on the epidemic history. We apply the method to data from a measles outbreak in Niamey, Niger and show that, despite a bimodal age distribution of cases, the estimated age-specific force of infection is unimodal and concentrated in young children (<5 years) consistent with previous analyses of age-specific rates in the region.

Use of Lot Quality Assurance Sampling (LQAS) to estimate vaccination coverage helps guide future vaccination efforts.

Inadequate evaluation of vaccine coverage after mass vaccination campaigns, such as used in national measles control programmes, can lead to inappropriate public health responses. Overestimation of vaccination coverage may leave populations at risk, whilst underestimation can lead to unnecessary catch-up campaigns. The problem is more complex in large urban areas where vaccination coverage may be heterogeneous and the programme may have to be fine-tuned at the level of geographic subunits. Lack of accurate population figures in many contexts further complicates accurate vaccination coverage estimates. During the evaluation of a mass vaccination campaign carried out in N'Djamena, the capital of Chad, Lot Quality Assurance Sampling was used to estimate vaccination coverage. Using this method, vaccination coverage could be evaluated within smaller geographic areas of the city as well as for the entire city. Despite the lack of accurate population data by neighbourhood, the results of the survey showed heterogeneity of vaccination coverage within the city. These differences would not have been identified using a more traditional method. The results can be used to target areas of low vaccination coverage during follow-up vaccination activities.

Time is of the essence: exploring a measles outbreak response vaccination in Niamey, Niger.

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.

Unacceptably high mortality related to measles epidemics in Niger, Nigeria, and Chad.

BACKGROUND: Despite the comprehensive World Health Organization (WHO)/United Nations Children's Fund (UNICEF) measles mortality-reduction strategy and the Measles Initiative, a partnership of international organizations supporting measles mortality reduction in Africa, certain high-burden countries continue to face recurrent epidemics. To our knowledge, few recent studies have documented measles mortality in sub-Saharan Africa. The objective of our study was to investigate measles mortality in three recent epidemics in Niamey (Niger), N'Djamena (Chad), and Adamawa State (Nigeria). METHODS AND FINDINGS: We conducted three exhaustive household retrospective mortality surveys in one neighbourhood of each of the three affected areas: Boukoki, Niamey, Niger (April 2004, n = 26,795); Moursal, N'Djamena, Chad (June 2005, n = 21,812); and Dong District, Adamawa State, Nigeria (April 2005, n = 16,249), where n is the total surveyed population in each of the respective areas. Study populations included all persons resident for at least 2 wk prior to the study, a duration encompassing the measles incubation period. Heads of households provided information on measles cases, clinical outcomes up to 30 d after rash onset, and health-seeking behaviour during the epidemic. Measles cases and deaths were ascertained using standard WHO surveillance-case definitions. Our main outcome measures were measles attack rates (ARs) and case fatality ratios (CFRs) by age group, and descriptions of measles complications and health-seeking behaviour. Measles ARs were the highest in children under 5 y old (under 5 y): 17.1% in Boukoki, 17.2% in Moursal, and 24.3% in Dong District. CFRs in under 5-y-olds were 4.6%, 4.0%, and 10.8% in Boukoki, Moursal, and Dong District, respectively. In all sites, more than half of measles cases in children aged under 5 y experienced acute respiratory infection and/or diarrhoea in the 30 d following rash onset. Of measles cases, it was reported that 85.7% (979/1,142) of patients visited a health-care facility within 30 d after rash onset in Boukoki, 73.5% (519/706) in Moursal, and 52.8% (603/1,142) in Dong District. CONCLUSIONS: Children in these countries still face unacceptably high mortality from a completely preventable disease. While the successes of measles mortality-reduction strategies and progress observed in measles control in other countries of the region are laudable and evident, they should not overshadow the need for intensive efforts in countries that have just begun implementation of the WHO/UNICEF comprehensive strategy.

Understanding the dynamics of Ebola epidemics.

Ebola is a highly lethal virus, which has caused at least 14 confirmed outbreaks in Africa between 1976 and 2006. Using data from two epidemics [in Democratic Republic of Congo (DRC) in 1995 and in Uganda in 2000], we built a mathematical model for the spread of Ebola haemorrhagic fever epidemics taking into account transmission in different epidemiological settings. We estimated the basic reproduction number (R0) to be 2.7 (95% CI 1.9-2.8) for the 1995 epidemic in DRC, and 2.7 (95% CI 2.5-4.1) for the 2000 epidemic in Uganda. For each epidemic, we quantified transmission in different settings (illness in the community, hospitalization, and traditional burial) and simulated various epidemic scenarios to explore the impact of control interventions on a potential epidemic. A key parameter was the rapid institution of control measures. For both epidemic profiles identified, increasing hospitalization rate reduced the predicted epidemic size.

Estimating transmission intensity for a measles epidemic in Niamey, Niger: lessons for intervention.

The objective of this study is to estimate the effective reproductive ratio for the 2003-2004 measles epidemic in Niamey, Niger. Using the results of a retrospective and prospective study of reported cases within Niamey during the 2003-2004 epidemic, we estimate the basic reproductive ratio, effective reproductive ratio (RE) and minimal vaccination coverage necessary to avert future epidemics using a recent method allowing for estimation based on the epidemic case series. We provide these estimates for geographic areas within Niamey, thereby identifying neighbourhoods at high risk. The estimated citywide RE was 2.8, considerably lower than previous estimates, which may help explain the long duration of the epidemic. Transmission intensity varied during the course of the epidemic and within different neighbourhoods (RE range: 1.4-4.7). Our results indicate that vaccination coverage in currently susceptible children should be increased by at least 67% (vaccine efficacy 90%) to produce a citywide vaccine coverage of 90%. This research highlights the importance of local differences in vaccination coverage on the potential impact of epidemic control measures. The spatial-temporal spread of the epidemic from district to district in Niamey over 30 weeks suggests that targeted interventions within the city could have an impact.

Exploring the time to intervene with a reactive mass vaccination campaign in measles epidemics.

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.

High mortality in an internally displaced population in Ituri, Democratic Republic of Congo, 2005: results of a rapid assessment under difficult conditions.

The ongoing conflict in Ituri, Democratic Republic of Congo (DRC), has led to more than 50,000 deaths, more than 500,000 displaced civilians and continuing, unacceptably high, mortality since 1999. In February 2005, after a resurgence of violence and further displacements, Médecins Sans Frontières (MSF) launched an emergency response in three internally displaced persons (IDP) camps in Ituri. We performed a rapid health assessment in April 2005 in one of the IDP camps to evaluate mortality (due to violence or disease) and camp living conditions. The retrospective mortality survey, covering a recall period from 18 December 2004 to 27 March 2005, indicated a crude mortality rate of 4.1 deaths/10,000/day (95% CI: 2.8-5.4) and an under-five mortality rate of 6.9 deaths/10,000/day (95% CI: 4.4-9.4). Living conditions in the camp were extremely poor (average 286 persons per latrine). Despite efforts of the international community and humanitarian organizations, the security situation continues to deteriorate. Regular assessments should be undertaken to monitor the situation.

Risk factors associated with typhoid fever in Son La province, northern Vietnam.

Between July and December 2002, we undertook a hospital-based case-control study to identify risk factors associated with typhoid fever in Son La province, northern Vietnam. Among 617 suspected cases, 90 cases of typhoid fever were confirmed by blood or stool culture. One hundred and eighty controls (neighbours of typhoid cases matched for gender and age) were chosen. Participants were interviewed at home using a standardized questionnaire. Seventy-five per cent of cases were aged 10-44 years. No cases in patients aged less than 5 years were recorded in this study. In a conditional logistic regression analysis recent contact with a typhoid patient (OR = 3.3, 95% CI 1.7-6.2, P < 0.001), no education (OR = 2.0, 95% CI 1.0-3.7, P = 0.03) and drinking untreated water (OR = 3.9, 95% CI 2.0-7.5, P < 0.001) were independently associated with typhoid fever. Improving quality of drinking water must be a priority and health education strategies targeted at individuals with no schooling, and contacts of patients, would be expected to decrease the burden of typhoid fever.

Modeling the spread of annual influenza epidemics in the U.S.: the potential role of air travel.

The role of air travel in the global spread of influenza has been the subject of a significant body of research, but this question has yet to be explored within the U.S. The goal of this research is to explore whether knowledge of U.S. air travel patterns and volumes leads to better forecasting of epidemics. We report the results of a series of simulations for the 1998-1999 through 2000-2001 influenza seasons using a standard compartmental model coupled with air transportation data. These preliminary results suggest that air travel may play an important role in the spread of annual influenza within the U.S., particularly in cities with large air travel volumes.