Estimating Plasmodium falciparum Transmission Rates in Low-Endemic Settings Using a Combination of Community Prevalence and Health Facility Data

As some malaria control programs shift focus from disease control to transmission reduction, there is a need for transmission data to monitor progress. At lower levels of transmission, it becomes increasingly more difficult to measure precisely, for example through entomological studies. Many programs conduct regular cross sectional parasite prevalence surveys, and have access to malaria treatment data routinely collected by ministries of health, often in health management information systems. However, by themselves, these data are poor measures of transmission. In this paper, we propose an approach for combining annual parasite incidence and treatment data with cross-sectional parasite prevalence and treatment seeking survey data to estimate the incidence of new infections in the human population, also known as the force of infection. The approach is based on extension of a reversible catalytic model. The accuracy of the estimates from this model appears to be highly dependent on levels of detectability and treatment in the community, indicating the importance of information on private sector treatment seeking and access to effective and appropriate treatment.     

Health centre surveys as a potential tool for monitoring malaria epidemiology by area and over time

Background

Presently, many malaria control programmes use health facility data to evaluate the impact of their interventions. Facility-based malaria data, although useful, have problems with completeness, validity and representativeness and reliance on routinely collected health facility data might undermine demonstration of the magnitude of the impact of the recent scaleups of malaria interventions. To determine whether carefully conducted health centre surveys can be reliable means of monitoring area specific malaria epidemiology, we have compared malaria specific indices obtained from surveys in health centres with indices obtained from cross-sectional surveys conducted in their catchment communities.

Methods

A series of age stratified, seasonal, cross-sectional surveys were conducted during the peak malaria transmission season in 2008 and during the following dry season in 2009 in six ecologically diverse areas in The Gambia. Participants were patients who attended the health centres plus a representative sample from the catchment villages of these health facilities. Parasitaemia, anaemia, attributable proportion of fever and anti-MSP1-₁₉ antibody seroprevalence were compared in the health facility attendees and community participants.

Results

A total of 16,230 subjects completed the study; approximately half participated in the health centre surveys and half in the wet season surveys. Data from both the health centre and community surveys showed that malaria endemicity in The Gambia is now low, heterogeneous and seasonal. In the wet season, parasitaemia, seroprevalence and fever prevalence were higher in subjects seen in the health centres than in the community surveys. Age patterns of parasitaemia, attributable proportions of fever and seroprevalence rates were similar in subjects who participated in the community and health centre surveys.

Conclusion

Health centre surveys have potential as a surveillance tool for evaluating area specific malaria control activities and for monitoring changes in local malaria epidemiology over time.     

The Impact of Integrated Community Case Management of Childhood Diseases Interventions to Prevent Malaria Fever in Children Less than Five Years Old in Bauchi State of Nigeria

Background

Malaria accounts for about 300,000 childhood deaths and 30% of under-five year old mortality in Nigeria annually. We assessed the impact of intervention strategies that integrated Patent Medicines Vendors into community case management of childhood-diseases, improved access to artemisinin combination therapy (ACT) and distributed bed nets to households. We explored the influence of household socioeconomic characteristics on the impact of the interventions on fever in the under-five year olds in Bauchi State Nigeria.

Methods

A cross-sectional case-controlled, interventional study, which sampled 3077 and 2737 under-5 year olds from 1,588 and 1601 households in pre- and post-intervention periods respectively, was conducted from 2013 to 2015. Difference-in-differences and logistic regression analyses were performed to estimate the impact attributable to the interventions: integrated community case management of childhood illness which introduced trained public and private sector health providers and the possession of nets on the prevalence of fever.

Results

Two-week prevalence of fever among under-fives declined from 56.6% at pre-intervention to 42.5% at post-intervention. Fever-prevention fraction attributable to nets was statistically significant (OR = 0.217, 95% CI: 0.08–0.33). Children in the intervention group had significantly fewer incidence of fever than children in the control group had (OR = 0.765, 95% CI: 0.67–0.87). Although being in the intervention group significantly provided 23.5% protection against fever (95% CI: 0.13–0.33), the post-intervention likelihood of fever was also significantly less than at pre-intervention (OR = 0.57, 95% CI: 0.50–0.65). The intervention protection fraction against fever was statistically significant at 43.4% (OR = 0.434, 95% CI: 0.36–0.50). Logistic regression showed that the odds of fever were lower in households with nets (OR = 0.72, 95% CI: 0.60–0.88), among children whose mothers had higher education, in the post-intervention period (OR = 0.39, 95% CI: 0.33–0.46) and in the intervention group (OR = 0.52, 95% CI: 0.48–0.66). The odds of fever increased with higher socio-economic status of households (17.9%-19.5%). Difference-in-differences showed that the interventions significantly reduced occurrence of fever in the intervention group (OR = 1.70, 95% CI: 1.36–2.14).

Conclusion

The interventions were effective in reducing the prevalence and the likelihood of childhood malaria fever. Taken to scale, these can significantly reduce the burden of malaria fever in the under-five year old children.     

Estimating the Global Clinical Burden of Plasmodium falciparum Malaria in 2007

Background

The epidemiology of malaria makes surveillance-based methods of estimating its disease burden problematic. Cartographic approaches have provided alternative malaria burden estimates, but there remains widespread misunderstanding about their derivation and fidelity. The aims of this study are to present a new cartographic technique and its application for deriving global clinical burden estimates of Plasmodium falciparum malaria for 2007, and to compare these estimates and their likely precision with those derived under existing surveillance-based approaches.

Methods and Findings

In seven of the 87 countries endemic for P. falciparum malaria, the health reporting infrastructure was deemed sufficiently rigorous for case reports to be used verbatim. In the remaining countries, the mapped extent of unstable and stable P. falciparum malaria transmission was first determined. Estimates of the plausible incidence range of clinical cases were then calculated within the spatial limits of unstable transmission. A modelled relationship between clinical incidence and prevalence was used, together with new maps of P. falciparum malaria endemicity, to estimate incidence in areas of stable transmission, and geostatistical joint simulation was used to quantify uncertainty in these estimates at national, regional, and global scales.Combining these estimates for all areas of transmission risk resulted in 451 million (95% credible interval 349–552 million) clinical cases of P. falciparum malaria in 2007. Almost all of this burden of morbidity occurred in areas of stable transmission. More than half of all estimated P. falciparum clinical cases and associated uncertainty occurred in India, Nigeria, the Democratic Republic of the Congo (DRC), and Myanmar (Burma), where 1.405 billion people are at risk.Recent surveillance-based methods of burden estimation were then reviewed and discrepancies in national estimates explored. When these cartographically derived national estimates were ranked according to their relative uncertainty and replaced by surveillance-based estimates in the least certain half, 98% of the global clinical burden continued to be estimated by cartographic techniques.

Conclusions and Significance

Cartographic approaches to burden estimation provide a globally consistent measure of malaria morbidity of known fidelity, and they represent the only plausible method in those malaria-endemic countries with nonfunctional national surveillance. Unacceptable uncertainty in the clinical burden of malaria in only four countries confounds our ability to evaluate needs and monitor progress toward international targets for malaria control at the global scale. National prevalence surveys in each nation would reduce this uncertainty profoundly. Opportunities for further reducing uncertainty in clinical burden estimates by hybridizing alternative burden estimation procedures are also evaluated. Please see later in the article for the Editors'' Summary     

Worldwide incidence of malaria in 2009: estimates, time trends, and a critique of methods

Background

Measuring progress towards Millennium Development Goal 6, including estimates of, and time trends in, the number of malaria cases, has relied on risk maps constructed from surveys of parasite prevalence, and on routine case reports compiled by health ministries. Here we present a critique of both methods, illustrated with national incidence estimates for 2009.

Methods and Findings

We compiled information on the number of cases reported by National Malaria Control Programs in 99 countries with ongoing malaria transmission. For 71 countries we estimated the total incidence of Plasmodium falciparum and P. vivax by adjusting the number of reported cases using data on reporting completeness, the proportion of suspects that are parasite-positive, the proportion of confirmed cases due to each Plasmodium species, and the extent to which patients use public sector health facilities. All four factors varied markedly among countries and regions. For 28 African countries with less reliable routine surveillance data, we estimated the number of cases from model-based methods that link measures of malaria transmission with case incidence. In 2009, 98% of cases were due to P. falciparum in Africa and 65% in other regions. There were an estimated 225 million malaria cases (5th–95th centiles, 146–316 million) worldwide, 176 (110–248) million in the African region, and 49 (36–68) million elsewhere. Our estimates are lower than other published figures, especially survey-based estimates for non-African countries.

Conclusions

Estimates of malaria incidence derived from routine surveillance data were typically lower than those derived from surveys of parasite prevalence. Carefully interpreted surveillance data can be used to monitor malaria trends in response to control efforts, and to highlight areas where malaria programs and health information systems need to be strengthened. As malaria incidence declines around the world, evaluation of control efforts will increasingly rely on robust systems of routine surveillance. Please see later in the article for the Editors'' Summary     

Yellow Fever in Africa: Estimating the Burden of Disease and Impact of Mass Vaccination from Outbreak and Serological Data

Background

Yellow fever is a vector-borne disease affecting humans and non-human primates in tropical areas of Africa and South America. While eradication is not feasible due to the wildlife reservoir, large scale vaccination activities in Africa during the 1940s to 1960s reduced yellow fever incidence for several decades. However, after a period of low vaccination coverage, yellow fever has resurged in the continent. Since 2006 there has been substantial funding for large preventive mass vaccination campaigns in the most affected countries in Africa to curb the rising burden of disease and control future outbreaks. Contemporary estimates of the yellow fever disease burden are lacking, and the present study aimed to update the previous estimates on the basis of more recent yellow fever occurrence data and improved estimation methods.

Methods and Findings

Generalised linear regression models were fitted to a dataset of the locations of yellow fever outbreaks within the last 25 years to estimate the probability of outbreak reports across the endemic zone. Environmental variables and indicators for the surveillance quality in the affected countries were used as covariates. By comparing probabilities of outbreak reports estimated in the regression with the force of infection estimated for a limited set of locations for which serological surveys were available, the detection probability per case and the force of infection were estimated across the endemic zone.The yellow fever burden in Africa was estimated for the year 2013 as 130,000 (95% CI 51,000–380,000) cases with fever and jaundice or haemorrhage including 78,000 (95% CI 19,000–180,000) deaths, taking into account the current level of vaccination coverage. The impact of the recent mass vaccination campaigns was assessed by evaluating the difference between the estimates obtained for the current vaccination coverage and for a hypothetical scenario excluding these vaccination campaigns. Vaccination campaigns were estimated to have reduced the number of cases and deaths by 27% (95% CI 22%–31%) across the region, achieving up to an 82% reduction in countries targeted by these campaigns. A limitation of our study is the high level of uncertainty in our estimates arising from the sparseness of data available from both surveillance and serological surveys.

Conclusions

With the estimation method presented here, spatial estimates of transmission intensity can be combined with vaccination coverage levels to evaluate the impact of past or proposed vaccination campaigns, thereby helping to allocate resources efficiently for yellow fever control. This method has been used by the Global Alliance for Vaccines and Immunization (GAVI Alliance) to estimate the potential impact of future vaccination campaigns. Please see later in the article for the Editors'' Summary     

Estimating the Incidence of Acute Infectious Intestinal Disease in the Community in the UK: A Retrospective Telephone Survey

Objectives

To estimate the burden of intestinal infectious disease (IID) in the UK and determine whether disease burden estimations using a retrospective study design differ from those using a prospective study design.

Design/Setting

A retrospective telephone survey undertaken in each of the four countries comprising the United Kingdom. Participants were randomly asked about illness either in the past 7 or 28 days.

Participants

14,813 individuals for all of whom we had a legible recording of their agreement to participate

Outcomes

Self-reported IID, defined as loose stools or clinically significant vomiting lasting less than two weeks, in the absence of a known non-infectious cause.

Results

The rate of self-reported IID varied substantially depending on whether asked for illness in the previous 7 or 28 days. After standardising for age and sex, and adjusting for the number of interviews completed each month and the relative size of each UK country, the estimated rate of IID in the 7-day recall group was 1,530 cases per 1,000 person-years (95% CI: 1135–2113), while in the 28-day recall group it was 533 cases per 1,000 person-years (95% CI: 377–778). There was no significant variation in rates between the four countries. Rates in this study were also higher than in a related prospective study undertaken at the same time.

Conclusions

The estimated burden of disease from IID varied dramatically depending on study design. Retrospective studies of IID give higher estimates of disease burden than prospective studies. Of retrospective studies longer recall periods give lower estimated rates than studies with short recall periods. Caution needs to be exercised when comparing studies of self-reported IID as small changes in study design or case definition can markedly affect estimated rates.     

Influenza-Like-Illness and Clinically Diagnosed Flu: Disease Burden,Costs and Quality of Life for Patients Seeking Ambulatory Care or No Professional Care at All

This is one of the first studies to (1) describe the out-of-hospital burden of influenza-like-illness (ILI) and clinically diagnosed flu, also for patients not seeking professional medical care, (2) assess influential background characteristics, and (3) formally compare the burden of ILI in patients with and without a clinical diagnosis of flu. A general population sample with recent ILI experience was recruited during the 2011–2012 influenza season in Belgium. Half of the 2250 respondents sought professional medical care, reported more symptoms (especially more often fever), a longer duration of illness, more use of medication (especially antibiotics) and a higher direct medical cost than patients not seeking medical care. The disease and economic burden were similar for ambulatory ILI patients, irrespective of whether they received a clinical diagnosis of flu. On average, they experienced 5–6 symptoms over a 6-day period; required 1.6 physician visits and 86–91% took medication. An average episode amounted to €51–€53 in direct medical costs, 4 days of absence from work or school and the loss of 0.005 quality-adjusted life-years. Underlying illness led to greater costs and lower quality-of-life. The costs of ILI patients with clinically diagnosed flu tended to increase, while those of ILI patients without clinically diagnosed flu tended to decrease with age. Recently vaccinated persons experienced lower costs and a higher quality-of-life, but this was only the case for patients not seeking professional medical care. This information can be used directly to evaluate the implementation of cost-effective prevention and control measures for influenza. In particular to inform the evaluation of more widespread seasonal influenza vaccination, including in children, which is currently considered by many countries.     

Seasonally Dependent Relationships between Indicators of Malaria Transmission and Disease Provided by Mathematical Model Simulations

Evaluating the effectiveness of malaria control interventions on the basis of their impact on transmission as well as impact on morbidity and mortality is becoming increasingly important as countries consider pre-elimination and elimination as well as disease control. Data on prevalence and transmission are traditionally obtained through resource-intensive epidemiological and entomological surveys that become difficult as transmission decreases. This work employs mathematical modeling to examine the relationships between malaria indicators allowing more easily measured data, such as routine health systems data on case incidence, to be translated into measures of transmission and other malaria indicators. Simulations of scenarios with different levels of malaria transmission, patterns of seasonality and access to treatment were run with an ensemble of models of malaria epidemiology and within-host dynamics, as part of the OpenMalaria modeling platform. For a given seasonality profile, regression analysis mapped simulation results of malaria indicators, such as annual average entomological inoculation rate, prevalence, incidence of uncomplicated and severe episodes, and mortality, to an expected range of values of any of the other indicators. Results were validated by comparing simulated relationships between indicators with previously published data on these same indicators as observed in malaria endemic areas. These results allow for direct comparisons of malaria transmission intensity estimates made using data collected with different methods on different indicators. They also address key concerns with traditional methods of quantifying transmission in areas of differing transmission intensity and sparse data. Although seasonality of transmission is often ignored in data compilations, the models suggest it can be critically important in determining the relationship between transmission and disease. Application of these models could help public health officials detect changes of disease dynamics in a population and plan and assess the impact of malaria control interventions.     

Illness-related practices for the management of childhood malaria among the Bwatiye people of north-eastern Nigeria

Background

A wide range of childhood illnesses are accompanied by fever,, including malaria. Child mortality due to malaria has been attributed to poor health service delivery system and ignorance. An assessment of a mother's ability to recognize malaria in children under-five was carried out among the Bwatiye, a poorly-served minority ethnic group in north-eastern Nigeria.

Methods

A three-stage research design involving interviews, participatory observation and laboratory tests was used to seek information from 186 Bwatiye mothers about their illness-related experiences with childhood fevers.

Results

Mothers classified malaria into male (fever that persists for longer than three days) and female (fever that goes away within three days) and had a system of determining when febrile illness would not be regarded as malaria. Most often, malaria would be ignored in the first 2 days before seeking active treatment. Self-medication was the preferred option. Treatment practices and sources of help were influenced by local beliefs, the parity of the mother and previous experience with child mortality.

Conclusion

The need to educate mothers to suspect malaria in every case of febrile illness and take appropriate action in order to expose the underlying "evil" will be more acceptable than an insistence on replacing local knowledge with biological epidemiology of malaria. The challenge facing health workers is to identify and exploit local beliefs about aetiology in effecting management procedures among culturally different peoples, who may not accept the concept of biological epidemiology.     

Likely health outcomes for untreated acute febrile illness in the tropics in decision and economic models; a Delphi survey

Background

Modelling is widely used to inform decisions about management of malaria and acute febrile illnesses. Most models depend on estimates of the probability that untreated patients with malaria or bacterial illnesses will progress to severe disease or death. However, data on these key parameters are lacking and assumptions are frequently made based on expert opinion. Widely diverse opinions can lead to conflicting outcomes in models they inform.

Methods and Findings

A Delphi survey was conducted with malaria experts aiming to reach consensus on key parameters for public health and economic models, relating to the outcome of untreated febrile illnesses. Survey questions were stratified by malaria transmission intensity, patient age, and HIV prevalence. The impact of the variability in opinion on decision models is illustrated with a model previously used to assess the cost-effectiveness of malaria rapid diagnostic tests. Some consensus was reached around the probability that patients from higher transmission settings with untreated malaria would progress to severe disease (median 3%, inter-quartile range (IQR) 1–5%), and the probability that a non-malaria illness required antibiotics in areas of low HIV prevalence (median 20%). Children living in low transmission areas were considered to be at higher risk of progressing to severe malaria (median 30%, IQR 10–58%) than those from higher transmission areas (median 13%, IQR 7–30%). Estimates of the probability of dying from severe malaria were high in all settings (medians 60–73%). However, opinions varied widely for most parameters, and did not converge on resurveying.

Conclusions

This study highlights the uncertainty around potential consequences of untreated malaria and bacterial illnesses. The lack of consensus on most parameters, the wide range of estimates, and the impact of variability in estimates on model outputs, demonstrate the importance of sensitivity analysis for decision models employing expert opinion. Results of such models should be interpreted cautiously. The diversity of expert opinion should be recognised when policy options are debated.     

Changing Malaria Epidemiology and Diagnostic Criteria for Plasmodium falciparum Clinical Malaria

Background

In tropical Africa, where malaria is highly endemic, low grade infections are asymptomatic and the diagnosis of clinical malaria is usually based on parasite density. Here we investigate how changes in malaria control and endemicity modify diagnostic criteria of Plasmodium falciparum attacks.

Methods and Findings

Parasitological and clinical data from the population of Dielmo, Senegal, monitored during 20 years, are analyzed in a random-effect logistic regression model to investigate the relationship between the level of parasitemia and risk of fever. Between 1990 and 2010, P. falciparum prevalence in asymptomatic persons declined from 85% to 1% in children 0–3 years and from 34% to 2% in adults ≥50 years. Thresholds levels of parasitemia for attributing fever episodes to malaria decreased by steps in relation to control policies. Using baseline threshold during following periods underestimated P. falciparum attacks by 9.8–20.2% in children and 18.9–40.2% in adults. Considering all fever episodes associated with malaria parasites as clinical attacks overestimated P. falciparum attacks by 42.2–68.5% in children and 45.9–211.7% in adults.

Conclusions

Malaria control modifies in all age-groups the threshold levels of parasitemia to be used for the assessment of malaria morbidity and to guide therapeutic decisions. Even under declining levels of malaria endemicity, the parasite density method must remain the reference method for distinguishing malaria from other causes of fever and assessing trends in the burden of malaria.     

Case Fatality Rates Based on Population Estimates of Influenza-Like Illness Due to Novel H1N1 Influenza: New York City,May–June 2009

Background

The public health response to pandemic influenza is contingent on the pandemic strain''s severity. In late April 2009, a potentially pandemic novel H1N1 influenza strain (nH1N1) was recognized. New York City (NYC) experienced an intensive initial outbreak that peaked in late May, providing the need and opportunity to rapidly quantify the severity of nH1N1.

Methods and Findings

Telephone surveys using rapid polling methods of approximately 1,000 households each were conducted May 20–27 and June 15–19, 2009. Respondents were asked about the occurrence of influenza-like illness (ILI, fever with either cough or sore throat) for each household member from May 1–27 (survey 1) or the preceding 30 days (survey 2). For the overlap period, prevalence data were combined by weighting the survey-specific contribution based on a Serfling model using data from the NYC syndromic surveillance system. Total and age-specific prevalence of ILI attributed to nH1N1 were estimated using two approaches to adjust for background ILI: discounting by ILI prevalence in less affected NYC boroughs and by ILI measured in syndromic surveillance data from 2004–2008. Deaths, hospitalizations and intensive care unit (ICU) admissions were determined from enhanced surveillance including nH1N1-specific testing. Combined ILI prevalence for the 50-day period was 15.8% (95% CI:13.2%–19.0%). The two methods of adjustment yielded point estimates of nH1N1-associated ILI of 7.8% and 12.2%. Overall case-fatality (CFR) estimates ranged from 0.054–0.086 per 1000 persons with nH1N1-associated ILI and were highest for persons ≥65 years (0.094–0.147 per 1000) and lowest for those 0–17 (0.008–0.012). Hospitalization rates ranged from 0.84–1.34 and ICU admission rates from 0.21–0.34 per 1000, with little variation in either by age-group.

Conclusions

ILI prevalence can be quickly estimated using rapid telephone surveys, using syndromic surveillance data to determine expected “background” ILI proportion. Risk of severe illness due to nH1N1 was similar to seasonal influenza, enabling NYC to emphasize preventing severe morbidity rather than employing aggressive community mitigation measures.     

Estimating the Burden of Paratyphoid A in Asia and Africa

Despite the increasing availability of typhoid vaccine in many regions, global estimates of mortality attributable to enteric fever appear stable. While both Salmonella enterica serovar Typhi (S. Typhi) and serovar Paratyphi (S. Paratyphi) cause enteric fever, limited data exist estimating the burden of S. Paratyphi, particularly in Asia and Africa.We performed a systematic review of both English and Chinese-language databases to estimate the regional burden of paratyphoid within Africa and Asia. Distinct from previous reviews of the topic, we have presented two separate measures of burden; both incidence and proportion of enteric fever attributable to paratyphoid. Included articles reported laboratory-confirmed Salmonella serovar classification, provided clear methods on sampling strategy, defined the age range of participants, and specified the time period of the study.A total of 64 full-text articles satisfied inclusion criteria and were included in the qualitative synthesis. Paratyphoid A was commonly identified as a cause of enteric fever throughout Asia. The highest incidence estimates in Asia came from China; four studies estimated incidence rates of over 150 cases/100,000 person-years. Paratyphoid A burden estimates from Africa were extremely limited and with the exception of Nigeria, few population or hospital-based studies from Africa reported significant Paratyphoid A burden.While significant gaps exist in the existing population-level estimates of paratyphoid burden in Asia and Africa, available data suggest that paratyphoid A is a significant cause of enteric fever in Asia. The high variability in documented incidence and proportion estimates of paratyphoid suggest considerable geospatial variability in the burden of paratyphoid fever. Additional efforts to monitor enteric fever at the population level will be necessary in order to accurately quantify the public health threat posed by S. Paratyphi A, and to improve the prevention and treatment of enteric fever.     

Two-year evaluation of Intermittent Preventive Treatment for Children (IPTc) combined with timely home treatment for malaria control in Ghana

Background

Intermittent preventive treatment (IPT) has recently been accepted as an important component of the malaria control strategy. Intermittent preventive treatment for children (IPTc) combined with timely treatment of malaria related febrile illness at home to reduce parasite prevalence and malaria morbidity in children aged between six and 60 months in a coastal community in Ghana. This paper reports persistence of reduced parasitaemia two years into the intervention. The baseline and year-one-evaluation findings were published earlier.

Objective

The main objective in the second year was to demonstrate whether the two interventions would further reduce parasite prevalence and malaria-related febrile illness in the study population.

Methods

This was an intervention study designed to compare baseline and evaluation findings without a control group. The study combined home-based delivery of intermittent preventive treatment for children (IPTc) aged 6 - 60 months and home treatment of suspected febrile malaria-related illness within 24 hours. All children aged 6 - 60 months received home-based delivery of intermittent preventive treatment using amodiaquine + artesunate, delivered at home by community assistants every four months (6 times in 24 months). Malaria parasite prevalence surveys were conducted before the first and after the third and sixth IPTc to the children. The evaluation surveys were done four months after the third and sixth IPTc was given.

Results

Parasite prevalence which reduced from 25% to 3.0% at year-one evaluation had reduced further from 3% to 1% at year-two-evaluation. At baseline, 13.8% of the children were febrile (axilary temperature of ≥37.5°C) compared to 2.2% at year-one-evaluation while 2.1% were febrile at year-two-evaluation.

Conclusion

The year-two-evaluation result indicates that IPTc given three times in a year (every four months) combined with timely treatment of febrile malaria illness, is effective to reduce malaria parasite prevalence in children aged 6 to 60 months in the study community. This must give hope to malaria control programme managers in sub-Saharan Africa where the burden of the disease is most debilitating.

     

Age-Specific Malaria Mortality Rates in the KEMRI/CDC Health and Demographic Surveillance System in Western Kenya, 2003–2010

Recent global malaria burden modeling efforts have produced significantly different estimates, particularly in adult malaria mortality. To measure malaria control progress, accurate malaria burden estimates across age groups are necessary. We determined age-specific malaria mortality rates in western Kenya to compare with recent global estimates. We collected data from 148,000 persons in a health and demographic surveillance system from 2003–2010. Standardized verbal autopsies were conducted for all deaths; probable cause of death was assigned using the InterVA-4 model. Annual malaria mortality rates per 1,000 person-years were generated by age group. Trends were analyzed using Poisson regression. From 2003–2010, in children <5 years the malaria mortality rate decreased from 13.2 to 3.7 per 1,000 person-years; the declines were greatest in the first three years of life. In children 5–14 years, the malaria mortality rate remained stable at 0.5 per 1,000 person-years. In persons ≥15 years, the malaria mortality rate decreased from 1.5 to 0.4 per 1,000 person-years. The malaria mortality rates in young children and persons aged ≥15 years decreased dramatically from 2003–2010 in western Kenya, but rates in older children have not declined. Sharp declines in some age groups likely reflect the national scale up of malaria control interventions and rapid expansion of HIV prevention services. These data highlight the importance of age-specific malaria mortality ascertainment and support current strategies to include all age groups in malaria control interventions.     

Dengue incidence in urban and rural Cambodia: results from population-based active fever surveillance, 2006-2008

Background

Dengue vaccines are now in late-stage development, and evaluation and robust estimates of dengue disease burden are needed to facilitate further development and introduction. In Cambodia, the national dengue case-definition only allows reporting of children less than 16 years of age, and little is known about dengue burden in rural areas and among older persons. To estimate the true burden of dengue in the largest province of Cambodia, Kampong Cham, we conducted community-based active dengue fever surveillance among the 0-to-19–year age group in rural villages and urban areas during 2006–2008.

Methods and Findings

Active surveillance for febrile illness was conducted in 32 villages and 10 urban areas by mothers trained to use digital thermometers combined with weekly home visits to identify persons with fever. An investigation team visited families with febrile persons to obtain informed consent for participation in the follow-up study, which included collection of personal data and blood specimens. Dengue-related febrile illness was defined using molecular and serological testing of paired acute and convalescent blood samples. Over the three years of surveillance, 6,121 fever episodes were identified with 736 laboratory-confirmed dengue virus (DENV) infections for incidences of 13.4–57.8/1,000 person-seasons. Average incidence was highest among children less than 7 years of age (41.1/1,000 person-seasons) and lowest among the 16-to-19–year age group (11.3/1,000 person-seasons). The distribution of dengue was highly focal, with incidence rates in villages and urban areas ranging from 1.5–211.5/1,000 person-seasons (median 36.5). During a DENV-3 outbreak in 2007, rural areas were affected more than urban areas (incidence 71 vs. 17/1,000 person-seasons, p<0.001).

Conclusion

The large-scale active surveillance study for dengue fever in Cambodia found a higher disease incidence than reported to the national surveillance system, particularly in preschool children and that disease incidence was high in both rural and urban areas. It also confirmed the previously observed focal nature of dengue virus transmission.     

Malaria Prevalence,Spatial Clustering and Risk Factors in a Low Endemic Area of Eastern Rwanda: A Cross Sectional Study

Background

Rwanda reported significant reductions in malaria burden following scale up of control intervention from 2005 to 2010. This study sought to; measure malaria prevalence, describe spatial malaria clustering and investigate for malaria risk factors among health-centre-presumed malaria cases and their household members in Eastern Rwanda.

Methods

A two-stage health centre and household-based survey was conducted in Ruhuha sector, Eastern Rwanda from April to October 2011. At the health centre, data, including malaria diagnosis and individual level malaria risk factors, was collected. At households of these Index cases, a follow-up survey, including malaria screening for all household members and collecting household level malaria risk factor data, was conducted.

Results

Malaria prevalence among health centre attendees was 22.8%. At the household level, 90 households (out of 520) had at least one malaria-infected member and the overall malaria prevalence for the 2634 household members screened was 5.1%. Among health centre attendees, the age group 5–15 years was significantly associated with an increased malaria risk and a reported ownership of ≥4 bednets was significantly associated with a reduced malaria risk. At the household level, age groups 5–15 and >15 years and being associated with a malaria positive index case were associated with an increased malaria risk, while an observed ownership of ≥4 bednets was associated with a malaria risk-protective effect. Significant spatial malaria clustering among household cases with clusters located close to water- based agro-ecosystems was observed.

Conclusions

Malaria prevalence was significantly higher among health centre attendees and their household members in an area with significant household spatial malaria clustering. Circle surveillance involving passive case finding at health centres and proactive case detection in households can be a powerful tool for identifying household level malaria burden, risk factors and clustering.     

Symptomatic Dengue Disease in Five Southeast Asian Countries: Epidemiological Evidence from a Dengue Vaccine Trial

Dengue incidence has increased globally, but empirical burden estimates are scarce. Prospective methods are best-able to capture all severities of disease. CYD14 was an observer-blinded dengue vaccine study conducted in children 2–14 years of age in Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The control group received no vaccine and resembled a prospective, observational study. We calculated the rates of dengue according to different laboratory or clinical criteria to make inferences about dengue burden, and compared with rates reported in the passive surveillance systems to calculate expansion factors which describe under-reporting. Over 6,933 person-years of observation in the control group there were 319 virologically confirmed dengue cases, a crude attack rate of 4.6%/year. Of these, 92 cases (28.8%) were clinically diagnosed as dengue fever or dengue hemorrhagic fever by investigators and 227 were not, indicating that most symptomatic disease fails to satisfy existing case definitions. When examining different case definitions, there was an inverse relationship between clinical severity and observed incidence rates. CYD14’s active surveillance system captured a greater proportion of symptomatic dengue than national passive surveillance systems, giving rise to expansion factors ranging from 0.5 to 31.7. This analysis showed substantial, unpredictable and variable under-reporting of symptomatic dengue, even within a controlled clinical trial environment, and emphasizes that burden estimates are highly sensitive to case definitions. These data will assist in generating disease burden estimates and have important policy implications when considering the introduction and health economics of dengue prevention and control interventions.     

Incorporating Scale Dependence in Disease Burden Estimates: The Case of Human African Trypanosomiasis in Uganda

Background

The WHO has established the disability-adjusted life year (DALY) as a metric for measuring the burden of human disease and injury globally. However, most DALY estimates have been calculated as national totals. We mapped spatial variation in the burden of human African trypanosomiasis (HAT) in Uganda for the years 2000–2009. This represents the first geographically delimited estimation of HAT disease burden at the sub-country scale.

Methodology/Principal Findings

Disability-adjusted life-year (DALY) totals for HAT were estimated based on modelled age and mortality distributions, mapped using Geographic Information Systems (GIS) software, and summarised by parish and district. While the national total burden of HAT is low relative to other conditions, high-impact districts in Uganda had DALY rates comparable to the national burden rates for major infectious diseases. The calculated average national DALY rate for 2000–2009 was 486.3 DALYs/100 000 persons/year, whereas three districts afflicted by rhodesiense HAT in southeastern Uganda had burden rates above 5000 DALYs/100 000 persons/year, comparable to national GBD 2004 average burden rates for malaria and HIV/AIDS.

Conclusions/Significance

These results provide updated and improved estimates of HAT burden across Uganda, taking into account sensitivity to under-reporting. Our results highlight the critical importance of spatial scale in disease burden analyses. National aggregations of disease burden have resulted in an implied bias against highly focal diseases for which geographically targeted interventions may be feasible and cost-effective. This has significant implications for the use of DALY estimates to prioritize disease interventions and inform cost-benefit analyses.