Epidemiological impact of vaccination on the dynamics of two childhood diseases in rural Senegal

Measles and pertussis are ubiquitous vaccine-preventable diseases, which remain an important public health problem in developing countries. Hence, developing a deep understanding of their transmission dynamics remains imperative. To achieve this, we compared the impact of vaccination at both individual and population levels in a Senegalese rural community. This study represents the first such comparative study in tropical conditions and constitutes a point of comparison with other studies of disease dynamics in developed countries. Changes in the transmission rates of infections are reflected in their mean ages at infection and basic reproductive ratio calculated before and after vaccination. We explored persistence of both infections in relation to population size in each village and found the inter-epidemic period for the whole area using wavelets analysis. As predicted by epidemiological theory, we observed an increase in the mean age at infection and a decrease in the reproductive ratio of both diseases. We showed for both the pre- vaccination and vaccine eras that persistence depends on population size. After vaccination, persistence decreased and the inter-epidemic period increased. The observed changes suggest that vaccination against measles and pertussis induced a drop in their transmission. Similarities in disease dynamics to those of temperate regions such as England and Wales were also observed.     

Tropheryma whipplei: a common bacterium in rural Senegal

Background

Tropheryma whipplei is known as the cause of Whipple''s disease, but it is also an emerging pathogen, detected in stool, that causes various chronic localized infections without histological digestive involvement and is associated with acute infections, including gastroenteritis and bacteremia.

Methods/Principal Findings

We conducted a study in 2008 and 2009 using 497 non-diarrheic and diarrheic stool samples, 370 saliva samples, 454 sera samples and 105 samples obtained from water samples in two rural Sine-Saloum villages (Dielmo and Ndiop) in Senegal. The presence of T. whipplei was investigated by using specific quantitative PCR. Genotyping was performed on positive samples. A serological analysis by western blotting was performed to determine the seroprevalence and to detect seroconversion. Overall, T. whipplei was identified in 31.2% of the stool samples (139/446) and 3.5% of the saliva samples (13/370) obtained from healthy subjects. The carriage in the stool specimens was significantly (p<10⁻³) higher in children who were between 0 and 4 years old (60/80, 75%) compared to samples obtained from individuals who were between 5 to 10 years old (36/119, 30.2%) or between 11 and 99 years old (43/247, 17.4%). The carriage in the stool was also significantly more common (p = 0.015) in subjects with diarrhea (25/51, 49%). We identified 22 genotypes, 16 of which were new. Only one genotype (#53) was common to both villages. Among the specific genotypes, one (#52) was epidemic in Dielmo (15/28, 53.4%, p<10⁻³) and another (#49) in Ndiop (27.6%, p = 0.002). The overall seroprevalence was estimated at 72.8% (291/400). Seroconversion was detected in 66.7% (18/27) of children for whom PCR became positive in stools between 2008 and 2009.

Conclusions/Significance

T. whipplei is a common bacterium in the Sine-Saloum area of rural Senegal that is contracted early in childhood. Epidemic genotypes suggest a human transmission of the bacterium.     

Plasmodium falciparum clinical malaria: lessons from longitudinal studies in Senegal

Development of new antimalaria strategies and particularly vaccines, needs an in-depth understanding of the relationships between transmission, infection, immunity, morbidity and mortality. The intensive and longitudinal collection of entomological, parasitological and clinical data from the Senegalese populations of Dielmo (250-300 inhabitants), exposed to a perennial and intense transmission (about 200 infective bites/person/year) and of Ndiop (300-350 inhabitants) exposed to a seasonal transmission (about 20 infective bites/person/year), allows to respond to many questions about this subject. The acquisition of an antimalaria immunity as one gets older appears to reduce parasite density, complexity of infection, risk of new patent infection after a suppressive treatment but does not reduce the prevalence (as assessed by PCR) of infection which is commonly chronic and asymptomatic. The existence of a pyrogenic threshold effect of parasitaemia allows the individual diagnosis of malaria attacks. P. falciparum genotyping suggests that successive malaria attacks are due to distinct recently inoculated parasite populations that multiply initially without restriction, a dominant population is generally responsible of the clinical manifestations and all new populations do not trigger systematically attacks. The initial intensity of clinical manifestations does not differ perceptibly among children and adults, is not related to the duration of the attacks, does not allow the distinction between several types of attacks, is not predictive of their severity, and the clearance of parasites and manifestations is longer among youngest persons. The risk of malaria attacks is lower as one gets older and among carriers of AS haemoglobin, is higher when transmission increases and during pregnancy up to three months after delivery, and vary between children. The risk of malaria attack per infective bite is negatively related to the intensity of transmission. Because of their high sensitivity in malaria case detection, this type of small community-based studies are powerful and useful for the identification of protective immunological mechanisms as well as for testing rapidly and cheaply the clinical efficacy of any intervention such as antimalarial vaccines and drug therapy or prophylaxis. As a lot of vaccine candidates and drug combinations will be screened or tested in the perspective of the 'Roll-Back Malaria' programme, more attention must be given to longitudinal studies of this type.     

Determinants of malnutrition in Senegal: Individual, household, community variables, and their interaction

The relationship between poverty and nutrition is a two-sided one: on the one hand, economic growth (which is generally associated with an eradication of poverty) leads to reduced malnutrition. On the other hand, nutrition is one of the key ingredients for human capital formation, which in turn represents one of the fundamental factors of growth. There are numerous studies that show the correlates of malnutrition using both household- and community-level variables. However, few of these studies allow for the potential endogeneity of community infrastructure or indicate their interplay with characteristics of the mother. The current study considers the socio-economic determinants of child malnutrition and investigates how programs compensate for the increased risks facing young mothers and their children or substitute for a low social status of the mother in the household. The empirical results show that children of mothers giving birth at a young age are disadvantaged in terms of their anthropometric status. Interaction effects of the presence of a non-governmental organization (NGO) or a health post in the village with characteristics of the mother stress the important role played by these institutions in helping disadvantaged mothers overcome their difficulties. These findings have implications for efficient program design and represent a further step towards gaining an improved understanding of the complex determinants of child (mal)nutrition.     

Climate and health: Observation and modeling of malaria in the Ferlo (Senegal)

The aim of this work, undertaken in the framework of QWeCI (Quantifying Weather and Climate Impacts on health in the developing countries) project, is to study how climate variability could influence malaria seasonal incidence. It will also assess the evolution of vector-borne diseases such as malaria by simulation analysis of climate models according to various climate scenarios for the next years. Climate variability seems to be determinant for the risk of malaria development (Freeman and Bradley, 1996 [1], Lindsay and Birley, 1996 [2], Kuhn et al., 2005 [3]). Climate can impact on the epidemiology of malaria by several mechanisms, directly, via the development rates and survival of both pathogens and vectors, and indirectly, through changes in vegetation and land surface characteristics such as the variability of breeding sites like ponds.     

Severe malaria in Burkina Faso: urban and rural environment

The age distribution and the clinical patterns of severe malaria (SM) were compared in patients from urban areas characterized by relatively low transmission, and from rural areas where the mean inoculation rates are at least twenty fold higher. The mean age of the urban and rural patients was 4.8 +/- 3.0 and 2.2 +/- 1.9 respectively (p < 0.000). The prevalence of coma was higher in the urban subsample (53.6 vs 28.9%, p < 0.000) while that of severe anemia (hemoglobin < 5 g/dl) was higher in rural patients (47.4 vs 14.8%, p < 0.000). Our data, in line with previous results obtained comparing rural areas characterized by different inoculation rates, show that the epidemiological context influences the clinical presentation of SM.     

Infant and early childhood mortality in the Sine-Saloum region of Senegal

Infant and early childhood mortality in Senegal's Sine-Saloum region was investigated through use o f data from a 1982-83 family health survey. The survey involved interviews with 1894 married women 15-44 years of age living in extended family residential units in rural areas. Given evidence of substantial underreporting of early deaths, at least among children born before 1980, an adjustment factor was applied to the survey data. Infant mortality was estimated to be about 113/1000 live births and mortality before age 5 years was 263/1000. Strong mortality differentials, particularly after infancy, were noted according to the 2 socioeconomic variables included in the analysis: type of house and father's occupation. The probability of dying at ages 1-4 years was 50% higher among children living in traditional homes than among those in modern homes as well as among children whose fathers' were engaged in primary sector occupations (farming, livestock, fishing). Infant mortality showed no sex differential, while mortality at ages 1-4 years was 18% higher among females. Diarrheal and respiratory diseases were the 2 leading causes of death, killing at least 15% of all children by 5 years of age. Tetanus was an important cause of death during infancy, while measles and malaria were significant causes only after the 1st birthday. For all causes of death, the effect of socioeconomic status is higher in early childhood than in infancy, presumably because of the protective effect of breastfeeding. 82% of children who died had fever during their terminal illness, 51% had diarrhea, 39% had a cough, and 14% a rash. At least some mortality in this area might be prevented through treatment of these symptoms. However, calculating the degree to which particular interventions such as oral rehydration for diarrhea would reduce mortality is a complex task, requiring knowledge of replacement mortality, effectiveness of interventions, and the numbers of mothers who would utilize them.     

The unexpected importance of mosquito oviposition behaviour for malaria: non-productive larval habitats can be sources for malaria transmission

Background

Mosquitoes commute between blood-meal hosts and water. Thus, heterogeneity in human biting reflects underlying spatial heterogeneity in the distribution and suitability of larval habitat as well as inherent differences in the attractiveness, suitability and distribution of blood-meal hosts. One of the possible strategies of malaria control is to identify local vector species and then attack water bodies that contain their larvae.

Methods

Biting and host seeking, not oviposition, have been the focus of most previous studies of mosquitoes and malaria transmission. This study presents a mathematical model that incorporates mosquito oviposition behaviour.

Results

The model demonstrates that oviposition is one potential factor explaining heterogeneous biting and vector distribution in a landscape with a heterogeneous distribution of larval habitat. Adult female mosquitoes tend to aggregate around places where they oviposit, thereby increasing the risk of malaria, regardless of the suitability of the habitat for larval development. Thus, a water body may be unsuitable for adult mosquito emergence, but simultaneously, be a source for human malaria.

Conclusion

Larval density may be a misleading indicator of a habitat's importance for malaria control. Even if mosquitoes could be lured to oviposit in sprayed larval habitats, this would not necessarily mitigate – and might aggravate – the risk of malaria transmission. Forcing mosquitoes to fly away from humans in search of larval habitat may be a more efficient way to reduce the risk of malaria than killing larvae. Thus, draining, fouling, or filling standing water where mosquitoes oviposit can be more effective than applying larvicide.     

Plasmodium falciparum genotype population dynamics in asymptomatic children from Senegal

In areas where malaria is endemic, infected individuals generally harbor a mixture of genetically distinct Plasmodium falciparum parasite populations. For the first time, we studied temporal variations of blood parasite densities and circulating genotypes in asymptomatic Senegalese children, at time intervals as short as 4-12 h. Twenty-one Senegalese children, presenting with an asymptomatic P. falciparum infection, were sampled eight times within three days. Parasite density was assessed by thick blood smears, and all infecting genotypes were quantified by the fragment-analysis method. Parasite densities showed dramatic fluctuations up to a 1 to 1,000 ratio, with at least one peak of parasite density. Polyclonal infections were detected in all children, with a multiplicity of infection of 5.2-6.8 genotypes per child. A single sample never reflected the full complexity of the parasite populations hosted by a given individual. Genotypes with different behaviors were detected in all children, some genotypes undergoing major fluctuations, while others were highly stable during the follow-up. A single peripheral blood sampling does not reflect the total parasite load. Repeated sampling is needed to have a more detailed scheme of parasite population dynamics and a better knowledge of the true complexity of an infection.     

Spatial dynamics of pertussis in a small region of Senegal

Extended time-series analysis of infectious diseases raises two issues: the spread of disease, and its persistence in space and time. Most studies are based on both data and models, corresponding to conditions encountered in developed countries. The present work sought to determine the impact of local heterogeneity on these two issues, regarding pertussis in tropical conditions. First, we tested the 'cities and villages' model in a small community of 30 villages in rural Senegal. Second, we focused on the impact of population size and density, as well as geographic distance, on population dynamics of pertussis. Results showed that pertussis initially arrived in urban centres, and then spread to surrounding areas. Both population size and density are implicated in the persistence of pertussis within the study area, whereas geographical distance between villages is not. This is the first study on pertussis in a developing country carried out on a very fine spatial scale. Furthermore, it confirms previous results for measles in England and Wales.     

Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal

Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p<10(-4), Ndiop). While regions of linkage show little overlap with genes known to be involved in severe malaria, the four regions appear to overlap with regions linked to asthma or atopy related traits, suggesting that common immune related pathways may be involved.     

Performance of integrated household constructed wetland for domestic wastewater treatment in rural areas

As environmental legislation has become stricter in recent years, the issue of wastewater treatment in rural areas has become an increasing concern. Choice of the most suitable on-site purification systems is based on the key issues of affordability and appropriateness in Chinese rural areas. This paper describes an integrated household constructed wetland (IHCW) system planted with willow (Salix babylonica) to treat household domestic wastewater in rural villages in northern China. The precast frame structure of IHCW is strong and waterproof. It can be mass-produced and installed per a standard set of specifications. The IHCW has achieved high overall removal efficiencies for BOD₅, TSS, NH₄-N, and TP: 96.0%, 97.0%, 88.4% and 87.8%, respectively. A 0.4 m biomass layer cover on the system provided significant system thermal insulation, maintaining high treatment performance in freezing winter conditions. The system is cost effective and does not need any operational energy inputs, demonstrating its feasibility for single-family use in developing countries.     

Transmission intensity and drug resistance in malaria population dynamics: implications for climate change

Although the spread of drug resistance and the influence of climate change on malaria are most often considered separately, these factors have the potential to interact through altered levels of transmission intensity. The influence of transmission intensity on the evolution of drug resistance has been addressed in theoretical studies from a population genetics' perspective; less is known however on how epidemiological dynamics at the population level modulates this influence. We ask from a theoretical perspective, whether population dynamics can explain non-trivial, non-monotonic, patterns of treatment failure with transmission intensity, and, if so, under what conditions. We then address the implications of warmer temperatures in an East African highland, where, as in other similar regions at the altitudinal edge of malaria's distribution, there has been a pronounced increase of cases from the 1970s to the 1990s. Our theoretical analyses, with a transmission model that includes different levels of immunity, demonstrate that an increase in transmission beyond a threshold can lead to a decrease in drug resistance, as previously shown, but that a second threshold may occur and lead to the re-establishment of drug resistance. Estimates of the increase in transmission intensity from the 1970s to the 1990s for the Kenyan time series, obtained by fitting the two-stage version of the model with an explicit representation of vector dynamics, suggest that warmer temperatures are likely to have moved the system towards the first threshold, and in so doing, to have promoted the faster spread of drug resistance. Climate change and drug resistance can interact and need not be considered as alternative explanations for trends in disease incidence in this region. Non-monotonic patterns of treatment failure with transmission intensity similar to those described as the 'valley phenomenon' for Uganda can result from epidemiological dynamics but under poorly understood assumptions.     

Misfortunes never come singly: Structural change,multiple shocks and child malnutrition in rural Senegal

This study considers the two most pronounced shocks Senegalese subsistence farmers struggle with, namely increasing purchase prices and droughts. We assess the relationship of these self-reported shocks with child health in a multi-shock approach to account for concomitance of adverse events from the natural, biological, economic and health sphere. We employ a unique farming household panel dataset containing information on children living in poor, rural households in eight regions of Senegal in 2009 and 2011 and account for structural changes occurring between survey periods due to the large scale, national Nutrition Enhancement Program. By zooming in to the micro level we demonstrate that Senegal as a Sahelian country, mainly reliant on subsistence agriculture, is very vulnerable to climate variability and international price developments: According to our conservative estimates, the occurrence of a drought explains 25% of the pooled weight-for-age standard deviation, income losses 31%. Our multi-shock analysis reveals that the shocks are perceived as more severe in 2011 with droughts explaining up to 44% of the standard deviation of child health, increased prices up to 21%. Yet, the concomitance of droughts and increased prices after the structural change, i.e. the Nutrition Enhancement Program, indicates that the health of children experiencing both shocks in 2011 has improved. We argue that these results are driven by the increase in rural household income as theoretically outlined in the agricultural household model. Thus, adequate policy responses to shocks do not only depend on the nature but also on the concomitance of hazardous events.     

Malaria-related health-seeking behaviour and challenges for care providers in rural Ethiopia: implications for control

A range of activities are currently underway to improve access to malaria prevention and control interventions. As disease control strategies change over time, it is crucial to understand the health-seeking behaviour and the local socio-cultural context in which the changes in interventions operate. This paper reflects on how people in an area of seasonal malaria perceive the causes and transmission of the disease, and what prevention and treatment measures they practise to cope with the disease. It also highlights some of the challenges of malaria treatment for health care providers. The study was undertaken in 2003 in Adami Tulu District in south-central Ethiopia, where malaria is a major health problem. Pre-tested structured questionnaires and focus group discussions were conducted among men and women. Malaria, locally known as busa, was perceived as the most important cause of ill health in the area. Respondent's perception and knowledge about the cause and transmission of the disease were relatively high. The newly introduced insecticide-treated nets were not popular in the area, and only 6.4% of households possessed at least one. The results showed that patients use multiple sources of health care for malaria treatment. Public health facilities, private clinics and community health workers were the main providers of malaria treatment. Despite higher treatment costs, people preferred to use private health care providers for malaria treatment due to the higher perceived quality of care they offer. In conclusion, effort in the prevention and control of malaria should be intensified through addressing not only public facilities, but also the private sector and community-based control interventions. Appropriate and relevant information on malaria should be disseminated to the local community. The authors propose the provision of effective antimalarial drugs and malaria prevention tools such as subsidized or free insecticide-treated nets.     

Increase of malaria attacks among children presenting concomitant infection by Schistosoma mansoni in Senegal

Background

Parasites incur periodic mutations which must ultimately be eliminated to maintain their genetic integrity.

Methods

It is hypothesised that these mutations are eliminated not by the conventional mechanisms of competition between parasites in different hosts but primarily by competition between parasites within the same infection.

Results

This process is enhanced by the production of a large number of parasites within individual infections, and this may significantly contribute to parasitic virulence.

Conclusions

Several features of the most virulent human malaria parasite Plasmodium falciparum can usefully be re-interpreted in this light and lend support to this interpretation. More generally, it constitutes a novel explanation for the evolution of virulence in a wider range of microparasites.     

Accuracy of rapid tests for malaria and treatment outcomes for malaria and non-malaria cases among under-five children in rural Ghana

Background

WHO now recommends test-based management of malaria across all transmission settings. The accuracy of rapid diagnostic test (RDT) and the outcome of treatment based on the result of tests will influence acceptability of and adherence to the new guidelines.

Method

We conducted a study at the Kintampo hospital in rural Ghana to evaluate the performance of CareStart, a HRP-2 based RDT, using microscopy as reference. We applied IMCI treatment guidelines, restricted ACT to RDT-positive children and followed-up both RDT-positive (malaria) and RDT-negative (non-malaria) cases over 28 days.

Results

436 children were enrolled in the RDT evaluation and 391 (children with haemoglobin >8.0 gm/dl) were followed-up to assess treatment outcomes. Mean age was 25.4 months (s.d. 14.6). Sensitivity and specificity of the RDT were 100.0% and 73.0% respectively. Over the follow-up period, 32 (18.5%) RDT-negative children converted to positive, with 7 (4.0%) of them presenting with fever. More children in the non-malaria group made unscheduled visits than children in the malaria group (13.3% versus 7.7%) On all scheduled follow-up visits, proportion of children having a temperature higher than that recorded on day 0 was higher in the non-malaria group compared to the malaria group. Reports of unfavourable treatment outcomes by caregivers were higher among the non-malaria group than the malaria group.

Conclusions

The RDT had good sensitivity and specificity. However a minority of children who will not receive ACT based on RDT results may develop clinical malaria within a short period in high transmission settings. This could undermine caregivers'' and health workers'' confidence in the new guidelines. Improving the quality of management of non-malarial febrile illnesses should be a priority in the era of test-based management of malaria.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00832754","term_id":"NCT00832754"}}NCT00832754     

Estimating the burden of malaria in Senegal: Bayesian zero-inflated binomial geostatistical modeling of the MIS 2008 data

The Research Center for Human Development in Dakar (CRDH) with the technical assistance of ICF Macro and the National Malaria Control Programme (NMCP) conducted in 2008/2009 the Senegal Malaria Indicator Survey (SMIS), the first nationally representative household survey collecting parasitological data and malaria-related indicators. In this paper, we present spatially explicit parasitaemia risk estimates and number of infected children below 5 years. Geostatistical Zero-Inflated Binomial models (ZIB) were developed to take into account the large number of zero-prevalence survey locations (70%) in the data. Bayesian variable selection methods were incorporated within a geostatistical framework in order to choose the best set of environmental and climatic covariates associated with the parasitaemia risk. Model validation confirmed that the ZIB model had a better predictive ability than the standard Binomial analogue. Markov chain Monte Carlo (MCMC) methods were used for inference. Several insecticide treated nets (ITN) coverage indicators were calculated to assess the effectiveness of interventions. After adjusting for climatic and socio-economic factors, the presence of at least one ITN per every two household members and living in urban areas reduced the odds of parasitaemia by 86% and 81% respectively. Posterior estimates of the ORs related to the wealth index show a decreasing trend with the quintiles. Infection odds appear to be increasing with age. The population-adjusted prevalence ranges from 0.12% in Thillé-Boubacar to 13.1% in Dabo. Tambacounda has the highest population-adjusted predicted prevalence (8.08%) whereas the region with the highest estimated number of infected children under the age of 5 years is Kolda (13940). The contemporary map and estimates of malaria burden identify the priority areas for future control interventions and provide baseline information for monitoring and evaluation. Zero-Inflated formulations are more appropriate in modeling sparse geostatistical survey data, expected to arise more frequently as malaria research is focused on elimination.