Physical fitness and nutritional anthropometric status of children from disadvantaged communities in the Nelson Mandela Bay region.

Background: Information about the relationships between physical fitness, body composition and nutrition has increased in recent years; however, little is known about physical fitness and the coexistence of under-/overnutrition among children living in disadvantaged areas. Objectives: To determine the physical fitness status and its association with body composition, growth and selected socio-demographics in primary schoolchildren from disadvantaged communities in the Nelson Mandela Bay region. Methods: Nine hundred and sixty-five children (49% girls, M=9.5 years) participated in this cross-sectional study. Height and weight were measured to establish body mass index, and height-for-age z-scores. Physical fitness was assessed using tests from the Eurofit Physical Fitness test battery (flexibility, upper/lower body muscular strength and cardiorespiratory fitness). Between-group differences and cross-sectional associations were examined with univariate (Chi2-tests, analyses of variance) and multivariate methods (mixed linear/logistic regression). Results: Most children had normal weight (76.7%), while 4.5% were underweight and 18.7% were overweight/obese. Underweight children and children with stunted growth (11.5%) had lower average upper body strength (p<0.001). Overweight/obese children had lower scores in weight-bearing activities (p<0.001). Children with higher socio-economic status were more likely to be overweight and obese (p<0.001). In the multivariate analyses, sex, age, body mass index, and stunting were associated with children's physical fitness. Conclusion: Fitness assessments seem to be a relevant measure of the current health status of children in disadvantaged settings. Compared to international norms, the children in this study had relatively low scores for both upper- and lower body muscular strength. Therefore, effective school-based intervention programmes should be developed to improve children's physical fitness in disadvantaged schools.

Repeated doses of Praziquantel in Schistosomiasis Treatment (RePST) - single versus multiple praziquantel treatments in school-aged children in Côte d'Ivoire: a study protocol for an open-label, randomised controlled trial.

BACKGROUND: Large scale administration of the anthelminthic drug praziquantel (PZQ) to at-risk populations is the cornerstone of schistosomiasis control, although persisting high prevalence of infections in some areas and growing concerns of PZQ resistance have revealed the limitations of this strategy. Most studies assessing PZQ efficacy have used relatively insensitive parasitological diagnostics, such as the Kato-Katz (KK) and urine-filtration methods, thereby overestimating cure rates (CRs). This study aims to determine the efficacy of repeated PZQ treatments against Schistosoma mansoni infection in school-aged children in Côte d'Ivoire using the traditional KK technique, as well as more sensitive antigen- and DNA-detection methods. METHODS: An open-label, randomised controlled trial will be conducted in school-aged children (5 to 18 years) from the region of Taabo, Côte d'Ivoire, an area endemic for S. mansoni. This 8-week trial includes four two-weekly standard doses of PZQ in the "intense treatment" intervention group and one standard dose of PZQ in the "standard treatment" control group. The efficacy of PZQ will be evaluated in stool samples using the KK technique and real-time PCR as well as in urine using the point-of-care circulating cathodic antigen test and the up-converting phosphor, lateral flow, circulating anodic antigen assay. The primary outcome of the study will be the difference in CR of intense versus standard treatment with PZQ on individuals with a confirmed S. mansoni infection measured by KK. Secondary outcomes include the difference in CR and intensity reduction rate between the intense and standard treatment groups as measured by the other diagnostic tests, as well as the accuracy of the different diagnostic tests, and the safety of PZQ. DISCUSSION: This study will provide data on the efficacy of repeated PZQ treatment on the clearance of S. mansoni as measured by several diagnostic techniques. These findings will inform future mass drug administration policy and shed light on position of novel diagnostic tools to evaluate schistosomiasis control strategies. TRIAL REGISTRATION: The study is registered at EudraCT (2016-003017-10, date of registration: 22 July 2016) and ( NCT02868385 , date of registration: 16 August 2016).

Prevalence rates of six selected infectious diseases among African migrants and refugees: a systematic review and meta-analysis.

The objective of this paper was to systematically review the literature on the prevalence of selected infectious diseases among migrants/refugees of African origin and to provide policy makers and health care professionals with evidence-based information. We pursued a systematic review and meta-analysis to determine the prevalence of six selected infectious diseases (i.e., syphilis, helminthiasis, schistosomiasis, intestinal protozoa infections, hepatitis B, and hepatitis C) among migrants/refugees of African origin. Three electronic databases (i.e., PubMed, EMBASE, and ISI Web of Science) were searched without language restrictions. Relevant data were extracted and random-effects meta-analyses conducted. Only adjusted estimates were analyzed to help account for heterogeneity and potential confounding. We assessed the quality of evidence using the GRADE approach. The results were stratified by geographical region. Ninety-six studies were included. The evidence was of low quality due to the small numbers of countries, infectious diseases, and participants included. African migrants/refugees had median (with 95% confidence interval [95% CI]) prevalence for syphilis, helminthiasis, schistosomiasis, intestinal protozoa infection, hepatitis B, and hepatitis C of 6.0% [95% CI: 2.0-7.0%], 13.0% [95% CI: 9.5-14.5%], 14.0% [95% CI: 13.0-17.0%], 15.0% [95% CI: 10.5-21.0%], 10.0% [95% CI: 6.0-14.0%], and 3.0% [95% CI: 1.0-4.0%], respectively. We found high heterogeneity regardless of the disease (I 2; minimum 97.5%, maximum 99.7%). The relatively high prevalence of some infectious diseases among African migrants/refugees warrants for systematic screening. The large heterogeneity of the available published data does not allow for stratifying such screening programs according to the geographical origin of African migrants/refugees.

Policy Support and Resources Mobilization for the National Schistosomiasis Control Programme in The People's Republic of China.

Schistosomiasis remains a public health problem in many developing countries around the world. After the founding of The People's Republic of China, from 1949 till date, all levels of government, from central to local, have been attaching great importance to schistosomiasis control in The People's Republic of China. With considerable policy support and resources mobilization, the national schistosomiasis control programmes have been implemented during the past 65years. Here, we summarize the successful experience of schistosomiasis control during the process. Recommendations for the future management of the Chinese national schistosomiasis elimination programme are put forward after considering the remaining challenges, shortcomings and lessons learnt from 65years of schistosomiasis control drives in The People's Republic of China. They will help to sustain past achievements, foster the attainment of the ultimate goal of schistosomiasis elimination for the country and provide reference for schistosomiasis control programme in other countries.

Epidemiology of community-onset bloodstream infections in Bouaké, central Côte d'Ivoire.

Bacterial bloodstream infections (BSI) account for considerable morbidity worldwide, but epidemiological data from resource-constrained tropical settings are scarce. We analysed 293 blood cultures from patients presenting to a regional referral hospital in Bouaké, central Côte d'Ivoire, to determine the aetiology of community-onset BSI. The prevalence of bacteraemia was 22.5%, with children being most commonly affected. Enterobacteriaceae (predominantly Klebsiella pneumoniae and Salmonella enterica) accounted for 94% of BSI. Staphylococcus aureus was the only relevant Gram-positive pathogen. Clinical signs and symptoms were not significantly associated with blood culture positivity after controlling for malaria.

Application in Europe of a urine-based rapid diagnostic test for confirmation of Schistosoma mansoni infection in migrants from endemic areas.

In February 2015, a male patient from Eritrea with persistent abdominal pain and rectal bleeding was diagnosed with Schistosoma mansoni infection upon examination of a rectal biopsy. In May 2015, repeated stool microscopy identified S. mansoni infection in another Eritrean patient with abdominal pain and considerable eosinophilia (34%). Use of point-of-care circulating cathodic antigen (POC-CCA) tests on urine confirmed S. mansoni infection in both patients. Wider application of non-invasive POC-CCA urine tests will improve schistosomiasis diagnosis and clinical management in migrants.

New diagnostic tools in schistosomiasis.

Schistosomiasis is a water-based parasitic disease that affects over 250 million people. Control efforts have long been in vain, which is one reason why schistosomiasis is considered a neglected tropical disease. However, since the new millennium, interventions against schistosomiasis are escalating. The initial impetus stems from a 2001 World Health Assembly resolution, urging member states to scale-up deworming of school-aged children with the anthelminthic drug praziquantel. Because praziquantel is safe, efficacious and inexpensive when delivered through the school platform, diagnosis before drug intervention was deemed unnecessary and not cost-effective. Hence, there was little interest in research and development of novel diagnostic tools. With the recent publication of the World Health Organization (WHO) Roadmap to overcome the impact of neglected tropical diseases in 2020, we have entered a new era. Elimination of schistosomiasis has become the buzzword and this has important ramifications for diagnostic tools. Indeed, measuring progress towards the WHO Roadmap and whether local elimination has been achieved requires highly accurate diagnostic assays. Here, we introduce target product profiles for diagnostic tools that are required for different stages of a schistosomiasis control programme. We provide an update of the latest developments in schistosomiasis diagnosis, including microscopic techniques, rapid diagnostic tests for antigen detection, polymerase chain reaction (PCR) assays and proxy markers for morbidity assessments. Particular emphasis is placed on challenges and solutions for new technologies to enter clinical practice.

Combined stool-based multiplex PCR and microscopy for enhanced pathogen detection in patients with persistent diarrhoea and asymptomatic controls from Côte d'Ivoire.

Infectious diarrhoea ranks among the leading causes of morbidity worldwide. Although most acute diarrhoeal episodes are self-limiting, the diagnosis and treatment of persistent diarrhoea (≥2 weeks) are cumbersome and require laboratory identification of the causative pathogen. Stool-based PCR assays have greatly improved the previously disappointing pathogen detection rates in high-income countries, but there is a paucity of quality data from tropical settings. We performed a case-control study to elucidate the spectrum of intestinal pathogens in patients with persistent diarrhoea and asymptomatic controls in southern Côte d'Ivoire. Stool samples from 68 patients and 68 controls were obtained and subjected to molecular multiplex testing with the Luminex(®) Gastrointestinal Pathogen Panel (GPP), microscopy and rapid antigen detection tests for the diagnosis of diarrhoeagenic pathogens. Overall, 20 different bacteria, parasites and viruses were detected by the suite of diagnostic methods employed. At least one pathogen was observed in 84% of the participants, and co-infections were observed in >50% of the participants. Enterotoxigenic Escherichia coli (32%), Giardia intestinalis (29%) and Shigella species (20%) were the predominant pathogens, and Strongyloides stercoralis (10%) was the most prevalent helminth. Pathogen frequencies and numbers of co-infections were similar in patients and controls. Although the Luminex(®) GPP detects a broad range of pathogens, microscopy for helminths and intestinal protozoa remains necessary to cover the full aetiological spectrum in tropical settings. We conclude that highly sensitive multiplex PCR assays constitute a useful screening tool, but that positive results might need to be confirmed by independent methods to discriminate active infection from asymptomatic faecal shedding of nucleic acids.

Comparison of the Kato-Katz method and ether-concentration technique for the diagnosis of soil-transmitted helminth infections in the framework of a randomised controlled trial.

Soil-transmitted helminth infections are a major public health problem. An accurate diagnosis is important in order to identify individuals and communities in need of intervention, and for monitoring drug efficacy and potential emergence of resistance. We compared the accuracy of the Kato-Katz method and ether-concentration technique for the diagnosis of soil-transmitted helminth infections within a randomised controlled trial. Quadruplicate Kato-Katz thick smears (duplicate Kato-Katz from two stool samples each) were examined before (baseline) and 3 weeks after treatment (follow-up). Additionally, at baseline and follow-up, the first stool sample was subjected to an ether-concentration method. We determined the prevalence, sensitivity, negative predictive value, diagnostic agreement and cure rates for single and duplicate Kato-Katz thick smears from the first stool sample, quadruplicate Kato-Katz thick smears produced from two stool samples and single ether-concentration as compared to our 'gold' standard (i.e. quadruplicate Kato-Katz plus ether-concentration). Quadruplicate Kato-Katz revealed a higher sensitivity than single ether-concentration for Trichuris trichiura at baseline (94.3 % vs. 88.5 %, p = 0.002) and follow-up (93.8 % vs. 83.5 %, p < 0.001). In contrary, at follow-up, ether-concentration showed a higher sensitivity than quadruplicate Kato-Katz for Ascaris lumbricoides diagnosis (86.7 % vs. 46.7 %, p = 0.012). The ether-concentration method showed similar or slightly higher sensitivity than the Kato-Katz technique based on a single stool sample for all soil-transmitted helminth infections. The estimated cure rates were heavily dependent on the diagnostic technique and sampling effort. In conclusion, data on the prevalence of soil-transmitted helminth infections and the efficacy of anthelminthics are greatly influenced by the diagnostic method and sampling effort. The ether-concentration technique is a valuable alternative to the Kato-Katz method for helminth diagnosis.

Contrasting the distribution of phenotypic and molecular variation in the freshwater snail Biomphalaria pfeifferi, the intermediate host of Schistosoma mansoni.

Population differentiation was investigated by confronting phenotypic and molecular variation in the highly selfing freshwater snail Biomphalaria pfeifferi, the intermediate host of Schistosoma mansoni. We sampled seven natural populations separated by a few kilometers, and characterized by different habitat regimes (permanent/temporary) and openness (open/closed). A genetic analysis based on five microsatellite markers confirms that B. pfeifferi is a selfer (s≈0.9) and exhibits limited variation within populations. Most pairwise FST were significant indicating marked population structure, though no isolation by distance was detected. Families from the seven populations were monitored under laboratory conditions over two generations (G1 and G2), allowing to record several life-history traits, including growth, fecundity and survival, over 25 weeks. Marked differences were detected among populations for traits expressed early in the life cycle (up to sexual maturity). Age and size at first reproduction had high heritability values, but such a trend was not found for early reproductive traits. In most populations, G1 snails matured later and at a larger size than G2 individuals. Individuals from permanent habitats matured at a smaller size and were more fecund than those from temporary habitats. The mean phenotypic differentiation over all populations (QST) was lower than the mean genetic differentiation (FST), suggesting stabilizing selection. However, no difference was detected between QST and FST for both habitat regime and habitat openness.

Risk of Vibrio transmission linked to the consumption of crustaceans in coastal towns of Côte d'Ivoire.

The purpose of this study was to assess the risk of Vibrio spp. transmission from crustaceans to humans in two coastal towns of Côte d'Ivoire. Bacteriologic analysis was performed on 322 crustacean samples obtained from six markets in Abidjan and one in Dabou. Suspected Vibrio colonies were identified by morphological, cultural, biochemical, and molecular tests and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. PCR assays were used to further characterize Vibrio strains. A survey on consumption of crustaceans was conducted among 120 randomly selected households in Abidjan. Overall, Vibrio spp. were isolated from 7.8% of the crustacean samples studied, at levels as high as 6.3 log CFU/g. Of the Vibrio strains identified, 40% were V. alginolyticus, 36% were V. parahaemolyticus, and 24% were nontoxigenic V. cholerae; the latter two species can cause mild to severe forms of seafood-associated gastroenteritis. Among interviewed households, 11.7% reported daily consumption of crustaceans, confirming the high probability of exposure of human population to Vibrio spp., and 7.5% reported symptoms of food poisoning after consumption of crustaceans. The absence of genes encoding major virulence factors in the studied strains, i.e., cholera toxin (ctxA and ctxB) in V. cholerae and thermostable direct hemolysin (tdh) and thermostable direct hemolysin-related hemolysin (trh) in V. parahaemolyticus, does not exclude the possibility of exposure to pathogenic strains. However, human infections are not common because most households (96.7%) boil crustaceans, usually for at least 45 min (85.9% of households) before consumption.

Modelling the geographical distribution of co-infection risk from single-disease surveys.

BACKGROUND: The need to deliver interventions targeting multiple diseases in a cost-effective manner calls for integrated disease control efforts. Consequently, maps are required that show where the risk of co-infection is particularly high. Co-infection risk is preferably estimated via Bayesian geostatistical multinomial modelling, using data from surveys screening for multiple infections simultaneously. However, only few surveys have collected this type of data. METHODS: Bayesian geostatistical shared component models (allowing for covariates, disease-specific and shared spatial and non-spatial random effects) are proposed to model the geographical distribution and burden of co-infection risk from single-disease surveys. The ability of the models to capture co-infection risk is assessed on simulated data sets based on multinomial distributions assuming light- and heavy-dependent diseases, and a real data set of Schistosoma mansoni-hookworm co-infection in the region of Man, Côte d'Ivoire. The data were restructured as if obtained from single-disease surveys. The estimated results of co-infection risk, together with independent and multinomial model results, were compared via different validation techniques. RESULTS: The results showed that shared component models result in more accurate estimates of co-infection risk than models assuming independence in settings of heavy-dependent diseases. The shared spatial random effects are similar to the spatial co-infection random effects of the multinomial model for heavy-dependent data. CONCLUSIONS: In the absence of true co-infection data geostatistical shared component models are able to estimate the spatial patterns and burden of co-infection risk from single-disease survey data, especially in settings of heavy-dependent diseases.

[Bio-ecological characteristics of Anopheles gambiae s.s. in irrigated rice fields of central Côte d'Ivoire]. / Caractéristiques bioécologiques d'Anopheles gambiae s.s. en zones de riziculture irriguée au centre de la Côte d'Ivoire.

This longitudinal entomological survey was conducted between September 2008 and September 2009 in the villages of Abokro and Yaokoffikro located in an irrigated rice farming area of central Côte d'Ivoire. The purpose was to investigate the bio-ecological characteristics of Anopheles gambiae s.s. during the gonotrophic cycle. In both villages, adult mosquitoes were captured in 72 light traps, collected on humans subjects at a rate of 72 man-night from 6 p.m. to 6 a.m., and knocked down using pyrethroid spray inside 60 sentinel houses in the early morning. A total of 10,312 adult mosquitoes were collected in Abokro and 7,662 in Yaokoffikro. Anopheles was the dominant genus at both locations. Light traps were three times more efficient in Abokro than in Yaokoffikro. In both places, An. gambiae s.s. biting rates increased gradually up to a peak observed between midnight and 1 a.m. In Abokro, most An. gambiae s.s. were collected inside sleeping rooms. The endophagic rate and indoor resting density was 67.4% (n = 4798) and 14.9 females per bedroom per night, respectively, in Abokro as compared to 49.3% (n = 6775) and 2.9 females per bedroom per day, respectively, in Yaokoffikro.

Spatial dispersion and characterisation of mosquito breeding habitats in urban vegetable-production areas of Abidjan, Côte d'Ivoire.

Although urban agriculture (UA) in the developing world may enhance nutrition and local economies, it may also lead to higher densities of mosquito breeding sites and, consequently, to increased transmission of malarial parasites. If targeted interventions against malaria vectors are to be successful in urban areas, the habitats that support Anopheles breeding need to be identified and detected. Mosquito breeding sites have recently been characterised, and the factors associated with productive Anopheles habitats identified, in market gardens of Abidjan, Côte d'Ivoire. Two surveys were conducted in seven vegetable-production areas, one towards the end of the rainy season and one during the dry season. A standardized methodology was used for habitat characterisation and the detection of Anopheles larvae and mosquito pupae. Overall, 454 and 559 potential mosquito-breeding sites were recorded in the rainy-season and dry-season surveys, respectively. In the rainy season, Anopheles larvae and mosquito pupae were found in 29.7% and 5.5% of the potential breeding sites, respectively, whereas the corresponding percentages in the dry season were 24.3% and 8.6%. The potential breeding sites in an agricultural zone on the periphery of Abidjan were those least likely to be positive for Anopheles larvae and mosquito pupae whereas 'agricultural trenches' between seedbeds were the sites most likely to be positive. In a spatially-explicit Bayesian multivariate logistic-regression model, although one out of every five such wells was also found to harbour Anopheles larvae, irrigation wells were found to be the least productive habitats, of those sampled, for pupae. In the study area, simple and cost-effective strategies of larval control should be targeted at agricultural trenches, ideally with the active involvement of local stakeholders (i.e. urban farmers and urban agricultural extension services).

Effects of seasonality and irrigation on malaria transmission in two villages in Côte d'Ivoire.

The seasonality of malaria transmission was investigated in two villages in central Côte d'Ivoire: one usually with irrigated rice farming (Zatta) and one without (Tiémélékro). Adult mosquitoes were collected, from February 2002 to August 2005, inside and outside sentinel houses. In Tiémélékro, the biting rate of Anopheles gambiae s.s. showed a significant difference between the dry and rainy season only in 2003 (P<0.001). The corresponding rates for An. funestus s.s. showed significant seasonal differences in both 2002 and 2003 (P<0.001 for each year). In Zatta in 2003-2004, when irrigated rice farming was interrupted, there was no significant difference between the An. gambiae s.s. biting rates recorded in the dry and rainy seasons. In both 2002 and 2005, however, when irrigated rice farming was practised, the An. gambiae s.s. biting rate recorded in Zatta during the rainy season was significantly higher than that seen in the dry season (P<0.001 for each year). With just one exception (in Tiémélékro in 2005, the prevalence of Plasmodium infection in the An. funestus was significantly higher in the rainy season than in the dry season), no significant seasonal differences were seen in the prevalences of Plasmodium infection among the An. gambiae or An. funestus. In conclusion, although malaria transmission is quite stable in central Côte d'Ivoire throughout the year, it can be distinctly modified by irrigated rice farming.

[Epidemiological baseline situation before the construction of a small dam in five villages of Bouaké, central Côte-d'Ivoire]. / Situation épidémiologique avant la mise en eau du barrage hydroagricole de cinq villages de Bouaké, centre Côte-d'Ivoire

Abstract From June 2007 to June 2008, entomological, malacological and parasitological investigations were carried out in five villages in close proximity to a small dam of Raf-fierkro in Bouaké, central Côte-d'Ivoire. The objective of the study was to identify vectors and intermediate host snails of parasitic diseases related to water, and to assess the prevalence of malaria, schistosomiasis and soil-transmitted helminthiasis before dam construction. Mosquitoes were caught by human landing catches, snails were collected in water bodies, and microscopic analyses of blood, stool and urine samples were carried out. Two malaria vector species were identified:Anopheles gambiae and Anopheles funestus. The average infective rate of An. gambiae ranged between 3.1 and 4.5 %. The infective rate of An. funestus was 1 % in all sites. The entomological inoculation rate ranged between 343.1 and 427.1 infective bites per person per year (ib/p/y)for An. gambiae and between 14.6 and 40.1 ib/p/y for An. funestus. Three species of were found: Plasmodium falciparum (predominant species), Plasmodium ovale and Plasmodium malariae. There were no intermediate host snails of schistosomiasis with the exception of Biomphalaria pfeifferi,intermediate host snail of Schistosoma mansoni in Ahougui. The prevalence of urinary and intestinal schistosomiasis and soil-transmitted helminthiasis was low. Our studies revealed important transmission of malaria, with the presence of three plasmodial species, whereas schistosomiasis and soil-transmitted helminthiasis were present, but only at low frequencies.

[Malaria transmission in an area of high coverage with long lasting insecticidal nets in central Côte d'Ivoire]. / Transmission du paludisme en zone de haute couverture en moustiquaires imprégnées d'insecticide de longue durée, au centre de la Côte d'Ivoire.

The purpose of this study was to assess malaria transmission in an area of high coverage with long-lasting insecticidal nets (LLINs) in central Côte d'Ivoire. Two four-day larva collections were carried out in April and July 2008. Adult mosquito samples were collected by conducting human bait catches during a total of 80 man-nights. Vector infection rates were determined using an ELISA circumsporozoite antibody test. A total of 1582 mosquitoes were captured. Mansonia was the dominant genus in the culcidian fauna followed by Anopheles that was dominant in the anopheline fauna. The only Plasmodium vector was An. gambiae s.l. The high household bednet coverage rate probably accounted for the relatively low biting rate: 0.75 to 4.15 bites per person per night (b/p/n). Households not using bednets appear to have benefited from a passive protection effect associated with high LLIN coverage. Biting and entomological inoculation rates were 2.25 to 4.1 b/p/n (range) and 0.184 ib/p/n respectively in households that did not use LLINs and 0.75 to 4.15 b/p/n (range) and 0.341 ib/p/n respectively in households using LLINs.

Bidirectional correlation of NMR and capillary electrophoresis fingerprints: a new approach to investigating Schistosoma mansoni infection in a mouse model.

We demonstrate the statistical integration of nuclear magnetic resonance (NMR) spectroscopy and capillary electrophoresis (CE) data in order to describe a pathological state caused by Schistosoma mansoni infection in a mouse model based on urinary metabolite profiles. Urine samples from mice 53 days post infection with S. mansoni and matched controls were analyzed via NMR spectroscopy and CE. The two sets of metabolic profiles were first processed and analyzed independently and were subsequently integrated using statistical correlation methods in order to facilitate cross assignment of metabolites. Using this approach, metabolites such as 3-ureidopropionate, p-cresol glucuronide, phenylacetylglycine, indoxyl sulfate, isocitrate, and trimethylamine were identified as differentiating between infected and control animals. These correlation analyses facilitated structural elucidation using the identification power of one technique to enhance and validate the other, but also highlighted the enhanced ability to detect functional correlations between metabolites, thereby providing potential for achieving deeper mechanistic insight into the biological process.