Regular deworming and seasonality are potential challenges but also offer opportunities for hookworm elimination.

The global health community has targeted the elimination of neglected tropical diseases (NTDs) including soil-transmitted helminthiasis by 2030. The elimination strategy has not changed from that of control using regular mass drug administration (MDA) with albendazole, WASH and education. Already doubts have been expressed about this achievement, principally because drugs do not interrupt transmission. We report here the findings of a cohort study aimed to identify host modifiable and environmental factors associated with hookworm infection and reinfection in rural communities in Kintampo North Municipality, Ghana. Faecal samples of 564 consented participants were screened for intestinal parasites at baseline, 9 months and 24 months using the Kato-Katz method. At each time point, positive cases were treated with a single dose of albendazole (400 mg) and their samples were again screened 10-14 days post-treatment to record treatment failures. The hookworm prevalence at the three-time points was 16.7%, 9.22% and 5.3% respectively, whilst treatment failure rates were 17.25%, 29.03% and 40.9% respectively. The intensities of hookworm infection (in eggs per gram) at the time points were 138.3, 40.5 and 135, which showed a likely association with wet and dry seasons. We posit that the very low intensity of hookworm infections in humans during the dry season offers a window of opportunity for any intervention that could drastically reduce the community worm burden before the rainy season.

Increased ShTAL1 IgE responses post-Praziquantel treatment may be associated with a reduced risk to re-infection in a Ghanaian S. haematobium-endemic community.

BACKGROUND: Evidence from recent studies in Schistosoma mansoni-endemic areas show an age-associated immunity that is positively correlated with IgE titres to Schistosoma mansoni-specific tegumental allergen-like protein 1 (SmTAL1). The structural homology between SmTAL1 and the S. haematobium-specific TAL1 (ShTAL1) has been verified, yet it remains unclear whether similar age- and immune-associated trends characterize ShTAL1. This community-based intervention study was conducted to assess whether ShTAL1IgE responses post-treatment with praziquantel (PZQ) might be associated with a reduced risk to re-infection with S. haematobium. METHODOLOGY/PRINCIPAL FINDINGS: This study was conducted at Agona Abodom, Central Region, Ghana, and involved 114 participants aged 6 to 55 years. EDTA blood samples were collected at baseline and 7 weeks after PZQ treatment (Follow-up). Baseline and Follow-up titres of specific IgG1, IgG4, and IgE antibodies to the S. haematobium-specific adult worm antigen (ShAWA), the Sh-specific soluble egg antigen (ShSEA), and the Sh-specific tegumental-allergen-like 1 protein (ShTAL1) in plasma samples were measured using sandwich ELISA. Participants at both time points also provided stool and urine for helminth egg detection by microscopy. Prevalence of S. haematobium at baseline was 22.80%, and decreased to 3.50% at Follow-up. The egg reduction rate (ERR) was 99.87%. Overall plasma levels of ShTAL1-IgE increased 7 weeks post-PZQ treatment, and with increasing age; whiles S. haematobium infection prevalence and intensity decreased. For S. haematobium-infected participants who were egg-negative at Follow-up (N = 23), minimal median levels of ShTAL1-IgE were observed for all age groups prior to treatment, whilst median levels increased considerably among participants aged 12 years and older at Follow-up; and remained minimal among participants aged 11 years or less. In the univariate analysis, being aged 12 years or older implied an increased likelihood for ShTAL1-IgE positivity [12-14 years (cOR = 9.64, 95% CI = 2.09-44.51; p = 0.004); 15+ years (cOR = 14.26, 95% CI = 3.10-65.51; p = 0.001)], and this remained significant after adjusting for confounders [12-14 years (aOR = 22.34, 95% CI = 2.77-180.14; p = 0.004); ≥15 years (aOR = 51.82, 95% CI = 6.44-417.17; p < 0.001)]. Conversely, median ShTAL1-IgG4 titres were hardly detectible at Follow-up. CONCLUSIONS/SIGNIFICANCE: These findings demonstrate that increased IgE levels to ShTAL1 7 weeks after PZQ treatment could be associated with a reduced risk to re-infection, and adds to the large body of evidence suggesting a protective role of the treatment-induced ShTAL1 antigen in schistosomiasis infections. It was also quite clear from this work that apart from being persistently S. haematobium-positive, elevated ShTAL1-IgG4 levels at Follow-up could be indicative of susceptibility to re-infection. These outcomes have important implications in vaccine development, and in shifting the paradigm in mass chemotherapy programmes from a 'one-size-fits-all' approach to more sub-group-/participant-specific strategies in endemic areas.

Low Microfilaremia Levels in Three Districts in Coastal Ghana with at Least 16 Years of Mass Drug Administration and Persistent Transmission of Lymphatic Filariasis.

Ghana has been implementing mass drug administration (MDA) of ivermectin and albendazole for the elimination of lymphatic filariasis (LF) since the year 2000, as part of the Global Programme to Eliminate Lymphatic Filariasis (GPELF). It was estimated that 5⁻6 years of treatment would be sufficient to eliminate the disease. Tremendous progress has been made over the years, and treatment has stopped in many disease endemic districts. However, despite the successful implementation of MDA, there are districts with persistent transmission. In this study we assessed the epidemiology of LF in three adjoining districts that have received at least 16 years of MDA. The assessments were undertaken one year after the last MDA. 1234 adults and 182 children below the age of 10 years were assessed. The overall prevalence of circulating filarial antigen in the study participants was 8.3% (95% CI: 6.9⁻9.9), with an estimated microfilaria prevalence of 1.2%. The microfilarial intensity in positive individuals ranged from 1 to 57 microfilariae/mL of blood. Higher antigen prevalence was detected in males (13.0%; 95% CI: 10.3⁻16.2) compared to females (5.5%; 95% CI: 4.1⁻7.2). The presence of infection was also highest in individuals involved in outdoor commercial activities, with the risks of infection being four- to five-fold higher among farmers, fishermen, drivers and artisans, compared to all other occupations. Using bednets or participating in MDA did not significantly influence the risk of infection. No children below the age of 10 years were found with infection. Detection of Wb123 antibodies for current infections indicated a prevalence of 14.4% (95% CI: 8.1⁻23.0) in antigen-positive individuals above 10 years of age. No antibodies were detected in children 10 years or below. Assessment of infection within the An. gambiae vectors of LF indicated an infection rate of 0.9% (95% CI: 0.3⁻2.1) and infectivity rate of 0.5% (95% CI: 0.1⁻1.6). These results indicate low-level transmission within the districts, and suggest that it will require targeted interventions in order to eliminate the infection.

Community-based trial of annual versus biannual single-dose ivermectin plus albendazole against Wuchereria bancrofti infection in human and mosquito populations: study protocol for a cluster randomised controlled trial.

BACKGROUND: The Global Programme for the Elimination of Lymphatic Filariasis (GPELF) has been in operation since the year 2000, with the aim of eliminating the disease by the year 2020, following five to six rounds of effective annual mass drug administration (MDA). The treatment regimen is ivermectin (IVM) in combination with diethylcarbamazine (DEC) or albendazole (ALB). In Ghana, MDA has been undertaken since 2001. While the disease has been eliminated in many areas, transmission has persisted in some implementation units that had experienced 15 or more rounds of MDA. Thus, new intervention strategies could eliminate residual infection in areas of persistent transmission and speed up the lymphatic filariasis (LF)-elimination process. This study, therefore, seeks to test the hypothesis that biannual treatment of LF-endemic communities will accelerate the interruption of LF in areas of persistent transmission. METHODS: A cluster randomised trial will be implemented in LF-endemic communities in Ghana. The interventions will be yearly or twice-yearly MDA delivered to entire endemic communities. Allocation to study group will be by clusters identified using the prevalence of LF. Clusters will be randomised to one of two groups: receiving either (1) annual treatment with IVM + ALB or (2) annual MDA with IVM + ALB, followed by an additional MDA 6 months later. The primary outcome measure is the prevalence of LF infection, assessed by four cross-sectional surveys. Entomological assessments will also be undertaken to evaluate the transmission intensity of the disease in the study clusters. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, microfilaria prevalence will be assessed longitudinally. A nested process evaluation, using semi-structured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system. DISCUSSION: It is expected that this study will add to the existing evidence on the need for alternative intervention strategies for the elimination of LF in Ghana and in other African countries that are facing similar challenges or are at the beginning of their LF-elimination programmes. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03036059 . Registered on 26 January 2017. Pan African Clinical Trials Registry, ID: PACTR201702002012425 . Registered on 23 February 2017.

Peanut-specific IgE antibodies in asymptomatic Ghanaian children possibly caused by carbohydrate determinant cross-reactivity.

BACKGROUND: The prevalence of peanut allergy has increased in developed countries, but little is known about developing countries with high peanut consumption and widespread parasitic infections. OBJECTIVE: We sought to investigate peanut allergy in Ghana. METHODS: In a cross-sectional survey among Ghanaian schoolchildren (n = 1604), data were collected on reported adverse reactions to peanut, peanut sensitization (serum specific IgE and skin reactivity), consumption patterns, and parasitic infections. In a subset (n = 43) IgE against Ara h 1, 2, 3, and 9 as well as cross-reactive carbohydrate determinants (CCDs) was measured by using ImmunoCAP. Cross-reactivity and biological activity were investigated by means of ImmunoCAP inhibition and basophil histamine release, respectively. RESULTS: Adverse reactions to peanut were reported in 1.5%, skin prick test reactivity in 2.0%, and IgE sensitization (≥0.35 kU/L) in 17.5% of participants. Moreover, 92.4% of those IgE sensitized to peanut (≥0.35 kU/L) had negative peanut skin prick test responses. Schistosoma haematobium infection was positively associated with IgE sensitization (adjusted odds ratio, 2.29; 95% CI, 1.37-3.86). In the subset IgE titers to Ara h 1, 2, 3, and 9 were low (<1.3 kU/L), except for 6 moderately strong reactions to Ara h 9. IgE against peanut was strongly correlated with IgE against CCDs (r = 0.89, P < .0001) and could be almost completely inhibited by CCDs, as well as S haematobium soluble egg antigen. Moreover, IgE to peanut showed poor biological activity. CONCLUSIONS: Parasite-induced IgE against CCDs might account largely for high IgE levels to peanut in our study population of Ghanaian schoolchildren. No evidence of IgE-mediated peanut allergy was found.

Molecular diagnosis of Schistosoma infections in urine samples of school children in Ghana.

Recent studies using an internal transcribed spacer (ITS)-based real-time polymerase chain reaction (PCR) for the detection of Schistosoma DNA in urine samples has shown high sensitivity and specificity when performed on controls and known microscopy-positive samples. In this study, using 730 urine samples collected from children in five primary schools from different communities in the Greater Accra region of Ghana, specific detection of Schistosoma DNA showed excellent sensitivity of 100% and 85.2% in urines with > 50 eggs/10 mL urine and ≤ 50 eggs/10 mL of urine, respectively. Additionally, Schistosoma-specific DNA was amplified in 102 of 673 samples in which Schistosoma eggs could not be detected with microscopy. Taking microscopy and/or PCR-positive samples as true positives, the negative predictive value calculated was 94.6-100% for each school sampled as compared with 54.3-95.7% using microscopy. This ITS-based real-time PCR proves to be a powerful tool in epidemiological surveys of schistosomiasis providing more precise and sensitive results than microscopy.

High body mass index is not associated with atopy in schoolchildren living in rural and urban areas of Ghana.

BACKGROUND: Factors which determine the development of atopy and the observed rural-urban gradient in its prevalence are not fully understood. High body mass index (BMI) has been associated with asthma and potentially atopy in industrialized countries. In developing countries, the transition from rural to urban areas has been associated with lifestyle changes and an increased prevalence of high BMI; however, the effect of high BMI on atopy remains unknown in this population. We therefore investigated the association between high BMI and atopy among schoolchildren living in rural and urban areas of Ghana. METHODS: Data on skin prick testing, anthropometric, parasitological, demographic and lifestyle information for 1,482 schoolchildren aged 6-15 years was collected. Atopy was defined as sensitization to at least one tested allergen whilst the Centres for Disease Control and Prevention (CDC, Atlanta) growth reference charts were used in defining high BMI as BMI ≥ the 85th percentile. Logistic regression was performed to investigate the association between high BMI and atopy whilst adjusting for potential confounding factors. RESULTS: The following prevalences were observed for high BMI [Rural: 16%, Urban: 10.8%, p < 0.001] and atopy [Rural: 25.1%, Urban: 17.8%, p < 0.001]. High BMI was not associated with atopy; but an inverse association was observed between underweight and atopy [OR: 0.57, 95% CI: 0.33-0.99]. Significant associations were also observed with male sex [Rural: OR: 1.49, 95% CI: 1.06-2.08; Urban: OR: 1.90, 95% CI: 1.30-2.79], and in the urban site with older age [OR: 1.76, 95% CI: 1.00-3.07], family history of asthma [OR: 1.58, 95% CI: 1.01-2.47] and occupational status of parent [OR: 0.33, 95% CI: 0.12-0.93]; whilst co-infection with intestinal parasites [OR: 2.47, 95% CI: 1.01-6.04] was associated with atopy in the rural site. After multivariate adjustment, male sex, older age and family history of asthma remained significant. CONCLUSIONS: In Ghanaian schoolchildren, high BMI was not associated with atopy. Further studies are warranted to clarify the relationship between body weight and atopy in children subjected to rapid life-style changes associated with urbanization of their environments.

Food allergy in Ghanaian schoolchildren: data on sensitization and reported food allergy.

BACKGROUND: Epidemiological data on food allergy are scarce in African countries. We studied the prevalence of food sensitization in Ghanaian schoolchildren. METHODS: Children (5-16 years; n = 1,714) from 9 Ghanaian schools were given parental consent to participate in the study. Adverse reactions and food consumption were determined by a questionnaire and atopy by skin prick testing (SPT) to peanut and 6 fruits. Subjects with positive SPTs were considered cases (n = 43) and matched with at least 1 control (n = 84), using age, sex, and school as matching criteria. Serum samples from case-control sets were analyzed for specific IgE (sIgE) to foods that elicited a positive SPT response in cases. RESULTS: Overall, 11% of 1,407 children reported adverse reactions to foods, and 5% of 1,431 children showed a positive SPT reaction mostly directed against peanut and pineapple (both 2%). Although there was a positive association between adverse reactions and SPT responses to any food allergen in the urban children (adjusted OR = 3.6, 95% CI 1.2-10.8), most of the reported adverse reactions were not in children showing an SPT reaction to the specific food item. sIgE sensitization was very variable for the different foods, ranging from 0 to 100% in cases, and from 0 to 25% among controls. High IgE levels for a food item significantly increased the risk of SPT positivity to any food item in the urban, but not in the rural, schoolchildren. CONCLUSIONS: Specific foods were identified to be allergenic in Ghana. We show a good association between SPT and sIgE in urban, but not in rural, schoolchildren. However, there was no clear association between reported adverse reactions to food and SPT or sIgE.

Enhanced Toll-like receptor responsiveness associated with mitogen-activated protein kinase activation in Plasmodium falciparum-infected children.

Acute Plasmodium falciparum infection is associated with strongly upregulated cytokine responses that are at least partly the result of activation of Toll-like receptors (TLRs). Whether and how TLR expression/responsiveness changes upon malarial infection is, however, currently not well understood. To assess this, we examined expression of TLRs and used the TLR ligand lipopolysaccharide (LPS) and Pam(3)Cys to stimulate peripheral blood mononuclear cells (PBMCs) from Ghanaian schoolchildren who live in a rural area where P. falciparum is endemic. Expression of TLR2 was higher, and responses to its ligand, Pam(3)Cys, were enhanced in P. falciparum-infected children compared to their uninfected counterparts. In cells from the same children, stimulation by Pam(3)Cys resulted in higher p38 mitogen-activated protein kinase activation and higher cytokine production. In vitro experiments confirmed that preincubation of PBMCs with P. falciparum-infected red blood cells enhanced responsiveness to TLR ligands. Taken together, the data indicate that P. falciparum-infected children in areas where malaria is endemic have an altered innate immune system, which might be important for the balance between immunity and pathology when new infections are encountered or when novel vaccines are introduced.

Lower expression of TLR2 and SOCS-3 is associated with Schistosoma haematobium infection and with lower risk for allergic reactivity in children living in a rural area in Ghana.

BACKGROUND: Helminth infections are prevalent in rural areas of developing countries and have in some studies been negatively associated with allergic disorders and atopy. In this context little is known of the molecular mechanisms of modulation involved. We have characterized the innate immune responses, at the molecular level, in children according to their helminth infection status and their atopic reactivity to allergens. METHODOLOGY/PRINCIPAL FINDINGS: The mRNA expression of several genes of the innate immune system that have been associated with microbial exposure and allergy was examined in 120 school children in a rural area in Ghana. Helminth infections were common and atopy rare in the study area. The analysis of gene expression in ex vivo whole blood samples reflected the levels of corresponding proteins. Using this approach in a population of school children in whom the presence of Schistosoma haematobium infection was associated with protection from atopic reactivity, we found that the level of TLR2 and SOCS-3, genes associated with atopy in the children, were significantly downregulated by presence of S. haematobium infection. CONCLUSIONS: S. haematobium infections modulate the expression of genes of the innate immune system (TLR2 and SOCS-3); these are genes that are associated with increased allergic inflammatory processes, providing a molecular link between the negative association of this infection and atopy in rural children in Ghana.