Irene A. Larbi

Background: Worldwide, 451 million people and up to 156 million children are infected with hookworm, causing an estimated 3.2 million disability-adjusted life-years annually. We conducted a two-year longitudinal cohort study of hookworm infection with a random selection of 274 school-age children (4–16 yrs) in rural Ghana to identify nutritional and environmental exposures impacting hookworm infection and response to treatment. Methods: Every six months (baseline Jan 2013) we collected anthropometric measurements, pre- and post-treatment fecal samples, and blood samples. Household surveys and multiple-pass twenty-four-hour recalls were conducted at baseline and 18 months. Results: Seventy-eight participants (28.5%) were absent from at least 1 time point. Of the 196 that were screened at all five time points, 87 (44.4%) were hookworm-infected>1 time. Assessment of albendazole treatment response was conducted on 83 participants. Sixty (72.3%) were cleared of hookworm infections while 23 (27.5%) remained infected post-treatment (ERR: 0–99%). Treatment efficacy was more likely among children aged over 9.66 years (HR: 1.55; 95% CI: 1.18, 2.04) and those from food-insecure households (HR: 2.26; 95% CI: 1.06, 4.81). Hookworm infection status and albendazole treatment outcome at baseline and 18 months were the dominant influences on infections at 6 and 24 months, respectively. Future risk of infection at both 6 and 24 months had significant environmental and nutritional predictors, although the variables differed. Conclusions: Global school-based deworming has been associated with reduced rates of hookworm infection among schoolchildren in Africa; however, additional strategies will be necessary for long-term, sustainable control. This study reports on an innovative two-year longitudinal study of school age children with repeated cycles of testing and treatment. We modelled hookworm infection as a function of predictors that were measured six months prior, thereby strengthening the assessment of causal relationships between environmental, infection and nutritional risk factors.

Background: The current global aim for onchocerciasis is to eliminate transmission of infection by administering ivermectin once a year or biannually. However, when ivermectin treatment is given annually for 9–10 y, some individuals still carry low microfilariae (mf) levels, which may allow continued transmission. Methods: At four different times (0, 8, 90, 365 days) after treatment with ivermectin, 1608 newly emerged Simulium sanctipauli (Pra form) flies were fed on 35 volunteers, with initial dermal microfilarial loads ranging from 0 to >30 Onchocerca volvulus mf/mg skin. Ten days after feeding, the number and load of mf in these flies were assessed by dissection. Results: Notably, even at the lowest skin-snip mf densities—including those showing zero infection—flies can still ingest O. volvulus mf and become infected; 29% of the 1608 fed flies picked up mf. The lowest skin mf levels were recorded on Day 90 after treatment, at which time vector mf uptake increased by 21% with every unit increase in skin mf density (P < .000). Conclusions: Very low dermal mf levels can still support parasite transmission. Consequently, widespread low O. volvulus infection in human populations with highly productive vector-breeding sites could significantly affect efforts to eliminate transmission.

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.

Anemia remains a serious public health concern, globally, affecting learning ability and physical development of children. Anemic children are at a higher risk of diminished economic productivity and low earning capacity in adulthood due to impaired school performance and reduced work capacity. Anemia contributes to about a quarter of Africa’s nutrition-related Disability Adjusted Life Years. The objective of this study was to determine the prevalence of anemia and its associated risk factors among school-aged children (SAC) between ages 9 and 15 years in urban Ghana. The analysis included a randomly selected subsample of 1,634 children from a larger study on nutrition of SAC enrolled between 2009 and 2012 in private and public basic schools in the Accra and Kumasi Metropolis in Ghana. Socio-demographic and household characteristics were collected with questionnaires. Weight and height were taken to the nearest 0.1kg and 0.1cm, respectively. Dietary information was collected using a food frequency questionnaire. Data were analyzed using IBM SPSS Statistic version 23. The relationship between hemoglobin levels and socio-demographic variables, and predictors of hemoglobin levels were determined using Chi-square and binary logistic regression. The mean hemoglobin concentration of the study participants was 12.9±1.3 g/dL. In Kumasi, SAC had higher mean hemoglobin concentration (13.1±1.2 g/dL) compared to those from Accra (12.6±1.3 g/dL; p=0.001). Mean hemoglobin concentration was significantly higher among males than females (13.0±1.4 g/dL vs 12.8±1.2 g/dL; p=0.002). Prevalence of anemia was 20.4%; mild anemia was most common (13.6% of total sample). Anemia cases were higher in public schools (24.6%) compared to private (18.2%). Two-thirds of anemia cases (64.0%) were from schools in Accra. Males had significantly higher prevalence of anemia (26.5%) than females (15.9%; p <0.05). In the adjusted logistic regression model, only city of residence (OR+1.65, 95% CI: 1.44–1.83), thinness (OR=2.60, 95% CI: 1.11-5.75), stunting (OR=1.85, 95% CI: 1.99-3.10) and overweight (OR=0.60, 95% CI: 0.36-0.94) were significantly associated with anemia. In this study, anemia was significantly associated with location and nutritional status. Key words: anemia, Ghana, hemoglobin, schoolchildren, urban settings, metropolis, Accra, Kumasi

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.

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.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of ivermectin on malaria transmission and mosquito survival.

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. 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. 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. ClinicalTrials.gov, ID: NCT03036059 . Registered on 26 January 2017. Pan African Clinical Trials Registry, ID: PACTR201702002012425 . Registered on 23 February 2017.

Recent studies indicate that urbanization is having a pronounced effect on disease patterns in developing countries. To understand the immunological basis of this, we examined mRNA expression in whole blood of genes involved in immune activation and regulation in 151 children aged 5-13 years attending rural, urban low socioeconomic status (SES) and urban high-SES schools in Ghana. Samples were also collected to detect helminth and malaria infections. Marked differences in gene expression were observed between the rural and urban areas as well as within the urban area. The expression of both interleukin (IL)-10 and programmed cell death protein 1 increased significantly across the schools from urban high SES to urban low SES to rural (P-trend <0.001). Although IL-10 gene expression was significantly elevated in the rural compared with the urban schools (P<0.001), this was not associated with parasitic infection. Significant differences in the expression of toll-like receptors (TLRs) and their signaling genes were seen between the two urban schools. Genetic differences could not fully account for the gene expression profiles in the different groups as shown by analysis of IL-10, TLR-2 and TLR-4 gene polymorphisms. Immune gene expression patterns are strongly influenced by environmental determinants and may underlie the effects of urbanization seen on health outcomes.