Towards Understanding the Microepidemiology of Lymphatic Filariasis at the Community Level in Ghana.

Studies on the distribution of lymphatic filariasis (LF) have mostly focused on reporting prevalence at the community level and distribution at the district levels. Understanding the distribution patterns at community levels may help in designing surveillance strategies. This study aimed to characterize the spatial distribution of LF infections in four hotspot communities in Ghana. The research, involving 252 participants, collected demographic data, mass drug administration (MDA) information, household GPS coordinates, and antigen detection test results. The LF prevalence varied significantly among the communities, with Asemda having the highest (33.33%) and Mempeasem having the lowest (4.44%). Females had lower odds of infection than males (OR = 2.67, p = 0.003 CI: 1.39-5.13). Spatial analysis using kernel density, Anselin Local Moran's, Getis-Ord Gi models, Ordinary Least Squares, and Geographic Weighted Regression revealed mixed patterns of spatial autocorrelation. This study identified LF hotspots, indicating clusters of high or low prevalence with some areas showing disparities between MDA coverage and LF positivity rates. Despite these hotspots, the overall distribution of LF appeared random, suggesting the importance of purposeful sampling in surveillance activities. These findings contribute valuable insights into the micro-epidemiology of LF, emphasizing the need for community-specific investigations to understand the factors influencing the effectiveness of MDA programs in controlling filarial infections. The study highlights the importance of refining surveillance strategies based on community-level distribution patterns.

A Comparative Study of Lymphatic Filariasis-Related Perceptions among Treated and Non-Treated Individuals in the Ahanta West Municipality of Ghana.

Background: Ghana joined the Global Programme to Eliminate Lymphatic Filariasis (GPELF), established in the year 2000, with the aim of eliminating the disease as a public health problem through annual mass treatment of entire endemic populations. Since 2001, the country has implemented mass drug administration (MDA) in endemic districts, with great reductions in the population at risk for infection. However, in many districts, the elimination programme is faced with the presence of hotspots, which may be due in part to individuals not taking part in MDA (either intentionally or unintentionally) who may serve as reservoirs to sustain transmission. This paper compares the LF-related perceptions among individuals who regularly take the MDA drugs and those who seldom or never take part in the MDA in the Ahanta West Municipality of Ghana to determine community acceptable ways to implement an intervention aimed to track, engage, and treat individuals who regularly miss MDA or to test individuals who intentionally refuse MDA and treat them if positive for LF. Methods: This was a mixed method study employing questionnaire surveys and focus group discussions (FDG) for data collection. Survey participants were randomly selected from the 2019 treatment register to stratify respondents into treated and non-treated groups. FGD participants were selected purposively such that there are at least two non-treated persons in each discussion session. Results: Over 90% of the respondents were aware of the disease. Poor hygiene/dirty environment was wrongly reported by most respondents (76.8%) as the causes. MDA awareness was very high among both treated (96.9%) and non-treated (98.6%) groups. A low sense of vulnerability to LF infection was evident by a reduction in the number of people presenting clinical manifestations of the disease in communities. Slightly more, 65 (29.0%) of the non-treated group compared to the 42 (19.4%) treated group reported ever experiencing adverse effects of the MDA drugs. Barriers to MDA uptake reported in both groups were poor planning and implementation of the MDA, lack of commitments on the part of drug distributors, and adverse drug reactions. About 51% of the non-treated group reported never taking the drugs even once in the last five years, while 61% among the treated group took the MDA drug consistently in the past five years. Respondents in both groups believed that, when engaged properly, most non-treated persons will accept to take the drug but insisted community drug distributors (CDDs) must be trained to effectively engage people and have time for those they will be engaging in dialogue. The chiefs emerged as the most influential people who can influence people to take MDA drugs. Conclusions: The reduction in risk perception among respondents, adverse reactions and the timing of MDA activities may be influencing MDA non-participation in the study area; however, respondents think that non-treated individuals will accept the interventions when engaged properly by the CDDs.

Application of multiplex amplicon deep-sequencing (MAD-seq) to screen for putative drug resistance markers in the Necator americanus isotype-1 ß-tubulin gene.

Global control of hookworm infections relies on periodic Mass Drug Administration of benzimidazole drugs to high-risk groups, regardless of infection status. Mutations in the isotype-1 ß-tubulin gene have been identified in veterinary nematodes, resulting in structural changes and reduced drug-binding. In Ghana, previous studies have demonstrated significant variability in albendazole effectiveness among people infected with the hookworm Necator americanus, although the mechanisms underlying deworming response have not been defined. Using hookworm egg samples from a cross-sectional study in Ghana, we developed a multiplex amplicon deep sequencing (MAD-seq) method to screen genomic regions encapsulating putative drug-resistance markers in N. americanus isotype-1 ß-tubulin gene. Three single nucleotide polymorphisms (SNPs) corresponding to resistance-associated mutations (F167Y, E198A, F200Y) within the coding region of the isotype-1 ß-tubulin gene were characterized using MAD-seq in 30 matched pre- and post-treatment samples from individuals with persistent infection following therapy. Post-sequence analysis showed that the highest mean alternative nucleotide allele at each PCR amplicon was 0.034% (167amplicon) and 0.025% (198/200amplicon), suggesting minimal allelic variation. No samples contained the F167Y SNP, while one contained low-frequency reads associated with E198A (3.15%) and F200Y (3.13%). This MAD-seq method provides a highly sensitive tool to monitor the three putative benzimidazole resistance markers at individual and community levels. Further work is required to understand the association of these polymorphisms to treatment response.

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.

COVID-19 related perception among some community members and frontline healthcare providers for NTD control in Ghana.

INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in a major breakdown of health service provision in the fight against neglected tropical diseases (NTDs). COVID-19 may impact NTDs service delivery in varied ways. As the Ghana NTD programme planned to resume MDA activities, we examined the COVID-19 related perceptions and practices among some community members and frontline health workers for NTD control activities in the country. METHODS: The study was conducted in seven communities in the Ahanta West district of Ghana. This was a qualitative study using in-depth interviews (IDI) and focus group discussions (FGDs) for data collection. Participants were purposively selected from varied backgrounds to represent both beneficiaries and service providers directly involved in NTD programme implementation. Trained and experienced qualitative data collectors conducted the FGD and IDI sessions in the local Twi language, while health worker sessions were conducted in English. Discussions were audio-recorded and transcribed directly into English. Data was analysed using an iterative process. The transcripts were pre-coded using the broad themes, entered into a computer using Microsoft Word, and then imported into the MAXQDA software for thematic content analysis to select relevant representative narratives for presentation. RESULTS: Participants were aware of the COVID-19 pandemic and referred to it appropriately as 'coronavirus', COVID-19, and often as 'the new disease'. Though many respondents could not describe the route of transmission, most of them reported that it is transmitted through touch or sharing of common items. They reported some signs/symptoms like fever, headache and difficulty breathing, and prevention methods like the use of hand sanitiser, washing of hands and sneezing appropriately. Respondents have reported that COVID-19 has negatively affected their daily lives by limiting their movements and therefore work. It also came to light that COVID-19 has also negatively affected the NTD programme implementation, especially mass drug administration (MDA) activities, leading to the postponement of the yearly MDA. The COVID-19 pandemic has negatively affected clinic attendance; people are afraid that they may be tested for COVID-19 at the clinic. CONCLUSION: COVID-19 has negatively affected the NTD programme. Education and the provision of personal protective equipment will be required to build the confidence of frontline care providers including community drug distributors and community members in order to enhance quality service and participation in future MDA activities.

In vitro activities of crude extracts and triterpenoid constituents of Dichapetalum crassifolium Chodat against clinical isolates of Schistosoma haematobium.

Dichapetalum crassifolium Chodat (Dichapetalaceae) is widely distributed in Africa, Tropical Asia and Latin America. As part of our quest for potential bioactive lead compounds for various neglected tropical diseases, we report the anti-schistosomal potential of the crude extracts and chemical constituents of the stems and roots of Dichapetalum crassifolium. Column chromatography of extracts of the stems and roots led to the isolation and identification of three oleanane-type triterpenoids, friedelan-3ß-ol (1), friedelan-3-one (2), and maslinic acid (3); the ursane-type tritepenoid, pomolic acid (4) and the dammarane-type tetracyclic triterpenoids, dichapetalin A (5) and dichapetalin M (6). Dichapetalin A was isolated from only the roots. Isolated compounds were identified by comparison of their physico-chemical and spectral data with published data. The highest in vitro anti-schistosomal activity (IC50) of the crude extracts against clinical isolates of Schistosoma haematobium (Bilharz 1852) was 248.6 µg/ml for the ethyl acetate extract of the root while dichapetalin A gave the highest activity at 151.1 µg/ml among the compounds compared with the 15.5 µg/ml for the standard drug, praziquantel. The rest of the compounds showed activities in the order 177.9, 191.0, and 378.1 µg/ml respectively for mixture of ß-sitosterol/stigmasterol, dichapetalin M and friedelan-3-one. The least active extract was the methanol extract of the stem (893.7 µg/ml). The constituents of D. crassifolium showed activity against the S. haematobium that are below praziquantel. It is envisaged that the presence of multiple layers and the minute sizes of pores in the egg shells, may preclude penetration of eggs by the compounds.

Dogs and pigs are transport hosts of Necator americanus: Molecular evidence for a zoonotic mechanism of human hookworm transmission in Ghana.

Hookworm infection (Necator americanus and Ancylostoma spp) causes significant morbidity in resource-limited countries. Dog and pig ownership is associated with human infection, although the mechanism through which animals increase risk remains unknown. We first confirmed this association in Kintampo North, Ghana, using a retrospective analysis and serology, followed by a prospective molecular study of animal faeces. As a proxy of exposure to dog faeces, we analysed immunoreactivity of human serum to the zoonotic nematode Toxocara canis. Anti-Toxocara antibodies were present in 62% of samples (n = 89), and reactivity was associated with dog ownership. A subsequent prospective study revealed that 43% of dog and 56% of pig faecal samples contained hookworm eggs by microscopy. PCR analysis confirmed the presence of N. americanus DNA in 47% of samples from dogs and 56% pig samples. Nematode larvae were successfully cultured from samples collected from 36 dogs and seven pigs. These results demonstrate that dogs and pigs have a likely role in the transmission of N. americanus in endemic communities.

Review of MDA registers for Lymphatic Filariasis: Findings, and potential uses in addressing the endgame elimination challenges.

BACKGROUND: Lymphatic filariasis (LF) is endemic in Ghana, and the country has implemented the GPELF strategy since 2000 with significant progress made in the control of the disease. However, after several years of mass drug administration (MDA) implementation, there is persistent transmission in 17 of the 98 endemic districts in the country. Current approaches to surveillance are clearly unable to target untreated individuals and new strategies are required to address the endgame challenges to enhance LF elimination as a public health problem in endemic countries. Community registers are used during MDAs to enumerate community members, their age, gender, house numbers, and records of their participation in MDAs. These MDA registers represent an untapped opportunity to identify and characterize non-compliance and inform appropriate programmatic actions. In this study, we analyzed the data presented in the registers to assess the coverage and individuals' compliance in MDA. METHODS: The information in the MDA registers were assessed to verify the reported coverages obtained from the district. The community registers were obtained from the district health offices and the data from each individual record was entered into a database. A simple questionnaire was used to cross-check the participation of study participants in the 2017 MDA. The questionnaire solicited data on: participation in the 2017 MDA, reasons for not taking part in the MDA, adverse events experienced, what was done for the adverse events, and willingness to participate in subsequent MDAs. RESULTS: We found that 40.1% of the population in the registers missed at least one MDA in 3 years (2016-2018) and the majority of them were between 10-30 years of age. The results of the questionnaire assessment indicated that 13.8% of the respondents did not receive treatment in 2017 for various reasons, the most prominent among them being "absence/travel" (37.1%). Data in the registers were used to verify the treatment coverage for the years 2017 and 2018, and reviewed against the reported coverage obtained from the district. Significant differences between the reported and verified coverages were only observed in four communities. However, the assessment also revealed that the reported coverage was only accurate in 33.3% of cases. CONCLUSIONS: The MDA registers allow for the identification of eligible individuals who were not reached during any MDA round. Thus, the MDA registers could be utilized at the community and programme levels to identify missing and untreated individuals, appropriately address their non-compliance to MDA, and thereby improve MDA coverage in each implementation unit and monitor the progress towards elimination of LF. The challenges observed through the review of the registers also offer opportunities to improve the training given to the community drug distributors.

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.

An assessment of mosquito collection techniques for xenomonitoring of anopheline-transmitted Lymphatic Filariasis in Ghana.

Monitoring vectors is relevant to ascertain transmission of lymphatic filariasis (LF). This may require the best sampling method that can capture high numbers of specific species to give indication of transmission. Gravid anophelines are good indicators for assessing transmission due to close contact with humans through blood meals. This study compared the efficiency of an Anopheles gravid trap (AGT) with other mosquito collection methods including the box and the Centres for Disease Control and Prevention gravid, light, exit and BioGent-sentinel traps, indoor resting collection (IRC) and pyrethrum spray catches across two endemic regions of Ghana. The AGT showed high trapping efficiency by collecting the highest mean number of anophelines per night in the Western (4.6) and Northern (7.3) regions compared with the outdoor collection methods. Additionally, IRC was similarly efficient in the Northern region (8.9) where vectors exhibit a high degree of endophily. AGT also showed good trapping potential for collecting Anopheles melas which is usually difficult to catch with existing methods. Screening of mosquitoes for infection showed a 0.80-3.01% Wuchereria bancrofti and 2.15-3.27% Plasmodium spp. in Anopheles gambiae. The AGT has shown to be appropriate for surveying Anopheles populations and can be useful for xenomonitoring for both LF and malaria.

An Evaluation of Treatment Outcomes in a Cohort of Clients on the DOTS Strategy, 2012-2016.

We present, for the first time, an evaluation of treatment outcomes in a cohort at a TB referral centre in the Central Region of Ghana. Of the 213 clients placed on DOTS, 59.2% (126/213) were sputum smear-positive. An overall cure rate of 90.2% (51.6% cured + 37.6% completed) and a death rate of 8.5% (18/213) were estimated. Of the number of clients who died, 5.7% (12/213) were males (χ2 = 2.891, p = 0.699; LR = 3.004, p = 0.699). Deaths were only recorded among clients who were > 19 years old (χ2 = 40.319, p = 0.099; LR = 41.244, p = 0.083). Also, 0.9% (2/213) was lost to follow-up, while 1.4% (3/213) had treatment failure. In total, 13.6% (7.0%, 15/213 males, and 6.6%, 14/213 females) of clients who were placed on DOTS were HIV seropositive. Ages of 40-49 years had the highest number, 13/213 (6.1%), infected with HIV, though the difference among the remaining age groups was not statistically significant (χ2 = 9.621, p = 0.142). Furthermore, 7.0% (15/213) had TB/HIV coinfection. Out of them, 9 were cured and 5 died at home, while 1 had treatment failure. Tuberculosis/HIV infection prevention advocacy and interventions that address sociodemographic determinants of unfavourable treatment outcomes are urgently required to augment national efforts towards control.

Community perspectives on persistent transmission of lymphatic filariasis in three hotspot districts in Ghana after 15 rounds of mass drug administration: a qualitative assessment.

BACKGROUND: The Global Program for the Elimination of Lymphatic Filariasis (GPELF) started operation in 2000 and aimed at eliminating the disease by the year 2020, following 5-6 rounds of effective annual Mass Drug Administration (MDA). The MDA programme took off in Ghana in 2001 and has interrupted transmission in many areas while it has persisted in some areas after 10 or more rounds of MDA. This study was to appreciate community members' perspectives on MDA after over 15 years of implementation. Findings will inform strategies to mobilise community members to participate fully in MDA to enhance the disease elimination process. METHODS: This was a qualitative study, employing key-informant in-depth-interviews. Respondents were selected based on their recognition by community members as opinion leaders and persons who were knowledgeable about the topic of interest in the community. A snowball sampling technique was used to select respondents. RESULTS: Respondents were well informed about the MDA with most of them saying, it has been implemented for over 12 years. They were aware that the MDA was for the treatment/control of LF (elephantiasis). It came to light that MDA compliance was affected by five related barriers. These are; Medication, Personal, Health system, Disease and Social structure related barriers. Adverse effects of the drugs and the fact that many people perceived that they were not susceptibility to the infection have grossly affected the ingestion of the drugs. CONCLUSION: There is a need for community mobilization and promotional activities to explain the expected adverse reactions associated with the drugs to the people. Also the importance of why every qualified person in the community must comply with MDA must be emphasized.

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.

Twelve-month longitudinal parasitological assessment of lymphatic filariasis-positive individuals: impact of a biannual treatment with ivermectin and albendazole.

OBJECTIVE: Mass drug administration (MDA) for the control of lymphatic filariasis (LF), in Ghana, started in the year 2000. While this had great success in many implementation units, there remain areas with persistent transmission, after more than 10 years of treatment. A closer examination of the parasite populations could help understand the reasons for persistent infections and formulate appropriate strategies to control LF in these areas of persistent transmission. MATERIALS AND METHODS: In a longitudinal study, we assessed the prevalence of microfilaraemia (mf) in two communities with 12 years of MDA in Ghana. In baseline surveys 6 months after the National MDA in 2014, 370 consenting individuals were tested for antigenaemia using immunochromatographic test (ICT) cards and had their mf count determined through night blood surveys. 48 ICT positives, of whom, 17 were positive for mf, were treated with 400 µg/kg ivermectin + 400 mg albendazole and subsequently followed for parasitological assessment at 3-month intervals for 1 year. This overlapped with the National MDA in 2015. RESULTS: There was a 68% parasite clearance 3 months after treatment. The pre-treatment mf count differed significantly from the post-treatment mf counts at 3 months (P = 0.0023), 6 months (P = 0.0051), 9 months (P = 0.0113) and 12 months (P = 0.0008). CONCLUSION: In these settings with persistent LF transmission, twice-yearly treatment may help accelerate LF elimination. Further large-scale evaluations are required to ascertain these findings.

An evaluation of Wb123 antibody elisa in individuals treated with ivermectin and albendazole, and implementation challenges in Africa.

The development of antibody testing for the diagnosis of lymphatic filariasis (LF) is intended to enhance the monitoring and evaluation activities of the Global Program for the Elimination of LF. This is due to the fact that antibody tests are expected to be the most sensitive at detecting exposure to LF compared to antigen that takes longer to develop. To this end a new antibody-based enzyme linked immunosorbent assay (ELISA) to Wuchereria bancrofti antigen Wb123 has been developed and further designed into a point of care rapid diagnostic test, under evaluation. In pre-treatment surveys, individuals were tested for antigen using the immuno-chromatographic test (ICT) card, and night blood microfilariae, after which all positives were treated using Ivermectin and Albendazole. The Wb123 ELISA was tested in antigen positive individuals, three months after they were treated. Samples were also tested for ICT and night blood microfilariae. The results revealed a reduction in microfilariae and ICT prevalence after treatment. Antigen and antibody prevalence increased with age. However, there was no correlation with the antibody responses observed. The mean WB123 antibody titers were higher among ICT positives, but not significantly different from ICT negative persons. While the Wb123 is targeted for use in untreated populations, further evaluations and guidelines will be required to define its use in populations that have undergone treatment for the control of LF.

Point of care diagnosis of multiple schistosome parasites: Species-specific DNA detection in urine by loop-mediated isothermal amplification (LAMP).

Schistosomes are easily transmitted and high chance of repeat infection, so if control strategies based on targeted mass drug administration (MDA) are to succeed it is essential to have a test that is sensitive, accurate and simple to use. It is known and regularly demonstrated that praziquantel does not always eliminate an infection so in spite of the successes of control programs a residual of the reservoir survives to re-infect snails. The issue of diagnostic sensitivity becomes more critical in the assessment of program effectiveness. While serology, such as antigen capture tests might improve sensitivity, it has been shown that the presence of species-specific DNA fragments will indicate, most effectively, the presence of active parasites. Polymerase chain reaction (PCR) can amplify and detect DNA from urine residue captured on Whatman No. 3 filter paper that is dried after filtration. Previously we have detected S. mansoni and S. haematobium parasite-specific small repeat DNA fragment from filtered urine on filter paper by PCR. In the current study, we assessed the efficacy of detection of 86 urine samples for either or both schistosome parasites by PCR and loop-mediated isothermal amplification (LAMP) that were collected from a low to moderate transmission area in Ghana. Two different DNA extraction methods, standard extraction kit and field usable LAMP-PURE kit were also evaluated by PCR and LAMP amplification. With S. haematobium LAMP amplification for both extractions showed similar sensitivity and specificity when compared with PCR amplification (100%) verified by gel electrophoresis. For S. mansoni sensitivity was highest for LAMP amplification (100%) for standard extraction than PCR and LAMP with LAMP-PURE (99% and 94%). The LAMP-PURE extraction produced false negatives, which require further investigation for this field usable extraction kit. Overall high positive and negative predictive values (90% - 100%) for both species demonstrated a highly robust approach. The LAMP approach is close to point of care use and equally sensitive and specific to detection of species-specific DNA by PCR. LAMP can be an effective means to detect low intensity infection due to its simplicity and minimal DNA extraction requirement. This will enhance the effectiveness of surveillance and MDA control programs of schistosomiasis.

Effectiveness of Albendazole for Hookworm Varies Widely by Community and Correlates with Nutritional Factors: A Cross-Sectional Study of School-Age Children in Ghana.

Mass drug administration (MDA) targeting school-age children is recommended by the World Health Organization for the global control of soil-transmitted helminth (STH) infections. Although considered safe and cost-effective to deliver, benzimidazole anthelminthics are variably effective against the three most common STHs, and widespread use has raised concern about the potential for emerging resistance. To identify factors mediating response to albendazole, we conducted a cross-sectional study of hookworm infection in the Kintampo North Municipality of Ghana in 2011. Among 140 school-age children residing in five contiguous communities, the hookworm prevalence was 59% (82/140). The overall cure rate following administration of single-dose albendazole (400 mg) was 35% (27/76), with a community-wide fecal egg reduction rate (ERR) of 61% (95% confidence interval: 51.8-71.1). Significant disparities were observed in albendazole effectiveness by community, with a cure rate as low as 0% (N = 24) in Jato Akuraa and ERRs ranging from 53% to 95% across the five study sites. Individual host factors associated with response to deworming treatment included time since last meal, pretreatment blood hemoglobin level, and mid-upper arm circumference. These data demonstrate significant community-level variation in the effectiveness of albendazole, even among populations living in close proximity. Identification of host factors that influence response to albendazole, most notably the timing of drug administration and nutritional factors, creates an opportunity to enhance the effectiveness of deworming through targeted interventions. These findings also demonstrate the importance of measuring anthelminthic response as part of the monitoring and evaluation of community-based deworming programs.

Accuracy of point-of-care testing for circulatory cathodic antigen in the detection of schistosome infection: systematic review and meta-analysis.

OBJECTIVE: To assess the accuracy of point-of-care testing for circulatory cathodic antigen in the diagnosis of schistosome infection. METHODS: We searched MEDLINE, EMBASE, LILACS and other bibliographic databases for studies published until 30 September 2015 that described circulatory cathodic antigen testing compared against one to three Kato-Katz tests per subject - for Schistosoma mansoni - or the filtration of one 10-ml urine sample per subject - for S. haematobium. We extracted the numbers of true positives, false positives, true negatives and false negatives for the antigen testing and performed meta-analyses using a bivariate hierarchical regression model. FINDINGS: Twenty-six studies published between 1994 and 2014 met the inclusion criteria. In the detection of S. mansoni, a single antigen test gave a pooled sensitivity of 0.90 (95% confidence interval, CI: 0.84-0.94) and a pooled specificity of 0.56 (95% CI: 0.39-0.71; n = 7) when compared against a single Kato-Katz test. The corresponding values from comparisons with two to three Kato-Katz tests per subject were 0.85 (95% CI: 0.80-0.88) and 0.66 (95% CI: 0.53-0.76; n = 14), respectively. There appeared to be no advantage in using three antigen tests per subject instead of one. When compared against the results of urine filtration, antigen testing for S. haematobium showed poor sensitivity and poor specificity. The performance of antigen testing was better in areas of high endemicity than in settings with low endemicity. CONCLUSION: Antigen testing may represent an effective tool for monitoring programmes for the control of S. mansoni.

Assessing Lymphatic Filariasis Data Quality in Endemic Communities in Ghana, Using the Neglected Tropical Diseases Data Quality Assessment Tool for Preventive Chemotherapy.

BACKGROUND: The activities of the Global Programme for the Elimination of Lymphatic Filariasis have been in operation since the year 2000, with Mass Drug Administration (MDA) undertaken yearly in disease endemic communities. Information collected during MDA-such as population demographics, age, sex, drugs used and remaining, and therapeutic and geographic coverage-can be used to assess the quality of the data reported. To assist country programmes in evaluating the information reported, the WHO, in collaboration with NTD partners, including ENVISION/RTI, developed an NTD Data Quality Assessment (DQA) tool, for use by programmes. This study was undertaken to evaluate the tool and assess the quality of data reported in some endemic communities in Ghana. METHODS: A cross sectional study, involving review of data registers and interview of drug distributors, disease control officers, and health information officers using the NTD DQA tool, was carried out in selected communities in three LF endemic Districts in Ghana. Data registers for service delivery points were obtained from District health office for assessment. The assessment verified reported results in comparison with recounted values for five indicators: number of tablets received, number of tablets used, number of tablets remaining, MDA coverage, and population treated. Furthermore, drug distributors, disease control officers, and health information officers (at the first data aggregation level), were interviewed, using the DQA tool, to determine the performance of the functional areas of the data management system. FINDINGS: The results showed that over 60% of the data reported were inaccurate, and exposed the challenges and limitations of the data management system. The DQA tool is a very useful monitoring and evaluation (M&E) tool that can be used to elucidate and address data quality issues in various NTD control programmes.

Isolation, characterization, and anthelminthic activities of a novel dichapetalin and other constituents of Dichapetalum filicaule.

CONTEXT: Dichapetalum filicaule Breteler (Dichapetalaceae) is a rare species occurring only in Côte d'Ivoire and Ghana. Although research on several species of the genus has produced interesting bioactive compounds, particularly the Dichapetalins, a novel class of triterpenoids with antineoplastic properties, there is virtually no information on the ethnobotanical uses and chemical constituents of D. filicaule. OBJECTIVE: The phytochemical and anthelminthic activities of the constituents of D. filicaule were investigated. MATERIALS AND METHODS: Chemical constituents of the petroleum ether, chloroform-acetone, and methanol root extracts of D. filicaule were isolated by column chromatography and characterized by their physico-chemical properties, 1-D and 2-D NMR spectroscopy and mass spectrometry. In vitro anthelminthic activity of the extracts and compounds against the human hookworm, Necator americanus, Stiles 1902 (Nematoda: Ancylostomatidae) was determined within a concentration range of 2500-250 µg/ml using the Egg Hatch Inhibition (EHI) Assay. The hookworm species were identified using a published polymerase chain reaction (PCR) method. RESULTS: A new dichapetalin, dichapetalin X (1), together with the known dichapetalin A (2), pomolic acid (3), glycerol monostearate (4), D:A-friedooleanan-3ß-ol (5), and D:A-friedooleanan-3-one (6) were isolated. Compounds 1, 2, and 4 exhibited EHI with IC50 values of 523.2, 162.4, and 306.0 µg/ml, respectively, against the hookworm. The positive control albendazole gave an IC50 value of 93.27 µg/ml. DISCUSSION AND CONCLUSION: This is the first report of the phytochemical investigation of D. filicaule. The study has yielded a new dichapetalin and also demonstrated the potential anthelminthic properties of the constituents.