Modelling the cost of engage & treat and test & treat strategies towards the elimination of lymphatic filariasis in Ghana.

BACKGROUND: Despite several years of LF-MDA implementation, Ghana still has some districts with mf prevalence >1%, partly due to poor treatment coverage levels resulting from non-participation in MDA. To address the challenges, we implemented Engage & Treat (E&T) and Test & Treat (T&T) strategies for individuals who miss or refuse MDA respectively, in a hotspot district, enabling us to reach many of those who seldom, or never, take part in MDA. This financial cost study was undertaken to analyse data on the LF-MDA, E&T and T&T implementation in 2021 and the financial cost to inform the rollout of the E&T and T&T as mop-up strategies in future LF-MDAs. METHODS: This costing study analysed cost data from the 2021 LF-MDA implementation activities carried out by the Neglected Tropical Diseases (NTD) programme of the Ghana Health Service and the SENTINEL study, carried out in Ahanta West district for the two interventions (i.e., E&T and T&T). The 2021 Ghana Population and Housing Census data was used to estimate the LF-MDA-eligible population. The financial cost per person treated was estimated and these costs were applied to the projected population to obtain the financial cost for subsequent years. RESULTS: Implementing MDA mop-up strategies either through the E&T or T&T to improve coverage comes at an additional cost to the elimination goals. For example, in 2024 the projected cost per person treated by the routine LF-MDA is estimated at US$0.83. The cost using the integrated LF-MDA and the E&T, T&T led by the NTD programme or T&T integrated into the health system was estimated at US$1.62, US$2.88, and US$2.33, respectively, for the same year. Despite the increased cost, the proposed combined LF-MDA and mop-up strategies will have a higher estimated population treated for 2024 (i.e., 1,392,211) compared to the routine LF-MDA approach (i.e., 988,470) for the same year. CONCLUSION: Combining LF-MDA with E&T/T&T mop-up strategies, despite their high costs, may provide NTD Programmes with the options of improving treatment coverage and reaching the LF elimination target sooner, given that the routine LF-MDA alone approach has been implemented for many years with some districts yet to reach the elimination targets.

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.

Elimination of lymphatic filariasis in west African urban areas: is implementation of mass drug administration necessary?

Lymphatic filariasis in Africa is caused by the parasite Wuchereria bancrofti and remains a major cause of morbidity and disability in 74 countries globally. A key strategy of the Global Programme for the Elimination of Lymphatic Filariasis, which has a target elimination date of 2020, is the treatment of entire endemic communities through mass drug administration of albendazole in combination with either ivermectin or diethylcarbamazine. Although the strategy of mass drug administration in combination with other interventions, such as vector control, has led to elimination of the infection and its transmission in many rural communities, urban areas in west Africa present specific challenges to achieving the 2020 targets. In this Personal View, we examine these challenges and the relevance of mass drug administration in urban areas, exploring the rationale for a reassessment of policy in these settings. The community-based mass treatment approach is best suited to rural areas, is challenging and costly in urban areas, and cannot easily achieve the 65% consistent coverage required for elimination of transmission. In our view, the implementation of mass drug administration might not be essential to interrupt transmission of lymphatic filariasis in urban areas in west Africa. Evidence shows that transmission levels are low and that effective mass drug distribution is difficult to implement, with assessments suggesting that specific control measures against filariasis in such dynamic settings is not an effective use of limited resources. Instead, we recommend that individuals who have clinical disease or who test positive for W bancrofti infection in surveillance activities should be offered antifilarial drugs through a passive surveillance approach, as well as morbidity management for their needs. We also recommend that more precise studies are done, so that mass drug administration in urban areas is considered if sustainable transmission is found to be ongoing. Otherwise, the limited resources should be directed towards other elements of the lymphatic filariasis programme.

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.

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.

Increased pfmdr1 gene copy number and the decline in pfcrt and pfmdr1 resistance alleles in Ghanaian Plasmodium falciparum isolates after the change of anti-malarial drug treatment policy.

BACKGROUND: With the introduction of artemisinin-based combination therapy (ACT) in 2005, monitoring of anti-malarial drug efficacy, which includes the use of molecular tools to detect known genetic markers of parasite resistance, is important for first-hand information on the changes in parasite susceptibility to drugs in Ghana. This study investigated the Plasmodium falciparum multidrug resistance gene (pfmdr1) copy number, mutations and the chloroquine resistance transporter gene (pfcrt) mutations in Ghanaian isolates collected in seven years to detect the trends in prevalence of mutations. METHODS: Archived filter paper blood blots collected from children aged below five years with uncomplicated malaria in 2003-2010 at sentinel sites were used. Using quantitative real-time polymerase chain reaction (qRT-PCR), 756 samples were assessed for pfmdr1 gene copy number. PCR and restriction fragment length polymorphism (RFLP) were used to detect alleles of pfmdr1 86 in 1,102 samples, pfmdr1 184, 1034, 1042 and 1246 in 832 samples and pfcrt 76 in 1,063 samples. Merozoite surface protein 2 (msp2) genotyping was done to select monoclonal infections for copy number analysis. RESULTS: The percentage of isolates with increased pfmdr1 copy number were 4, 27, 9, and 18% for 2003-04, 2005-06, 2007-08 and 2010, respectively. Significant increasing trends for prevalence of pfmdr1 N86 (×(2) = 96.31, p <0.001) and pfcrt K76 (×(2) = 64.50, p <0.001) and decreasing trends in pfmdr1 Y86 (x(2) = 38.52, p <0.001) and pfcrt T76 (x(2) = 43.49, p <0.001) were observed from 2003-2010. The pfmdr1 F184 and Y184 prevalence showed an increasing and decreasing trends respectively but were not significant (×(2) = 7.39,p=0.060; ×(2) = 7.49, p = 0.057 respectively). The pfmdr1 N86-F184-D1246 haplotype, which is alleged to be selected by artemether-lumefantrine showed a significant increasing trend (×(2) = 20.75, p < 0.001). CONCLUSION: Increased pfmdr1 gene copy number was observed in the isolates analysed and this finding has implications for the use of ACT in the country although no resistance has been reported. The decreasing trend in the prevalence of chloroquine resistance markers after change of treatment policy presents the possibility for future introduction of chloroquine as prophylaxis for malaria risk groups such as children and pregnant women in Ghana.

A quick and cost effective method for the diagnosis of Mycobacterium ulcerans infection.

BACKGROUND: Buruli ulcer (BU), a neglected tropical skin disease caused by Mycobacterium ulcerans, has been reported in over 30 countries worldwide and is highly endemic in rural West and Central Africa. The mode of transmission remains unknown and treatment is the only alternative to disease control. Early and effective treatment to prevent the morbid effects of the disease depends on early diagnosis; however, current diagnosis based on clinical presentation and microscopy has to be confirmed by PCR and other tests in reference laboratories. As such confirmed BU diagnosis is either late, inefficient, time consuming or very expensive, and there is the need for an early diagnosis tool at point of care facilities. In this paper we report on a simple, quick and inexpensive diagnostic test that could be used at point of care facilities, in resource-poor settings. METHODS: The methodology employed is based on the loop mediated isothermal amplification (LAMP) technique. Four sets of Primers, targeting the mycolactone encoding plasmid genome sequence of M. ulcerans were designed. The BU-LAMP assay was developed and tested on five M. ulcerans strains from patients in Ghana and two American Type Culture Control (ATCC) reference isolates; Ghana #970321 (D19F9) and Benin #990826 (D27D14). We also tested the assay on other closely related, mycolactone-producing mycobacterial strains; M. marinum 1218, M. marinum DL240490, M. liflandii and M. pseudoshotsii, as well as experimentally infected laboratory animal and clinical samples. RESULTS: The results revealed a high specificity of the BU-LAMP assay for selectively detecting M. ulcerans. Compared to the conventional IS-2404 PCR, the new assay is cheaper and simpler and ten times more sensitive. Test results can be obtained within 1 hour. CONCLUSIONS: This study indicates that the BU-LAMP assay could be suitable for early disease diagnosis and application in low-resource health facilities.

Four ways geographic information systems can help to enhance health service planning and delivery for infectious diseases in low-income countries.

Focusing specifically on infectious diseases in low-income countries, this paper discusses four ways Geographic Information Systems (GIS) can facilitate health service planning and delivery: (1) deeper insight into where health care services should be located; (2) improved health surveillance and real-time planning for disease control and population health; (3) stronger accountability and evidence-informed dialogue between funders and the service providers and; (4) greater opportunities to translate complex data into more accessible formats which policymakers can quickly interpret and act on. Taking its use beyond just a research instrument, GIS is a way to undertake multidisciplinary work and improve health service planning and delivery.