Integrated transmission assessment surveys (iTAS) of lymphatic filariasis and onchocerciasis in Cross River, Taraba and Yobe States, Nigeria.

BACKGROUND: Integrated transmission assessment surveys (iTAS) have been recommended for evaluation of the transmission of both lymphatic filariasis (LF) and onchocerciasis as the prevalence of both diseases moves toward their respective elimination targets in Nigeria. Therefore, we conducted an iTAS between May and December 2017 in five local government areas (LGAs), also known as implementation units (IUs), in states of Cross River, Taraba and Yobe in Nigeria. METHODS: The TAS comprised two phases: the Pre-iTAS and the iTAS itself. Three states (Cross River, Taraba and Yobe), comprising five LGAs and 20 communities that have completed five rounds of combined treatment with ivermectin and albendazole for LF and 12 total rounds of ivermectin, were selected for inclusion in the study. All participants were tested with the Filariasis Test Strip (FTS; Alere Inc.) and the Biplex rapid Diagnostic Test (RDT; identifying filaria antigens Ov16/Wb123; Abbott diagnosctics Korea Inc.). Pre iTAS included 100 children ages 5-9 in each 4 communities and 300 individuals ages 10 and older in a subset of two communities.  For the iTAS, only LGAs where antigenemia prevalence in all sampled communities during the Pre-iTAS was < 2% for LF were selected. RESULTS: Of the five LGAs included in the study, four met the cutoff of the Pre-iTAS and were included in the iTAS; the Ikom LGA was excluded from the iTAS due to antigenemia prevalence. A total of 11,531 school-aged children from 148 schools were tested for LF and onchocerciasis across these four LGAs, including 2873 children in Bade, 2622 children in Bekwara, 3026 children in Gashaka and 3010 children in Karim Lamido. Using the FTS, all samples from Bade and Karim Lamido were negative, whereas 0.2% of the samples from Bekwara and Gashaka were positive. Using the Biplex RDT, LF prevalence in Bade, Bekwara, Gashaka and Karim Lamido was < 0.1%, 0.5%, 0.4% and < 0.1%, respectively. Moreover, all samples from Bade and Karim Lamido were negative for onchocerciasis, whereas 3.1% and 1.8% of the samples from Bekwara and Gashaka were positive, respectively. CONCLUSION: This study has provided additional information on the current burden of onchocerciasis and LF in the four IUs sampled where mass drug administration (MDA) for both infections has been ongoing for years. The study identifies that LF-MDA can be safely stopped in all four of the IUs studied, but that MDA for onchocerciasis needs to continue, even though this may pose a challenge for LF surveillance. Based on the preliminary results from all four sites, this study has fulfilled the primary objective of determining the programmatic feasibility of an iTAS as a tool to simultaneously assess onchocerciasis and LF prevalence in areas co-endemic for the two infections that have completed the recommended treatment for one or both infections, and to make decisions on how to proceed.

Assessing Hypoendemic Onchocerciasis in Loa loa Endemic Areas of Southeast Nigeria.

Nigeria changed its goal for onchocerciasis from control to transmission elimination. Under the control program, ivermectin mass drug administration (MDA) focused only on hyper/meso-endemic local government areas (LGAs) identified by Rapid Epidemiological Mapping of Onchocerciasis as having ≥ 20% nodule rates. Because transmission is likely in some LGAs where nodule rates are < 20%, the new elimination paradigm requires MDA expansion. Determining which hypoendemic areas require MDA, termed onchocerciasis elimination mapping, is a major challenge. In 2016, we studied 19 ivermectin-naive hypoendemic LGAs in southern Nigeria that bordered LGAs under MDA. Fifty adults and 50 children (aged 5-10 years) were tested in 110 villages for onchocerciasis IgG4 antibody using an Ov16 rapid diagnostic test (RDT). A 10% subset of subjects provided a blood spot for confirmatory Ov16 ELISA. The mean prevalence of RDT positives was 0.5% in the 5,276 children tested (village range, 0.0-4.0%) versus 3.3% in 5,302 adults (village range, 0.0-58.0%). There was 99.3% agreement between the Ov16 RDT and ELISA. Six different MDA launch thresholds were applied to the RDT results based on different recommendations by the Nigeria Onchocerciasis Elimination Committee and the Onchocerciasis Technical Advisory Subgroup of the WHO. Mass drug administration targets for the same area varied tenfold by threshold chosen, from one LGA (population to be treated 221,935) to 13 LGAs (population 2,426,987). Because the Ov16 threshold selected will have considerable cost and resource implications, the decision to initiate MDA should incorporate entomological data demonstrating onchocerciasis transmission.

Post-Treatment Surveillance for Lymphatic Filariasis in Plateau and Nasarawa States, Nigeria: Results of Transmission Assessment Surveys.

Following the halt of mass drug administration (MDA) for lymphatic filariasis (LF), the WHO recommends at least 4 years of post-treatment surveillance (PTS) to confirm that transmission recrudescence or importation does not occur. The primary means of evaluation during PTS is repeated transmission assessment surveys (TASs) conducted at 2- to 3-year intervals after TAS-1 stop-MDA surveys. This study reports the results of TAS-2 and TAS-3 surveys in Plateau and Nasarawa states (pop. 6.9 million) of Nigeria divided into a minimum of seven evaluation units (EUs) per TAS. A total of 26,536 first- and second-year primary school children (approximately 6-7 years old) were tested for circulating filarial antigen (CFA) between 2014 and 2017. Of 12,313 children tested in TAS-2 surveys, only five (0.04%) were CFA positive, with no more than two positive samples from any one EU, which was below the critical value of 20 per EU. Of 14,240 children tested in TAS-3 surveys, none (0%) were CFA positive. These results indicate that LF transmission remains below sustainable transmission levels and suggest that elimination of transmission has been achieved in Plateau and Nasarawa, Nigeria.

Integrated risk mapping and landscape characterisation of lymphatic filariasis and loiasis in South West Nigeria.

Nigeria has the heaviest burden of lymphatic filariasis (LF) in sub-Saharan Africa, which is caused by the parasite Wuchereria bancrofti and transmitted by Anopheles mosquitoes. LF is targeted for elimination and the national programme is scaling up mass drug administration (MDA) across the country to interrupt transmission. However, in some regions the co-endemicity of the filarial parasite Loa loa (loiasis) is an impediment due to the risk of severe adverse events (SAEs) associated with the drug ivermectin. To better understand factors influencing LF elimination in loiasis areas, this study conducted a cross-sectional survey on the prevalence and co-distribution of the two infections, and the potential demographic, landscape, human movement, and intervention-related risk factors at a micro-level in the South West zone of Nigeria. In total, 870 participants from 10 communities on the fringe of a meso-endemic loiasis area of Osun State were selected. LF prevalence was measured by clinical assessment and using the rapid immunochromatographic test (ICT) to detect W. bancrofti antigen. Overall LF prevalence was low with ICT positivity ranging from 0 to 4.7%, with only 1 hydrocoele case identified. Males had significantly higher ICT positivity than females (3.2% vs 0.8%). Participants who did not sleep under a bed net had higher ICT positivity (4.0%) than those who did (1.3%). ICT positivity was also higher in communities with less tree coverage/canopy height (2.5-2.8%) than more forested areas with greater tree coverage/canopy height (0.9-1.0%). In comparison, loiasis was determined using the rapid assessment procedure for loiasis (RAPLOA), and found in all 10 communities with prevalence ranging from 1.4% to 11.2%. No significant difference was found by participants' age or sex. However, communities with predominately shrub land (10.4%) or forested land cover (6.2%) had higher prevalence than those with mosaic vegetation/croplands (2.5%). Satellite imagery showed denser forested areas in higher loiasis prevalence communities, and where low or no ICT positivity was found. Only one individual was found to be co-infected. GPS tracking of loiasis positive cases and controls also highlighted denser forested areas within higher loiasis risk communities and the sparser land cover in lower-risk communities. Mapping LF-loiasis distributions against landscape characteristics helped to highlight the micro-heterogeneity, identify potential SAE hotspots, and determine the safest and most appropriate treatment strategy.

In Southern Nigeria Loa loa Blood Microfilaria Density is Very Low Even in Areas with High Prevalence of Loiasis: Results of a Survey Using the New LoaScope Technology.

Ivermectin treatment can cause central nervous system adverse events (CNS-AEs) in persons with very high-density Loa loa microfilaremia (≥ 30,000 mf/mL blood). Hypoendemic onchocerciasis areas where L. loa is endemic have been excluded from ivermectin mass drug administration programs (MDA) because of the concern for CNS AEs. The rapid assessment procedure for L. loa (RAPLOA) is a questionnaire survey to assess history of eye worm. If ≥ 40% of respondents report eye worm, this correlates with ≥ 2% prevalence of very high-density loiasis microfilaremia, posing an unacceptable risk of CNS-AEs after MDA. In 2016, we conducted a L. loa study in 110 ivermectin-naïve, suspected onchocerciasis hypoendemic villages in southern Nigeria. In previous RAPLOA surveys these villages had prevalences between 10% and 67%. We examined 10,605 residents using the LoaScope, a cell phone-based imaging device for rapidly determining the microfilaria (mf) density of L. loa infections. The mean L. loa village mf prevalence was 6.3% (range 0-29%) and the mean individual mf count among positives was 326 mf/mL. The maximum individual mf count was only 11,429 mf/mL, and among 2,748 persons sampled from the 28 villages with ≥ 40% RAPLOA, the ≥ 2% threshold of very high Loa mf density could be excluded with high statistical confidence (P < 0.01). These findings indicate that ivermectin MDA can be delivered in this area with extremely low risk of L. loa-related CNS-AEs. We also concluded that in Nigeria the RAPLOA survey methodology is not predictive of ≥ 2% prevalence of very high-density L. loa microfilaremia.

Criteria to Stop Mass Drug Administration for Lymphatic Filariasis Have Been Achieved Throughout Plateau and Nasarawa States, Nigeria.

Nigeria has the largest population at risk for lymphatic filariasis (LF) in Africa. This study used a transmission assessment survey (TAS) to determine whether mass drug administration (MDA) for LF could stop in 21 districts, divided into four evaluation units (EUs), of Plateau and Nasarawa States, Nigeria, after 8-12 years of annual albendazole-ivermectin treatment. A total of 7,131 first- and second-year primary school children (approximately 6-7 years old) were tested for LF antigen by immunochromatographic test (ICT) from May to June 2012. The target sample size of 1,692 was exceeded in each EU (range = 1,767-1,795). A total of 25 (0.4%) individuals were ICT positive, with the number of positives in each EU (range = 3-11) less than the TAS cutoff of 20, meaning that LF transmission had been reduced below sustainable levels. As a result, 3.5 million annual albendazole-ivermectin treatments were halted in 2013. Combined with the previous halt of MDA for LF in other parts of Plateau and Nasarawa, these are the first Nigerian states to stop LF MDA statewide. Posttreatment surveillance is ongoing to determine if LF transmission has been interrupted.

Is mass drug administration against lymphatic filariasis required in urban settings? The experience in Kano, Nigeria.

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF), launched in 2000, has the target of eliminating the disease as a public health problem by the year 2020. The strategy adopted is mass drug administration (MDA) to all eligible individuals in endemic communities and the implementation of measures to reduce the morbidity of those suffering from chronic disease. Success has been recorded in many rural endemic communities in which elimination efforts have centered. However, implementation has been challenging in several urban African cities. The large cities of West Africa, exemplified in Nigeria in Kano are challenging for LF elimination program because reaching 65% therapeutic coverage during MDA is difficult. There is therefore a need to define a strategy which could complement MDA. Thus, in Kano State, Nigeria, while LF MDA had reached 33 of the 44 Local Government Areas (LGAs) there remained eleven 'urban' LGAs which had not been covered by MDA. Given the challenges of achieving at least 65% coverage during MDA implementation over several years in order to achieve elimination, it may be challenging to eliminate LF in such settings. In order to plan the LF control activities, this study was undertaken to confirm the LF infection prevalence in the human and mosquito populations in three urban LGAs. METHODS: The prevalence of circulating filarial antigen (CFA) of Wuchereria bancrofti was assessed by an immuno-chromatography test (ICT) in 981 people in three urban LGAs of Kano state, Nigeria. Mosquitoes were collected over a period of 4 months from May to August 2015 using exit traps, gravid traps and pyrethrum knock-down spray sheet collections (PSC) in different households. A proportion of mosquitoes were analyzed for W. bancrofti, using dissection, loop-mediated isothermal amplification (LAMP) assay and conventional polymerase chain reaction (PCR). RESULTS: The results showed that none of the 981 subjects (constituted of <21% of children 5-10 years old) tested had detectable levels of CFA in their blood. Entomological results showed that An. gambiae s.l. had W. bancrofti DNA detectable in pools in Kano; W. bancrofti DNA was detected in between 0.96% and 6.78% and to a lesser extent in Culex mosquitoes where DNA was detected at rates of between 0.19% and 0.64%. DNA analysis showed that An. coluzzii constituted 9.9% of the collected mosquitoes and the remaining 90.1% of the mosquitoes were Culex mosquitoes. CONCLUSION: Despite detection of W. bancrofti DNA within mosquito specimens collected in three Kano urban LGAs, we were not able to find a subject with detectable level of CFA. Together with other evidence suggesting that LF transmission in urban areas in West Africa may not be of significant importance, the Federal Ministry of Health advised that two rounds of MDA be undertaken in the urban areas of Kano. It is recommended that the prevalence of W. bancrofti infection in the human and mosquito populations be re-assessed after a couple of years.

Lymphatic filariasis baseline survey in two sentinel sites of Ogun state, Nigeria.

INTRODUCTION: In preparation for Mass Drug Administration by National Lymphatic Filariasis Elimination Programme, a baseline epidemiological investigation on lymphatic filariasis (LF) was conducted in two sentinel sites of Ogun State, Nigeria. The study was carried out in Ado-Odo Ota and Abeokuta South Local Government Areas (LGAs) to determine LF prevalence, microfilarial density and the abundance of Wucheraria bancrofti in the mosquito vectors. METHODS: Microscopic examination of thick blood smears of 299 and 288 participants from Ado-Odo Ota and Abeokuta South LGAs was conducted. Visual observations of clinical manifestations of chronic infection and questionnaire administration were also conducted. Indoor resting mosquitoes were collected using the pyrethrum spray technique and CDC light traps and mosquitoes were dissected for filarial larvae. RESULTS: Microfilaria prevalences were 4.0% and 2.4% in Ado-odo Ota and Abeokuta South LGAs. The microflarial density (mfd) was 30.6mf/ml and 23.9 mf/ml in the same areas. No clinical manifestations of the infection were found at both sites. Knowledge of LF by inhabitants was very low in the two areas. Anopheles gambiae s.l and Culex species mosquitoes were collected but none was found positive for stage L3 infective larvae. CONCLUSION: Mass awareness campaigns on the goal of mass drug administration, cause of LF, mode of transmission, the relationship between infection and clinical signs/symptoms is advocated so as to increase acceptance and support of the control programme by the community.

An investigation of the disparity in estimates of microfilaraemia and antigenaemia in lymphatic filariasis surveys.

BACKGROUND: The diagnosis of lymphatic filariasis (LF) is based typically on either microfilaraemia as assessed by microscopy or filarial antigenaemia using an immuno-chromatographic test. While it is known that estimates of antigenaemia are generally higher than estimates of microfilaraemia, the extent of the difference is not known. METHODS: This paper presents the results of an extensive literature search for surveys that estimated both microfilaraemia and antigenaemia in order to better understand the disparity between the two measures. RESULTS AND CONCLUSIONS: In some settings there was a very large disparity, up to 40-70%, between estimates of microfilaraemia and antigenaemia. Regression analysis was unable to identify any predictable relationship between the two measures. The implications of findings for risk mapping and surveillance of LF are discussed.

Modelling the distribution and transmission intensity of lymphatic filariasis in sub-Saharan Africa prior to scaling up interventions: integrated use of geostatistical and mathematical modelling.

BACKGROUND: Lymphatic filariasis (LF) is one of the neglected tropical diseases targeted for global elimination. The ability to interrupt transmission is, partly, influenced by the underlying intensity of transmission and its geographical variation. This information can also help guide the design of targeted surveillance activities. The present study uses a combination of geostatistical and mathematical modelling to predict the prevalence and transmission intensity of LF prior to the implementation of large-scale control in sub-Saharan Africa. METHODS: A systematic search of the literature was undertaken to identify surveys on the prevalence of Wuchereria bancrofti microfilaraemia (mf), based on blood smears, and on the prevalence of antigenaemia, based on the use of an immuno-chromatographic card test (ICT). Using a suite of environmental and demographic data, spatiotemporal multivariate models were fitted separately for mf prevalence and ICT-based prevalence within a Bayesian framework and used to make predictions for non-sampled areas. Maps of the dominant vector species of LF were also developed. The maps of predicted prevalence and vector distribution were linked to mathematical models of the transmission dynamics of LF to infer the intensity of transmission, quantified by the basic reproductive number (R0). RESULTS: The literature search identified 1267 surveys that provide suitable data on the prevalence of mf and 2817 surveys that report the prevalence of antigenaemia. Distinct spatial predictions arose from the models for mf prevalence and ICT-based prevalence, with a wider geographical distribution when using ICT-based data. The vector distribution maps demonstrated the spatial variation of LF vector species. Mathematical modelling showed that the reproduction number (R0) estimates vary from 2.7 to 30, with large variations between and within regions. CONCLUSIONS: LF transmission is highly heterogeneous, and the developed maps can help guide intervention, monitoring and surveillance strategies as countries progress towards LF elimination.

Lymphatic filariasis in Nigeria; micro-stratification overlap mapping (MOM) as a prerequisite for cost-effective resource utilization in control and surveillance.

BACKGROUND: Nigeria has a significant burden of lymphatic filariasis (LF) caused by the parasite Wuchereria bancrofti. A major concern to the expansion of the LF elimination programme is the risk of serious adverse events (SAEs) associated with the use of ivermectin in areas co-endemic with Loa filariasis. To better understand this, as well as other factors that may impact on LF elimination, we used Micro-stratification Overlap Mapping (MOM) to highlight the distribution and potential impact of multiple disease interventions that geographically coincide in LF endemic areas and which will impact on LF and vice versa. METHODOLOGY/PRINCIPAL FINDINGS: LF data from the literature and Federal Ministry of Health (FMoH) were collated into a database. LF prevalence distributions; predicted prevalence of loiasis; ongoing onchocerciasis community-directed treatment with ivermectin (CDTi); and long-lasting insecticidal mosquito net (LLIN) distributions for malaria were incorporated into overlay maps using geographical information system (GIS) software. LF was prevalent across most regions of the country. The mean prevalence determined by circulating filarial antigen (CFA) was 14.0% (n = 134 locations), and by microfilaria (Mf) was 8.2% (n = 162 locations). Overall, LF endemic areas geographically coincided with CDTi priority areas, however, LLIN coverage was generally low (<50%) in areas where LF prevalence was high or co-endemic with L. loa. CONCLUSIONS/SIGNIFICANCE: The extensive database and series of maps produced in this study provide an important overview for the LF Programme and will assist to maximize existing interventions, ensuring cost effective use of resources as the programme scales up. Such information is a prerequisite for the LF programme, and will allow for other factors to be included into planning, as well as monitoring and evaluation activities given the broad spectrum impact of the drugs used.