Stopping Mass Drug Administration Research Articles

Determining post-treatment surveillance criteria for predicting the elimination of Schistosoma mansoni transmission

BackgroundThe World Health Organization (WHO) has set elimination (interruption of transmission) as an end goal for schistosomiasis. However, there is currently little guidance on the monitoring and evaluation strategy required once very low prevalence levels have been reached to determine whether elimination or resurgence of the disease will occur after stopping mass drug administration (MDA) treatment.MethodsWe employ a stochastic individual-based model of Schistosoma mansoni transmission and MDA impact to determine a prevalence threshold, i.e. prevalence of infection, which can be used to determine whether elimination or resurgence will occur after stopping treatment with a given probability. Simulations are run for treatment programmes with varying probabilities of achieving elimination and for settings where adults harbour low to high burdens of infection. Prevalence is measured based on using a single Kato-Katz on two samples per individual. We calculate positive predictive values (PPV) using PPV ≥ 0.9 as a reliable measure corresponding to ≥ 90% certainty of elimination. We analyse when post-treatment surveillance should be carried out to predict elimination. We also determine the number of individuals across a single community (of 500–1000 individuals) that should be sampled to predict elimination.ResultsWe find that a prevalence threshold of 1% by single Kato-Katz on two samples per individual is optimal for predicting elimination at two years (or later) after the last round of MDA using a sample size of 200 individuals across the entire community (from all ages). This holds regardless of whether the adults have a low or high burden of infection relative to school-aged children.ConclusionsUsing a prevalence threshold of 0.5% is sufficient for surveillance six months after the last round of MDA. However, as such a low prevalence can be difficult to measure in the field using Kato-Katz, we recommend using 1% two years after the last round of MDA. Higher prevalence thresholds of 2% or 5% can be used but require waiting over four years for post-treatment surveillance. Although, for treatment programmes where elimination is highly likely, these higher thresholds could be used sooner. Additionally, switching to more sensitive diagnostic techniques, will allow for a higher prevalence threshold to be employed.

Lymphatic filariasis transmission in Rufiji District, southeastern Tanzania: infection status of the human population and mosquito vectors after twelve rounds of mass drug administration

BackgroundControl of lymphatic filariasis (LF) in most of the sub-Saharan African countries is based on annual mass drug administration (MDA) using a combination of ivermectin and albendazole. Monitoring the impact of this intervention is crucial for measuring the success of the LF elimination programmes. This study assessed the status of LF infection in Rufiji district, southeastern Tanzania after twelve rounds of MDA.MethodsCommunity members aged between 10 and 79 years were examined for Wuchereria bancrofti circulating filarial antigens (CFA) using immunochromatographic test cards (ICTs) and antigen-positive individuals were screened for microfilaraemia. All study participants were examined for clinical manifestation of LF and interviewed for drug uptake during MDA rounds. Filarial mosquito vectors were collected indoor and outdoor and examined for infection with W. bancrofti using a microscope and quantitative real-time polymerase chain reaction (qPCR) techniques.ResultsOut of 854 participants tested, nine (1.1%) were positive for CFA and one (0.1%) was found to be microfilaraemic. The prevalence of hydrocele and elephantiasis was 4.8% and 2.9%, respectively. Surveyed drug uptake rates were high, with 70.5% of the respondents reporting having swallowed the drugs in the 2014 MDA round (about seven months before this study). Further, 82.7% of the respondents reported having swallowed the drugs at least once since the inception of MDA programme in 2000. Of the 1054 filarial vectors caught indoors and dissected to detect W. bancrofti infection none was found to be infected. Moreover, analysis by qPCR of 1092 pools of gravid Culex quinquefasciatus collected outdoors resulted in an estimated infection rate of 0.1%. None of the filarial vectors tested with qPCR were found to be infective.ConclusionAnalysis of indices of LF infection in the human population and filarial mosquito vectors indicated a substantial decline in the prevalence of LF and other transmission indices, suggesting that local transmission was extremely low if occurring at all in the study areas. We, therefore, recommend a formal transmission assessment survey (TAS) to be conducted in the study areas to make an informed decision on whether Rufiji District satisfied WHO criteria for stopping MDA.

Trachoma prevalence remains below threshold in five districts after stopping mass drug administration: results of five surveillance surveys within a hyperendemic setting in Amhara, Ethiopia.

BackgroundThe World Health Organization (WHO) recommends conducting trachoma surveillance surveys in districts where the elimination targets have been met and following a minimum 2-year period after cessation of mass drug administration (MDA) in order to determine the sustainability of low trachoma levels.MethodsIn 2015, population-based surveillance surveys were conducted in five districts of Amhara, Ethiopia. All five districts had a prior trachomatous inflammation–follicular (TF) prevalence among children 1–9 y of age of <5% determined by an impact survey and had not received MDA for ≥2 y. Surveys included examinations for trachoma clinical signs and conjunctival swabbing to determine Chlamydia trachomatis infection prevalence.ResultsApproximately 1000 children 1–9 y of age were examined for TF and 200 children 1–5 y of age were swabbed per district. All five surveillance districts had a TF prevalence of <5% and infection was only detected in one district. The prevalence of trachomatous trichiasis in adults ≥15 y of age was ≥1% in all districts.ConclusionsIn a trachoma hyperendemic region, a TF prevalence <5% was successfully maintained in five districts for ≥2 years after stopping MDA. MDA is still not warranted for these districts, however, the S, F and E components of the SAFE strategy should continue.

Impact of community-based integrated mass drug administration on schistosomiasis and soil-transmitted helminth prevalence in Togo.

BackgroundTogo has conducted annual, integrated, community-based mass drug administration (MDA) for soil-transmitted helminths (STH) and schistosomiasis since 2010. Treatment frequency and target populations are determined by disease prevalence, as measured by baseline surveys in 2007 and 2009, and WHO guidelines. Reported programmatic treatment coverage has averaged over 94%. Togo conducted a cross-sectional survey in 2015 to assess the impact of four to five years of MDA on these diseases.Methodology/Principal findingsIn every sub-district in the country outside the capital, the same schools were visited as at baseline and a sample of fifteen children age 6 to 9 years old was drawn. Each child submitted urine and a stool sample. Urine samples were tested by dipstick for the presence of blood as a proxy measure of Schistosoma haematobium infection. Stool samples were analyzed by the Kato-Katz method for STH and Schistosoma mansoni. At baseline, 17,100 children were enrolled at 1,129 schools in 562 sub-districts; in 2015, 16,890 children were enrolled at the same schools. The overall prevalence of both STH and schistosomiasis declined significantly, from 31.5% to 11.6% for STH and from 23.5% to 5.0% for schistosomiasis (p<0.001 in both instances). Egg counts from both years were available only for hookworm and S. mansoni; intensity of infection decreased significantly for both infections from 2009 to 2015 (p<0.001 for both infections). In areas with high baseline prevalence, rebound of hookworm infection was noted in children who had not received albendazole in the past 6 months.Conclusions/SignificanceAfter four to five years of MDA in Togo, the prevalence and intensity of STH and schistosomiasis infection were significantly reduced compared to baseline. Data on STH indicate that stopping MDA in areas with high baseline prevalence may result in significant rebound of infection. Togo’s findings may help refine treatment recommendations for these diseases.

Operational Performance of the Onchocerca volvulus "OEPA" Ov16 ELISA Serological Assay in Mapping, Guiding Decisions to Stop Mass Drug Administration, and Posttreatment Surveillance Surveys.

Onchocerciasis is a neglected tropical disease targeted for elimination. The World Health Organization (WHO) has developed guidelines for the verification of onchocerciasis elimination that include entomological and epidemiological criteria. The latter require demonstrating with statistical confidence that the infection prevalence in children is less than 0.1%, necessitating an assay with a high degree of specificity. We present an analysis of the performance of the Onchocerciasis Elimination Program for the Americas (OEPA) version of the Ov16 enzyme-linked immunosorbant assay (ELISA) when used under operational conditions. In Africa and Latin America, the assay demonstrated 99.98% specificity in 69,888 children in 20 foci where transmission was believed to be interrupted. The assay produced a prevalence estimate equal to that of skin snip microscopy when applied in putatively hypo-endemic zones of Ethiopia. The OEPA Ov16 ELISA demonstrated the specificity required to be effectively deployed to verify transmission elimination under the WHO guidelines, while exhibiting a sensitivity equivalent to skin snip microscopy to identify hypo-endemic areas.

Interruption of onchocerciasis transmission in Bioko Island: Accelerating the movement from control to elimination in Equatorial Guinea.

BackgroundOnchocerciasis, also known as river blindness, is a parasitic disease. More than 99 percent of all cases occur in Africa. Bioko Island (Equatorial Guinea) is the only island endemic for onchocerciasis in the world. Since 2005, when vector Simulium yahense was eliminated, there have not been any reported cases of infection. This study aimed to demonstrate that updated WHO criteria for stopping mass drug administration (MDA) have been met.Methodology/Principal findingsA cross-sectional study was conducted from September 2016 to January 2017. Participants were 5- to 9-year-old school children. Onchocerciasis/lymphatic Filariasis (LF, only in endemic districts) rapid diagnostic tests (RDTs) were performed. Blood spots were collected from RDT positive children and 10 percent of the RDT negatives to determine Ov16 and Wb123 IgG4 antibodies through enzyme-linked immunosorbent assay (ELISA). Skin snips were collected from RDT positives. Filarial detection was performed by PCR in positives and indeterminate sera. Black fly collection was carried out in traditional breeding sites. A total of 7,052 children, ranging from 5 to 9 years of age, were included in the study. Four children (0.06%) were Ov16 IgG4 RDT positives, but negative by ELISA Ov16, while 6 RDT negative children tested positive by ELISA. A total of 1,230 children from the Riaba and Baney districts were tested for LF. One child was Wb123 RDT positive (0.08%), but ELISA negative, while 3 RDT negative children were positive by Wb123 ELISA. All positive samples were negative by PCR for onchocerciasis and LF (in blood spot and skin snip). All fly collections and larval prospections in the traditional catching and prospection sites were negative.Conclusions/SignificanceWHO criteria have been met, therefore MDA in Bioko Island can be stopped. Three years of post-treatment surveillance should be implemented to identify any new occurrences of exposure or infection.

Surveillance for lymphatic filariasis after stopping mass drug administration in endemic districts of Togo, 2010\u20132015

BackgroundTogo is a country previously endemic for lymphatic filariasis (LF). In 2010, following nine years of mass drug administration (MDA) for LF, the country established a post-treatment surveillance (PTS) system. We present here the results of these PTS activities, carried out from 2010 to 2015, as well as the findings of follow-up investigations in 2016 to confirm the absence of infection in previously infected individuals.MethodsThe routine surveillance established in 2010 consisted of a network of 47 laboratories, which searched for Wuchereria bancrofti microfilaria on nocturnal blood smears collected for malaria diagnosis and an additional network of 20 peripheral health facilities, which collected dried blood spots and tested them for Og4C3 antigen. Two transmission assessment surveys (TAS) were also undertaken, as recommended by WHO, in 2012 and 2015. Any positive case identified through any surveillance activity was immediately retested by nocturnal smear and confirmed cases were immediately investigated by screening family members and neighboring household members. In 2016, 32 of the 40 positive cases detected during TAS or laboratory and health facility network activities were traced and whether confirmed positive by nocturnal smear or not were tested again simultaneously by filariasis test strip (FTS), Og4C3 and a nocturnal blood smear to rule out any active infection.ResultsFrom 2010 to 2015, the laboratory network identified one microfilaria-positive individual (0.0% of 26,584 persons tested) and the peripheral health facility network detected 19 Og4C3-positive individuals (0.28% of 6788 persons tested). All 19 Og4C3 cases were negative for microfilaremia by nocturnal blood smear. In the 2012 and 2015 TAS, thirteen and six ICT/FTS positive cases, respectively, were identified, which were significantly below the critical cut-off (18–20 cases) across all evaluation units. Three of the six ICT/FTS-positive cases from the 2015 TAS were positive by nocturnal smear; immediate investigation identified one additional microfilaria-positive individual. Epidemiological investigation revealed that four of the five cases of microfilaremia were imported from another country in the region. In 2016, 32 of the 40 positive cases detected by at least one test during all surveillance activities were traced: four (12.5%) individuals were still positive by FTS but all 32 individuals were negative for microfilaremia and Og4C3 antigen.ConclusionThe results of post-treatment surveillance in Togo have demonstrated that W. bancrofti filariasis is no longer of public health concern in Togo, more than six years after stopping MDA. Every possible effort should be made to maintain surveillance in order to promptly detect any resurgence and preserve this achievement.

Prevalence of trachoma in the Kayes region of Mali eight years after stopping mass drug administration.

BackgroundIn 2009, three years after stopping mass treatment with azithromycin, a trachoma impact survey in four health districts in the Kayes region of Mali found a prevalence of trachomatous inflammation—follicular (TF) among children aged 1 to 9 years of >5% and a trachomatous trichiasis (TT) prevalence within the general population (≥1-year-old) of <1%. As a result, the government’s national trachoma program expanded trichiasis surgery and related activities required to achieve trachoma elimination.Methodology/Principal findingsIn 2015, to assess progress towards elimination, a follow-up impact survey was conducted in the Kayes, Kéniéba, Nioro and Yélimané health districts. The survey used district level two-stage cluster random sampling methodology with 20 clusters of 30 households in each evaluation unit. Subjects were eligible for examination if they were ≥1 year. TF and TT cases were identified and confirmed by experienced ophthalmologists. In total 14,159 people were enumerated and 11,620 (82%) were examined. TF prevalence (95% confidence interval (CI)) was 0.5% (0.3–1%) in Kayes, 0.8% (0.4–1.7%) in Kéniéba, 0.2% (0–0.9%) in Nioro and 0.3% (0.1–1%) in Yélimané. TT prevalence (95% CI) was 0.04% (0–0.25%) in Kayes, 0.29% (0.11–0.6%) in Kéniéba, 0.04% (0–0.25%) in Nioro and 0.07% (0–0.27%) in Yélimané.Conclusions/SignificanceEight years after stopping MDA and intensifying trichiasis surgery outreach campaigns, all four districts reached the TF elimination threshold of <5% and three of four districts reached the TT elimination threshold of <0.1%.

Detecting and confirming residual hotspots of lymphatic filariasis transmission in American Samoa 8 years after stopping mass drug administration.

The Global Programme to Eliminate Lymphatic Filariasis (LF) aims to eliminate the disease as a public health problem by 2020 by conducting mass drug administration (MDA) and controlling morbidity. Once elimination targets have been reached, surveillance is critical for ensuring that programmatic gains are sustained, and challenges include timely identification of residual areas of transmission. WHO guidelines encourage cost-efficient surveillance, such as integration with other population-based surveys. In American Samoa, where LF is caused by Wuchereria bancrofti, and Aedes polynesiensis is the main vector, the LF elimination program has made significant progress. Seven rounds of MDA (albendazole and diethycarbamazine) were completed from 2000 to 2006, and Transmission Assessment Surveys were passed in 2010/2011 and 2015. However, a seroprevalence study using an adult serum bank collected in 2010 detected two potential residual foci of transmission, with Og4C3 antigen (Ag) prevalence of 30.8% and 15.6%. We conducted a follow up study in 2014 to verify if transmission was truly occurring by comparing seroprevalence between residents of suspected hotspots and residents of other villages. In adults from non-hotspot villages (N = 602), seroprevalence of Ag (ICT or Og4C3), Bm14 antibody (Ab) and Wb123 Ab were 1.2% (95% CI 0.6–2.6%), 9.6% (95% CI 7.5%-12.3%), and 10.5% (95% CI 7.6–14.3%), respectively. Comparatively, adult residents of Fagali’i (N = 38) had significantly higher seroprevalence of Ag (26.9%, 95% CI 17.3–39.4%), Bm14 Ab (43.4%, 95% CI 32.4–55.0%), and Wb123 Ab 55.2% (95% CI 39.6–69.8%). Adult residents of Ili’ili/Vaitogi/Futiga (N = 113) also had higher prevalence of Ag and Ab, but differences were not statistically significant. The presence of transmission was demonstrated by 1.1% Ag prevalence (95% CI 0.2% to 3.1%) in 283 children aged 7–13 years who lived in one of the suspected hotspots; and microfilaraemia in four individuals, all of whom lived in the suspected hotspots, including a 9 year old child. Our results provide field evidence that integrating LF surveillance with other surveys is effective and feasible for identifying potential hotspots, and conducting surveillance at worksites provides an efficient method of sampling large populations of adults.

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.

Evaluation of Onchocerciasis Transmission in Tanzania: Preliminary Rapid Field Results in the Tukuyu Focus, 2015.

To compare diagnostic tests for onchocerciasis in a setting that has suppressed transmission, a randomized, age-stratified study was implemented in an area in Tanzania that had received 15 rounds of annual mass drug administration (MDA) with ivermectin. Study participants (N = 948) from 11 villages underwent a questionnaire, skin examination, skin snips, and blood draw. The burden of symptomatic disease was low. Ov-16 antibody rapid diagnostic test (RDT) results were positive in 38 (5.5%) participants, with 1 (0.5%), 1 (0.4%), and 2 (0.8%) in children aged 0-5, 6-10, and 11-15 years, respectively. Despite significant impact of MDA on transmission, the area would have failed to meet World Health Organization serologic criteria for stopping MDA if a full evaluation had been conducted. The specificity of the RDT, which is 97-98%, may result in the identification of a number of false positives that would exceed the current stop MDA threshold.

Surveillance efforts after mass drug administration to validate elimination of lymphatic filariasis as a public health problem in Vanuatu

BackgroundVanuatu was formerly highly endemic for lymphatic filariasis (LF), caused by Wuchereria bancrofti and transmitted by Anopheles mosquitoes. After a baseline survey showing 4.8% antigen prevalence in 1998, the country conducted nationwide (in one implementation unit) annual mass drug administration (MDA) with albendazole and diethylcarbamazine citrate from 2000 to 2004 and achieved prevalence of 0.2% by 2006 in a representative nationwide cluster survey among all age groups.MethodsPost MDA surveillance was conducted from 2006 to 2012. After MDA, the country was divided for surveillance into three evaluation units (EUs) formed by grouping provinces according to baseline prevalence: EU1: Torba, Sanma and Malampa; EU2: Penama; EU3: Shefa and Tafea. The study compiled all past data and information on surveys in Vanuatu from the country programme. This paper reviews the surveillance activities done after stopping MDA to validate the interruption of transmission and elimination of LF as a public health problem.ResultsPost-MDA surveillance consisting of at least three transmission assessment surveys (TAS) in each of the three EUs was conducted between 2006 and 2012. Sentinel and spot check surveys identified a few villages with persistent high prevalence; all antigen positive cases in these sites were treated and additional targeted MDA conducted for 3 years in 13 villages in one area of concern. All three EUs passed all TAS in 2007, 2010 and 2012 respectively, with no positives found except in EU2 (Penama province) in 2012 when 2 children tested positive for circulating filariasis antigen. Assessment of the burden of chronic filariasis morbidity found 95 cases in 2003 and 32 remaining cases in 2007, all aged over 60 years.ConclusionsVanuatu has achieved validation of elimination of LF as a public health problem. Post-validation surveillance is still recommended especially in formerly highly endemic areas.

Assessment of lymphatic filariasis prior to re-starting mass drug administration campaigns in coastal Kenya

BackgroundLymphatic filariasis (LF) is a debilitating disease associated with extensive disfigurement and is one of a diverse group of diseases referred to as neglected tropical diseases (NTDs) which mainly occur among the poorest populations. In line with global recommendations to eliminate LF, Kenya launched its LF elimination programme in 2002 with the aim to implement annual mass drug administration (MDA) in order to interrupt LF transmission. However, the programme faced financial and administrative challenges over the years such that sustained annual MDA was not possible. Recently, there has been renewed interest to eliminate LF and the Kenyan Ministry of Health, through support from World Health Organization (WHO), restarted annual MDA in 2015. The objective of this study was to evaluate the current status of LF infection in the endemic coastal region of Kenya before MDA campaigns were restarted.ResultsTen sentinel sites in Kwale, Kilifi, Tana River, Lamu, and Taita-Taveta counties in coastal Kenya were selected for participation in a cross-sectional survey of LF infection prevalence. At least 300 individuals in each sentinel village were sampled through random house-to-house visits. During the day, the point-of-care immunochromatographic test (ICT) was used to detect the presence of Wuchereria bancrofti circulating filarial antigen in finger prick blood samples collected from residents of the selected sentinel villages. Those individuals who tested positive with the ICT test were requested to provide a night-time blood sample for microfilariae (MF) examination. The overall prevalence of filarial antigenaemia was 1.3% (95% CI: 0.9–1.8%). Ndau Island in Lamu County had the highest prevalence (6.3%; 95% CI: 4.1–9.7%), whereas sites in Kilifi and Kwale counties had prevalences < 1.7%. Mean microfilarial density was also higher in Ndau Island (234 MF/ml) compared to sentinel sites in Kwale and Kilifi counties (< 25 MF/ml). No LF infection was detected in Tana River and Taita-Taveta counties. Overall, more than 88% of the study participants reported to have used a bed net the previous night.ConclusionsPrevalence of LF infection is generally very low in coastal Kenya, but there remain areas that require further rounds of MDA if the disease is to be eliminated as a public health problem in line with the ongoing global elimination efforts. However, areas where there was no evidence of LF transmission should be considered for WHO-recommended transmission assessment surveys in view of stopping MDA.

Measuring Trachomatous Inflammation-Intense (TI) When Prevalence Is Low Provides Data on Infection With Chlamydia trachomatis.

PurposeClinical trachoma is the current measure of effectiveness of antibiotic and environmental improvements in trachoma endemic communities. Impact assessments measure only trachomatous inflammation-follicular (TF). Trachomatous inflammation-intense (TI) is not used for decisions on stopping mass drug administration (MDA) or achieving intervention goals. We tested the supposition that TI was not associated with Chlamydia trachomatis when disease prevalence is low.MethodsIn 35 communities undergoing MDA as part of a larger project, 110 children ages 1 to 9 years were randomly selected in each community for surveys at baseline, 6, and 12 months. Both eyelids were graded for TF and TI, and a swab for detection of C. trachomatis infection was taken.ResultsOverall TF prevalence was 5% at baseline. Cases of TI alone constituted 15% of trachoma; 37% of TI cases had infection. At 6 and 12 months, the proportion of trachoma cases that had TI only was 13% and 20%; infection rates were similar to the rates in cases with TF alone.ConclusionsDespite low prevalence of trachoma, infection rates for TF alone and TI alone were similar at each time point. The exclusion of cases of TI alone when reporting trachoma prevalence discards additional information on infection. Trachomatous inflammation-intense could be considered as part of impact surveys.

COMMUNITY KNOWLEDGE, ATTITUDES AND PRACTICES (KAP) DURING MDA INTEGRATED MALARIA ELIMINATION AND SCHISTOSOMIASIS AND SOIL-TRANSMITTED HELMINTHS CONTROL STUDY IN NGODHE ISLAND, LAKE VICTORIA, KENYA

BackgroundKnowledge, attitudes and practices (KAP) of communities where mass drug administration based integrated malaria elimination and control of schistosomiasis and soil transmitted helminths (STH) is targeted will be critical in...

Potential Value of Triple Drug Therapy with Ivermectin, Diethylcarbamazine, and Albendazole (IDA) to Accelerate Elimination of Lymphatic Filariasis and Onchocerciasis in Africa.

The Global Program to Eliminate Lymphatic Filariasis (GPELF) has made significant progress in many countries. GPELF has delivered 5,600 million treatments to more than 763 million people living in 61 countries between the years 2000 and 2014, and it was estimated to have prevented 36 million clinical cases and saved 175 million disability adjusted life years (DALYs) [1]. Although elimination of LF is a major goal of the London Declaration on Neglected Tropical Diseases (NTDs), it is unlikely that LF will be eliminated by the target year of 2020 [2]. The key strategy of the elimination program comprises repeated annual rounds of mass drug administration (MDA) to populations at risk of acquiring the infection with diethylcarbamazine (DEC) plus albendazole outside of Africa and with ivermectin plus albendazole in Africa [3]. MDA reduces microfilariae (Mf) in human blood that are necessary for transmission by mosquito vectors, and one aim of the program is to interrupt transmission. Repeated rounds of MDA are required because current regimens fail to kill all adult worms and completely clear Mf following single-dose treatments. Successful programs have sustained annual MDA with high compliance for several years. Seventy-three countries were considered to be endemic for LF in 2015, and 55 of them still required MDA [4]. The GPELF has lagged in sub-Saharan Africa, where only 2 of 35 LF-endemic countries have stopped MDA and started post-MDA surveillance. Many countries in this region have either not started MDA or have less than 65% geographical coverage. Hence, a more effective treatment strategy could have a major impact on LF elimination in Africa. The goal of onchocerciasis intervention in Africa has also shifted in recent years from control towards elimination [5, 6]. As with LF, the key strategy for onchocerciasis intervention is MDA. In most countries, this is accomplished with annual community-directed treatment with ivermectin (CDTi). Modeling studies predict that current strategies will permit many countries to reach targets for stopping MDA for onchocerciasis by 2028, but intervention is likely to be required for a much longer period in some areas (especially in Central Africa) [7]. While annual or semiannual CDTi for 15 to 17 years eliminated the infection in some areas, it was not sufficient to stop transmission in others [8, 9]. Therefore, extensive research is currently ongoing to identify drugs that are more effective than ivermectin. Drug development studies are time and resource intensive, and it is unlikely that a novel drug for onchocerciasis will be registered to significantly advance the progress of onchocerciasis elimination within the next 5 years. In this paper, we discuss the potential value of combination therapy with three currently approved drugs (ivermectin, DEC, and albendazole, or IDA) for advancing LF and onchocerciasis elimination programs in Africa. Because DEC treatment can cause ocular adverse events in persons with heavy Onchocerca volvulus infections, studies of the new combination will have to be conducted with proper precautions. Therefore, this paper also discusses prior experience with DEC in onchocerciasis patients and a strategy for studying the effects of IDA in patients with onchocerciasis.

One Hundred Years After Its Discovery in Guatemala by Rodolfo Robles, Onchocerca volvulus Transmission Has Been Eliminated from the Central Endemic Zone.

We report the elimination of Onchocerca volvulus transmission from the Central Endemic Zone (CEZ) of onchocerciasis in Guatemala, the largest focus of this disease in the Americas and the first to be discovered in this hemisphere by Rodolfo Robles Valverde in 1915. Mass drug administration (MDA) with ivermectin was launched in 1988, with semiannual MDA coverage reaching at least 85% of the eligible population in > 95% of treatment rounds during the 12-year period, 2000-2011. Serial parasitological testing to monitor MDA impact in sentinel villages showed a decrease in microfilaria skin prevalence from 70% to 0%, and polymerase chain reaction (PCR)-based entomological assessments of the principal vector Simulium ochraceum s.l. showed transmission interruption by 2007. These assessments, together with a 2010 serological survey in children 9-69 months of age that showed Ov16 IgG4 antibody prevalence to be < 0.1%, meeting World Health Organization (WHO) guidelines for stopping MDA, and treatment was halted after 2011. After 3 years an entomological assessment showed no evidence of vector infection or recrudescence of transmission. In 2015, 100 years after the discovery of its presence, the Ministry of Health of Guatemala declared onchocerciasis transmission as having been eliminated from the CEZ.

Evaluation of human and mosquito based diagnostic tools for defining endpoints for elimination of Anopheles transmitted lymphatic filariasis in Ghana.

The decision to stop mass drug administration (MDA) and monitor recrudescence has to be made when endpoints for elimination of lymphatic filariasis (LF) have been achieved. Highly sensitive and specific diagnostic tools are required to do this. The main objective of this study was to determine most effective diagnostic tools for assessing interruption of LF transmission. The presence of filarial infection in blood and mosquito samples was determined using five diagnostic tools: Brugia malayi-14 (BM14) antibody detection ELISA, Onchocerca gibsoni antigen (Og4C3) based ELISA, PCR, immunochromatography (ICT) card test and blood smear. The study was carried out in two communities in the Central Region of Ghana. OG4C3 was found to be the most sensitive test but ICT, the second most sensitive, was the most field applicable. PCR was found to be the most specific. Thirteen out of 30 pools of anopheles mosquitoes tested positive for the DNA of Wuchereria bancrofti. Very low antigen prevalence in primary school children indicates that MDA is working, so children born since the intervention was put in place are not getting infected. Inclusion of xenomonitoring in monitoring the effectiveness of MDA will give a better indication as to when transmission has been interrupted especially in areas where microfilaria prevalence is lower than 1%.

Cessation of mass drug administration for lymphatic filariasis in Zanzibar in 2006: was transmission interrupted?

BackgroundLymphatic filariasis (LF) is targeted for elimination through annual mass drug administration (MDA) for 4–6 years. In 2006, Zanzibar stopped MDA against LF after five rounds of MDA revealed no microfilaraemic individuals during surveys at selected sentinel sites. We asked the question if LF transmission was truly interrupted in 2006 when MDA was stopped.Methodology/Principal FindingsIn line with ongoing efforts to shrink the LF map, we performed the WHO recommended transmission assessment surveys (TAS) in January 2012 to verify the absence of LF transmission on the main Zanzibar islands of Unguja and Pemba. Altogether, 3275 children were tested on both islands and 89 were found to be CFA positive; 70 in Pemba and 19 in Unguja. The distribution of schools with positive children was heterogeneous with pronounced spatial variation on both islands. Based on the calculated TAS cut-offs of 18 and 20 CFA positive children for Pemba and Unguja respectively, we demonstrated that transmission was still ongoing in Pemba where the cut-off was exceeded.ConclusionsOur findings indicated ongoing transmission of LF on Pemba in 2012. Moreover, we presented evidence from previous studies that LF transmission was also active on Unguja shortly after stopping MDA in 2006. Based on these observations the government of Zanzibar decided to resume MDA against LF on both islands in 2013.

A comprehensive assessment of lymphatic filariasis in Sri Lanka six years after cessation of mass drug administration.

BackgroundThe Sri Lankan Anti-Filariasis Campaign conducted 5 rounds of mass drug administration (MDA) with diethycarbamazine plus albendazole between 2002 and 2006. We now report results of a comprehensive surveillance program that assessed the lymphatic filariasis (LF) situation in Sri Lanka 6 years after cessation of MDA.Methodology and Principal FindingsTransmission assessment surveys (TAS) were performed per WHO guidelines in primary school children in 11 evaluation units (EUs) in all 8 formerly endemic districts. All EUs easily satisfied WHO criteria for stopping MDA. Comprehensive surveillance was performed in 19 Public Health Inspector (PHI) areas (subdistrict health administrative units). The surveillance package included cross-sectional community surveys for microfilaremia (Mf) and circulating filarial antigenemia (CFA), school surveys for CFA and anti-filarial antibodies, and collection of Culex mosquitoes with gravid traps for detection of filarial DNA (molecular xenomonitoring, MX). Provisional target rates for interruption of LF transmission were community CFA <2%, antibody in school children <2%, and filarial DNA in mosquitoes <0.25%. Community Mf and CFA prevalence rates ranged from 0–0.9% and 0–3.4%, respectively. Infection rates were significantly higher in males and lower in people who denied prior treatment. Antibody rates in school children exceeded 2% in 10 study sites; the area that had the highest community and school CFA rates also had the highest school antibody rate (6.9%). Filarial DNA rates in mosquitoes exceeded 0.25% in 10 PHI areas.ConclusionsComprehensive surveillance is feasible for some national filariasis elimination programs. Low-level persistence of LF was present in all study sites; several sites failed to meet provisional endpoint criteria for LF elimination, and follow-up testing will be needed in these areas. TAS was not sensitive for detecting low-level persistence of filariasis in Sri Lanka. We recommend use of antibody and MX testing as tools to complement TAS for post-MDA surveillance.