Rounds Of Mass Drug Administration Research Articles

Impact of mass drug administration for elimination of lymphatic filariasis in Nepal

BackgroundLymphatic filariasis (LF) is a neglected tropical disease transmitted by mosquitoes. Nepal has implemented a national effort to eliminate LF by 2020 through mass drug administration (MDA) using diethylcarbamazine (DEC) and albendazole (ALB). We assessed the impact of MDAs on LF in selected districts of Nepal after the recommended six MDA rounds had been completed.Methodology and principal findingsBaseline surveys were conducted in seven districts and mapping data were used as baseline in the other three districts before starting MDA in 2009. LF antigen (Ag) prevalence ranged from 1.06% to 20% among districts included in the baseline and mapping study. The number of people who received DEC and ALB were recorded during each MDA round and population-based cluster surveys were conducted at least once in each district during the life of the program. The reported MDA coverage in five districts was consistently at least 65%. Two districts achieved the targeted coverage in four out of five rounds and the rest three districts achieved the target only in the first round. A pre-transmission assessment survey (pre-TAS) was conducted in one sentinel site and at least one spot check site in each of the districts after five MDA rounds. In pre-TAS, all the sites of five districts (Pyuthan, Arghakhanchi, Kaski, Bhaktapur, and Kathmandu) and all but one spot check site of Lalitpur district had LF Ag < 2% (ranging from 0.0% to 1.99%). Transmission assessment survey (TAS) was conducted in six evaluation units (EUs) consisting of six districts qualified on pre-TAS. Though MDA coverage of 65% was not achieved in three districts (Kathmandu, Lalitpur and Bhaktapur), Nepal government in consultation with World Health Organization (WHO) decided to conduct TAS. All six EUs achieved the LF Ag threshold required to stop MDA in TAS, despite the low reported MDA coverage in those three districts.ConclusionsAlthough Nepal has achieved significant progress towards LF elimination, five rounds of MDA were not sufficient to disrupt the transmission cycle in all districts, probably because of high baseline prevalence.

First evidence of lymphatic filariasis transmission interruption in Cameroon: Progress towards elimination.

BackgroundLymphatic filariasis (LF) is among the 10 neglected tropical diseases targeted for control or elimination by 2020. For LF elimination, the World Health Organization (WHO) has proposed a comprehensive strategy including (i) interruption of LF transmission through large-scale annual treatment (or mass drug administration (MDA)) of all eligible individuals in endemic areas, and (ii) alleviation of LF-associated suffering through morbidity management and disability prevention. In Cameroon, once-yearly mass administration of ivermectin and albendazole has been implemented since 2008. The aim of this study was to assess progress towards the elimination goal, looking specifically at the impact of six rounds of MDA on LF transmission in northern Cameroon.MethodologyThe study was conducted in the North and Far North Regions of Cameroon. Five health districts that successfully completed six rounds of MDA (defined as achieving a treatment coverage ≥ 65% each year) and reported no positive results for Wuchereria bancrofti microfilariaemia during routine surveys following the fifth MDA were grouped into three evaluation units (EU) according to WHO criteria. LF transmission was assessed through a community-based transmission assessment survey (TAS) using an immunochromatographic test (ICT) for the detection of circulating filarial antigen (CFA) in children aged 5–8 years old.Principal findingsA total of 5292 children (male/female ratio 1.04) aged 5–8 years old were examined in 97 communities. Positive CFA results were observed in 2, 8 and 11 cases, with a CFA prevalence of 0.13% (95% CI: 0.04–0.46) in EU#1, 0.57% (95% CI: 0.32–1.02) in EU#2, and 0.45% (95% CI: 0.23–0.89) in EU#3.Conclusion/SignificanceThe positive CFA cases were below WHO defined critical cut-off thresholds for stopping treatment and suggest that transmission can no longer be sustained. Post-MDA surveillance activities should be organized to evaluate whether recrudescence can occur.

Burden of trachoma in five counties of Eastern Equatoria state, South Sudan: Results from population-based surveys.

BackgroundIn order to decrease the prevalence of trachoma within the country, the Republic of South Sudan has implemented components of the SAFE strategy in various counties since 2001. Five counties in Eastern Equatoria state were surveyed in order to monitor progress of programmatic interventions and determine if additional rounds of Mass Drug Administration with azithromycin were needed.Methodology/ Principal findingsFive counties (Budi, Lafon, Kapoeta East, Kapoeta South and Kapoeta North) were surveyed from April to October 2015. A cross-sectional, multi-stage, cluster-random sampling was used. All present, consenting residents of selected households were examined for all clinical signs of trachoma using the World Health Organization (WHO) simplified grading system. 14,462 individuals from 3,446 households were surveyed. The prevalence of trachomatous inflammation-follicular (TF) in children ages one to nine years ranged from 17.4% (95% Confidence Interval (CI): 11.4%, 25.6%) in Budi county to 47.6%, (95% CI: 42.3%, 53.0%) in Kapoeta East county. Trachomatous trichiasis (TT) was also highly prevalent in those 15 years and older, ranging between 2.6% (95% CI: 1.6%, 4.0%) in Kapoeta South to 3.9% (95% CI: 2.4%, 6.1%) in Lafon. The presence of water and sanitation were low in all five counties, including two counties which had a complete absence of latrines in all surveyed clusters.Conclusions/ SignificanceTo our knowledge, these were the first trachoma surveys conducted in the Republic of South Sudan since their independence in 2011. The results show that despite years of interventions, four of the five surveyed counties require a minimum of five additional years of SAFE strategy implementation, with the fifth requiring at minimum three more years.

The importance of patient compliance in repeated rounds of mass drug administration (MDA) for the elimination of intestinal helminth transmission

BackgroundSystematic non-compliance to chemotherapeutic treatment among a portion of the eligible population is thought to be a major obstacle to the elimination of helminth infections by mass drug administration (MDA). MDA for helminths is repeated at defined intervals such as yearly or every 2 years, as a consequence of the inability of the human host to develop fully protective immunity to reinfection. As such, how an individual complies to these repeated rounds of MDA can have a significant impact on parasite transmission. The importance of this factor is poorly understood at present. Few epidemiological studies have examined longitudinal trends in compliance in the many communities in areas of endemic helminth infection that are undergoing MDA. Reducing systematic non-compliance will obviously increase the number of individuals treated, but it may also alter the dynamics of parasite transmission.MethodsHere we develop an individual-based stochastic model of helminth transmission and MDA treatment to investigate how different patterns of compliance influence the impact of MDA for two groups of helminths, the soil transmitted nematode infections and the schistosome parasites. We study the effect of several alternative treatment and compliance patterns on the dynamics of transmission.ResultsWe find that the impact of different compliance patterns, ranging from random treatment at each round of chemotherapy to systematic non-compliance by a proportion of the population, is very dependent on both transmission intensity in a defined setting and the type of infection that the treatment is targeted at. Systematic non-compliance has a greater impact on the potential for elimination of Schistosoma mansoni transmission by intensive MDA, than it does on Ascaris lumbricoides.ConclusionsWe discuss the implications of our findings for the prioritisation of resources in MDA programmes and for monitoring and evaluation programme design. The key message generated by the analyses is that great care must be taken to record individual longitudinal patterns of compliance at each round of MDA as opposed to just recording overall coverage.

Multiplex Serologic Assessment of Schistosomiasis in Western Kenya: Antibody Responses in Preschool Aged Children as a Measure of Reduced Transmission.

Currently, impact of schistosomiasis control programs in Schistosoma mansoni–endemic areas is monitored primarily by assessment of parasitologic indicators only. Our study was conducted to evaluate the use of antibody responses as a way to measure the impact of schistosomiasis control programs. A total of 3,612 serum samples collected at three time points from children 1–5 years of age were tested for antibody responses to two schistosome antigens (soluble egg antigen [SEA] and Sm25) by multiplex bead assay. The overall prevalence of antibody responses to SEA was high at baseline (50.0%). After one round of mass drug administration (MDA), there was minimal change in odds of SEA positivity (odds ratio [OR] = 1.02, confidence interval [CI] = 0.79–1.32, P = 0.89). However, after two rounds of treatment, there was a slight decrease in odds of SEA positivity (OR = 0.80, CI = 0.63–1.02, P = 0.08). In contrast to the SEA results, prevalence of antibody responses to Sm25 was lowest at baseline (14.1%) and higher in years 2 (19.8%) and 3 (18.4%). After one round of MDA, odds of Sm25 positivity increased significantly (OR = 1.51, CI = 1.14–2.02, P = 0.005) and remained significantly higher than baseline after two rounds of MDA (OR = 1.37, CI = 1.07–1.76, P = 0.01). There was a significant decrease in the proportion of 1-year-olds with positive SEA responses from 33.1% in year 1 to 13.2% in year 3 and a corresponding decrease in the odds (OR = 3.25, CI = 1.75–6.08, P < 0.001). These results provide preliminary evidence that schistosomiasis program impact can be monitored using serologic responses.

Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study.

SummaryBackgroundMass drug administration for elimination of Plasmodium falciparum malaria is recommended by WHO in some settings. We used consensus modelling to understand how to optimise the effects of mass drug administration in areas with low malaria transmission.MethodsWe collaborated with researchers doing field trials to establish a standard intervention scenario and standard transmission setting, and we input these parameters into four previously published models. We then varied the number of rounds of mass drug administration, coverage, duration, timing, importation of infection, and pre-administration transmission levels. The outcome of interest was the percentage reduction in annual mean prevalence of P falciparum parasite rate as measured by PCR in the third year after the final round of mass drug administration.FindingsThe models predicted differing magnitude of the effects of mass drug administration, but consensus answers were reached for several factors. Mass drug administration was predicted to reduce transmission over a longer timescale than accounted for by the prophylactic effect alone. Percentage reduction in transmission was predicted to be higher and last longer at lower baseline transmission levels. Reduction in transmission resulting from mass drug administration was predicted to be temporary, and in the absence of scale-up of other interventions, such as vector control, transmission would return to pre-administration levels. The proportion of the population treated in a year was a key determinant of simulated effectiveness, irrespective of whether people are treated through high coverage in a single round or new individuals are reached by implementation of several rounds. Mass drug administration was predicted to be more effective if continued over 2 years rather than 1 year, and if done at the time of year when transmission is lowest.InterpretationMass drug administration has the potential to reduce transmission for a limited time, but is not an effective replacement for existing vector control. Unless elimination is achieved, mass drug administration has to be repeated regularly for sustained effect.FundingBill & Melinda Gates Foundation.

Lymphatic filariasis elimination efforts in Rufiji, southeastern Tanzania: decline in circulating filarial antigen prevalence in young school children after twelve rounds of mass drug administration and utilization of long-lasting insecticide-treated nets

Lymphatic filariasis (LF) is a parasitic infection transmitted by mosquito vectors, and in Sub-Saharan Africa it is caused by the nematode Wuchereria bancrofti. The disease has been targeted for global elimination with the annual mass drug administration (MDA) strategy. Vector control is known to play an important complementary role to MDA in reducing the transmission of LF. The effects of an MDA and insecticide-treated net intervention implemented in an endemic area of southeastern Tanzania are reported here. A cross-sectional study assessing W. bancrofti circulating filarial antigen (CFA) was conducted in five primary schools in five different villages. Standard one pupils aged 6-9 years were screened for CFA using immunochromatographic test cards (ICT), with a total of 413 screened in 2012 and 659 in 2015. Just after CFA testing, the children were interviewed on their participation in the MDA campaign. Moreover, 246 heads of households in 2012 and 868 in 2015 were interviewed on their participation in MDA and utilization of long-lasting insecticide-treated nets (LLINs). The prevalence of CFA for the 413 children tested in 2012 was 14.3%, while it was 0.0% for the 659 children tested in 2015. The Tanzanian National Lymphatic Filariasis Elimination Programme reported annual treatment coverage for Rufiji District ranging from 54.3% to 94.0% during the years 2002-2014. The surveyed treatment was 51.6% in 2011 and 57.4% in 2014. With regard to LLINs, possession and utilization increased from 63.4% and 59.2%, respectively, in 2012, to 92.5% and 75.4%, respectively, in 2015. The findings suggest that 12 rounds of MDA complemented with vector control through the use of insecticide-treated nets resulted in a marked reduction in W. bancrofti CFA in young school children.

Reaching endpoints for lymphatic filariasis elimination- results from mass drug administration and nocturnal blood surveys, South Gujarat, India.

BackgroundFollowing the World Health Assembly resolution on Elimination of lymphatic filariasis (ELF) as a public health problem by the year 2020, a Global Program (GPELF) was launched in 1997 to help endemic countries to initiate national programs. The current strategy to interrupt transmission of LF, is administration of once-yearly, single-dose, two-drug regimen (Albendazole with Diethylcarbamazine (DEC) to be used in endemic areas with the goal of reaching 65% epidemiological coverage for 4–6 years. We report findings of independent assessment from year 2010 to 2015 for last six rounds, after initial five rounds of Mass Drug Administration (MDA) since 2005 for ELF in endemic area of Gujarat.MethodsIndependent assessment of MDA was performed to find coverage and compliance indicators, reasons for non-coverage and non-compliance in five Implementation Units (IUs). Pre, during and post MDA evaluations were done in three phases. The impact of MDA was measured by microfilaraemia survey. A total of eight sites, four random and four fixed sentinel sites were selected to calculate microfilaria rate (MF) per IUs per year. In years 2010 to 2015, we report results from 125,936 nocturnal blood smears and 17551 population in 120 selected clusters. Four clusters were selected per year in each of the five IUs for assessment of MDA round.ResultPost MDA survey showed drug coverage between 81%-88% and epidemiological coverage 77%-89% across years. Main reasons for non-coverage were drug administrator related (the team did not visit or missed people) while non-compliance was population related (fear of side effects, sickness, people forgot or absent). During MDA findings show that the directly observed consumption is considerably improved from 58% in 2010 to 82% in 2015. The knowledge about benefits of drug provided also increased from 59% to 90% over the years. The current MF rate is less than one in all IUs with an overall 68% percent decrease from baseline year 2005 to year 2015. The average MF rate of Gujarat is 0.44 for year 2015.ConclusionsThe findings show that achieving adequate epidemiological and drug coverage is possible by actual field level operation of the program in large endemic areas. The results and feedback from independent assessment, performed regularly, could guide the policymakers and program managers for mid-term corrections and to frame strategies to enhance program. Monitoring of coverage and impact indicator together informs decisions for reaching end-point of MDA. The impact indicator- microfilaria rate in all IUs of South Gujarat Region has reached and remained less than one percent signaling end-points of MDA. Post MDA stringent monitoring in form of TAS is recommended to keep vigil on maintenance of elimination achieved.

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.

Assessing the interruption of the transmission of human helminths with mass drug administration alone: optimizing the design of cluster randomized trials

BackgroundA method is outlined for the use of an individual-based stochastic model of parasite transmission dynamics to assess different designs for a cluster randomized trial in which mass drug administration (MDA) is employed in attempts to eliminate the transmission of soil-transmitted helminths (STH) in defined geographic locations. The hypothesis to be tested is: Can MDA alone interrupt the transmission of STH species in defined settings? Clustering is at a village level and the choice of clusters of villages is stratified by transmission intensity (low, medium and high) and parasite species mix (either Ascaris, Trichuris or hookworm dominant).ResultsThe methodological approach first uses an age-structured deterministic model to predict the MDA coverage required for treating pre-school aged children (Pre-SAC), school aged children (SAC) and adults (Adults) to eliminate transmission (crossing the breakpoint in transmission created by sexual mating in dioecious helminths) with 3 rounds of annual MDA. Stochastic individual-based models are then used to calculate the positive and negative predictive values (PPV and NPV, respectively, for observing elimination or the bounce back of infection) for a defined prevalence of infection 2 years post the cessation of MDA. For the arm only involving the treatment of Pre-SAC and SAC, the failure rate is predicted to be very high (particularly for hookworm-infected villages) unless transmission intensity is very low (R0, or the effective reproductive number R, just above unity in value).ConclusionsThe calculations are designed to consider various trial arms and stratifications; namely, community-based treatment and Pre-SAC and SAC only treatment (the two arms of the trial), different STH transmission settings of low, medium and high, and different STH species mixes. Results are considered in the light of the complications introduced by the choice of statistic to define success or failure, varying adherence to treatment, migration and parameter uncertainty.

ADVERSE EVENT (AE) REPORTING FROM MALARIA MASS DRUG ADMINISTRATION (MDA) ROUNDS CONDUCTED IN SOUTHERN ZAMBIA

BackgroundThe National Malaria Control Centre (NMCC) of the Ministry of Health in Zambia is conducting a large-scale mass drug administration (MDA) community randomised-controlled trial to evaluate the effectiveness of different...

INTERRUPTED BANCROFTIAN FILARIASIS EXPOSURE RATES IN CHILDREN AFTER TWELVE ROUNDS OF MASS DRUG ADMINISTRATION AND USE OF LONG-LASTING INSECTICIDAL NETS IN RUFIJI DISTRICT, TANZANIA

BackgroundTanzania started implementing the WHO strategy of mass drug administration (MDA) with ivermectin and albendazole to eliminate lymphatic filariasis (LF) in Rufiji District, which had a baseline prevalence of 49%...

The significant scale up and success of Transmission Assessment Surveys 'TAS' for endgame surveillance of lymphatic filariasis in Bangladesh: One step closer to the elimination goal of 2020.

BackgroundBangladesh had one of the highest burdens of lymphatic filariasis (LF) at the start of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) with an estimated 70 million people at risk of infection across 34 districts. In total 19 districts required mass drug administration (MDA) to interrupt transmission, and 15 districts were considered low endemic. Since 2001, the National LF Programme has implemented MDA, reduced prevalence, and been able to scale up the WHO standard Transmission Assessment Survey (TAS) across all endemic districts as part of its endgame surveillance strategy. This paper presents TAS results, highlighting the momentous geographical reduction in risk of LF and its contribution to the global elimination target of 2020.Methodology/Principal findingsThe TAS assessed primary school children for the presence of LF antigenaemia in each district (known as an evaluation unit—EU), using a defined critical cut-off threshold (or ‘pass’) that indicates interruption of transmission. Since 2011, a total of 59 TAS have been conducted in 26 EUs across the 19 endemic MDA districts (99,148 students tested from 1,801 schools), and 22 TAS in the 15 low endemic non-MDA districts (36,932 students tested from 663 schools). All endemic MDA districts passed TAS, except in Rangpur which required two further rounds of MDA. In total 112 students (male n = 59; female n = 53), predominately from the northern region of the country were found to be antigenaemia positive, indicating a recent or current infection. However, the distribution was geographically sparse, with only two small focal areas showing potential evidence of persistent transmission.Conclusions/SignificanceThis is the largest scale up of TAS surveillance activities reported in any of the 73 LF endemic countries in the world. Bangladesh is now considered to have very low or no risk of LF infection after 15 years of programmatic activities, and is on track to meet elimination targets. However, it will be essential that the LF Programme continues to develop and maintain a comprehensive surveillance strategy that is integrated into the health infrastructure and ongoing programmes to ensure cost-effectiveness and sustainability.

Modelling Anti-Ov16 IgG4 Antibody Prevalence as an Indicator for Evaluation and Decision Making in Onchocerciasis Elimination Programmes.

BackgroundOnchocerciasis is targeted for elimination in Africa through annual or biannual ivermectin mass drug administration (MDA). An immunodiagnostic test, based on the detection of human IgG4 antibodies in the blood to the Onchocerca volvulus-specific antigen Ov16, is one of the recommended tools for determining whether transmission is interrupted and mass treatment can stop. For different transmission settings, the relationship between post-MDA Ov16 antibody prevalence in children (measured 1 year after the last round of MDA) and the duration and coverage of MDA, the mf prevalence in the population, and the probability that onchocerciasis is eventually eliminated is explored through mathematical modelling.MethodologyThe ONCHOSIM model was extended with new output on the Ov16 antibody serostatus of individuals. Seroconversion was assumed to be triggered by the first worm establishing in the host, with seroconversion occurring either before maturation, after maturation or only after the start of mf production. We are mainly interested in seroconversion rates in children, and for now ignore the possibility of seroreversion to simplify the model.Principal findingsYearly repeated MDA leads to a strong reduction in the parasite acquisition rate in humans. This reduces the seroconversion rate in newborns and young children, while those who seroconverted before the start of control remain antibody positive. Both the microfiladermia prevalence in the population aged 5 years and above and the Ov16 antibody prevalence in children under 10 declined with increasing duration of MDA. The association between either of these indicators and the model-predicted probability of elimination was not influenced much by the assumed treatment coverage levels, but was found to depend on baseline endemicity levels, assumptions regarding the trigger of seroconversion, and diagnostic test characteristics (sensitivity and specificity).ConclusionsBetter understanding of the dynamics of Ov16 antibody responses is required for accurate interpretation of seroprevalence data and more precise estimation of endpoint for MDA. Our study demonstrates that this endpoint will be dependent on baseline endemicity levels, which should be taken into account in guidelines for defining when to stop MDA.

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.

Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: a modelling study

Lymphatic filariasis is targeted for elimination as a public health problem by 2020. The principal approach used by current programmes is annual mass drug administration with two pairs of drugs with a good safety profile. However, one dose of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole) has been shown to clear the transmissible stage of the helminth completely in treated individuals. The aim of this study was to use modelling to assess the potential value of mass drug administration with the triple-drug regimen for accelerating elimination of lymphatic filariasis in different epidemiological settings. We used three different transmission models to compare the number of rounds of mass drug administration needed to achieve a prevalence of microfilaraemia less than 1% with the triple-drug regimen and with current two-drug regimens. In settings with a low baseline prevalence of lymphatic filariasis (5%), the triple-drug regimen reduced the number of rounds of mass drug administration needed to reach the target prevalence by one or two rounds, compared with the two-drug regimen. For areas with higher baseline prevalence (10-40%), the triple-drug regimen strikingly reduced the number of rounds of mass drug administration needed, by about four or five, but only at moderate-to-high levels of population coverage (>65%) and if systematic non-adherence to mass drug administration was low. Simulation modelling suggests that the triple-drug regimen has potential to accelerate the elimination of lymphatic filariasis if high population coverage of mass drug administration can be achieved and if systematic non-adherence with mass drug administration is low. Future work will reassess these estimates in light of more clinical trial data and to understand the effect on an individual country's programme. Bill & Melinda Gates Foundation.

Short-term Impact of Mass Drug Administration With Dihydroartemisinin Plus Piperaquine on Malaria in Southern Province Zambia: A Cluster-Randomized Controlled Trial.

BackgroundMass drug administration (MDA) using dihydroartemisinin plus piperaquine (DHAp) represents a potential strategy to clear Plasmodium falciparum infections and reduce the human parasite reservoir.MethodsA cluster-randomized controlled trial in Southern Province, Zambia, was used to assess the short-term impact of 2 rounds of community-wide MDA and household-level (focal) MDA with DHAp compared with no mass treatment. Study end points included parasite prevalence in children, infection incidence, and confirmed malaria case incidence.ResultsAll end points significantly decreased after intervention, irrespective of treatment group. Parasite prevalence from 7.71% at baseline to 0.54% after MDA in lower-transmission areas, resulting in an 87% reduction compared with control (adjusted odds ratio, 0.13; 95% confidence interval, .02–.92;P = .04). No difference between treatment groups was observed in areas of high transmission. The 5-month cumulative infection incidence was 70% lower (crude incidence rate ratio, 0.30; 95% confidence interval, .06–1.49; P = .14) and 58% lower (0.42; .18–.98;P = .046) after MDA compared with control in lower- and higher-transmission areas, respectively. No significant impact of focal MDA was observed for any end point.ConclusionsTwo rounds of MDA with DHAp rapidly reduced infection prevalence, infection incidence, and confirmed case incidence rates, especially in low-transmission areas.Clinical Trials RegistrationNCT02329301.

Dynamics of antigenemia and transmission intensity of Wuchereria bancrofti following cessation of mass drug administration in a formerly highly endemic region of Mali.

BackgroundAfter seven annual rounds of mass drug administration (MDA) in six Malian villages highly endemic for Wuchereria bancrofti (overall prevalence rate of 42.7%), treatment was discontinued in 2008. Surveillance was performed over the ensuing 5 years to detect recrudescence.MethodsCirculating filarial antigen (CFA) was measured using immunochromatographic card tests (ICT) and Og4C3 ELISA in 6–7 year-olds. Antibody to the W. bancrofti infective larval stage (L3) antigen, Wb123, was tested in the same population in 2012. Microfilaraemia was assessed in ICT-positive subjects. Anopheles gambiae complex specimens were collected monthly using human landing catch (HLC) and pyrethrum spray catch (PSC). Anopheles gambiae complex infection with W. bancrofti was determined by dissection and reverse transcriptase polymerase chain reaction (RT-PCR) of mosquito pools.ResultsAnnual CFA prevalence rates using ICT in children increased over time from 0% (0/289) in 2009 to 2.7% (8/301) in 2011, 3.9% (11/285) in 2012 and 4.5% (14/309) in 2013 (trend χ 2 = 11.85, df =3, P = 0.0006). Wb123 antibody positivity rates in 2013 were similar to the CFA prevalence by ELISA (5/285). Although two W. bancrofti-infected Anopheles were observed by dissection among 12,951 mosquitoes collected by HLC, none had L3 larvae when tested by L3-specific RT-PCR. No positive pools were detected among the mosquitoes collected by pyrethrum spray catch. Whereas ICT in 6–7 year-olds was the major surveillance tool, ICT positivity was also assessed in older children and adults (8–65 years old). CFA prevalence decreased in this group from 4.9% (39/800) to 3.5% (28/795) and 2.8% (50/1,812) in 2009, 2011 and 2012, respectively (trend χ 2 = 7.361, df =2, P = 0.0067). Some ICT-positive individuals were microfilaraemic in 2009 [2.6% (1/39)] and 2011 [8.3% (3/36)], but none were positive in 2012 or 2013.ConclusionAlthough ICT rates in children increased over the 5-year surveillance period, the decrease in ICT prevalence in the older group suggests a reduction in transmission intensity. This was consistent with the failure to detect infective mosquitoes or microfilaraemia. The threshold of ICT positivity in children may need to be re-assessed and other adjunct surveillance tools considered.

Population-Based Trachoma Mapping in Six Evaluation Units of Papua New Guinea

ABSTRACTPurpose: We sought to determine the prevalence of trachomatous inflammation – follicular (TF) in children aged 1–9 years, and trachomatous trichiasis (TT) in those aged ≥15 years, in suspected trachoma-endemic areas of Papua New Guinea (PNG).Methods: We carried out six population-based prevalence surveys using the protocol developed as part of the Global Trachoma Mapping Project.Results: A total of 19,013 individuals were sampled for inclusion, with 15,641 (82.3%) consenting to participate. Four evaluation units had prevalences of TF in children ≥10%, above which threshold the World Health Organization (WHO) recommends mass drug administration (MDA) of azithromycin for at least three years; Western Province (South Fly/Daru) 11.2% (95% confidence interval, CI, 6.9–17.0%), Southern Highlands (East) 12.2% (95% CI 9.6–15.0%), Southern Highlands (West) 11.7% (95% CI 8.5–15.3%), and West New Britain 11.4% (95% CI 8.7–13.9%). TF prevalence was 5.0–9.9% in Madang (9.4%, 95% CI 6.1–13.0%) and National Capital District (6.0%. 95% CI 3.2–9.1%) where consideration of a single round of MDA is warranted. Cases of TT were not found outside West New Britain, in which four cases were seen, generating an estimated population-level prevalence of TT in adults of 0.10% (95% CI 0.00–0.40%) for West New Britain, below the WHO elimination threshold of 0.2% of those aged ≥15 years.Conclusion: Trachoma is a public health issue in PNG. However, other than in West New Britain, there are few data to support the idea that trachoma is a cause of blindness in PNG. Further research is needed to understand the stimulus for the active trachoma phenotype in these populations.

Improving Coverage and Compliance in Mass Drug Administration for the Elimination of LF in Two 'Endgame' Districts in Indonesia Using Micronarrative Surveys.

BackgroundAs the Global Programme to Eliminate Lymphatic Filariasis (LF) approaches its 2020 goal, an increasing number of districts will enter the endgame phase where drug coverage rates from mass drug administration (MDA) are used to assess whether MDA can be stopped. As reported, the gap between reported and actual drug coverage in some contexts has overestimated the true rates, thus causing premature administration of transmission assessment surveys (TAS) that detect ongoing LF transmission. In these cases, districts must continue with additional rounds of MDA. Two districts in Indonesia (Agam District, Depok City) fit this criteria—one had not met the pre-TAS criteria and the other, had not passed the TAS criteria. In both cases, the district health teams needed insight into their drug delivery programs in order to improve drug coverage in the subsequent MDA rounds.Methodology/Principal FindingsTo inform the subsequent MDA round, a micronarrative survey tool was developed to capture community members’ experience with MDA and the social realm where drug delivery and compliance occur. A baseline survey was implemented after the 2013 MDA in endemic communities in both districts using the EPI sampling criteria (n = 806). Compliance in the last MDA was associated with perceived importance of the LF drugs for health (p<0.001); perceived safety of the LF drugs (p<0.001) and knowing someone in the household has complied (p<0.001). Results indicated that specialized messages were needed to reach women and younger men. Both districts used these recommendations to implement changes to their MDA without additional financial support. An endline survey was performed after the 2014 MDA using the same sampling criteria (n = 811). Reported compliance in the last MDA improved in both districts from 57% to 77% (p<0.05). Those who reported having ever taken the LF drug rose from 79% to 90% (p<0.001) in both sites.Conclusions/SignificanceMicronarrative surveys were shown to be a valid and effective tool to detect operational issues within MDA programs. District health staff felt ownership of the results, implementing feasible changes to their programs that resulted in significant improvements to coverage and compliance in the subsequent MDA. This kind of implementation research using a micronarrative survey tool could benefit underperforming MDA programs as well as other disease control programs where a deeper understanding is needed to improve healthcare delivery.