Effect Of Mass Drug Administration Research Articles

Statistical analysis plan for the LAKANA trial: a cluster-randomized, placebo-controlled, double-blinded, parallel group, three-arm clinical trial testing the effects of mass drug administration of azithromycin on mortality and other outcomes among 1–11-month-old infants in Mali

BackgroundThe Large-scale Assessment of the Key health-promoting Activities of two New mass drug administration regimens with Azithromycin (LAKANA) trial in Mali aims to evaluate the efficacy and safety of azithromycin (AZI) mass drug administration (MDA) to 1–11-month-old infants as well as the impact of the intervention on antimicrobial resistance (AMR) and mechanisms of action of azithromycin. To improve the transparency and quality of this clinical trial, we prepared this statistical analysis plan (SAP).Methods/designLAKANA is a cluster randomized trial that aims to address the mortality and health impacts of biannual and quarterly AZI MDA. AZI is given to 1–11-month-old infants in a high-mortality setting where a seasonal malaria chemoprevention (SMC) program is in place. The participating villages are randomly assigned to placebo (control), two-dose AZI (biannual azithromycin-MDA), and four-dose AZI (quarterly azithromycin-MDA) in a 3:4:2 ratio. The primary outcome of the study is mortality among the intention-to-treat population of 1–11-month-old infants. We will evaluate relative risk reduction between the study arms using a mixed-effects Poisson model with random intercepts for villages, using log link function with person-years as an offset variable. We will model outcomes related to secondary objectives of the study using generalized linear models with considerations on clustering.ConclusionThe SAP written prior to data collection completion will help avoid reporting bias and data-driven analysis for the primary and secondary aims of the trial. If there are deviations from the analysis methods described here, they will be described and justified in the publications of the trial results.Trial registrationClinicalTrials.gov ID NCT04424511. Registered on 11 June 2020.

Water, Sanitation, and Hygiene (WASH) Factors Influencing the Effectiveness of Mass Drug Administration to Eliminate Trachoma as a Public Health Problem in Malawi

ABSTRACT Purpose Following a national population-based trachoma survey in Malawi one round of azithromycin mass drug administration (MDA) was carried out, with a post-MDA impact survey showing TF prevalence below 5% and considered eliminated as a public health problem. However, active trachoma was still present in over 200 children. We assessed whether water, sanitation, and hygiene (WASH) factors were associated with ongoing presence of TF in children aged 1–9 years following MDA. Methods A secondary analysis was performed on a sub-set of the post-MDA impact survey data for children aged 1–9 years. We used a logistic regression analysis, adjusted for clustering at the household and village level. Results Among 16,142 children aged 1–9 years, 209 (1.3%) had TF after MDA. Factors associated with a significantly lower odds of TF after MDA were living in a household with a handwashing facility (aOR: 0.37) and living in a household where water for washing is located further away from the home (30 min away aOR: 0.39, p = .034, or more than 1 h away aOR: 0.31, p = .018) compared with water in the yard. Conclusion The inverse association between a domestic handwashing facility and TF is consistent with previous findings, but the association of increasing distance to collect water for washing with a reduced risk of TF was unexpected and may reflect the impact of drought and unmeasured behavioural factors related to water usage. A more comprehensive collection of sociodemographic and WASH factor information in population-based trachoma surveys will provide insight into achieving and maintaining low levels of trachoma.

Testing the effects of mass drug administration of azithromycin on mortality and other outcomes among 1–11-month-old infants in Mali (LAKANA): study protocol for a cluster-randomized, placebo-controlled, double-blinded, parallel-group, three-arm clinical trial

BackgroundMass drug administration (MDA) of azithromycin (AZI) has been shown to reduce under-5 mortality in some but not all sub-Saharan African settings. A large-scale cluster-randomized trial conducted in Malawi, Niger, and Tanzania suggested that the effect differs by country, may be stronger in infants, and may be concentrated within the first 3 months after treatment. Another study found no effect when azithromycin was given concomitantly with seasonal malaria chemoprevention (SMC). Given the observed heterogeneity and possible effect modification by other co-interventions, further trials are needed to determine the efficacy in additional settings and to determine the most effective treatment regimen.MethodsLAKANA stands for Large-scale Assessment of the Key health-promoting Activities of two New mass drug administration regimens with Azithromycin. The LAKANA trial is designed to address the mortality and health impacts of 4 or 2 annual rounds of azithromycin MDA delivered to 1–11-month-old (29–364 days) infants, in a high-mortality and malaria holoendemic Malian setting where there is a national SMC program. Participating villages (clusters) are randomly allocated in a ratio of 3:2:4 to three groups: placebo (control):4-dose AZI:2-dose AZI. The primary outcome measured is mortality. Antimicrobial resistance (AMR) will be monitored closely before, during, and after the intervention and both among those receiving and those not receiving MDA with the study drugs. Other outcomes, from a subset of villages, comprise efficacy outcomes related to morbidity, growth and nutritional status, outcomes related to the mechanism of azithromycin activity through measures of malaria parasitemia and inflammation, safety outcomes (AMR, adverse and serious adverse events), and outcomes related to the implementation of the intervention documenting feasibility, acceptability, and economic aspects. The enrolment commenced in October 2020 and is planned to be completed by the end of 2022. The expected date of study completion is December 2024.DiscussionIf LAKANA provides evidence in support of a positive mortality benefit resulting from azithromycin MDA, it will significantly contribute to the options for successfully promoting child survival in Mali, and elsewhere in sub-Saharan Africa.Trial registrationClinicalTrials.gov NCT04424511. Registered on 11 June 2020.

Simulating the Impacts of Augmenting Intensive Vector Control with Mass Drug Administration or Test-and-Treat Strategies on the Malaria Infectious Reservoir.

Highly effective vector control can reduce malaria burden significantly, but individuals with parasitemia provide a potential reservoir for onward transmission. We performed an empirical, non-parametric simulation based on cohort data from Tororo District, Uganda-an area with historically high but recently reduced malaria transmission-to estimate the effects of mass drug administration (MDA) and test-and-treat on parasite prevalence. We estimate that a single round of MDA would have accelerated declines in parasite prevalence dramatically over 2 years (cumulative parasite prevalence ratio [PPR], 0.34). This decline was mostly during the first year of administration (PPR, 0.23) and waned by 23 months (PPR, 0.74). Test-and-treat using a highly sensitive diagnostic had nearly the same effect as MDA at 1 year (PPR, 0.27) and required many fewer treatments. The impact of test-and-treat using a standard diagnostic was modest (PPR, 0.58 at 1 year). Our analysis suggests that in areas experiencing a dramatic reduction in malaria prevalence, MDA or test-and-treat with a highly sensitive diagnostic may be an effective way of reducing or eliminating the infectious reservoir temporarily. However, for sustained benefits, repeated rounds of the intervention or additional interventions are required.

Mass drug administration of ivermectin, diethylcarbamazine, plus albendazole compared with diethylcarbamazine plus albendazole for reduction of lymphatic filariasis endemicity in Papua New Guinea: a cluster-randomised trial

SummaryBackgroundA single co-administered dose of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole) has been shown to be safe and more efficacious for clearing Wuchereria bancrofti microfilariae than the standard two-drug regimen of diethylcarbamazine plus albendazole in clinical trials. However, the effectiveness of mass drug administration with the triple-drug regimen compared with the two-drug regimen is unknown. We compared the effectiveness of mass drug administration with the triple-drug and two-drug regimens for reducing microfilariae prevalence to less than 1% and circulating filarial antigen prevalence to less than 2%, levels that are unlikely to sustain transmission of lymphatic filariasis, in Papua New Guinea.MethodsThis open-label, cluster-randomised study was done in 24 villages in a district endemic for lymphatic filariasis in Papua New Guinea. Villages paired by population size were randomly assigned to receive mass drug administration with a single dose of the triple-drug oral regimen of ivermectin (200 μg per kg of bodyweight) plus diethylcarbamazine (6 mg per kg of bodyweight) plus albendazole (400 mg) or a single dose of the two-drug oral regimen of diethylcarbamazine (6 mg per kg of bodyweight) plus albendazole (400 mg). This is a follow-on study of a previously reported safety study (ClinicalTrials.govNCT02899936). All residents aged 5 years or older and non-pregnant women were asked to participate. After cross-sectional night blood microfilariae and circulating filarial antigen surveys, mass drug administration was provided at baseline and repeated 12 months later. The primary outcomes were mean prevalence of microfilariae and circulating filarial antigen at 12 months and 24 months, assessed in all residents willing to participate at each timepoint. This study is registered with ClinicalTrials.gov, NCT03352206.FindingsBetween Nov 18, 2016, and May 26, 2017, 4563 individuals were enrolled in 24 clusters; 12 clusters (2382 participants) were assigned to the triple-drug regimen and 12 clusters (2181 participants) to the two-drug regimen. Mean drug ingestion rates (of residents aged ≥5 years) were 66·1% at baseline and 63·2% at 12 months in communities assigned to the triple-drug regimen and 65·9% at baseline and 54·9% at 12 months in communities assigned to the two-drug regimen. Microfilariae prevalence in the triple-drug regimen group decreased from 105 (4·4%) of 2382 participants (95% CI 3·6–5·3) at baseline to nine (0·4%) of 2319 (0·1–0·7) at 12 months and four (0·2%) of 2086 (0·1–0·5) at 24 months. In the two-drug regimen group, microfilariae prevalence decreased from 93 (4·3%) of 2181 participants (95% CI 3·5–5·2) at baseline to 29 (1·5%) of 1963 (1·0–2·1) at 12 months and eight (0·4%) of 1844 (0·2–0·9) at 24 months (adjusted estimated risk ratio 4·5, 95% CI 1·4–13·8, p=0·0087, at 12 months; 2·9, 95% CI 1·0–8·8, p=0·058, at 24 months). The prevalence of circulating filarial antigen decreased from 523 (22·0%) of 2382 participants (95% CI 20·3–23·6) at baseline to 378 (16·3%) of 2319 (14·9–17·9) at 12 months and 156 (7·5%) of 2086 (6·4–8·7) at 24 months in the triple-drug regimen group and from 489 (22·6%) of 2168 participants (20·7–24·2) at baseline to 358 (18·2%) of 1963 (16·7–20·1) at 12 months and 184 (10·0%) of 1840 (8·7–11·5) at 24 months in the two-drug regimen group; after adjustment, differences between groups were not significant.InterpretationMass administration of the triple-drug regimen was more effective than the two-drug regimen in reducing microfilariae prevalence in communities to less than the target level of 1%, but did not reduce circulating filarial antigen prevalence to less than 2%. These results support the use of mass drug administration with the triple-drug regimen to accelerate elimination of lymphatic filariasis.FundingBill & Melinda Gates Foundation.

An assessment of implementation and effectiveness of mass drug administration for prevention and control of schistosomiasis and soil-transmitted helminths in selected southern Malawi districts

BackgroundMass drug administration (MDA) is one of the key interventions recommended by WHO for prevention and control of neglected tropical diseases (NTD). In Malawi, MDA is widely carried out annually since 2009 for prevention and control of schistosomiasis and soil-transmitted helminths (STH). No study has been carried out to assess effectiveness of the MDA approach and to document perceptions of health providers and beneficiaries regarding use of MDA. This study was done to understand how well MDA is being implemented and to identify opportunities for improvement in MDA delivery in Malawi.MethodsDesigned as a cross-sectional and multi-methods research, the study was carried out in three southern Malawi districts of Chiradzulu, Mangochi and Zomba. In each district, four health centres and 16 villages were randomly selected to participate. A mixed-methods approach to data collection focusing on quantitative data for coverage and knowledge, attitudes and practices assessments; and qualitative data for assessing perceptions of health providers and beneficiaries regarding MDA was used. Quantitative data were processed and analyzed using IBM SPSS software version 26 while qualitative data were analysed using NVivo 12 for Windows.ResultsKnowledge levels about schistosomiasis and STH in the districts varied according to disease aspects asked about. Majority are more knowledgeable about what schistosomiasis is (78%) and whether STH are treatable with drugs (97%); with least knowledgeable about the organism that transmits schistosomiasis (18%), types of schistosomiasis (11%) and what causes STH (20%). In 2018 and 2019 the districts registered high coverage rates for praziquantel and albendazole using community-based MDA (73–100%) and using school-based MDA (75–91%). Both the health authorities and community members perceived the MDA approach as good because it brings treatment closer to people.ConclusionWith the high MDA coverage obtained in communities and schools, the effectiveness of MDA in the target districts is satisfactory. There are, however, several challenges including disproportionate knowledge levels, which are hampering progress towards attainment of the 2030 global NTD goals. There is a need for promotion of community participation and partnerships as well as implementation of other recommended interventions for sustainable prevention and control of schistosomiasis and STH.

Effect of Ivermectin mass drug administration on the COVID-19 Pandemic

Uttarakhand, a hilly state of India adopted the strategy of mass drug administration of ivermectin during the second wave of COVID-19 pandemic as a measure to control the peak due to failing health infrastructure and health facility with sudden cases surge. This study was hereby planned with an aim of analyzing the effect of mass drug administration of ivermectin on the COVID-19 pandemic progression in the State of Uttarakhand. The trend of pandemic progression in five states of India was studied taking case growth rate, active case rate and case fatality rate as indicators. The percentage change in the indicators with the progression of pandemic was calculated for all five states and compared. The projected increased number of deaths, the state of Uttarakhand would have experienced, if the state had the declining average case growth of the other states taken for study was also calculated. The data analysis shows that the Uttarakhand had a sharp fall in the active cases by 3 to 4 weeks post lockdown, the period corresponding with maximum coverage of ivermectin distribution in the state.

What are the effects of mass drug administration (MDA) for people living in an area with very low to low endemicity of Plasmodium falciparum and Plasmodium vivax malaria?

What are the effects of mass drug administration (MDA) for people living in an area with very low to low endemicity of Plasmodium falciparum and Plasmodium vivax malaria?

What are the effects of mass drug administration (MDA) for people living in an area with moderate to high endemicity of Plasmodium falciparum malaria?

What are the effects of mass drug administration (MDA) for people living in an area with moderate to high endemicity of Plasmodium falciparum malaria?

EVALUATION OF LYMPHATIC FILARIASIS AFTER TWO ROUNDS OF MASS DRUG ADMINISTRATION IN LAU LOCAL GOVERNMENT AREA OF TARABA STATE NIGERIA

This study was undertaken to evaluate the effects of Mass Drug Administration (MDA) on Wuchereria bancrofti (microfilariae) after two rounds of combined Ivermectin and Albendazole distribution. A total of 221 participants were recruited in three communities in Lau Local Government Area of Taraba State by convenience sampling method. Questionnaires and physical examinations were used to assess clinical manifestations associated with the infection. Blood samples were collected by finger prick method and stained with Giemsa stain for examination to establish the presence of W. bancrofti while immunochromatographic card test was performed to determine the presence of filarial antigen in serum. Previous data were used to determine the pre-drug prevalence of the parasite. The results showed that the drug did not significantly reduce the clinical manifestations reported among the patients. The microfilariae prevalence and microfilaria mean density after two rounds of drug administration was 19.5% and 1.49%, while the pre- MDA prevalence and microfilaria mean density was 27.8% and 2.44% respectively. There was a statistically significant decrease of microfilaria prevalence (P<0.05) after two rounds of MDA. There was no significant effect of MDA by age, sex and occupation-related microfilariae prevalence in the study area. In conclusion, the study reveals that microfilaria prevalence and load decreased after two rounds of MDA of combined Ivermectin and Albendazole distribution amongst the studied populations. Routine evaluation of the MDA is required to assess the impact of the drug for the eventual elimination of the infection.

Population genetics of African Schistosoma species.

Blood flukes within the genus Schistosoma (schistosomes) are responsible for the major disease, schistosomiasis, in tropical and sub-tropical areas. This disease is predominantly present on the African continent with more than 85% of the human cases. Schistosomes are also parasites of veterinary importance infecting livestock and wildlife. Schistosoma population genetic structure and diversity are important characteristics that may reflect variations in selection pressures such as those induced by host (mammalian and snail) environments, habitat change, migration and also treatment/control interventions, all of which also shape speciation and evolution of the whole Schistosoma genus. Investigations into schistosome population genetic structure, diversity and evolution has been an area of important debate and research. Supported by advances in molecular techniques with capabilities for multi-locus genetic analyses for single larvae schistosome genetic investigations have greatly progressed in the last decade. This paper aims to review the genetic studies of both animal and human infecting schistosome. Population genetic structures are reviewed at different spatial scales: local, regional or continental (i.e. phylogeography). Within species genetic diversities are discussed compared and the compounding factors discussed, including the effect of mass drug administration. Finally, the ability for intra-species hybridisation questions species integrities and poses many questions in relation to the natural epidemiology of co-endemic species. Here we review molecularly confirmed hybridisation events (in relation to human disease) and discuss the possible impact for ongoing and future control and elimination.

Understanding hard-to-reach communities: local perspectives and experiences of trachoma control among the pastoralist Maasai in northern Tanzania.

As progress to eliminate trachoma is made, addressing hard-to-reach communities becomes of greater significance. Areas in Tanzania, inhabited by the Maasai, remain endemic for trachoma. This study assessed the effectiveness of Mass Drug Administration (MDA) through an ethnographic study of trachoma amongst a Maasai community. The MDA experience in the context of the livelihoods of the Maasai in a changing political economy was explored using participant observation and household interviews. Factors influencing MDA effectiveness within five domains were analysed. 1) Terrain of intervention: Human movement hindered MDA, including seasonal migration, domestic chores, grazing and school. Encounters with wildlife were significant. 2) Socio-cultural factors and community agency: Norms around pregnancy led women to accept the drug but hide refusal to swallow the drug. Timing of Community Drug Distributor (CDD) visits conflicted with livestock grazing. Refusals occurred among the ilmurrani age group and older women. Mistrust significantly hindered uptake of drugs. 3) Strategies and motivation of drug distributors: Maa-speaking CDDs were critical to effective drug delivery. Maasai CDDs, whilst motivated, faced challenges of distances, encounters with wildlife and compensation. 4) Socio-materiality of technology: Decreases in side-effects over years have improved trust in the drug. Restrictions to swallowing drugs and/or water were relevant to post-partum women and the ilmurrani. 5) History and health governance: Whilst perceptions of the programme were positive, communities questioned government priorities for resources for hospitals, medicines, clean water and roads. They complained of a lack of information and involvement of community members in health care services. With elimination in sight, hard-to-reach communities are paramount as these are probably the last foci of infection. Effective delivery of MDA programmes in such communities requires a critical understanding of community experiences and responses that can inform tailored approaches to trachoma control. Application of a critical social science perspective should be embedded in planning and evaluation of all NTD programmes.

The effect of Mass Drug Administration for trachoma on antibodies to Chlamydia trachomatis pgp3 in children

A serologic test for antibodies to chlamydia may be a useful tool for trachoma surveillance. However, little is known about the longitudinal stability of antibody status, especially following Mass Drug Administration (MDA), which is critical to understanding serostatus in trachoma-endemic areas. A longitudinal cohort of 1908 children ages 1–9 years in Tanzania from 50 communities were followed at baseline and for 6 months after MDA. They were evaluated for clinical trachoma, conjunctival swabs were tested for chlamydial infection using GeneXpert platform, and blood spots were collected on filter paper and dried to test for antibodies to Chlamydia trachomatis pgp3 using the Luminex platform. 6.3% of children in the study had infection, and coverage with MDA was 97%. 670 (35%) were sero-positive for pgp3 antibodies at baseline, and 4.0% of these seroreverted to negative following MDA. Of those seronegative at baseline, 3.6% seroconverted. The individual change in log median fluorescence intensity(MFI-BG) values was -0.15 overall (p < .001). Seroconversion rates were lower following MDA and seroreversion rates were slightly higher compared to rates in this same cohort in the absence of MDA. MDA has a small effect on reduction of MFI-BG.

Effectiveness of Mass Drug Administration on Neglected Tropical Diseases in Schoolchildren in Zanzibar, Tanzania.

Soil-transmitted helminths and Schistosoma haematobium affect more than 3 billion people globally and mainly occur in sub-Saharan Africa. The present study assessed the overall infection status of a 1716-student cohort of schoolchildren in Zanzibar and applied mass drug administration (MDA) to the cohort from 2007 to 2009. Schools in Pemba, Zanzibar, had a much higher prevalence of soil-transmitted helminth infections than those in Unguja, and the Chaani, Ghana, and Machui schools of Unguja exhibited high S. haematobium infection rates. The MDA program only partially controlled parasite infections, owing to high rates of re-infection. The infection rate of S. haematobium across all 10 schools, for example, was only reduced by 1.8%, and even this change not significant, even though the S. haematobium infection rates of the Chaani and Mzambarauni schools were significantly reduced from 64.4 and 23.4%, respectively, at the first screening, to 7.3 and 2.3% at the last screening. The overall infection rate of Ascaris lumbricoides was reduced from 36.0% at the first screening to 22.6% at the last screening. However, the infection rates for both Trichuris trichiura and hookworm were generally unaffected by MDA. In the future, parasite control programs should involve strategically designed MDA schedules and holistic intervention (e.g., sanitation improvement, hygiene behavior changes, and control of intermediated hosts).

Effect of Mass Drug Administration with a Single Dose of Albendazole on Ascaris lumbricoides and Trichuris trichiura Infection among Schoolchildren in Yangon Region, Myanmar

Soil-transmitted helminths, including Ascaris lumbricoides and Trichuris trichiura, are important intestinal parasites mostly affecting younger people in developing countries. In 2014–2015, we performed mass fecal examinations targeting a total of 2,227 schoolchildren in 3 districts (South Dagon, North Dagon, and Hlaing-thar-yar) of Yangon Region, Myanmar, using the Kato-Katz thick smear technique. The egg positive children were subjected to a mass drug administration (MDA) using a single oral dose of 400 mg albendazole. The pre-treatment egg positive rate (EPG/person) of A. lumbricoides averaged 17.2% (15,532); it was 25.2% (21,796), 14.2% (11,816), and 12.8% (12,983) in 3 districts, respectively, and that of T. trichiura averaged 19.4% (1,074), and was 24.1% (1,040), 12.3% (852), and 21.2% (1,330) in 3 districts, respectively. Follow-up fecal examinations performed 4 months post-MDA revealed considerable decreases of A. lumbricoides prevalence (EPG/person) to av. 8.3% (12,429), and 13.7% (17,640), 8.0% (7,797), and 4.5% (11,849) in 3 districts, respectively. However, T. trichiura did not show any recognizable decrease in the prevalence (EPG/person) remaining at av. 18.2% (862), and 18.5% (888), 11.5% (812), and 23.3% (887) in 3 districts, respectively. The results demonstrated difficulty in short-term control of T. trichiura by MDA using albendazole and suggested necessity of either a long-term MDA (>10 years) or changing the albendazole regimen into 2~3-day course (total 800 or 1,200 mg), or using an alternative drug/drug combination.

Evaluation of the effect of mass drug administration against lymphatic filariasis in three health districts and public health implications: study of 12 epidemiological surveillance sites in Burkina Faso.

The implementation of mass drug administration (MDA) campaigns of albendazole (400mg) and ivermectin (150-200μm/kg) since 2001 has helped to change the epidemiological profile of lymphatic filariasis (LF) in many health districts in Burkina Faso. From 2002 to 2016, 14rounds of MDA have taken place in the Central East zone, with therapeutic coverage exceeding 65%. The objective of the current study was to evaluate the impact of MDA in the fight against LF at 12sentinel and spot-check sites. This descriptive cross-sectional study surveyed subjects aged 5 years and older between April and July 2017 at these 12sites. The blood smear performed on nocturnal samples was used to diagnose Wuchereria bancrofti infection. The study included 4364 subjects. Their mean age was 20.55years with a standard deviation of 14.22 and a range of 5to 96years. The overall prevalence of microfilaremia was 0.62% (27/4364), with rates exceeding 1% at three (3) sites. The average microfilaremia density was 106μf/mL. The overall prevalence of morbidity was low (0.91%), predominantly lymphedema (0.60%). The MDA strategy has helped to reduce the prevalence of LF significantly in Burkina Faso, but some outbreaks still have microfilarial prevalence greater than 1%. Continuation of the additional 2-year strategy with improved adherence to treatment and vector control would help break LF transmission.

Safety and effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum malaria: A pilot trial in four villages of Eastern Myanmar

Background: Artemisinin and partner drug-resistant falciparum malaria is expanding over the Greater Mekong Sub-region (GMS). Eliminating falciparum malaria in the GMS while drugs still retain enough efficacy could prevent global spread of antimalarial resistance. Eliminating malaria rapidly requires targeting the reservoir of asymptomatic parasite carriers. This pilot trial aimed to evaluate the acceptability, safety, feasibility and effectiveness of mass-drug administration (MDA) in reducing malaria in four villages in Eastern Myanmar. Methods: Villages with ≥30% malaria prevalence were selected. Long-lasting insecticidal bednets (LLINs) and access to malaria early diagnosis and treatment (EDT) were provided. Two villages received MDA immediately and two were followed for nine months pre-MDA. MDA consisted of a 3-day supervised course of dihydroartemisinin-piperaquine and single low-dose primaquine administered monthly for three months. Adverse events (AE) were monitored by interviews and consultations. Malaria prevalence was assessed by ultrasensitive PCR quarterly for 24 months. Symptomatic malaria incidence,entomological indices, and antimalarial resistance markers were monitored. Results: MDA was well tolerated. There were no serious AE and mild to moderate AE were reported in 5.6%(212/3931) interviews. In the smaller villages, participation to three MDA courses was 61% and 57%, compared to 28% and 29% in the larger villages. Baseline prevalence was higher in intervention than in control villages (18.7% (95%CI=16.1-21.6) versus 6.8%(5.2-8.7), p<0.0001) whereas three months after starting MDA, prevalence was lower in intervention villages (0.4%(0.04-1.3) versus 2.7%(1.7-4.1), p=0.0014). After nine months the difference was no longer significant (2.0%(1.0-3.5) versus 0.9%(0.04-1.8), p=0.10). M0-M9 symptomatic falciparum incidence was similar between intervention and control. Before/after MDA comparisons showed that asymptomatic P. falciparum carriage and anopheline vector positivity decreased significantly whereas prevalence of the artemisinin-resistance molecular marker remained stable. Conclusions: This MDA was safe and feasible, and, could accelerate elimination of P. falciparum in addition to EDT and LLINs when community participation was sufficient.

Safety and effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum malaria: A pilot trial in four villages of Eastern Myanmar.

Background: Artemisinin and partner drug-resistant falciparum malaria is expanding over the Greater Mekong Sub-region (GMS). Eliminating falciparum malaria in the GMS while drugs still retain enough efficacy could prevent global spread of antimalarial resistance. Eliminating malaria rapidly requires targeting the reservoir of asymptomatic parasite carriers. This pilot trial aimed to evaluate the acceptability, safety, feasibility and effectiveness of mass-drug administration (MDA) in reducing malaria in four villages in Eastern Myanmar. Methods: Villages with ≥30% malaria prevalence were selected. Long-lasting insecticidal bednets (LLINs) and access to malaria early diagnosis and treatment (EDT) were provided. Two villages received MDA immediately and two were followed for nine months pre-MDA. MDA consisted of a 3-day supervised course of dihydroartemisinin-piperaquine and single low-dose primaquine administered monthly for three months. Adverse events (AE) were monitored by interviews and consultations. Malaria prevalence was assessed by ultrasensitive PCR quarterly for 24 months. Symptomatic malaria incidence,entomological indices, and antimalarial resistance markers were monitored. Results: MDA was well tolerated. There were no serious AE and mild to moderate AE were reported in 5.6%(212/3931) interviews. In the smaller villages, participation to three MDA courses was 61% and 57%, compared to 28% and 29% in the larger villages. Baseline prevalence was higher in intervention than in control villages (18.7% (95%CI=16.1-21.6) versus 6.8%(5.2-8.7), p<0.0001) whereas three months after starting MDA, prevalence was lower in intervention villages (0.4%(0.04-1.3) versus 2.7%(1.7-4.1), p=0.0014). After nine months the difference was no longer significant (2.0%(1.0-3.5) versus 0.9%(0.04-1.8), p=0.10). M0-M9 symptomatic falciparum incidence was similar between intervention and control. Before/after MDA comparisons showed that asymptomatic P. falciparum carriage and anopheline vector positivity decreased significantly whereas prevalence of the artemisinin-resistance molecular marker remained stable. Conclusions: This MDA was safe and feasible, and, could accelerate elimination of P. falciparumin addition to EDT and LLINs when community participation was sufficient.

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.

Serological Responses to Filarial Antigens in Malian Children Attending Elementary Schools.

Dried blood spots (DBS) were collected from 805 children attending 42 elementary schools in the regions of Mopti, Sikasso, Koulikoro, and the regional capital of Bamako in Mali as part of an evaluation of a school health intervention. Eluted immunoglobulin (Ig) G from the DBS was assessed by a multiplex bead assay (MBA) for two filariasis antigens, Wuchereria bancrofti, Wb123, and Brugia malayi, Bm14, to determine the effectiveness of mass drug administration (MDA) programs to eliminate lymphatic filariasis (LF). The prevalence of positive IgG responses in the children to each antigen was less than 1%, indicating effectiveness of the MDA against LF. The MBA is an excellent serological platform that provides cost-effective opportunities to evaluate public health activities beyond the survey targets.