Assessment of spillover of antimicrobial resistance to untreated children 7 to 12 years old after mass drug administration of azithromycin for child survival in Niger: a secondary analysis of the MORDOR cluster-randomized trial.

BACKGROUND: The risk of antibiotic resistance is complicated by the potential for spillover effects from one treated population to another. Azithromycin mass drug administration programs report higher rates of antibiotic resistance among treatment arms in targeted groups. This study aims to understand the risk of spillover of antibiotic resistance to non-target groups in these programs. METHODS: Data was used from a cluster-randomized trial comparing the effect of biannual azithromycin and placebo distribution to children 1-59 months on child mortality. Nasopharyngeal samples from untreated children 7-12 years old were tested for genetic determinants of macrolide resistance (primary outcome) and resistance to other antibiotic classes (secondary outcomes). Linear regression was used to compare the community-level mean difference in prevalence by arm at the 24-month timepoint adjusting for baseline prevalence. RESULTS: 1,103 children 7-12 years old in 30 communities were included in the analysis (15 azithromycin, 15 placebo). Adjusted mean differences in prevalence of resistance determinants for macrolides, beta-lactams and tetracyclines were 3.4% (95% CI -4.1% to 10.8%, P-value 0.37), -1.2% (95% CI -7.9% to 5.5%, P-value 0.72), and -3.3% (95% CI -9.5% to 2.8%, P-value 0.61), respectively. CONCLUSIONS: We were unable to demonstrate a statistically significant increase in macrolide resistance determinants in untreated groups in an azithromycin mass drug administration program. While the result might be consistent with a small spillover effect, this study was not powered to detect such a small difference. Larger studies are warranted to better understand the potential for spillover effects within these programs.

How Does Treatment Coverage and Proportion Never Treated Influence the Success of Schistosoma mansoni Elimination as a Public Health Problem by 2030?

BACKGROUND: The 2030 target for schistosomiasis is elimination as a public health problem (EPHP), achieved when the prevalence of heavy-intensity infection among school-aged children (SAC) reduces to <1%. To achieve this, the new World Health Organization guidelines recommend a broader target of population to include pre-SAC and adults. However, the probability of achieving EPHP should be expected to depend on patterns in repeated uptake of mass drug administration by individuals. METHODS: We employed 2 individual-based stochastic models to evaluate the impact of school-based and community-wide treatment and calculated the number of rounds required to achieve EPHP for Schistosoma mansoni by considering various levels of the population never treated (NT). We also considered 2 age-intensity profiles, corresponding to a low and high burden of infection in adults. RESULTS: The number of rounds needed to achieve this target depends on the baseline prevalence and the coverage used. For low- and moderate-transmission areas, EPHP can be achieved within 7 years if NT ≤10% and NT <5%, respectively. In high-transmission areas, community-wide treatment with NT <1% is required to achieve EPHP. CONCLUSIONS: The higher the intensity of transmission, and the lower the treatment coverage, the lower the acceptable value of NT becomes. Using more efficacious treatment regimens would permit NT values to be marginally higher. A balance between target treatment coverage and NT values may be an adequate treatment strategy depending on the epidemiological setting, but striving to increase coverage and/or minimize NT can shorten program duration.

Compliance with tetracycline eye ointment during annual mass drug administration for trachoma control in the Amhara region, Ethiopia.

OBJECTIVES: A 6-week course of tetracycline eye ointment is an alternative to single -dose oral azithromycin in annual mass drug administration for trachoma control. Compliance with the recommended tetracycline eye ointment regimen has not been well characterised when administered as part of a trachoma control program. METHODS: A routine mass drug administration for trachoma was carried out in 40 communities in the Amhara region of Ethiopia. Two tubes of tetracycline eye ointment, to be administered twice daily for 6 weeks, was offered to all children under 6 months of age, to pregnant women who declined to take azithromycin, and to all individuals with a macrolide allergy. Seven weeks following the mass drug administration, a treatment compliance survey was performed for all community members documented to have received tetracycline eye ointment during the mass drug administration. RESULTS: Of the 491 individuals documented as having received tetracycline eye ointment from the treatment records, 367 completed the survey, of which 214 recalled being offered tetracycline eye ointment. A total of 105 (49%) respondents reported taking ≥1 daily dose of tetracycline eye ointment on most days of the week for at least the first week. Only 20 (9%) respondents reported taking at least 1 tetracycline eye ointment dose per week for 6 weeks. The most common reasons for low compliance included 'saving it for a future infection' and 'stopped because I (or my child) seemed healthy'. The odds of low compliance were greater for those who reported not having adequate counselling (e.g., odds ratio [OR] 5.3, 95% CI 2.5-28.9 when low compliance was defined as not taking a tetracycline eye ointment dose for most days of at least the first week). CONCLUSIONS: Compliance with tetracycline eye ointment was low when administered by a trachoma program during a routine mass drug administration, especially for those reporting inadequate counselling. Further research with a larger sample size and varied settings is warranted to better understand and improve compliance.

A dynamic game of lymphatic filariasis prevention by voluntary use of insecticide treated nets.

Lymphatic filariasis (LF) has been targeted for elimination as a public health concern by 2030 with a goal to keep the prevalence of LF infections under the 1% threshold. While mass drug administration (MDA) is a primary strategy recommended by WHO, the use of insecticide treated nets (ITN) plays a crucial role as an alternative strategy when MDA cannot be used. In this paper, we use imitation dynamics to incorporate human behavior and voluntary use of ITN into the compartmental epidemiological model of LF transmission. We find the equilibrium states of the dynamics and the ITN usage as it depends on epidemiological parameters and the cost of ITNs. We investigate the conditions under which the voluntary use of ITNs can keep the LF prevalence under the 1% threshold. We found that when the cost of using the ITNs is about 105 smaller than the perceived cost of LF, then the voluntary use of ITNs will eliminate LF as a public health concern. Furthermore, when the ITNs are given away for free, our model predicts that over 80% of the population will use them which would eliminate LF completely in regions where Anopheles are the primary vectors.

Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized. METHODS: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13-a molecular marker of artemisinin resistance. RESULT: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p < 0.001). In the MDA villages there was no significant change in the K13 proportions before and after MDA. The distribution of different K13 mutations changed substantially; F446I and P441L mutations increased in both MDA and non-MDA villages, while most other K13 mutations decreased. The proportion of C580Y mutations fell from 9.2% (43/467) before MDA to 2.3% (19/813) after MDA (p < 0.001). Similar changes occurred in the 487 villages where MDA was not conducted. CONCLUSION: The malaria elimination program in Kayin state, eastern Myanmar, led to a substantial reduction in falciparum malaria. Despite the intense use of artemisinin-based combination therapies, both in treatment and MDA, this did not select for artemisinin resistance.

Test-treat-track-test-treat (5T) approach for Schistosoma haematobium elimination on Pemba Island, Tanzania.

BACKGROUND: After decades of praziquantel mass drug administration (MDA), several countries approach schistosomiasis elimination. Continuing MDA in largely uninfected populations no longer seems justified. Alternative interventions to maintain the gains or accelerate interruption of transmission are needed. We report results, strengths, and shortcomings of novel test-treat-track-test-treat (5T) interventions in low Schistosoma haematobium prevalence areas on Pemba, Tanzania. METHODS: School- and household-based surveys were conducted in 2021 and 2022 to monitor the S. haematobium and microhematuria prevalence and assess the impact of interventions. In 2021, 5T interventions were implemented in 15 low-prevalence areas and included: (i) testing schoolchildren in primary and Islamic schools for microhematuria as a proxy for S. haematobium, (ii) treating positive children, (iii) tracking them to their households and to water bodies they frequented, (iv) testing individuals at households and water bodies, and (v) treating positive individuals. Additionally, test-and-treat interventions were implemented in the 22 health facilities of the study area. RESULTS: The S. haematobium prevalence in the school-based survey in 15 low-prevalence implementation units was 0.5% (7/1560) in 2021 and 0.4% (6/1645) in 2022. In the household-based survey, 0.5% (14/2975) and 0.7% (19/2920) of participants were infected with S. haematobium in 2021 and 2022, respectively. The microhematuria prevalence, excluding trace results, in the school-based survey was 1.4% (21/1560) in 2021 and 1.5% (24/1645) in 2022. In the household-based survey, it was 3.3% (98/2975) in 2021 and 5.4% (159/2920) in 2022. During the 5T interventions, the microhaematuria prevalence was 3.8% (140/3700) and 5.8% (34/594) in children in primary and Islamic schools, respectively, 17.1% (44/258) in household members, and 16.7% (10/60) in people at water bodies. In health facilities, 19.8% (70/354) of patients tested microhematuria-positive. CONCLUSIONS: The targeted 5T interventions maintained the very low S. haematobium prevalence and proved straightforward and feasible to identify and treat many of the few S. haematobium-infected individuals. Future research will show whether 5T interventions can maintain gains in the longer-term and expedite elimination. TRIAL REGISTRATION: ISRCTN, ISCRCTN91431493. Registered 11 February 2020, https://www.isrctn.com/ISRCTN91431493 .

Mass drug administration campaigns: comparing two approaches for schistosomiasis and soil-transmitted helminths prevention and control in selected Southern Malawi districts.

BACKGROUND: Mass drug administration is one of the key interventions recommended by WHO to control certain NTDs. With most support from donors, health workers distribute antihelminthic drugs annually in Malawi. Mean community coverage of MDA from 2018 to 2020 was high at 87% for praziquantel and 82% for albendazole. However, once donor support diminishes sustaining these levels will be challenging. This study intended to compare the use of the community-directed intervention approach with the standard practice of using health workers in delivery of MDA campaigns. METHODS: This was a controlled implementation study carried out in three districts, where four health centres and 16 villages in each district were selected and randomly assigned to intervention and control arms which implemented MDA campaigns using the CDI approach and the standard practice, respectively. Cross-sectional and mixed methods approach to data collection was used focusing on quantitative data for coverage and knowledge levels and qualitative data to assess perceptions of health providers and beneficiaries at baseline and follow-up assessments. Quantitative and qualitative data were analyzed using IBM SPSS software version 26 and NVivo 12 for Windows, respectively. RESULTS: At follow-up, knowledge levels increased, majority of the respondents were more knowledgeable about what schistosomiasis was (41%-44%), its causes (41%-44%) and what STH were (48%-64%), while knowledge on intermediate host for schistosomiasis (19%-22%), its types (9%-13%) and what causes STH (15%-16%) were less known both in intervention and control arm communities. High coverage rates for praziquantel were registered in intervention (83%-89%) and control (86%-89%) communities, intervention (59%-79) and control (53%-86%) schools. Costs for implementation of the study indicated that the intervention arm used more resources than the control arm. Health workers and community members perceived the use of the CDI approach as a good initiative and more favorable over the standard practice. CONCLUSIONS: The use of the CDI in delivery of MDA campaigns against schistosomiasis and STH appears feasible, retains high coverages and is acceptable in intervention communities. Despite the initial high costs incurred, embedding into community delivery platforms could be considered as a possible way forward addressing the sustainability concern when current donor support wanes. TRIAL REGISTRATION: Pan-African Clinical Trials Registry PACTR202102477794401, date: 25/02/2021.

Targeted Mass Azithromycin Distribution for Trachoma: A Community-Randomized Trial (TANA II).

BACKGROUND: Current guidelines recommend annual community-wide mass administration of azithromycin for trachoma. Targeting treatments to those most likely to be infected could reduce the amount of unnecessary antibiotics distributed. METHODS: In a cluster-randomized trial conducted from 1 November 2010 through 8 November 2013, 48 Ethiopian communities previously treated with annual mass azithromycin distributions for trachoma were randomized in equal numbers to (1) annual azithromycin distributions targeted to children aged 0-5 years, (2) annual azithromycin distributions targeted to households with a child aged 0-5 years found to have clinically active trachoma, (3) continued annual mass azithromycin distributions to the entire community, or (4) cessation of treatment. The primary outcome was the community prevalence of ocular chlamydia infection among children aged 0-9 years at month 36. Laboratory personnel were masked to treatment allocation. RESULTS: The prevalence of ocular chlamydia infection among children aged 0-9 years increased from 4.3% (95% confidence interval [CI], .9%-8.6%) at baseline to 8.7% (95% CI, 4.2%-13.9%) at month 36 in the age-targeted arm, and from 2.8% (95% CI, .8%-5.3%) at baseline to 6.3% (95% CI, 2.9%-10.6%) at month 36 in the household-targeted arm. After adjusting for baseline chlamydia prevalence, the 36-month prevalence of ocular chlamydia was 2.4 percentage points greater in the age-targeted group (95% CI, -4.8% to 9.6%; P = .50; prespecified primary analysis). No adverse events were reported. CONCLUSIONS: Targeting azithromycin treatment to preschool children was no different than targeting azithromycin to households with a child with clinically active trachoma. Neither approach reduced ocular chlamydia over the 3-year study. CLINICAL TRIALS REGISTRATION: NCT01202331.

When the Neighboring Village is Not Treated: Role of Geographic Proximity to Communities Not Receiving Mass Antibiotics for Trachoma.

BACKGROUND: Mass administration of azithromycin is an established strategy for decreasing the prevalence of trachoma in endemic areas. However, nearby untreated communities could serve as a reservoir that may increase the chances of chlamydia reinfection in treated communities. METHODS: As part of a cluster-randomized trial in Ethiopia, 60 communities were randomized to receive mass azithromycin distributions and 12 communities were randomized to no treatments until after the first year. Ocular chlamydia was assessed from a random sample of children per community at baseline and month 12. Distances between treated and untreated communities were assessed from global positioning system coordinates collected for the study. RESULTS: The pretreatment prevalence of ocular chlamydia among 0 to 9 year olds was 43% (95% confidence interval [CI], 39%-47%), which decreased to 11% (95% CI, 9%-14%) at the 12-month visit. The posttreatment prevalence of chlamydia was significantly higher in communities that were closer to an untreated community after adjusting for baseline prevalence and the number of mass treatments during the year (odds ratio, 1.12 [95% CI, 1.03-1.22] for each 1 km closer to an untreated community). CONCLUSIONS: Mass azithromycin distributions to wide, contiguous geographic areas may reduce the likelihood of continued ocular chlamydia infection in the setting of mass antibiotic treatments.

Effect of large-scale mass drug administration for malaria on mortality and morbidity in Angumu health zone, Ituri, Democratic Republic of Congo.

BACKGROUND: Angumu health zone in Ituri, Democratic Republic of Congo, is a highly malaria-endemic area with an overburdened health system and hosting internally displaced persons (IDP). The World Health Organization recommends mass drug administration (MDA) for malaria in complex emergencies. Therefore, three MDA rounds were implemented by Ministry of Public Health and Médecins sans Frontières from September 2020 to January 2021 in four health areas selected for epidemiological (high malaria incidence) and logistic reasons. Reported mortality and morbidity were compared in locations where MDA has been performed and locations where it has not. METHODS: A non-randomized controlled population-based retrospective mortality survey was conducted in March 2021. Two-stage cluster sampling was used in villages; all IDP sites were surveyed with systematic random sampling. The main (mortality rates) and secondary (morbidity) outcomes were estimated and compared between locations where MDA had been conducted and where it had not, using mixed Poisson and binomial regression models respectively. RESULTS: Data was collected for 2554 households and 15470 individuals, of whom 721 died in the 18-month recall period. The under-five mortality rate (U5MR) decreased in the locations where MDA had been implemented from 2.32 [1.48-3.16] "before" the MDA to 1.10 [0.5-1.71] deaths/10,000 children under 5 years/day "after", whereas it remained stable from 2.74 [2.08-3.40] to 2.67 [1.84-3.50] deaths/10,000 children/day in the same time periods in locations where MDA had not been implemented. The U5MR and malaria-specific mortality was significantly higher in non-MDA locations after MDA was implemented (aRR = 2.17 [1.36-3.49] and 2.60 [1.56-4.33], respectively, for all-cause and malaria-specific mortality among children < 5 years). Morbidity (all age and < 5 years, all cause or malaria-specific) appeared lower in MDA locations 2.5 months after last round: reported malaria-specific morbidity was 14.7% [11-18] and 25.0% [19-31] in villages and IDP sites where MDA had been implemented, while it was 30.4% [27-33] and 49.3% [45-54] in villages and IDP sites with no MDA. CONCLUSIONS: Despite traditional limitations associated with non-randomized controlled retrospective surveys, the documented sharp decrease of under-5 mortality and morbidity shows that MDA has the potential to become an important malaria-control tool in emergency settings. Based on these results, new MDA rounds, along with indoor residual spraying campaigns, have been planned in the health zone in 2022. A set of surveys will be conducted before, during and after these rounds to confirm the effect observed in 2021 and assess its duration.

Community acceptability, participation, and adherence to mass drug administration with primaquine for Plasmodium vivax elimination in Southern Thailand: a mixed methods approach.

BACKGROUND: Mass drug administration (MDA) with primaquine (PQ) is being considered for accelerating Plasmodium vivax elimination in remaining active foci. This study aimed to determine the acceptability of MDA with PQ in malaria endemic villages in a malarious setting in the South of Thailand undergoing MDA with PQ. METHODS: A cross-sectional mixed-methods approach was conducted in seven malaria endemic villages where MDA with PQ was implemented. The data were collected from community villagers and health workers using structured questionnaires, in-depth interviews, and focus group discussions. Descriptive statistics and logistic regression models were used for quantitative data analysis. Thematic analysis was applied for qualitative data. RESULTS: Among a total of 469 participants from the MDA villages, 293 participants were eligible for MDA with PQ and 79.86% (234) completed 14-days of PQ. The logistic regressions indicated that males (adjusted odds ratio: 2.52 [95% confidence interval: 1.33-4.81]) and those who are farmers (2.57 [1.12-5.90]) were most likely to participate in the MDA. Among 293 participants in the post-MDA study, 74.06% had originally agreed to participate in the MDA with PQ while 25.94% had originally reported not wanting to participate in the MDA. Of those who originally reported being willing to participate in the MDA, 71.23% followed through with participation in the first or second round. Conversely, 93.24% of those who originally reported not being willing to participate in the MDA did in fact participate in the MDA. Factors contributing to higher odds of agreeing to participate and following through with participation included being male (1.98 [1.06-3.69]) and correctly responding that malaria is preventable (2.32 [1.01-5.35]) with some differences by village. Five key themes emerged from the qualitative analyses: concern about side effects from taking PQ; disbelief that malaria could be eliminated in this setting; low overall concern about malaria infections; misunderstandings about malaria; and a general need to tailor public health efforts for this unique context. CONCLUSION: While the reported likelihood of participating in MDA was high in this setting, actual follow-through was relatively moderate, partially because of eligibility (roughly 71% of those in the follow-up survey who originally agreed to participate actually followed through with participation). One of the largest concerns among study participants was PQ-related side effects-and these concerns likely heavily influenced participant adherence to the MDA. The results of this study can be used to tailor future MDAs, or other public health interventions, in this and potentially other similar settings.

Prevalence of Schistosoma mansoni, soil-transmitted helminths and intestinal protozoa in orphans and street children in Mwanza city, Northern Tanzania.

BACKGROUND: Parasitic infections are highly prevalent in low-income environments worldwide. While orphans and street children represent a particularly vulnerable population group, they are often exempt from preventive interventions such as Mass Drug Administration. In part, this could be due to a lack of data showing the burden of disease in this group. This study aims to address this gap. METHODS: For this cross-sectional study, 144 orphans and 112 street children were screened for Schistosoma mansoni (S. mansoni), Schistosoma haematobium (S. haematobium), soil-transmitted helminths and intestinal protozoa using POC-CCA testing, urine filtration, and Kato-Katz technique. Nutritional status, water- and washing patterns were determined using a standardised questionnaire. Ultrasonography was performed to screen for organ abnormalities. RESULTS: The prevalence of S. mansoni determined by POC-CCA-test was 65.9% for orphans and 94.5% for street children. 19.2% of the orphans tested positive for S. mansoni in Kato Katz. Of the street children, 77.1% showed positive test results in Kato-Katz. Only 1.3% of the orphans stated in the questionnaire that they use the lake to wash, whereas 91.1% of the street children named the lake as at least one of their options for washing. Microscopy showed positive results for Giardia intestinalis (G. intestinalis) in 8.2% and for Entamoeba histolytica/dispar (E. histolytica/dispar) in 23% of orphans and 8.1% for G. intestinalis, and 23.8% for E. histolytica/dispar in street children. In the ultrasonography, we did not observe patterns that indicate severe periportal fibrosis. CONCLUSION: The results indicate a significantly higher rate of infections with S. mansoni in street children compared with orphans. This might be explained by the lack of access to adequate sanitation for street children as well as regular contact with the water of Lake Victoria. However, we did not find similar results concerning infection rates with protozoa. The study results show overall inadequate living conditions in this study population, which could be addressed by public health interventions.

Non-adherence to ivermectin in onchocerciasis-endemic communities with persistent infection in the Bono Region of Ghana: a mixed-methods study.

BACKGROUND: The World Health Organization has proposed that onchocerciasis elimination (interruption) of transmission be verified in 12 (approximately a third) endemic countries by 2030. The strategy to reach this goal is based on ivermectin Mass Drug Administration (MDA) with high geographical and therapeutic coverage. In addition to coverage, high levels of treatment adherence are paramount. We investigated factors associated with ivermectin intake in an area of Ghana with persistent Onchocerca volvulus infection. METHODS: In August 2021, a cross-sectional mixed-methods study was conducted in 13 onchocerciasis-endemic communities in the Bono Region of Ghana. Individuals aged ≥ 10 years were invited to participate in a questionnaire survey. A total of 48 focus group discussions and in-depth interviews with 10 community drug distributors and 13 community leaders were conducted. RESULTS: A total of 510 people participated in the study [median age: 32, interquartile range 30 (20‒50) years]; 274 (53.7%) were females. Of the total, 320 (62.7%) declared that they adhered to each treatment round and 190 (37.3%) admitted they had not taken ivermectin during at least one MDA round, since becoming eligible for treatment. Of 483 participants with complete information, 139 (28.8%) did not take ivermectin during the last round (March 2021), and 24 (5.0%) had never taken ivermectin (systematic non-adherers). Reasons for not taking ivermectin included previous experience/fear of side-effects, being absent during MDA, pregnancy, the desire to drink alcohol, and drug distribution challenges. Being male, having good knowledge and perception of the disease, and not having secondary or higher level of formal education were significantly associated with higher odds of ivermectin intake. CONCLUSIONS: A relatively high level of non-adherence to ivermectin treatment was documented. There is a need for targeted educational and behavioural change campaigns to reverse these trends and ensure a steady course toward meeting onchocerciasis elimination targets in Ghana.

Modelling mass drug administration strategies for reducing scabies burden in Monrovia, Liberia.

Scabies is a parasitic infestation with high global burden. Mass drug administrations (MDAs) are recommended for communities with a scabies prevalence of >10%. Quantitative analyses are needed to demonstrate the likely effectiveness of MDA recommendations. In this study, we developed an agent-based model of scabies transmission calibrated to demographic and epidemiological data from Monrovia. We used this model to compare the effectiveness of MDA scenarios for achieving scabies elimination and reducing scabies burden, as measured by time until recrudescence following delivery of an MDA and disability-adjusted-life-years (DALYs) averted. Our model showed that three rounds of MDA delivered at six-month intervals and reaching 80% of the population could reduce prevalence below 2% for three years following the final round, before recrudescence. When MDAs were followed by increased treatment uptake, prevalence was maintained below 2% indefinitely. Increasing the number of and coverage of MDA rounds increased the probability of achieving elimination and the number of DALYs averted. Our results suggest that acute reduction of scabies prevalence by MDA can support a transition to improved treatment access. This study demonstrates how modelling can be used to estimate the expected impact of MDAs by projecting future epidemiological dynamics and health gains under alternative scenarios.

Optimal Interruption of P. vivax Malaria Transmission Using Mass Drug Administration.

Plasmodium vivax is the most geographically widespread malaria-causing parasite resulting in significant associated global morbidity and mortality. One of the factors driving this widespread phenomenon is the ability of the parasites to remain dormant in the liver. Known as 'hypnozoites', they reside in the liver following an initial exposure, before activating later to cause further infections, referred to as 'relapses'. As around 79-96% of infections are attributed to relapses from activating hypnozoites, we expect it will be highly impactful to apply treatment to target the hypnozoite reservoir (i.e. the collection of dormant parasites) to eliminate P. vivax. Treatment with radical cure, for example tafenoquine or primaquine, to target the hypnozoite reservoir is a potential tool to control and/or eliminate P. vivax. We have developed a deterministic multiscale mathematical model as a system of integro-differential equations that captures the complex dynamics of P. vivax hypnozoites and the effect of hypnozoite relapse on disease transmission. Here, we use our multiscale model to study the anticipated effect of radical cure treatment administered via a mass drug administration (MDA) program. We implement multiple rounds of MDA with a fixed interval between rounds, starting from different steady-state disease prevalences. We then construct an optimisation model with three different objective functions motivated on a public health basis to obtain the optimal MDA interval. We also incorporate mosquito seasonality in our model to study its effect on the optimal treatment regime. We find that the effect of MDA interventions is temporary and depends on the pre-intervention disease prevalence (and choice of model parameters) as well as the number of MDA rounds under consideration. The optimal interval between MDA rounds also depends on the objective (combinations of expected intervention outcomes). We find radical cure alone may not be enough to lead to P. vivax elimination under our mathematical model (and choice of model parameters) since the prevalence of infection eventually returns to pre-MDA levels.

Cost and community acceptability of enhanced antibiotic distribution approaches for trachoma in the Republic of South Sudan: enhancing the A in SAFE (ETAS) study protocol.

BACKGROUND: The World Health Organization targeted trachoma for global elimination as a public health problem by 2030. Reaching elimination thresholds by the year 2030 in the Republic of South Sudan will be a considerable challenge, as the country currently has many counties considered hyper-endemic (> 30% trachomatous inflammation-follicular [TF]) that have yet to receive interventions. Evidence from randomized trials, modeling, and population-based surveys suggests that enhancements may be needed to the standard-of-care annual mass drug administration (MDA) to reach elimination thresholds in a timely manner within highly endemic areas. We describe a protocol for a study to determine the cost and community acceptability of enhanced antibiotic strategies for trachoma in South Sudan. METHODS: The Enhancing the A in SAFE (ETAS) study is a community randomized intervention costing and community acceptability study. Following a population-based trachoma prevalence survey in 1 county, 30 communities will be randomized 1:1 to receive 1 of 2 enhanced MDA interventions, with the remaining communities receiving standard-of-care annual MDA. The first intervention strategy will consist of a community-wide MDA followed by 2 rounds of targeted treatment to children ages 6 months to 9 years, 2 weeks and 4 weeks after the community MDA. The second strategy will consist of a community-wide biannual MDA approximately 6 to 8 months apart. The costing analysis will use a payer perspective and identify the total cost of the enhanced interventions and annual MDA. Community acceptability will be assessed through MDA coverage monitoring and mixed-methods research involving community stakeholders. A second trachoma-specific survey will be conducted 12 months following the original survey. DISCUSSION: ETAS has received ethical clearance and is expected to be conducted between 2022 and 2023. Results will be shared through subsequent manuscripts. The study's results will provide information to trachoma programs on whether enhanced interventions are affordable and acceptable to communities. These results will further help in the design of future trachoma-specific antibiotic efficacy trials. Enhanced MDA approaches could help countries recover from delays caused by conflict or humanitarian emergencies and could also assist countries such as South Sudan in reaching trachoma elimination as a public health problem by 2030. TRIAL REGISTRATION: This trial was registered on December 1st, 2022 (clinicaltrails.org: NCT05634759).

Health-seeking behaviour regarding schistosomiasis treatment in the absence of a mass drug administration (MDA) program: the case of endemic communities along Lake Albert in Western Uganda.

INTRODUCTION: Schistosomiasis poses a serious public health problem and a social challenge affecting over 240 million people, the majority of whom live in sub-Saharan Africa. The World Health Organization (WHO) recommends praziquantel (PZQ) drug treatment through regular mass drug administration (MDA) accompanied by social mobilisation and health education and sensitisation. With social mobilisation and health education and sensitisation, there is bound to be increased demand for the PZQ, especially in the case of endemic communities. However, it is not clear where communities go for PZQ treatment in the absence of PZQ MDA. We explored the health-seeking behaviours regarding schistosomiasis treatment among communities along Lake Albert in Western Uganda when MDA had delayed, to inform a review of the implementation policy for the achievement of the WHO's 2030 target of 75% coverage and uptake. METHODS AND MATERIALS: We conducted a community-based qualitative study in Kagadi and Ntoroko, an endemic community in January and February 2020. We interviewed 12 individuals: local leaders, village health teams, and health workers, and conducted 28 focus group discussion sessions with 251 purposively selected community members. The audio recordings of the data were transcribed and analyzed using a thematic analysis model. RESULTS: Generally, participants seldom seek medication for schistosomiasis-related signs and symptoms from government hospitals and health centres II, III and IV. Instead, they rely on community volunteers such as VHTs, private facilities, such as clinics and drug shops nearby, or traditional sources (e.g. witch doctors and herbalists). Results show that factors influencing people to seek treatment from sources other than the government are: the absence of PZQ drugs in the government health facility; health workers' negative attitude towards patients; long distances to the government hospitals and health facilities; poor and inaccessible roads; medication-related costs; and negative perceptions of the PZQ drug. CONCLUSIONS: Availability and accessibility of PZQ seem to be a big challenge. PZQ uptake is further hampered by health systems and community-related and socio-cultural factors. Thus there is a need to bring schistosomiasis drug treatment and services closer to endemic communities, stock nearby facilities with PZQ and encourage endemic communities to take the drug. Contextualised awareness-raising campaigns are needed to debunk myths and misconceptions surrounding the drug.

Human schistosomiasis in Nigeria: present status, diagnosis, chemotherapy, and herbal medicines.

Schistosomiasis is a neglected tropical disease caused by a parasitic, trematode blood fluke of the genus Schistosoma. With 20 million people infected, mostly due to Schistosoma haematobium, Nigeria has the highest burden of schistosomiasis in the world. We review the status of human schistosomiasis in Nigeria regarding its distribution, prevalence, diagnosis, prevention, orthodox and traditional treatments, as well as snail control strategies. Of the country's 36 states, the highest disease prevalence is found in Lagos State, but at a geo-political zonal level, the northwest is the most endemic. The predominantly used diagnostic techniques are based on microscopy. Other methods such as antibody-based serological assays and DNA detection methods are rarely employed. Possible biomarkers of disease have been identified in fecal and blood samples from patients. With respect to preventive chemotherapy, mass drug administration with praziquantel as well as individual studies with artemisinin or albendazole have been reported in 11 out of the 36 states with cure rates between 51.1 and 100%. Also, Nigerian medicinal plants have been traditionally used as anti-schistosomal agents or molluscicides, of which Tetrapleura tetraptera (Oshosho, aridan, Aidan fruit), Carica papaya (Gwanda, Ìbépe, Pawpaw), Borreria verticillata (Karya garma, Irawo-ile, African borreria), and Calliandra portoricensis (Tude, Oga, corpse awakener) are most common in the scientific literature. We conclude that the high endemicity of the disease in Nigeria is associated with the limited application of various diagnostic tools and preventive chemotherapy efforts as well as poor knowledge, attitudes, and practices (KAP). Nonetheless, the country could serve as a scientific base in the discovery of biomarkers, as well as novel plant-derived schistosomicides and molluscicides.

Critical medical ecology and intersectionality perspectives in schistosomiasis prevention and control in selected communities in Mindanao, the Philippines.

Schistosomiasis japonica remains a public health concern in many areas of the Philippines. Periodic Mass Drug Administration (MDA) to at-risk populations is the main strategy for morbidity control of schistosomiasis. Attaining MDA coverage targets is important for the reduction of morbidity and prevention of complications due to the disease, and towards achieving Universal Health Care. The study employed a qualitative case study design. Key informant interviews and focus group discussions were conducted to provide in-depth and situated descriptions of the contexts surrounding the implementation of MDA in two selected villages in known schistosomiasis-endemic provinces in Mindanao in the Philippines. Data analysis was done using the Critical Ecology for Medical Anthropology (CEMA) model coupled with the intersectionality approach. It was found that within various areas in the CEMA model, enabling as well as constraining factors have been encountered in MDA in the study settings. The interplay of income class, geographical location, gender norms and faith-based beliefs may have led to key populations being missed during the conduct of MDA in the study sites. The constraints faced by the target beneficiaries of MDA, as well as programme implementers, must be addressed to enhance service delivery and to control morbidity due to schistosomiasis. Improving compliance with MDA also requires a holistic, integrated approach to addressing barriers to participation, which are shaped by wider socio-political and power structures.

Coverage and compliance of mass drug administration (MDA) programme for elimination of lymphatic filariasis in an endemic district of eastern Uttar Pradesh, India.

BACKGROUND & OBJECTIVES: Lymphatic filariasis is targeted for elimination in India through mass drug administration (MDA) with diethylcarbamazine (DEC) combined with albendazole (ABZ). To assess the coverage, compliance and causes for non-compliance towards MDA in an endemic district of Uttar Pradesh (U.P.), north India. METHODS: A cross-sectional coverage evaluation survey was conducted in 24 rural and 6 urban clusters of Ghazipur district in eastern U.P. using multi-stage random sampling technique with probability proportional to estimated size (PPES). Data was collected in a semi-structured Performa from all the individuals in the selected households by interview technique. Bivariate analysis was performed to identify the factors associated with non-consumption of MDA drugs. RESULTS: A total of 1422 individuals were surveyed from 30 randomly selected subunits of which 1401 (98.5%) were eligible for MDA at the time of the round. Majority of the participants were in the age-group of 15-59 years (67.0%) and were males (53.3%). The overall coverage of MDA (both drugs) among the eligible population in Ghazipur district was 58.5%. Compliance among those who had received both the drugs was 61.6% with effective coverage of 36.0%. The coverage was significantly higher in rural areas compared to the urban clusters (p<0.0001). The most common reason quoted for not consuming drugs was fear of side effects (34.9%). However, the incidence of adverse events among those who consumed the drugs was only 2.5%. None of the socio-demographic variables showed a significant association with the compliance to the drugs. INTERPRETATION & CONCLUSION: Coverage and compliance of MDA in Ghazipur district of U.P., India was found to be below satisfactory levels. Targeted Information Education and Communication (IEC) campaigns focusing on the safety of drugs and the necessity of MDA, and mass mobilization with effective monitoring and supervision is the need of the hour for effective coverage of MDA Programme.