Impact of Community Mass Treatment with Azithromycin for Trachoma Elimination on the Prevalence of Yaws

Background

Community mass treatment with 30mg/kg azithromycin is central to the new WHO strategy for eradicating yaws. Both yaws and trachoma— which is earmarked for elimination by 2020 using a strategy that includes mass treatment with 20mg/kg azithromycin—are endemic in the Pacific, raising the possibility of an integrated approach to disease control. Community mass treatment with azithromycin for trachoma elimination was conducted in the Solomon Islands in 2014.

Methods

We conducted a study to assess the impact of mass treatment with 20mg/kg azithromycin on yaws. We examined children aged 5-14 years and took blood and lesion samples for yaws diagnosis.

Results

We recruited 897 children, 6 months after mass treatment. There were no cases of active yaws. Serological evidence of current infection was found in 3.6% (95% CI= 2.5-5.0%). This differed significantly between individuals who had and had not received azithromycin (2.8% vs 6.5%, p=0.015); the prevalence of positive serology in 5-14 year-olds had been 21.7% (95% CI=14.6%-30.9%) 6 months prior to mass treatment. Not receiving azithromycin was associated with an odds of 3.9 for infection (p=0.001). National figures showed a 57% reduction in reported cases of yaws following mass treatment.

Discussion

Following a single round of treatment we did not identify any cases of active yaws in a previously endemic population. We found a significant reduction in latent infection. Our data support expansion of the WHO eradication strategy and suggest an integrated approach to the control of yaws and trachoma in the Pacific may be viable.     

Prevalence of Trachoma at Sub-District Level in Ethiopia: Determining When to Stop Mass Azithromycin Distribution

Background

To eliminate blinding trachoma, the World Health Organization emphasizes implementing the SAFE strategy, which includes annual mass drug administration (MDA) with azithromycin to the whole population of endemic districts. Prevalence surveys to assess impact at the district level are recommended after at least 3 years of intervention. The decision to stop MDA is based on a prevalence of trachomatous inflammation follicular (TF) among children aged 1–9 years below 5% at the sub-district level, as determined by an additional round of surveys limited within districts where TF prevalence is below 10%. We conducted impact surveys powered to estimate prevalence simultaneously at the sub-district and district in two zones of Amhara, Ethiopia to determine whether MDA could be stopped.

Methodology

Seventy-two separate population-based, sub-district surveys were conducted in 25 districts. In each survey all residents from 10 randomly selected clusters were screened for clinical signs of trachoma. Data were weighted according to selection probabilities and adjusted for correlation due to clustering.

Principal Findings

Overall, 89,735 residents were registered from 21,327 households of whom 72,452 people (80.7%) were examined. The prevalence of TF in children aged 1–9 years was below 5% in six sub-districts and two districts. Sub-district level prevalence of TF in children aged 1–9 years ranged from 0.9–76.9% and district-level from 0.9–67.0%. In only one district was the prevalence of trichiasis below 0.1%.

Conclusions/Significance

The experience from these zones in Ethiopia demonstrates that impact assessments designed to give a prevalence estimate of TF at sub-district level are possible, although the scale of the work was challenging. Given the assessed district-level prevalence of TF, sub-district-level surveys would have been warranted in only five districts. Interpretation was not as simple as stopping MDA in sub-districts below 5% given programmatic challenges of exempting sub-districts from a highly regarded program and the proximity of hyper-endemic sub-districts.     

Mass Treatment with Azithromycin for Trachoma Control: Participation Clusters in Households

Background

Mass treatment to trachoma endemic communities is a critical part of the World Health Organization SAFE strategy. However, non-participation may not be at random, affecting coverage surveys and effectiveness if infection is differential.

Methodology/Principal Findings

As part of the Partnership for Rapid Elimination of Trachoma (PRET), 32 communities in Tanzania, and 48 in The Gambia had a detailed census taken followed by mass treatment with azithromycin. The target coverage in each community was >80% of children ages <10 years. Community treatment assistants observed treatment and recorded compliance, thus coverage at the community, household, and individual level could be determined. Within each community, we determined the actual proportions of households where all, some, or none of the children were treated. Assuming the coverage in children <10 years of the community was as observed and non-participation was at random, we did 500 simulations to derive expected proportions of households where all, some, or none of the children were treated. Clustering of household treatment was detected comparing greater-than-expected proportions of households where none or all of children were treated, and the intraclass correlation (ICC) was calculated. Tanzanian and Gambian mass treatment coverages for children <10 years of age ranged from 82–100% and 62–99%, respectively. Clustering of households where all children were treated or no children were treated was greater than expected. Compared to model simulations, all Tanzanian communities and 44 of 48 (91.7%) Gambian communities had significantly higher proportions of households where all children were treated. Furthermore, 30 of 32 (93.8%) Tanzanian communities and 34 of 48 (70.8%) Gambian communities had a significantly elevated proportion of households compared to the expected proportion where no children were treated. The ICC for Tanzania was 0.77 (95% CI 0.74–0.81) and for The Gambia was 0.55 (95% CI 0.51–0.59).

Conclusions/Significance

In programs aiming for high coverage, complete compliance or non-compliance with mass treatment clusters within households. Non-compliance cannot be assumed to be at random.     

Uptake of Mass Drug Administration Programme for Schistosomiasis Control in Koome Islands,Central Uganda

Introduction

Schistosomiasis is one of the neglected tropical diseases targeted for elimination in Uganda through the Mass Drug Administration (MDA) programme. Praziquantel has been distributed using community resource persons in fixed sites and house-to-house visits; however the uptake is still below target coverage. In 2011/2012 MDA exercise, uptake stood at 50% yet WHO target coverage is 75% at community level. We assessed the uptake of MDA and the associated factors in Koome Islands, Central Uganda.

Methods

In March 2013, we conducted a mixed methods cross sectional study in 15 randomly selected villages. We interviewed a total of 615 respondents aged 18 years and above using semi structured questionnaires and five key informants were also purposively selected. Univariate and multivariate analysis was done. MDA uptake was defined as self reported swallowing of praziquantel during the last (2012) MDA campaign. We conducted key informant interviews with Ministry of Health, district health personnel and community health workers.

Results

Self reported uptake of praziquantel was 44.7% (275/615), 95% confidence interval (CI) 40.8–48.7%. Of the 275 community members who said they had swallowed praziquantel, 142 (51.6%) reported that they had developed side effects. Uptake of MDA was more likely if the respondent was knowledgeable about schistosomiasis transmission and prevention (adjusted odds ratio [AOR] 1.85, 95% CI 1.22–2.81) and reported to have received health education from the health personnel (AOR 5.95, 95% CI 3.67–9.65). Service delivery challenges such as drug shortages and community health worker attrition also influenced MDA in Koome Islands.

Conclusions

Uptake of MDA for schistosomiasis control in Koome was sub optimal. Lack of knowledge about schistosomiasis transmission and prevention, inadequate health education and drug shortages are some of the major factors associated with low uptake. These could be addressed through routine health education and systematic drug supply for the successful elimination of schistosomiasis on the islands.     

Prevalence of abnormal glucose tolerance in six Solomon Islands populations

A survey of blood glucose levels in six Solomon Islands populations may support the hypothesis that susceptibility to diabetes is almost absent among non-Austronesian-speaking Melanesians regardless of their level of modernization. Among Austronesian-speaking Melanesians, however, diabetes is emerging. Differences in prevalence rates of diabetes between Austronesians and non-Austronesian speakers in this survey are significant (P less than .0001).     

Non-Participation during Azithromycin Mass Treatment for Trachoma in The Gambia: Heterogeneity and Risk Factors

Background

There is concern that untreated individuals in mass drug administration (MDA) programs for neglected tropical diseases can reduce the impact of elimination efforts by maintaining a source of transmission and re-infection.

Methodology/Principal Findings

Treatment receipt was recorded against the community census during three MDAs with azithromycin for trachoma in The Gambia, a hypo-endemic setting. Predictors of non-participation were investigated in 1–9 year olds using random effects logistic regression of cross-sectional data for each MDA. Two types of non-participators were identified: present during MDA but not treated (PNT) and eligible for treatment but absent during MDA (EBA). PNT and EBA children were compared to treated children separately. Multivariable models were developed using baseline data and validated using year one and two data, with a priori adjustment for previous treatment status. Analyses included approximately 10000 children at baseline and 5000 children subsequently. There was strong evidence of spatial heterogeneity, and persistent non-participation within households and individuals. By year two, non-participation increased significantly to 10.4% overall from 6.2% at baseline, with more, smaller geographical clusters of non-participating households. Multivariable models suggested household level predictors of non-participation (increased time to water and household head non-participation for both PNT and EBA; increased household size for PNT status only; non-inclusion in a previous trachoma examination survey and younger age for EBA only). Enhanced coverage efforts did not decrease non-participation. Few infected children were detected at year three and only one infected child was EBA previously. Infected children were in communities close to untreated endemic areas with higher rates of EBA non-participation during MDA.

Conclusions/Significance

In hypo-endemic settings, with good coverage and no association between non-participation and infection, efforts to improve participation during MDA may not be required. Further research could investigate spatial hotspots of infection and non-participation in other low and medium prevalence settings before allocating resources to increase participation.     

Prioritizing Countries for Interventions to Reduce Child Mortality: Tools for Maximizing the Impact of Mass Drug Administration of Azithromycin

Background

As new interventions to reduce childhood mortality are identified, careful consideration must be given to identifying populations that could benefit most from them. Promising reductions in childhood mortality reported in a large cluster randomized trial of mass drug administration (MDA) of azithromycin (AZM) prompted the development of visually compelling, easy-to-use tools that synthesize country-specific data on factors that would influence both potential AZM benefit and MDA implementation success.

Methodology/Principal Findings

We assessed the opportunity to reduce mortality and the feasibility of implementing such a program, creating Opportunity and Feasibility Indices, respectively. Countries with high childhood mortality were included. A Country Ranking Index combined key variables from the previous two Indices and applied a scoring system to identify high-priority countries. We compared four scenarios with varying weights given to each variable.Twenty-five countries met inclusion criteria. We created easily visualized tools to display the results of the Opportunity and Feasibility Indices. The Opportunity Index revealed substantial variation in the opportunity for an MDA of AZM program to reduce mortality, even among countries with high overall childhood mortality. The Feasibility Index demonstrated that implementing such a program would be most challenging in the countries that could see greatest benefit. Based on the Country Ranking Index, Equatorial Guinea would benefit the most from the MZA of AZM in three of the four scenarios we tested.

Conclusions/Significance

These visually accessible tools can be adapted or refined to include other metrics deemed important by stakeholders, and provide a quantitative approach to prioritization for intervention implementation. The need to explicitly state metrics and their weighting encourages thoughtful and transparent decision making. The objective and data-driven approach promoted by the three Indices may foster more efficient use of resources.     

Association between Ocular Bacterial Carriage and Follicular Trachoma Following Mass Azithromycin Distribution in The Gambia

Background

Trachoma, caused by ocular Chlamydia trachomatis infection, is the leading infectious cause of blindess, but its prevalence is now falling in many countries. As the prevalence falls, an increasing proportion of individuals with clinical signs of follicular trachoma (TF) is not infected with C. trachomatis. A recent study in Tanzania suggested that other bacteria may play a role in the persistence of these clinical signs.

Methodology/Principal Findings

We examined associations between clinical signs of TF and ocular colonization with four pathogens commonly found in the nasopharnyx, three years after the initiation of mass azithromycin distribution. Children aged 0 to 5 years were randomly selected from 16 Gambian communitites. Both eyes of each child were examined and graded for trachoma according to the World Health Organization (WHO) simplified system. Two swabs were taken from the right eye: one swab was processed for polymerase chain reaction (PCR) using the Amplicor test for detection of C. trachomatis DNA and the second swab was processed by routine bacteriology to assay for the presence of viable Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Prevalence of TF was 6.2% (96/1538) while prevalence of ocular C. trachomatis infection was 1.0% (16/1538). After adjustment, increased odds of TF were observed in the presence of C. trachomatis (OR = 10.4, 95%CI 1.32–81.2, p = 0.03), S. pneumoniae (OR = 2.14, 95%CI 1.03–4.44, p = 0.04) and H. influenzae (OR = 4.72, 95% CI 1.53–14.5, p = 0.01).

Conclusions/Significance

Clinical signs of TF can persist in communities even when ocular C. trachomatis infection has been controlled through mass azithromycin distribution. In these settings, TF may be associated with ocular colonization with bacteria commonly carried in the nasopharnyx. This may affect the interpretation of impact surveys and the determinations of thresholds for discontinuing mass drug administration.     

Prevalence of antibodies interactive with HTLV-I antigens in selected Solomon Islands populations

Serum samples obtained in 1986 from healthy individuals in three distinct Solomon Islands populations were screened for antibodies to human lymphotropic virus type I (HTLV-I). One of the populations tested lives on the remote Polynesian outlier atoll, Ontong Java. The other two groups, the Baegu and the Lau, are Melanesians living on Malaita, the most populous of the larger Solomon Islands. Eighty-eight of a total of 601 (14.6%) sera tested were repeatably reactive in an enzyme-linked immunosorbent assay (ELISA) that uses as antigen a lysate of HTLV-I viral particles. The prevalence of antibodies interactive with HTLV-I viral particles. The prevalence of antibodies interactive with HTLV-I antigens varied among the three groups, ranging from 8.5% (16/188) in the Baegu, through 13% (7/54) in the Lau, to 18.1% (65/359) among the Ontong Java population. The specificity of the screening ELISA was confirmed by protein immunoblot. No serum samples were obtained from children under 9 years of age. Although 121 of the 601 sera came from children between the ages of 9 and 19, none of these were reactive in the HTLV-I ELISA. Starting in the third decade, the prevalence of HTLV-I seropositivity increased with age, from 8.8% (10/113) between the ages of 20 and 29 to a peak of 25.9% (15/58) and 25% (15/60) in the sixth and seventh decade, respectively. This age-specific prevalence pattern is strikingly similar to that which is seen in populations where HTLV-I infection is endemic.     

The Relationship between Active Trachoma and Ocular Chlamydia trachomatis Infection before and after Mass Antibiotic Treatment

BackgroundTrachoma is a blinding disease, initiated in early childhood by repeated conjunctival infection with the obligate intracellular bacterium Chlamydia trachomatis. The population prevalence of the clinical signs of active trachoma; ‘‘follicular conjunctivitis” (TF) and/or ‘‘intense papillary inflammation” (TI), guide programmatic decisions regarding the initiation and cessation of mass drug administration (MDA). However, the persistence of TF following resolution of infection at both the individual and population level raises concerns over the suitability of this clinical sign as a marker for C. trachomatis infection.Conclusions/SignificancePrior to MDA, TF is a good indicator of the community prevalence of C. trachomatis infection. Following MDA, the prevalence of TF tends to overestimate the underlying infection prevalence. In order to prevent unnecessary additional rounds of MDA and to accurately ascertain when elimination goals have been reached, a cost-effective test for C. trachomatis that can be administered in low-resource settings remains desirable.     

Costs of Testing for Ocular Chlamydia trachomatis Infection Compared to Mass Drug Administration for Trachoma in The Gambia: Application of Results from the PRET Study

Background

Mass drug administration (MDA) treatment of active trachoma with antibiotic is recommended to be initiated in any district where the prevalence of trachoma inflammation, follicular (TF) is ≥10% in children aged 1–9 years, and then to continue for at least three annual rounds before resurvey. In The Gambia the PRET study found that discontinuing MDA based on testing a sample of children for ocular Chlamydia trachomatis(Ct) infection after one MDA round had similar effects to continuing MDA for three rounds. Moreover, one round of MDA reduced disease below the 5% TF threshold. We compared the costs of examining a sample of children for TF, and of testing them for Ct, with those of MDA rounds.

Methods

The implementation unit in PRET The Gambia was a census enumeration area (EA) of 600–800 people. Personnel, fuel, equipment, consumables, data entry and supervision costs were collected for census and treatment of a sample of EAs and for the examination, sampling and testing for Ct infection of 100 individuals within them. Programme costs and resource savings from testing and treatment strategies were inferred for the 102 EAs in the study area, and compared.

Results

Census costs were $103.24 per EA plus initial costs of $108.79. MDA with donated azithromycin cost $227.23 per EA. The mean cost of examining and testing 100 children was $796.90 per EA, with Ct testing kits costing $4.80 per result. A strategy of testing each EA for infection is more expensive than two annual rounds of MDA unless the kit cost is less than $1.38 per result. However stopping or deciding not to initiate treatment in the study area based on testing a sample of EAs for Ct infection (or examining children in a sample of EAs) creates savings relative to further unnecessary treatments.

Conclusion

Resources may be saved by using tests for chlamydial infection or clinical examination to determine that initial or subsequent rounds of MDA for trachoma are unnecessary.     

Impact of an Ivermectin Mass Drug Administration on Scabies Prevalence in a Remote Australian Aboriginal Community

Background

Scabies is endemic in many Aboriginal and Torres Strait Islander communities, with 69% of infants infected in the first year of life. We report the outcomes against scabies of two oral ivermectin mass drug administrations (MDAs) delivered 12 months apart in a remote Australian Aboriginal community.

Methods

Utilizing a before and after study design, we measured scabies prevalence through population census with sequential MDAs at baseline and month 12. Surveys at months 6 and 18 determined disease acquisition and treatment failures. Scabies infestations were diagnosed clinically with additional laboratory investigations for crusted scabies. Non-pregnant participants weighing ≥15 kg were administered a single 200 μg/kg ivermectin dose, repeated after 2–3 weeks if scabies was diagnosed, others followed a standard alternative algorithm.

Principal Findings

We saw >1000 participants at each population census. Scabies prevalence fell from 4% at baseline to 1% at month 6. Prevalence rose to 9% at month 12 amongst the baseline cohort in association with an identified exposure to a presumptive crusted scabies case with a higher prevalence of 14% amongst new entries to the cohort. At month 18, scabies prevalence fell to 2%. Scabies acquisitions six months after each MDA were 1% and 2% whilst treatment failures were 6% and 5% respectively.

Conclusion

Scabies prevalence reduced in the six months after each MDA with a low risk of acquisition (1–2%). However, in a setting where living conditions are conducive to high scabies transmissibility, exposure to presumptive crusted scabies and population mobility, a sustained reduction in prevalence was not achieved.

Clinical Trial Registration

Australian New Zealand Clinical Trial Register (ACTRN—12609000654257).     

Counting the Cost of Diabetes in the Solomon Islands and Nauru

Aim

To determine the costs associated with diabetes to governments, people with diabetes and their carers, and its impact on quality of life in two Pacific Island countries—the Solomon Islands and Nauru.

Materials and Methods

This cross-sectional cost of illness study was conducted on 330 people with type 2 diabetes (197 from the Solomon Islands and 133 from Nauru) using a structured cost of illness survey questionnaire adapted from the Australian DiabCo$t study. Quality of life was measured by the EQ-5D Visual Analogue Scale.

Results

There were 330 respondents (50% female; mean duration of diabetes 10.9 years; mean age 52.6 years). The estimated annual national cost of diabetes incurred by the Solomon Islands government was AUD12.8 million (AUD281 per person/year) and by Nauru government was AUD1.2 million (AUD747 per person/year). The major contribution to the government costs was inpatient services cost (71% in the Solomon Islands and 83% in Nauru). Annual expenditure for diabetes was approximately 20% of the governments’ annual health care expenditure. Considerable absenteeism and retirement from work due to diabetes was found.

Conclusions

This study found substantial public and personal costs associated with diabetes. The findings provide objective data on which health policy, funding and planning decisions about the prevention and control of diabetes in the Solomon Islands and Nauru can be reliably based and subsequently evaluated.     

Prevalence and Risk Factors for Trachoma in Central and Southern Malawi

Background

Trachoma, one of the neglected tropical diseases is suspected to be endemic in Malawi. Objectives: To determine the prevalence of trachoma and associated risk factors in central and southern Malawi.

Methodology/Principal Findings

A population based survey conducted in randomly selected clusters in Chikwawa district (population 438,895), southern Malawi and Mchinji district (population 456,558), central Malawi. Children aged 1–9 years and adults aged 15 and above were assessed for clinical signs of trachoma. In total, 1010 households in Chikwawa and 1016 households in Mchinji districts were enumerated within 108 clusters (54 clusters in each district). A total of 6,792 persons were examined for ocular signs of trachoma. The prevalence of trachomatous inflammation, follicular (TF) among children aged 1–9 years was 13.6% (CI 11.6–15.6) in Chikwawa and 21.7% (CI 19.5–23.9) in Mchinji districts respectively. The prevalence of trachoma trichiasis (TT) in women and men aged 15 years and above was 0.6% (CI 0.2–0.9) in Chikwawa and 0.3% (CI 0.04–0.6) in Mchinji respectively. The presence of a dirty face was significantly associated with trachoma follicular (TF) in both Chikwawa and Mchinji districts (P<0.001).

Conclusion/Significance

Prevalence rates of trachoma follicles (TF) in Central and Southern Malawi exceeds the WHO guidelines for the intervention with mass antibiotic distribution (TF>10%), and warrants the trachoma SAFE control strategy to be undertaken in Chikwawa and Mchinji districts.     

Molecular Xenomonitoring Using Mosquitoes to Map Lymphatic Filariasis after Mass Drug Administration in American Samoa

Background

Mass drug administration (MDA) programs have dramatically reduced lymphatic filariasis (LF) incidence in many areas around the globe, including American Samoa. As infection rates decline and MDA programs end, efficient and sensitive methods for detecting infections are needed to monitor for recrudescence. Molecular methods, collectively termed ‘molecular xenomonitoring,’ can identify parasite DNA or RNA in human blood-feeding mosquitoes. We tested mosquitoes trapped throughout the inhabited islands of American Samoa to identify areas of possible continuing LF transmission after completion of MDA.

Methodology/Principle Findings

Mosquitoes were collected using BG Sentinel traps from most of the villages on American Samoa''s largest island, Tutuila, and all major villages on the smaller islands of Aunu''u, Ofu, Olosega, and Ta''u. Real-time PCR was used to detect Wuchereria bancrofti DNA in pools of ≤20 mosquitoes, and PoolScreen software was used to infer territory-wide prevalences of W. bancrofti DNA in the mosquitoes. Wuchereria bancrofti DNA was found in mosquitoes from 16 out of the 27 village areas sampled on Tutuila and Aunu''u islands but none of the five villages on the Manu''a islands of Ofu, Olosega, and Ta''u. The overall 95% confidence interval estimate for W. bancrofti DNA prevalence in the LF vector Ae. polynesiensis was 0.20–0.39%, and parasite DNA was also detected in pools of Culex quinquefasciatus, Aedes aegypti, and Aedes (Finlaya) spp.

Conclusions/Significance

Our results suggest low but widespread prevalence of LF on Tutuila and Aunu''u where 98% of the population resides, but not Ofu, Olosega, and Ta''u islands. Molecular xenomonitoring can help identify areas of possible LF transmission, but its use in the LF elimination program in American Samoa is limited by the need for more efficient mosquito collection methods and a better understanding of the relationship between prevalence of W. bancrofti DNA in mosquitoes and infection and transmission rates in humans.     

Marine protected areas and resilience to sedimentation in the Solomon Islands

The ability of marine protected areas (MPAs) to provide protection from indirect stressors, via increased resilience afforded by decreased impact from direct stressors, remains an important and unresolved question about the role MPAs can play in broader conservation and resource management goals. Over a five-year period, we evaluated coral and fish community responses inside and outside three MPAs within the Roviana Lagoon system in Solomon Islands, where sedimentation pressure from upland logging is substantial. We found little evidence that MPAs decrease impact or improve conditions and instead found some potential declines in fish abundance. We also documented modest to high levels of poaching during this period. Where compliance with management is poor, and indirect stressors play a dominant role in determining ecosystem condition, as appears to be the case in Roviana Lagoon, MPAs may provide little management benefit.