Rounds Of Mass Treatment Research Articles

Two-year longitudinal survey reveals high genetic diversity of Schistosoma mansoni with adult worms surviving praziquantel treatment at the start of mass drug administration in Uganda

BackgroundA key component of schistosomiasis control is mass drug administration with praziquantel. While control interventions have been successful in several endemic regions, mass drug administration has been less effective in others. Here we focus on the impact of repeated praziquantel treatment on the population structure and genetic diversity of Schistosoma mansoni.MethodsWe examined S. mansoni epidemiology, population genetics, and variation in praziquantel susceptibility in parasites isolated from children across three primary schools in a high endemicity region at the onset of the Ugandan National Control Programme. Children were sampled at 11 timepoints over two years, including one week and four weeks post-praziquantel treatment to evaluate short-term impacts on clearance and evidence of natural variation in susceptibility to praziquantel.ResultsPrevalence of S. mansoni was 85% at baseline. A total of 3576 miracidia larval parasites, isolated from 203 individual children, were genotyped at seven loci. Overall, genetic diversity was high and there was low genetic differentiation, indicating high rates of parasite gene flow. Schistosome siblings were found both pre-treatment and four weeks post-treatment, demonstrating adult worms surviving treatment and natural praziquantel susceptibility variation in these populations at the beginning of mass drug administration. However, we did not find evidence for selection on these parasites. While genetic diversity decreased in the short-term (four weeks post-treatment), diversity did not decrease over the entire period despite four rounds of mass treatment. Furthermore, within-host genetic diversity was affected by host age, host sex, infection intensity and recent praziquantel treatment.ConclusionsOur findings suggest that praziquantel treatments have short-term impacts on these parasite populations but impacts were transient and no long-term reduction in genetic diversity was observed. High gene flow reduces the likelihood of local adaptation, so even though parasites surviving treatment were observed, these were likely to be diluted at the beginning of the Ugandan National Control Programme. Together, these results suggest that MDA in isolation may be insufficient to reduce schistosome populations in regions with high genetic diversity and gene flow.

Benchmarking the Cost per Person of Mass Treatment for Selected Neglected Tropical Diseases: An Approach Based on Literature Review and Meta-regression with Web-Based Software Application.

BackgroundAdvocacy around mass treatment for the elimination of selected Neglected Tropical Diseases (NTDs) has typically put the cost per person treated at less than US$ 0.50. Whilst useful for advocacy, the focus on a single number misrepresents the complexity of delivering “free” donated medicines to about a billion people across the world. We perform a literature review and meta-regression of the cost per person per round of mass treatment against NTDs. We develop a web-based software application (https://healthy.shinyapps.io/benchmark/) to calculate setting-specific unit costs against which programme budgets and expenditures or results-based pay-outs can be benchmarked.MethodsWe reviewed costing studies of mass treatment for the control, elimination or eradication of lymphatic filariasis, schistosomiasis, soil-transmitted helminthiasis, onchocerciasis, trachoma and yaws. These are the main 6 NTDs for which mass treatment is recommended. We extracted financial and economic unit costs, adjusted to a standard definition and base year. We regressed unit costs on the number of people treated and other explanatory variables. Regression results were used to “predict” country-specific unit cost benchmarks.ResultsWe reviewed 56 costing studies and included in the meta-regression 34 studies from 23 countries and 91 sites. Unit costs were found to be very sensitive to economies of scale, and the decision of whether or not to use local volunteers. Financial unit costs are expected to be less than 2015 US$ 0.50 in most countries for programmes that treat 100 thousand people or more. However, for smaller programmes, including those in the “last mile”, or those that cannot rely on local volunteers, both economic and financial unit costs are expected to be higher.DiscussionThe available evidence confirms that mass treatment offers a low cost public health intervention on the path towards universal health coverage. However, more costing studies focussed on elimination are needed. Unit cost benchmarks can help in monitoring value for money in programme plans, budgets and accounts, or in setting a reasonable pay-out for results-based financing mechanisms.

Decline in transmission of schistosomiasis mansoni in Oman.

BackgroundIntestinal schistosomiasis due to Schistosoma mansoni was first reported in Oman in 1979. We describe the trend in parasitological and serological prevalence of human infection with S. mansoni in the endemic area over the period 1982–2014, and the compliance of data generated by the national monitoring and evaluation system with schistosomiasis elimination criteria set by the Ministry of Health of Oman.MethodsParasitological and serological assessments were carried out on population (mainly children) living in the area at risk for schistosomiasis in Dhofar, the country’s only endemic Governorate, for a period of over 30 years. Kato-Katz thick smear and Indirect Haemagglutination Assay were the techniques employed.ResultsData indicate a progressive decline in prevalence of S. mansoni throughout the 1980s and the 1990s, a recrudescence in the early 2000s, and a more marked decrease following the implementation of six rounds of mass treatment with praziquantel from 2007 to 2013. Latest parasitological prevalence (2011) was 0%, while latest serological prevalence (2014) was 0.11%.ConclusionTransmission of schistosomiasis has reached very low levels in Oman. Elimination criteria established by the Ministry of Health of Oman (parasitological prevalence ≤ 1% and serological prevalence ≤ 5%) have been met since 2008. Further investigations are required to assess whether interruption of transmission has been achieved in some or all foci, in view of the establishment of a formal verification process under the auspices of WHO.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-016-0210-1) contains supplementary material, which is available to authorized users.

Collateral benefits arising from mass administration of azithromycin in the control of active trachoma in resource limited settings

IntroductionThe benefits of the use of antibiotics in the mass treatment for active trachoma and other diseases have been documented, but the secondary effects arising from such a programme have not been fully elucidated. The purpose of this study was to investigate the potential secondary benefits arising from the use of azithromycin in mass treatment of active trachoma in an economically challenged Kenyan nomadic community.MethodsHealth information reports for January 2005 to December 2010 were reviewed to determine the annual trends of infectious diseases in the two districts, Narok and Transmara. The year 2007 was considered as the baseline for mass drug administration (MDA). Odds ratios (OR) were used to describe the association.ResultsThe mass distribution coverage in Narok was 83% in 2008, 74% in 2009 and 63% in 2010. The odds for malaria (OR = 1.13; 95% CI 1.12-1.14), diarrhoeal diseases (OR = 1.04; 95% CI 1.01-1.06), urinary tract infections (UTIs) (OR = 1.21; 95% CI 1.17-1.26), intestinal worms (OR, 4.98; 95% CI 4.68-5.3), and respiratory diseases other than pneumonia (OR, 1.15; 95% CI 1.13-1.16) were higher after three rounds of mass treatment, indicating a better outcome. Before the intervention, there was a reducing trend in the odds for respiratory diseases. In Transmara (control), there was an increase in odds for malaria, respiratory infections, UTIs and intestinal worms. The odds for diarrhoeal diseases, skin diseases and pneumonia decreased throughout the study period.ConclusionMass distribution of azithromycin may have contributed to the decrease in the prevalence of the respiratory infections in Narok District.

Active trachoma two years after three rounds of azithromycin mass treatment in Cheha district Gurage zone, Southern Ethiopia

BackgroundAzithromycin mass distribution was given to residents of Gurage zone Cheha district in 2004, 2005 and 2006 for three consecutive years with more than 90% coverage. The effect of treatment in the study community was not yet determined. The present study was therefore designed to assess the effect of azithromycin on the prevalence of active trachoma two years after three rounds of mass treatment of the community at Cheha district, Gurage zone.MethodsA multistage stratified cluster random survey was employed to determine the prevalence of active trachoma among children aged 1 to 9. Selected children were examined for trachoma using the simplified WHO grading system and their households were assessed for trachoma risk factors.ResultsThis survey demonstrated that the prevalence of active trachoma in the study community was 22.8% (95% CI 18.24% - 27.36%) that was lower than that of Southern Nations, Nationalities, and People's Regional prevalence (33.2%) in 2006. Only 27.6% (95% CI 25.7% - 30.1%) of the study population had a safe and clean water supply, whereas 42.7% (95% CI 39.8% - 46.2%) of the visited households had simple pit latrines.ConclusionThis survey demonstrated that despite repeated mass oral azithromycin distributions, the prevalence of active trachoma was still high. Therefore, the other components of the SAFE strategy such as fly control program, improving the water sources, measures to improve face washing and construction of utilizable latrines that are being implemented through the health extension package have to be integrated with mass azithromycin treatment to eliminate active trachoma in the district.

Adverse reactions following mass drug administration with diethylcarbamazine in lymphatic filariasis endemic areas in the Northeast of Brazil

The Global Programme to Eliminate Lymphatic Filariasis was launched with the goal of eliminating this disease via the annual mass drug administration (MDA) of a single dose of antifilarial drugs. Adverse drug reactions following MDA are a major factor of poor treatment adherence in several countries. This study assessed the occurrence of adverse drug reactions (ADRs) following the first round of mass treatment in two communities treated with different dosages of diethylcarbamazine (DEC) in the City of Recife, Brazil. Population-based cross-sectional surveys were conducted in a random sample of the population living in both communities (Areas I and II). The dose of DEC recommended by the WHO (6mg/kg) was calculated based on the individual's weight-for-age. In Area II, weight differences between the genders were also considered when determining dosage. Data were obtained through interviews conducted in the first 12 to 48h and on the 5th day after MDA during household visits. A total of 487 and 365 individuals were interviewed in Areas I and II, respectively. The prevalence of ADRs in Area I (23.6; 95%CI: 19.1-29.5) was higher than in Area II (16.2; 95%CI:11.9-21.5)(p=0.0078). The prevalence of ADRs among females was higher than in males in Area I (p=0.0021). In Area II, no significant difference between the genders was observed (p=0.1840). Age was not associated with ADRs in either area. Adjusting MDA dosage schedules according to weight-for-age and sex may be may contribute to reduce the occurrence of adverse drug reactions in the population.

Risk Factors for Ocular Infection with Chlamydia trachomatis in Children 6 Months following Mass Treatment in Tanzania

BackgroundTrachoma is the leading infectious cause of blindness in the world, and for endemic communities, mass treatment with azithromycin reduces the pool of infection. High coverage is essential, especially in children as they are the infectious reservoir. However, infection remains post-mass treatment. We sought to determine risk factors for infection in children post-mass treatment.MethodologyAll children under 9 years in 4 villages in Tanzania were followed from baseline pre-mass treatment to six months post treatment. 1,991 children under nine years were enrolled in the longitudinal study and data on individual and household characteristics was collected at baseline. Clinical trachoma was determined by an ocular exam and infection detected by PCR of an eyelid swab. Azithromycin was offered and infection was reassessed at 6 months. A multilevel logistic regression model was used, accounting for household clustering of children for analysis.Principal FindingsBaseline infection was 23.7% and at 6 months was 10.4%, despite 95% coverage. Infection at baseline was positively associated with infection at 6 months (OR = 3.31, 95%CI 2.40–4.56) and treatment had a protective effect (OR = 0.45, 95%CI 0.25–0.80). The age group 2–4 years had an increased risk of infection at 6 months. The household characteristics predictive of infection at 6 months were increasing number of children infected in the household at baseline and increasing number of untreated children in the household.ConclusionsWhile one round of mass treatment with high coverage did decrease infection by over 50%, it appears that it is not sufficient to eliminate infection. Findings that young children (ages 2–4 years) and households with increasing numbers of infected and untreated children have a positive association with infection at 6 months suggest that such households could be targeted for more intensive follow up.

Mass Antibiotic Treatment Alone Does Not Eliminate Ocular Chlamydial Infection

Mass Antibiotic Treatment Alone Does Not Eliminate Ocular Chlamydial Infection

Impact of two rounds of mass treatment with diethylcarbamazine plus albendazole on Wuchereria bancrofti infection and the sensitivity of immunochromatographic test in Malindi, Kenya

Annual single-dose mass treatment of endemic populations with a combination of either diethylcarbamazine (DEC) or ivermectin plus albendazole is recommended as the mainstay of lymphatic filariasis elimination programmes. We evaluated the impact of two rounds of annual mass drug administration (MDA) of DEC and albendazole on bancroftian filariasis in a pilot elimination programme in an endemic area of Kenya. Overall prevalence of microfilaraemia decreased by 65.4%, whereas community microfilarial load decreased by 84% after the two MDAs. The prevalence of parasite antigenaemia determined by immunochromatographic test (ICT) declined significantly by 43.5% after the two MDAs. We also studied the effect of mass treatment on the sensitivity of the ICT. Although the sensitivity of the test before treatment was high (89.9%; kappa=0.909) sensitivity was lower after two MDAs (59.3%; kappa=0.644). The finding raises concern about the reliability of the ICT in long-term monitoring of infection and for establishing programmatic endpoints. The results of the present study indicate a relatively high effectiveness of MDA using a DEC/albendazole combination against Wuchereria bancrofti infection and, therefore, it may be a useful strategy to eliminate lymphatic filariasis in onchocerciasis-free areas.

Simultaneous Detection and Quantification of Ancylostoma duodenale, Necator americanus, and Oesophagostomum bifurcum in Fecal Samples Using Multiplex Real-Time PCR

A multiplex real-time PCR was developed and evaluated for the simultaneous detection of Ancylostoma duodenale, Necator americanus, and Oesophagostomum bifurcum in fecal samples. Using well-defined control samples (N = 150), known positive fecal samples (N = 50), and fecal samples from an area in Ghana where human infections with all 3 nematode species are endemic (N = 339), the method proved to be highly specific and sensitive. Cycle threshold (Ct) values, reflecting parasite-specific DNA load, showed significant correlation with the intensity of infection as measured by microscopy using Kato-Katz fecal smears or by species specific third-stage larval count after coproculture. The multiplex real-time PCR described combined with the simple fecal sample collection procedure and the potential for high throughput makes this approach a powerful diagnostic tool to study species-specific transmission patterns of human hookworm-like infections. Moreover, this procedure facilitates monitoring of intervention programs and allows species-specific detection of treatment failure following rounds of mass treatment.

Trachoma and OcularChlamydia trachomatisWere Not Eliminated Three Years after Two Rounds of Mass Treatment in a Trachoma Hyperendemic Village

The World Health Organization recommends mass treatment of trachoma-hyperendemic communities, but there are scant empiric data on the number of rounds of treatment that are necessary for sustainable reductions. The rates of active trachoma and infection with C. trachomatis were determined in a community 3.5 years after two rounds of mass treatment with azithromycin. Maindi village in Tanzania received a first round of mass treatment with azithromycin after a baseline survey for trachoma and infection. All residents aged 6 months and older were offered single-dose treatment with azithromycin (excluding pregnant women with no clinical trachoma, who were offered topical tetracycline). The residents were followed over an 18-month period, and, according to similar treatment criteria, were offered retreatment at 18 months. Five years after baseline (3.5 years after the second round of mass treatment), a new census and survey of current residents for trachoma and infection was conducted. Children are the sentinel markers of infection and trachoma in communities, so data are presented specifically for ages 0 to 7 years (preschool age) and 8 to 16 years. Treatment coverage was above 80% for all ages in the first round, and highest (90%) in preschool-aged children. Second-round coverage was lower, <70%, and 70% in preschool-aged children. At 5 years, trachoma rates were still lower than baseline, ranging from 45% in those aged 0 to 3 years to 8% in those aged 11 to 15 years (compared with 81% and 39% at baseline, respectively). Infection rates at baseline ranged from 71% to 57%, but were 27% to 17% at 5 years after two rounds of mass treatment. At 5 years, there were no differences in trachoma or infection rates, when comparing new residents who came after the second mass treatment with those who had been resident in the village during both rounds (P > 0.05). Infection rates were lower in those who had been treated twice or at 18 months than in those treated only at baseline or never treated. Although mass treatment appears to be associated with lower disease and infection rates in the long term, trachoma and C. trachomatis infection were not eliminated in this trachoma hyperendemic village 3.5 years after two rounds of mass treatment. Continued implementation of the SAFE strategy in this environment is needed.

Mass treatment with albendazole reduces the prevalence and severity of Oesophagostomum-induced nodular pathology in northern Ghana

Previous surveys conducted in northern Ghana where Oesophagostomum bifurcum is endemic showed that O. bifurcum-induced nodular pathology could be detected in up to 50% of the inhabitants. The impact of albendazole-based mass treatment to control both infection and morbidity is assessed and compared with the situation in a control area where no mass treatment has taken place. A significant reduction in the prevalence of infection based on stool cultures was achieved following two rounds of mass treatment in one year: from 52.6% (361/686) pre treatment to 5.2% (22/421) 1 year later (chi(1)(2)=210.1; P<0.001). At the same time, the morbidity marker of ultrasound-detectable nodules declined from 38.2% to 6.2% (chi(1)(2)=138.1; P<0.001). There was a shift from multinodular pathology, often seen in heavy infections, to uninodular lesions. In the control villages where no treatment took place, O. bifurcum infection increased from 17.8% (43/242) to 32.2% (39/121) (chi(1)(2)=9.6; P<0.001). Nodular pathology decreased slightly from 21.5% to 19.0%, but a higher proportion of these subjects developed multinodular pathology compared with baseline (chi(1)(2)=5.5; P=0.019). It is concluded that repeated albendazole treatment significantly reduces O. bifurcum-induced morbidity.

Complementary hypothesis concerning the community sexually transmitted disease mass treatment puzzle in Rakai, Uganda.

To study the dynamics of a mass treatment programme for sexually transmitted diseases (STD) on prevalence of STD and HIV incidence in order to help explain the results of the STD mass treatment community trial in Rakai, Uganda. The analysis is based on simulations of STD mass treatment interventions using a deterministic model describing the course of STD and HIV transmission over time and incorporating demographic, biological and behavioural parameters. The mass intervention modelled mimics that used in the Rakai community trial. Mass treatment decreases STD prevalence to a very low level compared with baseline but is unsuccessful at eradicating the infection. STD prevalences return to baseline fairly rapidly after each round of mass treatment. Under different realistic scenarios, the fraction of HIV cases prevented by STD mass treatment assuming uniform 80% coverage of high- and low-risk groups, over the 20-month period following the first round of treatment, was greater than 35%. If, however, differential coverage is assumed, for example that while the total coverage is still 80%, only 40 or 25% of those at high risk are treated, the HIV preventable fraction is reduced, to 19 and 15% respectively (undetectable given the statistical power of the study). The tremendous impact of differential coverage can also be observed even in the early stage of the HIV epidemic. In the Rakai trial, mass treatment may have had an effect, although transient, on all STD prevalences, which could have had positive repercussions for HIV incidence. This modelling exercise suggests that although an 80% coverage appears high, the differential coverage of low- and high-risk populations may seriously impair our ability to test the STD-HIV interaction hypothesis.