Periodic deworming programme in Brazil

To evaluate the periodic deworming programme (PDP) against soil-transmitted helminth infection and estimate the cost-benefit of this action in a Northeastern Brazilian State. An observational descriptive study was peformed by two branches: an epidemiological analysis of parasitological stool tests positivity in the 7 health micro-regions of Sergipe State, from January to June 2019, and a cost-benefitial analysis through comparison between estimated costs of PDP and conventional diagnose and treatment method from 2014 to 2018. From the 1110 parasitological stool tests evaluated, 317 were positive: 20 (1.8 %) for helminths and 307 (26.7%) for protozoan parasites. Among positive tests, 61 (19.2%) were in PDP age target group (5-14 years). An annual average of 255,283 Albendazole tablets (400mg, single dose) were distributed with an annual average coverage rate of 84.2%. To support the programme, approximately R$ 281,859.25 (US$ 89,775.67) were transferred per year to the state of Sergipe. PDP estimated cost-effectiveness was R$ 1.10 (US$ 0.34) per event prevented and generated a cost-minimization of approximately R$ 335.617,60 (US$124,568.00) when compared to the conventional diagnose and treat method. The positive rates of soil-transmitted helminth infection in parasitological tests in Sergipe were low and the recommendation for PDP seems to be currently inadequate. Most positive tests were for commensal protozoa species. PDP estimated cost is lower than conventional diagnose and treatment method. Protozoa infections prevention policies should be evaluated as they are the major parasitic infection in our community after PDP.

The World Health Organization (WHO) recommends annual prophylactic deworming by administring drugs such as Albendazole or Mebendazole to risk goups from regions where the prevalence of soil-transmitted helminth infection is 20 to 50% and bianual in regions above 50%, aiming to reduce the endemic rates by the year 2020. These groups are of schoolage children, women of childbearing age and adults in high-risk occupations (WHO, 2006;2017;Nath, et al., 2019).
In Brazil, the Health Ministry conducted a national survey between 2010-2015 in school-age children (7 to 17 years old) aiming to indentify the prevalence and stratify regions by endemic categories. Sergipe was classified as endemic for Schistossoma Mansoni (8.19% of prevalence) and high endemic risk for soil-transmitted helminths as Ascaris (12.86%), hookworm (6.62%), and Trichuris (16.99%) (Katz, 2018). However, Brazil's Ministry of Health continues to perform periodic deworming programme (PDP) against soil-transmitted helminth infection for 5-14 year-age individuals, and this programme has not been evaluated in its effetiveness and cost-benefit.
Therefore, this study aims to evaluate the PDP for soil-transmitted helminth infection through the estimate of intestinal parasite infection prevalence and cost-benefit analysis of PDP in Sergipe. The hypothesis is that PDP prophylactic treatment has reduced positivity for soil-transmitted helminthiasis in Sergipe and this strategy has a better economic cost-benefit outcome when compared to the conventional diagnose and treat positives method.

Methodology
This is an observational, descriptive study performed by two branches: epidemiological study of the prevalence of intestinal parasite infection and cost-benefit analysis of the PDP against soil-transmitted helminth infection in the state of Sergipe, Northeast-Brazil.

Study design
A cross-sectional epidemiological study was conducted to identify the prevalence of intestinal parasite infections through the analysis of parasitological stool tests from laboratories working for the Brazilian public health system -Unified Health Service (SUS) (Brazil, 1990 A, B).
All samples from the 7 health microregions of the state of Sergipe  were analysed in the period from january to june 2019, considering the most recent precessed samples and the sample size calculated for each microregion. No exclusion criteria was adopted. The variables age, city of residence, method of parasitological stool test, test result (positive or negative) and parasites found were considered. The age group 5 to 14 years, PDP target, was separately analized.

Sample Size
Considering a sample margin of error of 5%, confidence level of 95%, in a total population of Sergipe of 2.288.080 inhabitants (IBGE, 2010;Weyne, et al., 2004), a sample size of 368 was obtained. Due to data availability, a three-fold number was obtained, so the final sample size was 1110 individuals with a proportional distribution among the 7 health micro-regions of Sergipe

Cost-Benefit Analysis
PDP's coverage rate against soil-transmitted heminth infection in Sergipe was evaluated and a cost-benefit analysis was performed by an estimated cost-utility and costeffectiveness of the indicators of PDP in Sergipe from 2014 to 2018, compared with diagnosing and treating positive conventional methods. To reach these values, one of the analysed indicators was the PDP coverage rate.

Coverage rate
In Brazil, one of the PDP targets is 5 to 14-year-old public school students, who receives annualy Albendazole 400 mg, in a single dose, donated by WHO. The coverage rate was calculated using data from the practical guide for operating the "National campaing on leprosy, intestinal parasite infection, trachoma and schistosomiasis", a governmental programme in which PDP is inserted (Brazil, 2016 B).
The Coverage rate is the percentage of children treated (according to the Albendazole quantity distributed) considering the elegible children, those aged 5-14 years old according to the anual school census for public schools, so coverage rate was obtained by: number of children treated / number of 5-14 year-old children in public schools X 100 = (%).

Cost-Benefit Estimate
In order to estimate the costs, the amount provided was considered as an allowance for the campaign, which is considered the maximum amount available for conducting these Research, Society and Development, v. 9, n. 11, e100091110722, 2020 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v9i11.10722 actions. Although the giving amount is the finantial resource of the entire "National campaing on leprosy, intestinal parasite infection, trachoma and schistosomiasis", it was used as a basis to calculate the estimated costs of PDP 2015;2016 C;. This resource is transferred by the Brazilian Ministry of Health through the National Health Fund to Brazilian Cities to execute PDP. The finantial resource numbers for Sergipe municipalities, Northeast region and Brazil were analyzed and the values measured by the Extended National Consumer Price Index (IPCA) with corrections based on the 2018 inflation (Vanni, 2009). The cost-benefit estimate of the program was evaluated by comparing the value spent in two different scenarios: treating prophylactically and treating individuals with positive tests (Table 1). The prophylactic treatment of PDP against soil-trasmitted helminth infection in risk groups was named "Cost 1", considering the average of children treated annually, and the "Cost 2" corresponded to the conventional method of diagnosis and treatment of positives, it was estimated by multiplying the average number of children treated annually by the value of the diagnostic test R$ 1.65 (US$ 0.51) (SIGTAP, 2011;2013;2015) adding to the treatment value of about 16.99% (Katz, 2018) of individuals multiplied by R$ 5.77, factory price of Albendazole (400 mg, single dose), according to RENAME (National List of Essential Drug Products). Available in: http://portal.anvisa.gov.br/listas-de-precos. (RENAME, 2013;ANVISA, 2000). Research, Society and Development, v. 9, n. 11, e100091110722, 2020 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v9i11.10722 8 Cost-minimization was estimated by subtracting the cost 1 from cost 2 and costeffectiveness by the value (in US$) per event prevented, using the cost of each approach divided by the individuals of each methodology. For cost 1, the event prevented was the average number of children treated and, for Cost 2, the number of individuals diagnosed in addition to the individuals treated (Vanni, 2009;Brazil, 2014 B;Leone, 1981;Martins, 1996).

Ethical Considerations
This study was approved by the Ethics Committee (CEP) of the Federal University of Sergipe with the number CAAE 09377719.4.0000.5546. Informed Consent (TCLE) was exempted.

Discussion
Stool parasitological positive test rate for soil-transmitted helminth in Sergipe, including school-aged children from 5 to 14 years old, in this epidemiological study, was low.
It was observed that rates reported of soil-transmitted helminths was lower than those reported in the national survey conducted by Katz (2018). It is also lower than the guidelines for PDP, showing that the perpetuation of the programme should be questionned. However, an increase in the percentage of positive samples for protozoa was also noted, resulting in a change on the epidemiological profile of the intestinal parasite infection in Sergipe. This change was also described by Oliveira (2020), who monitored school-age children through Development, v. 9, n. 11, e100091110722, 2020 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v9i11.10722 parasitological stool tests for 5 years in Sergipe and showed a decrease in prevalence of soiltransmitted helminths and an increase of protozoa.
Basic sanitation improvement in Northeast region sanitation panel 36 as well as access to treated water and sewage collection system, expansion of the Family Health Strategy (ESF) and the PDP prophylactic treatment has achieved the goal of descreasing endemic rates for soil-transmitted helminth infection (Oliveira, et al., 2020;Brazil, 2017;Oishi, et al., 2019;Tefera, et al., 2015;Malta, et al., 2016;Brito, et al., 2018), when compared to the data of the survey conducted by Katz (2018) . Thus, the proportion of individuals infected by parasites is no longer adequate to the WHO recommendation for PDP (WHO, 2006;2017).
Many positives tests for protozoa had also been observed, mainly commensals, probably because Albendazole (400mg, single dose) is not effective for eliminating protozoa to this dosage (ANVISA, 2013) .This increase in protozoa (Oliveira, et al., 2020) may be linked to continuous water contamination, providing the risk of outbreaks of waterborne diseases, causing clinical and economic losses (Vasconcelos, et al., 2016).
Recent data estimates that 16.6% of the Brazilian population and 14.7% of Sergipe are still with no access to treated water; 47.6% of the Brazilian population and 77% of Sergipe are still without adequate sewage collection system (Brazil, 2017). About 258,826 hospitalizations and 2,340 deaths in Brazil, 1,757 hospitalizations and 36 deaths in Sergipe, were due to waterborne diseases in the year 2017 (Brazil, 2017). Although there were improvements in basic sanitation and better estimates than in previous years, addicional improvements are still needed (Bawman, 2009;Panilla, 2008).
According to the ordinances that authorizes finantial resources transfers to PDP, the Northeast region received an annual average of 44% of the total amount for the programme in the country due to the number of municipalities that joined the campaign. In Sergipe, despite the engagement in all the campaigns, the amount of the allowance represents about 4.78% in relation to the Northeast and 1.87% to Brazil, which is understandable because it is the smallest Brazilian state (IBGE, 2010;2015;2016 C;. Regarding the amount transferred after a correction for inflation, it can be said that there was no real increase in investiments; this is the result of public policy at the time and as actions carried out by SUS after suffering a direct impact (Takamatsu, 2006;Silva, et al., 2016;Brazil, 1998;2016 D;Santos 2014).
Regarding cost-benefitial estimates, the periodic prophylactic deworming treatment generated an average minimization of R$ 398,617.60 (1.41 times) compared to the conventional method. The cost-effectiveness analysis was also favorable showing that PDP is Research, Society and Development, v. 9, n. 11, e100091110722, 2020 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v9i11.10722 13 more economical: R$ 1.10 per event prevented. However, the prophylactic treatment that uses drugs universally must promote a negative burden, such as drug resistance and maintenance of endemicity (Diawara 2009;Hasen, et al., 2013;Zuccherato, et al., 2018;Furtado, et al., 2019;Matamoros, et al., 2019;Diawara, et al., 2013). At the same time, stopping the intervention in an unplanned manner can contribute to an increase in endemicity. It is worth remembering that the endemic rates are no longer adequate to the WHO recommendation for PDP against soil-transmitted helminth infection.
We recognize that not considering low sensitivity of stool parasitological stool tests and, consequently, a percentage of false-negatives has rebounded in the cost-benefitial analysis, that being one of the limitations of the study. However, in the absence of the PDP against soil-transmitted helminth infection, the major practice should be to treat positives, even with the limitations of the stool parasitological tests. Another limitation of our study is to consider, for cost-benefitial estimate, the number of children treated as a number of tablets distributed, the number of children eligible according to the school census and the expenditure of PDP for the average annual financial support provided in the respective ordinances of the "National Campaign for Leprosy, Intestinal Parasite Infection, Trachoma and Schistosomiasis". We recognize that these numerical values do not reflect exactly the cost to develop an estimate, which is the intention of this work. Although there are limitations, this is how this type of evaluation is usually done, so the strategy is sound.
In short, it is necessary to emphasize that WHO has reached the goal of reducing and eliminating the negative impacts caused by soil-transmitted helminths until the year 2020 through the administration of periodic deworming prophylactic treatment 9 . The perspective is that, after 2020, there will be a reassessment of this situation in order to reformulate the approach for soil-transmitted helminth infection rates around the world.

Conclusion
The actions developed for PDP in Sergipe in recent years, along with improvements in basic sanitation and coverage of the Family Health Strategy, have contributed to the reduction of endemic rates for soil-transmitted helminth infection and the cost-benefitial analysis of this intervention proved superior to the conventional method of diagnosis and treatment after positive test. However, according to the data presented in this study, the PDP approach of prophylactic treatment against soil-transmitted helminth infection in Sergipe is no longer adequate to WHO recommendations.
New studies are recommended in order to determine whether it is appropriate to continue with PDP and to evaluate if it is usefulness for policies that also aim at reducing infection by protozoa, the main etiological agents involved in intestinal parasitic infection in our community.

Conflict of interest
All authors have no conflicts to declare.