Review of 2022 WHO guidelines on the control and elimination of schistosomiasis.

Schistosomiasis is a helminthiasis infecting approximately 250 million people worldwide. In 2001, the World Health Assembly (WHA) 54.19 resolution defined a new global strategy for control of schistosomiasis through preventive chemotherapy programmes. This resolution culminated in the 2006 WHO guidelines that recommended empirical treatment by mass drug administration with praziquantel, predominately to school-aged children in endemic settings at regular intervals. Since then, school-based and community-based preventive chemotherapy programmes have been scaled-up, reducing schistosomiasis-associated morbidity. Over the past 15 years, new scientific evidence-combined with a more ambitious goal of eliminating schistosomiasis and an increase in the global donated supply of praziquantel-has highlighted the need to update public health guidance worldwide. In February, 2022, WHO published new guidelines with six recommendations to update the global public health strategy against schistosomiasis, including expansion of preventive chemotherapy eligibility from the predominant group of school-aged children to all age groups (2 years and older), lowering the prevalence threshold for annual preventive chemotherapy, and increasing the frequency of treatment. This Review, written by the 2018-2022 Schistosomiasis Guidelines Development Group and its international partners, presents a summary of the new WHO guideline recommendations for schistosomiasis along with their historical context, supporting evidence, implications for public health implementation, and future research needs.

The story of Lymphatic Filariasis elimination as a public health problem from Yemen.

In 2000, Yemen joined the WHO global efforts to eliminate lymphatic filariasis (LF) as a public health problem by initiating a National LF Elimination Programme (NLFEP), that was fully integrated with the National Leprosy Elimination Programme (NLEP), the Ministry of Public Health and Population. This article reviews the NLFEP extensive efforts and interventions to eliminate LF in Yemen. LF mapping was started in 2000, followed by five annual rounds of mass drug administration (MDA) with ivermectin and albendazole in 8 implementation units (IUs) during 2002-2006. The epidemiological coverage for all MDA rounds was ≥80%. Based on WHO guidelines of 2005, MDA was stopped in 7 IUs, additional MDA rounds were continued in one IU until 2011. Microfilaremia monitoring and evaluation, and MDA stopping surveys were conducted based on WHO guidelines of 2005 and 2011. Information about the presence of patients suffering from lymphoedema/elephantiasis and hydrocele was collected, and basic care provided to all chronic cases by NLEP coordinators, trained on LF morbidity management and disability prevention (MMDP). As of 2017, a total of 610 lymphoedema patients were trained on self-management, and 31 hydrocele patients were referred to local General Hospitals for surgery. The NLFEP made excellent progress due to integration with NLEP, strong collaboration with national and international bodies, intensive training and supervision, and the use of robust advocacy for mobilization of endemic communities. Transmission assessment surveys (TAS), conducted in 2013 and 2016, indicated 0% antigenemia levels in schoolchildren in the 8 IUs. Thus, after almost two decades of sustained effort, Yemen met the WHO criteria for successful elimination of LF as a public health problem. In 2019, WHO validated Yemen as the second country in the WHO' Eastern Mediterranean Region to successfully eliminate LF as a public health problem.

Test, Treat, Track, Test, and Treat Active Surveillance toward Elimination of Schistosomiasis: A Feasibility Study.

We assessed the feasibility of using a test, treat, track, test, and treat (5T) active surveillance strategy to identify and treat individuals with schistosomiasis in three very low-prevalence villages in Kafr El Sheikh Governorate, Egypt. Primary index cases (PICs) were identified using the point-of-care circulating cathodic antigen (POC-CCA) assay in schools, in rural health units (retesting individuals with positive Kato-Katz examinations over the previous 6 months), and at potential water transmission sites identified by PICs and field observations. Primary cases identified potential second-generation cases-people with whom they shared water activities-who were then tracked, tested, and treated if infected. Those sharing water activities with second-generation cases were also tested. The yield of PICs from the three venues were 128 of 3,576 schoolchildren (3.6%), 42 of 696 in rural health units (6.0%), and 83 of 1,156 at water contact sites (7.2%). There were 118 second- and 19 third-generation cases identified. Persons testing positive were treated with praziquantel. Of 388 persons treated, 368 (94.8%) had posttreatment POC-CCA tests 3-4 weeks after treatment, and 81.8% (301) became negative. The 67 persons remaining positive had negative results after a second treatment. Therefore, all those found positive, treated, and followed up were negative following one or two treatments. Analysis of efforts as expressed in person-hours indicates that 4,459 person-hours were required for these 5T activities, with nearly 65% of that time spent carrying out interviews, treatments, and evaluations following treatment. The 5T strategy appears feasible and acceptable as programs move toward elimination.

Contributions of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) to Schistosomiasis Control and Elimination: Key Findings and Messages for Future Goals, Thresholds, and Operational Research.

Herein, we summarize what we consider are major contributions resulting from the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) program, including its key findings and key messages from those findings. Briefly, SCORE's key findings are as follows: i) biennial mass drug administration (MDA) with praziquantel can control schistosomiasis to moderate levels of prevalence; ii) MDA alone will not achieve elimination; iii) to attain and sustain control throughout endemic areas, persistent hotspots need to be identified following a minimal number of years of annual MDA and controlled through adaptive strategies; iv) annual MDA is more effective than biennial MDA in high-prevalence areas; v) the current World Health Organization thresholds for decision-making based on the prevalence of heavy infections should be redefined; and vi) point-of-care circulating cathodic antigen urine assays are useful for Schistosoma mansoni mapping in low-to-moderate prevalence areas. The data and specimens collected and curated through SCORE efforts will continue to be critical resource for future research. Besides providing useful information for program managers and revision of guidelines for schistosomiasis control and elimination, SCORE research and outcomes have identified additional questions that need to be answered as the schistosomiasis community continues to implement effective, evidence-based programs. An overarching contribution of SCORE has been increased cohesiveness within the schistosomiasis field-oriented community, thereby fostering new and productive collaborations. Based on SCORE's findings and experiences, we propose new approaches, thresholds, targets, and goals for control and elimination of schistosomiasis, and recommend research and evaluation activities to achieve these targets and goals.

Elimination of lymphatic filariasis as a public health problem from the Arab Republic of Egypt.

Lymphatic filariasis (LF) has been known in Egypt since ancient times. By 1930s it was recognized to be a major public health problem in the Nile Delta, and to be caused by Wuchereria bancrofti and transmitted by Culex pipiens. Remarkably, as a result of widespread DEC treatment and intensive vector control by the Ministry of Health and Population (MoHP), the infection rate of LF declined in the 1960s. However, relaxation of these efforts resulted in resurgence of filariasis in the 1980s and 1990s. In 2000, Egypt was among the first countries to join the WHO global efforts to eliminate LF as a public health problem by initiating a national LF elimination programme (NLFEP). This article reviews the history of LF control activities and summarizes the NLFEP extensive interventions to eliminate LF in Egypt. Based on MoHP data, mass drug administration (MDA) with DEC and ALB was started in 2000 in 161 implementation units (IUs). Additional IUs were included in subsequent MDA rounds, with the last IU included in 2007. MDA stopping surveys were conducted based on WHO guidelines (2005; 2011). Information about the presence of those suffering from lymphoedema/elephantiasis and hydrocele patients was collected, and care provided to those needing care in five rural health units (RHU) by primary health care system providers who were given training on LF morbidity management and disability prevention (MMDP). The NLFEP made excellent progress due to strong collaboration between different ministries, through intensive training and supervision, and the use of advocacy for mobilization of endemic communities. The epidemiological coverage for all MDA rounds was effectively ≥80%. Antigenemia levels found in schoolchildren during transmission assessment surveys (TAS) in 166 IUs approximately 10 years after stopping MDA was 0%. In 2017, TAS conducted in additional 29 IUs indicated 0.1% antigenemia and 0% microfilaremia. In 2015, the registration of chronic LF patients was updated to 1472 lymphoedema and 18 hydrocele patients. Lymphoedema patients were trained on self-management, and hydrocele patients were referred to local General Hospitals for surgery. Thus, after over a decade of sustained effort, Egypt met the WHO criteria for successful elimination of LF as a public health problem. In December 2017, WHO validated Egypt as the first country in the Eastern Mediterranean Region to successfully achieve elimination.

Multiple Praziquantel Treatments of Schistosoma mansoni Egg-Negative, CCA-Positive Schoolchildren in a Very Low Endemic Setting in Egypt Do Not Consistently Alter CCA Results.

Forty-four Schistosoma mansoni egg-negative/circulating cathodic antigen (CCA) low-positive (trace or 1+) children in three districts of very low prevalence in Egypt were given three sequential praziquantel (PZQ) treatments. Stool and urine specimens were collected 3 months following the initial treatment, and 3 weeks following the second and following the third PZQ treatments, which were conducted 5 weeks apart. Stool specimens were examined by Kato-Katz (four slides/stool sample) and all S. mansoni egg-negative stools were further tested by the "miracidia hatching test" (MHT). Urine samples were examined by the point-of-care CCA assay (POC-CCA). Over the study period, all stool samples from study subjects remained S. mansoni egg negative and MHT negative. Of the POC-CCA test results, in the first day of the study 3 months following the initial treatment, 29.5% were negative, 61.4% CCA trace positives, and 9.1% CCA 1+ positives. Following each PZQ treatment, the test results fluctuated between 1+, trace, and negative, but did not consistently decrease. The proportions of POC-CCA-positive results obtained in the first day (70.5%) as compared with the last day of the study (72.7%) in all of the three districts were very similar. We conclude that CCA trace and 1+ readings, in Kato-Katz S. mansoni egg-negative children in this area with very low levels of intestinal schistosomiasis, are not consistently altered or rendered consistently negative following repeated PZQ treatments and are therefore likely to represent false-positive readings. This finding is of critical importance for countries such as Egypt as they approach elimination.

Translating preventive chemotherapy prevalence thresholds for Schistosoma mansoni from the Kato-Katz technique into the point-of-care circulating cathodic antigen diagnostic test.

BACKGROUND: Intervention guidelines against Schistosoma mansoni are based on the Kato-Katz technique. However, Kato-Katz thick smears show low sensitivity, especially for light-intensity infections. The point-of-care circulating cathodic antigen (POC-CCA) is a promising rapid diagnostic test detecting antigen output of living worms in urine and results are reported as trace, 1+, 2+, and 3+. The use of POC-CCA for schistosomiasis mapping, control, and surveillance requires translation of the Kato-Katz prevalence thresholds into POC-CCA relative treatment cut-offs. Furthermore, the infection status of egg-negative but antigen-positive individuals and the intensity-dependent sensitivity of POC-CCA should be estimated to determine its suitability for verification of disease elimination efforts. METHODOLOGY: We used data from settings in Africa and the Americas characterized by a wide range of S. mansoni endemicity. We estimated infection intensity-dependent sensitivity and specificity of each test at the unit of the individual, using a hierarchical Bayesian egg-count model that removes the need to define a 'gold' standard applied to data with multiple Kato-Katz thick smears and POC-CCA urine cassette tests. A simulation study was carried out based on the model estimates to assess the relation of the two diagnostic tests for different endemicity scenarios. PRINCIPAL FINDINGS: POC-CCA showed high specificity (> 95%), and high sensitivity (> 95%) for moderate and heavy infection intensities, and moderate sensitivity (> 75%) for light infection intensities, and even for egg-negative but antigen-positive infections. A 10% duplicate slide Kato-Katz thick smear prevalence corresponded to a 15-40% prevalence of ≥ trace-positive POC-CCA, and 10-20% prevalence of ≥ 1+ POC-CCA. The prevalence of ≥ 2+ POC-CCA corresponded directly to single slide Kato-Katz prevalence for all prevalence levels. CONCLUSIONS/SIGNIFICANCE: The moderate sensitivity of POC-CCA, even for very light S. mansoni infections where the sensitivity of Kato-Katz is very low, and the identified relationship between Kato-Katz and POC-CCA prevalence thresholds render the latter diagnostic tool useful for surveillance and initial estimation of elimination of S. mansoni. For prevalence below 10% based on a duplicate slide Kato-Katz thick smear, we suggest using POC-CCA including trace results to evaluate treatment needs and propose new intervention thresholds that need to be validated in different settings.

Mapping of Schistosoma mansoni in the Nile Delta, Egypt: Assessment of the prevalence by the circulating cathodic antigen urine assay.

In line with WHO recommendations on elimination of schistosomiasis, accurate identification of all areas of residual transmission is a key step to design and implement measures aimed at interrupting transmission in low-endemic settings. To this purpose, we assessed the prevalence of active S. mansoni infection in five pilot governorates in the Nile Delta of Egypt by examining schoolchildren (6-15 years) using the Urine-Circulating Cathodic Antigen (Urine-CCA) cassette test; we also carried out the standard Kato-Katz (KK) thick smear, the monitoring and evaluation tool employed by Egypt's national schistosomiasis control programme. Prevalence rates determined by the Urine-CCA test for all governorates were higher than those determined by KK (p<0.01). Of 35 districts surveyed in the five governorates, S. mansoni infection was detected in 19 districts (54.3%) using KK, and in 31 districts (88.6%) by Urine-CCA (χ2=9.94; P=0.0016). S. mansoni infections were detected by Urine-CCA, but not by KK in 12 districts (34.3%), and infection was not detected by either of the two diagnostic methods in four districts in Qalyubia governorate. Males and higher age-groups have significantly higher Urine-CCA prevalence rates. Based on the findings of the current S. mansoni mapping exercise, authorities of the Ministry of Health and Population (MoHP) adopted a new elimination strategy by readjusting thresholds for mass treatment with praziquantel and targeting all transmission areas. MoHP is now planning to remap in all other endemic governorates using Urine-CCA with the aim of identifying all areas of transmission where the elimination strategy should be applied.

Molecular characterization of Egyptian human and anima Echinococcus granulosus isolates by RAPD-PCR technique.

Five primers of known, but arbitrary nucleotide sequence (OPH-03, OPH-05, OPH-12, OPH-15, OPH-18) were used to detect genetic variability in Egyptian human, camel and pig E. granulosus isolates. OPH-03, OPH-05 & OPH-15 proved useful as genetic markers of strain variation, while OPH-12 and OPH-18 allowed distinction at the genus level i.e. diversified from Cysticercus tenuicollis. OPH-03 was the most effective giving sharp distinct banding pattern and the least values of similarity coefficients. Some variations were detected within E. granulosus isolates from the same host. The level of heterogeneity was low in three of the human isolates, camel and pig strains. Individual variation was detectable within other 3 human isolates. Human and camel isolates were the most related pair, having similar patterns and the highest similarity coefficients. The study implies that human cases in Egypt are of the camel/dog strain, and camels are important hosts for the transmission of human hydatidosis.

The evaluation of HLA-DRB1 antigens as susceptibility markers for unilocular cystic echinococcosis in Egyptian patients.

This is the first study dealing with the correlation between HLA antigens and cystic echinococcosis (CE) in Egyptian patients. The potential immunogenetic predisposition for susceptibility and resistance to unilocular echinococcosis was investigated by HLA-DRB1 typing; first by HLA-DRB1 amplification using PCR then using the allele-specific probing technique based on the reverse hybridization principle. The study was carried out on 35 patients with confirmed CE, and 100 apparently healthy individuals. A statistically significant positive association was found between HLA-DR3 and HLA-DR11 and the occurrence of CE. HLA-DR3 antigen was positively associated with the occurrence of isolated pulmonary cysts, multiple cysts, cysts >5 cm in size, non-cured disease and with a common radiological picture of hydatid cyst. A significant positive association of HLA-DR11 with the occurrence of cysts <5 cm in size was detected. This study demonstrates that carriers of DR-3 and DR-11 are at high risk for CE, and that those with DR-3 are more liable to complications.