Schistosomiasis in migrants: bridging the gap in Italy’s treatment guidelines and access Open Access

Human schistosomiasis is a chronic parasitic disease caused by helminth parasites of the genus Schistosoma. Approximately 250 million people are currently infected, with > 90% of global cases occurring in Sub-Saharan Africa (SSA) and ~12 000 annual all-age-related deaths occurring globally.¹

Schistosomiasis may cause severe and debilitating outcomes, such as portal hypertension with recurrent variceal bleeding, bladder cancer and hydroureteronephrosis.

Since 2011, the Central Mediterranean region has become a significant crossroads for migrants and refugees with impressive figures, many of them coming from schistosomiasis-endemic countries.²

Several studies have been conducted in Italy on the screening of schistosomiasis in African migrants, showing a high prevalence in this population.^3,4

A study conducted by National Institute for Health, Migration and Poverty, Rome and IRCCS Negrar in 2019–2020 estimated the prevalence of schistosomiasis in the largest cohort of African refugees and asylum seekers living in Italy.⁴ The study found a prevalence of 31% for schistosoma infection, particularly in migrants from West Africa (Mali, Guinea Conakry, Ivory Coast and Senegal).

However, healthcare workers’ awareness and knowledge about health issues that migrants may suffer from are insufficient, and this leads to diagnostic delay, inappropriate emergency room visits and avoidable hospitalisations, excessive invasive procedures and inappropriate treatments, causing significant costs to public health.

In 2017, a national guideline was developed to provide evidence-based recommendations on health assessments for migrants and asylum seekers upon their arrival in Italy.⁵ This document, along with the one produced by the European Centre for Disease Control,⁶ recommends serological screening for schistosomiasis to prevent complications and morbidity through early screening and treatment. It is also important for preventing local transmission and disease introduction.

Accordingly, in 2023, a multidisciplinary panel belonging to the Italian Society of Tropical Medicine and Global Health, with the scientific support of national scientific societies and international experts, developed a document on schistosomiasis management that included recommendations on migrant screening by screening and treatment for those who test positive.⁷

Furthermore, presumptive treatment and screening strategies are more favourable than the current passive diagnosis in the public health management of schistosomiasis in SSA migrants, especially in a long-term analysis and in low-prevalence countries.⁸ Several factors hinder the application of either serological screening or a presumptive treatment approach in the Italian setting, with the main barrier being the lack of treatment availability.

Gap in treatment availability

Despite the high burden of schistosomiasis among migrants in Italy and the guidelines recommendations, there is a significant problem with the availability of therapy.⁹

Although the WHO considers praziquantel (PZQ) an essential drug for schistosomiasis, bureaucratic obstacles in Italy have hampered its access.

In Italy, PZQ is not registered for human use or authorized for marketing. Access to marketing depends on pharmaceutical application and is evaluated by the Italian Agency of Drugs; this process has never been initiated in Italy. The only way to access PZQ is through drug importation, according to a procedure that follows the Decree of the Ministry of Health of 11 February 1997. See the steps for importation of a drug in Supplementary Table S1 available as Supplementary data at JTM online.

This is not an isolated Italian phenomenon. The accessibility of PZQ and other Neglected Tropical Diseases (NTDs) drugs is jeopardized in Europe. While Germany and France have good access to these medications,⁹ many other European countries do not. As a result, the ability for European countries to provide these drugs to countries without registration is quite limited.

Although this normative context, in Italy, PZQ is available in most centres for infectious and tropical diseases, where it is ordered and stored for inpatient use. However, each hospital needs to sign an agreement with an authorized international importer. As a result, the price may vary among hospitals depending on the specific agreement signed⁹ and is increased by the importation costs. Furthermore, imported drugs must be used under the personal responsibility of the prescribing physician, who may face legal prosecution in case of complications. However, PZQ is generally well-tolerated with only rare, transient, mild adverse events such as abdominal pain, headache and dizziness.

On the other hand, the drug is not available at the primary care level where screening usually occurs. Indeed, schistosomiasis prevention by PZQ administration is intended for a population that is still healthy and doesn’t need to seek hospital or outpatient care. This lack of immediate availability of the drug can be a problem when dealing with a highly mobile population such as migrants.

To add complexity, other countries where PZQ is registered and typically exported are currently facing shortages, resulting in a complete cessation of PZQ exportation.

Moreover, even if patients can purchase the drug upon medical prescription in pharmacies of other nearby countries, such as the Vatican and France, in most cases, the price makes this alternative unaffordable for most people affected, such as migrants. In some areas of our country, local law excludes reimbursement of imported medications by the Regional Health System, so the user must pay them in all cases.

Fortunately, since March 2024, the University of Naples Federico II, WHO Collaborating Centre for Diagnosis of Intestinal Helminths and Protozoa, has become a hub for the distribution of drugs for some NTDs donated by the WHO, including PZQ.

This means that national centres dealing with the management of migrants with schistosomiasis can now request certain NTD medications free of charge.

While these donations help address the issue to some extent, they are not sufficient to meet the significant demand for PZQ in Italy. The supply of these medications is limited, and the number of eligible migrant populations requiring treatment is substantial. As substantial is the cost of the health system to manage chronic schistosomiasis.

Estimating the PZQ requirement in Italy

We attempted to estimate the minimum amount of PZQ needed in Italy to comply with the guidelines mentioned above, based on the population census and the prevalence of schistosomiasis.

We calculated the estimated need for PZQ among the top 15 countries of origin for residents in Italy, focusing on SSA countries whose prevalence of schistosomiasis among migrants was well-documented in literature from Italy and neighbouring countries. When this data was unavailable, we used the 24,1% pool prevalence for SSA according to the systematic review of Asundi et al.¹⁰

Table 1 summarizes the findings and the estimate.

Overall, 128 717 people are estimated to be eligible for treatment based on screening. This means we would need ~1 544 604 tablets of PZQ according to the latest SIMET recommendation in terms of number of days of treatment.⁷

These estimates are based on the resident migrant population. However, it is important to highlight that every year, we see a continuous flow of migrants into Italy, especially those arriving by sea. This flow justifies the need of a stable and constant supply of PZQ to adhere to national and international guidelines.

When we look at the same countries mentioned earlier, we can estimate the number of PZQ doses needed to treat those migrants who arrived in Italy in 2022 and 2023, based on figures from the International Organization of Migration.²

In 2022 and 2023, 8597 and 28 712 people were eligible for treatment, respectively, when the approach was based on screening. According to the last SIMET recommendations (3-day treatment), this means ~103 175 and 344 544 tablets of PZQ in 2022 and 2023, respectively (see Table S2 available as Supplementary data at JTM online).

It is important to note that the estimated number of individuals requiring schistosomiasis treatment may be underestimated for several reasons. First, due to the lack of comprehensive prevalence data, the current estimation does not account for other significant immigrant populations among African countries, including Egypt (147 797 individuals) and other countries where the disease is endemic.

Secondly, recent evidence suggests that a screening approach may be less cost-effective than providing presumptive treatment. Therefore, it would be recommended that all migrants from endemic areas receive PZQ.⁸ Based on this information, the total number of people in Italy eligible for presumptive treatment, considering only the top 15 countries, would increase to 419 511, requiring 1 678 004 tablets for a one-day treatment).

Thirdly, in Italy, undocumented migrants or those awaiting resident permit (thus, not included in the figure in Table 1) have the right to access screening and treatment. This group is estimated to consist of ~600 000 individuals, potentially doubling the previous figures.

Conclusions

Access to PZQ is imperative in order to eliminate schistosomiasis, as outlined by WHO roadmap for 2021–2030.

The burden of schistosomiasis among migrants in our country highlights the need for formal registration and marketing as a class A drug, i.e. a free-of-charge drug corresponding to the definition of essential drug (WHO). Unfortunately, there is currently low commercial interest in drugs for NTDs like PZQ.

Donating a drug to a country with a structured healthcare system and legal regulations governing the importation of foreign drugs, such as Italy, does not constitute the best procurement solution. Instead, in line with epidemiological findings and demand, it's important to implement current guidelines, including adding PZQ to the national pharmaceutical formulary based on the WHO's essential medicines list. In Italy it is anticipated that with the new essential level of assistance, schistosomiasis screening will be available at the primary health care level. However, this public health measure will not be successful until PZQ is both available and affordable at the primary care level.

The authors of this publication hope that it will help to advocate for the registration and marketing of the drug in Italy. The ultimate goal is to bring attention to a disease that has significant consequences not only for those affected but also for public health, considering the high costs for the health system to manage complications and the risk of the disease re-emerging. Improved access to PZQ treatment will help address the double neglect: a disease, schistosomiasis and a fragile population, migrants.

Funding

A.A.'s work was funded by Italian Ministry of Health Fondi Ricerca Corrente–L2 to IRCCS Sacro Cuore Don Calabria Hospital.

Acknowledgements

We thank Prof. Laura Rinaldi and her collaborators from the University of Naples Federico II—WHO Collaborating Center for the Diagnosis of Helminths and Internal Protozoa—for their commitment to distributing NTD drugs through the WHO. We would like to thank Dr Antonio Montresor for the technical support on the management of NTDs to the Italian centres for infectious diseases and migrant health.

Thanks to Dr Habiba Ouattara for her daily commitment to breaking down barriers to access to the diagnosis and treatment of migrants suffering from schistosomiasis.

The authors are grateful to the ‘Italian Network on Neglected Tropical Diseases’ (IN-NTD) for search, dissemination, and advocacy activities in the field of public health.

Author contributions

A.C. contributed to conceptualization (supporting), data curation, investigation, methodology, writing—original draft; R.M. contributed to conceptualization (lead), data curation, investigation, methodology, supervision, writing—original draft; A.A., M.A., G.C., N.C. and L.Z. contributed to validation, writing—review & editing. All authors reviewed the article and read and approved the final article.

Conflict of interest: None declared.

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