Researchers at Oxford Population Health and the Uganda Ministry of Health have presented new evidence assessing the effectiveness of the current indicators used by the World Health Organization (WHO) to identify likely cases or communities affected by periportal fibrosis (PPF) as a result of schistosomiasis. The study is published in The Lancet Microbe.
Schistosomiasis is a tropical disease caused by a parasitic flatworm that is transmitted to humans through contact with freshwater sources such as lakes and slow-moving rivers. It is estimated to affect around 250 million people every year and more than 700 million people live in endemic areas where infections are common.
PPF is a late-stage complication of schistosomiasis where chronic and repeated infection causes damage to the vessels that supply blood to the liver and eventually in its most severe form to the liver tissue itself. There are currently no routine treatment or case management strategies for individuals with PPF. The only treatment available is for the infection, but does not reverse liver fibrosis.
Praziquantel is given to all people at risk of infection irrespective of their current disease status as part of a mass drug administration (MDA) programme. It is often assumed that early-in-life and frequent praziquantel administration will prevent irreversible diseases that occur as a result of a schistosome infection, such as PPF.
As a result of this assumption, current WHO guidelines rely on prevalence and intensity of infection as substitute indicators for understanding how to control and eliminate schistosomiasis-related disease. However, it is possible for PPF to outlast an initial schistosome infection and it is not currently known whether or not a past history of other diseases or coinfections can affect the risk of PPF, which is thought to be specific to schistosomiasis.
To find out whether the current guidelines could accurately identify cases of PPF, researchers looked at a random sample of people living in 1,442 households in 38 rural Ugandan villages between 3 January and 6 February 2022. The study was part of the SchistoTrack Cohort.
Key findings
- 344 (12.1%) of the 2,834 people aged between 5 and 90 years old who were examined were diagnosed with PPF;
- There was little evidence that current infection at any level was a reliable substitute indicator for assessing the prevalence of cases of PPF, even when looking at criteria used by WHO to identify areas where morbidity is assumed to be controlled or eliminated as a public health problem;
- Across all individuals, PPF prevalence was higher among males when compared to females, and among adults when compared to children;
- In tribes where people catch fish on a regular basis, the risk of PPF increased by 78.3% when compared with other tribes. This is likely to be due to increased water contact and in turn an increased risk of infection and reinfection indicating the length of individual exposure history and the importance of past infection over current infection;
- Having a history of another disease such as HIV, hepatitis B/C, or cirrhosis was associated with 2.81 fold increase in PPF – nearly four times the size of the effect of indicators related to past schistosome exposure.
- The differences in the number of cases between districts across Uganda were not found to be due to environmental or living conditions.
Dr Narcis Kabatereine, co-investigator of SchistoTrack at the Uganda Ministry of Health, said ‘This study shows that within the context of repeated MDA with praziquantel, PPF still persists. This means that blanket treatment campaigns with this drug alone cannot geographically eliminate PPF.’
Goylette Chami, Associate Professor and Robertson Fellow at Oxford Population Health, said ‘Current infection – no matter how measured – was a poor proxy indicator of the likelihood of having PPF and was not a reliable indicator for approximating morbidity in schistosomaisis-endemic communities.
‘Our results indicate that current WHO guidance for implementing MDA cannot be used to identify individuals with PPF or communities with a high burden of PPF. Additional studies are needed to extend our findings to other schistosomiasis-related diseases. Guidelines and tools such as updated ultrasound protocols are needed urgently to support endemic countries to monitor and target schistosomiasis-related morbidity.’
These findings have key implications for policy and treatment guidance. Current WHO guidelines should be used only for monitoring reductions in schistosome status and intensity and should not be used to assess the control or elimination of PPF, which was not correlated with current infections.