Decline in infection-related morbidities following drug-mediated reductions in the intensity of Schistosoma infection: A systematic review and meta-analysis

Abstract

BackgroundSince 1984, WHO has endorsed drug treatment to reduce Schistosoma infection and its consequent morbidity. Cross-sectional studies suggest pre-treatment correlation between infection intensity and risk for Schistosoma-related pathology. However, evidence also suggests that post-treatment reduction in intensity may not reverse morbidity because some morbidities occur at all levels of infection, and some reflect permanent tissue damage. The aim of this project was to systematically review evidence on drug-based control of schistosomiasis and to develop a quantitative estimate of the impact of post-treatment reductions in infection intensity on prevalence of infection-associated morbidity.Methodology/Principal findingsThis review was registered at inception with PROSPERO (CRD42015026080). Studies that evaluated morbidity before and after treatment were identified by online searches and searches of private archives. Post-treatment odds ratios or standardized mean differences were calculated for each outcome, and these were correlated to treatment-related egg count reduction ratios (ERRs) by meta-regression. A greater ERR correlated with greater reduction in odds of most morbidities. Random effects meta-analysis was used to derive summary estimates: after treatment of S. mansoni and S. japonicum, left-sided hepatomegaly was reduced by 54%, right-sided hepatomegaly by 47%, splenomegaly by 37%, periportal fibrosis by 52%, diarrhea by 53%, and blood in stools by 75%. For S. haematobium, hematuria was reduced by 92%, proteinuria by 90%, bladder lesions by 86%, and upper urinary tract lesions by 72%. There were no consistent changes in portal dilation or hemoglobin levels. In sub-group analysis, age, infection status, region, parasite species, and interval to follow-up were associated with meaningful differences in outcome.Conclusion/SignificanceWhile there are challenges to implementing therapy for schistosomiasis, and praziquantel therapy is not fully curative, reductions in egg output are significantly correlated with decreased morbidity and can be used to project diminution in disease burden when contemplating more aggressive strategies to minimize infection intensity.

Persistent Hotspots in Schistosomiasis Consortium for Operational Research and Evaluation Studies for Gaining and Sustaining Control of Schistosomiasis after Four Years of Mass Drug Administration of Praziquantel

“…The standard approach used by most programs is preventive chemotherapy by mass drug administration (MDA) 7 using the antischistosomal drug praziquantel (PZQ). 8,9 To provide evidence regarding different ways to control schistosomiasis through MDA, the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE; https://score.uga.edu/) has conducted five studies in four countries (i.e., Côte d'Ivoire, Kenya, Mozambique, and Tanzania) with harmonized protocols to evaluate alternative approaches to MDA. There were originally seven studies in five countries, but two studies in one country had to be redesigned because of protocol deviations in the randomization of study villages.…”

Ultrasound Evolution of Pediatric Urinary Schistosomiasis after Treatment with Praziquantel in a Highly Endemic Area

“…Although it is widely accepted that this should be a standard tool in the management of schistosomiasis, there is still limited use of this in wide areas of sub-Saharan Africa where the disease is endemic. A recent review of morbidity reduction associated with urinary schistosomiasis found just 15 studies that used ultrasound to detect urinary tract improvement after treatment; among them, nine analyzed both abnormalities in the bladder and in the upper urinary tract, six analyzed only the urinary bladder 13 ; just one was performed in central Africa, 15 and none were carried out in southern Africa. Moreover, the last of these studies was performed in 2008, and none included long-term assessment.…”

“…This finding is surprising because age is usually considered an important proxy for cumulative parasite exposure and subsequent tissue damage, and lesions are more difficult to reverse as infection progresses to a more chronic and fibrotic stage. 13,19 One explanation may be that the older children were more receptive to health education advice, and therefore became reinfected less frequently; another reason may be that younger children in this area, compared with older ones, are usually more affected by other comorbidities such as malnutrition and anemia. 20 As praziquantel requires a competent immune system to take effect, 21 it may be less effective in these children.…”

“…11,12 Some recent studies suggest that to establish the periodicity of chemotherapy administration, it may be useful to know the dynamics of some of the morbidity outcomes, including the evolution of urologic lesions after taking praziquantel considering initial morbidity, frequency of reinfection, age, and other factors. [13][14][15] After roughly 40 years of war, Angola has been recovering control and surveillance activities in recent years. A recent parasitological survey in the Cubal district in Central Angola showed a prevalence of urinary schistosomiasis of at least 61% in school-age children.…”

Gut microbiota signatures in Schistosoma japonicum infection-induced liver cirrhosis patients

“…Schistosomiasis is one of the most prevalent parasitic diseases in the world [1]. An estimated 240 million people are affected by this disease, together with 800 million more at risk of infection [2]. Worryingly, schistosomiasis alone is associated with a high disease burden of as much as 3.3 million disabilityadjusted life years (DALYs), accounting for more than 10% of the global burden of Neglected Tropical Diseases (NTDs) [3,4].…”