Tracking the spatial and longitudinal dynamics of mixed infections of urogenital and intestinal schistosomiasis in two sentinel rural communities from southern Malawi

691q-2026-02-17_14_02_19-rstb-2024-0520.pdf

Tracking the spatial and longitudinal dynamics of mixed infections of urogenital and intestinal schistosomiasis, inclusive of Schistosoma mattheei, in two sentinel rural communities from southern Malawi.

The World Health Organization's twenty thirty neglected tropical disease roadmap aims to eliminate schistosomiasis as a public health problem with preventive chemotherapy as a foundational strategy; however, mixed infections of Schistosoma haematobium with zoonotic species, inclusive of putative hybrids, present a potential challenge. We sought to address the importance of mixed species infections through a two-year, longitudinal epidemiological investigation at two villages in southern Malawi, Samama and Mthawira. Participants, approximately two thousand, were sampled at baseline, a twelve-month follow-up, and a twenty-four-month follow-up. Preventive chemotherapy was provided annually at baseline to follow-up one and biannually at follow-up one to follow-up two. Urine samples underwent microscopical examination and circulating cathodic antigen rapid-diagnostic testing, with egg-patent urine filters undergoing additional molecular screening for five non-Schistosoma haematobium species using real-time polymerase chain reaction. Prevalence of schistosomiasis by microscopy was statistically higher in Samama than Mthawira, plus or minus zero point zero five six three, P value equals one point three times ten to the negative eleven, as was mixed infections with Schistosoma mattheei, by real-time polymerase chain reaction, plus or minus zero point one seven, P value less than three point eight four times ten to the negative ten. By follow-up two, preventive chemotherapy reduced the prevalence of Schistosoma haematobium and Schistosoma mansoni, but that of Schistosoma mattheei remained relatively stable, rising by zero point nine eight percent at Samama, plus or minus zero point one nine, P value equals zero point four one, and decreasing by zero point four three percent at Mthawira, plus or minus zero point three nine, P value equals zero point three three. We conclude that treatment alone will not be sufficient for control of zoonotic Schistosoma mattheei, but additional interventions will be required.

One. Background

Among the parasitic neglected tropical diseases, schistosomiasis is currently the most significant, estimated to infect two hundred forty million people globally, resulting in an annual mortality rate of approximately thirteen thousand. Up to seven hundred seventy-nine million people are living at risk of the disease. Although the current mortality rate is believed to be an underestimate, some analyses suggest it may be as high as twenty-four thousand deaths per year. The majority, ninety-one percent, of active cases occur in sub-Saharan Africa and present either as urogenital or intestinal schistosomiasis, and sometimes as mixed infections of both, with all forms of the disease causing significant morbidity.

Urogenital schistosomiasis is primarily caused by the parasitic blood fluke Schistosoma haematobium, while intestinal schistosomiasis is primarily caused by Schistosoma mansoni. Infection by each blood fluke occurs through exposure to contaminated water where infected intermediate snail hosts of the respective genera Bulinus or Biomphalaria are present locally. The World Health Organization twenty thirty NTD Roadmap aims to eliminate schistosomiasis as a public health problem, defined as less than one percent proportion of heavy intensity schistosomiasis infections, in all seventy-eight endemic countries by twenty thirty. The foundational strategy is by preventive chemotherapy through mass drug administration with the anthelminthic praziquantel. For Schistosoma haematobium infections, heavy intensity infections are defined as fifty plus eggs per ten milliliters of urine. However, the World Health Organization Roadmap also identifies the lack of understanding surrounding the emergence of mixed infections, inclusive of hybrid and zoonotic schistosomes, implicated in urogenital schistosomiasis and their potential to derail current control efforts.

Since the early two thousands, hybrids between Schistosoma haematobium and Schistosoma bovis have been widely reported from communities in West Africa. They have since been reported from further afield in East Africa and outside the typical transmission zone, such as in Corsica and Spain. Studies looking at the introgression of Schistosoma haematobium and the zoonotic species Schistosoma bovis have suggested that hybridization events were rare and largely ancestral. In consideration of another veterinary schistosome species, Schistosoma mattheei, another zoonotic species common in livestock, particularly cattle, hybridization events have different introgression dynamics and appear more contemporary as shown in the laboratory and nature. More importantly, meticulous laboratory studies carried out by Wright and Ross demonstrated that Schistosoma haematobium cross Schistosoma mattheei hybrids exhibited heterosis in their ability to infect snails and experimental animals, as well as demonstrating increased growth rate and egg output.

It should also be noted that the historical environments, inclusive of aquatic and terrestrial habitats, and epidemiological conditions resulting in past hybridization events probably do not reflect today's zoonotic and anthroponotic transmission patterns, which are shaped by denser human and domestic animal populations following agricultural expansion.

The human population in sub-Saharan Africa has increased tenfold since nineteen hundred, from an estimated one hundred forty million to one point four billion, and cattle numbers have also increased from less than five million to over three hundred million across the same time scale. The decrease in nomadism coupled with the creation of both large- and small-scale water-management programs has probably increased the chances for non-target species infection for both zoonotic and anthroponotic schistosomes at these mixed species-transmission sites. In Malawi, the potential significance that mixed species, inclusive of hybrids or zoonotic infections, may have on the maintenance of urogenital schistosomiasis disease is unknown and requires investigation. To address this knowledge gap, the Wellcome Trust funded the Hybridisation in UroGenital Schistosomiasis investigation, which started in twenty twenty-one with the aim of revealing the transmission biology, epidemiological impact and clinical importance of Schistosoma mattheei hybrids in Malawi.

Our study reported here was carried out over a four-year period and involved veterinary and human-health studies, of which the latter consisted of a two-year longitudinal study enrolling approximately two thousand participants from two sentinel study communities in southern Malawi, based at Samama and Mthawira villages. Here, at least three species of the S. haematobium group are known to be endemic: S. haematobium, S. mattheei and S. bovis as well as S. mansoni, the incidence of the latter is increasing in southern Malawi. Prior studies noted S. mattheei (and S. haematobium) within locally sampled cattle and in a clinical case report. This raised key questions about the spread of mixed zoonotic and/or hybrid infections among the local populations, the variation in the prevalence of such schistosomes between sites and demographics and their infection dynamics after PC by MDA with PZQ.

Here, we describe the results of a two-year longitudinal study investigating the prevalence of urogenital and intestinal schistosomiasis, inclusive of mixed infections with S. mattheei species markers, in two study populations located in southern Malawi. Our objectives were to determine the prevalence of zoonotic Schistosoma species at both study sites across the two years of the longitudinal study, to identify any association between demographics relating to age and gender with putative-zoonotic Schistosoma sp. infection and to assess the spatial distribution of positive cases at the household level and identify any overt heterogeneities.