Advances in Parasitology Volume 115 Russell Stothard Full Chapter

Advances in Parasitology, Volume 115
Russell Stothard
Visit to download the full and correct content document:
https://ebookmass.com/product/advances-in-parasitology-volume-115-russell-stothar
d/
VOLUME ONE HUNDRED AND FIFTEEN
ADVANCES IN
PARASITOLOGY
SERIES EDITOR
D. ROLLINSON J. R. STOTHARD
Life Sciences Department Department of Tropical
The Natural History Museum, Disease Biology
London, United Kingdom Liverpool School of Tropical
d.rollinson@nhm.ac.uk Medicine, Liverpool, United Kingdom
russell.stothard@lstmed.ac.uk
EDITORIAL BOARD
T. J. C. ANDERSON K. KING
Department of Genetics, Texas Department of Zoology,
Biomedical Research Institute, University of Oxford,
San Antonio, TX, United States Oxford, United Kingdom
M. G. BASÁÑEZ M. G. ORTEGA-PIERRES
Professor of Neglected Tropical Professor of the Department of Genetics
Diseases, Department of Infectious and Molecular Biology,
Disease Epidemiology, Faculty of Centro de Investigación y de
Medicine (St Mary’s Campus), Estudios Avanzados IPN,
Imperial College London, Mexico City, Mexico
London, United Kingdom
D. L. SMITH
D. D. BOWMAN Johns Hopkins Malaria Research
Director Cornell CVM MPS—Veterinary Institute & Department of Epidemiology,
Parasitology, Professor of Parasitology, Johns Hopkins Bloomberg School
C4-119 VMC, Dept Micro & Immunol, of Public Health, Baltimore,
CVM Cornell University, Ithaca, MD, United States
NY, United States
R. B. GASSER R. C. A. THOMPSON
Head, WHO Collaborating Centre
Faculty of Veterinary and Agricultural
for the Molecular Epidemiology
Sciences, The University of Melbourne,
of Parasitic Infections, Principal
Parkville, VIC, Australia
Investigator, Environmental
A. L. GRAHAM Biotechnology CRC (EBCRC),
Professor of Ecology & Evolutionary Biology, School of Veterinary and Biomedical
Co-Director of the Global Health Program, Sciences, Murdoch University,
Princeton University, Princeton, Murdoch, WA, Australia
NJ, United States
X.-N. ZHOU
J. KEISER Professor, Director, National Institute of
Head, Helminth Drug Development Unit, Parasitic Diseases,
Department of Medical Parasitology and Chinese Center for Disease Control
Infection Biology, Swiss Tropical and Public and Prevention, Shanghai,
Health Institute, Basel, Switzerland People’s Republic of China
VOLUME ONE HUNDRED AND FIFTEEN
ADVANCES IN
PARASITOLOGY
Edited by
DAVID ROLLINSON
Life Sciences Department
The Natural History Museum,
RUSSELL STOTHARD
Department of Tropical
Disease Biology
Liverpool School of Tropical
Medicine, Liverpool, United Kingdom
Academic Press is an imprint of Elsevier
125 London Wall, London EC2Y 5AS, United Kingdom
The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom
50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States
525 B Street, Suite 1650, San Diego, CA 92101, United States
First edition 2022
Copyright © 2022 Elsevier Ltd. All rights reserved.
No part of this publication may be reproduced or transmitted in any form or by any means, electronic
or mechanical, including photocopying, recording, or any information storage and retrieval system,
without permission in writing from the publisher. Details on how to seek permission, further
information about the Publisher’s permissions policies and our arrangements with organizations such
as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website:
www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the
Publisher (other than as may be noted herein).
Notices
Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our understanding, changes in research methods, professional practices, or medical
treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating
and using any information, methods, compounds, or experiments described herein. In using such
information or methods they should be mindful of their own safety and the safety of others, including
parties for whom they have a professional responsibility.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume
any liability for any injury and/or damage to persons or property as a matter of products liability,
negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas
contained in the material herein.
ISBN: 978-0-323-98871-1
ISSN: 0065-308X
For information on all Academic Press publications

visit our website at https://www.elsevier.com/books-and-journals
Publisher: Zoe Kruze

Acquisitions Editor: Leticia Lima
Developmental Editor: Cindy Angelita Gardose
Production Project Manager: Abdulla Sait
Cover Designer: Mark Rogers
Typeset by STRAIVE, India
Contents
Contributors vii
1. An update on female and male genital schistosomiasis and

a call to integrate efforts to escalate diagnosis, treatment and
awareness in endemic and non-endemic settings: The time is now 1
Amaya L. Bustinduy, Bodo Randriansolo, Amy S. Sturt, Seke A. Kayuni,
Peter D.C. Leustcher, Bonnie L. Webster, Lisette Van Lieshout,
J. Russell Stothard, Hermann Feldmeier, and Margaret Gyapong
1. Introduction 3
2. Pathogenesis and clinical manifestations 9
3. Immunology 12
4. Diagnosis of genital schistosomiasis 13
5. Co-infections and co-morbidities 21
6. Immigrants and returned travellers 24
7. Management of FGS and MGS 25
8. Disability, stigma and community awareness 29
9. Programme integration 30
10. Conclusions and way forward 33
Acknowledgements 33
References 33
2. Vertebrates as uninfected disseminators of helminth

eggs and larvae 45
Neil J. Morley
1. Introduction 46
2. Terminology and definitions of helminth zoochory 48
3. Features of different vertebrates that affect their ability to disseminate
parasites 49
4. Endozoochory 54
5. Ectozoochory 127
6. Long-distance dispersal 138
7. Conclusion 143
References 146
v
vi Contents
3. Anthelmintic resistance in ruminants: challenges and solutions 171

J. Charlier, D.J. Bartley, S. Sotiraki, M. Martinez-Valladares, E. Claerebout,
G. von Samson-Himmelstjerna, S.M. Thamsborg, H. Hoste, E.R. Morgan,
and L. Rinaldi
1. Concerted action for combatting anthelmintic resistance in ruminants 173
2. Prevalence and impact of anthelmintic resistance 175
3. Gastrointestinal nematodes: current and future diagnosis 179
4. Diagnosis of anthelmintic resistance 185
5. Towards a sustainable use of anthelmintics 193
6. Prospects of new anthelmintics 197
7. Complementary control approaches 198
8. Facilitating behavioural change 206
9. Conclusions 210
Acknowledgements 211
References 211
Further reading 226
Contributors
D.J. Bartley
Disease Control, Moredun Research Institute, Penicuik, United Kingdom
Amaya L. Bustinduy
Department of Clinical Research, London School of Hygiene & Tropical Medicine,
J. Charlier
Kreavet, Kruibeke, Belgium
E. Claerebout
Ghent University, Faculty of Veterinary Medicine, Laboratory of Parasitology, Merelbeke,
Belgium
Hermann Feldmeier
Charite University Medicine Berlin, Institute of Microbiology, Infectious Diseases and
Immunology, Berlin, Germany
Margaret Gyapong
Institute of Health Research, University of Health and Allied Sciences, Ho, Ghana
H. Hoste
INRAE, UMR 1225 IHAP INRAE/ENVT, Toulouse University, Toulouse, France
Seke A. Kayuni
Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool,
United Kingdom; MASM Medi Clinics Limited, Blantyre, Malawi
Peter D.C. Leustcher
Centre for Clinical Research, North Denmark Regional Hospital, Hjoerring; Department of
Clinical Medicine, Aalborg University, Aalborg, Denmark
M. Martinez-Valladares
Instituto de Ganaderı́a de Montaña (CSIC-Universidad de León), Departamento de Sanidad
Animal, León, Spain
E.R. Morgan
Institute for Global Food Security, Queen’s University Belfast, Belfast, United Kingdom
Neil J. Morley
School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey,
United Kingdom
Bodo Randriansolo
Association K’OLO VANONA, Antananarivo, Madagascar
L. Rinaldi
University of Naples Federico II, Unit of Parasitology and Parasitic Diseases, Department of
Veterinary Medicine and Animal Production, CREMOPAR, Napoli, Italy
vii
viii Contributors
S. Sotiraki
Veterinary Research Institute, Hellenic Agricultural Organisation ELGO-DIMITRA,
Thessaloniki, Greece
J. Russell Stothard
Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool,
United Kingdom
Amy S. Sturt
Section of Infectious Diseases, Veterans Affairs Palo Alto Health Care System, Palo Alto,
United States
S.M. Thamsborg
Veterinary Parasitology, University of Copenhagen, Frederiksberg C, Denmark
Lisette Van Lieshout
Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands
G. von Samson-Himmelstjerna
Institute for Parasitology and Tropical Veterinary Medicine, Veterinary Centre for
Resistance Research, Freie Universit€at Berlin, Berlin, Germany
Bonnie L. Webster
Natural History Museum, London, United Kingdom
CHAPTER ONE
An update on female and male

genital schistosomiasis and
a call to integrate efforts
to escalate diagnosis, treatment
and awareness in endemic
and non-endemic settings:
The time is now
Amaya L. Bustinduya,∗, Bodo Randriansolob, Amy S. Sturtc,
Seke A. Kayunid,e, Peter D.C. Leustcherf,g, Bonnie L. Websterh,
Lisette Van Lieshouti, J. Russell Stothardd, Hermann Feldmeierj,
and Margaret Gyapongk
a
Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United
Kingdom
b
Association K’OLO VANONA, Antananarivo, Madagascar
c
Section of Infectious Diseases, Veterans Affairs Palo Alto Health Care System, Palo Alto, United States
d
Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
e
MASM Medi Clinics Limited, Blantyre, Malawi
f
Centre for Clinical Research, North Denmark Regional Hospital, Hjoerring, Denmark
g
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
h
Natural History Museum, London, United Kingdom
i
Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands
j
Charite University Medicine Berlin, Institute of Microbiology, Infectious Diseases and Immunology, Berlin,
Germany
k
Institute of Health Research, University of Health and Allied Sciences, Ho, Ghana
∗
Corresponding author: e-mail address: amaya.bustinduy@lshtm.ac.uk
Contents
1. Introduction 3
1.1 Selection criteria 3
1.2 Epidemiology and geographical distribution of genital schistosomiasis 3
1.3 Life cycle and transmission 4
1.4 FGS and MGS in less common Schistosoma species 7
1.5 The importance of different hybrids of S. haematobium group species
(including minor species contributing to FGS/MGS) 8
2. Pathogenesis and clinical manifestations 9
2.1 Female genital schistosomiasis (FGS) 9
2.2 Male genital schistosomiasis (MGS) 11
Advances in Parasitology, Volume 115 Copyright #2022 Elsevier Ltd 1

ISSN 0065-308X All rights reserved.
https://doi.org/10.1016/bs.apar.2021.12.003
2 Amaya L. Bustinduy et al.
3. Immunology 12
3.1 Vaginal environment in FGS 12
3.2 Immune activation during pregnancy 13
4. Diagnosis of genital schistosomiasis 13
4.1 FGS diagnostics 13
4.2 Molecular diagnostics (nucleic acid amplification tests) 17
4.3 MGS diagnostics 19
4.4 Immunopathology in MGS 20
5. Co-infections and co-morbidities 21
5.1 Human immunodeficiency virus (HIV) 21
5.2 Human papillomavirus (HPV) and FGS 22
6. Immigrants and returned travellers 24
7. Management of FGS and MGS 25
7.1 FGS treatment 25
7.2 Treatment of MGS 28
7.3 Pregnancy 28
8. Disability, stigma and community awareness 29
8.1 Case study: Ghana 29
9. Programme integration 30
10. Conclusions and way forward 33
Acknowledgements 33
References 33
Abstract
The last decades have brought important insight and updates in the diagnosis, man-
agement and immunopathology of female genital schistosomiasis (FGS) and male
genital schistosomiasis (MGS). Despite sharing a common parasitic aetiological agent,
FGS and MGS have typically been studied separately. Infection with Schistosoma
haematobium manifests with gender-specific clinical manifestations and consequences
of infection, albeit having a similar pathogenesis within the human genital tract.
Schistosoma haematobium is a known urinary bladder carcinogen, but its potential caus-
ative role in other types of neoplasia, such as cervical cancer, is not fully understood.
Furthermore, the impact of praziquantel treatment on clinical outcomes remains largely
underexplored, as is the interplay of FGS/MGS with relevant reproductive tract infections
such as HIV and Human Papillomavirus. In non-endemic settings, travel and immigrant
health clinics need better guidance to correctly identify and treat FGS and MGS. Our
review outlines the latest advances and remaining knowledge gaps in FGS and MGS
research. We aim to pave a way forward to formulate more effective control measures
and discuss elimination targets. With a growing community awareness in health prac-
titioners, scientists and epidemiologists, alongside the sufferers from these diseases,
we aspire to witness a new generation of young women and men free from the
downstream disabling manifestations of disease.
An update on female and male genital schistosomiasis 3
1. Introduction
As a neglected tropical disease (NTD), interventions against schisto-
somiasis are featured within the recently outlined WHO 2021–30
Roadmap (WHO, 2021a). Preventive chemotherapy against urogenital
and intestinal schistosomiasis-related morbidity is strongly encouraged and
disease-specific control targets are also defined. However, the detection
and management of disease sequelae within the female and male genital
tracts due to urogenital schistosomiasis, remain unaddressed. In this review,
we seek to highlight the importance and often overlooked connections
between female genital schistosomiasis (FGS) and male genital schistosomi-
asis (MGS), addressing disease-specific needs and challenges in endemic and
non-endemic settings, respectively. Our review presents a comprehensive
summary of the recent published evidence about FGS and MGS to ulti-
mately inform policy makers to support integrative approaches for disease
management.
1.1 Selection criteria

References were searched in PubMed and Medline databases using the key
words ‘female genital schistosomiasis’, ‘male genital schistosomiasis’, ‘genital
or urogenital schistosomiasis’, ‘praziquantel’, for the last 10 years (2011–21)
with the terms ‘AND’, ‘OR’. A total of 324 articles were identified.
Abstracts were reviewed for suitability and were included in this review if
they pertained to any discipline related to FGS and MGS. A total of 123 arti-
cles related specifically to FGS published in the last decade were screened
and 85 were reviewed. No clinical trials were identified. For MGS, 56 arti-
cles were retrieved and only 32 were found to be related to the topic. A sea-
rch for articles covering both FGS and MGS retrieved 29 results but only
3 studied both diseases jointly. Historical articles were included where
relevant
1.2 Epidemiology and geographical distribution of genital

schistosomiasis
The global distribution of FGS is estimated to be around 50 million people
limited to S. haematobium endemic areas in sub-Saharan Africa (SSA)
(Christinet et al., 2016). Urinary schistosomiasis (viz. S. haematobium eggs
in urine) and FGS often co-exist, and are commonly referred to as urogenital
schistosomiasis. For example, a Tanzanian study reported concurrent FGS
diagnosed by histopathology in 62% of 543 women with urinary schistoso-

miasis (Poggensee et al., 1998). Overall, there are fewer studies evaluating
FGS compared with the broader disease definition of urogenital schistoso-
miasis, including urine-based diagnostics with and without genital involve-
ment. Thus, accurate geographical estimates for FGS are lacking and remain
an extrapolation from the broader disease manifestations. Estimates for
MGS are scarce and also rely on extrapolation of a wider range of clinical
manifestations attributed to S. haematobium (Kayuni et al., 2019a).
Genital schistosomiasis is an inflammatory parasitic disease caused when
eggs from the waterborne blood fluke S. haematobium, are lodged within the
reproductive organs. Genital schistosomiasis affects both females and males
(Colley et al., 2014; Kjetland et al., 2012; Yu et al., 2013). FGS and MGS are
not yet included in the global burden of disease estimates of 1.44 million
disability-adjusted life years (DALYs) attributed to schistosomiasis, despite
the well-known disabling morbidities associated with FGS (DALYs and
Collaborators, 2018). Control efforts for schistosomiasis, noting urogenital
and intestinal manifestations, broadly focus on decreasing heavy intensity
infections leading to severe morbidity in school-aged children in the urinary
tract, and in the liver and spleen, respectively (Savioli et al., 2017; WHO,
2020). This approach neglects to recognize manifestations related to genital
disease that are often difficult to quantify such as infertility, ectopic pregnan-
cies, sexual dysfunction and menstrual disorders (Bustinduy et al., 2017;
Helling-Giese et al., 1996a; Kjetland et al., 2008; Stothard et al., 2020b).
WHO has recognized the hidden manifestations of FGS as a public health
problem whereas MGS remains unacknowledged, not only by its sufferers
but also overlooked in health statistics captured across the continent of
Africa and other schistosome endemic locations (WHO, 2020). Fig. 1 shows
the limited number of countries with reported FGS and MGS studies.
The recognition of gender differences is necessary, as they may impact
exposure, transmission, manifestation and treatment for genital schistosomi-
asis (Ozano et al., 2020). Importantly, there are several differences in disease
awareness and social stigma for each disease manifestation (Mazigo
et al., 2021).
1.3 Life cycle and transmission

The life cycle of the waterborne Schistosoma species is complex but can be
highly efficient when certain temperature and humidity environmental
conditions are met; this can result in universal exposure and infection in
Fig. 1 Countries with FGS (A) and MGS (B) case reports and studies in S. haematobium
endemic areas in sub-Saharan Africa published to date. Panel (A) is adapted from
Sturt, A.S., Webb, E.L., Francis, S.C., Hayes, R.J., Bustinduy, A., 2020a. Beyond the barrier:
female genital schistosomiasis as a potential risk factor for HIV-1 acquisition. Acta
Trop. 209, 105524 and Panel (B) is adapted from Kayuni, S., Lampiao, F., Makaula, P.,
Juziwelo, L., Lacourse, E.J., Reinhard-Rupp, J., Leutscher, P.D.C., Stothard, J.R., 2019b. A sys-
tematic review with epidemiological update of male genital schistosomiasis (MGS): a call for
integrated case management across the health system in sub-Saharan Africa Parasite
Epidemiol. Control 4, e00077.
communities that have unsafe water contact (Satayathum et al., 2006). In

Africa, two main Schistosoma species infect humans, S. haematobium and
S. mansoni (Lai et al., 2015). While cross-specific worm pairings occur
within a co-infected host, it is likely that successful mating between these
two species is very rare although such mixed worm pairs may lead to ectopic
egg deposition (e.g. S. mansoni eggs in urine) and associated pathology
(Stothard et al., 2020a) (Fig. 2).
Schistososoma mansoni primarily causes hepatosplenic and intestinal
disease, while S. haematobium is strongly associated with urogenital manifes-
tations. In mixed heavy infections, S. mansoni eggs can be excreted in the
urine (mansonuria), contributing to urinary tract disease. This is most likely
resultant from mixed worm pairings between S. haematobium and S. mansoni,
with S. mansoni females being carried by S. haematobium males to the uro-
genital system (Doehring et al., 1986). Schistosoma haematobium infections
are endemic in Africa, the Middle East, and now also in Corsica (France)
(WHO, 2020), while S. mansoni is distributed in Africa, the Middle East
and also the Americas (Colley et al., 2014). While co-infection with both
Fig. 2 The life cycle of S. haematobium. Adapted from Countdown (https://countdown.

lstmed.ac.uk).
parasites is common, its epidemiological occurrence is only rarely reported,

even by WHO. In 2012, for example, 163 million men and women in Africa
were infected with either of these two Schistosoma species with about a quar-
ter having dual infections. Some 57 million (35%) are school aged children
(Lai et al., 2015). Much of the pathological description of S. haematobium’s
related disease has focused on urinary abnormalities, ignoring the less obvi-
ous genital complications of the disease (Bustinduy et al., 2021).
FGS is defined by the detection of parasite eggs or DNA in genital tissue
or in secretions. Schistosoma eggs (also referred to as ova) are immunogenic,
and once tissue-entrapped they invoke granulomatous inflammation. The
accumulation of eggs in genital tissues over time results in subsequent mor-
bidity and organ dysfunction (Kjetland et al., 2014). Worm migration pat-
terns of adult schistosomes and the accessibility of genital organs via the
pelvic venous plexus explain why genital manifestations are so common
in S. haematobium infections and their disease sequelae more noticeable in
sexually active adults. Signs and symptoms therefore overlap with many sex-
ually transmitted infections (Poggensee et al., 2000). Depending on where
Fig. 3 Schistosoma haematobium egg deposition in the female and male genital tracts
causing female and male genital schistosomiasis. Graphic components courtesy of
https://smart.servier.com/.
eggs are released, clinical pathology develops in the vulva and vagina, cervix,
uterus, fallopian tubes and the ovaries (Kjetland et al., 2012) (Fig. 3). All gen-
ital organs may be affected simultaneously, and their dynamics change
through time concurrent with administration with praziquantel, the only
available deworming medication that is active against Schistosoma spp.
(WHO, 2020).
Male genital schistosomiasis (MGS) is a specific chronic manifestation of
schistosomiasis, associated with presence of Schistosoma eggs and pathologies in
male genital fluids and organs of men inhabiting or visiting schistosomiasis-
endemic areas. Of the 54 countries in Africa, only 20 of them have formally
reported FGS and 17 countries have MGS reported cases in the literature
(Kayuni et al., 2019b; Sturt et al., 2020a).
1.4 FGS and MGS in less common Schistosoma species

Although uncommon, genital manifestations of the disease are not always
directly related to infections with S. haematobium alone. In a Tanzanian
study, 5% (19/359) of women who underwent gynaecological exam had
S. mansoni eggs detected in cervical tissue and 52.6% (10/19) had both
S. haematobium and S. mansoni eggs present in genital samples (Poggensee
et al., 2001a). In S. mansoni endemic areas in Brazil there are reported
FGS cases affecting the fallopian tubes (Faria et al., 2010) and presenting
as ovarian tumours (Cavalcanti et al., 2011; Feldmeier et al., 1998).
There are several reports of MGS caused by species other than
S. haematobium; for example, a case of testicular schistosomiasis leading to

secondary infertility was reported in a S. mansoni endemic area in Nigeria
(Adisa et al., 2012) and prostate involvement reported in a patient with
Schistosoma japonicum living by the Yangtze river in China (Yu et al., 2013).
1.5 The importance of different hybrids of S. haematobium

group species (including minor species contributing
to FGS/MGS)
There are currently 23 Schistosoma species, 13 of which are found in
sub-Saharan Africa, which are split into three species groups.
S. haematobium resides within the S. haematobium species group, which con-
sists of nine closely related species all of which share the characteristic of ter-
minal spined ova. Apart from S. haematobium two other species within this
group are considered to be human pathogens S. guineensis and S. intercalatum,
both of which cause intestinal schistosomiasis in specific foci in central
African regions. Other species within the group are considered pathogens
of mammalian livestock and/or wildlife. Of note is the occurrence of
S. haematobium hybrids; S. haematobium-guineensis, S. haematobium-bovis,
S. haematobium-curassoni, S. haematobium-mattheei, the latter three involve
livestock Schistosoma species and raise concerns over zoonoses and animal
reservoir hosts. Mixed species combinations are likely to result in ectopic
egg excretion and/or deposition, though there is still much to learn about
these hybrid forms, together with their potential impact on schistosomiasis
control. This has been observed for co-infections between S. haematobium
and S. mansoni where the species are urogenital and intestinal forms,
respectively.
Schistosoma intercalatum and Schistosoma guineensis have not been specifi-
cally reported to be involved FGS or MGS, either alone or in combination
with an underlying S. haematobium. However, this association has never
actually been investigated. This absence, together with that of any morbidity
impact of S. haematobium hybrid forms is more likely to represent a deficit in
application of precise species-specific diagnostic methods per se rather than
these species’ inability to colonize veins surrounding the genitalia and
deposit eggs therein.
The same molecular genetic markers that have been used to characterize
these species and hybrid forms collected from their human hosts, could be
applied for a more in-depth analysis of clinical materials associated with FGS
and MGS. This could involve the evaluation of ejaculate or cervicovaginal
samples with molecular diagnostics, to gauge the extent to which existing
S. haematobium-hybrids contribute to genital schistosomiasis. A further

research need is an improved understanding of not just the epidemiology
of S. haematobium-hybrids, but also their role in inflammation, and
organ-specific responses, including FGS and MGS (Baay et al., 2004;
Kayuni et al., 2019a; Leutscher et al., 2009).
2. Pathogenesis and clinical manifestations

2.1 Female genital schistosomiasis (FGS)
FGS was specifically recognized in the medical literature over 100 years ago
(Madden, 1899), but it is still often incorrectly reported and seldom treated.
This is partly due to overlapping symptoms with sexually transmitted infections
(Christinet et al., 2016; Kjetland et al., 2012). As a neglected gynaecological
condition in SSA, FGS is not frequently considered in clinical practice, with
both patients and practitioners alike unaware of the disease and its downstream
sexual and reproductive health consequences (Ngwenya, 2016).
The pathogenesis of FGS is the result of a complex inflammatory
immune response driven by the antigens released from both viable eggs,
which have been entrapped in genital tissue, and adult worms located in
small veins of the pelvis (Fig. 3). Inflammation occurs in all strata of the gen-
ital tissue including the small blood vessels ( Jourdan et al., 2011a, 2013).
Schistosomiasis related inflammation extends beyond egg-deposition site
eventually affecting entire organs (Ramarokoto et al., 2014; Schanz et al.,
2010). Lesions in the vulva, vagina and the cervix are easiest to detect
and can be identified with a colposcope (Yirenya-Tawiah et al., 2011).
Deeper lesions in the uterus, the Fallopian tubes and the ovaries are challeng-
ing to assess (Andrianjafitrimo et al., 2019) but the ensuing pathology is asso-
ciated with chronic morbidity and can sometimes be life-threatening
(Kjetland et al., 2010; Norseth et al., 2014; Schanz et al., 2010; Swai
et al., 2006) and often negatively impacts women’s reproductive health
(Laroche et al., 2016; Laxman et al., 2008).
Studies in Niger, Malawi and Zimbabwe have found that up to 75% of
women with urinary schistosomiasis also have S. haematobium eggs distrib-
uted in the genital tissues (Kjetland et al., 1996, 2005; Poggensee et al., 1998;
Renaud et al., 1989). However, just as importantly, at least 20% of women
with Schistosoma genital involvement did not have eggs present in the urine
(Poggensee et al., 1998). These data highlight the non-linear relationship
between egg detection by different diagnostic methods and established
genital morbidity.
Vulvar or vaginal ulcerations and papillomata have been associated with

FGS (Goldsmith et al., 1993; Laven et al., 1998; Yirenya-Tawiah et al.,
2011). These may lead to stigmatization if the findings are misinterpreted
as being caused by a sexually transmitted infection (Goldsmith et al.,
1993). Consequences of FGS may include post-coital pain and bleeding
which are not uniquely identifiable as associated with schistosomiasis. Of
special concern, women with FGS in rural Zimbabwean had a twofold
greater odds of prevalent HIV infection (Kjetland et al., 2006).
Recent population-based and ecological studies have linked FGS with
female infertility and sub-fecundity in endemic communities (Kjetland
et al., 2010; Miller-Fellows et al., 2017; Woodall and Kramer, 2018).
More recently, the Bilharzia and HIV (BILHIV) study in Zambia (Sturt
et al., 2020b), found a twofold increase in delayed conception in women
with FGS as diagnosed by DNA-based detection methods (Mills, 2021).
FGS occurs in women of all age groups, including young girls, and is
associated with important, frequently debilitating and stigmatizing morbid-
ity. Women with FGS report spontaneous or post-coital bleeding, vaginal
discharge, pain during sexual intercourse, pelvic pain, irregular menstruation
and infertility (Kjetland et al., 2008, 2010). Across studies in Zambia and
Zimbabwe, a higher proportion of young women were found to have more
detectable Schistosoma DNA in their genital tract than older women
(Kjetland et al., 2009; Sturt et al., 2020b). Additionally, young girls with uri-
nary S. haematobium may present with gynaecological symptoms prior to
their sexual debut, in particular bloody or foul-smelling vaginal discharge
(Hegertun et al., 2013). These symptoms are frequently attributed to STIs
by health care providers, contributing to the associated stigma. As a conse-
quence, many women are not encouraged to pursue medical help at health
centers and are seeking help from traditional healers (Madagascar KAP study,
Randriansolo, B, personal communication). Vagino-vesical fistulae in
women are unlikely to heal if concomitant schistosomiasis is left untreated
(Richter et al., 2008).
2.1.1 Pregnancy and placental involvement

The placenta may also be involved during chronic Schistosoma infection,
however foetal outcomes of prematurity or lower birth weight are primarily
due to the effect of schistosomiasis on the mother, in conjunction with pro-
tein loss and anaemia (Schleenvoigt et al., 2014). Maternal iron deficiency
during pregnancy is also associated with iron deficiency among infants

(Abioye et al., 2019; Friedman et al., 2007; Mombo-Ngoma et al., 2017;
Siegrist and Siegrist-Obimpeh, 1992). Importantly, the effect of underlying
FGS on pregnancy outcomes has not been explored.
2.2 Male genital schistosomiasis (MGS)

The first case of MGS was reported in 1911 (Madden, 1911). This was
followed by several case reports, post-mortem and histopathological research
studies in the subsequent decades (Corachan et al., 1994; Gelfand et al., 1970;
Leutscher et al., 2000). Like FGS, MGS is underreported and often not rec-
ognized by medical providers in endemic areas. Schistosome eggs passing
through or being entrapped in the tissues of prostate, seminal vesicles, vas
deferens, epididymis and testis, trigger immune reactions and granulomata
formation (Kayuni et al., 2019b). In addition to granulomatous inflammation,
post-mortem and histopathological studies have shown egg-induced lesions
such as fibrosis and calcifications which can also be detected on radiological
examinations (Al-Saeed et al., 2003; Ramarakoto et al., 2008; Vilana
et al., 1997).
In MGS, changes of sperm consistency or blood in semen
(haematospermia) are often presenting symptoms (Corachan et al.,
1994). A particular observation in retuning travellers, haematospermia can
present in the early stages of MGS (Barlow and Meleney, 1949; Feldmeier
et al., 1999; Schwartz et al., 2002) and in some instances at a young age
(Rambau et al., 2011). Symptoms associated with semen quality and outflow
include, coital or ejaculatory pain, abnormal ejaculates, and occasional spe-
rmaturia (presence of spermatozoa in urine). Additionally, orchitis, prostatitis,
dyspareunia, and hydrocele are also associated with MGS. Other potential
symptoms include pelvic pain, erectile and ejaculatory dysfunction or para-
phimosis. To date, the epidemiology, diagnostic testing, specific clinical man-
ifestations and case management of MGS are not well or widely described.
There are little data regarding the current burden of and morbidity among
local inhabitants in endemic areas of SSA.
The aetiology of symptom underreporting in MGS is likely multi-
factorial including stigma associated with genital tract infections and the
potential impact on fertility-despite the quality of the semen being
preserved (Leutscher et al., 2009). Studies in Madagascar and Malawi have
demonstrated resolution of symptoms after anti-schistosomal therapy
(Kayuni et al., 2019a,b; Leutscher et al., 2000, 2009). This finding has
increased interest in including men-at-risk of schistosomiasis during mass
drug administration campaigns in endemic areas.
3. Immunology
3.1 Vaginal environment in FGS
Chronic egg deposition in genital tissues results in the clinical manifestations
associated with FGS (Kjetland et al., 2005). However, studying the natural
history of S. haematobium egg deposition in human genital tissue through to
the formation of cervicovaginal lesions is not ethically permissible and there
are no well described clinical manifestations during acute infection in
humans (Odegaard and Hsieh, 2014). These limitations restrict the current
knowledge to an extrapolation r from animal models. A murine FGS model
has been created through the microinjection of viable S. haematobium eggs
into the vaginal walls of female BALB/c mice (Richardson et al., 2014).
Eight weeks after vaginal egg injection, mice developed egg-associated
granulomata surrounded by eosinophils, neutrophils, and lymphocytes.
Both Schistosoma infection and subsequent egg patency stimulate
immune responses, though divergent in character. Acute schistosomiasis,
also known as Katayama Syndrome is thought to occur in response to the
migration of the immature schistosomula and evokes an initial T helper type
1 (Th1) response (Ross et al., 2007). As the schistosomes mature and pro-
duce eggs, a T helper type 2 (Th2) response prevails, stimulated primarily by
antigens present on schistosome eggs (Pearce and MacDonald, 2002). Both
Th1 and Th2 responses can be associated with morbidity (Fallon, 2000),
while granuloma formation (Pearce and MacDonald, 2002) and clinically
detected hepatic fibrosis in S. mansoni are associated with a Th2 response
(Mutengo et al., 2018). However, a carefully orchestrated balance between
Th1 and Th2 responses is required as an unopposed Th1 response has been
associated with mortality in murine hosts (Fallon, 2000; Fallon et al., 2000).
Studying local cytokines and chemokines can provide additional infor-
mation regarding downstream biological processes associated with
Schistosoma egg deposition. Murine studies emphasize the importance of
studying the immune environment local to egg deposition (Fu et al.,
2012; Richardson et al., 2014). For example, a Luminex multiplex
bead-based immunoassay was used to evaluate cytokine responses in a study
of mice with urinary S. haematobium infection highlighted a Th2 cytokine
bias (interleukin [IL]- 4, IL-13, and IL-5) in the local bladder environment
(Fu et al., 2012). However, when similar techniques were used to evaluate
cytokine concentrations in systemic circulation of mice with FGS, only

differences in RANTES were detected (Richardson et al., 2014).
While the immunology of human Schistosoma infections has been widely
explored, data regarding the immunologic microenvironment in FGS are
limited. In human studies, women with S. haematobium infection, in the
absence of evaluation for genital involvement, have also been shown to have
altered levels of IL-15 in cervicovaginal lavage as well as differences in the
expression of genes associated with regulating extracellular matrix deposi-
tion, angiogenesis, and protease activity in the cervical mucosa (Dupnik
et al., 2019). Recent data on the immunology of FGS suggest the impor-
tance of an evaluation stratified by a measure of the burden of schistosome
infection. In the BILHIV study in Zambia when participants with a medium
to high Schistosoma DNA concentration was detected in any genital speci-
men (cervical or vaginal swab or cervicovaginal lavage (CVL)), higher con-
centrations of Th2 (IL-5) and pro-inflammatory (TNF-α) cytokines were
detected in CVL after adjusting for multiple comparisons and potential
confounders (Sturt et al., 2021a).
3.2 Immune activation during pregnancy

There are currently no studies on pregnancy outcomes or placental involve-
ment in women infected with S. haematobium (Bustinduy et al., 2017).
Studies in the Philippines have shown elevated inflammatory cytokines
(Kurtis et al., 2011) and high levels of endotoxin, a systemic immune activa-
tion marker, in pregnant women whose placentas were concomitantly
infected with Schistosoma japonicum compared to non-infected women
(McDonald et al., 2014). Furthermore, women with high levels of endotoxin
had adverse pregnancy outcomes including prematurity (McDonald et al.,
2014). Despite clear differences in the pathophysiology of S. haematobium
and S. japonicum, which target different organ systems there appears to be
common pro-inflammatory pathways. Further research is needed in women
with FGS to understand gestational issues and in the case of pregnant women
infected with S. haematobium pre-gestational female genital schistosomiasis.
4. Diagnosis of genital schistosomiasis

4.1 FGS diagnostics
Conventional FGS diagnosis is challenging, as it relies on costly equipment
and high-level specialized training seldom available in resource-limited set-
tings. This hinders the accurate estimation of disease burden and challenges
study comparisons due to differences in FGS case definitions. For example,

egg visualization in the genital mucosa is sufficient but not necessary for FGS
diagnosis. Concerns of increasing the risk of HIV acquisition have
preempted the routine use of biopsies for FGS diagnosis (Kjetland et al.,
2012). As a consequence, well conducted histopathological studies are
scarce. Recently, the wider availability of molecular diagnostic assays
allowed methods like PCR to aid in the diagnostic accuracy of FGS, as well
as for MGS, by identifying Schistosoma DNA within samples acquired from
the genital tract (Downs et al., 2013; Kjetland et al., 2009; Kayuni et al.,
2019a; Pillay et al., 2014; Sturt et al., 2020b, 2021a).
4.1.1 Traditional colposcopy

A visual FGS diagnosis involves using a colposcope to obtain a magnified and
illuminated view of the cervix and vaginal walls and fornices (Norseth et al.,
2014). FGS-associated lesions in the vulva/vagina and the cervix are the
most visible and have therefore been described in detail (Norseth et al.,
2014). Characteristic clinical findings associated with FGS include grainy
sandy patches, homogenous sandy patches and rubbery papules (Kjetland
et al., 2014; Norseth et al., 2014; Randrianasolo et al., 2015). Abnormal
vessels have also been described in FGS ( Jourdan et al., 2013) (Fig. 4).
The grains of the sandy patches are approximately 0.05 mm 0.2 mm
long, are shaped like grains of rice, they may be single Schistosoma ovum
or exist in clusters of up to 300 (Randrianasolo et al., 2015). These individual
grains (viz. eggs) are deep or superficially situated in the mucosa, with a char-
acteristic yellow, off-white or golden colour. The deeply situated grains
merge into sub-mucosal plaque-like formations with uneven edges and sha-
des of texture. Sometimes, the mucosa is mottled beneath the surface. The
mucosal surface over the deeply grained patches is smooth and grains are not
mobile. The superficial grains have a distinct shape and colour. Grains can
Fig. 4 FGS atlas of visual diagnosis (WHO, 2015). From left to right: Grainy sandy pat-
ches, homogeneous sandy patches, abnormal vessels and rubbery papules.
often be distinguished easily from each other even when they are clustered
together (WHO, 2015).
The homogeneous yellow sandy patches are defined as sandy looking
areas with no visible grains when using the 15 times magnification setting
on the colposcope, appearing as homogenous, yellow areas (Kjetland et al.,
2005). Rubbery papules were initially found and described in Madagascar
(Randrianasolo et al., 2015), but have been described elsewhere (Ekpo
et al., 2017). They are spheroid, pustuloid, firm (hence rubbery), beige papules
that may give the cervicovaginal mucosa an irregular surface. The rubbery
papules may stand alone, or can be found concurrently with sandy patches.
They are often surrounded by various degrees of vascularisation at their base
(Randrianasolo et al., 2015).
Traditional colposcopes are expensive pieces of equipment that are sel-
dom available in resource-constrained settings, where access to electricity
and adequate infrastructure is limited. Furthermore, they require specialist
training to operate. Where colposcopy is not possible, The Female Genital
Schistosomiasis Pocket Atlas has been developed by the WHO as a visual aid
and is free of charge. This resource was created to raise awareness about
FGS and to facilitate clinical diagnosis by clinical health-care professionals
working particularly in rural areas where schistosomiasis is endemic (WHO,
2015) (Fig. 4).
Alternative means of visual diagnosis in-lieu of colposcopy or medical
expertise are urgently needed to increase FGS surveillance at scale. There
are attempts to develop artificial intelligence visual reading algorithms based
on a computer colour analysis (Holmen et al., 2015b). The computer anal-
ysis identifies the region of interest (the ectocervical mucosa) and splits the
image in multiple colour channels, based on the characteristic colour prop-
erties of the FGS lesions (yellow sandy patches). This method shows prom-
ising results in terms of accuracy, but the specificity needs to be refined
(Holmen et al., 2015a).
4.1.2 Hand-held colposcopy and other hand-held devices

The use of simple electronic devices such as handheld cameras, mobile
phone cameras, or other can be an alternative to document FGS lesions with
acceptable results and have been used in an ongoing study in Madagascar
(Randriansolo, B. Personal communication).
Handheld colposcopy has been widely used for the diagnosis of cervical
cancer in remote settings. A recent systematic review of different available
handheld devices for the diagnosis of cervical cancer screening included
Fig. 5 Images obtained by hand-held colposcopy from women in Zambia and Malawi.
They were all PCR positive for Schistosoma haematobium from genital samples. Outlined
areas highlight homogeneous sandy patches (A, C, D), grainy sandy patches (E, F) and
clusters of eggs (B).
smartphones, a digital camera and several handheld colposcopes, their avail-

ability, price and image quality. The study concluded that two handheld
colposcopes, the Gynocular and Mobile ODT could be potentially useful
for FGS diagnosis (Softeland et al., 2021). In two studies in Malawi and
Zambia, hand-held colposcopy (Mobile ODT) enabled the detection of
FGS lesions as shown in Fig. 5 (Bustinduy, AL. BILHIV study, Personal
communication).
4.1.3 Ultrasound scans and other radiological imaging

The role of advanced imaging modalities such as ultrasonography, CT scan,
and MR scan can aid in assessing the severity and complications of schisto-
some infection (Sah et al., 2015). Ultrasound is a non-invasive imaging
method that cannot detect schistosome infection but rather is used to assess
Schistosoma-induced pathology (Skelly, 2013). Despite the use of more sen-
sitive transvaginal probes, specific schistosomiasis related lesions of the
female reproductive tract are difficult to diagnose by ultrasound
(Ramarakoto et al., 2008). Ultrasound may be helpful in diagnosing com-

plications related to genital schistosomiasis such as sterility, vesico-vaginal
fistulae (Ben-Chetrit et al., 2015; Richter et al., 2008; Schanz et al.,
2010; Schleenvoigt et al., 2014) and gestation issues such as ectopic pregnan-
cies due to granulomatous tubal obstruction (Laroche et al., 2016; Laxman
et al., 2008; Sheorey et al., 2004).
4.1.4 Parasitology diagnosis

It is possible to identify eggs upon microscopy of genital samples through
wet preps or pap smears. However, this technique is not frequently used,
as several studies have demonstrated its low sensitivity ( Jourdan et al.,
2011b; Pillay et al., 2016; Poggensee et al., 2001b).
4.2 Molecular diagnostics (nucleic acid amplification tests)

4.2.1 Real time PCR
Due to their high specificity and sensitivity, DNA detection methods have
become a feasible option for the diagnosis of schistosomiasis (Hoekstra et al.,
2021; Utzinger et al., 2015). Specifically, for FGS, parasite DNA detection
from cervicovaginal lavage has been postulated as a highly specific diagnostic
method with potential to monitor treatment effect (Downs et al., 2013;
Randrianasolo et al., 2015; Sturt et al., 2020b). Although specificity was high,
some studies reported low sensitivities in the detection of Schistosoma DNA in
cervicovaginal lavage samples, ranging from 15% to 53% using visual methods
as the diagnostic reference for FGS (Galappaththi-Arachchige et al., 2018;
Kjetland et al., 2009). More recently, the BILHIV study in Zambia reported
a sensitivity of 80% when Schistosoma PCR was performed on vaginal and cer-
vical swabs obtained through home-based self-sampling and were compared
with detectable Schistosoma DNA in any positive genital sample as a composite
reference. The sensitivity increased to 89% when women with active schis-
tosomiasis, as defined by a positive circulating anodic antigen, were included
(Sturt et al., 2020b). Vaginal and cervical self-sampling at home for FGS
screening was well accepted by participants and can offer a scalable option
for FGS screening and surveillance (Rutty Phiri et al., 2020).
4.2.2 Isothermal diagnostics

Novel molecular diagnostics specifically isothermal (low constant tempera-
ture) molecular diagnostics such as Recombinase Polymerase Amplification
(RPA) (Archer et al., 2020b; Rosser et al., 2015; Rostron et al., 2019) and
Loop Mediated Isothermal Amplification (LAMP) (Gandasegui et al., 2018)

offer an alternative to PCR-based amplification. These assays are better suited
for use in resource-limited settings as they require only minimal equipment,
can be performed using a crude DNA extraction process that can be easily
prepared under field conditions. Results can be rapidly obtained in less than
1 h (Archer et al., 2020a; Lodh et al., 2017).
A previously developed RPA assay (the RT-ShDra1-RPA (Sh-RPA)) has
been used to detect trace levels of Schistosoma ova-derived DNA within
egg-spiked laboratory samples (able to detect a single S. haematobium egg
within 100 μL ddH2O), as well as in clinical urine samples from patients
with very low infection intensities (1–3 eggs per/10 mL) (Archer et al.,
2020b; Frimpong et al., 2021; Rosser et al., 2015; Rostron et al., 2019).
The method is simple, quick (<20 min), portable, low-footprint (can run
at temperatures from 25 to 42 °C) and can be performed using crude sample
preparations.
The Sh-RPA assay has also been piloted to detect S. haematobium DNA
in FGS samples collected as part of BILHIV study in Zambia (Sturt et al.,
2020b). The rapid and portable Sh-RPA assay was able to reliably detect
and amplify S. haematobium DNA within vaginal self-swab samples and pro-
vider obtained cervicovaginal lavage (CVL) using two crude extraction
methods that can be easily and rapidly carried out in field settings. Based
on RT-PCR as the reference test (Sturt et al., 2020b), the Sh-RPA assay
proved to be highly sensitive and specific for self-swab samples, 93.3%
and 96.6%, respectively (Archer, J et al. manuscript under review).
LAMP also has the potential for field-based/point-of-care diagnosis and
assays have been developed for the three main Schistosoma species,
S. haematobium, S. mansoni and S. japonicum. LAMP performs at tempera-
tures between 60 and 65 °C and takes from 30 to 60 min. Its set up can
be simple with low equipment requirements although its design can be com-
plex, needing up to six primers. An assay for urogenital schistosomiasis
proved sensitive and specific, 100% and 86.7%, respectively (Gandasegui
et al., 2018) but has not been tested for FGS diagnosis.
The ease of use, low-resource needs, simplicity and feasibility demon-
strated by LAMP and RPA in field conditions together with the acceptable
level of reproducibility achieved in a reference laboratory, support the use of
these isothermal assays as effective molecular diagnostics for urogenital schis-
tosomiasis in remote endemic areas. These assays have great potential for
field-based point-of-care diagnosis of FGS using self-swab samples.
4.2.3 Histopathology
Direct examination of cervical tissue obtained by biopsy from a suspicious
lesion can be promptly examined by crushing the biopsy specimen between
two glass slides. This technique, known as quantitative crushed biopsy allows
examination for S. haematobium eggs at 100 and provides indisputable evi-
dence of FGS (Poggensee et al., 2001b). However, since eggs may cluster in
the cervix, biopsy and the subsequent histopathology may miss eggs
(Helling-Giese et al., 1996b; Randrianasolo et al., 2015).
4.3 MGS diagnostics

To date, optimal MGS diagnosis remains largely undefined (Kayuni et al.,
2019b). Currently, semen microscopy is considered the standard technique
for diagnosing active MGS. Since Schistosoma eggs can be visualized and
quantified in semen, microscopy can also assess MGS infection intensity.
However, sensitivity and cultural misgivings around the submission and
handling of semen in most rural endemic areas pose challenges for MGS
diagnosis (Kayuni et al., 2019a).
Fig. 6 S. haematobium egg in semen at 400 magnification. Photo credit. S. Kayuni.

4.3.1 Parasitology and molecular diagnostics in MGS

As in FGS, the diagnosis of urinary schistosomiasis is often used as a proxy for
the presence of MGS (Downs et al., 2011). However, this practice lacks sen-
sitivity, as there are reports of schistosome eggs detected in the semen of
patients with no eggs present in the urine (Schwartz et al., 2002; van
Delft et al., 2007) (Fig. 6).
Semen samples need to be processed within 2–3 h of submission and
technicians must allow the semen to liquefy. Thereafter, a drop of well-
mixed semen can be placed on a glass slide with coverslip and light micros-
copy using 40 and 100 magnification can be used to visualize for schis-
tosome eggs. Results can be recorded as eggs visualized per ml of ejaculate
(Kayuni et al., 2019a). Different preservation techniques have been devel-
oped to increase the sensitivity of the assays (Kenguele et al., 2014).
If available, molecular tests can be performed on semen for the detection
of Schistosoma DNA (Kayuni et al., 2019a). Alternative diagnostic methods
for MGS include the detection of soluble egg antigen (SEA) and eosinophil
cationic protein (ECP) in urine and semen and circulating anodic antigen in
serum. The concentration of these proteins correlates with urinary schisto-
some egg excretion but are still not available for clinical diagnosis (Leutscher
et al., 2008).
4.4 Immunopathology in MGS

A single study in Madagascar has explored the immune activation through
seminal egg-induced inflammation in individuals with MGS (Leutscher
et al., 2005). Elevated cytokines (IL-4, IL-6, IL-10 and TNF-α) and
increased leukocytes (eosinophils, lymphocytes) were significantly elevated
in the semen of men with MGS compared to those with no Schistosoma
infection, controlling for sexually transmitted infections (Leutscher et al.,
2005). MGS infection intensity, defined by seminal egg count, was strongly
associated with elevated seminal cytokine concentrations including Th2
(IL-4), regulatory (IL-10), Th1 (IFN-γ) and pro-inflammatory (TNF-α)
immune proteins. Local inflammation is hypothesized to increase viral shed-
ding in the ejaculate from co-infected HIV positive men with MGS, hence
putting the female partner at additional risk of being infected with HIV in
particular if this woman also suffers from egg-induced lesions in the lower
genital tract (Leutscher et al., 2000; Midzi et al., 2017), but longitudinal
studies are needed to confirm this.
Another random document with
no related content on Scribd:
Julia Redmond shook her head. She did not want compliments. The
eyes of the two women met and read each other.
"Couldn't you be frank with me, Madame? It is so easy to be frank."
It was, indeed, impossible for Julia Redmond to be anything else. The

comtesse, who was only a trifle older than the young girl, felt like her
mother just then. She laughed.
"But be frank—about what?"
"You see," said Julia Redmond swiftly, "I care absolutely nothing for the
Duc de Tremont, nothing."
"You don't love him?" returned Madame de la Maine, with deep

accentuation. "Is it possible?"
The girl smiled.
"Yes, quite possible. I think he is a perfect dear. He is a splendid friend

and I am devoted to him, but I don't love him at all, not at all."
"Ah!" breathed Madame de la Maine, and she looked at the American

girl guardedly.
For a moment it was like a passage of arms between a frank young

Indian chief and a Jesuit. Julia, as it were, shook her feathers and her beads.
"And I don't care in the least about being a duchess! My father made his
money in oil. I am not an aristocrat like my aunt," she said.
"Then," said the Comtesse de la Maine, forgetting that she was a Jesuit,
"you will marry Robert de Tremont simply to please your aunt?"
"But nothing on earth would induce me to marry him!" cried Julia

Redmond. "That's what I'm telling you, Madame. I don't love him!"
The Comtesse de la Maine looked at her companion and bit her lip. She
blushed more warmly than is permitted in the Faubourg St.-Germain, but
she was young and the western influence is pernicious.
"I saw at once that you loved him," said Julia Redmond frankly. "That's
why I speak as I do."
The Comtesse de la Maine drew back and exclaimed.
"Oh," said Julia Redmond, "don't deny it. I shan't like you half so well if
you do. There is no shame in being in love, is there?—especially when the
man you love, loves you."
The Comtesse de la Maine broke down, or, rather, she rose high. She
rose above all the smallness of convention and the rules of her French
formal education.
"You are wonderful," she said, laughing softly, her eyes full of tears.
"Will you tell me what makes you think that he is fond of me?"
"But you know it so well," said Julia. "Hasn't he cared for you for a long
time?"
Madame de la Maine wondered just how much Julia Redmond had

heard, and as there was no way of finding out, she said graciously:
"He has seemed to love me very dearly for many years; but I am poor; I
have a child. He is ambitious and he is the Duc de Tremont."
"Nonsense," said Julia. "He loves you. That's all that counts. You will be
awfully happy. You will marry the Duc de Tremont, won't you? There's a
dear."
"Happy," murmured the other woman, "happy, my dear friend, I never

dreamed of such a thing!"
"Dream of it now," said Julia Redmond swiftly, "for it will come true."
CHAPTER XIX
THE MAN IN RAGS
The Marquise d'Esclignac, under the stars, interviewed the native

soldier, the beggar, the man in rags, at the foot of the veranda. There was a
moon as well as stars, and the man was distinctly visible in all his squalor.
"What on earth is he talking about, Robert?"
"About Sabron, marraine," said her godson laconically.
The Marquise d'Esclignac raised her lorgnon and said:
"Speak, man! What do you know about Monsieur de Sabron? See, he is

covered with dirt—has leprosy, probably." But she did not withdraw. She
was a great lady and stood her ground. She did not know what the word
"squeamish" meant.
Listening to the man's jargon and putting many things together, Tremont
at last turned to the Marquise d'Esclignac who was sternly fixing the beggar
with her haughty condescension:
"Marraine, he says that Sabron is alive, in the hands of natives in a

certain district where there is no travel, in the heart of the seditious tribes.
He says that he has friends in a caravan of merchants who once a year pass
the spot where this native village is."
"The man's a lunatic," said the Marquise d'Esclignac calmly. "Get

Abimelec and put him out of the garden, Robert. You must not let Julia hear
of this."
"Marraine," said Tremont quietly, "Mademoiselle Redmond has already

seen this man. He has come to see her to-night."
"How perfectly horrible!" said the Marquise d'Esclignac. Then she

asked rather weakly of Tremont: "Don't you think so?"
"Well, I think," said Tremont, "that the only interesting thing is the truth
there may be in what this man says. If Sabron is a captive, and he knows
anything about it, we must use his information for all it is worth."
"Of course," said the Marquise d'Esclignac, "of course. The war
department must be informed at once. Why hasn't he gone there?"
"He has explained," said Tremont, "that the only way Sabron can be
saved is that he shall be found by outsiders. One hint to his captors would
end his life."
"Oh!" said the Marquise d'Esclignac. "I don't know what to do, Bob!
What part can we take in this?"
Tremont pulled his mustache. Mimi had circled round the beggar,
snuffing at his slippers and his robe. The man made no objection to the little
creature, to the fluffy ball surrounded by a huge bow, and Mimi sat
peacefully down in the moonlight, at the beggar's feet.
"Mimi seems to like him," said the Marquise d'Esclignac helplessly,

"she is very particular."
"She finds that he has a serious and convincing manner," said Tremont.
Now the man, who had been a silent listener to the conversation, said in
fairly comprehensible English to the Marquise d'Esclignac:
"If the beautiful grandmother could have seen the Capitaine de Sabron
on the night before the battle—"
"Grandmother, indeed!" exclaimed the marquise indignantly. "Come,

Mimi! Robert, finish with this creature and get what satisfaction you can
from him. I believe him to be an impostor; at any rate, he does not expect
me to mount a camel or to lead a caravan to the rescue."
Tremont put Mimi in her arms; she folded her lorgnon and sailed
majestically away, like a highly decorated pinnace with silk sails, and
Tremont, in the moonlight, continued to talk with the sincere and
convincing Hammet Abou.
CHAPTER XX
JULIA DECIDES
Now the young girl had his letters and her own to read. They were
sweet and sad companions and she laid them side by side. She did not
weep, because she was not of the weeping type; she had hope.
Her spirits remained singularly even. Madame de la Maine had given

her a great deal to live on.
"Julia, what have you done to Robert?"
"Nothing, ma tante"
"He has quite changed. This excursion to Africa has entirely altered
him. He is naturally so gay," said the Marquise d'Esclignac. "Have you
refused him, Julia?"
"Ma tante, he has not asked me to be the Duchess de Tremont."
Her aunt's voice was earnest.
"Julia, do you wish to spoil your life and your chances of happiness? Do
you wish to mourn for a dead soldier who has never been more than an
acquaintance? I won't even say a friend."
What she said sounded logical.
"Ma tante, I do not think of Monsieur de Sabron as dead, you know."

"Well, in the event that he may be, my dear Julia."
"Sometimes," said the girl, drawing near to her aunt and taking the older
lady's hand quietly and looking in her eyes, "sometimes, ma tante, you are
cruel."
The marquise kissed her and sighed:
"Robert's mother will be so unhappy!"
"But she has never seen me, ma tante."
"She trusts my taste, Julia."
"There should be more than 'taste' in a matter of husband and wife, ma

tante."
After a moment, in which the Marquise d'Esclignac gazed at the

bougainvillea and wondered how any one could admire its crude and vulgar
color, Miss Redmond asked:
"Did you ever think that the Duc de Tremont was in love?"
Turning shortly about to her niece, her aunt stared at her.
"In love, my dear!"
"With Madame de la Maine."
The arrival of Madame de la Maine had been a bitter blow to the

Marquise d'Esclignac. The young woman was, however, much loved in
Paris and quite in the eye of the world. There was no possible reason why
the Marquise d'Esclignac should avoid her.
"You have been hearing gossip, Julia."
"I have been watching a lovely woman," said the girl simply, "and a
man. That's all. You wouldn't want me to marry a man who loves another
woman, ma tante, when the woman loves him and when I love another
man?"
She laughed and kissed her aunt's cheek.
"Let us think of the soldier," she murmured, "let us think just of him, ma
tante, will you not?"
The Marquise d'Esclignac struck her colors.
In the hallway of the villa, in a snowy gibbeh, (and his clean-washed

appearance was much in his favor) Hammet Abou waited to talk with the
"grandmother" and the excellency.
He pressed both his hands to his forehead and his breast as the ladies
entered the vestibule. There was a stagnant odor of myrrh and sandalwood
in the air. The marble vestibule was cool and dark, the walls hung with
high-colored stuffs, the windows drawn to keep out the heat.
The Duc de Tremont and Madame de la Maine came out of the salon
together. Tremont nodded to the Arab.
"I hope you are a little less—" and he touched his forehead smiling, "to-
day, my friend."
"I am as God made me, Monsieur."
"What have you got to-day?" asked Julia Redmond anxiously, fixing her
eager eyes upon Hammet.
It seemed terrible to her that this man should stand there with a vital
secret and that they should not all be at his feet. He glanced boldly around
at them.
"There are no soldiers here?"
"No, no, you may speak freely."

The man went forward to Tremont and put a paper in his hands,
unfolding it like a chart.
"This is what monsieur asked me for—a plan of the battle-field. This is

the battle-field, and this is the desert."
Tremont took the chart. On the page was simply a round circle, drawn
in red ink, with a few Arabian characters and nothing else. Hammet Abou
traced the circle with his fingers tipped with henna.
"That was the battle, Monsieur."
"But this is no chart, Hammet Abou."
The other continued, unmoved:
"And all the rest is a desert, like this."
Tremont, over the man's snowy turban, glanced at the others and
shrugged. Every one but Julia Redmond thought he was insane. She came
up to him where he stood close to Tremont. She said very slowly in French,
compelling the man's dark eyes to meet hers:
"You don't wish to tell us, Hammet Abou, anything more. Am I not
right? You don't wish us to know the truth."
Now it was the American pitted against the Oriental. The Arab, with
deference, touched his forehead before her.
"If I made a true plan," he said coolly, "your excellency could give it to-
morrow to the government."
"Just what should be done, Julia," said the Marquise d'Esclignac, in

English. "This man should be arrested at once."
"Ma tante," pleaded Julia Redmond.
She felt as though a slender thread was between her fingers, a thread
which led her to the door of a labyrinth and which a rude touch might cause
her to lose forever.
"If you had money would you start out to find Monsieur de Sabron at
once?"
"It would cost a great deal, Excellency."
"You shall have all the money you need. Do you think you would be
able to find your way?"
"Yes, Excellency."
The Duc de Tremont watched the American girl. She was bartering with
an Arabian for the salvation of a poor officer. What an enthusiast! He had
no idea she had ever seen Sabron more than once or twice in her life. He
came forward.
"Let me talk to this man," he said with authority, and Julia Redmond did
not dispute him.
In a tone different from the light and mocking one that he had hitherto
used to the Arab, Tremont began to ask a dozen questions severely, and in
his answers to the young Frenchman, Hammet Abou began to make a
favorable impression on every one save the Marquise d'Esclignac, who did
not understand him. There was a huge bamboo chair on a dais under a
Chinese pagoda, and the Marquise d'Esclignac took the chair and sat
upright as on a throne. Mimi, who had just been fed, came in tinkling her
little bells and fawned at the sandals on Hammet Abou's bare feet. After
talking with the native, Tremont said to his friends:
"This man says that if he joins a Jewish caravan, which leaves here to-
morrow at sundown, he will be taken with these men and leave the city
without suspicion, but he must share the expenses of the whole caravan.
The expedition will not be without danger; it must be entered into with
great subtlety. He is either," said Tremont, "an impostor or a remarkable
man."
"He is an impostor, of course," murmured the Marquise d'Esclignac.
"Come here, Mimi."
Tremont went on:
"Further he will not disclose to us. He has evidently some carefully laid
plan for rescuing Sabron."
There was a pause. Hammet Abou, his hands folded peacefully across
his breast, waited. Julia Redmond waited. The Comtesse de la Maine, in her
pretty voice, asked quickly:
"But, mes amis, there is a man's life at stake! Why do we stand here
talking in the antechamber? Evidently the war office has done all it can for
the Capitaine de Sabron. But they have not found him. Whether this fellow
is crazy or not, he has a wonderful hypothesis."
A brilliant look of gratitude crossed Julia Redmond's face. She glanced

at the Comtesse de la Maine.
"Ah, she's got the heart!" she said to herself. "I knew it." She crossed
the hall to the Comtesse de la Maine and slipped her arm in hers.
"Has Monsieur de Sabron no near family?"
"No," said the Marquise d'Esclignac from her throne. "He is one of
those unfamilied beings who, when they are once taken into other hearts are
all the dearer because of their orphaned state."
Her tone was not unkind. It was affectionate.
"Now, my good man," she said to Hammet Abou, in a language totally

incomprehensible to him, "money is no object in this question, but what
will you do with Monsieur de Sabron if you find him? He may be an
invalid, and the ransom will be fabulous."
The Comtesse de la Maine felt the girl's arm in hers tremble. Hammet
Abou answered none of these questions, for he did not understand them. He
said quietly to Tremont:
"The caravan starts to-morrow at sundown and there is much to do."
Tremont stood pulling his mustache. He looked boyish and charming,

withal serious beyond his usual habit. His eyes wandered over to the corner
where the two women stood together.
"I intend to go with you, Hammet Abou," said he slowly, "if it can be
arranged. Otherwise this expedition does not interest me."
Two women said:
"Oh, heavens!" at once.
Robert de Tremont heard the note of anxiety in the younger voice alone.
He glanced at the Comtesse de la Maine.
"You are quite right, Madame," he said, "a man's life is at stake and we
stand chaffing here. I know something of what the desert is and what the
natives are. Sabron would be the first to go if it were a question of a brother
officer."
The Marquise d'Esclignac got down from her throne, trembling. Her
eyes were fixed upon her niece.
"Julia," she began, and stopped.
Madame de la Maine said nothing.
"Robert, you are my godson, and I forbid it. Your mother—"
"—is one of the bravest women I ever knew," said her godson. "My
father was a soldier."
Julia withdrew her arm from the Comtesse de la Maine as though to

leave her free.
"Then you two girls," said the Marquise d'Esclignac, thoroughly

American for a moment, "must forbid him to go." She fixed her eyes sternly
upon her niece, with a glance of entreaty and reproach. Miss Redmond said
in a firm voice:
"In Monsieur de Tremont's case I should do exactly what he proposes."
"But he is risking his life," said the Marquise d'Esclignac. "He is not
even an intimate friend of Monsieur de Sabron!"
Tremont said, smiling:
"You tell us that he has no brother, marraine. Eh bien, I will pass as his
brother."
A thrill touched Julia Redmond's heart. She almost loved him. If, as her
aunt had said, Sabron had been out of the question...
"Madame de la Maine," said the Marquise d'Esclignac, her hands

shaking, "I appeal to you to divert this headstrong young man from his
purpose."
The Comtesse de la Maine was the palest of the three women. She had
been quietly looking at Tremont and now a smile crossed her lips that had
tears back of it—one of those beautiful smiles that mean so much on a
woman's face. She was the only one of the three who had not yet spoken.
Tremont was waiting for her. Hammet Abou, with whom he had been in
earnest conversation, was answering his further questions. The Marquise
d'Esclignac shrugged, threw up her hands as though she gave up all
questions of romance, rescue and disappointed love and foolish girls, and
walked out thoroughly wretched, Mimi tinkling at her heels. The Comtesse
de la Maine said to Julia:
"Ma chère, what were the words of the English song you sang last night
—the song you told me was a sort of prayer. Tell me the words slowly, will
you?"
They walked out of the vestibule together, leaving Hammet Abou and
Tremont alone.
CHAPTER XXI
MASTER AND FRIEND
Pitchouné, who might have been considered as one of the infinitesimal

atoms in the economy of the universe, ran over the sands away from his
master. He was an infinitesimal dot on the desert's face. He was only a
small Irish terrier in the heart of the Sahara. His little wiry body and his
color seemed to blend with the dust. His eyes were dimmed by hunger and
thirst and exhaustion, but there was the blood of a fighter in him and he was
a thoroughbred. Nevertheless, he was running away. It looked very much
like it. There was no one to comment on his treachery; had there been,
Pitchouné would not have run far.
It was not an ordinary sight to see on the Sahara—a small Irish terrier
going as fast as he could.
Pitchouné ran with his nose to the ground. There were several trails for
a dog to follow on that apparently untrodden page of desert history. Which
one would he choose? Without a scent a dog does nothing. His nostrils are
his instinct. His devotion, his faithfulness, his intelligence, his heart—all
come through his nose. A man's heart, they say, is in his stomach—or in his
pocket. A dog's is in his nostrils. If Pitchouné had chosen the wrong
direction, this story would never have been written. Michette did not give
birth to the sixth puppy, in the stables of the garrison, for nothing. Nor had
Sabron saved him on the night of the memorable dinner for nothing.
With his nose flat to the sands Pitchouné smelt to east and to west, to
north and south, took a scent to the east, decided on it—for what reason will
never be told—and followed it. Fatigue and hunger were forgotten as hour
after hour Pitchouné ran across the Sahara. Mercifully, the sun had been
clouded by the precursor of a wind-storm. The air was almost cool.
Mercifully, the wind did not arise until the little terrier had pursued his
course to the end.
There are occasions when an animal's intelligence surpasses the human.

When, toward evening of the twelve hours that it had taken him to reach a
certain point, he came to a settlement of mud huts on the borders of an
oasis, he was pretty nearly at the end of his strength. The oasis was the only
sign of life in five hundred miles. There was very little left in his small
body. He lay down, panting, but his bright spirit was unwilling just then to
leave his form and hovered near him. In the religion of Tatman dogs alone
have souls.
Pitchouné panted and dragged himself to a pool of water around which

the green palms grew, and he drank and drank. Then the little desert
wayfarer hid himself in the bushes and slept till morning. All night he was
racked with convulsive twitches, but he slept and in his dreams, he killed a
young chicken and ate it. In the morning he took a bath in the pool, and the
sun rose while he swam in the water.
If Sabron or Miss Redmond could have seen him he would have seemed
the epitome of heartless egoism. He was the epitome of wisdom. Instinct
and wisdom sometimes go closely together. Solomon was only instinctive
when he asked for wisdom. The epicurean Lucullus, when dying, asked for
a certain Nile fish cooked in wine.
Pitchouné shook out his short hairy body and came out of the oasis pool
into the sunlight and trotted into the Arabian village.
* * * * * *
*
Fatou Anni parched corn in a brazier before her house. Her house was a
mud hut with yellow walls. It had no roof and was open to the sky. Fatou
Anni was ninety years old, straight as a lance—straight as one of the lances
the men of the village carried when they went to dispute with white people.
These lances with which the young men had fought, had won them the last
battle. They had been victorious on the field.
Fatou Anni was the grandmother of many men. She had been the
mother of many men. Now she parched corn tranquilly, prayerfully.
"Allah! that the corn should not burn; Allah! that it should be sweet;
Allah! that her men should be always successful."
She was the fetish of the settlement. In a single blue garment, her black
scrawny breast uncovered, the thin veil that the Fellaheen wear pushed back
from her face, her fine eyes were revealed and she might have been a
priestess as she bent over her corn!
"Allah! Allah Akbar!"
Rather than anything should happen to Fatou Anni, the settlement

would have roasted its enemies alive, torn them in shreds. Some of them
said that she was two hundred years old. There was a charmed ring drawn
around her house. People supposed that if any creature crossed it uninvited,
it would fall dead.
The sun had risen for an hour and the air was still cool. Overhead, the
sky, unstained by a single cloud, was blue as a turquoise floor, and against
it, black and portentous, flew the vultures. Here and there the sun-touched
pools gave life and reason to the oasis.
Fatou Anni parched her corn. Her barbaric chant was interrupted by a
sharp bark and a low pleading whine.
She had never heard sounds just like that. The dogs of the village were
great wolf-like creatures. Pitchouné's bark was angelic compared with
theirs. He crossed the charmed circle drawn around her house, and did not
fall dead, and stood before her, whining. Fatou Anni left her corn, stood
upright and looked at Pitchouné. To her the Irish terrier was an apparition.
The fact that he had not fallen dead proved that he was beloved of Allah. He
was, perhaps, a genie, an afrit.
Pitchouné fawned at her feet. She murmured a line of the Koran. It did
not seem to affect his demonstrative affection. The woman bent down to
him after making a pass against the Evil Eye, and touched him, and
Pitchouné licked her hand.
Fatou Anni screamed, dropped him, went into the house and made her
ablutions. When she came out Pitchouné sat patiently before the parched
corn, and he again came crawling to her.
The Arabian woman lived in the last hut of the village. She could satisfy
her curiosity without shocking her neighbors. She bent down to scrutinize
Pitchouné's collar. There was a sacred medal on it with sacred inscriptions
which she could not read. But as soon as she had freed him this time,
Pitchouné tore himself away from her, flew out of the sacred ring and
disappeared. Then he ran back, barking appealingly; he took the hem of her
dress in his mouth and pulled her. He repeatedly did this and the
superstitious Arabian believed herself to be called divinely. She cautiously
left the door-step, her veil falling before her face, came out of the sacred
ring, followed to the edge of the berry field. From there Pitchouné sped
over the desert; then he stopped and looked back at her. Fatou Anni did not
follow, and he returned to renew his entreaties. When she tried to touch him
he escaped, keeping at a safe distance. The village began to stir. Blue and
yellow garments fluttered in the streets.
"Allah Akbar," Fatou Anni murmured, "these are days of victory, of

recompense."
She gathered her robe around her and, stately and impressively, started
toward the huts of her grandsons. When she returned, eight young warriors,
fully armed, accompanied her. Pitchouné sat beside the parched corn,
watching the brazier and her meal. Fatou Anni pointed to the desert.
She said to the young men, "Go with this genie. There is something he
wishes to show us. Allah is great. Go."
* * * * * *
*
When the Capitaine de Sabron opened his eyes in consciousness, they

encountered a square of blazing blue heaven. He weakly put up his hand to
shade his sight, and a cotton awning, supported by four bamboo poles, was
swiftly raised over his head. He saw objects and took cognizance of them.
On the floor in the low doorway of a mud hut sat three little naked children
covered with flies and dirt. He was the guest of Fatou Anni. These were
three of her hundred great-great-grandchildren. The babies were playing
with a little dog. Sabron knew the dog but could not articulate his name. By
his side sat the woman to whom he owed his life. Her veil fell over her face.
She was braiding straw. He looked at her intelligently. She brought him a
drink of cool water in an earthen vessel, with the drops oozing from its
porous sides. The hut reeked with odors which met his nostrils at every
breath he drew. He asked in Arabic:
"Where am I?"
"In the hut of victory," said Fatou Anni.
Pitchouné overheard the voice and came to Sabron's side. His master
murmured:
"Where are we, my friend?"
The dog leaped on his bed and licked his face. Fatou Anni, with a whisk
of straw, swept the flies from him. A great weakness spread its wings above
him and he fell asleep.
Days are all alike to those who lie in mortal sickness. The hours are
intensely colorless and they slip and slip and slip into painful wakefulness,
into fever, into drowsiness finally, and then into weakness.
The Capitaine de Sabron, although he had no family to speak of, did

possess, unknown to the Marquise d'Esclignac, an old aunt in the provinces,
and a handful of heartless cousins who were indifferent to him.
Nevertheless he clung to life and in the hut of Fatou Anni fought for
existence. Every time that he was conscious he struggled anew to hold to
the thread of life. Whenever he grasped the thread he vanquished, and
whenever he lost it, he went down, down.
Fatou Anni cherished him. He was a soldier who had fallen in the battle
against her sons and grandsons. He was a man and a strong one, and she
despised women. He was her prey and he was her reward and she cared for
him; as she did so, she became maternal.
His eyes which, when he was conscious, thanked her; his thin hands that
moved on the rough blue robe thrown over him, the devotion of the dog—
found a responsive chord in the great-grandmother's heart. Once he smiled
at one of the naked, big-bellied great-great-grandchildren. Beni Hassan,
three years old, came up to Sabron with his finger in his mouth and
chattered like a bird. This proved to Fatou Anni that Sabron had not the Evil
Eye. No one but the children were admitted to the hut, but the sun and the
flies and the cries of the village came in without permission, and now and
then, when the winds arose, he could hear the stirring of the palm trees.
Sabron was reduced to skin and bone. His nourishment was insufficient,
and the absence of all decent care was slowly taking him to death. It will
never be known why he did not die.
Pitchouné took to making long excursions. He would be absent for days,

and in his clouded mind Sabron thought the dog was reconnoitering for him
over the vast pink sea without there—which, if one could sail across as in a
ship, one would sail to France, through the walls of mellow old Tarascon, to
the château of good King René; one would sail as the moon sails, and
through an open window one might hear the sound of a woman's voice
singing. The song, ever illusive and irritating in its persistency, tantalized
his sick ears.
Sabron did not know that he would have found the château shut had he
sailed there in the moon. It was as well that he did not know, for his
wandering thought would not have known where to follow, and there was
repose in thinking of the Château d'Esclignac.
It grew terribly hot. Fatou Anni, by his side, fanned him with a fan she
had woven. The great-great-grandchildren on the floor in the mud fought
together. They quarreled over bits of colored glass. Sabron's breath came
panting. Without, he heard the cries of the warriors, the lance-bearers—he
heard the cries of Fatou Anni's sons who were going out to battle. The
French soldiers were in a distant part of the Sahara and Fatou Anni's
grandchildren were going out to pillage and destroy. The old woman by his
side cried out and beat her breast. Now and then she looked at him
curiously, as if she saw death on his pale face. Now that all her sons and
grandsons had gone, he was the only man left in the village, as even boys of
sixteen had joined the raid. She wiped his forehead and gave him a potion
that had healed her husband after his body had been pierced with arrows. It
was all she could do for a captive.
Toward sundown, for the first time Sabron felt a little better, and after
twenty-four hours' absence, Pitchouné whined at the hut door, but would
not come in. Fatou Anni called on Allah, left her patient and went out to see
what was the matter with the dog. At the door, in the shade of a palm, stood
two Bedouins.
It was rare for the caravan to pass by Beni Medinet. The old woman's
superstition foresaw danger in this visit. Her veil before her face, her
gnarled old fingers held the fan with which she had been fanning Sabron.
She went out to the strangers. Down by the well a group of girls in
garments of blue and yellow, with earthen bottles on their heads, stood
staring at Beni Medinet's unusual visitors.
"Peace be with you, Fatou Anni," said the older of the Bedouins.
"Are you a cousin or a brother that you know my name?" asked the
ancient woman.
"Every one knows the name of the oldest woman in the Sahara," said
Hammet Abou, "and the victorious are always brothers."
"What do you want with me?" she asked, thinking of the helplessness of
the village.
Hammet Abou pointed to the hut
"You have a white captive in there. Is he alive?"
"What is that to you, son of a dog?"

"The mother of many sons is wise," said Hammet Abou portentously,
"but she does not know that this man carries the Evil Eye. His dog carries
the Evil Eye for his enemies. Your people have gone to battle. Unless this
man is cast out from your village, your young men, your grandsons and
your sons will be destroyed."
The old woman regarded him calmly.
"I do not fear it," she said tranquilly. "We have had corn and oil in
plenty. He is sacred."
For the first time she looked at his companion, tall and slender and
evidently younger.
"You favor the coward Franks," she said in a high voice. "You have
come to fall upon us in our desolation."
She was about to raise the peculiar wail which would have summoned
to her all the women of the village. The dogs of the place had already begun
to show their noses, and the villagers were drawing near the people under
the palms. Now the young man began to speak swiftly in a language that
she did not understand, addressing his comrade. The language was so
curious that the woman, with the cry arrested on her lips, stared at him.
Pointing to his companion, Hammet Abou said:
"Fatou Anni, this great lord kisses your hand. He says that he wishes he
could speak your beautiful language. He does not come from the enemy; he
does not come from the French. He comes from two women of his people
by whom the captive is beloved. He says that you are the Mother of sons
and grandsons, and that you will deliver this man up into our hands in
peace."
The narrow fetid streets were beginning to fill with the figures of
women, their beautifully colored robes fluttering in the light, and there were
curious eager children who came running, naked save for the bangles upon
their arms and ankles.
Pointing to them, Hammet Abou said to the old sage:

Advances in Parasitology Volume 115 Russell Stothard Full Chapter

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Advances in Parasitology Volume 115 Russell Stothard Full Chapter

Uploaded by

Copyright:

Available Formats

Advances in Parasitology, Volume 115

First edition 2022

Copyright © 2022 Elsevier Ltd. All rights reserved.

For information on all Academic Press publications

Publisher: Zoe Kruze

1. An update on female and male genital schistosomiasis and

2. Vertebrates as uninfected disseminators of helminth

3. Anthelmintic resistance in ruminants: challenges and solutions 171

An update on female and male

Advances in Parasitology, Volume 115 Copyright #2022 Elsevier Ltd 1

1.1 Selection criteria

1.2 Epidemiology and geographical distribution of genital

diagnosed by histopathology in 62% of 543 women with urinary schistoso-

1.3 Life cycle and transmission

communities that have unsafe water contact (Satayathum et al., 2006). In

Fig. 2 The life cycle of S. haematobium. Adapted from Countdown (https://countdown.

parasites is common, its epidemiological occurrence is only rarely reported,

1.4 FGS and MGS in less common Schistosoma species

S. haematobium; for example, a case of testicular schistosomiasis leading to

1.5 The importance of different hybrids of S. haematobium

S. haematobium-hybrids contribute to genital schistosomiasis. A further

2. Pathogenesis and clinical manifestations

Vulvar or vaginal ulcerations and papillomata have been associated with

2.1.1 Pregnancy and placental involvement

during pregnancy is also associated with iron deficiency among infants

2.2 Male genital schistosomiasis (MGS)

cytokine concentrations in systemic circulation of mice with FGS, only

3.2 Immune activation during pregnancy

4. Diagnosis of genital schistosomiasis

study comparisons due to differences in FGS case definitions. For example,

4.1.1 Traditional colposcopy

4.1.2 Hand-held colposcopy and other hand-held devices

smartphones, a digital camera and several handheld colposcopes, their avail-

4.1.3 Ultrasound scans and other radiological imaging

(Ramarakoto et al., 2008). Ultrasound may be helpful in diagnosing com-

4.1.4 Parasitology diagnosis

4.2 Molecular diagnostics (nucleic acid amplification tests)

4.2.2 Isothermal diagnostics

Loop Mediated Isothermal Amplification (LAMP) (Gandasegui et al., 2018)

4.3 MGS diagnostics

Fig. 6 S. haematobium egg in semen at 400 magnification. Photo credit. S. Kayuni.

4.3.1 Parasitology and molecular diagnostics in MGS

4.4 Immunopathology in MGS

"Couldn't you be frank with me, Madame? It is so easy to be frank."

It was, indeed, impossible for Julia Redmond to be anything else. The

"But be frank—about what?"

"You don't love him?" returned Madame de la Maine, with deep

The girl smiled.

"Yes, quite possible. I think he is a perfect dear. He is a splendid friend

"Ah!" breathed Madame de la Maine, and she looked at the American

For a moment it was like a passage of arms between a frank young

"But nothing on earth would induce me to marry him!" cried Julia

The Comtesse de la Maine drew back and exclaimed.

Madame de la Maine wondered just how much Julia Redmond had

"Happy," murmured the other woman, "happy, my dear friend, I never

THE MAN IN RAGS

The Marquise d'Esclignac, under the stars, interviewed the native

"What on earth is he talking about, Robert?"

"About Sabron, marraine," said her godson laconically.

The Marquise d'Esclignac raised her lorgnon and said:

"Speak, man! What do you know about Monsieur de Sabron? See, he is

"Marraine, he says that Sabron is alive, in the hands of natives in a

"The man's a lunatic," said the Marquise d'Esclignac calmly. "Get