| dc.description.abstract |
Diarrheal diseases collectively constitute a serious public health challenge
globally. The causative agents of diarrheal disease include adenovirus (serotypes
40 and 41), Aeromonas spp, Entamoeba histolytica, Cryptosporidium spp.,
Escherichia coli strains, norovirus (NoV), non-typhoidal Salmonella spp.,
rotavirus A (RVA), Shigella spp., Vibrio cholerae and Clostridium difficile. Among
these, rotavirus, Cryptosporidium spp., and Shigella spp. are the three
aetiological agents responsible for most deaths in children under 5 years old. The
distributions of these pathogens are overlapping and they coexist in many
endemic areas, particularly in low-income countries. Accurate diagnosis and
molecular characterization of diarrheal pathogens are necessary for surveillance,
prevention, and control of diarrhea. To obtain accurate epidemiological data,to
support diarrheal disease control and elimination intervention strategies in
Gabon, four studies were conducted as part of this thesis.
First, the prevalence of pathogens found in stool samples in outpatient Gabonese
children < 5 years with diarrhea was for the first time systematically investigated
to describe the local spectrum of infectious agents. The most frequently identified
were enteroinvasive Escherichia coli (EIEC) /Shigella and Enterotoxigenic
Escherichia coli (ETEC), followed by Giardia lamblia, Cryptosporidium spp. and
rotavirus. The emergent ETEC, EIEC /Shigella, Cryptosporidium spp. and
rotavirus were frequently detected in combination. The most frequently observed
combinations of pathogens were EIEC/Shigella and ETEC, ETEC and rotavirus
as well as Cryptosporidium and EIEC/Shigella. This information serves as
baseline for recommendation for interventions and diagnostic algorithms to public
health stakeholders.
The second study was nested in a broader community-based project and aimed
to evaluate cryptosporidiosis diagnosis by a rapid diagnostic test (CerTest Crypto
RDT) against a composite reference of quantitative polymerase chain reaction
(qPCR) and restriction fragment length polymorphism (RFLP)-PCR in African
children from four countries (Gabon, Ghana, Madagascar, and Tanzania)
admitted to a hospital with diarrhea. The performance of this RDT varied across the four study sites. Overall, the test showed a low sensitivity for the detection
of Cryptosporidium parvum and C. hominis.
This work included the comprehensive investigation of rotavirus
genotypes and antigenic epitope variability in the VP7 and VP4 proteins of
circulating rotavirus A strains compared to vaccine strains, as the third part of this
dissertation. Rotavirus A was detected in 55 % (98/177) of hospitalized children
with gastroenteritis and 21 % (14/67) of the control children. The most common
genotypes were G1, G3, G8, G9, G12, with G8 and G9 being reported for the first
time in Gabon. All of these G genotypes were associated either with P[6] or P[8]
genotypes. Several amino acid mutations associated with immune evasion were
detected on antigenic epitopes of VP7 (sites 94, 147) and VP8* (sites 89, 116,
146, 150) of Gabonese strains, which may lead to reduced efficacy of available
RotaTeq and Rotarix vaccines.
The fourth study was designed to determine the prevalence and genetic diversity
of four main enteric viruses (Norovirus, Sapovirus, Astrovirus and Aichvirus A) in
hospitalized children <5 years with gastroenteritis and community controls
without gastroenteritis. Norovirus (14.7 %; 26/177) and astrovirus (7.3 %; 13/177)
were the most prevalent in children with diarrhea, while in the healthy group
norovirus (9 %; 6/67) followed by aichivirus A (6 %; 4/67) were predominant. The
predominant norovirus genogroup was GII, consisting mostly of genotype
GII.P31-GII.4 Sydney. This study provides the first report on the detection of
Aichvirus A in Gabon and Central Africa.
This thesis provides the epidemiological and genetic baseline data that will be
essential for advocating a much-needed management of diarrhea as
recommended by the WHO. Moreover, these results show that the
implementation of a national vaccination program against rotavirus is necessary
and urgent in Gabon. The findings related to the performance of CerTest Crypto
RDT in Africa will support implementation of diarrhea control and elimination
efforts in endemic areas. Future work should focus on the development of
laboratory methods to improve the sensitivity of cryptosporidiosis detection and
on expanding the use of routine diagnosis. |
en |
