Chromoblastomycosis and sporotrichosis are endemic fungal infections of tropical and subtropical regions, including Madagascar. The causal fungi develop in the soil or on plants and infect humans ...through wounds, either directly (wounding by the plant, through thorns, for example), or through the contact of an existing wound with contaminated soil. For this reason, the lesions predominantly occur on the limbs, and these fungi principally infect people working outside with bare hands and/or feet. The subcutaneous lesions of chromoblastomycosis are initially nodular, subsequently becoming warty, tumoral, cauliflower-like and pruriginous, which promotes dissemination. The chronic nature of the infection and its progression over long periods lead to highly disabling lesions in essentially rural and agricultural populations. The lesions of sporotrichosis are also nodular, but more ulcerous, and they form an extended chain following the route of the lymph vessels. Pus, squamous or skin biopsy specimens are used for the mycological examination of these mycoses. Treatment depends on the severity and form of the lesions and is based on antifungal drugs sometimes combined with physical methods. There has been no study of these infections for more than two decades in Madagascar, despite the large numbers of cases seen by doctors in all parts of the island. The nature, diversity and distribution of the plants responsible for contamination have not been described in Madagascar. In this review, we described these two endemic mycoses in terms of their epidemiological, mycological, clinical and therapeutic characteristics, focusing particularly on Madagascar, which is one of the leading foci of these two infections worldwide.
Background. After the 2001–2002 poliomyelitis outbreak due to recombinant vaccine-derived polioviruses (VDPVs) in the Toliara province of Madagascar, another outbreak reoccurred in the same province ...in 2005. Methods. We conducted epidemiological and virological investigations for each polio case patient and for their contacts. Results. From May to August 2005, a total of 5 cases of acute flaccid paralysis were reported among unvaccinated or partially vaccinated children 2–3 years old. Type-3 or type-2 VDPV was isolated from case patients and from healthy contacts. These strains were classified into 4 recombinant lineages that showed complex mosaic genomic structures originating from different vaccine strain serotypes and probably from human enterovirus C (HEV-C) species. Genetic relatedness could be observed among these 4 lineages. Vaccination coverage of the population was very low (>50%). Conclusions. The broad distribution of VDPVs in the province and their close genetic relationship indicate intense and rapid cocirculation and coevolution of the vaccine strains and of their related HEV-C strains. The occurrence of an outbreak due to VDPV ∼3 years after a previous outbreak indicates that a short period with low vaccination coverage is enough to create favorable conditions for the emergence of VDPV in this setting.
IntroductionExisting risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our ...objective was to derive and validate a novel risk assessment tool to identify children aged 2–59 months at risk of hospitalised pneumonia-related mortality across various settings.MethodsWe used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool.ResultsA total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84).ConclusionsThe PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality.
Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores.
We applied ...the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules.
The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73).
In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting.
Abstract
Background
Schistosoma
antigen detection in urine is a valuable diagnostic approach for schistosomiasis control programmes because of the higher sensitivity compared to parasitological ...methods and preferred sampling of urine over stool. Highly accurate diagnostics are important in low
Schistosoma
transmission areas. Pregnant women and young children could particularly benefit from antigen testing as praziquantel (PZQ) can be given to only confirmed
Schistosoma
cases. This prevents the unborn baby from unnecessary exposure to PZQ. We present here the protocol of a diagnostic study that forms part of the freeBILy project. The aim is to evaluate the accuracy of circulating anodic antigen (CAA) detection for diagnosis of
Schistosoma haematobium
infections in pregnant women and to validate CAA as an endpoint measure for anti-
Schistosoma
drug efficacy. The study will also investigate
Schistosoma
infections in infants.
Methods
A set of three interlinked prospective, observational studies is conducted in Gabon. The upconverting phosphor lateral flow (UCP-LF) CAA test is the index diagnostic test that will be evaluated. The core trial, sub-study A, comprehensively evaluates the accuracy of the UCP-LF CAA urine test against a set of other
Schistosoma
diagnostics in a cross-sectional trial design. Women positive for
S. haematobium
will proceed with sub-study B and will be randomised to receive PZQ treatment immediately or after delivery followed by weekly sample collection. This approach includes comparative monitoring of CAA levels following PZQ intake and will also contribute further data for safety of PZQ administration during pregnancy. Sub-study C is a longitudinal study to determine the incidence of
S. haematobium
infection as well as the age for first infection in life-time.
Discussion
The freeBILy trial in Gabon will generate a comprehensive set of data on the accuracy of the UCP-LF CAA test for the detection of
S. haematobium
infection in pregnant women and newborn babies and for the use of CAA as a marker to determine PZQ efficacy. Furthermore, incidence of
Schistosoma
infection in infants will be reported. Using the ultrasensitive diagnostics, this information will be highly relevant for
Schistosoma
prevalence monitoring by national control programs as well as for the development of medicaments and vaccines.
Trial registration
The registration number of this study is
NCT03779347
(
clinicaltrials.gov
, date of registration: 19 December 2018).
Four poliomyelitis outbreaks caused by vaccine-derived polioviruses have been reported recently, including one in Madagascar in 2002. In all cases, the viral strains involved were recombinant between ...poliovirus vaccine strains and nonpoliovirus strains, probably enterovirus species C. Nevertheless, little is known about the circulation and epidemiology of enteroviruses in the regions where these outbreaks occurred. To assess the circulation of enteroviruses (particularly enterovirus species C) in Madagascar, we genetically characterized 55 enterovirus strains isolated between 1994 and 2002. The strains were identified and compared by partially sequencing the region encoding the VP1 capsid protein. Phylogenetic analysis and pairwise comparison with prototype enterovirus strains distinguished two different species: 25 isolates belonged to human enterovirus B species, and 30 isolates were identified as coxsackievirus A13, A15, A17, A18, A20, A21, and A24, belonging to the human enterovirus species C. The relatively high frequency and the wide distribution of species C coxsackie A viruses in different regions of Madagascar suggest that they had been silently and widely circulating in the country during the whole study period. The circulation of coxsackie A viruses, combined with the low routine oral polio vaccine coverage, may have played a role in the emergence of the recent outbreak in Madagascar.
Chromoblastomycosis (CBM) and sporotrichosis (SP) are endemic mycosis in Madagascar that occurred following injury and telluric contamination. CBM is mostly due to Fonsecaea pedrosoi or ...Cladophialophora carrionii and affects usually the subcutaneous tissue, whereas SP is caused by Sporothrix schenckii by invading the lymphatic system of the arms and legs. These fungal infections are considered neglected diseases because of poor resources allocated to their diagnosis, monitoring or prevention.
The general objective was to assess the current prevalence of these mycosis in Madagascar. The specific objectives were to characterize the causative fungal species and their habitat in order to prevent contamination, and to set up a sustainable clinical and laboratory network to allow proper case management and to provide a molecular-based species identification.
The study comprised a prospective clinical study that started in March 2013. Patients were recruited during field investigations and consultations provided in a dermatology department. Pus, biopsy and squamous were sampled from the lesions. Informed consent from the patients and ethical approval from the Ministry of Health were obtained. Histopathological and mycological analysis (direct examination and culture on Sabouraud-Cycloheximide) were performed. We have developed a PCR-based strategy that was validated on reference strains provided by BCCM/IHEM (Belgian Coordinated Collections of Micro organism). First, two sets of universal primers (NL-1/NL4 and ITS5/ITS4) were used to confirm the fungal origin of the lesions. Then, specific primers (SSHF31/SSHR97, Fon-F/Fon-R, EdF/EdR) were used for fungal species identification.
Ninety two patients were enrolled. Mean age was 38.7 years and men were predominant with 71.7 % of cases. Overall, 47.8 % were farmers, 30.4 % self-employed, 12.0 % students and 9.8 % unemployed. Clinically, 32.6 % of cases were suspected having CBM and presented with crusted, verrucous and tumoral lesions ; 34.8 % of cases were suspected having SP characterized mainly by ulcerative and nodular lesions of the lymphatic system of the lower limbs. Mycological analysis confirmed 33 cases of SP and 13 cases of CBM. The molecular diagnosis confirmed 34 Sporothrix sp, leading to a SP prevalence of 37 % and 1 Cladophialophora sp and 16 Fonsecaea sp leading to a CBM prevalence of 18.5 %. One mycetoma probably of bacterial origin was also diagnosed. CBM cases were predominant in the north-east, east and south part of the island, whereas SP cases were located mainly in the central highlands.
These results confirmed that CBM and SP persist at a high frequency in Madagascar. The availability of a reliable PCR tool in routine and the clinical expertise gained during this study will help the national authorities to set up a proper control and prevention program. An environmental survey is planned to describe the spread of the causative agents in the environment in an attempt to prevent the contamination.
Summary From July 1995 to December 1996, 3185 stool specimens from healthy children aged 6–59 months attending 6 dispensaries in the Antananarivo area were examined for poliovirus. The children had ...been routinely immunized according to the Expanded Programme on Immunization (EPI) schedule and received the last dose of oral polio vaccine (OPV) more than 1 month before stool collection. 99.4% of the children were immunized with at least 3 doses of OPV. HEp‐2 cell culture revealed virus infections in 192 stools (6.0%), including 9 poliovirus (0.3%) and 183 nonpolio enterovirus isolates (5.7%). Infections occurred throughout the year, but incidence was higher during the hot and rainy season (P= 0.01). Using a neutralization test with monoclonal antibodies and PCR‐RFLP in two genomic regions coding for the VP1 capsid and RNA polymerase, 4 wild polioviruses (3 type 1 and 1 type 3) and 5 vaccine‐related polioviruses (2 Sabin 1‐like variants, 1 Sabin 2‐like and 2 Sabin 3‐like) strains were identified. The wild polioviruses were isolated at the beginning and the end of the dry season. Similar RFLP patterns were observed for the 3 wild type 1 polioviruses. Comparison of partial genomic sequences in the VP1/2 A region of 1 of the wild type 1 isolates with 2 wild type strains isolated in Antananarivo in 1992 and 1993 showed a divergence of at least 10% between the strains, suggesting at least two different pathways of transmission during this period. Our findings demonstrate that immunization with 3 doses of OPV did not prevent intestinal carriage of wild poliovirus strains, and that there is a risk of wild poliovirus transmission to susceptible children in the area. Multiple strategies are required to improve immunization coverage in Madagascar.
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