Case Report: Three cases of suspected female genital schistosomiasis and precancerous lesions for cervical cancer in a highly endemic country—from clinical management to public health implications

Female genital schistosomiasis (FGS) is a chronic manifestation of schistosomiasis, usually caused by Schistosoma haematobium infection, which can be responsible for infertility, ectopic pregnancy, and abortion, and is associated with an increased prevalence of HIV infection. No screening programs are currently recommended for FGS. Colposcopy, the conventionally suggested diagnostic tool for FGS, is also considered a crucial screening tool for cervical cancer (CC). We performed an experimental screening via colposcopy for FGS at primary healthcare centers (PHCCs) in the Boeny region of Madagascar, allowing for the detection of patients with both FGS signs and HPV-related dysplasia (HPV-dy). All suspected FGS cases were treated with praziquantel on the day of colposcopy, and all images of suspected CC or HPV-dy were re-assessed by a gynecologist and, if needed, patients were then provided with additional colposcopy for histologic diagnosis and treatment. We describe three cases of FGS and HPV-related precancerous lesions detected during the project, discussing the state of art of the relationship between CC, FGS and HPV and the real-life challenges encountered in terms of both patient compliance and the diagnostic and treatment cascade. Despite the current diagnostic limitations, a screening for FGS via colposcopy may contribute to the early identification of CC or precancerous lesions. The addition of visual inspection with acetic acid (VIA) during colposcopy for FGS screening could improve its impact on CC screening. In addition, although there is limited evidence of the effectiveness of praziquantel in FGS, treatment should in any case be proposed for suspicious lesions, given its safety and ease of administration. The benefit of combined screening could be maximised by increasing the availability of good quality services and improve awareness of both diseases among wome

A cluster randomized controlled trial for assessing POC-CCA test based praziquantel treatment for schistosomiasis control in pregnant women and their young children: study protocol of the freeBILy clinical trial in Madagascar.

BACKGROUND: Mass drug administration (MDA) of praziquantel is one of the main control measures against human schistosomiasis. Although there are claims for including pregnant women, infants and children under the age of 5 years in high-endemic regions in MDA campaigns, they are usually not treated without a diagnosis. Diagnostic tools identifying infections at the primary health care centre (PHCC) level could therefore help to integrate these vulnerable groups into control programmes. freeBILy (fast and reliable easy-to-use-diagnostics for eliminating bilharzia in young children and mothers) is an international consortium focused on implementing and evaluating new schistosomiasis diagnostic strategies. In Madagascar, the study aims to determine the effectiveness of a test-based schistosomiasis treatment (TBST) strategy for pregnant women and their infants and children up until the age of 2 years. METHODS: A two-armed, cluster-randomized, controlled phase III trial including 5200 women and their offspring assesses the impact of TBST on child growth and maternal haemoglobin in areas of medium to high endemicity of Schistosoma mansoni. The participants are being tested with the point of care-circulating cathodic antigen (POC-CCA) test, a commercially available urine-based non-invasive rapid diagnostic test for schistosomiasis. In the intervention arm, a POC-CCA-TBST strategy is offered to women during pregnancy and 9 months after delivery, for their infants at 9 months of age. In the control arm, study visit procedures are the same, but without the POC-CCA-TBST procedure. All participants are being offered the POC-CCA-TBST 24 months after delivery. This trial is being integrated into the routine maternal and child primary health care programmes at 40 different PHCC in Madagascar's highlands. The purpose of the trial is to assess the effectiveness of the POC-CCA-TBST for controlling schistosomiasis in young children and mothers. DISCUSSION: This trial assesses a strategy to integrate pregnant women and their children under the age of 2 years into schistosomiasis control programmes using rapid diagnostic tests. It includes local capacity building for clinical trials and large-scale intervention research. TRIAL REGISTRATION: Pan-African Clinical Trial Register PACTR201905784271304. Retrospectively registered on 15 May 2019

Chromoblastomycosis and sporotrichosis in Madagascar : epidemiological, clinical and diagnostic updates

La chromoblastomycose (CBM) et la sporotrichose (SPT) sont des infections fongiques chroniques des tissus sous-cutanés. Elles touchent surtout les membres, après blessure végétale ou souillure tellurique. Les principaux agents fongiques responsables de CBM appartiennent aux genres Fonsecaea et Cladophialophora tandis que Sporothrix est à l’origine de la SPT. A Madagascar, les études menées entre 1955 et 1994 ont montré une prévalence de la CMB à 0,5/100 000 habitants faisant considérer ce pays comme le premier foyer mondial. Depuis, aucune donnée n’a permis d’actualiser ces observations. Malgré les nombreux cas de SPT observés par les médecins, son épidémiologie à Madagascar n’a jamais été décrite.L'objectif général était d'évaluer l’incidence actuelle de ces mycoses à Madagascar. Les objectifs spécifiques étaient de caractériser les espèces fongiques responsables et de mettre en place un réseau clinico-biologique pérenne permettant une gestion adaptée des patients et l’utilisation de méthodes moléculaires pour l’identification des souches.Une étude prospective conduite entre mars 2013 et juin 2017 a donné lieu à des consultations dans les régions ou dans le service de dermatologie de l’hôpital universitaire d’Antananarivo et a permis d’inclure des patients présentant des lésions sous-cutanées chroniques. Les méthodes conventionnelles de diagnostic mycologique ont été complétées par des méthodes moléculaires (PCR, séquençage, MALDI-TOF-MS). Les cas ont été classés au cours de réunions de concertation clinico-biologique.Au total, 148 patients d’âge moyen de 41 ans avec une prédominance d’hommes (75,0%) ont été inclus : 63 cas de SPT (42,5%) et 50 cas de CBM (33,8%) ont été confirmés. L’incidence annuelle de le CBM a été estimée à 0,38/100 000 habitants dans la région Sava au Nord où les cas prédominent avec au niveau du district Anosibe An’Ala (à l’Est) une incidence maximale de 1,12/100 000. Alors que la CBM était prédominante dans le Nord-Est, l'Est et le Sud de l'île, étonnamment, la SPT était presque exclusivement localisée sur les hautes terres centrales. L’incidence globale moyenne de SPT était de 0,17/100 000 habitants dans les hauts plateaux et de 0,07/100 000 pour l’ensemble de Madagascar. Pour la SPT, le risque est plus élevé chez les jeunes (< 18 ans) et les formes cutanéo-lymphatiques des membres supérieurs sont les plus fréquentes. Pour la CBM, le risque de contamination est élevé chez les agriculteurs et les professions de services et la majorité des lésions (82,9%) était localisée au niveau des membres inférieurs. Sur le plan mycologique, 63 Sporothrix schenckii, 7 Cladophialophora carrionii, 29 Fonsecaea sp dont 22 F. nubica ont été identifiés. Pour le genre Fonseceae, l’identification de l’espèce nubica remplace l‘espèce pedrosoi initialement proposée pour les isolats malgaches et souligne l’importance de l’identification moléculaire pour une classification précise des espèces.Cette première étude sur la SPT humaine à Madagascar a permis d’actualiser les données épidémiologiques mondiales et de classer Madagascar avec un niveau endémique modéré alors qu’il était considéré comme faible jusque-là. La CBM persiste à une incidence élevée et comparable à celle décrite jusqu’en 1994, illustrant l’absence de contrôle de cette mycose dans le pays. La constitution d’un réseau clinico-biologique local stable et les nouveaux outils diagnostics mis en place dans ce travail (PCR et le MALDI-TOF MS), vont faciliter la conduite de programmes de surveillance et de contrôle alors que l’OMS a récemment classé la CBM en maladie tropicale négligée. Une enquête environnementale est en cours pour détecter les sources de contamination dans l’environnement. Le réseau mis en place permettra dans un futur proche de nouvelles études thérapeutiques (nouveaux schémas thérapeutiques) ou génétique (facteurs d’hôtes) sur la CBM et SPT mais également sur d’autres mycoses endémiques et encore négligées à MadagascarChromoblastomycosis (CBM) and sporotrichosis (SPT) are chronic subcutaneous or cutanéo-lymphatic infections found mostly in tropical and subtropical regions. Studies carried out by the Institut Pasteur of Madagascar between 1955 and 1994 provided an inventory of the number of cases of CBM and identified this country as the leading focus of this mycosis worldwide. Mean incidence was estimated at about 0.5/100,000 inhabitants at the time. No new data have been obtained to update the epidemiological situation. About SPT, only sporadic cases have been reported in Madagascar, due to the absence of specific surveillance. CBM is usually caused by dematiaceous fungi, principally Fonsecaea spp. and Cladophialophora spp. The causal agent of SPT is Sporothrix schenckii, a dimorphic hyphomycete.The objectives of this study was to update the data on epidemiology and to evaluate the current burden of these two fungal infections. In addition, we aimed to set up a durable local bio-clinical network and to implement molecular tools to ensure reliable species identification (PCR, sequencing, mass spectrometry).A prospective study, involving the recruitment of patients with suspect lesions was undertaken from March 2013 to June 2017. Patients were included in the dermatology department of the univerity hospital of Antananarivo and through field campaigns in rural areas. Clinical samples were collected and analyzed with conventional mycological methods and molecular tools. Classification of the cases was achieved by the confrontation of mycological and clinical features.Among the 148 patients (mean age 41; male 75.0%): 63 SPT cases (42.5%) and 50 CBM cases (33.8%) were diagnosed. The highest annual incidence of CBM was estimated at 0.38/100,000 inhabitants in the Sava region located to the north. At the district level, the peak incidence was 1.12/100,000 at Anosibe An’Ala, eastern part of the country. Whereas CBM predominated at the periphery of the island, SPT was surprinsgly concentrated in the highlands where the mean incidence was 0.17/100,000 inhabitants. The incidence in the whole country was 0.07/100,000. SPT likelihood of infection was higher in young (<18 years) and the cutaneo-lymphatic forms of the upper limbs were the most frequent. For CBM, farmers and service workers were at high risk and the lesions were mostly (82.9%) located to the lower limbs. The mycological analyses revealed 63 strains of Sporothrix schenckii, 7 of Cladophialophora carrionii, 29 of Fonsecaea sp including 22 F. nubica. F. nubica identification corrected the one of F. pedrosoi previously found in Madagascar, highlighting the need for a molecular analysis of the strains.This is the first study describing human SPT in Madagascar. The SPT burden can now be considered as moderate instead of low as it was described before. It reveals an unexpected concentration of the patients in the central highlands. CBM burden was found at a high level, regrettably similar to the one described 20 years ago, showing the lack of control of this infection. The implementation of a durable bio-clinical network and of the new molecular tools (PCR et le MALDI-TOF MS) developed in this work will easy the development of surveillance programs, especially as the WHO recently added CBM in the neglected tropical diseases list. The network that was built for this work will be used for further therapeutic trials on new schedules of treatment, new drugs or new formulations as well as genetic studies about predisposing factors of CBM and SPT and others deep fungal infections that are still neglected in Madagascar. Yet, an environmental survey is ongoing to describe the sources of contamination

Schistosomiasis elimination in Madagascar: challenges and opportunities for implementing the new WHO guidelines

Madagascar is one of the countries with the highest burden of schistosomiasis worldwide. The release from the WHO of the new 2021–2030 neglected tropical disease (NTD) roadmap alongside with the schistosomiasis guidelines sets the ambitious goal of eliminating schistosomiasis as a public health problem worldwide. In Madagascar, implementation barriers exist. This paper has the objective of identifying strengths, weaknesses, opportunities and threats in order to build on their basis practices and policies that can help the country to align with the international global health agenda and reach the ambitious goal set by the WHO

Molecular Diagnosis of Two Major Implantation Mycoses: Chromoblastomycosis and Sporotrichosis

International audienceChromoblastomycosis and sporotrichosis are the two main implantation mycoses that are now recognized as fungal neglected tropical diseases (NTDs). Their laboratory diagnosis mainly relies on direct microscopy, histopathology, and identification of the fungus by culture. However, to be appropriately used, these techniques require mycological expertise that is not widely available and may be absent in peripheral health care facilities in endemic areas. In addition, they lack sensitivity and specificity, and the culture for isolation and identification can have a long time-to-results period. Molecular methods, including matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), have been developed in well-equipped reference laboratories. They greatly improve the rapidity and accuracy of diagnosis; in particular, for species identification. Recently, PCR and sequencing have paved the way for more user-friendly point-of-care tests, such as those based on LAMP or RCA technologies, which can be used in basic healthcare settings and even in field consultations

Evaluation of ID Fungi Plates Medium for Identification of Molds by MALDI Biotyper

International audienceMALDI-TOF mass spectrometry (MS) identification of pathogenic filamentous fungi is often impaired by difficulties in harvesting hyphae embedded in the medium and long extraction protocols. The ID Fungi Plate (IDFP) is a novel culture method developed to address such difficulties and improve the identification of filamentous fungi by MALDI-TOF MS. We cultured 64 strains and 11 clinical samples on IDFP, Sabouraud agar-chloramphenicol (SAB), and ChromID Candida agar (CAN2). We then compared the three media for growth, ease of harvest, amount of material picked, and MALDI-TOF identification scores after either rapid direct transfer (DT) or a long ethanol-acetonitrile (EA) extraction protocol

MALDI-TOF MS in a Medical Mycology Laboratory: On Stage and Backstage

International audienceThe implementation of MALDI-TOF MS in medical microbiology laboratories has revolutionized practices and significantly reduced turnaround times of identification processes. However, although bacteriology quickly benefited from the contributions of this technique, adjustments were necessary to accommodate the specific characteristics of fungi. MALDI-TOF MS is now an indispensable tool in clinical mycology laboratories, both for the identification of yeasts and filamentous fungi, and other innovative uses are gradually emerging. Based on the practical experience of our medical mycology laboratory, this review will present the current uses of MALDI-TOF MS and the adaptations we implemented, to allow their practical execution in a daily routine. We will also introduce some less mainstream applications, like those for fungemia, or even still under development, as is the case for the determination of sensitivity to antifungal agents or typing methods

Dermatophyte infection caused by Nannizzia gypsea: A rare case report from Madagascar

We report a rare case of dermatophyte infection of the glabrous skin (Tinea corporis) caused by Nannizzia gypsea (formerly Microsporum gypseum). A 22-year-old Malagasy female who reported close contact reportedly with cats, presented a single round lesion with a peripheral, active, squamous and pruriginous inflammatory bead. Morphologic species identification was confirmed by sequencing the internal transcribed spacer (ITS) region of the genome. Specific treatment with oral loratadine and topical miconazole cream was effective. Keywords: Nannizzia gypsea, Dermatophyte infection, ITS region, Madagasca

Endemic Chromoblastomycosis Caused Predominantly by Fonsecaea nubica , Madagascar1

International audienc

Sickle-cell disease in febrile children living in a rural village of Madagascar and association with malaria and respiratory infections

International audienceBACKGROUND: In Madagascar, the last study on sickle cell disease (SCD) was done in the early 1980s. The country is known as endemic for malaria and respiratory infections. The main objective of this study was to estimate the prevalence of SCD; the secondary objective was to evaluate its association with malaria and respiratory infections. METHODS: This is a cross-sectional study which was carried out in a rural village in the south east coast of Madagascar between May 2011 and November 2013. Participants were children aged between 2-59 months presenting with fever measured by axillary temperature >=37.5~°C at inclusion. Genotyping of haemoglobin S was done by PCR and malaria was diagnosed by Rapid Diagnostic Test. Research for viral and atypical bacterial respiratory pathogens was performed on nasopharyngeal swabs. Uni-and multivariate polytomous logistic regression was done to assess associations between microbiological results and SCD status, with HbAA phenotype as reference. RESULTS: A total of 807 children were analysed. Prevalence of SCD among febrile children was 2.4% (95% CI, 1.5-3.7%) and that of SCT was 23.8% (95% CI, 20.9-26.9%). There was no difference in the prevalence of malaria infection according to haemoglobin status (p = 0.3). Rhinovirus (22.5%), adenovirus (14.1%), and bocavirus (11.6%) were the most common respiratory pathogens detected. After univariate analysis, patients with SCD were more frequently infected by parechovirus (p = 0.01), while patients with SCT were more prone to RSV A or B infection (p = 0.01). After multivariate analysis, HbAS phenotype was associated with higher risk of RSV A and B infection compared to HbAA (adjusted OR = 1.9; 95% CI: 1.2-3.1, p = 0.009), while HbSS phenotype was associated with higher risk of parechovirus infection (adjusted OR = 6.0; 95% CI: 1.1-31.3, p = 0.03) compared to HbAA, independently of age, gender, period per quarter, and the other viruses. CONCLUSION: The prevalence of SCD among under-five children presenting with fever was high in the study population. No association was found between SCT and malaria but few viruses, especially parechovirus, seem to play an important role in the occurrence of pneumoniae among SCD patients