Measuring and Treating Schistosomiasis morbidity in pre-school age children and Women at risk of FGS

Transcription

1 Measuring and Treating Schistosomiasis morbidity in pre-school age children and Women at risk of FGS GSA Meeting Jutta Reinhard-Rupp Head of Merck Global Health Institute Baltimore, November 5 th, 2017 Merck KGaA Darmstadt, Germany

2 Morbidities as a consequence of a parasitic infections Disablers versus Killers While the epidemiological magnitude of the neglected tropical diseases is comparable to malaria, tuberculosis or HIV, the sense of medical urgency for many of them is less appreciated because of the slow and debilitating evolution even if in many cases lethal. For most of these diseases there are known preventive measures or acute medical treatments, however, much less is available to address the chronic consequences of these infections. 2

3 The clinical pathology due to Schistosomiasis (according to WHO*) Morbidity General S. mansoni/ S. haematobium S. japonicum Non specific signs and symptoms in acute phase Anemia Anemia Organ specific pathology Hepatomegaly Vesicular wall hardening Splenomegaly Bladder cancer Ectopic egg granulomas Ectopic egg granulomas Altrenative venous circulation Genital schistosomiasis Developmental impairment Cognitive dysfunction Kidney malfunction Genital schistosomiasis Cognitive dysfunction Delayed growth/stunting Delayed growth/stunting 3 *

4 Current estimated (WHO*) total number of individuals with morbidity and mortality due to S. haematobium and S. mansoni infection in Sub-Saharan Africa Schistosome species Estimated morbidity and mortality in millions** S. haematobium (at risk of infection 436m, infected 112m) Haematuria during previous 2 weeks 71 (52-89) Dysuria during previous 2 weeks 32 (17-55) Minor bladder morbidity 76 (67-92) Major bladder morbidity 24 (15-31) Moderate hydronephrosis 9. 6 Major hydronephrosis 9.6 Non-functioning kidney [1.7] Non-functioning kidney (deaths/year) [0.15] Bladder cancer (deaths/year) Males [0.011] Females [0.0023] S. mansoni (at risk of infection 393m, infected 54m) Diarrhoea during previous 2 weeks 0.78 ( ) Blood in stool during previous 2 weeks 4.4 ( ) Hepatomegaly (mid-sternal line) 8.5 Splenomegaly [6.3] Ascites [0.29] Haematemesis (ever) [0.93] Haematemesis (deaths/year) [0.13] BAD NEWS No information on morbidity and mortality related to genital tract * ** 90% confidence interval in parentheses

5 GOOD NEWS WHO Chapter on Genital manifestations of schistosomiasis The clinical manifestations of genital schistosomiasis occur both in women and in men FGS: The most frequently observed signs and symptoms are abdominal and pelvic pain presenting in forms such as dyspareunia, dysmenorrhea, leucorrhoea, menstrual disorders, post-coital bleeding or simple contact bleeding (during an examination), cervicitis, endometritis and salpingitis. The disease evolves most often in a chronic manner. These genital lesions can cause complications such as early abortion, ectopic pregnancy and infertility Differential diagnosis must be done systematically to screen for cancers (of the vulva, vagina, cervix, endometrium), sexually transmitted infections and urogenital tuberculosis. Clinical diagnosis of female genital schistosomiasis is mainly done by visual inspection and histological methods Incorrect diagnostic of genital schistosomiasis lesions frequently leads to debilitating and irreversible operations such as ovarectomy, salpingotomiy and hysterectomy. It is therefore of utmost importance to sensitize health workers and raise awareness of urogenital schistosomiasis, particularly in endemic countries. Early treatment, especially in childhood, is the most effective intervention to prevent the occurrence and development of complications associated with urogenital schistosomiasis. The WHO recommended policy of regularly treating school-age children with praziquantel should be reinforced and extended, to involve collaborations with programmes for preventing HIV and other sexually transmitted infections. 5

6 Female Genital Schistosomiasis (FGS) Genital manifestations of schistosomiasis have been fully recognized either in males and females, the oldest report on female genital manifestation of schistosomiasis: A case of bilharzia of the vagina was published in the Lancet in 1899 by F.C. Madden 6 All female genital organs can be involved: the vulva, the vagina, the cervix, the uterus, the Fallopian tubes and ovaries.

7 Mapping of publications on FGS ( ) 7 Int J Para. 2016, 46, : Female genital schistosomiasis (FGS): from case reports to a call for concerted action against this neglected gynaecological disease. Christinet V, Lazdins-Helds JK, Stothard JR, Reinhard-Rupp J

8 Onset of morbidity in children 8 Parasitology. 2017, 144, : One hundred years of neglect in paediatric schistosomiasis Bustinduy AL, Wright S, Joekes EC, Kabatereine NB, Reinhard-Rupp J, King CH, Stothard JR

9 Burden of FGS Children Schistosome infections diagnosed under the age of 2 yr; morbidity data scarce Women currently no conclusive data; estimated that between 20 and 150 million women are affected (Hotez and Whitham, 2014). Prevalence of FGS From community-based studies assessing the cervico-vaginal form of FGS striking differences have been reported: Madagascar 33% (95%CI : 19 51) Niger 75% (95%CI : 65 87) Prevalence and intensity categories of S. haematobium infection stratified by age categories for Azaguié Makouguié (A) and Azaguié M'Bromé (B) in Azaguié district, south Côte d'ivoire, in mid S. haematobium infection intensities were categorized into light (1 49 eggs/10 ml urine) and heavy ( 50 eggs/10 ml urine) 9 Am J Trop Med Hyg Jul;89(1):32-41 Epidemiology of schistosomiasis in two high-risk communities of south Cote d'ivoire with particular emphasis on pre-school-aged children. Coulibaly JT 1, N'Gbesso YK, N'Guessan NA, Winkler MS, Utzinger J, N'Goran EK.

10 Diagnosis, prevention and treatment of FGS Diagnosis : The clinical diagnosis of FGS (only vulvo-vaginal form) is through a gynaecological examination, now facilitated by the development of the WHO pocket atlas ( for clinical health-care professionals. Prevention : Regular praziquantel treatment starting early in childhood (including preschool age children) would be a preventive measure. Treatment : The current gold standard, is a single dose of 40mg/kg of praziquantel as PCT. However, no evidence is available that this regimen will prevent and eliminate the egg production to a level that reverses FGS. For a patient that presents herself with severe symptoms of FGS there are no validated therapeutic options to treat/ cure FGS. 10

11 Female Genital Schistosomiasis it should NOT remain the forgotten gynaecological disease NEED TO... Define the magnitude of the problem (epidemiology) Define the impact of the problem (cost, DALYs, etc) Better understand the pathology Optimize/ develop diagnostic tools Gynaecological Parasitological Biological Optimize/ develop therapeutic interventions Etiological treatment (PZQ regimens/doses) Clinical management of FGS (inflammation, immune modulation, wound healing, etc.) Develop medical capacity (gynaecology) at the primary health level Promote cross disease approach (NTDs, reproductive health, HIV/AIDS, Cancer, STD, Mental Health, etc.) for research and disease management & control

12 Global Health Institute Building Local Infrastructure for integrated Gynaecological Care March 2017: Inauguration of new gynaecology ward in Cameroon Donation from the Global Health Institute to set up a new gynaecological ward in the district hospital of Akonolinga (Cameroon) Support for the 1 st year-salaries for the new team Build local capacity to provide integrated gynaecological care to patients in need Create the basis for potential future clinical research on FGS the Foster partnerships: 12

13 Acknowledgement All colleagues working on and advocating for more awareness and concerted action against this neglected gynaecological disease Team of the Global Health Institute (of Merck KGaA, Darmstadt, Germany) THANK YOU for your ATTENTION!