Hutchinson-Gilford Progeria syndrome: Report of the first Togolese case.

The aim of this article is to describe the first case of Hutchinson-Gilford Progeria Syndrome (HGPS) in Togo and review all Africans cases. Our patient was a 12.8-year-old Togolese boy followed in our unit till he was 15-year-old for HGPS. He was the only child of non-consanguineous parents. The phenotypic findings were craniofacial dysmorphy, dwarfism, lipodystrophy, diffusely scattered hyperpigmented foci, pyriform thorax, nail dystrophy, decreased joint mobility, and camptodactyly. He had characteristic facies with prominent forehead, prominent eyes, absent ear lobule, thin nasal skin, convex nasal profile, micrognathia, and crowded teeth. Radiologicals findings were bilateral coxa valga, pyriform thorax, and acro-osteolysis. We sequenced the entire coding region of LMNA gene, and mutation analysis revealed a heterozygous mutation c.1824C>T (p.Gly608Gly). Our patient is therefore the fifth African and the fourth with classical mutation, first of Western Africa, and second of (sub-Saharan) African black race. The recurrence of HGPS is low like the cause is neomutation or germinal mosaicism.

Sero-epidemiology of peste des petits ruminants in Oromia and Afar regional states of Ethiopia.

Peste des petits ruminants (PPR) is a severe non-zoonotic viral disease of small ruminants caused by a morbillivirus closely related to rinderpest virus (RPV). The disease is widespread in Africa, the Middle East and Southern Asia. It is one of the priority animal diseases whose control is considered important for poverty alleviation in those regions because of the associated high economic losses. A sero-epidemiological study of PPR was conducted in Oromia and Afar regional states of Ethiopia. A total of 800 serum samples from sheep and goats were collected between October 2015 and March 2016 in Afar and Oromia, where no vaccination history has been recorded. These two regions are known to have a large population of small ruminants. The levels of PPR antibodies obtained in the two regions using the competitive enzyme-linked immunosorbent assay (cELISA) ID Screen® PPR Competition from IDvet (Montpellier, France) were similar, at 12.7% and 13.0% for Afar and Oromia, respectively. A seroprevalence of 12.9% for the two regions was obtained. The study also linked seropositivity to risk factors such as sex, age and species with a p-value of less than 0.05 (p = 0.0001, p = 0.0001 and p = 0.004, respectively).

La peste des petits ruminants (PPR) est une maladie virale non zoonotique des petits ruminants due à un morbillivirus apparenté au virus de la peste bovine. Cette maladie est très présente en Afrique, au Moyen-Orient et en Asie du Sud. Elle fait partie des maladies animales prioritaires qu'il est important de contrôler à des fins d'allègement de la pauvreté dans les régions affectées, en raison de l'ampleur des pertes économiques qui lui sont associées. Une étude séroépidémiologique sur la PPR a été conduite en éthiopie, couvrant les régions d'Oromia et d'Afar. Au total, 800 échantillons sériques issus d'ovins et de caprins ont été prélevés entre octobre 2015 et mars 2016 à Afar et Oromia, régions sans historique documenté de vaccination. Les populations de petits ruminants y sont nombreuses. La détection d'anticorps dirigés contre le virus de la PPR au moyen de l'épreuve immuno-enzymatique de compétition (cELISA) ID Screen® PPR Competition du laboratoire IDvet (Montpellier, France) a fait apparaître un niveau d'anticorps comparable dans les deux régions (12,7 % à Afar et 13,0 % à Oromia). Le taux de prévalence sérologique pour les deux régions était de 12,9 %. L'étude a également permis de relier la présence d'anticorps à certains facteurs de risque tels que le sexe, l'âge et l'espèce, avec un degré de signification (p) inférieur à 0,05 (respectivement, p = 0,0001, p = 0,0001 et p = 0,004).

La peste de pequeños rumiantes (PPR) es una grave enfermedad viral no zoonótica que afecta a los pequeños rumiantes, causada por un morbilivirus estrechamente emparentado con el virus de la peste bovina. Esta patología, muy extendida en África, Oriente Medio y el sur de Asia, es una de las enfermedades animales prioritarias cuyo control se considera importante para paliar la pobreza en esas regiones, dado que engendra cuantiosas pérdidas económicas. Los autores describen un estudio seroepidemiológico de la PPR efectuado en los estados regionales de Oromia y Afar (Etiopía). Entre octubre de 2015 y marzo de 2016 se reunieron en total 800 muestras séricas de ovejas y cabras de Afar u Oromia, regiones donde no se tiene registrado antecedente alguno de vacunación y donde se sabe que hay una numerosa cabaña de pequeños rumiantes. En ambas regiones, con aplicación del ensayo inmunoenzimático de competición (ELISAc) ID Screen® PPR Competition de IDvet (Montpellier, Francia), se obtuvieron niveles similares de anticuerpos contra el virus de la PPR: del 12,7% en Afar y del 13,0% en Oromia. El cálculo arroja una seroprevalencia del 12,9% en ambas regiones. El estudio puso también de relieve la existencia de un vínculo entre seropositividad y tres factores de riesgo, el sexo, la edad y la especie, con valores de p inferiores a 0,05 (respectivamente, p = 0,0001, p = 0,0001 y p = 0,004).

Plasmodium falciparum malaria in infants under 5 kg: retrospective surveillance of hospital records in five sub-saharan African countries.

OBJECTIVE: To investigate the disease burden, clinical features, treatment and outcomes of Plasmodium falciparum malaria in neonates and infants weighing <5 kg in five sub-Saharan African countries. METHODS: Pediatric hospital records were retrospectively reviewed for relevant cases. Details of clinical features, treatment and clinical outcomes were collected, and a descriptive analysis of data was carried out. RESULTS: The annual number of malaria cases ranged from 12 to 120 cases across hospitals and calendar years. The most frequent reason for seeking care was fever. Parasite density was low. Quinine was the most common treatment, followed by artemisinin-based combination therapy. The majority of patients recovered from their illness following treatment. CONCLUSION: Plasmodium falciparum malaria exists in this subpopulation. Further epidemiological data are needed to estimate malaria morbidity and mortality in young infants. Moreover, clinical evidence on the efficacy and safety of artemisinin-based combination therapies in this subpopulation is warranted.

A randomized trial of doxycycline for Mansonella perstans infection.

BACKGROUND: Mansonella perstans infection is common in areas of Africa where Wuchereria bancrofti, a causative agent of lymphatic filariasis, is endemic. M. perstans is refractory to standard antifilarial therapies. The recent discovery of bacterial endosymbionts (e.g., wolbachia) in most filarial species, including M. perstans, provides new therapeutic options for reducing microfilaremia. METHODS: In an open-label, randomized trial, we recruited subjects with M. perstans microfilaremia, with or without concomitant W. bancrofti infection, from four villages in Mali and randomly assigned them to receive doxycycline, at a dose of 200 mg daily for 6 weeks (106 subjects), or no treatment (110). At 6 months, subjects who were coinfected with W. bancrofti underwent a second random assignment, to treatment with a single dose of albendazole (400 mg) and ivermectin (150 microg per kilogram of body weight) or no treatment. Subjects were monitored daily during the first 6-week study period for adverse events. M. perstans and W. bancrofti microfilarial levels were assessed at 6, 12, and 36 months. RESULTS: At 12 months, 67 of 69 subjects who had received treatment with doxycycline only (97%) had no detectable M. perstans microfilariae per 60 microl of blood, as compared with 10 of 63 subjects who had received no treatment (16%) (relative risk, 6.18; 95% confidence interval, 3.63 to 11.89; P<0.001). At 36 months, M. perstans microfilaremia remained suppressed in 48 of 64 subjects who had received treatment with doxycycline only (75%), a finding that was consistent with a macrofilaricidal effect of doxycycline. Vomiting was more frequent in the doxycycline-treated group than in the untreated group (17% vs. 4%). CONCLUSIONS: These results are consistent with previous findings that M. perstans harbors the intracellular endosymbiont, wolbachia, and suggest that doxycycline is an effective therapy for M. perstans infection. (ClinicalTrials.gov number, NCT00340691.)

The impact of single versus mixed schistosome species infections on liver, spleen and bladder morbidity within Malian children pre- and post-praziquantel treatment.

BACKGROUND: In the developing world co-infections and polyparasitism within humans appear to be the rule rather than the exception, be it any combination of inter-specific and/or inter- and intra-Genera mixed infections. Mixed infections might generate synergistic or antagonistic interactions and thereby clinically affect individuals and/or impact parasite epidemiology. METHODS: The current study uniquely assesses both Schistosoma mansoni- and Schistosoma haematobium-related morbidity of the liver and the bladder as assessed by ultrasound as well as spleen and liver morbidity through clinical exams. The impact of praziquantel (PZQ) treatment on such potential inter-specific schistosome interactions and resulting morbidity using uniquely detailed longitudinal data (pre- and one year post-PZQ treatment) arising from the National Schistosomiasis Control Program in three areas of Mali: Ségou, Koulikoro and Bamako, is also evaluated. At baseline, data were collected from up to 2196 children (aged 7-14 years), 844 of which were infected with S. haematobium only, 124 with S. mansoni only and 477 with both. Follow-up data were collected from up to 1265 children. RESULTS: Results suggested lower liver morbidity in mixed compared to single S. mansoni infections and higher bladder morbidity in mixed compared to single S. haematobium infections. Single S. haematobium or S. mansoni infections were also associated with liver and spleen morbidity whilst only single S. haematobium infections were associated with bladder morbidity in these children (light S. haematobium infection OR: 4.3, p < 0.001 and heavy S. haematobium infection OR: 19, p < 0.001). PZQ treatment contributed to the regression of some of the forms of such morbidities. CONCLUSIONS: Whilst the precise biological mechanisms for these observations remain to be ascertained, the results illustrate the importance of considering mixed species infections in any analyses of parasite-induced morbidity, including that for the proposed Disability Adjusted Life Years (DALYs) revised estimates of schistosomiasis morbidity.

The association between child Schistosoma spp. infections and morbidity in an irrigated rice region in Mali: A localized study.

BACKGROUND: Schistosomiasis is one of the neglected tropical diseases endemic to Mali. There has been insufficient investigation of the morbidity burden in highly endemic irrigated rice areas with the ongoing mass drug administration with praziquantel. In February 2005, a year after an initial mass drug administration in 2004, we performed the first cross-sectional survey of schistosomiasis in the Kokry-Bozo village in the Office du Niger rice irrigation region. In the fourteen years since this survey, there has been almost no research into schistosomiasis morbidity in Mali due to lack of funding. Therefore, the 2005 survey supplies near-baseline data for any future research into the treatment impacts in the area. METHODS: One hundred and ninety-four children aged 6-14 years from two schools were assessed for bladder pathology by ultrasound, and for anaemia and micro-haematuria by laboratory tests. Schistosoma eggs were examined microscopically in fresh stool and urine samples. Multivariate logistic regression analysis quantified the association of Schistosoma infections with anaemia, bladder pathology and micro-haematuria. Akaike's information criterion was used to test the assumption of linear effects of infection intensity classes and used to compare across models. RESULTS: The overall prevalence of schistosomiasis in 189 school children was 97%; 17% (33/189) had a single infection (S. mansoni,13%, or S. haematobium, 4%) and 80% (156/189) were co-infected with S. mansoni and S. haematobium. The overall prevalence of S. mansoni with light infection was 27% (53/194), moderate infection was 24% (47/194) and heavy infection was 42% (81/194). Of the 194 of children investigated for S. haematobium 59% (114/194) had light infection and 26% (50/194) had heavy infection. No hookworm eggs were detected. The level of abnormal bladder pathology was 18% (35/189) with the highest found in 10-14 year old children. The prevalence of anaemia was 91% (172/189) and was twice as likely to be associated (OR 2.0, 95% CI 1.1-3.9) with S. mansoni infections than in children without infection. As infection intensity with S. mansoni increased the risk of anaemia (OR 2.0, 95% CI 1.1-3.9) also increased. As infection intensity with S. haematobium increased bladder pathology (OR 2.4, 95%CI 1.3-4.5), haematuria (OR 6.7, 95%CI 3.3-13.6) and micro-haematuria increased (OR 2.4, 95%CI 1.3-4.5). CONCLUSION: Our research contributes an important micro-geographical assessment of the heavy burden of schistosomiasis and associated morbidity in children who live in the rice irrigation regions. Our literature review found that there has been very limited research conducted on the impact of the treatment to control morbidity in the ON. Therefore, there is a need to do a comparable, but more extensive, study to identify any changes in morbidity and to indicate current requirements for the control programme. Our results from 2005 called for routine integration of iron supplementation, food fortification and diet diversification into the deworming program.

Immunization coverage and factors associated with incomplete vaccination in children aged 12 to 59 months in health structures in Lomé.

OBJECTIVE: To estimate the immunization coverage among children admitted for consultation or hospitalization in health structures of Lomé. RESULTS: A total of 797 respondent-child couples were included and 31.1% of them had their immunization cards. Complete immunization coverage was 69.3%, 95% confidence interval (65.9-72.5) and per antigen, it ranged from 83.1% for measles to 95.7% for BCG. Factors associated with incomplete immunization were the absence of immunization card (p < 0.001), respondents' sex (p < 0.001), level of education (p < 0.001), marital status (p < 0.001) and the level of the health structure in the organization of the Togolese health system (p < 0.001). Obstacles to immunization were mainly the lack of money to pay for immunization fees (38.4%) and forgetting the immunization appointment (28.1%).

Evidence of the impact of monovalent rotavirus vaccine on childhood acute gastroenteritis hospitalization in Togo.

BACKGROUND: Monovalent rotavirus vaccine (RV1) was introduced in the immunization schedule of Togo in June 2014. We evaluated the impact of rotavirus vaccines on acute gastroenteritis (AGE) and rotavirus-associated hospitalizations in Togolese children. METHODS: Sentinel surveillance for AGE (defined as ≥3 liquid or semi-liquid stools/24 h lasting <7 days) hospitalizations among children <5 years of age was conducted in two sites in the capital city, Lome. ELISA was used for diagnosis of rotavirus infection in children with AGE. Additionally, review of hospitalization registers was performed at five hospitals to assess trends in AGE hospitalizations among children aged <5 years. For the vaccine impact assessment, pre-rotavirus vaccine introduction (July 2010-June 2014) and post-rotavirus vaccine introduction (July 2014-June 2016) periods were compared for annual changes in proportions of hospitalizations associated with AGE and rotavirus. RESULTS: During the pre-vaccine period, sentinel surveillance showed that 1017 patients were enrolled and 57% (range, 53-62%) tested positive for rotavirus, declining to 42% (23% reduction) in the first post-vaccine year and to 26% (53% reduction) in the second post-vaccine year; declines were most marked among infants. The patient register review showed that, compared with pre-vaccine rotavirus seasons, declines in hospitalizations due to all-cause AGE during post-vaccine rotavirus seasons were 48% among <1 year age-group in both first and second years following vaccine introduction. Among 1-4 year olds no reduction was noted in the first year and a 19% decline occurred in the second year. CONCLUSIONS: We report rapid and marked reduction in the number of AGE hospitalizations and the proportion of AGE hospitalizations attributable to rotavirus in the first two years post- RV1 implementation in Togo. It is necessary to monitor long-term vaccine impact on rotavirus disease burden through continued surveillance.

Organomegaly in Mali before and after praziquantel treatment. A possible association with Schistosoma haematobium.

Continuous exposure to schistosome-infested water results in acute and chronic morbidity in all ages. We analysed occurence of organomegaly via ultrasonography and investigated a possible additive effect of dual-dose drug administration in 401 Schistosoma haematobium infected individuals from a highly endemic area in Mali. Mean intensity of infection at baseline (22.0 eggs per 10 ml) was reduced to 0.22 eggs per 10 ml 9 weeks after treatment (both treatments combined). Odds of persistent infection among those given dual-dose treatment was 41% of that in people given single dose (b = 0.41; p = 0.05; 95% CI 0.17-1.00), but after two years, 70.7% of the 157 participants, who completed the survey, were re-infected with no significant difference in prevalence and intensity of infection between treatment groups. Resolution of organomegaly occurred in all age groups after treatment. A novel association between Schistosoma haematobium infection and moderate portal vein enlargement was found in 35% (n: 55). Severe portal vein diameter enlargement was found in 3.2%. After two years, moderate hepatomegaly was present in 50.6%, moderate splenomegaly in 45.6% and moderate portal vein diameter enlargement in 19%. A subsequent dose of PZQ did not provide any additional long-term advantages.

Inflammation dynamics after praziquantel treatment of Schistosoma haematobium reflected by urinary eosinophil cationic protein.

Background: This cohort study assessed urinary eosinophil cationic protein (ECP) as an indicator for urinary tract morbidity and inflammation indication related to single-dose or dual-dose praziquantel (PZQ) treatment. Methods: Urinary ECP was measured at baseline, 24 h and 9 weeks after treatment (baseline 305, follow-up 204 participants, ages 2-40 years). Results: ECP was significantly associated with the intensity of infection at baseline (p<0.05). Levels at baseline were 8.31 times higher (p<0.01) in participants with bladder morbidity than in those without. There was no correlation with kidney morbidity and no significant effect of a repeated dose of PZQ 40 mg/kg. Baseline ECP and ECP after 9 weeks were associated with microhaematuria (geometric mean ratio at baseline 7.56 [95% confidence limit {CL} 2.34-24.45]; p<0.01) and macrohaematuria (geometric mean ratio at baseline 6.22 [95% CL 2.71-14.24]; p<0.001). Mean levels of ECP dropped significantly during the first follow-up period and far less so in the second follow-up period (mean ECP at baseline: 70.8 ng/mL; ECP at 24 h: 24.5 ng/mL; ECP at 9 weeks: 14.6 ng/mL). Conclusion: The urine ECP decrease happened immediately after treatment, reflecting the rapid action of PZQ on eggs in the bladder tissue. ECP in urine can be used as an indirect marker of the degree of local inflammatory reaction in the bladder and is not significantly affected by a repeated dose of PZQ.

Anemia and growth retardation associated with Schistosoma haematobium infection in Mali: a possible subtle impact of a neglected tropical disease.

Background: The aim of this cross-sectional study was to investigate a possible association of Schistosoma haematobium with child growth development and describe a plausible schistosomiasis-related anemia in children and adults in a highly schistosomiasis endemic area of Mali. Methods: Urine, feces and blood samples from 399 participants of both sexes (2-40 years of age) were analyzed and supplemented by anthropometric measurements. Results: S. haematobium prevalence was 79.8%, S. mansoni 13.2% and Plasmodium falciparum 80.2%. S. haematobium infection intensity as five categories was significantly associated with anemia; i.e., odds of having anemia in the highest and the next highest category was 3.25 (95% CL 1.61-6.55; p<0.01) and 2.45 (95% CL 1.28-4.70; p<0.01), respectively, of that in the three lower categories combined after adjusting for age group and gender and the interaction between the two factors. Anemia was most pronounced in the 2-5 year olds males (55.5%, n=98). P. falciparum infection was not significantly associated with anemia. Stunting (body mass index [BMI] for age z-score<-2.00) was observed in 2.6% (2/78) of the 2-5 years olds and in 7.7% (14/182) in the 6-19 years age group. Lower BMI-z-scores (as continuous variable) were associated with anemia (p<0.05) while high intensity of S. haematobium infection was not significant when adjusting for age group and anemia. Participants with malaria infection had lower z-scores (as continuous variables) of weight and height for age. Lower height for age z-scores were also associated with anemia. Conclusions: S. haematobium infection is likely to impact on child growth and possibly also anemia in all age groups and advocates for inclusion of whole populations into future control programes.

Assessment of ultrasound morbidity indicators of schistosomiasis in the context of large-scale programs illustrated with experiences from Malian children.

We assessed morbidity indicators for both Schistosoma haematobium and Schistosoma mansoni infections and evaluated the appropriateness of the World Health Organization (WHO) guidelines for ultrasound in schistosomiasis in the context of large-scale control interventions. Abdominal and urinary tract ultrasonography was performed on 2,247 and 2,822 school children, respectively, from 29 randomly selected schools in Mali before the implementation of mass anthelminthic drug administration. Using two-level logistic regression models, we examined associations of potential factors with the risk of having a positive ultrasound global score (morbidity indicative of S. haematobium infection), abnormal image pattern scores, dilatation of the portal vein, and/or enlarged liver (morbidity indicative of S. mansoni infection). The WHO protocol was found useful for detection of S. haematobium pathology but overestimated the risk of portal vein dilatation and left liver lobe enlargement associated with S. mansoni infection. We conclude that ultrasonography should be included in large-scale control interventions, where logistics allow, but cautiously.

Significantly reduced intensity of infection but persistent prevalence of schistosomiasis in a highly endemic region in Mali after repeated treatment.

BACKGROUND: Preventive chemotherapy against schistosomiasis has been implemented since 2005 in Mali, targeting school-age children and adults at high risk. A cross-sectional survey was conducted in 2010 to evaluate the impact of repeated treatment among school-age children in the highly-endemic region of Segou. METHODOLOGY/PRINCIPAL FINDINGS: The survey was conducted in six sentinel schools in three highly-endemic districts, and 640 school children aged 7-14 years were examined. Infections with Schistosoma haematobium and S. mansoni were diagnosed with the urine filtration and the Kato-Katz method respectively. Overall prevalence of S. haematobium infection was 61.7%, a significant reduction of 30% from the baseline in 2004 (p<0.01), while overall prevalence of S. mansoni infection was 12.7% which was not significantly different from the baseline. Overall mean intensity of S. haematobium and S. mansoni infection was 180.4 eggs/10 ml of urine and 88.2 epg in 2004 respectively. These were reduced to 33.2 eggs/10 ml of urine and 43.2 epg in 2010 respectively, a significant reduction of 81.6% and 51% (p<0.001). The proportion of heavy S. haematobium infections was reduced from 48.8% in 2004 to 13.8% in 2010, and the proportion of moderate and heavy S. mansoni infection was reduced from 15.6% in 2004 to 9.4% in 2010, both significantly (p<0.01). Mathematical modelling suggests that the observed results were in line with the expected changes. CONCLUSIONS/SIGNIFICANCE: Significant reduction in intensity of infection on both infections and modest but significant reduction in S. haematobium prevalence were achieved in highly-endemic Segou region after repeated chemotherapy. However, persistent prevalence of both infections and relatively high level of intensity of S. mansoni infection suggest that more intensified control measures be implemented in order to achieve the goal of schistosomiasis elimination. In addition, closer monitoring and evaluation activities are needed in the programme to monitor the drug tolerance and to adjust treatment focus.

Impact of Schistosoma haematobium infection on urinary tract pathology, nutritional status and anaemia in school-aged children in two different endemic areas of the Niger River Basin, Mali.

The aim of the present study was to contribute to define urinary schistosomiasis-related morbidity indicators and to understand the relationship between infection intensity and disease burden among school-aged children in different endemic areas of Mali. A cross sectional study was undertaken in two different endemic settings: Koulikoro district, along the river and Selingué dam area in the Niger River Basin in order to compare and describe morbidity related to Schistosoma haematobium infection. A total of 667 children aged 7-14 were enrolled in the study. Among these, 333 were from Koulikoro district (175 boys and 158 girls) and 334 from Selingué dam area (169 boys and 165 girls). The overall prevalence of S. haematobium in the two areas was 91.5%; Koulikoro (97.0%) and Selingué (85.9%) and this difference was significant after adjusting for age, sex and clustering within villages. Prevalence of heavy infection (≥ 50 eggs per 10 ml of urine), 57.6% in Koulikoro and 43.8% in Selingué, did not differ significantly after adjusting for age, sex and clustering within villages. The transmission of Schistosoma mansoni was mainly confined to Selingué dam area (12.5%) and was nearly absent in Koulikoro district (1.1%). Blood in urine was the most frequently reported clinical symptom, more common in Koulikoro (76.8%) than in Selingué (57.6%). In a multivariable logistic regression model adjusting for sex, age group, egg intensity category and clustering within villages, Selingué had higher prevalence of macro-haematuria, urinary tract pathology, upper urinary tract pathology and total pathology than Koulikoro, while micro-haematuria did not differ between the two areas. Morbidity measures increased to some extent with egg intensity category, especially micro-haematuria. The results obtained from this study are of importance for planning intervention as for monitoring and evaluation of control in different endemic settings in Mali.