Strengthening human genetics research in Africa: report of the 9th meeting of the African Society of Human Genetics in Dakar in May 2016.

The 9th meeting of the African Society of Human Genetics, in partnership with the Senegalese Cancer Research and Study Group and the Human Heredity and Health in Africa (H3Africa) Consortium, was held in Dakar, Senegal. The theme was Strengthening Human Genetics Research in Africa. The 210 delegates came from 21 African countries and from France, Switzerland, UK, UAE, Canada and the USA. The goal was to highlight genetic and genomic science across the African continent with the ultimate goal of improving the health of Africans and those across the globe, and to promote the careers of young African scientists in the field. A session on the sustainability of genomic research in Africa brought to light innovative and practical approaches to supporting research in resource-limited settings and the importance of promoting genetics in academic, research funding, governmental and private sectors. This meeting led to the formation of the Senegalese Society for Human Genetics.

Le 9ème congrès de la Société Africaine de Génétique Humaine, en partenariat avec le Groupe d'Etude et de Recherche sur le Cancer (GERC) et le Consortium H3Africa, s'est tenu à Dakar, au Sénégal. Le thème était «Renforcer la recherche en Génétique Humaine en Afrique¼. Les 210 participants sont venus de 21 pays africains et de six non africains. L'objectif était de valoriser la génétique et la génomique à travers l'Afrique avec comme but ultime d'améliorer la santé des populations, et de promouvoir les carrières des jeunes chercheurs Africains. Une session sur la pérennité de la recherche génomique a révélé des approches innovantes et pratiques supportant la recherche dans des contextes de ressources limitées et l'importance de promouvoir la formation universitaire en génétique, le financement de la recherche par les gouvernements et le privé. Ce congrès conduisit à la création de la Société Sénégalaise de Génétique Humaine.

[Profiles of IgG responses against CSP, GLURP and LSA-3NR2 in urban malaria (Dakar): relations with haemoglobin levels and parasite densities]. / Profils des réponses IgG dirigées contre CSP, GLURP et LSA-3NR2 dans le paludisme urbain à Dakar : influence sur l'hémoglobinémie et les parasitémies circulantes.

Malaria remains a major health problem in sub- Saharan African countries despite substantial decreases in morbidity and mortality due to sustained control programs. Vaccines candidates were mainly tested in rural endemic setting; however increasing proportion of the population is living in urban area. Evaluation of the qualitative or quantitative immune responses to key targets of anti-Plasmodium immunity requires further investigation in urban area. In a cohort of 144 patients with mild malaria living in Dakar, we analyzed IgG responses against target antigens of P. falciparum: CSP, LSA-3NR2 and GLURP by ELISA. A mean age of 15 yrs (4-65 yrs) was found and patients were separated in 59 adults (<15yrs) and 85 children (≤15 yrs). Parasites densities (0,01-15%) did not differ between the two age groups. In contrast, haemoglobin levels appeared lower in children (4.5-16.6 g/dl) (p<0.01). For the immune results, the most recognized antigens were GLURP and CSP compared to LSA-3NR2. Levels of IgG against these antigens were significantly different between the two age groups and they were positively correlated (rho = 0.32; p<0.001). In addition, levels of IgG anti-GLURP were associated with low parasitemia (≤1%) and absence of anemia (≥11g/dl), particularly in adults (p<0.001). In a multiple regression analysis, no significant relationship was found between parasite densities and IgG responses against all the tested antigens. Our study shows the implication of IgG anti-GLURP in humoral immune response against the parasite. The present work contributes to determine IgG levels that can be used as relevant immunologic biomarkers in urban clinical malaria.

[IgG responses to candidate malaria vaccine antigens in the urban area of Dakar (Senegal): evolution according to age and parasitemia in patients with mild symptoms]. / Analyses des réponses IgG dirigées contre des antigènes candidats vaccins dans le paludisme urbain non aggravé à Dakar (Sénégal): variations suivant l'âge et les densités parasitaires.

Malaria remains a major problem in African countries despite substantial decreases in morbidity and mortality due to sustained control programs. Studies for the evaluation of qualitative or quantitative Ab responses to key targets of anti-plasmodium immunity were mostly done in rural endemic setting compared to urban area. In a cohort of 200 patients with mild malaria and living in Dakar, we analyze total and subclasses IgG responses to a panel of P. falciparum blood stage antigens: MSP1p19, MSP3, EB200, GST-5 and R23. A mean age of 15 yrs (4 to 56 yrs) and parasitemia between 0.1 to 17% were found. Levels of IgG anti-MSP3 were higher in patients with low parasitemia (≤1%) and appear negatively correlated to parasite densities (Rho =. 0.54; p= 0.021). This correlation is more significant in children (≤ 15 yrs). In addition, an increase of IgG responses against MSP1p19 is highly observed in adults having a parasitemia less than 1%. In those patients, we find that IgG1 subclasses were predominant (p <0.01). Our study shows an association between Ab responses and parasitemia. This association is dependant to IgG anti-MSP3 in children and IgG anti-MSP1p19 in adults living in urban area.

[Evaluation of an immunoassay for calcitonin]. / Evaluation d'une methode de dosage de la calcitonine par chimio luminescence dans le suivi des cancers medullaires de la thyroïde.

INTRODUCTION: The calcitonin is the most specific and the most sensitive marker of medullary thyroid carcinoma (MTC) both for screening and postoperative follow-up of the patients. Its measurement is made either remotely , or after stimulation of pentagastrin secretion which the answer is amplified at the carrier of CMT. The aim of this study was to estimate a chimioluminescent method by comparing it with an immunoradiological method, manual, used as reference. Correlation study was done. MATERIALS AND METHODS: Two hundred and sixty three serums (263) were tested among which 64 resulting of healthy subjects and 199 resulting of patients affected) by medullary thyroid carcinoma. Statistical analysis of results was made by a study of correlation with the software OriginLab version 7.0. The manual technique used as reference method is radioimmunological (Elsa hCT, international Cisbio, Gif on Yvette, France). It was compared with a chimioluminescent technique (Nichols Advantage, Nichols Institute Diagnostics, CA, the USA). RESULTS: The coefficients of correlation obtained between both tests were: r = 0.76 (exactness study), r = 0.91 (after stimulation), r = 0.95 and 0.79 (staged samples), r = 0.99 (M TC patients). CONCLUSIONS: Both techniques correlate strictly and significantly. The correlation coefficients we obtained show us that Nichols Advantage Calcitonin is completely reliable and sensitive for the measurement of the hCT in the follow-up of the CMT.

[Decentralization of the immunological monitoring of people living with HIV/AIDS in a limiting setting with a low HIV seroprevalence: the experience of Senegal]. / Décentralisation du suivi immunologique des personnes vivant avec le VIH dans un pays à ressources limitées et à prévalence faible: expérience du Sénégal.

Our work aimed to propose a manual method of counting CD4 T lymphocytes which is an alternative magnetic immunoseparation followed by a reading with a fluorescence microscope as an alternative to the automated flow cytometry. This alternative technique is easier for use, less expensive and could answer the difficulties encountered for the monitoring CD4 T cells count in developing countries. The specific objectives were: 1) to train the technicians of the peripheral sites in order to make the numeration of the CD4 T lymphocytes more accessible at the peripheral level; 2) to equip the sites with necessary facilities for the T lymphocytes CD4 count; 3) to put in place a system of quality control permitting the reliability of the results. A hundred and fifty patients have been enrolled in three care services for people living with HIV/AIDS in Dakar. This population was constituted of 119 seropositive and 31 seronegative patients acting as control group to have some patients with high rates of T lymphocytes CD4. For the follow-up at peripheral level, the patients were constituted of the active line of the patients living with HIV/AIDS supported in the targeted sites. The measurements allowed studying concordances for different rates of lymphocytes: 0 to 199, 200 to 499 and over 500 cells by mm3. The results showed also a very good correlation (r = 0.97 or r = 0.98 according to the operator) between the two methods for CD4 rates inferior to 500 cells by mm3 among both the negative group and the HIV positive patients. We also discussed the profit of decentralization for the program and the patient, as well as the setting up of an external quality control to validate the alternative technique. According to the results, the Dynabeads is well correlated with the Facscount. It is a technique that can be used as an alternative in the zones with limited resources, low prevalence and for a small number of samples.

[Comparison of three chemiluminescent methods with a radioimmunoassay for thyroglobulin measurement in the follow-up of differentiated thyroid cancer]. / Comparaison de trois methodes chimioluminescentes avec une methode radioimmunologique de dosage de la thyroglobuline dans le suivi des cancers differencies de la thyroide.

INTRODUCTION: Serum thyroglobulin measurements play an integral role in clinical evaluation of patients with thyroid cancer. Serum thyroglobulin is a highly specific and sensitive tumor marker for detecting persistent or recurrent thyroid cancer but also for monitoring clinical status. Actually, chemiluminescent methods gain ground on the radioimmunological methods because they offer the practical advantage of a shorter incubation time, a wider range of measured values and a reagent marked antibody more stable, less fragile than those used on radioimmunoassay. The aim of this study was to compare, by correlation study, three chemiluminescent methods to the reference radioimmunological method usually used in laboratories. MATERIALS AND METHODS: Thyroglobulin was measured in 203 patients by the 3 following analyzers: Nichols Advantage (Nichols Institute Diagnostics, CA, USA), Immulite 2000 ( DPC Roche, Siemens, Los Angeles, USA) and Elecsys 2010 (Roche Diagnostics, Manheim, Germany); and by manual method (SELco Tg (Medipan Diagnostica, Berlin, Germany). Correlation analysis with OriginLab software version 7.0 was performed in order to compare thyroglobulin distribution values measured by the different methods. RESULTS: Correlation coefficients obtained were for Medipan/ Immulite 2000: 0.95 (n = 80); for Medipan/Elecsys: 0.97 (n = 31); for Medipan/Advantage: r = 0.96 (n = 73). CONCLUSIONS: Chemioluminescent technics we studied could be validly used in patients without anti-thyroglobulin antibody. The correlation coefficients we obtained allow us to select one of these automated methods after their performance was studied.

[Transferrine soluble receptors' contribution to the assessment of iron status in homozygous drepanocytic anemia]. / Apport des récepteurs solubles de la transferrine dans l'évaluation du statut en fer au cours de la drépanocytose homozygote.

Sickle cell anemia does not cause martial deprivation per se, but may worsen when iron deficiency exists, notably in tropical zone where infectious diseases and malnutrition are endemic mainly during childhood. This study was aimed to assess iron deficiency prevalence among children with sickle cell disease (SCD) and to determine the best parameters for its diagnosis. In addition to classical parameters, we measured transferrine's soluble receptors which can reveal an iron deficiency, either isolated or associated to another condition since its level is not influenced by chronic anemia. Assays were carried out in 40 homozygous SCD patients, aged 3 to 18 years, having an hemoglobin level < 11 g/dL and in 30 age-paired controls assumed to be healthy and having a negative Emmel test and an hemoglobin level < 11 g/dL. The results showed hyposideremia (serum iron < 60 microg/dL) in 17.5% of the patients. Ferritinemia, transferrinemia as well as total iron fixation capacity were in the normal range for the majority of SCD patients in spite of the frequency of hyposideremia and microcytic anemia (20%). Transferrine's saturation coefficient was low in 22.5% of patients, which can be due to martial deprivation or to inflammatory status. These results confirm the limitations of usual biochemical parameters in the diagnosis of iron deficiency in homozygous drepanocytosis. Soluble receptors' levels were increased in 60% of controls; that proves that iron deficiency prevalence is high in our countries. Higher levels were found in 97.5% of patients. However, receptors' levels are increased during haemolysis, thus it is difficult to ascertain the origin of the increase, but taking into account its index value can reduces misinterpretation. In addition, considering simultaneously microcytosis, hypochromia, transferrine's soluble receptor level and its index, we can speculate that martial deficiency occurs in 20% of SCD patients, a percentage close to the 17.1% obtained by other authors using only the combination of microcytosis and hypochromia. It results from this study that associating microcytosis and hypochromia could validly assess iron deficiency during drepanocytosis.

[Frequency of microalbuminuria during diabetes in Dakar, Senegal]. / Fréquence de la microalbuminurie au cours du diabète a Dakar (Senegal).

Nephropathy is one of the complications occuring during diabetes and it is diagnosed via microalbuminuria. From 1992 to 1999, five hundred and eighty seven (587) diabetic patients were recruited and distributed into two groups, A (n = 270) and B (n = 317). Microalbuminuria was determined by immunonephelemetry for group A and immunoturbidimetry for group B. The results showed respectively 15.5% and 20.19% pathological cases in the two groups (NS). Considering the distribution of patients with microalbuminuria according to the type of diabetes, there were 16.12% type 1 and 15.07% type 2 in group A against 22.60% and 18.13% in group B; no statistically significant differences were observed either in the same group or from one group to another. These frequencies might reflect the situation in the nineties; they are lower than those encountered in other populations. Nevertheless monitoring is needed through a regular schedule to prevent nephropathy.

[Laboratory diagnosis of monoclonal gammopathies. Prospective study of 14 cases in Dakar, Senegal]. / Diagnostic au laboratoire des gammapathies monoclonales. Etude prospective de 14 cas à Dakar, Sénégal.

Monoclonal gammapathies are detected because of clinical symptoms and biological tests confirm their presence. Wishing to investigate these diseases, we carried out a series of biochemical tests on 14 patients from October 1995 to July 1996: protein, cryoglobulin, electrophoresis of proteins, proteinuria of BENCE JONES, C-reactive protein, weight measuring of immunoglobulins (Ig), immunofixation of Ig, creatinine and calcium. The results we obtained confirmed the presence of 14 cases of myeloma with: -9 IgG myelomas with 6 kappa light chains and 3 lambda light chains -4 IgA myelomas with 2 kappa light chains and 2 lambda light chains -1 IgG kappa, Ig lambda biclonal gammapathy united to a cryoglobulin of class I. We observed a predominance of the IgG over the others Ig and the kappa over the alpha light chains. The proteinuria of BENCE JONES was present among 3 patients, hypercalcemia among 4 patients and hypercreatininemia in 1 patient with chronic renal failure.