Estimating the number of probable new SARS-CoV-2 infections among tested subjects from the number of confirmed cases.

OBJECTIVES: In most African countries, confirmed COVID-19 case counts underestimate the number of new SARS-CoV-2 infection cases. We propose a multiplying factor to approximate the number of biologically probable new infections from the number of confirmed cases. METHODS: Each of the first thousand suspect (or alert) cases recorded in South Kivu (DRC) between 29 March and 29 November 2020 underwent a RT-PCR test and an IgM and IgG serology. A latent class model and a Bayesian inference method were used to estimate (i) the incidence proportion of SARS-CoV-2 infection using RT-PCR and IgM test results, (ii) the prevalence using RT-PCR, IgM and IgG test results; and, (iii) the multiplying factor (ratio of the incidence proportion on the proportion of confirmed -RT-PCR+- cases). RESULTS: Among 933 alert cases with complete data, 218 (23%) were RT-PCR+; 434 (47%) IgM+; 464 (~ 50%) RT-PCR+, IgM+, or both; and 647 (69%) either IgG + or IgM+. The incidence proportion of SARS-CoV-2 infection was estimated at 58% (95% credibility interval: 51.8-64), its prevalence at 72.83% (65.68-77.89), and the multiplying factor at 2.42 (1.95-3.01). CONCLUSIONS: In monitoring the pandemic dynamics, the number of biologically probable cases is also useful. The multiplying factor helps approximating it.

[Realities for a Sickle Cell Disease Control Strategy in the World Health Organization African Region]. / Réalités pour une stratégie de lutte contre la drépanocytose dans la région africaine de l'Organisation Mondiale de la Santé: Compte rendu du 7e Symposium International du Réseau d'Étude de la Drépanocytose en Afrique Centrale (REDAC https://www.redacnetwork.org/) Antananarivo, Madagascar. 13 - 15 juin 2018.

The Network for the Study of Sickle Cell Disease in Central Africa or REDAC, is a network of African, European and American researchers whose aim is to combat sickle cell disease. Its congresses take place every year in the partner countries with international symposia alternating with workshops. REDAC enables host countries to obtain from local authorities a real involvement in the fight through resolutions in line with national strategies of fight. The Seventh International Symposium of REDAC was held in 2018 in Antananarivo, Madagascar under the auspices of the Malagasy Minister of Health and the Malagasy Senate Authorities. The theme chosen was that of strategies to combat sickle cell disease recommended by the WHO. The presentations focused on neonatal screening, early diagnosis, management of sickle cell disease and new therapies (marrow transplant, gene therapy and treatment with hydroxyurea).

[Hemogram findings in Congolese children with sickle cell disease in remission]. / L'hémogramme de l'enfant drépanocytaire congolais au cours des phases stationnaires.

INTRODUCTION: Sickle cell disease is associated with a wide range of clinical and laboratory findings depending on genetic modulators and environmental factors. The most severe forms of sickle cell disease occur in patients with the Bantu haplotype. The purpose of this study was to determine the hematological profile of Congolese patients with homozygous sickle cell disease during periods of remission. PATIENTS AND METHODS: Hemograms were performed in two series of patients with sickle cell disease in remission, i.e., one including 89 patients with a mean age of 8.7 years and the other including 42 patients with a mean age of 8.9 years. Hemograms were performed using an automated counter and reticulocytes were counted manually on peripheral blood smears. Fetal hemoglobin level (HbF) was measured by chromatography (HPLC). The mean values obtained were compared with those obtained in a sickle-cell-disease-free control group. Some parameters were also compared with those obtained in a group of patients exhibiting complications of sickle cell disease. RESULTS: Hemograms in the first series of patients demonstrated the following values: Hb: 7.2 g/dl; Hct 23.1%, red cells: 2.47 tera/L, leukocytes: 14.9 giga/L; VGM: 95.3 fL; CCMH:30.3% L and platelets:345,3 giga/L. Blood count showed 30.4% of polynuclear neutrophils, 33% de lymphocytes, 0.8% of polynuclear basophiles, 14% of monocytes, 7.8% of polynuclear eosinophils and 14% of erythroblasts. Mean HbF level was 7.2% and reticulocytes were at 88%. In the sickle cell disease-free group, the leukocyte rate was almost three fold higher than in the patient group exhibiting sickle cell disease in remission even though rates were higher than during complications. CONCLUSION: Hemogram profiles in Congolese patients with sickle cell disease are similar to those reported in the literature for subjects exhibiting the Bantou haplotype. Leukocytosis was associated with esinophilia and monocytosis suggested a topical state and chronic inflammation.

[Protein profile in 45 Congolese children with sickle cell anaemia]. / Etude du profil protéique de 45 enfants drépanocytaires homozygotes congolais.

Sickle cell anemia (SCA) is a genetic disorder characterized by severe hemolytic anemia, frequent vaso-occlusive events and infections. In tropical environment, people are continuously in contact with infection agents. The present study was undertaken to measure 10 protein parameters in order to test humoral immunity, nutrition status and the relation between inflammation and hemolysis in sickle cell anemia patients in 45 Congolese sickle cell children (15 females and 30 males, median age: 7 yrs) and a control group of 43 well healthy congolese group (18 females, 25 males; median age 18 yrs). Mean values for immunoglobulins (IgG, IgM, IgA), nutrition proteins (albumin, transthyretin and transferrin) and inflammatory and hemolysis markers (C3, CRP, A1GP: alpha1-Glycoprotein acid and haptoglobin) were compared between two groups. Hyperstimulation of humoral immunity was observed in the SCA group. Most significative difference was found with IgA (p < 0,001). Intravascular hemolysis was illustrated by a significant decrease of the haptoglobin/A1GP ratio, and was constantly present in SCA patients. We also described a significative decrease (p < 0,001) of haptoglobin/A1GP ratio between SCA patients with inflammatory syndrom when compared to those without inflammation. All data confirm that haemolysis is quite linked to inflammation in SCA. In addition, nutrition parameters were significantly decreased in SCA group vs healthy congolese group.

Evaluation of the application of national malaria treatment guidelines in private pharmacies in a rural area in the Democratic Republic of Congo.

In the Democratic Republic of the Congo, the first recourse in case of suspected malaria in the health system is the private pharmacy sector. This study was therefore designed to assess private provider adherence to national case management guidelines in Kimpese, a rural area of Central Kongo province. A descriptive cross-sectional survey of 103 pharmacies took place in March 2016. The study included 97 pharmacies. The artemether-lumefantrine combination recommended as the first-line treatment for uncomplicated P. falciparum malaria was available in 100% of pharmacies but only 3% stocked quality-assured medicines. The sulfadoxine-pyrimethamine recommended for intermittent preventive treatment of malaria in pregnant women and quinine, which is no longer part of national policy, were widely available (>97.0% of pharmacies). Among providers, fewer than 20% were aware of the national malaria treatment guidelines. The main reasons for non-adherence to national guidelines among private dispensers was the high cost (up to 10 times more expensive than sulfadoxine-pyrimethamine treatment) and adverse effects of artemisinin-based combination therapies. Governmental interventions to improve private sector engagement in implementation of the national guidelines and to prevent the spread of ineffective and non-quality assured antimalarial medicines must be intensified.

[Human papillomavirus genotype profile in Kinshasa, Democratic Republic of the Congo: implications for vaccination]. / Profil génotypique du papillomavirus humain rencontré dans l'environnement de Kinshasa: intérêt vaccinal.

UNLABELLED: Proposed anti-human papillomavirus (HPV) vaccines, i.e., Cervarix (Glaxomith-Kline) and Gardasil (Merck), are designed to prevent infection by two high-risk HPV types, i.e., 16 and 18, for which estimation mainly in Western Europe and North America have demonstrated a prevalence 60 to 70%. OBJECTIVE: The purpose of this study was to determine the genotype profile of HPV strains encountered in the women of childbearing age in Kinshasa, Democratic Republic of the Congo and discuss the implications of this profile for anti-HPV vaccination. METHODS: Data and specimen collection was carried out at a voluntary HIV screening and treatment facility. Genotyping of HPV was performed in 55 patients presenting dysplastic lesions of the uterine cervix including 47 (85.5%) who were HIV-seropositive. Detection and typing of HPV were performed using the Inno-Lipa technique (Innogenetics Line Probe Assay) from Glaxo-Smith-Kline. RESULTS: Tests for HPV were positive in 54 patients (98.2%). A total of 153 HPV strains were isolated. Twenty-three HPV types were identified including 83.0% with high oncogenic activity. In order of frequency the oncogenic types were as follows: 68, 35, 51, 52, 16, 31, 18, 17, 33, 45, 56, 58 and 59. Strain frequency per patient ranged from 1 to 8 (mean +/- standard deviation, 2.8 +/- 2,0). Types 16 and 18 accounted for 11.8% of the isolated strains (18/153) and were observed in 33.3% of patients (18/54). CONCLUSION: The findings of this study suggest that the HPV genotype profile in Kinshasa differs from the profile observed in Western Europe and North America. If confirmed by larger-scale studies, this result bodes poorly for the efficacy of anti-HPV vaccines in Kinshasa.

Access to artemisinin-based combination therapies and other anti-malarial drugs in Kinshasa.

OBJECTIVE: Artemisinin-based combination therapies have been available since 2005 in the Democratic Republic of the Congo to treat malaria and to overcome the challenge of anti-malarial drug resistance as well as to improve access to effective treatments. The private sector is the primary distribution source for anti-malarial drugs and thus, has a key position among the supply chain actors for a rational and proper use of anti-malarial drugs. We aimed to assess access to nationally recommended anti-malarial drugs in private sector pharmacies of the capital-city of Kinshasa. METHOD: We performed a cross-sectional survey of 404 pharmacies. RESULTS: Anti-malarial drugs were stocked in all surveyed pharmacies. Non-artemisinin-based anti-malarial therapies such as quinine or sulfadoxine-pyrimethamine, were the most frequently stocked drugs (93.8% of pharmacies). Artemisinin-based combination therapies were stocked in 88% of pharmacies. Artemether-lumefantrine combinations were the most frequently dispensed drugs (93% of pharmacies), but less than 3% were quality-assured products. Other non-officially recommended artemisinin-based therapies including oral monotherapies were widely available. CONCLUSION: Artemisinin-based combination therapies were widely available in the private pharmacies of Kinshasa. However, the private sector does not guarantee the use of nationally recommended anti-malarial drugs nor does it give priority to quality-assured anti-malarial drugs. These practices contribute to the risk of emergence and spread of resistance to anti-malarial drugs and to increasing treatment costs.

[Medicine and health in the Democratic Republic of Congo: from Independence to the Third Republic]. / Médecine et santé en République Démocratique du Congo: de l'Indépendance à la 3e République.

The birth and mortality rates in the Democratic Republic of Congo (DRC), a former Belgian colony, are high, i.e., 48.9/1000 and 17/1000 respectively. The DRC also has one of the highest maternal death rates in the world, i.e., 1289/100,000 live births. Health conditions have not improved since independence. Access to drinking water is limited, living conditions are poor, and food availability in households is low. The mean health services utilization rate in the DRC is estimated to be 0.15 visits/inhabitant/year. The incidence of transmissible diseases is rising. This increase is observed even for illnesses that were under control before independence such as sleeping sickness, onchocerciasis, leprosy, and tuberculosis. One the main causes of mortality and morbidity in the population is malaria that is responsible for the deaths of 150,000 to 250,000 children under the age of 5 every year. The HIV prevalence rate is 4.5% with 1.19 million persons with AIDS and 930,000 orphans whose parents died of AIDS. Other potentially epidemic diseases including bubonic plaque and Ebola hemorrhagic fever are serious threats. Non-transmissible diseases are also on the rise including diabetes, systemic arterial hypertension, cancer and neglected diseases such as sickle cell anemia. To meet these challenges, the country's health authorities have established a program called the Strategy for Reinforcement of the Health System (SRHS). One goal of the SRHS is to develop health zones in order to improve access to quality health care for the whole population.

[Is therapeutic progress in the management of sickle cell disease applicable in sub-Saharan Africa?]. / Les progrès thérapeutiques dans la prise en charge de la drépanocytose sont-ils applicables en Afrique subsaharienne?

The life expectancy of patients with sickle cell disease has improved in the United States and Europe thanks to the use of penicillin prophylaxis, appropriate immunizations, neonatal screening, implementation of a quality transfusional policy, hydroxyurea therapy, detection and treatment of cerebral vasculopathy, recognition of situations that can benefit from allogenic marrow transplantation, and improvements in bone marrow transplantation techniques. The cost of almost all these techniques is far beyond the means of health care systems in Africa where they cannot be used. However at least three, i.e., penicillin, vaccines, and hydroxyurea, could be easily accessible in the framework of defined therapeutic strategies. If daily penicillin and pneumococcal vaccine Pneumo 23 are required, it would likely be necessary to select a conjugated vaccine other than Prevenar that does not provide protection against all strains present in Africa. Neonatal screening is still a rare procedure in sub-Saharan countries. Periodic transfusion is steadily improving but exchange transfusion programs aimed in particular at preventing neurological complications are still unfeasible. Indications for hydroxyurea therapy in Africa are more common due to the lack of access to chronic transfusion and must be based on consensus decision. Use of bone marrow transplantation, i.e., the only currently available curative treatment, is still possible only in northern hemisphere countries where it is still restricted to children with severe forms and an HLA-compatible family donor.

[Iron status in 72 Congolese patients with sickle cell anemia]. / Le statut martial chez soixante-douze drépanocytaires homozygotes congolais.

Multiple blood transfusions, intestinal parasites, and high iron needs during the growth period are all factors that influence iron status in African children. To determine their iron status and its association with these factors, we studied 72 homozygous sickle-cell patients in a steady state in Kinshasa. Iron status was determined by a combination of several indicators: ferritin, transferrin, blood count, total iron binding capacity, transferrin saturation, and C-reactive protein. These results were compared with those from a matched control group without sickle-cell disease. Compared to the control group, 5 patients (11%) were iron-deficient, while 18 (35%) had an iron overload, probably due to multiple blood transfusions. This study shows the importance of periodic assessments of iron status in homozygous sickle cell patients to prevent and manage any iron imbalance.

Newborn screening for haemoglobinopathies: the Brussels experience.

OBJECTIVES: To determine the prevalence of haemoglobinopathies and the need for neonatal screening for haemoglobinopathies in Brussels. METHODS: Between December 1994 and June 1998 23,136 cord blood samples obtained in eight hospital nurseries of Brussels were systematically screened for haemoglobinopathies by isoelectric focusing. RESULTS: 45% of the newborns were from regions at risk for haemoglobinopathies. Sickle cell disease was diagnosed for 11 neonates (0.048%) and beta thalassaemia major for one neonate. Three hundred and fifty neonates (1.5%) were carriers for a haemoglobin variant, and Hb Bart's was found in 672 cases (2.9%). These prevalences are similar to those reported elsewhere in northern Europe. CONCLUSIONS: These results confirm the value of universal screening for haemoglobinopathies in Brussels.

Globin chains analysis: improved resolution by electrophoresis in urea-acetic acid-Triton X-100.

To improve the resolution and rapidity of globin chains separation, we have modified the basic technique of globin chain electrophoresis in urea-acetic acid-Triton X-100. Haemolysates from anticoagulated cord or adult blood samples were submitted to urea-acetic acid-Triton X-100 polyacrylamide gel electrophoresis using a 15% polyacrylamide gel cast in a mini slab cell which allows a rapid analysis of globin chains samples. After staining proteins with Coomassie brilliant blue R-250, the relative amounts of globin chains were determined by scanning. This new procedure has allowed us to obtain a better separation of the normal and abnormal globin chains than described previously. All the normal globin chains, i.e. A gamma, G gamma, delta, beta and alpha, are well separated by this modified technique. Semi-quantification of the G gamma/A gamma ratio has been performed. This simple and rapid method is also suitable for the global identification of the globin chain involved in the most common abnormal haemoglobin variants, except beta-S.

[Sickle cell anemia in the south of Zaire. Study of two series of 251 and 340 patients followed-up 1988-1992]. / La drépanocytose dans le sud du Zaïre. Etude de deux séries de 251 et 340 malades suivis entre 1988 et 1992.

BACKGROUND: This work concerns 591 sickle cell disease patients followed by the same paediatrics team in south Zaire. POPULATION: Two series of homozygous sickle cell patients were studied: 1) 251 in-patients hospitalized in Kolwezi during the period 1988-1989, and 2) 340 out-patients examined in Lubumbashi during the period 1990-1992. RESULTS: In the first series, a high proportion of children aged 3-5 years (30.7%) and 6-12 years (54%) was observed in comparison with a control group of patients hospitalized for anemia at the same time. The symptoms of the disease occurred during the first year of life in 80% of the children: hand-foot syndrome and/or anemia. Tooth decay was observed as soon as the age of 3 years with a high frequency (62%) as compared with the control group. Epistaxis, sometimes very important, was observed in 39.5% and 52% of the cases in children respectively aged 6-12 years and up to 13. A splenomegaly was noted during a longer period than in the control group, suggesting associated causing factors different from malaria, perhaps alpha thalassemia. The high frequency of viral contaminations due to transfusion is illustrated by the seropositivity prevalences of HIV (11.5%), HBV (10%) and in the children in Lubumbashi. CONCLUSION: The main interest of these series of children is to point out the clinical specificities of a cohort genetically homogenous, offering the opportunity of defining basis of inter-individual variability of sickle cell disease.

[Hereditary spherocytosis: one year study of erythrocyte membrane proteins]. / La spherocytose hereditaire: bilan d'une annee d'experience de l'etude des proteines de la membrane erythrocytaire.

Hereditary spherocytosis (HS) is a congenital hemolytic anemia which affects one person out of 5000 in Northern Europe. HS is caused by defects of the red cell membrane proteins involving mainly ankyrin or band 3, and less frequently, protein 4.2 or spectrin. The reduction of red cell osmotic resistance and the recognition of spherocytes on the peripheral blood smear are the primary laboratory tests necessary to evocate a diagnosis of hereditary spherocytosis. Analysis of the red cell membrane proteins using polyacrylamide gel electrophoresis is used to quantify individual proteins and to identify the protein defect related to a diagnosis of HS. Samples from 47 patients and 25 controls were studied by electrophoresis of the red cell membrane proteins. Protein deficiencies related to HS were demonstrated for 21 patients. In 4 other cases, abnormalities of membrane proteins unrelated to HS were also demonstrated. Electrophoresis of the red cell membrane proteins allows the identification of the protein deficiency related to HS and thus confirms the diagnosis of HS, but also points to the underlying molecular defect, the inheritance pattern and the clinical aspects of the disease.

[Neonatal screening for hemoglobinopathies in the Brussels region]. / Dépistage néonatal des hémoglobinopathies dans la région bruxelloise.

We realised this study in order to determine the frequency of abnormal haemoglobins and to appreciate the need for a neonatal screening for haemoglobinopathies in Brussels. Over a two year-period, 9575 cord blood samples were systematically screened. The study disclosed following results : 40% of newborns were from regions at risk for haemoglobinopathies and abnormal haemoglobins were present in 2.5% of the neonates tested. This frequency is similar to those reported elsewhere in North Europe. The most frequent abnormal haemoglobins were the Hb S, Bart's, C, D and E. Three cases of severe forms of sickle cell anaemia were identified. The frequency of abnormal haemoglobins and Hb S traits combined to the high rate of mixed marriages (16%) justifies the need for a universal screening for haemoglobinopathies in Brussels.

Foetal haemoglobin, erythrocytes containing foetal haemoglobin, and hematological features in congolese patients with sickle cell anaemia.

High HbF levels and F cells are correlated with reduced morbidity and mortality in sickle cell disease (SCD). This paper was designed to determine the HbF and F cells levels in Congolese sickle cell anemia (SCA) patients in order to determine their impact on the expression of SCD. Population and Method. HbF levels were measured in 89 SCA patients (mean age 11.4 yrs) using a standard HPLC method. F cell quantitation was done in a second group of SCA patients (n = 42, mean age 8.9 yrs) and compared with a control group (n = 47, mean age 5 yrs). F cells were quantified by a cytofluorometric system (MoAb-HbF-FITC; cut off at 0.5%). Results. The mean value of HbF was 7.2% ± 5.0 with heterogeneous distribution, most patients (76%) having HbF < 8%. Mean values of F-cells in SCA patients and control group were 5.4% ± 7.6 (median: 2.19%; range 0,0-30,3%) and 0.5% ± 1.6 (median 0.0, range 0-5.18), respectively. SCA patients with F cells >4.5% developed less painful crisis and had higher percentage of reticulocytes. Conclusion. Congolese SCA patients displayed low levels of HbF and F-cells that contribute to the severity of SCD.

Neonatal screening for sickle cell anaemia in the Democratic Republic of the Congo: experience from a pioneer project on 31 204 newborns.

BACKGROUND: Despite the high prevalence of sickle cell disease in Africa, a neonatal screening programme is available in only a few countries in the sub-Saharan region. AIM: To describe our experience of a pioneer study on 31,304 newborns screened systematically in the Democratic Republic of the Congo. METHODS: The prevalence of haemoglobinopathies was determined by a thin-layer isoelectric focusing method on dry filter-paper samples. RESULTS: Of the 31,204 newborns screened by isoelectric focusing, 5,276 (16.9%) displayed sickle cell trait and 428 (1.4%) were homozygous for haemoglobin S. No statistical differences were observed in the different ethno-linguistic groups, but some tribes displayed a higher prevalence of the betaS gene, attributable to a higher prevalence of malaria, and a greater frequency of haemoglobin S homozygotes, in part attributable to an endogamic marriage system. CONCLUSION: The neonatal screening programme has now been introduced in the Democratic Republic of the Congo, but the main challenges are to track all the new cases for a confirmatory test and to initiate early management.